1 00:00:00,000 --> 00:00:06,120 DR. ASHLEY VARGAS: Good morning, afternoon, evening,  depending on where you are. On behalf of NIH and   2 00:00:06,120 --> 00:00:11,700 as part of the Workshop Organizing Committee, I'm  so pleased to welcome you to day four in the very   3 00:00:11,700 --> 00:00:17,820 first day of a two-day workshop that is going to  focus on malnutrition in early life. Thank you   4 00:00:17,820 --> 00:00:22,980 for those of you that attended the previous three  days, and now we're going to move to a focus a little   5 00:00:22,980 --> 00:00:27,660 closer to my heart. My name's Ashley Vargas,  and I'm a registered dietician and a program   6 00:00:27,660 --> 00:00:32,820 director at the Eunice Kennedy Shriver National  Institute of Child Health and Human Development.   7 00:00:33,420 --> 00:00:38,280 Nutritional status and risk for malnutrition  begins in early life and shapes developmental,   8 00:00:38,280 --> 00:00:44,220 health, and disease outcomes throughout life and  across generations. While pregnant and lactating   9 00:00:44,220 --> 00:00:50,880 individuals and children are uniquely susceptible  to malnutrition, this also makes this time point   10 00:00:50,880 --> 00:00:58,680 pivotal in life. A small positive change can  have an outsized, lifelong effect. Therefore, the   11 00:00:58,680 --> 00:01:03,840 objectives of the next two days are to identify  research gaps and opportunities that advance   12 00:01:03,840 --> 00:01:11,220 malnutrition research in early life populations. Now it is my honor to introduce the NICHD Deputy   13 00:01:11,220 --> 00:01:17,400 Director, Dr. Alison Cernich. Dr. Cernich  is a board certified neuropsychologist with   14 00:01:17,400 --> 00:01:22,620 expertise in cognitive neuroscience, and,  in her role as deputy director, she works to   15 00:01:22,620 --> 00:01:28,860 implement our recent NICHD strategic plan where  nutrition has a prominent role. Dr. Cernich 16 00:01:28,860 --> 00:01:35,040 DR. ALISON CERNICH: Thanks so much, Ashley, and thanks  to all of you who are joining this focused part of   17 00:01:35,040 --> 00:01:41,220 the workshop. On behalf of NICHD, and our partners  at the Office of Nutrition Research, and the   18 00:01:41,220 --> 00:01:45,780 National Heart, Lung, and Blood Institute, I would  like to welcome you to the fourth day of this   19 00:01:45,780 --> 00:01:51,480 workshop on malnutrition in clinical settings.  Today and tomorrow you will have the opportunity   20 00:01:51,480 --> 00:01:57,360 to take a closer look at the myriad factors  influencing pediatric and family nutrition,   21 00:01:57,360 --> 00:02:03,360 malnutrition risk, treatment, access to  treatment, and the detrimental effects of   22 00:02:03,360 --> 00:02:08,640 malnutrition in the U.S. health care setting. For  the clinical practitioners in the audience, I   23 00:02:08,640 --> 00:02:14,640 know many of you see malnutrition in your patients  every day in the clinic, and there's a struggle   24 00:02:14,640 --> 00:02:20,820 to provide the right care to the right patient at  the right time to prevent and treat malnutrition.   25 00:02:22,260 --> 00:02:28,620 While it's 2022, and I...I think we can do better  for our youngest patients and their family.   26 00:02:29,220 --> 00:02:33,240 Today and tomorrow, I implore this group  of great minds to push boundaries and to   27 00:02:33,240 --> 00:02:37,200 think outside of the box to discuss  opportunities to advance the evidence   28 00:02:37,200 --> 00:02:42,840 base we have for clinicians to address  malnutrition seen every day across the U.S.,  29 00:02:42,840 --> 00:02:47,640 build on the ideas from the first three days  of this workshop, and discuss the science that   30 00:02:47,640 --> 00:02:52,500 we will use to address the critical  windows during pregnancy, lactation,   31 00:02:52,500 --> 00:02:58,740 infancy, and childhood as levers to raise  the nutritional health of our families.   32 00:02:59,580 --> 00:03:07,260 In closing, I want to thank our visionary  co-chairs, Doctors Mehta, Steiber, Seres, Cresci,   33 00:03:07,260 --> 00:03:14,940 and Rice, along with our NIH organizing committee,  Doctors Vargas, Lynch and Pratt, and certainly   34 00:03:14,940 --> 00:03:21,060 our sponsor, the Office of Nutrition Research,  for bringing this workshop together. While our   35 00:03:21,060 --> 00:03:26,580 NICHD strategic plan emphasizes the importance of  nutrition and lifelong health and is committed to   36 00:03:26,580 --> 00:03:31,800 supporting early life nutrition research, we are  so grateful for all the support we receive from   37 00:03:31,800 --> 00:03:38,820 throughout the NIH, for the specific focus on  lifespan nutrition. So thanks so much, Ashley. 38 00:03:38,820 --> 00:03:43,500 DR. ASHLEY VARGAS: Thank you, Dr. Cernich,  for your kind words and support.   39 00:03:44,460 --> 00:03:50,580 Now I have the honor of turning the virtual  microphone to our brilliant lead and our chair for   40 00:03:50,580 --> 00:03:56,280 the early life part of this workshop. Dr. Nilesh  Mehta of Harvard Medical School. Nilesh, to you. 41 00:03:56,280 --> 00:04:01,860 DR. NILESH MEHTA: Thank you so much, Dr. Vargas. Dr.  Cernich, thank you for introducing this session.   42 00:04:02,760 --> 00:04:09,300 And welcome all to this exciting day four.  We've had, as you heard, a very exciting adult   43 00:04:10,440 --> 00:04:15,900 workshop session group on days one, two,  and three. And I'm confident that the next   44 00:04:15,900 --> 00:04:21,480 two days we will see equally stimulating  discussions related to the early life.   45 00:04:22,200 --> 00:04:27,840 I'm excited to bring you this session. My name  is Nilesh Mehta. I'm a Professor of Anesthesia   46 00:04:28,560 --> 00:04:32,100 Critical Care Medicine at Harvard Medical  School. I work at Boston Children's Hospital.   47 00:04:33,300 --> 00:04:39,480 In the session today, we will focus on early life  malnutrition. This is an introductory session,   48 00:04:39,480 --> 00:04:46,020 which will review some of the definitions, the  burden, the epidemiology, and screening aspects   49 00:04:46,020 --> 00:04:51,840 of pediatric malnutrition. I'm delighted that  we are joined by a group of esteemed speakers   50 00:04:51,840 --> 00:04:56,760 who have been at the forefront of pediatric  malnutrition, advancing the field for years.   51 00:04:58,080 --> 00:05:03,300 The session will begin with Dr. Corkins from the  University of Tennessee Health Science Center,   52 00:05:03,300 --> 00:05:08,640 who will speak to newer concepts  of defining pediatric malnutrition.  53 00:05:08,640 --> 00:05:15,660 It will be followed by Dr. Patricia Becker, who  will speak on approaches to screening, assessing,   54 00:05:15,660 --> 00:05:22,080 and diagnosing pediatric malnutrition. After  that, Dr. Jimenez from the University of New   55 00:05:22,080 --> 00:05:26,640 Mexico Health Sciences will speak of her  experience with the application of recent   56 00:05:26,640 --> 00:05:33,180 tool in diagnosing pediatric malnutrition in  U.S. hospitals. And we will end the session with   57 00:05:33,180 --> 00:05:38,100 Professor Fenton from University of Calgary,  who will provide a unique perspective on   58 00:05:38,100 --> 00:05:43,440 malnutrition as it relates to preterm infants  and provide us with a bigger causal picture.   59 00:05:44,760 --> 00:05:52,560 After that, we will break into a Q&A session. I'm  delighted that I'll be joined by Dr. Todd Rice   60 00:05:52,560 --> 00:06:00,420 from Vanderbilt University Medical Center and Dr.  Vargas. And together, we will be delighted to take   61 00:06:00,420 --> 00:06:06,360 your questions and, with the help of our speakers,  have a lively discussion. This session goes on   62 00:06:06,360 --> 00:06:14,400 until 10 past 1, after which we break. And then we move  on to the next session, which is session eight.   63 00:06:15,480 --> 00:06:21,000 And I'm excited at this point, without  further ado, to once again welcome you all.  64 00:06:21,000 --> 00:06:27,660 Thank you so much for joining us today.  And I will now kick this off by moving   65 00:06:27,660 --> 00:06:32,160 on to Dr. Corkin's presentation on  defining pediatric malnutrition. 66 00:06:32,160 --> 00:06:41,040 DR. MARK CORKINS: I was asked to talk about defining  malnutrition, new concepts, and metrics.   67 00:06:42,180 --> 00:06:46,860 So here's my disclosures. You know, our intestinal  rehab clinic is a site for a Takeda-sponsored   68 00:06:46,860 --> 00:06:52,140 study. I am the PI on that, but I get no  direct income from that, so really have   69 00:06:52,140 --> 00:06:56,460 no potential conflicts of interest with this  presentation. So, when we're talking about   70 00:06:57,300 --> 00:07:02,940 malnutrition, where have we been? Well, I'm just kind of giving  the introduction and overview. First is marasmus,   71 00:07:02,940 --> 00:07:07,740 and that's just basically not enough energy  intake. This is your emaciated Third World kids,   72 00:07:07,740 --> 00:07:12,180 who just don't get enough calories. The other one  we learned when we were in school was kwashiorkor,   73 00:07:12,180 --> 00:07:17,040 it's a Ghanaian word that means "the sickness  when the new baby comes." And basically,   74 00:07:17,040 --> 00:07:21,420 they're switched from breast milk, which contains  protein, to carbohydrate-rich diets. And so,   75 00:07:21,420 --> 00:07:25,380 they're protein deficient. And so, they have  this edema that kinda of hides your malnutrition.   76 00:07:25,980 --> 00:07:32,640 The one that we get that has been used for years  in the developed world is failure to thrive. Now,   77 00:07:33,240 --> 00:07:38,100 it was thought to be originally institutionalized  orphans, and it's maternal deprivation.  78 00:07:38,100 --> 00:07:43,860 It's not diagnostic, it's not descriptive.  Parents don't like the term failure. And really,   79 00:07:43,860 --> 00:07:46,860 more or less, it's been decided that  probably this term should go away.   80 00:07:47,700 --> 00:07:53,340 Now, but when you do a deep dive and you look  at children, especially hospitalized children,   81 00:07:54,180 --> 00:08:01,380 you find you that there are children who are  malnourished. And this group, Joosten and Hulst,   82 00:08:01,380 --> 00:08:05,820 in 2008, did a review. Now, when they looked at  acute malnutrition, they found rates anywhere from   83 00:08:05,820 --> 00:08:13,020 6.1 to 32%. But different nations had different  methods. And so, it's kind of a hodgepodge.   84 00:08:13,680 --> 00:08:19,980 So, there was a recognition that malnutrition  in the developed world really happens in the   85 00:08:19,980 --> 00:08:25,440 presence of disease. And it's a disease process.  So the three mechanisms of malnutrition are you're   86 00:08:25,440 --> 00:08:30,300 losing too many nutrients, you're using too  many nutrients, or you're not taking in enough   87 00:08:30,300 --> 00:08:35,160 nutrients. And when Grover and his group looked  at the breakdown of kids who are malnourished,   88 00:08:35,160 --> 00:08:39,660 they found out they had some sort of primary  disease. And if you look at the bottom there   89 00:08:39,660 --> 00:08:45,900 on the left, 44% of them had multiple diagnoses. So malnutrition is happening in the presence of   90 00:08:45,900 --> 00:08:53,340 disease. And that sort of makes sense. So if you  know that we have kids with these chronic diseases   91 00:08:53,340 --> 00:08:57,660 now, that we're curing and treating, well,  that sets them up to be malnourished. They have   92 00:08:57,660 --> 00:09:03,540 inflammation, inflammation burns calories. They  have all sorts of extra medical needs. In fact,   93 00:09:04,500 --> 00:09:09,120 the U.S. Department of Health and Human Services  defines kids with acute or chronic illnesses,   94 00:09:09,120 --> 00:09:13,320 kids that have special health care needs. And  they have an increased risk for chronic physical,   95 00:09:13,320 --> 00:09:17,340 developmental, behavioral, and emotional  conditions that require health and health-related   96 00:09:17,340 --> 00:09:25,260 services beyond that of children generally. The  thing is, in the US, that's 14%. 14% of kids are   97 00:09:25,260 --> 00:09:29,040 those considered with special health care needs.  That's a big group. And so, it was a recognition   98 00:09:29,040 --> 00:09:34,320 that we needed a definition that worked in the  developed world for malnutrition. And there was a   99 00:09:34,320 --> 00:09:40,920 work group formed in April, 2010. Dieticians,  physicians, (UNKNOWN) GI doc, yours truly,   100 00:09:40,920 --> 00:09:44,940 actually, endocrinology, critical care, primary  care, chronic care, nurses, pharmacists.  101 00:09:44,940 --> 00:09:49,080 It was very multidisciplinary. And actually  librarians, who helped pull literature. And   102 00:09:49,080 --> 00:09:53,880 we actually published that in March 2013. It was  endorsed by the American Society for Parenteral   103 00:09:53,880 --> 00:09:57,360 and Enteral Nutrition, the Academy of Nutrition  and Dietetics, and the American Academy of   104 00:09:57,360 --> 00:10:03,540 Pediatrics. Now, when this group started looking  at things, we looked at potential functional   105 00:10:03,540 --> 00:10:08,160 measures. We really wanted functional measures to  look at. Well, lean body mass measurement. Well,   106 00:10:08,160 --> 00:10:12,840 that's not that easy to do in kids. Not even in  a research setting is it that easy to do. Muscle   107 00:10:12,840 --> 00:10:16,200 strength. Well, that depends on if you train or  not, or you're male, or you're female, where you're   108 00:10:16,200 --> 00:10:22,680 at in puberty. Neurocognitive outcomes. Well,  that's great except that's also influenced by   109 00:10:22,680 --> 00:10:28,440 a lot of other factors, socioeconomic factors.  Some of it's genetic. Immune function, well,   110 00:10:28,440 --> 00:10:33,120 how do you measure immune function? Duration  of illness. Hey, that is a functional measure,   111 00:10:33,120 --> 00:10:37,260 but are you going to give somebody an illness  to measure how well their function works?  112 00:10:37,260 --> 00:10:42,060 So, that's an ethical issue. Tanner Stages. And  I will admit, I was in part of the group that   113 00:10:42,060 --> 00:10:48,180 looked in depth at Tanner Stages, huge genetic  input into Tanner Stages. There's a five-year   114 00:10:48,180 --> 00:10:51,780 swing. If your mother went to puberty early,  you're probably going to go into puberty early. If   115 00:10:51,780 --> 00:10:55,920 your mother went late, it's late. And so, how  can you use that as a nutrition marker? Well,   116 00:10:55,920 --> 00:11:01,020 you really can't. So, when the group got really  down to the brass tax, basically the only thing   117 00:11:01,020 --> 00:11:07,200 that the literature put out that you could follow,  that was very objective, was anthropometrics:   118 00:11:07,200 --> 00:11:11,880 weight, height, length, body mass index, mid-upper  arm circumference. And mid-upper arm circumference   119 00:11:11,880 --> 00:11:16,080 is the one that surprised everybody that the  literature showed that that was a very accurate   120 00:11:16,080 --> 00:11:20,700 measure. It's primarily been used in Third World  countries, and it's actually a very good predictor   121 00:11:20,700 --> 00:11:24,780 of mortality and morbidity. The other thing that  came out of the literature is that we should be   122 00:11:24,780 --> 00:11:31,320 reporting this data as z-scores, how far they are  from the median weight of the same reference data.  123 00:11:31,320 --> 00:11:36,840 And actually, WHO has been recommending that  we use z-scores since 1977. Our residents and   124 00:11:36,840 --> 00:11:40,980 fellows love z-scores because it's continuous,  and it's not a percentile. Less than the one   125 00:11:40,980 --> 00:11:46,680 percentile is how far? Because that less than  the one percentile is a big range sometimes.   126 00:11:49,140 --> 00:11:52,380 Anthropometrics, obviously the problems  are, of course, you need an accurate weight.   127 00:11:54,360 --> 00:11:59,160 For up to two years of age, we're still  using the 2006 WHO charts, and a supine   128 00:11:59,160 --> 00:12:06,720 length measurement for kids age two to 20 years of  age. We're using the CDC 2000 growth charts with   129 00:12:06,720 --> 00:12:13,260 a standing height measurement for plotting. Now,  ideally of course, we would use changes, weight,   130 00:12:13,260 --> 00:12:18,120 length, velocity over time as opposed to a  single measurement. But I'll tell you, the   131 00:12:18,120 --> 00:12:22,560 work group that looked at this really recognized  an ability that we needed to be able to make an   132 00:12:22,560 --> 00:12:28,740 encounter diagnosis. Because you see kids, they're  malnourished and you want to intervene, you need   133 00:12:28,740 --> 00:12:34,860 to intervene, you shouldn't wait. Basically,  created tables for both. Acute versus chronic,   134 00:12:34,860 --> 00:12:39,960 well, NCHS defines chronic as anyone the last  over three months, so that was defined for us.  135 00:12:41,640 --> 00:12:49,800 Here is the single encounter chart, ok, and this'll  be in your slide set. And here's the   136 00:12:49,800 --> 00:12:53,940 multiple points. And this is basically looking  at the changes in velocity with time. Again,   137 00:12:53,940 --> 00:13:00,300 this is probably the ideal. Of course, what really  falls out of this is when you start to talk about   138 00:13:00,300 --> 00:13:05,040 malnutrition, it is an etiology-based  diagnosis now. So, when you see a child,   139 00:13:05,040 --> 00:13:11,700 they meet the parameters for malnourishment, you  say, "Hey, is it acute or chronic? Is it mild,   140 00:13:11,700 --> 00:13:16,980 moderate, or severe? Is it illness related or  non illness related?" And state the illness and   141 00:13:16,980 --> 00:13:24,780 you include the medical etiology as part of the  diagnosis. This is a chronic, severe malnutrition   142 00:13:24,780 --> 00:13:33,240 in the face of congenital heart disease. And you  can say type of chronic congenital heart disease.   143 00:13:33,240 --> 00:13:41,640 And that is the diagnosis, that's the malnutrition  diagnosis in full. So that's kind of...a quick overview of the   144 00:13:41,640 --> 00:13:46,920 new concepts in malnutrition now that we're  approaching malnutrition with in children.   145 00:13:48,840 --> 00:13:55,380 I was asked to talk about research gaps.  Well, number one, based on this data we   146 00:13:55,380 --> 00:14:00,180 have currently, number one, research  gaps are accurate anthropometrics.  147 00:14:00,180 --> 00:14:05,760 Now, weights aren't too bad, although  they're currently not perfect.   148 00:14:07,980 --> 00:14:13,860 Length and height though, are lots of issues with  measuring those. And some kids can't be measured   149 00:14:13,860 --> 00:14:18,480 in the standard length board or standing height,  so there are proxy measures. Well, number one,   150 00:14:18,480 --> 00:14:24,120 we can measure the distance if you're a golfer  to the flag pole, so there should be good ways   151 00:14:24,120 --> 00:14:28,140 to measure length in height better than just  tape measure or length board. There should be   152 00:14:28,140 --> 00:14:33,120 some sort of technologic approach to do that. The  proxy measures, we need more studies on better   153 00:14:33,120 --> 00:14:38,700 proxy measures and better tables and data on proxy  measures. Functional measures, I talked about some   154 00:14:38,700 --> 00:14:44,100 that didn't work, but we need studies on other  functional measures, something that's measurable   155 00:14:44,100 --> 00:14:50,280 over time in a predictable fashion that will  correlate with the nutritional status. Now EHR,   156 00:14:50,280 --> 00:14:55,560 good grief. There's a bunch of things that can  be done there. We need to have some sort of a   157 00:14:55,560 --> 00:15:00,240 system that can look at error measurements. "Oh,  this height's too far, this length's too short.  158 00:15:00,240 --> 00:15:06,840 This needs to be redone." And a smart system  should be able to figure that out and do that. The   159 00:15:06,840 --> 00:15:14,040 other thing is, special disease curves. We have  some available, but they should be incorporated   160 00:15:14,040 --> 00:15:18,120 into the EHRs. The EHR is a perfect place to  do that. There's a Turner's growth curve. If   161 00:15:18,120 --> 00:15:22,440 you have a child with Turner's, you should be able  to go to a menu and select Turner's growth curves.   162 00:15:22,440 --> 00:15:27,180 And some of the more common disorders, there  should be growth curves for those children   163 00:15:27,180 --> 00:15:32,040 that are available to help you track  what normal growth is for them. Alright,   164 00:15:32,040 --> 00:15:36,480 I appreciate your attention, and I'll look forward  to discussing this later as a part of the group. 165 00:15:36,480 --> 00:15:42,780 DR. PATRICIA BECKER: I am Patricia Becker and I  am presenting on pediatric malnutrition risk   166 00:15:42,780 --> 00:15:51,660 screening, assessment, and diagnosis. Malnutrition  risk screening should utilize validated tools.   167 00:15:53,100 --> 00:15:59,100 Those tools should have moderate to high  user reliability and outcomes validity.   168 00:15:59,880 --> 00:16:06,000 They should be usable in all patient  care settings. Pediatric malnutrition   169 00:16:06,000 --> 00:16:12,000 risk screening tools should be adaptable to  both paper and electronic medical records.   170 00:16:12,720 --> 00:16:19,500 Children should be screened for malnutrition risk  in all patient care settings, within 24 hours of   171 00:16:19,500 --> 00:16:26,160 admission in acute care, and upon presentation  in the outpatient and primary care settings.   172 00:16:28,020 --> 00:16:35,220 Tools that meet these criteria include the  pediatric nutrition screening tool, PNST.   173 00:16:36,060 --> 00:16:41,580 It is used by the Canadian health care  system, the Australian health system,   174 00:16:41,580 --> 00:16:45,960 Boston Children's Hospital, and by  our hospital, Dayton Children's.   175 00:16:47,040 --> 00:16:53,820 It is comprised of four questions. It is adaptable  to both paper and electronic medical records.   176 00:16:54,360 --> 00:17:02,220 It stratifies children into severe, moderate,  or no risk. Children with severe or moderate   177 00:17:02,220 --> 00:17:08,100 risk should be referred to a registered  dietician nutritionist for further assessment.  178 00:17:09,960 --> 00:17:17,700 This is the PNST. The URL for this tool  is located at the bottom of this slide.   179 00:17:19,920 --> 00:17:28,440 The screening tool for nutrition Risk of Nutritional status  and Growth STRONGkids is in use by the Canadian   180 00:17:28,440 --> 00:17:36,960 Healthcare System and the Academy/ASPEN Indicators  of Malnutrition for Pediatrics Validation Study.   181 00:17:37,620 --> 00:17:45,840 It is comprised of four questions. It is adaptable  to both paper and electronic medical records.   182 00:17:45,840 --> 00:17:54,300 It stratifies children into severe, moderate,  or no risk. Children with severe or moderate   183 00:17:54,300 --> 00:18:00,840 risk should be referred to a registered dietician  nutritionist for further nutritional assessment.   184 00:18:03,900 --> 00:18:11,400 Here are the screen questions for STRONGkids.  They include questions related to the child's   185 00:18:11,400 --> 00:18:18,840 medical condition, nutrition focused physical  assessment, GI symptoms, nutrient intake,   186 00:18:18,840 --> 00:18:26,340 and weight growth assessment. The URL for this  tool is located at the bottom of this slide.   187 00:18:28,440 --> 00:18:36,360 The screening tool for assessment of malnutrition  and pediatrics, STAMP, is a five step malnutrition   188 00:18:36,360 --> 00:18:43,080 risk screening tool that includes questions  on height and weight measurement compared to   189 00:18:43,080 --> 00:18:49,680 percentile tables and severity of medical  diagnosis' impact on nutritional status.  190 00:18:50,700 --> 00:18:58,800 The Electronic Health Record STAMP is the adapted  tool for the electronic medical record that has   191 00:18:58,800 --> 00:19:06,240 been validated and updated to include current  criteria. The citations are included here.   192 00:19:08,460 --> 00:19:17,340 This website provides information on its use  in practice. This URL directs the user to the   193 00:19:17,340 --> 00:19:27,660 percentile-based tool. Here is an example  of that tool. The URL is provided below.   194 00:19:30,240 --> 00:19:37,380 This information shows the adaptation of  STAMP from the percentiles to the z-score   195 00:19:37,380 --> 00:19:46,380 for use in the electronic medical record.  For the assessment of malnutrition tools   196 00:19:46,380 --> 00:19:52,620 for use include the Subjective Global  Nutrition Assessment for pediatrics.   197 00:19:54,540 --> 00:20:02,460 SGNA for pediatrics is currently the only  validated tool for pediatric nutrition assessment.   198 00:20:03,240 --> 00:20:09,660 It is often used as the reference standard  for validation of other tools and criteria.   199 00:20:10,560 --> 00:20:19,140 Concerns with the 2012 version are outdated and  unvalidated measures, such as percentage of ideal   200 00:20:19,140 --> 00:20:24,420 body weight for children, and changes  in weight over a period of six months   201 00:20:25,080 --> 00:20:32,160 plus weight loss percentage, and use  of percentiles versus z-score data.  202 00:20:34,500 --> 00:20:41,880 The highlighted areas here show the criteria that  would benefit from updating to current standards   203 00:20:41,880 --> 00:20:50,220 and validation. They include weight and weight  change over the past six months and weight loss   204 00:20:50,220 --> 00:20:58,680 percentage. Appropriateness of weight for height,  as stated for ideal body weight greater than 90%,   205 00:20:59,760 --> 00:21:08,580 75 to 90%, or less than 75%, and adequacy of  intake with vague terms such as adequate,   206 00:21:08,580 --> 00:21:12,900 somewhat adequate, and very inadequate starvation.   207 00:21:15,480 --> 00:21:25,740 Highlighted areas include criteria that were  updated to include the Academy/ASPEN Indicators of   208 00:21:25,740 --> 00:21:32,220 Malnutrition for Pediatrics, which were validated  for use by the Canadian Malnutrition Task Force.   209 00:21:32,820 --> 00:21:37,380 The citations and website  are indicated here as well.   210 00:21:41,460 --> 00:21:50,580 The revised SGNA also includes more  detailed assessment of adequacy of intake,   211 00:21:53,460 --> 00:22:03,240 as well as a clearer description of functional  capacity. For your information, I am also   212 00:22:03,240 --> 00:22:13,320 presenting information on malnutrition diagnosis  for pediatrics. The Academy of Nutrition and   213 00:22:13,320 --> 00:22:22,740 Dietetics and ASPEN consensus derived Indicators  of Malnutrition for Pediatrics, the AAIMP   214 00:22:22,740 --> 00:22:30,120 have been in common use since their publication  in December of 2014, with over 80 citations.  215 00:22:31,080 --> 00:22:37,440 They are currently undergoing a multi-center  research study to validate these criteria.   216 00:22:40,200 --> 00:22:46,260 Criteria for mild, moderate, and severe  malnutrition have been established for   217 00:22:46,260 --> 00:22:54,540 children ages one month to 18 years. Documentation  should include the criteria and be supported   218 00:22:54,540 --> 00:23:01,440 by the modifiers of chronicity, the presence of  inflammation, and their relationship to illness,   219 00:23:02,040 --> 00:23:09,180 as well as inclusion of information on  nutrition-focused physical examination findings.   220 00:23:11,940 --> 00:23:18,720 Criteria for pre-term infants and neonates  were not included in the AAIM for pediatrics.   221 00:23:19,380 --> 00:23:23,760 These were proposed in the  paper published in 2018.   222 00:23:24,360 --> 00:23:33,000 These recommended indicators have been in use  since that time. The indicators include weight,   223 00:23:33,000 --> 00:23:41,280 length, gross velocity, and adequacy of  intake-based criteria. In our NICU, we are   224 00:23:41,280 --> 00:23:48,360 finding approximately 15% of the population meet  the criteria with agreement from our providers.   225 00:23:51,180 --> 00:23:58,140 To support practice, pathways for providing  malnutrition care for children can be helpful for   226 00:23:58,140 --> 00:24:04,860 the health care team. The following three slides  show examples from the Canadian Malnutrition   227 00:24:04,860 --> 00:24:11,460 Task Force, ASPEN, and the Children's Hospital  of Philadelphia, all of which are open source.  228 00:24:12,120 --> 00:24:21,300 They can be helpful in support nutrition care for  children. The Canadian Malnutrition Task Force   229 00:24:21,300 --> 00:24:28,740 Pathway outlines the steps in nutrition  care, screening, assessment, diagnosis,   230 00:24:28,740 --> 00:24:36,000 and treatment or nutrition care. The URL for this  pathway is located at the bottom of this slide.   231 00:24:37,860 --> 00:24:45,060 The ASPEN Pediatric Malnutrition Pathway for  Children ages one month to 18 years is shown here.   232 00:24:45,600 --> 00:24:50,040 The URL for the pathway is located  at the bottom of this slide.   233 00:24:51,660 --> 00:24:58,080 Here is an example of one of several  malnutrition-related clinical pathways available   234 00:24:58,080 --> 00:25:06,120 from the Children's Hospital of Philadelphia, and  the URL is at the bottom of this slide as well.   235 00:25:08,460 --> 00:25:13,380 Thank you for your attention. Please  feel free to contact me at the email   236 00:25:13,380 --> 00:25:17,460 addresses provided should you  have questions or comments. 237 00:25:17,460 --> 00:25:23,940 DR. ELIZABETH JIMENEZ: Hello, My name is Elizabeth  Yakes Jiminez, and I'll be discussing application   238 00:25:23,940 --> 00:25:30,120 of the Pediatric Academy and ASPEN Indicators to  diagnose malnutrition in hospitalized patients,   239 00:25:30,780 --> 00:25:33,540 otherwise known as the pediatric AAIM tool.   240 00:25:37,380 --> 00:25:42,600 We know that malnutrition is associated with  poor clinical outcomes and increased health care   241 00:25:42,600 --> 00:25:48,120 utilization in hospitalized patients, but  is likely underdiagnosed and undertreated.   242 00:25:48,660 --> 00:25:56,520 A recent study found only a 6.4% prevalence of a  coded diagnosis of malnutrition for U.S. pediatric   243 00:25:56,520 --> 00:26:05,100 patients in 2019. One barrier to improving  diagnostic practice is the lack of a systematic,   244 00:26:05,100 --> 00:26:09,900 universally-accepted method of diagnosing  malnutrition in the hospitalized pediatric   245 00:26:09,900 --> 00:26:16,020 patients. As Patricia Becker explained in  her presentation, the pediatric AAIM tool   246 00:26:16,020 --> 00:26:22,080 was developed through a consensus process. More  information is needed about the tool's predictive   247 00:26:22,080 --> 00:26:30,240 validity and implementation before concluding  that it should be widely used. To examine the   248 00:26:30,240 --> 00:26:36,120 predictive validity of the pediatric AAIM tool, we  are conducting a cohort study with U.S. hospitals.  249 00:26:36,900 --> 00:26:40,380 For those interested in detailed  information on the study design,   250 00:26:40,380 --> 00:26:45,960 including inclusion and exclusion criteria,  a published protocol paper is available.   251 00:26:47,160 --> 00:26:52,860 At baseline, we are collecting some data for all  patients enrolled in the study. This includes   252 00:26:52,860 --> 00:26:58,920 sociodemographic information, medical history,  a STRONGkids' malnutrition screener score,   253 00:26:59,460 --> 00:27:05,340 duration and type of initial nutrition care,  and an RDN-determined complexity measure.   254 00:27:05,880 --> 00:27:10,260 If a physician orders biomarkers of  inflammation, those are also captured.   255 00:27:10,860 --> 00:27:15,900 From within this full study group, which  will be used to examine study staffing aims,   256 00:27:15,900 --> 00:27:22,200 we randomly selected a group of children for whom  the pediatric AAIM tool and a nutrition-focused   257 00:27:22,200 --> 00:27:27,720 physical exam are being completed. Children  are randomly selected to be included in the   258 00:27:27,720 --> 00:27:32,760 AAIM subgroup stratified approximately  one-to-one as high or moderate versus   259 00:27:32,760 --> 00:27:39,540 low-risk for malnutrition based on the STRONGkids' screener score. 90 days after discharge,   260 00:27:39,540 --> 00:27:46,440 we pull information on dietician follow-up care,  hospital readmissions, ER visits, and length of   261 00:27:46,440 --> 00:27:52,740 stay from the medical record, along with ICD-10  Codes to calculate measures of disease severity,   262 00:27:52,740 --> 00:27:59,520 including the MSDRG relative weight, the  Charleston Comorbidity Index, and the Pediatric   263 00:27:59,520 --> 00:28:03,120 Complex Chronic Conditions Measure. Thus far,   264 00:28:06,300 --> 00:28:14,040 29 hospital sites have initiated data collection,  and 23 sites have completed data collection.   265 00:28:14,580 --> 00:28:21,720 I will be presenting data from 166 patients in the  pediatric AAIM subgroup, from 22 hospital sites.   266 00:28:22,380 --> 00:28:27,720 As data are still being collected for the study,  all results included in this presentation should   267 00:28:27,720 --> 00:28:33,780 be considered preliminary. Data collection  for the study started in August 2019, and a   268 00:28:33,780 --> 00:28:39,420 substantial proportion of the data were collected  after the onset of the COVID-19 pandemic.   269 00:28:41,820 --> 00:28:50,280 Hospital sites are located across 19 states and  Washington D.C. Hospitals currently represented   270 00:28:50,280 --> 00:28:58,680 in the analysis have a median of 187 licensed  beds, a median average census of 154 patients,   271 00:28:58,680 --> 00:29:06,600 and a median case mix index of 1.77. Almost  all are affiliated with a medical school and   272 00:29:06,600 --> 00:29:15,060 located in population-dense areas, and about  a third are critical access hospitals. About   273 00:29:15,060 --> 00:29:21,180 three-fourths of the dieticians collecting data  for the study have advanced degrees, and about 40%   274 00:29:21,180 --> 00:29:26,520 have additional advanced certifications related  to pediatric nutrition or nutrition support.  275 00:29:27,420 --> 00:29:32,400 Participating dieticians are experienced  practitioners, with a median of nine years   276 00:29:32,400 --> 00:29:38,160 of experience in dietetics, and seven and a half  years of experience in inpatient nutrition care.   277 00:29:40,260 --> 00:29:45,120 Patients currently enrolled in the study are  about evenly divided between boys and girls,   278 00:29:45,120 --> 00:29:51,300 and have a median age of 4 years. Overall,  about a third of patients are less than 2,   279 00:29:51,300 --> 00:29:59,280 half are 2 to 11.9 years, and about a fourth  are adolescents. 61% of patients are White,   280 00:29:59,280 --> 00:30:08,280 19% are Black, and 23% are Hispanic.  Based on the STRONGkids screening tool,   281 00:30:08,280 --> 00:30:14,700 about half of children are at moderate risk of  malnutrition and about a third are at high risk.   282 00:30:15,300 --> 00:30:20,700 A similar distribution is seen for  dietician-assessed patient complexity, with about   283 00:30:20,700 --> 00:30:27,060 half of patients rated by the dietician as medium  complexity and a third rated as high complexity.   284 00:30:27,960 --> 00:30:32,940 High complexity patients are defined as  requiring nutrition interventions with frequent   285 00:30:32,940 --> 00:30:40,140 reassessments, for example, patients with chronic  or nutritionally complex diseases, new or modified   286 00:30:40,140 --> 00:30:46,800 enteral or parenteral nutrition, or requiring  new or complex comprehensive nutrition education.  287 00:30:48,060 --> 00:30:54,120 Using the pediatric AAIM tool, the dieticians  determined that 57% of patients have malnutrition,   288 00:30:54,120 --> 00:30:58,860 about evenly divided between mild,  moderate, and severe malnutrition.   289 00:30:59,520 --> 00:31:01,800 This reflects the design of the study.   290 00:31:04,200 --> 00:31:09,660 Dieticians reported spending a median of an hour  on initial care for the children included in the   291 00:31:09,660 --> 00:31:16,320 study, and frequently document nutrition diagnoses  related to inadequate oral intake, malnutrition,   292 00:31:16,320 --> 00:31:24,600 altered GI function, and inadequate energy intake.  During the 90-day follow-up period, about half   293 00:31:24,600 --> 00:31:30,000 of children did not have any contacts with the  dietician related to oral nutrition supplements,   294 00:31:30,000 --> 00:31:37,320 enteral nutrition, or parenteral nutrition.  Another 19% had one contact, with about a   295 00:31:37,320 --> 00:31:42,240 fourth of children having two or more nutrition  support contacts during the three months after   296 00:31:42,240 --> 00:31:50,760 discharge. About a third of patients spent some  time in the ICU during their admission, while very   297 00:31:50,760 --> 00:31:55,740 few were diagnosed with sepsis, had non-healing  wounds, or died during the enrollment admission.   298 00:31:56,580 --> 00:32:01,380 For the analysis, we used a composite 90-day  outcome that adds together the number of   299 00:32:01,380 --> 00:32:07,020 hospital readmissions and ER visits that the  child had during the 90 days after discharge.  300 00:32:07,560 --> 00:32:12,300 This ranged from zero to eight. The  median length of stay was five days.   301 00:32:13,020 --> 00:32:18,180 Finally, we calculated three different disease  severity indices, all of which can be interpreted   302 00:32:18,180 --> 00:32:24,420 as higher numbers indicating more severe disease  or more intensive use of health care resources.   303 00:32:26,940 --> 00:32:31,860 The study data analysis focuses on whether  children and teens with the diagnosis of   304 00:32:31,860 --> 00:32:36,960 malnutrition, based on the pediatric AAIM  tool, have more ER visits and readmissions   305 00:32:36,960 --> 00:32:42,720 and/or longer length of stay, compared to  children without the diagnosis of malnutrition.   306 00:32:43,440 --> 00:32:48,780 In our multilevel Poisson and generalized linear  models, we controlled for disease severity,   307 00:32:48,780 --> 00:32:55,140 ICU stays, and socio-demographics, since there  is evidence that these factors may be related   308 00:32:55,140 --> 00:33:00,900 both to malnutrition and health care outcomes,  and also included a random effective site.   309 00:33:01,620 --> 00:33:07,620 In addition, we examined the relationship between  individual indicators, the STRONGkids screening   310 00:33:07,620 --> 00:33:13,680 tool, RDN-assessed complexity, and the health care  outcomes, controlling for the same factors.   311 00:33:16,380 --> 00:33:21,360 As mentioned on the previous slide, all models  controlled for a measure of disease severity,   312 00:33:21,360 --> 00:33:26,040 ICU stay during admission,  child age, and biological sex.  313 00:33:26,700 --> 00:33:32,340 Overall, children who scored at high  versus low risk on the STRONGkids screener,   314 00:33:32,340 --> 00:33:37,080 or who were assessed as high versus  low complexity by the dietician,   315 00:33:37,080 --> 00:33:44,220 had higher incidents of ER visits and readmissions  and longer length of stay. However, there was no   316 00:33:44,220 --> 00:33:51,840 relationship between a pediatric AAIM diagnosis  of malnutrition and health care outcomes. When we   317 00:33:51,840 --> 00:33:57,360 examine the relationship between dietician's use  of individual indicators and total ER visits and   318 00:33:57,360 --> 00:34:04,080 readmissions, only dietician use of deceleration  and weight for length or height z-score to support   319 00:34:04,080 --> 00:34:09,720 a diagnosis of malnutrition, was significantly  associated with a higher incidence of the outcome.   320 00:34:10,440 --> 00:34:15,600 Deceleration and weight for length or height  z-score is one of the longitudinal measures and   321 00:34:15,600 --> 00:34:21,900 may be more useful to understand change in status,  but it was unable to be assessed for 41 children.   322 00:34:23,340 --> 00:34:28,800 Only dietician use of length or height for age  z-score to support a diagnosis of malnutrition   323 00:34:28,800 --> 00:34:34,740 was significantly associated with longer length  of stay. Interestingly, from an implementation   324 00:34:34,740 --> 00:34:40,080 perspective, the same relationship with length  of stay is not observed when using objective   325 00:34:40,080 --> 00:34:45,780 length or height for age z-score cutoffs. And the dietician chose to use length or   326 00:34:45,780 --> 00:34:51,600 height for age z-score as an indicator only about  30 to 40% of the time when the z-score was less   327 00:34:51,600 --> 00:34:57,240 than negative two. So the dietician may be  recognizing when linear growth restriction   328 00:34:57,240 --> 00:35:03,060 is unrelated to chronic malnutrition and taking  that into account during the diagnostic process.   329 00:35:05,520 --> 00:35:10,860 While the findings from this work are preliminary,  they identify the need for additional work to   330 00:35:10,860 --> 00:35:15,780 determine the best tool to diagnose malnutrition  in hospitalized pediatric patients.   331 00:35:16,440 --> 00:35:22,080 Additional studies could consider relationships  between a malnutrition diagnosis and other   332 00:35:22,080 --> 00:35:27,720 outcomes, such as child development and quality  of life, when identifying the best tool to use.   333 00:35:28,560 --> 00:35:33,900 Once a validated tool is identified, it  will be necessary to identify the level of   334 00:35:33,900 --> 00:35:40,020 dietician staffing needed to provide nutrition  care that improves outcomes. To determine if   335 00:35:40,020 --> 00:35:46,260 diagnosed malnutrition resolves with nutrition  intervention and to understand biological and   336 00:35:46,260 --> 00:35:51,480 environmental factors that are associated  with non-response to nutrition intervention.  337 00:35:54,240 --> 00:35:58,020 Thank you very much for taking the  time to listen to this presentation. 338 00:35:58,020 --> 00:36:06,780 DR. TANIS FENTON: Today I've been asked to talk about  malnutrition with respect to preterm infants and   339 00:36:06,780 --> 00:36:13,200 the bigger malnutrition causal picture. So  part one, preterm infants and malnutrition.   340 00:36:14,100 --> 00:36:20,220 Preterm infants are challenging to nourish.  At birth, they have limited nutrition stores   341 00:36:20,220 --> 00:36:27,600 as well as no or limited oral feeding  abilities. They're separated while they're   342 00:36:27,600 --> 00:36:34,200 in intensive care from their families. Some  have had poor growth in utero, and some have   343 00:36:34,200 --> 00:36:41,040 limited tolerance of parenteral and/or enteral  nutrition, so they are a challenge to nourish.   344 00:36:42,720 --> 00:36:49,500 A concern I have about diagnosing  malnutrition or poor infant growth   345 00:36:49,500 --> 00:36:55,740 for preterm infants is that extrauterine growth  restriction is a very popular categorization.   346 00:36:56,820 --> 00:37:05,820 This graph shows the rise in the use of the term  extrauterine growth restriction in Medline through   347 00:37:05,820 --> 00:37:13,380 the PubMed search engine. Extrauterine growth  restriction is usually defined as a weight less   348 00:37:13,380 --> 00:37:21,180 than a 10th or a 3rd percentile at about 36  weeks post menstrual age. And you can see from   349 00:37:21,180 --> 00:37:27,840 the pattern here that over the past 20 years,  with a little bit of an exception, there's been   350 00:37:28,740 --> 00:37:33,960 an approximate exponential rise  in the use of this categorization.  351 00:37:35,580 --> 00:37:44,100 The reason I don't value using this categorization  is that extrauterine growth restriction is not   352 00:37:44,100 --> 00:37:50,880 related to cognitive outcomes. Here are  six studies that examine this question at   353 00:37:50,880 --> 00:37:58,140 either the 3rd or 10th percentile, or seventh  percentile at 36 to 40 weeks. We also looked at   354 00:37:58,140 --> 00:38:09,360 continuous all percentiles at 36 weeks. And in all  cases, this categorization was not associated with   355 00:38:09,360 --> 00:38:16,560 low cognitive scores. We looked at both the  Bayley and IQ scores at three years of age.   356 00:38:17,880 --> 00:38:27,960 So a group of very smart dieticians have put  together some malnutrition indicators led by   357 00:38:27,960 --> 00:38:36,240 Dr. Dena Goldberg. These indicators  are declines in weight for age z-scores,   358 00:38:36,240 --> 00:38:41,400 and also relative to that needed  to maintain expected growth rates,   359 00:38:41,400 --> 00:38:49,500 a low weight gain velocity, and consecutive  days of inadequate protein and energy.   360 00:38:51,420 --> 00:38:57,000 These indicators have not yet been validated,  so this is a good topic for a research project. 361 00:38:58,580 --> 00:39:06,960 The reason why the X uterine growth  restriction is probably not associated with   362 00:39:06,960 --> 00:39:14,160 poor cognitive scores is the usual weight change  pattern of preterm infants. This graph is showing   363 00:39:14,160 --> 00:39:22,440 weekly cohorts of preterm infants and how weight  loss is, is common amongst most preterm infants.   364 00:39:22,440 --> 00:39:30,540 You can see that at the 10th percentile, the  shaded area is, the bottom of the shaded area   365 00:39:30,540 --> 00:39:39,600 is approximately equal to this 10th percentile  on the growth chart. And this shaded area is   366 00:39:39,600 --> 00:39:47,640 the interquartile range, which means it's the 25th  to the 75th percentile. So, this graph is showing   367 00:39:47,640 --> 00:39:54,120 that 25% of these preterm infants weighed less  than the 25th percentile after their postnatal   368 00:39:54,120 --> 00:40:01,440 weight loss. And these infants were selected  to be the healthiest of preterm infants from   369 00:40:01,440 --> 00:40:11,340 the healthiest of pregnancies, no morbidities,  minimal respiratory support needed. And yet 25% of   370 00:40:11,340 --> 00:40:20,280 them weighed less than the 10th percentile after  the postnatal weight loss. The average of their Z   371 00:40:20,280 --> 00:40:30,780 change, Z score changes was 0.8. But I proposed to  you that we can't expect that all preterm infants   372 00:40:30,780 --> 00:40:41,340 should only lose an average of 0.8 Z scores. And the actual range of Z score change for this   373 00:40:41,340 --> 00:40:51,720 sample of preterm infants ranged from no change  at all to a loss of two Z scores. So, what we   374 00:40:51,720 --> 00:40:57,240 need for preterm infants are defined measures  that are highly predictive of adverse outcomes.   375 00:40:58,800 --> 00:41:06,180 So, the American Academy of Pediatrics and ESPGHAN  have put forward some growth guidelines over the   376 00:41:06,180 --> 00:41:12,600 years that have really passed the test of time.  They both recommend that preterm infants grow   377 00:41:12,600 --> 00:41:21,120 at approximately the rate of a normal fetus. And  they don't recommend achievement of any particular   378 00:41:21,120 --> 00:41:28,920 percentiles, but rather looking for a growth  pattern that is approximately parallel to that   379 00:41:28,920 --> 00:41:36,240 of the fetus. And what that looks like on growth  charts is growth that approximately parallel to   380 00:41:36,240 --> 00:41:42,480 growth chart curve. So, you can see this little  girl on the left. She lost some weight and she   381 00:41:42,480 --> 00:41:49,020 didn't keep up perfectly to intrauterine growth  rates, but then she was able to maintain weight   382 00:41:49,020 --> 00:41:54,600 gain that was approximately parallel, as well as  length that was approximately parallel. Her head   383 00:41:54,600 --> 00:42:00,120 did a little bit of catch up before her term. This little boy, on the other hand, was not   384 00:42:00,120 --> 00:42:06,900 doing well. Both his weight and his length were  continuing to fall off, fall away from the growth   385 00:42:06,900 --> 00:42:13,980 chart curves. Even his head was falling off  the, the growth chart curves. So, this is the   386 00:42:13,980 --> 00:42:21,480 growth that is recommended as undesirable by the  American Academy of Pediatrics and ESPGHAN and I   387 00:42:21,480 --> 00:42:28,920 agree with them. So, this brings us to Part  2, the bigger malnutrition causal picture.   388 00:42:30,300 --> 00:42:36,000 So, the problem is often assumed to be that poor  nutrition leads to poor growth and malnutrition   389 00:42:36,000 --> 00:42:44,640 leads to poor outcomes. But I propose to you  that the actual causal relationships are much   390 00:42:44,640 --> 00:42:50,880 more complex, and the factors that are important  include the social determinants of health,   391 00:42:51,420 --> 00:42:58,980 prenatal factors, inadequate nutrition is  a factor. Also, stress in the NICU has been   392 00:42:58,980 --> 00:43:06,300 associated with outcomes as well as morbidities.  So, all of these factors lead directly to poor   393 00:43:06,300 --> 00:43:13,860 outcomes. They can also lead to poor growth and  malnutrition. But it's not really clear if there   394 00:43:13,860 --> 00:43:21,120 is a causal link here as there was in the 1980s. But I'm hoping that in North America,   395 00:43:21,120 --> 00:43:28,860 the nutritional care for the most  part does not lead to poor outcomes   396 00:43:29,520 --> 00:43:38,460 directly here. So, for pediatrics, the diagram  is a little bit different because pediatrics are   397 00:43:38,460 --> 00:43:44,400 removed somewhat from prenatal factors. Not to  say that those factors aren't important at all,   398 00:43:44,400 --> 00:43:50,760 but it's probably better to include the  factor of environment for pediatrics.   399 00:43:53,100 --> 00:43:59,520 And I proposed to you that there was some value  in the traditional consideration for failure   400 00:43:59,520 --> 00:44:07,080 to thrive, that there were organic causes,  meaning medical causes, as well as non-organic   401 00:44:07,080 --> 00:44:13,380 or non-medical etiologies. And this  is true of malnutrition as well.   402 00:44:14,460 --> 00:44:18,120 So, I proposed to you that  what we need is, first of all,   403 00:44:18,120 --> 00:44:22,740 we need malnutrition measures that are  highly predictive of adverse outcomes.   404 00:44:23,940 --> 00:44:30,600 And so that we can then work to improve the  nutrition and the outcomes of, of the infants.   405 00:44:32,160 --> 00:44:39,120 I think it's well established that the  best malnutrition measures are based on   406 00:44:39,120 --> 00:44:45,480 serial measurements to assess both growth and  nutritional status and not one time measures.  407 00:44:46,740 --> 00:44:53,160 And we need to consider several anthropometric  measures and not only weight. And I think this   408 00:44:53,160 --> 00:44:59,880 workshop is an opportunity that we could take to  encourage the electronic medical record companies   409 00:44:59,880 --> 00:45:04,860 to show several of the anthropometric  measures simultaneously. For example,   410 00:45:04,860 --> 00:45:10,320 for preterm infants, it's highly valuable to  look at weight length and head circumference   411 00:45:10,320 --> 00:45:17,760 at the same time on your screen, on your computer  screen. For older infants, it's important to show   412 00:45:17,760 --> 00:45:25,920 length or height with weight for age, or BMI, to  be able to assess infants and and children well.   413 00:45:28,200 --> 00:45:33,540 And then we need to consider the etiology,  since it will help determine the solution.   414 00:45:35,040 --> 00:45:41,160 That is, the etiology of malnutrition helps  to determine the solution to the malnutrition.   415 00:45:42,060 --> 00:45:44,580 So, I wish to thank you for  your time and attention.   416 00:45:52,920 --> 00:46:00,240 DR. NILESH MEHTA: For these excellent stimulating kickoffs to  all of our speakers, Dr. Corkins, Dr. Backer,   417 00:46:00,240 --> 00:46:07,380 Dr. Jimenez, Dr. Fenton, I truly appreciate  it. At this point, I would like to welcome Dr.   418 00:46:07,380 --> 00:46:13,020 Todd Rice, from Vanderbilt University, who  will be joining me for the Q&A session.  419 00:46:13,620 --> 00:46:19,920 Welcome, Todd. And, and once again,  before we kick this off, a brief   420 00:46:21,840 --> 00:46:27,840 temperature on what's happening. Well, on the  other side, and we have over 70 participants   421 00:46:27,840 --> 00:46:37,080 online right now, and it's really a big deal for  us to have gathered in this forum. And to that end,   422 00:46:37,080 --> 00:46:44,880 I truly wish to thank the NIH Office of Nutrition  Research, our scientific program leadership from   423 00:46:45,480 --> 00:46:52,080 Dr. Christopher Lynch, Dr. Charlotte Pratt, Dr.  Ashley Vargas, on behalf of all the co-chairs,   424 00:46:52,080 --> 00:46:57,060 we really thank you for this opportunity and  giving both the adult and pediatric community   425 00:46:57,060 --> 00:47:07,500 this platform. Thanks so much to Dr. Kimberly  Barch, to Marc Dennis and today, Israel Gonzalez   426 00:47:07,500 --> 00:47:13,800 for all the behind the scenes technical support  that we've seen. And of course, thank you so   427 00:47:13,800 --> 00:47:19,020 much to Dr. Cernich for being present here  today and once again providing this platform.   428 00:47:19,800 --> 00:47:28,560 So, with that said, I see many of our  speakers already on here, and we can jump   429 00:47:28,560 --> 00:47:36,780 right in. One of the beauties of this session is  it follows the adult malnutrition research gaps   430 00:47:36,780 --> 00:47:43,440 sessions over the last three days, last week. And I thought if Dr. Rice could kick us off by   431 00:47:44,340 --> 00:47:53,951 some similarities, some themes that you saw in the  adult sessions that you are hearing here in the pediatrics today. Dr. Rice. 432 00:47:53,951 --> 00:48:01,440 DR. TODD RICE: Yeah. Thanks Nilesh,  and great presentations to the panel. You know, the   433 00:48:01,440 --> 00:48:08,940 adult sessions, many of the participants and, and  current people watching may have actually watched   434 00:48:08,940 --> 00:48:15,540 the adult sessions, too. But quickly, kind of some  similarities in malnutrition is that I think we're   435 00:48:15,540 --> 00:48:20,880 all looking for that elusive perfect marker.  We don't have it yet in the adult world. And it   436 00:48:20,880 --> 00:48:27,540 sounds like that's true in the pediatric world also.  The scores are pretty good at predicting   437 00:48:28,380 --> 00:48:33,900 malnutrition as defined by poor outcomes. But and  this is something we spent some time talking about   438 00:48:33,900 --> 00:48:42,300 on the, on the adult side is, but importantly,  we haven't bridged the gap for predicting the   439 00:48:42,300 --> 00:48:47,760 patients that we can actually intervene in and,  and change the outcomes. And so, there's lots   440 00:48:47,760 --> 00:48:52,140 of scores in the adult world that say, if your  score is X on this or greater than X on this,   441 00:48:53,040 --> 00:48:58,620 you're more likely to have a poor outcome. But what we don't have very much of is a marker   442 00:48:58,620 --> 00:49:03,900 that says, if your score is this, you're likely to  have a poor outcome. And if we intervene with the   443 00:49:03,900 --> 00:49:09,000 nutrition therapy or nutritional support therapy,  we can change that outcome and make it different.   444 00:49:09,840 --> 00:49:13,980 One of the things, interestingly, and somebody  in the panel, and maybe even you, Dr. Mehta,   445 00:49:13,980 --> 00:49:20,580 can comment on it, that is becoming very popular  in the adult world are imaging to try and diagnose   446 00:49:20,580 --> 00:49:28,500 malnutrition. So, ultrasound of muscle bodies, or  people love CT scans of kind of the L3-L4. So,   447 00:49:28,500 --> 00:49:34,860 as muscle at that level to try and, and they  reasonably predict, again, poor outcomes   448 00:49:34,860 --> 00:49:40,740 and we think malnutrition. We didn't have a  specific talk about that in the pediatric side,   449 00:49:40,740 --> 00:49:45,660 but I'm intrigued to know if that's something  that's truly different in the adult world. If   450 00:49:45,660 --> 00:49:48,480 it's something in the pediatric world, you  all have tried and said it doesn't work and   451 00:49:48,480 --> 00:49:53,040 we've given up on it. Or if it's the, maybe  that's all too common in the pediatric world.   452 00:49:55,620 --> 00:49:59,520 DR. NILESH MEHTA: Thanks, Dr. Rice. Brilliant. I appreciate you giving   453 00:49:59,520 --> 00:50:05,640 us a nice overview of how things are similar and  how things are different, which, as you've heard,   454 00:50:06,180 --> 00:50:12,720 surely imaging. And I will let our speakers jump  in. I just wanted to remind everyone to use the   455 00:50:12,720 --> 00:50:20,580 question box on your, on your platform and thank  you for all the questions that you've put in. We'd   456 00:50:20,580 --> 00:50:26,100 love to get more, and I will interrupt this  discussion if I see new questions pouring in.   457 00:50:26,100 --> 00:50:33,720 But we have plenty of questions that we could  kick this off with. Alright. Dr. Corkins,   458 00:50:34,500 --> 00:50:41,280 a couple of questions related to the low  resource community that you alluded to.   459 00:50:42,180 --> 00:50:48,060 And one of them is, it seems like and this is  from Dr. Christopher Duggan from Boston Children's.   460 00:50:48,060 --> 00:50:53,760 It seems like, seems like this approach assumes  that malnutrition in the low resource countries   461 00:50:53,760 --> 00:50:58,860 developing world is not generally associated  with illnesses. But, but of course, many episodes   462 00:50:58,860 --> 00:51:03,780 of severe and moderate acute malnutrition in  children in resource poor countries are linked   463 00:51:03,780 --> 00:51:09,120 with infectious or other inflammatory stresses. Does it make sense, Dr. Duggan asked to have   464 00:51:09,120 --> 00:51:14,640 two definitions of malnutrition, one for, one for  industrialized countries and another for other countries. 465 00:51:14,640 --> 00:51:23,940 DR. MARK CORKINS: Yes, it does make sense. At least it  makes sense to me. So, in the developing world,   466 00:51:25,020 --> 00:51:32,040 it sometimes is a chicken and the egg. And are  they malnourished? Does it lower their threshold   467 00:51:32,040 --> 00:51:38,760 for infection? But infection certainly  will worry, worrisomely, I think that's,   468 00:51:38,760 --> 00:51:43,320 I think that's a word, make their malnutrition  worse. And sometimes it is a vicious cycle.   469 00:51:45,120 --> 00:51:52,800 In the U.S., for the most part, we believe most of  our children are well-nourished. Again, that's a   470 00:51:52,800 --> 00:52:00,540 supposition. That's a big supposition. But we  see malnutrition in the US and developed world   471 00:52:01,140 --> 00:52:10,560 in conjunction with disease and disease  seems to be step one. So, now that not,   472 00:52:10,560 --> 00:52:16,500 not every child in the U.S. and malnourished also  has a disease, there are some social as well.   473 00:52:17,640 --> 00:52:25,500 But a lot of the non-nutrition we see  does start with disease. Like I said,  474 00:52:25,500 --> 00:52:31,260 the special health care needs from the, from the  government handbook, 14% of the kids in the U.S.  475 00:52:31,260 --> 00:52:36,240 have a special health care need. And those are the  ones that we tend to see developing malnutrition.   476 00:52:36,840 --> 00:52:44,760 So, there, there does seem to be kind of  a two, two categories here. Of course,   477 00:52:44,760 --> 00:52:52,200 there's overlap. But I think one of the important  things is that we recognize there is malnutrition.   478 00:52:53,700 --> 00:53:01,080 And I can still remember when I was young and  skinny and my hair was brown. And we'd see this   479 00:53:01,080 --> 00:53:04,800 kid and they were underweight and they'd say,  well, they have congenital heart disease. And   480 00:53:04,800 --> 00:53:09,180 it was almost like it was accepted, Oh, well,  this kid has cancer. And we would accept that.   481 00:53:10,440 --> 00:53:15,480 And the value of this kind of approach in the  developed world is we like, wait a minute,   482 00:53:16,020 --> 00:53:21,600 yes, they have a disease, but they're malnourished  and you don't ignore it. And we need to intervene.   483 00:53:22,680 --> 00:53:27,960 You know, to talk to Dr. Rice's question,  one of the biggest issues is, is the ethics   484 00:53:27,960 --> 00:53:34,020 of intervention. Because if my kid's going to  enter a study of malnutrition intervention,   485 00:53:34,020 --> 00:53:36,540 I don't want them randomized  to the non intervention group.   486 00:53:38,280 --> 00:53:40,860 You know, don't put my kid in  the non intervention group.  487 00:53:40,860 --> 00:53:45,000 I want my kid in the intervention group,  you know. And so, that is a problem as far   488 00:53:45,000 --> 00:53:50,940 as outcomes because a lot of it becomes then, you  know, retrospective studies, which are very weak.   489 00:53:51,840 --> 00:53:59,400 Even observational again, is it, is it ethical  to, to not intervene, even if you quote unquote,   490 00:53:59,400 --> 00:54:05,880 don't do any harm? Or how do you, how do you  study outcomes in a way that is going to give you data that you can use? 491 00:54:05,880 --> 00:54:11,700 DR. NILESH MEHTA: Thanks Dr. Corkins,  DR. TODD RICE: Let me come out really quickly that I agree,   492 00:54:11,700 --> 00:54:16,800 I agree with you. That's, I suspect I don't do  pediatrics, but I suspect that that's an even   493 00:54:16,800 --> 00:54:21,120 bigger ethical problem in the ped side than it  is in the adult side. And it's still a problem   494 00:54:21,120 --> 00:54:28,980 that we have on the adult side. One of the ways  potentially around that would be to try and come   495 00:54:28,980 --> 00:54:34,500 up with different tailored interventions and then  apply those as your two arms. So, everybody's   496 00:54:34,500 --> 00:54:42,420 getting some intervention, but we're trying to  differentiate, you know, what the, what the actual   497 00:54:43,200 --> 00:54:49,140 details of the intervention are that may be  either helpful or the most helpful, as opposed   498 00:54:49,140 --> 00:54:56,760 to not providing any nutritional support to a  group that clearly has markers of malnourishment.  499 00:54:59,220 --> 00:55:06,960 DR. NILESH MEHTA: Thank you, Dr. Rice. A few questions for  Miss Becker. One from Dr. Seres, David Seres from   500 00:55:06,960 --> 00:55:13,200 Columbia University. STAMP and other tools  are validated against SGA and each other and   501 00:55:13,200 --> 00:55:17,940 our predictable overall outcome. But have they  been validated to predict, which patients will   502 00:55:17,940 --> 00:55:22,560 have improved outcomes if a nourishment based  intervention is applied to the individual?   503 00:55:29,100 --> 00:55:30,480 You might be muted.   504 00:55:40,920 --> 00:55:44,880 Ms. Becker, we can't hear you. You might  be muted. If you go to the top right,   505 00:55:44,880 --> 00:55:48,960 there's a mute camera and  a mute audio button there.   506 00:56:02,820 --> 00:56:04,631 DR. MARK CORKINS: She's going high tech on us. 507 00:56:04,631 --> 00:56:14,760 DR. NILESH MEHTA: Yeah. Yeah Jiminez.  Ms. Becker, we still can't hear you. We'll come  right back to you while you sort that out. You  know, there's been a similar team in terms of   508 00:56:14,760 --> 00:56:22,080 what are these markers or screening tools or  diagnostic criteria being used for. I wonder if,   509 00:56:22,080 --> 00:56:26,760 Dr. Jimenez, you want to take a crack at  this confusion between screening tools and   510 00:56:26,760 --> 00:56:31,740 diagnostic indicators, which require a  more detailed assessment. For example,   511 00:56:31,740 --> 00:56:36,840 STRONGkids being a screening tool will  detect risk of malnutrition and the AIMP is a,   512 00:56:36,840 --> 00:56:42,660 you know, suggesting a diagnostic criteria. Any comments on how it's being used currently   513 00:56:42,660 --> 00:56:50,880 and how you chose STRONGkids in your paper  to compare with AIMP? It's a really excellent   514 00:56:50,880 --> 00:56:57,120 DR. ELIZABETH JIMENEZ: It's a really excellent question. I was actually discussing this with  Dr. Steiber last week and also a little bit   515 00:56:57,120 --> 00:57:03,900 with Ms. Becker and some other folks from the  pediatric nutrition practice group. I think,   516 00:57:03,900 --> 00:57:11,280 you know, we, we looked at trying to think about  maybe next steps here, the overlap between the   517 00:57:11,280 --> 00:57:17,340 pediatric subjective global nutrition assessment  that Ms. Becker talked about in her presentation,   518 00:57:17,340 --> 00:57:25,200 the AAIM indicators and the STRONGkids screening  tool. And it's interesting because there's   519 00:57:25,200 --> 00:57:30,960 some aspects that are included in the pediatric  subjective global nutrition assessment that are   520 00:57:30,960 --> 00:57:39,900 not in the AAIM indicators that are in the STRONGkids screener. And those are namely, GI symptoms,   521 00:57:39,900 --> 00:57:46,140 kind of metabolic stress related to underlying  disease or surgery and the nutrition focused   522 00:57:46,140 --> 00:57:55,920 physical exam. And so, the distinction is, is  maybe not as clear with the STRONGkids screener   523 00:57:55,920 --> 00:58:04,800 as, as some other screening tools, which are much  simpler, like the MST, for example, in adults.  524 00:58:04,800 --> 00:58:12,960 And so, you know, I think it's a good question for  us going forward. And we chose it because it had,   525 00:58:13,500 --> 00:58:20,340 you know, the the academy of nutrition and  dietetics has kind of done scoping reviews and   526 00:58:20,340 --> 00:58:26,100 looking at screening tools in pediatrics.  And it had good metrics for the study.   527 00:58:26,820 --> 00:58:33,960 DR. MARK CORKINS: And I'm hoping, go ahead. I was going to comment.  I was actually on that task force with Pat.   528 00:58:35,100 --> 00:58:43,620 Part of it's statistical, screening is a  broad net. Screening is designed to find it,   529 00:58:43,620 --> 00:58:50,640 not miss it. And so, statistically,  you want, you want a high   530 00:58:51,900 --> 00:58:55,500 sensitivity, but low specificity. In other  words, you're going to accept some false   531 00:58:55,500 --> 00:58:59,100 positives when you're screening. You don't  want to miss somebody when you're screening   532 00:58:59,100 --> 00:59:04,800 them. With a diagnostic test, you're trying to  get at high sensitivity, but you're also trying   533 00:59:04,800 --> 00:59:11,340 to get a high specificity. If you say it's not, it's  not. And so, in a way, the difference literally   534 00:59:11,340 --> 00:59:20,400 is in the statistics and the nitty gritty.  Again, when you're doing a screen, the goal is   535 00:59:21,060 --> 00:59:25,080 anybody who is at risk, you're going to pick them  up and then you're going to have to assess them.  536 00:59:26,400 --> 00:59:30,840 And that, that's a different statistical approach.  And then it's interesting because some parameters   537 00:59:31,380 --> 00:59:35,520 are great screens, but terrible  diagnostic criteria. In other words,   538 00:59:35,520 --> 00:59:39,360 almost everybody who is malnourished is going to have  this, but then there's also some folks who are   539 00:59:39,360 --> 00:59:47,951 not malnourished. You're also going to have that,  that kind of thing. And so in a way, it's the how broad, the net you want to throw out. 540 00:59:47,951 --> 00:59:50,340 DR. NILESH MEHTA: Thanks,  (UNKNOWN). OK. Dr. Jimenez, you want to jump in?   541 00:59:51,240 --> 00:59:55,140 I just want to comment a little bit further  because I think we thought it was interesting   542 00:59:55,140 --> 01:00:02,400 how the dieticians were using the anthropometric  indicators in the study, particularly length for   543 01:00:02,400 --> 01:00:08,520 age Z score. They were not using it in many  cases, only about 40% of the cases when kids   544 01:00:08,520 --> 01:00:14,280 had a score of less than negative two, did they  use it to support a diagnosis of malnutrition? And   545 01:00:14,280 --> 01:00:20,460 I think that's because, you know, linear growth  restriction can have many causes that are kind   546 01:00:20,460 --> 01:00:26,880 of nutrition and non-nutrition related. And so,  they were using their clinical judgment to really   547 01:00:27,480 --> 01:00:35,760 interpret when it was nutrition related. So, I think, you know, the anthropometric   548 01:00:35,760 --> 01:00:44,400 measures can sometimes be too broad as well, when  we're trying to think about nutrition related   549 01:00:44,400 --> 01:00:51,896 causes. And I don't know if Dr. Fenton wants to  comment further. DR. NILESH MEHTA: Go ahead, Dr. Fenton.   550 01:00:51,896 --> 01:01:01,380 DR. TANIS FENTON: One thing I'd like to comment on is a series of a couple of  papers published out of New Zealand, in which they  551 01:01:01,380 --> 01:01:06,960 addressed the question, what are the effects  of macronutrient supplementation for small,   552 01:01:06,960 --> 01:01:13,020 for gestational age or preterm infants? There are  two papers published just this year by Lynne and   553 01:01:13,020 --> 01:01:18,540 Harding and other collaborators, and it's quite  interesting. They called it the Essence study   554 01:01:19,080 --> 01:01:25,740 and they looked for existing randomized trial  data and then they requested the data. So,   555 01:01:25,740 --> 01:01:33,960 they did individual participant meta-analyses,  which is a nice complicated technique and, and the   556 01:01:33,960 --> 01:01:40,260 strength of these studies. And the results are  really interesting because they, they looked at   557 01:01:40,260 --> 01:01:46,380 two sets of outcomes. One were cognitive outcomes  and the other were metabolic risk outcomes,   558 01:01:46,980 --> 01:01:53,880 and they found that there was no increase  in metabolic risk in terms of higher BMIs or   559 01:01:53,880 --> 01:01:59,820 other markers of metabolic risk after  the macronutrient supplementation.  560 01:01:59,820 --> 01:02:05,940 In terms of growth, they didn't see huge  differences, but some differences in male   561 01:02:05,940 --> 01:02:13,140 toddlers. But I think these studies are useful  because, you know, as Dr. Corkins mentioned,   562 01:02:13,140 --> 01:02:18,000 it's hard to randomize because parents might  not want it. Dr. Mehta mentioned, you know,   563 01:02:18,000 --> 01:02:23,880 we can compare, you know, essentially standard  of care with a treatment or two treatments.   564 01:02:24,600 --> 01:02:31,020 And so, people don't have to feel they're  getting poor care. They're getting essentially   565 01:02:31,020 --> 01:02:37,200 in the placebo group. But studies have been  done. And I think these two meta-analyses,   566 01:02:37,200 --> 01:02:44,640 you know, give us some guidance about what we  already know and, and how we can go forward.   567 01:02:46,380 --> 01:02:54,720 DR. NILESH MEHTA: Thanks Dr. Fenton. It appears that in addition  to understanding which variables or parameters   568 01:02:54,720 --> 01:02:59,700 you incorporate into the screening or diagnostic  test, it's also crucial to understand what is   569 01:02:59,700 --> 01:03:03,540 the outcome. What are you assessing them  for? And as you alluded, is this related   570 01:03:03,540 --> 01:03:07,980 to longer term functional outcomes? Is it  related to, as Dr. Seres was asking,   571 01:03:07,980 --> 01:03:15,060 response to nutritional interventions, or is  it a risk predictor of subsequent malnutrition?  572 01:03:15,060 --> 01:03:20,400 And those studies appear to be modelled together  in the literature, and it's important to ask them.   573 01:03:21,300 --> 01:03:25,320 Professor Fenton, there's a question from  Suzanna Attia from University of Kentucky.   574 01:03:25,320 --> 01:03:30,540 In the community screening for malnutrition,  what's the utility of weight for length Z scores for term and preterm infants? 575 01:03:30,540 --> 01:03:39,120 DR. TANIS FENTON: What a really good question. So, after an infant,   576 01:03:39,840 --> 01:03:48,101 after a preterm birth, we can't use the WHO growth standard until they reach 40 weeks post   577 01:03:48,101 --> 01:03:54,899 menstrual age because there's no space on those  charts. So, there are preterm growth charts for   578 01:03:54,900 --> 01:04:03,240 them. But once they've reached 40 weeks or  50 weeks, if they're using MyChart, then they   579 01:04:03,240 --> 01:04:12,000 they do need to go to the accepted standard of  the, you know, which the WHO growth standard.   580 01:04:12,840 --> 01:04:19,980 So, to assess weight and to assess growth,  we need to look beyond weight and a lot of   581 01:04:19,980 --> 01:04:25,680 papers in the literature, a systematic  review we published in 2017 found that   582 01:04:25,680 --> 01:04:33,720 50% of studies that looked at preterm infant  growth only looked at weight. And so, yes,   583 01:04:33,720 --> 01:04:40,440 you're right. We need to look at length as well. In terms of weight for length, it is the accepted   584 01:04:41,400 --> 01:04:49,800 recommended way to look at weight and length  together, although it's not perfect because   585 01:04:49,800 --> 01:04:58,980 when infants grow from term age to six months,  whether they were preterm or term, there are   586 01:04:58,980 --> 01:05:09,060 changes in body proportionality And yet the weight  for length approach doesn't consider changes with   587 01:05:09,060 --> 01:05:16,800 age. The same age is used from zero to 24 months.  And actually I have a PhD student looking at   588 01:05:16,800 --> 01:05:23,640 this question. We're looking at five million data  points to see how well the distributions look for   589 01:05:23,640 --> 01:05:30,960 weight, for length at various ages versus looking,  using BMI at the younger ages. But anyway, I don't   590 01:05:30,960 --> 01:05:37,920 have a firm answer about the best approach.  Excuse me. But I think we need to consider both   591 01:05:37,920 --> 01:05:44,640 weight and length in the early weeks, even just by  making sure we're seeing both plotted at the same   592 01:05:44,640 --> 01:05:51,900 time and then using at this point the recommended  approach, which is to use weight through length.   593 01:05:51,900 --> 01:05:57,600 DR. MARK CORKINS: And also, there's a little data on that  upper arm circumference. Even in the preemie,   594 01:05:57,600 --> 01:06:01,380 there was a study that looked at it and tracked  it, and it did change appropriately with time.  595 01:06:01,380 --> 01:06:06,300 They're just not normal for preterm  infants. DR. NILESH MEHTA: Thank you both. 596 01:06:06,300 --> 01:06:08,257 DR. TANIS FENTON: Once they reach, sorry, Doctor. 597 01:06:08,257 --> 01:06:10,257 DR. NILESH MEHTA: Oh, go on, please. 598 01:06:10,257 --> 01:06:12,257 DR. TANIS FENTON: Once they reach 40 to 50 weeks, post menstrual age or, 599 01:06:14,760 --> 01:06:21,120 you know, term age, you know, the appropriate  growth recommendations or growth references   600 01:06:21,120 --> 01:06:26,760 to use are those that we use for non-term  infants. We just need to make sure we're,   601 01:06:26,760 --> 01:06:32,760 sorry, for term infants, we just need to make  sure we're correcting the age for them. And then, yes. Thank you. 602 01:06:33,420 --> 01:06:40,320 DR. NILESH MEHTA: In terms of the specific topic  that we are trying to address in this seminar,   603 01:06:40,320 --> 01:06:49,500 which is the gaps and future avenues for us,  any responses to Dr. Rice's question about   604 01:06:49,500 --> 01:06:58,020 imaging in our early life patients? Is it, is  it beginning to be assessed adequately? Are we   605 01:06:58,020 --> 01:07:04,740 going to see any imaging areas, ultrasound? And  maybe we should throw in bio impedance into that?   606 01:07:05,760 --> 01:07:09,780 DR. MARK CORKINS: To my knowledge, there's no literature  at this point on any of that.   607 01:07:11,280 --> 01:07:19,440 You know and I, you know, it's hard to know,  like infants, it may not be affected. You know,   608 01:07:19,440 --> 01:07:24,240 the we looked at handgrip strength in kids,  but, you know, male and female was different.  609 01:07:24,240 --> 01:07:30,240 How far they were along in puberty was different,  where they, they did athletics that changed it.   610 01:07:30,240 --> 01:07:35,820 You know, they train, in other words. But, you  know, younger kids, does it make a difference?   611 01:07:36,960 --> 01:07:44,160 Infants, would it make a difference? To my  knowledge, nobody's looked at it. 612 01:07:44,160 --> 01:07:51,240 DR. TANIS FENTON: Yeah. I agree. I haven't seen it in in the pre-term or infant  literature either. But I think with pediatrics,   613 01:07:51,240 --> 01:07:59,700 we have some tools that are additionally useful  that, you know, are not exactly the same for,   614 01:07:59,700 --> 01:08:06,900 for adults. And that is, you know, growth is  normal. And for an adult, generally maintaining   615 01:08:06,900 --> 01:08:14,280 weight is normal, but for infants and children,  growth is normal. So, we can assess their growth   616 01:08:14,280 --> 01:08:23,640 patterns, which gives us more information.  Now, there is a tendency now for people to   617 01:08:23,640 --> 01:08:29,160 look at body composition for preterm infants. And  actually, I'm quite concerned about it because   618 01:08:30,240 --> 01:08:37,560 we know that after birth, whether a baby's preterm  or term, they put on body fat, they increase their   619 01:08:37,560 --> 01:08:44,760 proportion of body fat. And that happens at a  younger post menstrual age with preterm infants.  620 01:08:44,760 --> 01:08:49,800 And there's been quite a few papers that  in, especially in their introduction,   621 01:08:49,800 --> 01:08:56,340 talk about this concern about the body  fat at term age of preterm infants.   622 01:08:57,360 --> 01:09:08,340 But if you look at any data for older ages, like  for around three months of post term age, they the   623 01:09:08,340 --> 01:09:13,980 preterm infants do not any longer have a higher  body fat percentage. So, it's just a comparison.   624 01:09:13,980 --> 01:09:20,340 At 40 weeks, we see it higher. So, I actually  think that what's happening with body composition   625 01:09:20,340 --> 01:09:27,780 assessment clinically and in research for preterm  infants is raising alarm bells that should not be   626 01:09:27,780 --> 01:09:32,100 raised. We need to look at the bigger picture  and see what our expectations should be.   627 01:09:32,940 --> 01:09:38,580 DR. NILESH MEHTA: That's a great point. Thank you. Along those lines,  Professor Fenton, there's a question to you which   628 01:09:38,580 --> 01:09:44,520 actually is relevant to all our speakers in  terms of actual validation of these tools.   629 01:09:45,600 --> 01:09:50,700 And this question specifically is from Austin  Mikulski from University of Michigan at the CS Mart.   630 01:09:51,840 --> 01:09:55,920 If, if we need NICU dieticians were to  contribute towards a validation effort   631 01:09:55,920 --> 01:10:00,480 for the proposed malnutrition indicators, and  specifically for preterm neonatal population,   632 01:10:00,480 --> 01:10:04,980 what do we validate against and what  outcome measures should we focus on?  633 01:10:05,880 --> 01:10:14,160 DR. TANIS FENTON: Yeah. The most common outcomes that are used  for, especially preterm infants are cognitive   634 01:10:14,160 --> 01:10:21,960 outcomes. And, you know, the Bayleyis a routine  measure that's often used in a lot of studies   635 01:10:21,960 --> 01:10:28,860 and then in a lot of just general care of, of  preterm infants in follow up. And then some,   636 01:10:28,860 --> 01:10:36,420 some places also have IQ data. And the older  is usually better because, you know, you can   637 01:10:36,420 --> 01:10:41,460 imagine a young infant, particularly if they're  tired, probably don't do an excellent job of a   638 01:10:41,460 --> 01:10:49,620 Bayley at 21 months of age. But when children get  older, they can express their intelligence better.   639 01:10:49,620 --> 01:10:59,760 But generally, it is cognitive outcomes that are  used for, for, for validation of these measures.   640 01:11:01,920 --> 01:11:07,680 DR. NILESH MEHTA: Dr. Corkins, Dr. Jiminez, Dr. Becker's trying  to get her audio fixed, but anyone else jump in   641 01:11:07,680 --> 01:11:13,680 for pediatrics in terms of outcomes? DR. MARK CORKINS: Outcomes are, are, you know, it is interesting   642 01:11:13,680 --> 01:11:20,340 because there are some big population data  that better nutrition interventions produce.   643 01:11:20,340 --> 01:11:24,240 You know, like, for instance, higher IQ  scores. We're talking like some of the   644 01:11:26,220 --> 01:11:30,300 third world countries, some of the developing  world studies certainly show higher IQ scores.  645 01:11:31,800 --> 01:11:41,940 There is the the study out at Appalachia in the  U.S. where they had, they intervene in the preschool   646 01:11:41,940 --> 01:11:47,520 age group and they had better outcomes, less  cardiovascular disease, less obesity later on.   647 01:11:47,520 --> 01:11:54,300 It's the, you know, thrifty hypothesis. But it,  the troubled IQ is there is a genetic component.   648 01:11:54,300 --> 01:12:03,660 You know, if you're from Lake Wobegon, you know,  all the children are above average. So, you know,   649 01:12:03,660 --> 01:12:12,300 what is the norm? What is the IQ? Because IQ is  a range. And so, you need a big group and again,   650 01:12:12,300 --> 01:12:16,080 you'd have to compare a big group, you know,  with some sort of intervention without,   651 01:12:16,080 --> 01:12:22,560 with and without to see a difference because  there is going to be the normal spread of IQ.   652 01:12:26,340 --> 01:12:31,860 DR. ELIZABETH JIMENEZ: And I'll just agree that development is a  really important outcome in pediatrics with the other speakers. 653 01:12:31,860 --> 01:12:40,740 DR. TANIS FENTON: And as Dr. Corkins  mentioned, the metabolic concerns, which,   654 01:12:40,740 --> 01:12:47,280 you know, the Lynn and Harding meta-analyses  indicated no concern. But you're right,   655 01:12:47,280 --> 01:12:52,920 that is, those are other outcomes that need to be  examined because people are concerned about them.  656 01:12:55,140 --> 01:12:58,500 DR. NILESH MEHTA: Thank you all. Dr. Becker, can you hear us?   657 01:13:04,080 --> 01:13:11,640 Sorry, I'm sorry that you're struggling with your  audio. One question for the group. Do you know of   658 01:13:11,640 --> 01:13:16,920 ready solutions for electronic health records  where some of these tools have been adopted   659 01:13:16,920 --> 01:13:22,800 that can be taken by other children's hospitals,  where these applications can be put on to some of   660 01:13:22,800 --> 01:13:29,640 the predominant EHRs in the country right now?  Patricia Becker talked about the EHR STAMP.   661 01:13:30,300 --> 01:13:35,100 And most children's hospitals are struggling,  developing their own way to incorporate it.   662 01:13:37,920 --> 01:13:43,140 DR. MARK CORKINS: It's funny because you have to ask them to  switch disease scores, we had to ask them,   663 01:13:43,140 --> 01:13:49,920 you know, hey, we want Z scores, not percentiles.  You know, we still, it's in the queue supposedly   664 01:13:49,920 --> 01:13:56,400 to get the drop, I'd like a dropdown to get some of  the special curves. I would love to see some sort   665 01:13:56,400 --> 01:14:03,000 of artificial intelligence. Look at this, you  know, I talked about gaps, for instance. Now,   666 01:14:03,000 --> 01:14:06,660 it's not their fault, but like orthopedics clinic,  if you have a kid who goes to orthopedics clinic   667 01:14:06,660 --> 01:14:10,920 and they have a cast on, the weight  is out of line with the rest of them.  668 01:14:10,920 --> 01:14:15,900 And there should be some sort of intelligence  system to look at that and say that weight point   669 01:14:16,800 --> 01:14:22,920 is not accurate. Now, again, they've got  a cast on, so the orthopedics clinics,   670 01:14:23,880 --> 01:14:28,860 somebody needs to realize that, you know, somehow  the system needs to figure out that point needs   671 01:14:28,860 --> 01:14:37,740 to have an asterisk by it. But again, some sort of  smart system to look at the data and it should be   672 01:14:37,740 --> 01:14:43,860 able to somehow be automatic that they're preterm  as opposed to having to tell it it's preterm.   673 01:14:44,940 --> 01:14:47,903 DR. NILESH MEHTA: Agreed. Dr. Jimenez, you had a comment?  674 01:14:47,903 --> 01:14:49,800 DR. ELIZABETH JIMENEZ: Yeah. I just wanted to point out, 675 01:14:49,800 --> 01:14:55,380 I think the research gap in this area is really  the need for implementation science to figure   676 01:14:55,380 --> 01:15:01,800 out best practices and how to do this across  sites in terms of screening and referral and   677 01:15:01,800 --> 01:15:09,300 diagnosis. I think we do a lot of multi-site  studies and see lots and lots of variability   678 01:15:09,300 --> 01:15:14,700 across sites and how it's done and what the  capabilities are of the electronic medical record.   679 01:15:16,440 --> 01:15:23,280 DR. TANIS FENTON: I have a point to add. Excuse me. So,  I think as I mentioned in my talk, that   680 01:15:23,280 --> 01:15:28,620 we really need to have the growth charts shown  to us with more than one parameter every time.  681 01:15:28,620 --> 01:15:36,780 And that's simple, and I think it's doable. And  I've worked with medical record companies both   682 01:15:37,440 --> 01:15:49,320 as a provider of a growth chart and also as a, a  user in the system. And they, talking with them,   683 01:15:49,320 --> 01:15:55,080 they can do these kind of things, but they say,  they, they often say they can't, but they   684 01:15:55,080 --> 01:15:59,700 can, you know, they can do that. And that's a  simple thing. And we already have the intelligence   685 01:16:00,240 --> 01:16:05,340 to do that. And it might mean, you know, the  growth chart will be smaller, but you could   686 01:16:05,340 --> 01:16:14,100 see the whole thing. I think that that really  should be step one for pediatrics to, because   687 01:16:14,100 --> 01:16:20,100 if you're not looking at the growth pattern, then  what are you doing? You know, step one,   688 01:16:21,060 --> 01:16:26,400 Dr. Becker talked about it. Dr. Corkins talked about, you know, the importance of   689 01:16:27,960 --> 01:16:36,300 looking at some of these things. And I think that  should be step one is that everybody contact their   690 01:16:36,300 --> 01:16:46,260 representative for their EMR in their hospital and  say, we want to see, you know, two or three growth   691 01:16:46,260 --> 01:16:52,080 parameters at a time. And if there is enough  request, I think the companies will, will bend   692 01:16:52,080 --> 01:16:58,980 to it because they, they have been responding  by putting growth charts into their system.  693 01:16:58,980 --> 01:17:02,812 So, anyway, that that would be my suggestion,  number one. 694 01:17:02,812 --> 01:17:10,750 DR. NILESH MEHTA: Great comments. Great comments. I think I'm obviously conscious that I've dragged  you longer than you were slated to, but there   695 01:17:10,750 --> 01:17:16,080 is a lot of important information that you've  imparted, a lot of interesting discussion. It   696 01:17:16,080 --> 01:17:21,600 sounds like variability is the, is the theme right  now, both in adult and pediatrics in this concept   697 01:17:21,600 --> 01:17:29,520 of how do we address or even diagnose or detect  malnutrition. The vendor piece that you have all   698 01:17:29,520 --> 01:17:35,580 alluded to is very relevant and I think together  we might have a voice to try and influence some   699 01:17:35,580 --> 01:17:41,820 of that. And then it comes to the validity of  these. And when we talk about validation, we are   700 01:17:41,820 --> 01:17:47,760 interested in important outcomes. No longer are  hospital outcomes enough both in the community and   701 01:17:47,760 --> 01:17:54,420 in hospital. The longer term outcomes, functional  outcomes that so many were alluded to by you. And,   702 01:17:54,420 --> 01:17:59,880 and that seems to be some of the take home  points. The question we are asking from   703 01:17:59,880 --> 01:18:04,320 these screening tools or diagnostic  tools as to what we want them to do.  704 01:18:04,320 --> 01:18:11,820 It's 18 past, I'm conscious that at 1:25 we start  the next session. So, I want to give you at least   705 01:18:11,820 --> 01:18:18,420 7 minutes to take a break. On behalf of Dr.  Rice and myself and Dr. Vargas and the entire   706 01:18:18,420 --> 01:18:27,480 ONR team at NIH, thank you to the speakers. I  really appreciate it. Your talks were concise,   707 01:18:27,480 --> 01:18:31,260 but stimulating. And thank you to all of  you who have joined almost close to 100   708 01:18:31,260 --> 01:18:38,280 folks online and enjoy the rest of the session.  See you at session number eight soon. Thank you. 709 01:18:38,280 --> 01:18:45,540 DR. GAIL CRESCI: Hello and welcome to Malnutrition in  Clinical Settings, Research Gaps and Opportunities   710 01:18:45,540 --> 01:18:53,100 for Early Life. This is Session eight on Early  Life Research Considerations. My name is Gail   711 01:18:53,100 --> 01:18:58,200 Cresci and I'm an associate professor at the  Cleveland Clinic, Lerner College of Medicine of   712 01:18:58,200 --> 01:19:04,620 Case Western Reserve University, and full staff in  the departments of Pediatric Gastroenterology and   713 01:19:04,620 --> 01:19:10,140 Information and Immunity at the Cleveland Clinic  in Cleveland, Ohio. I am also the immediate past   714 01:19:10,140 --> 01:19:16,200 president of the American Society for Parenteral  and Enteral Nutrition. I will be your moderator   715 01:19:16,200 --> 01:19:22,560 for this session. We have a phenomenal panel  of experts presenting on this topic today.   716 01:19:23,160 --> 01:19:27,960 For detailed information regarding their  backgrounds, please refer to the Speaker   717 01:19:27,960 --> 01:19:35,400 tab and the left hand column of this page, and you  can also go to the main page of the Labroots under   718 01:19:35,400 --> 01:19:43,440 the Speakers tab for their bios. This session is  broken into two parts with three segments. The   719 01:19:43,440 --> 01:19:50,040 first two segments will be presented in this Part  one. In segment one, we will hear about the unique   720 01:19:50,040 --> 01:19:57,960 challenges in early life research on malnutrition. Dr. Marie Revilla will discuss opportunities to   721 01:19:57,960 --> 01:20:02,400 address challenges in conducting  dietary assessment during infancy.   722 01:20:03,180 --> 01:20:08,640 Dr. Barbara Medoff-Cooper will address the  challenges of growth faltering after neonatal   723 01:20:08,640 --> 01:20:16,200 surgery for complex congenital heart disease  and Dr. Maureen Black will discuss complexities   724 01:20:16,200 --> 01:20:22,140 of children being dependent on food systems  and caregivers in research and malnutrition.   725 01:20:23,100 --> 01:20:29,400 We will then transition into the second session  when we will review a summary of evidence on   726 01:20:29,400 --> 01:20:35,820 malnutrition in early life. Lisa Moloney will  present on the Academy of Nutrition and Dietetics,   727 01:20:35,820 --> 01:20:42,660 Systematic Reviews and Practice Guidelines for  Pediatric Malnutrition and Dr. Sharon Irving will   728 01:20:42,660 --> 01:20:48,900 discuss Pediatric Malnutrition and the Research  Landscape with the use of the ASPEN guidelines.   729 01:20:49,800 --> 01:20:54,960 The presentations will be followed by a live  question and answer period with the speakers.   730 01:20:55,740 --> 01:21:01,200 During the session, we would like you to please  share your questions for the presenters in the   731 01:21:01,200 --> 01:21:06,780 chat box. We will try to address as many as  we can during the question and answer period.  732 01:21:07,920 --> 01:21:10,440 So without further ado, here we go. 733 01:21:17,700 --> 01:21:21,900 DR. MARIE KAINOA FIALKOWSKI REVILLA: (UNKNOWN)  Hello, everyone, Mahalo. Thank you for including   734 01:21:21,900 --> 01:21:27,000 me on this session focused on early life  malnutrition research organized by the National   735 01:21:27,000 --> 01:21:34,020 Institutes of Health. Before I begin, I would like  to also Mahalo or thank the amazing team of   736 01:21:34,020 --> 01:21:38,760 researchers spread across the United States and  Australia for their work in using technology   737 01:21:38,760 --> 01:21:46,080 to advance dietary assessment approaches. Listed  on this slide is my disclosures for you to view.   738 01:21:50,340 --> 01:21:56,100 Nutrition plays a significant role in the first  1,000 days of life, establishing the foundation   739 01:21:56,100 --> 01:22:01,620 for optimum health, growth and neurodevelopment  across the lifespan. In this presentation,   740 01:22:01,620 --> 01:22:09,420 we're going to focus specifically on the period  between birth and 12 months. Infant dietary   741 01:22:09,420 --> 01:22:14,160 assessment is essential for monitoring adequate  growth and development during this time period.   742 01:22:15,720 --> 01:22:21,900 However, as infants are unable to report for  themselves, it is a process reliant on surrogate   743 01:22:21,900 --> 01:22:27,480 reporters such as parents, grandparents and other  types of caregivers. There are significant burdens   744 01:22:27,480 --> 01:22:33,660 that surrogates face, including the amount of  time it takes to complete the assessment, having...not   745 01:22:33,660 --> 01:22:38,580 having the information on the details of food that  may have been prepared elsewhere, such as daycare,   746 01:22:39,300 --> 01:22:45,060 the potential bias in the types of foods that  surrogates may report, as well as the difficulty   747 01:22:45,060 --> 01:22:52,020 to ascertain the amount that was eaten because of  spillage or spit up as shown here on this image.  748 01:22:55,140 --> 01:23:00,120 It has been found that the weighted food  record provides the best estimate of energy,   749 01:23:00,120 --> 01:23:05,220 but note this poses a significant  amount of burden on surrogate reporters.   750 01:23:05,220 --> 01:23:09,600 The 24 hour dietary recall has also been  commonly done in the clinical setting,   751 01:23:09,600 --> 01:23:13,260 but it has been found to overestimate  energy and nutrient intake.   752 01:23:14,640 --> 01:23:19,260 So given those challenges, what opportunities  exist in technology to advance the field?   753 01:23:20,880 --> 01:23:26,040 The incorporation of technology as a dietary  assessment is an opportunity for the field as   754 01:23:26,040 --> 01:23:31,440 we know that smartphone adoption is widespread,  especially in adults of childbearing age.   755 01:23:33,540 --> 01:23:39,780 With that, there are, simply put, two ways in  which technology has been incorporated into   756 01:23:39,780 --> 01:23:45,600 dietary assessment for infants. The first is  with images and the second is with automation.   757 01:23:46,620 --> 01:23:52,080 In regards to images, there are two approaches.  The first is having images assist a traditional method   758 01:23:52,080 --> 01:23:57,480 of dietary assessment, and the second is with  images serving as the dietary assessment method.   759 01:23:58,440 --> 01:24:01,860 Let's first examine image assisted methods.   760 01:24:05,160 --> 01:24:11,940 A study by Johansson et al in 22 healthy infants  in Sweden compared the energy estimated using an   761 01:24:11,940 --> 01:24:17,940 image assisted record with regular food records. These estimates were also compared to total energy   762 01:24:17,940 --> 01:24:25,860 expenditure determined by doubly labeled water.  They had 38 reporters complete a five day record   763 01:24:25,860 --> 01:24:32,160 in which two main meals included before and  after images of the infant's food. These images   764 01:24:32,160 --> 01:24:37,860 were taken on a standardized plate and emailed to  researchers directly from the participants phone.   765 01:24:40,140 --> 01:24:45,240 What they found was that estimated energy  intake did not differ significantly between   766 01:24:45,240 --> 01:24:51,420 image assisted records and regular records. The  main difference in energy intake estimated from   767 01:24:51,420 --> 01:24:56,820 food records with the active images substance  and metabolizable energy calculated from doubly   768 01:24:56,820 --> 01:25:04,680 labeled water was about 366 kilojoules, which  translates to about a 10% overestimation. This   769 01:25:04,680 --> 01:25:08,160 is a little bit on the high side, but  within range of what has been found in   770 01:25:08,160 --> 01:25:15,600 other validation studies. However, there are  limits of agreement were narrower. However,   771 01:25:15,600 --> 01:25:20,520 some notable points to make is that this study  did not use image assistance for all meals and   772 01:25:20,520 --> 01:25:28,020 snacks due to concerns regarding surrogate burden. There was also the subjectivity of the devices in   773 01:25:28,020 --> 01:25:32,760 regards to lighting and angles that may have  influenced the ability to evaluate the images   774 01:25:32,760 --> 01:25:40,800 submitted. At the end of the article, the authors  commented that a mobile phone application would   775 01:25:40,800 --> 01:25:47,040 have improved the quality of data collected.  So this segues us nicely into the following   776 01:25:47,040 --> 01:25:52,560 approach to doing dietary assessment using  images, which is the image based approach.   777 01:25:53,700 --> 01:25:59,880 This approach was used in a feasibility study of  the mobile food record in 70 infants in Hawaii.   778 01:26:01,800 --> 01:26:06,300 The mobile food record is a part of the  technology Assisted Dietary Assessment,   779 01:26:06,300 --> 01:26:13,440 Technology Assisted Dietary Assessment System  or TADA. The mobile food record has been used   780 01:26:13,440 --> 01:26:21,360 almost across the entire lifespan. The advantages  of the mobile food record is that it provides easy   781 01:26:21,360 --> 01:26:27,300 access to dietary intake data, such as energy,  nutrients, food groups or dietary patterns. It   782 01:26:27,300 --> 01:26:32,580 also provides the context of eating such as on  a highchair table shown in the before image.   783 01:26:32,580 --> 01:26:38,820 It can give you a location via GPS, a date  and [inaudible] time stamp for beginning and eating   784 01:26:38,820 --> 01:26:43,440 occasions which provides duration of eating. And in addition, it can provide you food   785 01:26:43,440 --> 01:26:47,100 waste as to what you can see on the  after image of the food on the floor.   786 01:26:50,160 --> 01:26:55,020 The mobile food record used in this  feasibility, in this feasibility study   787 01:26:55,020 --> 01:27:00,420 was designed specifically for use in infant.  There was a before and after eating image   788 01:27:00,420 --> 01:27:08,580 button with infant appropriate icon as well as a  timer used to capture a breastfeeding duration.   789 01:27:12,180 --> 01:27:17,040 Surrogate reporters were instructed  to take before and after images of   790 01:27:17,040 --> 01:27:20,880 their infants' meals, which included this  additional marker which is the square   791 01:27:20,880 --> 01:27:26,880 checkerboard that you see in the bottom  images to help with image evaluation.   792 01:27:29,760 --> 01:27:37,020 What we found was that over 90% of surrogate  reporters found the mFR easier to use And   793 01:27:37,020 --> 01:27:41,460 over three quarters of participants found the  mFR enjoyable to use and would use it again.   794 01:27:42,900 --> 01:27:49,800 Feedback received from the mFR center on the  ease of its use and its user friendly nature.   795 01:27:55,200 --> 01:28:01,140 Surrogate reporters were easily able to capture  their infant meals, including the packaged one.   796 01:28:04,140 --> 01:28:08,040 Surrogates also commented  on the ability to complete   797 01:28:08,040 --> 01:28:12,360 their assessments with the mFR being  much easier than writing things down.  798 01:28:12,360 --> 01:28:17,160 And it was easy to go wherever they went  because their phone was always with them.   799 01:28:17,160 --> 01:28:23,220 As you can see here, the images submitted by  a surrogate reporter of an outing to Costco.   800 01:28:28,080 --> 01:28:32,160 The other unique feature was  the transferability of the mFR   801 01:28:32,160 --> 01:28:36,900 to other caregivers, as reflected in this  comment where the app was downloaded onto   802 01:28:36,900 --> 01:28:43,020 the grandparents' device so they may  record the infant participants intake.   803 01:28:45,060 --> 01:28:51,300 As a result of this feasibility study, additional  innovations for add to the mobile food report   804 01:28:51,300 --> 01:28:58,080 such as the addition of a bottle button, the  accessibility across more types of devices,   805 01:28:58,080 --> 01:29:03,420 and the incorporation of food annotation  and images that will soon become automated.   806 01:29:07,920 --> 01:29:11,280 So the last approach to mentioned  is the automated approach.   807 01:29:12,180 --> 01:29:19,560 Specifically, the automated self-administered  24 hour or ASA24 dietary assessment tool is a   808 01:29:19,560 --> 01:29:25,140 free web based dietary assessment tool. The  ASA24 can do multiple automatically coded,   809 01:29:25,140 --> 01:29:31,800 self-administered, 24 hour vehicle and or  single or multiday food records. The ASA24 is   810 01:29:31,800 --> 01:29:39,540 also accessible using current mobile devices. In the just released 2022 edition, the ASA24   811 01:29:39,540 --> 01:29:45,300 now has an infant feeding option for meals and  snacks to make it easier for surrogate reporters   812 01:29:45,300 --> 01:29:51,300 to record the number of feedings especially early  on when feeding is frequent throughout the day.   813 01:29:54,720 --> 01:29:58,920 However, the field is still in need of  further innovation. The validation of   814 01:29:58,920 --> 01:30:03,600 these methods against biomarkers are needed,  as well as determining an appropriate method   815 01:30:03,600 --> 01:30:08,160 to estimate the contribution of  human milk intake within infants.   816 01:30:11,040 --> 01:30:15,180 Mahalo- Thank you for allowing me to  share this information with you today. 817 01:30:15,180 --> 01:30:20,040 DR. BARBARA MEDOFF-COOPER: Today, I'll  be addressing the Challenges of Growth   818 01:30:20,040 --> 01:30:24,240 Faltering after Neonatal Surgery for  Complex Congenital Heart Disease.   819 01:30:25,620 --> 01:30:31,740 I am the co-founder of the Neoneur LLC  and we've received funds from National   820 01:30:31,740 --> 01:30:34,800 Institute of Nursing Research and  Saving Tiny Hearts Foundation.   821 01:30:36,300 --> 01:30:41,760 Growth faltering is a major concern for infants  with complex CHD. During this presentation,   822 01:30:41,760 --> 01:30:46,440 topics will include a definition of  growth faltering, factors contributing   823 01:30:46,440 --> 01:30:51,180 to growth faltering, the role of feeding  difficulties, and then some of the challenges.   824 01:30:54,000 --> 01:30:58,020 There are many terms used in the literature  to describe an infant who does not exhibit   825 01:30:58,680 --> 01:31:03,840 the expected growth trajectory, their growth  faltering, growth failure, failure to thrive   826 01:31:04,680 --> 01:31:09,960 and of course malnutrition. In this graph, we  see a typical example of Weight for Age Z score,   827 01:31:09,960 --> 01:31:15,900 it's decreasing across to 2% tabs which  is one definition of growth failure.   828 01:31:16,800 --> 01:31:21,660 My work we use the definition of  Weight for Age Z score of less than -2.   829 01:31:24,520 --> 01:31:29,040 Infants with complex CHD are usually born  full term, and within normal weight ranges.  830 01:31:29,040 --> 01:31:35,040 Nutritional issues often emerge shortly after  surgery, and often persist throughout the first   831 01:31:35,040 --> 01:31:41,340 years of life. 20%-50% of infants are at risk  for vocal cord paralysis, it's often related   832 01:31:41,340 --> 01:31:46,860 the type of surgery and the growth failure is  associated with an array of health problems.   833 01:31:48,180 --> 01:31:51,720 There are both short term and long term  consequences of growth faltering or   834 01:31:51,720 --> 01:31:57,660 (UNKNOWN) failure. Short term includes prolonged  length of stay, readmissions and oral aversion.   835 01:31:58,260 --> 01:32:05,640 Long term includes poor growth, about 20%-30% of  infants will have delayed motor and or cognitive   836 01:32:05,640 --> 01:32:12,060 skills as well as behavioral problems. And the  behavior problems include both ADHD and autism.   837 01:32:12,840 --> 01:32:17,160 We do know also that decrease in  Weight for Age Z score of more   838 01:32:17,160 --> 01:32:22,080 than 0.67 is strongly associated with  mortality during the first year of life.   839 01:32:23,820 --> 01:32:28,020 These are just some of the factors have been  hypothesized as contributing to growth faltering.   840 01:32:28,020 --> 01:32:35,040 Depending on the publication list may vary. The  true challenge is how to address these issues. For   841 01:32:35,040 --> 01:32:42,480 infants with the most complex CHD, 89% are risk  for failing to meet CDC standards for adequate   842 01:32:42,480 --> 01:32:48,900 growth at some point in the first year of life. These are data from one of my studies,   843 01:32:48,900 --> 01:32:56,340 the mean Weight for Age Z score change from surgery  discharge was -1.5 for all the infants,   844 01:32:56,340 --> 01:33:05,340 but the infants with most complex CHD given the  HLHS if it was -1.7. Orally fed infants do   845 01:33:05,340 --> 01:33:10,140 better than infants that were supported with  a feeding tube. I think the histogram clearly   846 01:33:10,140 --> 01:33:17,331 demonstrates a shift to the left in Weight for Age  Z Score. To orient the slide, the x axis represents Z   847 01:33:17,331 --> 01:33:23,940 scores and the y axis frequency. You can see  at the top histogram that there was a normal   848 01:33:23,940 --> 01:33:31,920 distribution Weight for Age Z score at birth. At  surgery, not much of a change, but by 22 days,   849 01:33:31,920 --> 01:33:40,140 you see that median Weight for Age Z score was -2.  And so that was a significant shift to the left.   850 01:33:41,640 --> 01:33:49,140 Publications for a wide array of cardiac centers  have validated our findings. The discharge, 50% of   851 01:33:49,140 --> 01:33:55,380 infants continued to be dependent to some degree  of tube feedings. The discharge protocols varies.   852 01:33:55,380 --> 01:34:00,540 However, some infants, sent infants home with  feeding tubes and teach parents how to reinsert   853 01:34:00,540 --> 01:34:06,120 them. Others sent infants home with feeding  tubes, but the parents have to bring the babies   854 01:34:06,120 --> 01:34:11,940 back to the ER to have the feeding tube inserted. Other centers sent babies home with gastric   855 01:34:11,940 --> 01:34:16,860 tubes and other centers just keep the babies  in the hospital until they can get the oral feed.   856 01:34:17,640 --> 01:34:22,680 We do know the longer an infant is tube  fed, the more difficult is to wean them. And   857 01:34:22,680 --> 01:34:29,880 there are concerns about potential link between  prolonged tube feeding and speech. Research has   858 01:34:29,880 --> 01:34:34,380 confirmed that there is an association between  neurologic compromise and poor feeding skills.   859 01:34:35,100 --> 01:34:40,320 From imaging studies, we have come to realize  that full term infants with the most complex   860 01:34:40,320 --> 01:34:45,600 defects are more likely to have brain development  that looks more like an infant born 35 weeks.   861 01:34:46,380 --> 01:34:54,540 To complicate the picture, both periventricular  leukomalacia and strokes are often present   862 01:34:54,540 --> 01:35:01,740 before and during and after surgery. What is not  associated with feeding disorders is birth weight,   863 01:35:01,740 --> 01:35:08,640 gestational age, preoperative, hemodynamics, and  environmental factors. Environmental factors   864 01:35:08,640 --> 01:35:16,620 include age of mother, number of older siblings,  and parental education. Safe feeding is not   865 01:35:16,620 --> 01:35:21,360 about buying, but about the coordination  of sucking and swallowing and breathing.  866 01:35:21,360 --> 01:35:27,000 The ability to achieve full oral feeding is  the most significant factor associated with   867 01:35:27,000 --> 01:35:33,060 developmental outcomes. I don't want us to forget  the fact that we have a newborn who has undergone   868 01:35:33,060 --> 01:35:39,120 open heart surgery. This is a major insult,  this tiny being. Stabilization of physiologic   869 01:35:39,120 --> 01:35:45,540 systems needs to be take place. Many systems have  been impacted by the surgery, including the GI   870 01:35:45,540 --> 01:35:51,180 system. And on top of that, we give the infants  plenty of pain medications, which decreases the   871 01:35:51,180 --> 01:35:57,120 infant's ability to achieve an alert behavioral  state which is needed for effective oral feeding.   872 01:35:57,120 --> 01:36:00,600 And we have to remember that this is an  infant, they are still recovering from the   873 01:36:00,600 --> 01:36:04,380 birthing process. It's no wonder  that feeding is a major concern.   874 01:36:07,800 --> 01:36:13,260 Feeding protocols appear to be an important  element in the fight to ameliorate GF.   875 01:36:14,040 --> 01:36:19,620 This is a graphic representation of pediatric  acute care cardiology collaborative pathway   876 01:36:19,620 --> 01:36:26,460 that is being used in participating cardiac  centers. This does not preclude the 150 pediatric   877 01:36:26,460 --> 01:36:34,260 cardiac centers in developing their own pathways. As of 2021, only living clinical pathways have   878 01:36:34,260 --> 01:36:38,460 been published, nine with positive outcomes.  But we know there are many more out there   879 01:36:39,060 --> 01:36:44,580 including the pathway that's been developed at  the Children's Hospital Philadelphia, my home   880 01:36:44,580 --> 01:36:51,240 institution. Developing a clinical pathway is  not for the faint of heart, convincing a full care   881 01:36:51,240 --> 01:36:57,300 team which was multidisciplinary that all infants  should have both pre and post operative parenteral   882 01:36:57,300 --> 01:37:03,840 nutrition was the first challenge I should say,  battle. The next battle was trying to convince   883 01:37:03,840 --> 01:37:10,260 everyone that we needed to have feeding tubes  placed in every baby immediately after surgery.   884 01:37:11,220 --> 01:37:16,680 But other elements were easy to incorporate,  enteral feeding readiness assessments,   885 01:37:17,700 --> 01:37:23,460 promotion of human milk especially considerations  for breastfeeding and fortification guidelines,   886 01:37:23,460 --> 01:37:30,900 infant driven feeding practices and feeding  tolerance evaluations recommended by the SLPs.   887 01:37:34,080 --> 01:37:39,420 Feeding assessments are crucial and should  be part of every feeding protocol. There are   888 01:37:39,420 --> 01:37:43,920 various ways to make these assessments clearly  the bedside nurse and the parents are always   889 01:37:43,920 --> 01:37:50,100 making assessments of how an infant is feeding. For centers with dedicated SLPs with speech and   890 01:37:50,100 --> 01:37:58,620 language pathologist, frequent evaluations need to  be routine. A tool used by some SLPs is the NOMAS   891 01:37:58,620 --> 01:38:05,160 which is the Neonatal Oral Motor Assessment Scale.  This is an observation tool that can be subjected   892 01:38:05,160 --> 01:38:11,340 to interrater reliability issues, but has been  used in research. In my work, we've been using a   893 01:38:11,340 --> 01:38:16,800 feeding device which allows us to see the pattern  of sucking and tracking behaviors over time.   894 01:38:18,900 --> 01:38:24,060 The organization of feeding can serve as a proxy  for an infant central nervous system integrity.   895 01:38:24,060 --> 01:38:28,680 We look at the length of sucking bursts,  type an infant needs to recover from one   896 01:38:28,680 --> 01:38:32,340 burst and start sucking again which  we believe is a measure of fatigue.   897 01:38:33,060 --> 01:38:39,480 And you can see these two different of traces.  On the left, we have an infant that's fairly   898 01:38:39,480 --> 01:38:46,740 disorganized or I should say very disorganized, we  have few sucks, low pause, and few more sucks. If   899 01:38:46,740 --> 01:38:52,160 we look at the whole trace, we can see this baby's  not ready for full oral feeding. On the right,   900 01:38:52,160 --> 01:38:58,620 is a baby that's organized, is ready for full oral  feeding, it is not already on oral for feeding.  901 01:38:59,580 --> 01:39:04,200 And then we track them over time we'll see  that again we'll have further improvement.   902 01:39:09,000 --> 01:39:15,420 So just a reminder that addressing growth  faltering does not stop at discharge. Rather,   903 01:39:15,420 --> 01:39:18,120 the challenge continues sometimes  for months and for years.   904 01:39:18,960 --> 01:39:24,060 We need to increase a coordination with  particular attention to feeding, virtual   905 01:39:24,060 --> 01:39:29,220 home visits for feeding management, something  that I did for five years we'll open it another   906 01:39:29,220 --> 01:39:34,320 study from an NINR and we found that it  made a big difference the way parents were   907 01:39:34,320 --> 01:39:40,020 managing families, the babies in comorbidity  management assisting families in managing   908 01:39:40,020 --> 01:39:45,480 multiple visits and coordination between  primary care and cardiology and speech.   909 01:39:47,940 --> 01:39:52,860 So in summary, growth faltering has serious  consequences. Adherence to feeding protocol   910 01:39:52,860 --> 01:39:59,220 appears to ameliorate some loss in the Weight for  Age Z score, the attention to feeding skills is   911 01:39:59,220 --> 01:40:02,520 an essential component and interesting  growth faltering. Thank you very much. 912 01:40:02,520 --> 01:40:08,760 DR. MAUREEN BLACK: Greetings. My name is  Maureen Black, and I have been asked to   913 01:40:08,760 --> 01:40:15,960 discuss the Complexities of Children Being  Dependent on Food Systems and Caregivers in   914 01:40:15,960 --> 01:40:23,400 Research on Malnutrition. The operative word  is malnutrition which may include underweight,   915 01:40:23,400 --> 01:40:30,120 overweight, or nutritional deficiencies such  as micronutrient deficiencies, not getting   916 01:40:30,120 --> 01:40:38,640 the recommended amount of specific nutrients. To  address the role of food systems and caregivers,   917 01:40:38,640 --> 01:40:46,560 we turn to nutritional ecology, what is  nutritional ecology? Nutritional ecology   918 01:40:46,560 --> 01:40:53,040 represents the interactions between children  and environments. This is how it works.   919 01:40:53,880 --> 01:41:01,740 Children are complex internal biological systems  that grow from conception through infancy,   920 01:41:01,740 --> 01:41:11,040 childhood and adolescence. The environment, the  rest of it represents complex external systems,   921 01:41:11,040 --> 01:41:17,760 such as climate, geopolitical,  social, food, home, and so on.   922 01:41:19,860 --> 01:41:28,140 And food systems refer to the acquisition of food,  it could be growing food, getting milk from cows,   923 01:41:28,140 --> 01:41:35,700 plus processing and making food available.  Caregivers are part of a family system,   924 01:41:35,700 --> 01:41:40,740 and are the final common pathway  in interactions with children.  925 01:41:42,120 --> 01:41:49,620 Now the distal environment has a major impact  on food systems. For example, if the climate is   926 01:41:49,620 --> 01:41:59,700 too hot or dry, growing could be disrupted. If  the event of a conflict, such as the conflict in   927 01:41:59,700 --> 01:42:09,960 Ukraine could disrupt the distribution of food,  or policies may dry up, drive up food prices.   928 01:42:10,920 --> 01:42:17,640 Food Systems have a major impact on getting food  to children and families through food availability   929 01:42:17,640 --> 01:42:25,320 such as in stores, accessibility, the ability to  get to the store, affordability, the ability to   930 01:42:25,320 --> 01:42:30,600 pay for the food, and then acceptability, food  that the family is able and willing to eat.   931 01:42:31,800 --> 01:42:38,940 Caregivers are part of families and many aspects  of family life influence food and play a role   932 01:42:38,940 --> 01:42:47,220 in malnutrition. Food Security refers to the  availability and access of enough food for a   933 01:42:47,220 --> 01:42:53,940 family to live an active lifestyle. Among many  children, food insecurity is invisible and not   934 01:42:53,940 --> 01:43:01,500 associated with underweight or overweight, but it  may be associated with poor health and development   935 01:43:01,500 --> 01:43:10,140 and micronutrient deficiencies. Services such as  SNAP and school feeding programs can assist   936 01:43:10,140 --> 01:43:19,200 families and children and prevent food insecurity. Material hardships, primarily represented by   937 01:43:19,200 --> 01:43:25,260 poverty pose a major threat to malnutrition.  Families may have difficult choices to make,   938 01:43:25,260 --> 01:43:37,380 eat or eat. Nutrition security and nutrition  insecurity refers to foods that are needed in   939 01:43:37,380 --> 01:43:43,560 terms to support health essential nutrients. The  lack of these nutrients could lead to specific   940 01:43:43,560 --> 01:43:52,500 nutritional deficiencies. Food skills are another  aspect of nutritional ecology that are important   941 01:43:52,500 --> 01:43:59,100 to consider. Caregivers who lack preparation  skills are more likely to rely on heavily   942 01:43:59,100 --> 01:44:08,220 processed foods that may be low in nutrients, and  thus increase the likelihood for malnutrition.   943 01:44:09,000 --> 01:44:16,020 How food is used in a family is critically  important beyond response to hunger and   944 01:44:16,020 --> 01:44:23,940 provision of nutrients and in celebratory occasions.  When food is used to manage behavior or emotions,   945 01:44:23,940 --> 01:44:35,820 it can increase the risk for malnutrition, and  for eating disorders. Daily routines and chaos can   946 01:44:35,820 --> 01:44:42,720 have an impact on children's nutrition. The daily  routines will help children gauge their eating   947 01:44:42,720 --> 01:44:50,220 but without a mealtime structure, children are  likely to snack, often consuming food with little   948 01:44:50,220 --> 01:45:00,540 nutritional value and a risk of malnutrition. So, food parenting then refers to the interaction   949 01:45:00,540 --> 01:45:06,360 between children and caregivers' around  food, often focused on issues of control   950 01:45:06,360 --> 01:45:14,160 and caregivers response to children. This is a  closer look at food parenting. This conceptual   951 01:45:14,160 --> 01:45:21,960 map was developed by Vaughn and colleagues.  You can see coercive control includes behaviors   952 01:45:21,960 --> 01:45:28,920 such as pressuring the child to eat more, or  restricting the child's food choices. Structure   953 01:45:28,920 --> 01:45:36,540 refers to modeling and mealtime structure. And  autonomy refers to the child gaining independence   954 01:45:37,380 --> 01:45:46,140 in eating. A graduate student and I validated  this conceptual model using the comprehensive   955 01:45:46,140 --> 01:45:53,760 feeding practices questionnaire with mothers of  preschoolers. We identified three patterns as   956 01:45:53,760 --> 01:46:03,480 you can see. The most prevalent was controlling,  that's the gray pattern that was high in coercive   957 01:46:03,480 --> 01:46:10,920 control, and low in structure and autonomy.  However, we identified the other two patterns   958 01:46:10,920 --> 01:46:18,120 balancing and regulating that were high in  structure and autonomy. What we found is that the   959 01:46:18,120 --> 01:46:25,500 regulating pattern was associated with lower BMI  in preschoolers than the controlling pattern was.  960 01:46:26,040 --> 01:46:33,000 But we see that food systems and caregivers  play important roles in the nutritional   961 01:46:33,000 --> 01:46:39,420 ecology of malnutrition. They can certainly  influence children's nutritional status,   962 01:46:39,420 --> 01:46:45,000 so that's malnutrition, but they can also  influence children's health both chronic   963 01:46:45,000 --> 01:46:51,120 conditions as well as acute or infectious  conditions. It can influence dietary choice,   964 01:46:51,120 --> 01:46:58,080 it can influence eating attitudes, and then  they can also influence physical activity,   965 01:46:58,080 --> 01:47:04,200 children's school performance, cognition,  socioemotional development and mental health.   966 01:47:04,800 --> 01:47:12,960 So nutritional ecology, can play an important role  in children's development beyond only looking at   967 01:47:12,960 --> 01:47:20,760 malnutrition. But if we think about malnutrition,  we see that the research requires a comprehensive   968 01:47:20,760 --> 01:47:29,040 assessment of children's nutritional ecology  including both distal and proximal components   969 01:47:29,040 --> 01:47:36,780 such as the food system, and the household and  family. In order to do this research needs to be   970 01:47:36,780 --> 01:47:48,000 driven by at a theoretical model that hypothesizes  the pathways linking the systems. So there are   971 01:47:48,000 --> 01:47:55,080 many research gaps related to malnutrition and  related to incorporating the nutritional ecology.  972 01:47:55,080 --> 01:48:02,280 We'll give an example. So an example may  be does the school feeding program protect   973 01:48:02,280 --> 01:48:09,120 against malnutrition in communities with low  food access? Well, this portrays children   974 01:48:09,120 --> 01:48:16,980 and we can evaluate their nutritional status. And  if we look at the response to the school program,   975 01:48:16,980 --> 01:48:22,440 we will find that some children are doing  well, some children are doing better than   976 01:48:22,440 --> 01:48:28,500 other children. But looking at this alone is  really a very incomplete picture, recognizing   977 01:48:28,500 --> 01:48:34,440 what we now know about nutritional ecology. So  we need a broader picture. So we start again   978 01:48:34,440 --> 01:48:41,040 with the children. And maybe this time we look at  the caregiver and the caregiver's interaction with   979 01:48:41,040 --> 01:48:47,040 the child, some of those feeding patterns as well  as availability of food in the household. So we   980 01:48:47,040 --> 01:48:53,640 look at the family, and again, the availability  of food and some of the feeding practices. And   981 01:48:53,640 --> 01:48:59,760 then we think maybe we should consider the food  systems, what is the availability of food within   982 01:48:59,760 --> 01:49:05,460 the community and how is that related to the  family? Do they have the resources to acquire   983 01:49:05,460 --> 01:49:12,480 the food, and then we might look at the climate. Again, is it, is the climate impacting the systems   984 01:49:12,480 --> 01:49:20,340 that's impacting that family and the caregiver?  Now, when we look at the school feeding programs,   985 01:49:20,340 --> 01:49:26,700 we can look at whether there's a moderating effect  or whether the school feeding programs then can   986 01:49:26,700 --> 01:49:32,820 protect the child from some of the challenges  that may be happening at the caregiver level.   987 01:49:33,720 --> 01:49:38,940 So in conclusion, we know that we need  to look at the food ecology to understand   988 01:49:38,940 --> 01:49:51,480 malnutrition and other aspects of children's  development. And OK, and I would like to end   989 01:49:51,480 --> 01:49:58,080 by thanking the colleagues that I'm working  with, and an NICHD sponsored program called   990 01:49:58,080 --> 01:50:07,800 BOND-KIDS. We're focused on the environmental  aspect. BOND-KIDS stands for Biological Origins   991 01:50:07,800 --> 01:50:13,620 of Nutrition and Diet, Knowledge Indicating  Dietary Sufficiency. Thank you very much. 992 01:50:13,620 --> 01:50:21,180 DR. SHARON Y IRVING: Hello, and thank you to the  organizing committee for inviting me to be a part   993 01:50:21,180 --> 01:50:26,220 of this workshop. My name is Sharon Irving,  and I will talk to you today about pediatric   994 01:50:26,220 --> 01:50:32,580 malnutrition, the research landscape, where are  we, what are we learned, all in relation to the use   995 01:50:32,580 --> 01:50:39,780 of the ASPEN guidelines. I have no financial  disclosures pertinent to this presentation.   996 01:50:41,880 --> 01:50:48,660 The guidelines that I'm going to discuss are  those that were published in 2017 between the   997 01:50:48,660 --> 01:50:53,340 Society of Critical Care Medicine and the American  Society for parenteral and enteral nutrition.   998 01:50:53,940 --> 01:50:59,340 This publication marked the first collaboration  of these two very large important organizations   999 01:50:59,340 --> 01:51:05,400 on to discuss nutrition therapy for  critically ill children. It is not the   1000 01:51:05,400 --> 01:51:11,400 first guidelines that were published for this  population as that occurred in 2009. However,   1001 01:51:11,400 --> 01:51:17,580 it was the first time for these two organizations.  The target population was truly that pediatric   1002 01:51:17,580 --> 01:51:22,380 population of greater than one month and  less than or equal to 18 years of age.   1003 01:51:23,760 --> 01:51:29,280 They also had to have a presumed intensive  care stay of greater than two days.  1004 01:51:31,680 --> 01:51:36,480 Since its publication which was done both  in the Journal of parenteral and enteral   1005 01:51:36,480 --> 01:51:43,260 nutrition and pediatric critical care  medicine, those two publications, these   1006 01:51:43,260 --> 01:51:50,580 guidelines have enjoyed more than 225 citations  worldwide. And when I say worldwide, the global   1007 01:51:50,580 --> 01:51:55,500 reach of these guidelines has been European  countries, countries on the African continent,   1008 01:51:56,100 --> 01:52:01,200 throughout the Middle East, Central and  South America, East Asia and Australia.   1009 01:52:04,440 --> 01:52:10,020 When we talk about pediatric malnutrition, and  I know my colleague, Dr. Corkins has talked about   1010 01:52:10,020 --> 01:52:15,120 this earlier today, we need to truly understand  what we're talking about. And so I'm just going to  1011 01:52:15,120 --> 01:52:22,020 quickly summarize here what I am talking about  in terms of this. It's that imbalance that occurs   1012 01:52:22,020 --> 01:52:29,460 between nutrient intake and requirement and  that imbalance so it results in deficiencies   1013 01:52:29,460 --> 01:52:38,520 or excesses, excesses in energy, protein, or  micronutrients that encompass the underweight,   1014 01:52:38,520 --> 01:52:43,620 the overweight and micronutrient deficiencies.  And that definition that I've provided for   1015 01:52:43,620 --> 01:52:48,360 you here is a combination of the one from  ASPEN and from World Health Organization.  1016 01:52:49,020 --> 01:52:53,640 So when we go back to the guidelines, we  have to look at what impact does nutrition   1017 01:52:53,640 --> 01:52:59,880 status have on outcomes in these children?  And what are the best practices to screen   1018 01:52:59,880 --> 01:53:06,900 and identify those patients most at risk? So  then, of course, you go to the literature.   1019 01:53:08,520 --> 01:53:13,800 So I looked at systematic reviews. The first  one I will present for you here is by Toh and   1020 01:53:13,800 --> 01:53:19,620 colleagues and it's looking at the association  between admission body mass index and outcomes   1021 01:53:19,620 --> 01:53:25,860 in this population. They define nutrition status  which I have for you here. Their overall aim was   1022 01:53:25,860 --> 01:53:31,260 to compare the outcomes that are typical when  you look at this population of critically ill   1023 01:53:31,260 --> 01:53:36,480 children. And that is mortality, their length of  stay, their duration of mechanical ventilation,   1024 01:53:36,480 --> 01:53:42,960 and they based it all on nutrition status as  they had defined it. Their primary outcome was   1025 01:53:42,960 --> 01:53:49,620 mortality. They looked across randomized  control trials, retro and prospective   1026 01:53:49,620 --> 01:53:56,660 observational studies, and their population was  less than 18 years of age with a PICU admission. 1027 01:53:56,660 --> 01:54:03,120 They reviewed 20 studies, only one  of which was a randomized controlled trial.   1028 01:54:03,120 --> 01:54:07,740 The studies were across income categories  and were mixed patient populations.   1029 01:54:08,940 --> 01:54:16,800 What did they find? Underweight and obese patients  did not have increased risk of mortality. They had   1030 01:54:16,800 --> 01:54:22,620 no difference in mechanical ventilation, length  of stay across the weight categories by either   1031 01:54:22,620 --> 01:54:30,300 Z score or percentiles. However, in studies  that use BMI Z scores, there was an increased   1032 01:54:30,300 --> 01:54:36,060 risk of mortality in the underweight patients.  They did find an increased length of stay for   1033 01:54:36,060 --> 01:54:41,520 these underweight patients and also for the  overweight or the obese patient. They had to   1034 01:54:41,520 --> 01:54:48,840 do a sensitivity analysis in this systematic  review and meta-analysis because of mixed PICU   1035 01:54:48,840 --> 01:54:53,460 populations in some of the studies. And they  want their results to be as clean as possible.   1036 01:54:53,460 --> 01:54:59,400 And they found that there was an increased odds  of mortality for underweight and overweight in   1037 01:54:59,400 --> 01:55:05,460 these mixed studies. And so what I've presented  for you here are two of their forest plots that   1038 01:55:05,460 --> 01:55:13,200 defining their or describing their results. In Fig. A, the underweight significantly   1039 01:55:13,200 --> 01:55:20,280 increased odds for mortality by these z scores,  but not so in using percentiles. Figure B in the   1040 01:55:20,280 --> 01:55:26,760 overweight and obese population did not have  significant differences in odds for mortality   1041 01:55:26,760 --> 01:55:36,600 with poor Z scores or percentiles. So what did  they conclude? They found no differences in   1042 01:55:36,600 --> 01:55:43,380 clinical outcomes comparing underweight, normal  or typical weight or overweight obese patients.   1043 01:55:44,160 --> 01:55:50,820 However, the studies that use BMI z-scores  demonstrated increased risk of mortality   1044 01:55:50,820 --> 01:55:57,240 in the underweight patients. They found  differences in classification of weight   1045 01:55:57,240 --> 01:56:03,000 categories and that different studies  used different growth reference standards.   1046 01:56:04,260 --> 01:56:09,780 They identified a need for standardization  of classification of nutrition status in the   1047 01:56:09,780 --> 01:56:16,080 critically ill child. And the methodology  was very heterogeneric across the studies.   1048 01:56:18,300 --> 01:56:24,180 So then, of course, you have to look at the  obese. And so in 2019, Alipoor and colleagues   1049 01:56:24,180 --> 01:56:30,780 published a systematic review with meta  analysis of the association of obesity with   1050 01:56:30,780 --> 01:56:36,540 morbidity and mortality in this population. They defined obesity as I have for you here.   1051 01:56:36,540 --> 01:56:45,120 Their primary aim was to examine the  association of obesity across outcomes   1052 01:56:45,120 --> 01:56:49,500 of interest in critically ill children.  They looked at observational studies,   1053 01:56:49,500 --> 01:56:56,460 prospective or retrospective. And mortality,  again, was their primary outcome. However, they   1054 01:56:56,460 --> 01:57:02,040 did identify secondary outcomes to include length  of stay and duration of mechanical ventilation.   1055 01:57:04,740 --> 01:57:10,920 What did they find? That obese children had  increased mortality. There was an increase of   1056 01:57:10,920 --> 01:57:16,080 hospital length of stay, there was a longer  duration that they needed to be mechanically   1057 01:57:16,080 --> 01:57:21,900 ventilated and therefore had a longer PICU  length of stay. They also identified   1058 01:57:21,900 --> 01:57:29,100 different cutoffs for the determination of obesity  and the presence of a mass amount of heterogeneity   1059 01:57:29,100 --> 01:57:36,900 between the studies and their findings, one  of the graphs that they had, their forest plot   1060 01:57:36,900 --> 01:57:44,700 I've put for you here demonstrates that the meta  analysis of the studies investigating mortality   1061 01:57:44,700 --> 01:57:50,880 showed that they had a lot of congruence  around the centrality of these studies.  1062 01:57:50,880 --> 01:57:57,000 But again, how things were  described was very heterogenetic.   1063 01:58:00,540 --> 01:58:06,180 So what about screening? What do we do with  that? So Ventura and colleagues published in 2022   1064 01:58:06,180 --> 01:58:11,400 screening tool, a nutritional screening tool for  critically ill children in a systematic review.   1065 01:58:12,300 --> 01:58:17,880 They defined screening tool as that what was  used to assess from malnutrition, risk of   1066 01:58:17,880 --> 01:58:24,060 undernutrition and the associated outcomes. Their  primary aim was the use of nutritional screening   1067 01:58:24,060 --> 01:58:31,020 tools in hospitalized children, and they focused  to see methodology of tool development, tool  1068 01:58:31,020 --> 01:58:37,860 application and tool validity. They had the same  targeted population of greater than one month and   1069 01:58:37,860 --> 01:58:44,460 less than 18 years of age. Their secondary aim was  relevance of the tool in critically ill children.   1070 01:58:45,540 --> 01:58:53,220 They found 103 studies and 25 of which were cohort  studies. Only three of the studies, however,   1071 01:58:53,220 --> 01:59:03,420 included PICU patients, and the validation of the  tools was performed on ten. So what did they find?   1072 01:59:03,420 --> 01:59:09,120 Two of the three studies successfully tested  prediction of nutrition status deterioration.  1073 01:59:10,500 --> 01:59:20,040 Only one of the three studies was able to  identify hospital length of stay. 91 of the   1074 01:59:20,040 --> 01:59:27,180 studies assessed one or more nutritional outcomes.  However, there was no standardization in what that   1075 01:59:27,180 --> 01:59:33,180 definition was. And in one of their charts that  I thought was of interest here, they identified   1076 01:59:33,180 --> 01:59:39,660 the variables that they looked at for screening  tools for nutritional outcomes, and they broke it   1077 01:59:39,660 --> 01:59:45,900 down into clinical nutrition status, laboratory,  and dietary intake. And what I thought was of   1078 01:59:45,900 --> 01:59:51,900 interest here is that only one study identified  severity of illness as a variable of interest.   1079 01:59:56,760 --> 02:00:03,660 Why does this matter and what is the importance?  Because we identify and we define malnutrition   1080 02:00:03,660 --> 02:00:09,060 based on anthropometric measures for the most part,  which I've shown you in both of these systematic   1081 02:00:09,060 --> 02:00:15,420 reviews, we have to take into consideration are  there differences in anthropometrics? And so I   1082 02:00:15,420 --> 02:00:20,460 will present for you now a couple of studies  that do define that. So Morisaki looked at   1083 02:00:20,460 --> 02:00:26,820 social and anthropometric factors across  races and ethnicity based on birth weight.  1084 02:00:27,840 --> 02:00:33,780 They looked at 14 different races and ethnicities  and they found that the average birth weight   1085 02:00:33,780 --> 02:00:42,180 differed by greater than 100g in most races, with  the exception of those that I've identified here.   1086 02:00:42,180 --> 02:00:50,820 Their z-score comparison by gestational age  of 34 to 41 weeks differed by 0.1 standard   1087 02:00:50,820 --> 02:00:59,100 deviations and again, with these exceptions. Once  they adjusted all factors that minimally change   1088 02:00:59,100 --> 02:01:05,460 birth weight discrepancy for Black infants, and  national birth weight reference charts that we   1089 02:01:05,460 --> 02:01:11,760 currently use may not be inclusive of all of  the races and ethnicities. Further exploration   1090 02:01:11,760 --> 02:01:19,800 of maternal characteristics may be necessary to  better explain variability of birth weight in U.S.   1091 02:01:19,800 --> 02:01:27,540 infants. So there is some discrepancy. Taking it  to an older population, Hawkes and colleagues in   1092 02:01:27,540 --> 02:01:33,120 2020 looked at sitting height to standing height  ratio reference charts for children in the US.   1093 02:01:33,120 --> 02:01:40,740 They used NHANES data and looked at more than  9,500 children with an aim to really develop   1094 02:01:40,740 --> 02:01:46,980 these reference charts for sitting height to  standing height ratio of children in the U.S.  1095 02:01:46,980 --> 02:01:51,420 Their age range was a little bit different than  all of the previous studies, and it was greater   1096 02:01:51,420 --> 02:01:58,380 than or equal to two years of age to less than 18  years of age. They looked at non-Hispanic Black,   1097 02:01:58,380 --> 02:02:06,060 non-Hispanic white, and Mexican-American as the  demographic ancestry of their populations. And in   1098 02:02:06,060 --> 02:02:12,660 the U.S., non-Hispanic Black children have a lower  sitting height to height ratio across all age   1099 02:02:12,660 --> 02:02:18,600 groups. And this is something for us to consider  in terms of interpretation of our anthropometric.   1100 02:02:20,460 --> 02:02:25,020 So when we go back to the guidelines and  malnutrition, the impact on the nutrition   1101 02:02:25,020 --> 02:02:30,000 status, how is that addressed? So we  found one randomized controlled trial   1102 02:02:30,000 --> 02:02:36,660 that there was a heterogeneity of measures and  classifications of nutrition status. However,   1103 02:02:36,660 --> 02:02:42,720 when we looked at BMI z-scores, it did identify  an increased risk of mortality in underweight   1104 02:02:42,720 --> 02:02:47,880 patients. When we look at best practices on  screening and nutritional status of these   1105 02:02:47,880 --> 02:02:54,240 children and who's at risk, the systematic review  of the screening tools found no standardization   1106 02:02:54,240 --> 02:02:59,100 of definition of nutritional outcomes. None were validated in critically ill children,   1107 02:02:59,100 --> 02:03:04,560 and the severity of illness is a factor to  consider. So where are we and what's missing?   1108 02:03:04,560 --> 02:03:10,182 We need to consider demographic ancestry and  anthropometric measurements. There are age   1109 02:03:10,182 --> 02:03:15,360 related differences that we also need to think  about. We need a uniform strategy for nutrition   1110 02:03:15,360 --> 02:03:22,320 status assessment that is applicable across all  populations of children from critically ill and   1111 02:03:22,320 --> 02:03:28,440 hospitalized children. We need to standardize our  definitions for nutritional outcomes. There's a   1112 02:03:28,440 --> 02:03:35,160 role of obesity in outcomes and all of the  associated corollaries, and we need to peel   1113 02:03:35,160 --> 02:03:41,580 back the onion on that. Reliable tools are needed  to predict risk of nutrition status deterioration.   1114 02:03:41,580 --> 02:03:48,120 We need to standardize our methods and measures  to monitor efficacy of nutrition therapy, and   1115 02:03:48,120 --> 02:03:54,960 the identification of novel biomarkers to track  status during critical illness is badly needed.   1116 02:03:55,620 --> 02:04:04,320 I thank you so...thank you so much. Here are a list  of references that I use for this presentation. I   1117 02:04:04,320 --> 02:04:06,960 appreciate your time and your attention. Thank you. 1118 02:04:06,960 --> 02:04:14,760 LISA MOLONEY: Hello, my name is Lisa Moloney  and I'm a nutrition researcher at the Academy of   1119 02:04:14,760 --> 02:04:19,200 Nutrition and Dietetics. Today I'll be discussing  the Academy's systematic reviews and practice   1120 02:04:19,200 --> 02:04:25,560 guidelines for pediatric malnutrition. I have no  conflicts of interest to disclose other than that   1121 02:04:25,560 --> 02:04:30,840 I am an employee of the Academy of Nutrition and  and Dietetics. So for today's learning objectives,   1122 02:04:30,840 --> 02:04:34,560 we will describe the evidence analysis  library, nutrition screening for pediatric   1123 02:04:34,560 --> 02:04:40,200 systematic reviews, validity and reliability of  nutrition screening tools for identifying risk of   1124 02:04:40,200 --> 02:04:45,960 malnutrition related to under or over nutrition  in the pediatric population, provide an overview   1125 02:04:45,960 --> 02:04:50,400 of the very low birth weight, preterm infant  evidence based nutrition practice guideline and   1126 02:04:50,400 --> 02:04:56,100 identify limitations in research, applications  to practice and areas for further research.   1127 02:04:58,740 --> 02:05:02,460 So the Academy follows a standard  process for conducting systematic   1128 02:05:02,460 --> 02:05:07,320 reviews. They are conducted by a panel of  volunteer experts. A systematic search is   1129 02:05:07,320 --> 02:05:12,840 conducted within multiple electronic databases. Each of the included articles are evaluated for   1130 02:05:12,840 --> 02:05:17,280 risk of bias, and we evaluate the certainty  of evidence following the grade process.   1131 02:05:17,280 --> 02:05:22,140 The guideline development process that is  also conducted by that same as our panel   1132 02:05:22,680 --> 02:05:26,700 will utilize the evidence and decision  framework that takes evidence, harms   1133 02:05:26,700 --> 02:05:31,260 benefits, cost and implementation factors into  consideration when developing the recommendation,   1134 02:05:31,260 --> 02:05:37,200 and each of our guidelines go for external review  with content experts who use the Agreed II tool.   1135 02:05:39,120 --> 02:05:44,400 So here is our malnutrition screening systematic  review team our volunteer panel members,   1136 02:05:44,400 --> 02:05:52,260 Project manager, Lead analyst, Medical Librarian,  Academy Staff and Evidence Analyst. Pediatric   1137 02:05:52,260 --> 02:05:58,080 malnutrition screening is a process to identify a  child under 18 years of age who is at nutritional   1138 02:05:58,080 --> 02:06:02,880 risk for a nutrition related problems and should be  referred to a dietitian or nutrition assessment.   1139 02:06:03,600 --> 02:06:08,580 Malnutrition screening may be conducted in  any practice setting. Tools should be quick,   1140 02:06:08,580 --> 02:06:15,420 easy to use, valid and reliable for the patient  population and setting, process and parameters   1141 02:06:15,420 --> 02:06:20,700 established by the institution should be developed  by a multidisciplinary team, including dietitians.  1142 02:06:21,240 --> 02:06:25,620 It should be performed by medical professionals  who have been trained in the screening process,   1143 02:06:25,620 --> 02:06:30,120 and screening should occur within a  designated appropriate time frame.   1144 02:06:33,540 --> 02:06:38,160 So what does it mean to say a tool is  valid? The ability of nutrition screening   1145 02:06:38,160 --> 02:06:42,720 tools to identify those at malnutrition  risk versus those who are not at risk.   1146 02:06:43,260 --> 02:06:47,100 Validity should compare the results of a  screening tool with a reference standard,   1147 02:06:47,700 --> 02:06:53,100 reference standards could include anthropometrics  at a given time or changes over time,   1148 02:06:53,100 --> 02:06:58,800 the Pediatric Subjective Global Nutrition  Assessment Tool or full dietitian assessment.   1149 02:07:00,540 --> 02:07:04,860 Seven tools for screening for malnutrition  risk in the in-patient hospital setting   1150 02:07:04,860 --> 02:07:10,020 were identified in the literature. STAMP,  STRONGkids, Pediatric Yorkhill Malnutrition   1151 02:07:10,020 --> 02:07:14,520 Score, a Pediatric Malnutrition Screening  Tool, the Pediatric Nutrition Screening Tool,   1152 02:07:14,520 --> 02:07:20,400 Pediatric Nutrition Risk Score, Integrated  Management of Childhood Screening, Pediatric   1153 02:07:20,400 --> 02:07:25,800 Digital Scale, Malnutrition Risk Screening Tool.  All tools except PeDiSMART had moderate validity,   1154 02:07:25,800 --> 02:07:31,440 STAMP had the oral highest quality evidence. No evidence meaning inclusion criteria was found   1155 02:07:31,440 --> 02:07:35,340 to evaluate the validity and reliability  of the PeDiSMART for identifying risk of   1156 02:07:35,340 --> 02:07:42,720 malnutrition related to under or over nutrition  in the pediatric population. Three tools were   1157 02:07:42,720 --> 02:07:48,600 designated for use in the community setting. The  Electronic Kids, E-KINDEX Nutrition Screening tool   1158 02:07:48,600 --> 02:07:55,680 for every preschooler NutriSTEP and the toddler  NutriSTEP. E-KINDEX, a NutriSTEP had low validity,   1159 02:07:55,680 --> 02:08:00,900 NutriSTEP that for toddlers had moderate validity.  Available evidence for all tools was limited.   1160 02:08:03,420 --> 02:08:07,980 Tools used to identify malnutrition risk should  be valid and reliable for the target population   1161 02:08:07,980 --> 02:08:13,860 and setting. While no screening tool can be 100%  accurate, pediatric nutrition screening tools   1162 02:08:13,860 --> 02:08:18,480 should have at least moderate to high validity  and reliability based on strong or fair evidence.   1163 02:08:19,140 --> 02:08:22,920 The systematic review concluded that  tools meeting this goal were STAMP,   1164 02:08:22,920 --> 02:08:27,060 STRONGkids and PYMS and the inpatient setting and   1165 02:08:27,060 --> 02:08:31,680 NRST CF in the specialty setting, though  none of these tools had high validity.  1166 02:08:35,640 --> 02:08:40,380 Limitation to these nutrition screening tools  include a few studies examining each tool,   1167 02:08:40,380 --> 02:08:45,960 heterogeneity among studies examining a common  tool and lack of tools that included indicators   1168 02:08:45,960 --> 02:08:50,820 that are currently recommended to identify  pediatric malnutrition. Future studies are needed   1169 02:08:50,820 --> 02:08:55,560 that include malnutrition screening tools that use  academy ASPEN indicators for identification and   1170 02:08:55,560 --> 02:09:01,500 documentation of pediatric malnutrition. Multiple  studies are needed for commonly used tools as well   1171 02:09:01,500 --> 02:09:06,420 as additional information on how training for and  user of the tools affect validity and reliability.   1172 02:09:09,780 --> 02:09:13,680 So next I will cover the very low birth  weight preterm infant until nutrition   1173 02:09:13,680 --> 02:09:20,280 evidence based nutrition practice guideline.  So the preterm project was a collaboration   1174 02:09:20,280 --> 02:09:24,120 of the National Institute of Health and the  Academy of Nutrition and Dietetics. So the   1175 02:09:24,120 --> 02:09:27,720 goal was to evaluate available evidence  to support guidelines for nutrition care.   1176 02:09:28,260 --> 02:09:33,600 So this project had two phases. Phase 1 was led  by the NIH and Phase 2 was led by the Academy.  1177 02:09:36,360 --> 02:09:41,820 So here is our pre-term infant expert panel.  So the same setup as the malnutrition screening   1178 02:09:41,820 --> 02:09:45,540 panel. So with our panel members, we  had a patient advocate, project manager,   1179 02:09:45,540 --> 02:09:51,960 lead analyst and a librarian. So multiple  systematic reviews were conducted to support   1180 02:09:51,960 --> 02:09:56,160 the guideline including systematic reviews  that compared to fortifiers, protein amount,   1181 02:09:56,160 --> 02:10:01,380 calorie and fat intake and SRs compared milk  to formula and human milk with donor milk.   1182 02:10:03,600 --> 02:10:08,940 So here are the recommendations that were  developed based on the evidence, the decision   1183 02:10:08,940 --> 02:10:16,020 framework and the conducted SRs. So for protein  amount, health care practitioners should provide   1184 02:10:16,020 --> 02:10:23,040 3.5g-4.0g of protein per kilogram of body weight.  For type of fat, health care practitioners should   1185 02:10:23,040 --> 02:10:29,100 not routinely supplement additional enteral  long chain fatty acids. Formula enrichment is   1186 02:10:29,100 --> 02:10:34,080 recommended compared to standard formula for the  preterm very low birth weight preterm population.   1187 02:10:35,760 --> 02:10:39,120 Human milk should be fortified  when possible. Mother,   1188 02:10:39,120 --> 02:10:44,340 fortified mother's milk should be provided. Health care practitioners should provide fortified   1189 02:10:44,340 --> 02:10:49,500 human milk regardless of source of maternal  or donor. And when quantity of maternal milk   1190 02:10:49,500 --> 02:10:54,240 is insufficient, health care practitioners should  supplement very low birth weight preterm infants   1191 02:10:54,240 --> 02:10:58,740 with donor milk during the time that infants  are at high risk for necrotizing enterocolitis.   1192 02:11:01,800 --> 02:11:07,560 So implementation considerations for the protein  amount are the lack of the ability to measure   1193 02:11:07,560 --> 02:11:13,200 specific nutrition composition of human milk. If  practitioners lack access to human milk analysis,   1194 02:11:13,200 --> 02:11:18,120 practitioners must rely on estimated  intake. For human milk fortification,   1195 02:11:18,120 --> 02:11:22,200 this will require suitable area and  staff education for safe preparation   1196 02:11:22,920 --> 02:11:27,660 and an acceptable feeding protocol that indicates  when fortification has started, advanced and   1197 02:11:27,660 --> 02:11:32,460 stopped. As far as maternal milk recommendation,  this will require a multidisciplinary approach   1198 02:11:32,460 --> 02:11:37,440 to educate patients of very low birth weight,  preterm infants and the benefits of human milk,   1199 02:11:37,440 --> 02:11:41,520 how to effectively initiate milk production  and how to maintain milk supply throughout   1200 02:11:41,520 --> 02:11:46,560 hospital stay and post-discharge period. So support may include educational materials   1201 02:11:46,560 --> 02:11:53,580 and access to high quality pumping equipment and  ongoing lactation services. Implementation of the   1202 02:11:53,580 --> 02:11:58,440 maternal milk supplementation recommendation also  will require a multidisciplinary team approach   1203 02:11:58,440 --> 02:12:03,960 when implementing donor milk programs in NICUs.  It will require policies and protocols to track   1204 02:12:03,960 --> 02:12:09,540 donor milk, and the FDA recommends against  acquiring donor milk directly from individuals   1205 02:12:09,540 --> 02:12:14,400 or online. Donor milk should be obtained  from a source that has screened milk donors.   1206 02:12:17,520 --> 02:12:24,120 As far as research and research gaps and  future research, more research is needed   1207 02:12:24,120 --> 02:12:29,760 on all investigated topics for very low birth  weight, preterm infants for our protein systematic   1208 02:12:29,760 --> 02:12:35,400 reviews, the amount of protein provided, how  it was provided and how it was reported had a   1209 02:12:35,400 --> 02:12:40,320 very high heterogeneity, and there was a lack of  isocaloric studies that evaluated greater than   1210 02:12:40,320 --> 02:12:48,540 versus less than 4g/kg of body weight per day.  The fat SRs only found studies that evaluated   1211 02:12:48,540 --> 02:12:52,980 omega three fatty acids and there was very little  evidence found a non protein energy intake.  1212 02:12:53,520 --> 02:12:58,500 As far as the human milk studies, of course these  were limited to observational studies. They did   1213 02:12:58,500 --> 02:13:04,020 not identify or control over known confounding  socio and economic factors. Additional information   1214 02:13:04,020 --> 02:13:09,780 is needed on the amount and type afforded  bias, as well as access to the nutrient   1215 02:13:09,780 --> 02:13:16,200 composition of mothers' milk in real time. And  that concludes today's presentation. Thank you. 1216 02:13:21,260 --> 02:13:28,140 DR. GAIL CRESCI: Wow, thank you so much to our  fabulous team of presenters.   1217 02:13:28,140 --> 02:13:33,000 That was really a wealth of information. Before  we get started with the Q&A, I, of course,   1218 02:13:33,000 --> 02:13:40,740 need to thank our NIH scientific program contacts  for assisting with this wonderful event, Ashley   1219 02:13:40,740 --> 02:13:46,620 Vargas, Charlotte Pratt and Christopher Lynch,  as well as our working group members that have   1220 02:13:46,620 --> 02:13:52,500 helped with this, including Nilesh Mehta,  Dr. Todd Rice, David Seres, Alison Steiber and   1221 02:13:52,500 --> 02:13:58,980 myself. And of course we couldn't do this without  our logistical support. Kimberly Barch has   1222 02:13:58,980 --> 02:14:05,760 been amazing in helping with everything. Mark  Dennis and of course our colleagues at Labroots,   1223 02:14:05,760 --> 02:14:12,240 including Brett Long, you've been fabulous in  keeping us on track and moving forward. We   1224 02:14:12,240 --> 02:14:18,240 really have some really amazing questions here  for our presenters, so I'm just going to dive right   1225 02:14:18,240 --> 02:14:24,000 in. And as I was sifting through these questions  that were coming in, I was trying to think about   1226 02:14:24,000 --> 02:14:30,660 a sequential way to ask them. So I'm going to do  whatever worked in my mind for this. And so   1227 02:14:30,660 --> 02:14:38,400 the first question goes off to Dr. Medoff-Cooper. At your center, what is the earliest time point   1228 02:14:38,400 --> 02:14:44,400 when an infant admitted for open heart surgery  is assessed by the SLP and has intervention? 1229 02:14:44,400 --> 02:14:52,620 DR. BARBARA MEDOFF-COOPER: Thank you for that question.  It really depends on the infant obviously. We have   1230 02:14:52,620 --> 02:15:01,080 some infants that are being fed before surgery and  those infants are commonly assessed from with   1231 02:15:01,080 --> 02:15:12,180 SLPs. Infants that are not being fed pre-surgery  that as soon as oral feeding is being initiated,   1232 02:15:13,140 --> 02:15:17,400 the SLPs will start working with these  infants. Almost all of our infants   1233 02:15:17,400 --> 02:15:24,840 have the speech language pathologist  referral just as feeding as beginning. 1234 02:15:27,000 --> 02:15:32,220 DR. GAIL CRESCI: That's great. Thank you. So  you know how transition from inpatient,   1235 02:15:32,220 --> 02:15:37,740 outpatient, particularly in this early  life population is so important because as   1236 02:15:38,520 --> 02:15:44,160 these infants and children can bounce back  and forth through both environments. So having   1237 02:15:44,160 --> 02:15:50,580 that continuity of nutritional support is so  important. So these questions go out to Dr. Black.   1238 02:15:51,780 --> 02:15:58,320 And the first one is are there specific questions  about the nutritional ecology in which a child   1239 02:15:58,320 --> 02:16:04,620 lives that would help improve the screening or  the choice of treatment for pediatric malnutrition   1240 02:16:04,620 --> 02:16:10,140 that could be incorporated into the electronic  health record or the clinical care process?   1241 02:16:12,480 --> 02:16:20,160 DR. MAUREEN BLACK: Thank you very much for the question and the  answer to that is yes, with the electronic medical   1242 02:16:20,160 --> 02:16:28,500 record, for example, there's a two-item screen  for food security, sometimes referred to as the   1243 02:16:28,500 --> 02:16:35,760 hunger vital sign that has been incorporated into  a number of electronic medical records. What this   1244 02:16:35,760 --> 02:16:44,040 does then is alert the clinician about the food  security status of the household under really,   1245 02:16:44,040 --> 02:16:51,000 ideal conditions, there are examples of that  information in the food, in the electronic medical   1246 02:16:51,000 --> 02:16:59,880 record then being transmitted either to with  permission, of course, either to work or to a   1247 02:16:59,880 --> 02:17:05,280 food bank so that it's not only learning about  the family, but it's connecting them with some   1248 02:17:05,280 --> 02:17:15,059 resources to improve their food security status. So that's the most obvious example of   1249 02:17:15,060 --> 02:17:23,520 one that I can think of. It's just very helpful to  understand what's going on at a family level to be   1250 02:17:23,520 --> 02:17:30,780 able to move forward and come up with some rest of  the evaluation and some interventions that can be   1251 02:17:30,780 --> 02:17:38,399 implemented within the family. Excellent. And so  a continuation of that. So you have those type of   1252 02:17:38,399 --> 02:17:46,019 resources, then what about maybe those that don't  get into that resource system or that do even,   1253 02:17:46,800 --> 02:17:53,460 how would you address food deserts and food swamps  in this context and how to help families navigate through these challenges?   1254 02:17:53,460 --> 02:17:59,820 DR. MAUREEN BLACK: Thank you. These are  very interesting questions and illustrate how   1255 02:17:59,820 --> 02:18:06,899 important it is to understand the contexts in  where families live. It also illustrates the   1256 02:18:06,899 --> 02:18:14,639 role that nutrition can play beyond a single  family, and that is advocating in a community   1257 02:18:14,640 --> 02:18:21,780 that there be more resources available for  families who are living in a food desert or   1258 02:18:21,780 --> 02:18:27,599 a food swamp and who don't have transportation.  It's very, very difficult that even if they're   1259 02:18:27,600 --> 02:18:33,060 aware of the interventions and want to follow  through, that it can be very difficult to do.  1260 02:18:33,060 --> 02:18:42,000 So I would say that the nutrition community  has a wonderful opportunity to work with   1261 02:18:42,000 --> 02:18:51,300 existing municipalities or existing services  beyond individual families and children,   1262 02:18:51,300 --> 02:18:59,280 really to try and help them so that the...the onus  is not always on the families, but on the broader   1263 02:18:59,280 --> 02:19:06,540 community to sort out how to provide services for  their communities. Also, there are examples of   1264 02:19:07,680 --> 02:19:14,220 the communities that have done some innovative  things, either working through libraries.   1265 02:19:14,220 --> 02:19:22,560 There's online grocery shopping to try and help  families who are living in very difficult places.   1266 02:19:23,700 --> 02:19:27,960 DR. GAIL CRESCI: Thank you, thank you for that response.  So in thinking a little bit more now,   1267 02:19:27,960 --> 02:19:34,260 so we have our patient identified to need some  nutritional assistance. The patient is getting   1268 02:19:34,260 --> 02:19:42,000 assistance. How do we monitor that? So this  question is for Dr. Revilla and was the mFR easy to   1269 02:19:42,000 --> 02:19:50,580 use when children had care outside of their home,  like were daycare providers, for example, easily   1270 02:19:50,580 --> 02:19:56,519 able to adhere to taking the photos with the  marker. And then were the parents able to verify   1271 02:19:56,520 --> 02:20:02,399 the foods in the photos at the end of the day? Then that gets translated back to the clinician   1272 02:20:02,399 --> 02:20:06,839 to have a better understanding of what might  be going on nutritionally with the patient. 1273 02:20:06,840 --> 02:20:14,460 DR. MARIE KAINOA FIALKOWSKI REVILLA: Yeah, mahalo for the question.  Thank you. It was actually something that   1274 02:20:14,460 --> 02:20:22,200 was unexpected that we found in our pilot study.  It was actually the impetus of the parents that   1275 02:20:22,200 --> 02:20:28,080 they just went and downloaded it on grandma's  phone or auntie's phone or the sitter's phone   1276 02:20:28,979 --> 02:20:34,080 when the child wasn't with them. And for some of  the parents, we collected data for four days and   1277 02:20:34,080 --> 02:20:40,260 it was three out of the four days that there was  some meal that was reported by another caregiver.   1278 02:20:41,580 --> 02:20:43,800 And so based on our,   1279 02:20:45,180 --> 02:20:50,939 we had surveys and things with the parents and  based on what they told us, it worked out great   1280 02:20:50,939 --> 02:20:57,540 and it helped them. And we were still able  to do content verification with the parents,   1281 02:20:58,319 --> 02:21:05,519 with the images that were submitted. However, we  do need to do further research to kind of examine   1282 02:21:05,520 --> 02:21:10,920 if that wasn't necessarily at the onset what we  were planning on doing. And so now that we found   1283 02:21:10,920 --> 02:21:16,380 that this occurs, because this was the first time  that the mFR, the mobile food record had been used   1284 02:21:16,380 --> 02:21:24,300 in infants, we thought: Oh, we need to examine  this further to see if there are any differences   1285 02:21:24,300 --> 02:21:29,819 and if there's differences in quality of images. But it was at the impetus of the parents and   1286 02:21:29,819 --> 02:21:34,319 they would train the other caregivers. So  I guess it does also speak to the utility   1287 02:21:35,819 --> 02:21:42,240 of the technology to hopefully reduce one  of the burdens of dietary assessment. So   1288 02:21:42,240 --> 02:21:47,219 hopefully we'll have more to come to address that  question. That was a great question. Thank you. 1289 02:21:47,220 --> 02:21:54,240 DR. GAIL CRESCI: Yeah, it's definitely a needed area  of research and but what part of your research,   1290 02:21:54,240 --> 02:21:59,760 have you been able to identify if  addressing these feeding behaviors   1291 02:22:00,960 --> 02:22:09,240 using this...the mFR, has it been able to show  ability to impact growth failure for these   1292 02:22:09,240 --> 02:22:14,580 vulnerable infants or any children  with complex physiologic challenges? 1293 02:22:14,580 --> 02:22:19,559 DR. MARIE REVILLA: Yeah, I put in the  response to that one. You know,   1294 02:22:19,560 --> 02:22:24,121 that's not something that we've actually  explored yet. So I don't really have   1295 02:22:25,740 --> 02:22:31,740 much to clarify on that response. Maybe  some of my colleagues might be able   1296 02:22:32,640 --> 02:22:38,040 to add further. Not at this time, though.  That's a very important question, though. Thank you. 1297 02:22:38,040 --> 02:22:45,720 DR. GAIL CRESCI: So that's a future direction we need to  go, is try to move to that stage. So let's now   1298 02:22:45,720 --> 02:22:52,800 move to our guidelines. Our systematic reviews and  guidelines conversations because what guidelines   1299 02:22:52,800 --> 02:22:56,700 tend to do because we're reviewing the  literature, they really identify gaps,   1300 02:22:58,260 --> 02:23:06,899 that...what we we are missing. And so I'm just  curious between Dr. Irving and Dr. Moloney,   1301 02:23:06,899 --> 02:23:11,700 this question for both of you  because you both listed several gaps,   1302 02:23:11,700 --> 02:23:16,019 future directions. If you had to pick  one to start with, what would it be? 1303 02:23:16,020 --> 02:23:18,201 DR. SHARON IRVING: I'll jump in. 1304 02:23:18,201 --> 02:23:21,359 DR. GAIL CRESCI: Yeah, sure. 1305 02:23:22,500 --> 02:23:27,359 DR. SHARON IRVING: I would say definitions. One of the  things that I've found consistently in looking   1306 02:23:27,359 --> 02:23:32,639 at guidelines and looking at even the systematic  reviews and how they evaluated the guidelines   1307 02:23:34,500 --> 02:23:40,500 that they included was that there was such  heterogeneity in definitions, definitions   1308 02:23:40,500 --> 02:23:47,520 about nutrition status, definition about when  do you hit that cutoff. So I would say that   1309 02:23:47,520 --> 02:23:56,640 some common definitions to address this across  age groups would be for, in my mind, an important   1310 02:23:56,640 --> 02:24:04,200 first step so that as people are engaging in  research and even in QI projects, you know what   1311 02:24:04,200 --> 02:24:09,291 you're dealing with and you are measuring apples  to apples and oranges to oranges. Dr. Moloney. 1312 02:24:09,291 --> 02:24:17,040 DR. GAIL CRESCI: Dr. Moloney may be... 1313 02:24:17,040 --> 02:24:27,960 DR. SHARON IRVING: Frozen. That would be number one for  me would be those to standardised definitions. I   1314 02:24:27,960 --> 02:24:35,580 think that's one of the biggest challenges that  we have. And so it makes for very difficult   1315 02:24:36,600 --> 02:24:40,319 assessments, but it also makes  for difficult comparisons. 1316 02:24:40,319 --> 02:24:46,380 DR. GAIL CRESCI: Well, another question for you, Dr.  Irving, with all the guidelines in the scoring   1317 02:24:46,380 --> 02:24:53,280 systems, do any of these predict poor outcomes?  Did any of the research help to clarify whether   1318 02:24:53,280 --> 02:25:01,080 any of these definition or guidelines predicts  an individual patients to help us identify   1319 02:25:01,080 --> 02:25:07,740 who will need or respond to nutritional  nourishment based on their interventions? 1320 02:25:07,740 --> 02:25:15,840 DR. SHARON IRVING: Well, that's a great question. Excuse  me. And, you know, the guidelines that I used as   1321 02:25:15,840 --> 02:25:21,660 my base to do my comparison is in critically  ill infants and children, right. And so none   1322 02:25:21,660 --> 02:25:27,660 of the tools out there have been validated in that  group. So that's the first thing to recognize. So   1323 02:25:27,660 --> 02:25:34,740 therefore, when you talk about predicting what  populations or subpopulations and subgroups will   1324 02:25:34,740 --> 02:25:41,340 benefit from nutrition and can these tools  identify that, that's a really tough place   1325 02:25:41,340 --> 02:25:47,700 to be because of what I said previously. One, the  definitions are so variable and two, none of them   1326 02:25:47,700 --> 02:25:54,660 have been really validated in pediatric critical  care. The third component of that is there's only   1327 02:25:54,660 --> 02:26:00,359 three of the tools that are out there that  were even in their original development,   1328 02:26:00,359 --> 02:26:09,359 even included some critically ill children. So  it makes it really difficult to overlay that onto   1329 02:26:09,359 --> 02:26:15,420 this population. And then the last point that  I'll make there, that those of us that work in   1330 02:26:15,420 --> 02:26:20,580 the critical care environment and actually  even in the inpatient environment, severity   1331 02:26:20,580 --> 02:26:26,880 of illness is such a large component of this. And there's only one of those tools that even   1332 02:26:26,880 --> 02:26:33,740 included that. So I think we have lots of work to  do and lots of area for research and development. 1333 02:26:33,740 --> 02:26:40,380 DR. GAIL CRESCI: Thank you. Oh, yeah, yeah, please.  We have time for one more. So yeah, Lisa,   1334 02:26:40,380 --> 02:26:41,580 we're waiting to hear from you. 1335 02:26:41,580 --> 02:26:44,939 DR. LISA MOLONEY: Sorry, I had a little  bit of technology issue. Yes,   1336 02:26:44,939 --> 02:26:48,899 I would definitely concur that we had a lot of  trouble. So when we try to aggregate the data,   1337 02:26:48,899 --> 02:26:53,639 the definitions are certainly a huge  concern. A lot of nutrition screening   1338 02:26:53,640 --> 02:26:59,880 and nutrition assessment using being used  interchangeably as far as the tools went. Also,   1339 02:26:59,880 --> 02:27:04,080 when it came to trying to aggregate the data, just  the way that things were reported. So we didn't   1340 02:27:04,080 --> 02:27:09,120 have enough raw data that we needed to truly  aggregate all of the available evidence. But   1341 02:27:10,140 --> 02:27:15,240 right out of the gate, the first issue that  we did have was the definitions and the lack   1342 02:27:15,240 --> 02:27:19,760 of standardization between screening and  assessment and what outcomes were reported. 1343 02:27:19,760 --> 02:27:24,840 DR. GAIL CRESCI: And would you say that is  what contributes to the heterogeneity   1344 02:27:26,399 --> 02:27:29,339 that you had noticed amongst the evidence base? 1345 02:27:29,340 --> 02:27:33,899 DR. LISA MOLONEY: Yeah. So, I mean, as far as the  screening and the assessment systematic reviews   1346 02:27:33,899 --> 02:27:39,839 we've been conducting that we had heterogeneity  and difference in...different reference standards that were being   1347 02:27:39,840 --> 02:27:45,960 used that the tools were compared to. And then as  far as the intervention studies, the interventions   1348 02:27:45,960 --> 02:27:51,840 might have been fairly similar, but what they were  compared to were rigorously different. So it was   1349 02:27:51,840 --> 02:27:58,260 just the overall study design was hard to compare  apples to apples with most of these studies. 1350 02:27:58,260 --> 02:28:02,819 DR. GAIL CRESCI: So in 30 seconds, can  you tell us how would we design   1351 02:28:02,819 --> 02:28:06,479 a study to get around this heterogeneity issue? 1352 02:28:06,479 --> 02:28:14,459 DR. LISA MOLONEY: I think it would be, I think a  multidisciplinary approach would definitely be   1353 02:28:14,460 --> 02:28:19,380 helpful when it came with screening and assessment  for everyone to provide what exactly is that gold   1354 02:28:19,380 --> 02:28:24,720 standard in nutrition research? It's not exactly  easy...30 seconds is a tough one to do.   1355 02:28:25,500 --> 02:28:29,520 I think it's also referral back to these  systematic reviews would also be helpful.   1356 02:28:31,020 --> 02:28:36,060 But yeah, we had heterogeneity not just in the  outcome, but then also in these interventions. 1357 02:28:36,060 --> 02:28:37,201 DR. GAIL CRESCI: OK. 1358 02:28:37,484 --> 02:28:39,819 DR. LISA MOLONEY: Sorry, it's probably  not, I don't know gold standard answer. 1359 02:28:39,819 --> 02:28:45,899 DR. GAIL CRESCI: No, I know the magic ball. So, okay, well,  I want to thank everyone for your participation.   1360 02:28:46,439 --> 02:28:53,460 We had up to 86 participants, and thank you to  our presenters for such an engaging discussion.   1361 02:28:53,460 --> 02:28:59,280 We will now take a quick break before the second  part of this Session 8 will begin at 2:50pm.   1362 02:29:02,460 --> 02:29:03,180 Thank you. 1363 02:29:03,180 --> 02:29:08,400 DR. GAIL CRESCI: Hello, and welcome to  Malnutrition in Clinical Settings,   1364 02:29:09,180 --> 02:29:15,300 Research Gaps and Opportunities. And this  is part two of session eight on Early Life   1365 02:29:15,300 --> 02:29:21,060 Research Considerations. My name is Gail Cresci,  and I'm an associate professor in the Cleveland   1366 02:29:21,060 --> 02:29:24,600 Clinic Lerner College of Medicine of  the Case Western Reserve University,   1367 02:29:24,600 --> 02:29:30,600 and full staff in the Department of Pediatric  Gastroenterology and Inflammation and Immunity   1368 02:29:30,600 --> 02:29:36,000 at the Cleveland Clinic in Cleveland, Ohio. I am  also the immediate past president of the American   1369 02:29:36,000 --> 02:29:41,220 Society for Parenteral and Enteral Nutrition.  I will be your moderator for this session.   1370 02:29:42,240 --> 02:29:48,420 We have a phenomenal panel of experts presenting  on this topic today. For detailed information   1371 02:29:48,420 --> 02:29:53,819 regarding their backgrounds, please refer to the  speaker tab on the left column of this screen,   1372 02:29:53,819 --> 02:30:01,740 or you can go to the main page under the speaker  tab and also find their bios. This session focuses  1373 02:30:01,740 --> 02:30:08,460 on disease and condition-specific malnutrition in  early life. There are many disease conditions that   1374 02:30:08,460 --> 02:30:13,560 impact nutritional status in early life.  Unfortunately, due to time limitations,   1375 02:30:13,560 --> 02:30:19,260 we are not able to cover every disease  state, but we certainly have many to discuss.   1376 02:30:20,160 --> 02:30:27,300 Dr. Tamara S. Hannon will discuss changes in  metabolism focusing on gestational diabetes.   1377 02:30:27,300 --> 02:30:33,120 Dr. Edmond Wickman will discuss a unique  form of malnutrition in pediatric obesity.   1378 02:30:33,840 --> 02:30:40,200 Dr. Andrea Garber will discuss the inability  to meet nutrient needs in anorexia nervosa.   1379 02:30:40,800 --> 02:30:46,080 Dr. Elena Ladas will discuss the double  burden of malnutrition in childhood cancer.   1380 02:30:46,920 --> 02:30:53,220 Dr. Lori Bechard will discuss the inability to  meet nutrient needs in pediatric critically ill.   1381 02:30:54,180 --> 02:30:58,979 Dr. David Sasken will discuss nutritional  therapies and inflammatory bowel disease   1382 02:30:58,979 --> 02:31:06,959 and implications of malnutrition and disease.  Dr. Bruno Chumpitazi will discuss carbohydrate   1383 02:31:06,960 --> 02:31:13,680 malabsorption in irritable bowel syndrome.  Alexandra Carey will discuss nutritional   1384 02:31:13,680 --> 02:31:17,340 strategies in the malnutrition  child with short bowel syndrome.   1385 02:31:17,340 --> 02:31:25,140 And lastly, Dr. Jalal Abu-Shaweesh will discuss malnutrition  in immune related necrotizing enterocolitis.   1386 02:31:25,859 --> 02:31:32,339 The presentations will be followed by a live  question and answer period with the speakers. I   1387 02:31:32,340 --> 02:31:38,220 encourage you as the sessions are being presented  to please submit your questions in the question   1388 02:31:38,220 --> 02:31:45,420 and answer box. We will try to address as many  questions as we can during the live q&a session.   1389 02:31:46,380 --> 02:31:53,520 So, without further ado, here we go. 1390 02:31:53,520 --> 02:31:59,520 DR. TAMARA S HANNON:  Thank you for the invitation to present on type  2 diabetes in youth and gestational diabetes.   1391 02:32:00,359 --> 02:32:05,099 I would like to disclose that I am a  consultant and serve on a pediatric   1392 02:32:05,100 --> 02:32:09,720 clinical trials advisory board for  Eli Lilly Incorporated, but we will   1393 02:32:09,720 --> 02:32:13,380 not be discussing pharmaceutical  products or clinical trials here.   1394 02:32:15,120 --> 02:32:22,019 I would like to start with a case history of 12  year old Mariah who presents with increasing body   1395 02:32:22,020 --> 02:32:28,201 mass index. Her mother had gestational diabetes  but does not know her current diabetes status.   1396 02:32:29,040 --> 02:32:34,979 Her maternal grandparents have diabetes, eye,  and kidney disease and cardiovascular disease.   1397 02:32:35,640 --> 02:32:45,420 Mariah has (INAUDIBLE) indicative of insulin resistance and  her hemoglobin a1c is 6.3% just below the cutoff   1398 02:32:45,420 --> 02:32:53,220 point for diabetes. How do we intervene  in the generational cycle of diabetes?  1399 02:32:53,220 --> 02:33:02,280 It is well known that type two diabetes is  increasing in youth. The search for diabetes in   1400 02:33:02,280 --> 02:33:09,359 youth multicenter study has reported a continued  increase since the study began in the year 2000,   1401 02:33:09,359 --> 02:33:15,000 particularly among minority race and  ethnic groups. The incidence rates for   1402 02:33:15,000 --> 02:33:21,960 type two diabetes in youth show a dramatic  increase in non Hispanic black youth. This   1403 02:33:21,960 --> 02:33:31,319 has further increased during the COVID pandemic  as rates increased by 77% between March 2020 and   1404 02:33:31,319 --> 02:33:38,340 March 2021, as determined by a multicenter  hospital base case ascertainment study.  1405 02:33:41,160 --> 02:33:45,240 Is there an ideal intervention  for 12 year old Mariah?   1406 02:33:45,840 --> 02:33:50,700 Effective prevention strategies for type  2 diabetes have not been determined.   1407 02:33:51,600 --> 02:33:58,140 Treatment of impaired glucose tolerance for pre  diabetes with diabetes medications including   1408 02:33:58,140 --> 02:34:04,500 Metformin or insulin does not stop the progressive  beta cell dysfunction in this age group.   1409 02:34:05,760 --> 02:34:12,180 So, early recognition and intensive treatment are  recommended but patients often have gaps in care. 1410 02:34:14,340 --> 02:34:20,700 There are barriers to seeking care.  Diabetes is a stigmatized disease.   1411 02:34:20,700 --> 02:34:27,300 Failing and OGTT feels bad whether you're  a child or an adult. Moreover, the reality   1412 02:34:27,300 --> 02:34:33,060 for families living with type two diabetes is  often trying to make ends meet due to poverty,   1413 02:34:33,060 --> 02:34:38,760 lack of basic needs, and lack of access  to medical, social and community support. 1414 02:34:41,939 --> 02:34:48,540 Mariah is now 21 years old, and presents during  the second trimester of her first pregnancy.   1415 02:34:49,380 --> 02:34:54,479 Her diabetes status is unknown. She  has never had prenatal counseling or   1416 02:34:54,479 --> 02:34:58,259 reproductive health care. And given  her family and past medical history,   1417 02:34:58,260 --> 02:35:02,760 it is likely that her pregnancy has  already been impacted by hyperglycemia.   1418 02:35:04,200 --> 02:35:12,780 According to the International Diabetes Federation  in 2019 20 million or 16% of live births had   1419 02:35:12,780 --> 02:35:20,639 hyperglycemia in pregnancy. One in six births was  affected by gestational diabetes. Most cases of   1420 02:35:20,640 --> 02:35:27,781 hyperglycemia in pregnancy were in low and middle  income countries or areas of the United States. 1421 02:35:29,580 --> 02:35:33,540 We learned through the today's  study pregnancy outcomes   1422 02:35:34,140 --> 02:35:42,840 study of young women who were diagnosed  with type 2 diabetes during adolescence,   1423 02:35:46,080 --> 02:35:53,340 over 15 years of the combined today's study  data collection 260 pregnancies were reported   1424 02:35:53,340 --> 02:36:01,920 by 141 young women. Those reporting of pregnancy  have lower household incomes at baseline with a   1425 02:36:01,920 --> 02:36:07,859 higher proportion of non Hispanic black race  ethnicity. The average age at first pregnancy   1426 02:36:07,859 --> 02:36:14,219 was 20.5 years with an average duration of  diabetes prior to the pregnancy of 7.3 years.   1427 02:36:14,939 --> 02:36:21,899 Approximately one third had chronic hypertension, one third  had glycemic failure and a quarter had diabetes   1428 02:36:21,899 --> 02:36:28,019 neuropathy before pregnancy. There were  high rates of pregnancy loss, stillbirth,   1429 02:36:28,020 --> 02:36:34,920 preterm birth, maternal complications,  SGA and LGA, and neonatal hypoglycemia.   1430 02:36:35,460 --> 02:36:40,439 Antenatal glycemia predicts  poor outcomes in young women. 1431 02:36:44,520 --> 02:36:51,359 The demographics and increased incidence rates  of type 2 diabetes in youth in the U.S. will be   1432 02:36:51,359 --> 02:36:58,979 associated with increased high risk pregnancies  in the U.S. In the near future, even more youth   1433 02:36:58,979 --> 02:37:06,479 will be at both genetic and metabolic risk for  type 2 diabetes or have type 2 diabetes. 1434 02:37:09,060 --> 02:37:16,439 Mariah is now back with her three month old  infant. Her baby is growing well on breast milk,   1435 02:37:16,439 --> 02:37:23,460 and she can no longer breastfeed due to work  obligations. She and her baby are eligible for   1436 02:37:23,460 --> 02:37:28,740 WIC, the special Supplemental Nutrition  Program for Women, Infants and Children.   1437 02:37:29,580 --> 02:37:35,340 She would like information on how  to feed her baby with formula. 1438 02:37:39,479 --> 02:37:47,519 A very recent publication out just last week has  highlighted potential increased risk for rapid   1439 02:37:47,520 --> 02:37:54,840 weight gain in infants receiving lactose reduced  formula that is made with corn syrup solids.   1440 02:37:55,740 --> 02:38:02,160 This formula is glucose rich,  rather than galactose rich. 1441 02:38:03,479 --> 02:38:09,839 WIC data from more than 15,000 children  who stopped breastfeeding by three months   1442 02:38:09,840 --> 02:38:15,899 of age were analyzed to compare weights  and links of children grouped as those   1443 02:38:15,899 --> 02:38:23,399 who were ever issued formula with corn  syrup solids 23% of the children versus   1444 02:38:23,399 --> 02:38:29,219 those who were never issued formula with  corn syrup solids, most of the children.   1445 02:38:30,479 --> 02:38:39,959 As you see here, both males and females who  were issued formula with corn syrup solids   1446 02:38:39,960 --> 02:38:48,420 had steeper trajectories of increase for weight  for length Z score up until two years of age. 1447 02:38:50,460 --> 02:38:55,020 The difference between those  who ever received formula with   1448 02:38:55,020 --> 02:39:00,541 corn syrup solids and those who  had not remained at age four. 1449 02:39:04,500 --> 02:39:10,439 The association's remained significant,  independent of maternal weight status,   1450 02:39:10,439 --> 02:39:17,219 total formula issued and breastfeeding duration,  and were not modified by child race or sex.   1451 02:39:17,939 --> 02:39:27,059 This study provides additional formula, if you  will, for thought about how to feed children   1452 02:39:27,780 --> 02:39:29,700 who cannot breastfeed. 1453 02:39:32,580 --> 02:39:37,680 There are many research gaps that  should be evident from my presentation,   1454 02:39:37,680 --> 02:39:44,220 including how can generations of women  with diabetes help us learn more? When   1455 02:39:44,220 --> 02:39:48,480 and how should young women with multiple  risk factors for diabetes be treated?   1456 02:39:50,220 --> 02:39:55,440 And how should infants and young children  be fed to decrease the risk for diabetes?   1457 02:39:56,700 --> 02:40:07,500 There are many in targets for research across the  spectrum of research to address these questions.   1458 02:40:09,120 --> 02:40:15,599 I will leave the rest for discussion. Thank you.   1459 02:40:15,600 --> 02:40:20,880 DR. TREY WICKHAM: Good afternoon. I'm Trey Wickham from Virginia  Commonwealth University and it's my honor to   1460 02:40:20,880 --> 02:40:24,180 present at the NIH malnutrition  and clinical settings workshop.   1461 02:40:25,020 --> 02:40:30,121 I receive funding support from the National  Institutes of Health as well as WW International.   1462 02:40:31,800 --> 02:40:38,040 The World Health Organization considers your  obesity disease and places it on the spectrum   1463 02:40:38,040 --> 02:40:44,880 of malnutrition in children. Let's explore how  pediatric obesity may represent a unique form   1464 02:40:44,880 --> 02:40:50,280 of malnutrition. Both malnutrition and obesity  result from significant perturbations in energy   1465 02:40:50,280 --> 02:40:56,700 metabolism, are associated with increased risk of  disease, affect children's physical, emotional,   1466 02:40:56,700 --> 02:41:01,740 and social development, and are significantly  influenced by social determinants of health   1467 02:41:01,740 --> 02:41:07,920 including poverty and food insecurity. Moreover,  youth with obesity may be at increased risk of   1468 02:41:07,920 --> 02:41:13,380 other forms of malnutrition including fiber,  protein, vitamin, and mineral deficiencies.   1469 02:41:14,340 --> 02:41:22,439 As such, obesity is a highly prevalent form of  malnutrition, affecting approximately one out of   1470 02:41:22,439 --> 02:41:28,859 four to five youth in the United States with  higher rates among marginalized populations.   1471 02:41:30,180 --> 02:41:37,859 Consistent with the WHO definition of malnutrition  as an imbalance in energy metabolism, long term   1472 02:41:37,859 --> 02:41:43,439 positive energy balance where energy intake  exceeds energy expenditure is central to the   1473 02:41:43,439 --> 02:41:49,859 development of obesity. Yet this paradigm has  been used to inappropriately and detrimentally   1474 02:41:49,859 --> 02:41:55,620 oversimplify the pathogenesis of obesity,  suggesting that the condition is solely the   1475 02:41:55,620 --> 02:42:01,500 results of apparent behaviors, including poor  dietary choices and limited physical activity.   1476 02:42:02,580 --> 02:42:09,840 In contrast, robust data supports the role of  complex neuro humoral pathways in the regulation   1477 02:42:09,840 --> 02:42:16,020 of energy intake and expenditure. Moreover,  alterations in these pathways that lead to a   1478 02:42:16,020 --> 02:42:21,540 positive energy balance are well described in  patients with obesity, providing a biologic   1479 02:42:21,540 --> 02:42:28,200 basis for many observed behaviors. Moreover,  weight loss triggers compensatory changes in   1480 02:42:28,200 --> 02:42:35,099 these pathways that push the patient to regain  weight, leading to increased energy intake and   1481 02:42:35,100 --> 02:42:43,260 reduced energy expenditure. Thus, obesity results  from not only sustained positive energy balance,   1482 02:42:43,260 --> 02:42:50,520 but a resetting of the body weight setpoint  and an increased level. In summary, obesity   1483 02:42:50,520 --> 02:42:55,620 is a complex chronic disease that frequently  emerges during childhood and adolescence and   1484 02:42:55,620 --> 02:43:01,140 results from an interplay of a myriad of genetic,  environmental, metabolic and behavioral factors.   1485 02:43:02,700 --> 02:43:07,859 Clearly, genetics plays a prominent role in the  regulation of body weights and pathogenesis of   1486 02:43:07,859 --> 02:43:13,620 obesity. Moreover, as highlighted by other  speakers already today, epigenetic changes,   1487 02:43:13,620 --> 02:43:19,380 including those resulted from factors in the fetal  environment and early postnatal life appear to   1488 02:43:19,380 --> 02:43:25,319 influence the risk of obesity as well as other  metabolic disorders. Lastly, the gut microbiome   1489 02:43:25,319 --> 02:43:29,819 which we know is established early during  childhood and plays a prominent role of health   1490 02:43:29,819 --> 02:43:36,840 has also been implicated in the development of  obesity. Yet data regarding the role of epigenetic   1491 02:43:36,840 --> 02:43:43,080 and microbiome changes have largely been derived  from animal studies, and the role in human   1492 02:43:43,080 --> 02:43:50,220 physiology is less clear, representing one area  for further research. Relevant to our focus today   1493 02:43:50,220 --> 02:43:56,220 on early life, we know that certain behavioral  factors including breastfeeding, sugared beverage   1494 02:43:56,220 --> 02:44:02,160 intake, and impaired sleep appear to contribute  to obesity. I also wish to highlight the role of   1495 02:44:02,160 --> 02:44:08,099 environmental and social factors in this complex  disease, including contributions from agricultural   1496 02:44:08,100 --> 02:44:14,399 policy, food industry, factors within the built  environment, socio economic factors and the   1497 02:44:14,399 --> 02:44:20,759 potential role of endocrine disrupting chemicals.  To further highlight research opportunities in the   1498 02:44:20,760 --> 02:44:28,200 field we do need to rigorously investigates how  even well intentioned policy changes and impacts   1499 02:44:28,200 --> 02:44:35,460 obesity and other components of health. We  further also need to clarify the biologic pathways   1500 02:44:35,460 --> 02:44:41,220 by which endocrine disrupting chemicals may  contribute to energy imbalance and obesity risk.  1501 02:44:42,420 --> 02:44:48,060 Behavioral weight management including and components dietary modification, increased physical   1502 02:44:48,060 --> 02:44:55,140 activity, and behavior change in support are at  the core foundation of the treatment of pediatric   1503 02:44:55,140 --> 02:45:01,979 obesity. Extensive research has failed to  demonstrate that a dietary approach that targets   1504 02:45:01,979 --> 02:45:09,120 any specific macronutrient category is superior  to others in regards to weight loss. However,   1505 02:45:09,120 --> 02:45:14,939 there are interesting data regarding the potential  impact of ultra processed foods on the previously   1506 02:45:14,939 --> 02:45:21,000 outlined feedback pathways controlling energy  metabolism. Evidence supported recommendations   1507 02:45:21,000 --> 02:45:26,100 highlight that parental involvement is essential  component of pediatric weight management.   1508 02:45:26,880 --> 02:45:32,280 In fact, results show that in youth younger  than age 11 exclusively targeting parents or   1509 02:45:32,280 --> 02:45:38,160 caregivers results in similar clinical responses  to those interventions that include youth as well.   1510 02:45:38,160 --> 02:45:43,800 Although parental engagement and adolescent weight  management is still recommended the most effective   1511 02:45:43,800 --> 02:45:48,300 approach during this unique developmental  period is not well defined and warrants   1512 02:45:48,300 --> 02:45:54,899 further investigation as our group is currently  doing. I also wish to address concerns based   1513 02:45:54,899 --> 02:46:01,500 on observational studies that have been proposed  linking unsupervised dieting to increase dieting,   1514 02:46:01,500 --> 02:46:08,880 or eating disorder risk among youth. Yet,  evidence does not suggest that supervised   1515 02:46:08,880 --> 02:46:15,540 empirically supported behavioral weight management  treatment increases eating disorder risk. Indeed,   1516 02:46:15,540 --> 02:46:22,500 family based behavioral weight management has the  potential to buffer eating disorder risk given its   1517 02:46:22,500 --> 02:46:29,340 focus on healthy sense of self regulation of  energy balance and weights. Another research   1518 02:46:29,340 --> 02:46:34,260 gap is determining which youth will respond to  behavioral weights management most effectively  1519 02:46:34,260 --> 02:46:38,939 data like these from Danielson and colleagues  suggest that behavioral weight management   1520 02:46:38,939 --> 02:46:46,080 responses are greatest in youth when initiated  early in life and among those with less severe   1521 02:46:46,080 --> 02:46:53,160 obesity. Moreover, we need research to identify  the minimal amount of BMI or weight change that   1522 02:46:53,160 --> 02:46:58,859 results in clinically significant improvements  among the pediatric population and adults mild   1523 02:46:58,859 --> 02:47:05,280 to moderate weight losses of three to 5% have  been shown to result consistently and metabolic   1524 02:47:05,280 --> 02:47:11,519 improvements, yet a similar threshold has not  been robustly and clearly defined in the pediatric   1525 02:47:11,520 --> 02:47:18,720 population. For older youth with severe obesity  is it is unlikely that lifestyle modification   1526 02:47:18,720 --> 02:47:24,899 alone will adequately treat that patient's obesity  and consideration of pharmacotherapy as well as   1527 02:47:24,899 --> 02:47:32,700 Metabolic and Bariatric surgery is recommended.  Four pharmacologic agents are currently approved   1528 02:47:32,700 --> 02:47:38,399 for the treatment of obesity and youth younger  than age 18. Although newer agents demonstrate   1529 02:47:38,399 --> 02:47:44,939 more robust weight losses studies clearly show  that patients typically experience weight regain   1530 02:47:44,939 --> 02:47:52,319 when these medications are discontinued. Thus,  although pharmacotherapy law does likely represent   1531 02:47:52,319 --> 02:47:58,500 an important treatment modality in severe  pediatric obesity, it is essential to continue   1532 02:47:58,500 --> 02:48:04,260 to follow youth on these medications longer  term to more fully assess risks and benefits.   1533 02:48:04,260 --> 02:48:10,500 In contrast to the limited data regarding  pediatric obesity pharmacotherapy, they are   1534 02:48:10,500 --> 02:48:16,620 increasingly robust data regarding the clinical  efficacy, safety and durability of Metabolic and   1535 02:48:16,620 --> 02:48:23,280 Bariatric Surgery among youth with severe obesity.  In fact, the results of Teen-LABS as well as other   1536 02:48:23,280 --> 02:48:29,519 studies have demonstrated weight losses among  youth after weight bariatric surgery that are   1537 02:48:29,520 --> 02:48:35,940 comparable to adult counterparts with likely  even higher rates of comorbidity resolution.  1538 02:48:38,040 --> 02:48:43,500 In light of this robust data, the American Academy  of Pediatrics recently issued a policy statement   1539 02:48:43,500 --> 02:48:48,899 emphasizing the potential role of bariatric  surgery in the care of youth with obesity,   1540 02:48:48,899 --> 02:48:54,599 as well as a call to action to reduce barriers  and enhance access for eligible youths.  1541 02:48:55,979 --> 02:49:03,540 Research unfortunately confirms that individuals  with obesity including youth frequently face   1542 02:49:03,540 --> 02:49:11,819 stigma, bias and discrimination across multiple  social domains, including healthcare. Moreover,   1543 02:49:11,819 --> 02:49:17,040 evidence suggests that patients experiencing  stigma during health care are less likely to   1544 02:49:17,040 --> 02:49:24,840 follow up and more likely to engage in unhealthy  behaviors such as unsupervised dieting.   1545 02:49:24,840 --> 02:49:30,540 In summary, I've attempted to highlight multiple  research gaps that impair understanding regarding   1546 02:49:30,540 --> 02:49:36,960 the pathogenesis and treatment of pediatric  obesity, a unique form of malnutrition. In brief,   1547 02:49:36,960 --> 02:49:42,180 these include the lack of understanding of  the risk of new nutritional deficiencies among   1548 02:49:42,180 --> 02:49:47,640 affected youth mechanisms by which the prenatal  environment and the microbiome potentially   1549 02:49:47,640 --> 02:49:53,460 impact energy homeostasis, establishing  thresholds that define clinically significant   1550 02:49:53,460 --> 02:49:58,979 weight loss in this younger population. The  potential impact and supervise family based   1551 02:49:58,979 --> 02:50:03,839 behavioral weight management on disordered  patterns of eating. The long term metabolic   1552 02:50:03,840 --> 02:50:09,240 benefits and risk of both pharmacotherapy and  bariatric surgery, as well as interventions   1553 02:50:09,240 --> 02:50:14,399 that effectively address provider bias and  reduce stigma towards patients with obesity.  1554 02:50:14,399 --> 02:50:21,000 DR. ANDREA GARBER: Hello, I'm Andrea Garber. I'm  a Professor of Pediatrics at the University of   1555 02:50:21,000 --> 02:50:25,620 California, San Francisco, and Director  of Nutrition for Our Eating Disorders   1556 02:50:25,620 --> 02:50:30,660 Program. Very pleased to be part of this  conference on malnutrition, and to speak   1557 02:50:30,660 --> 02:50:36,540 to you today about our advances in the treatment  of malnutrition in patients with anorexia nervosa.   1558 02:50:37,560 --> 02:50:43,800 Anorexia nervosa is a psychiatric diagnosis with  behaviors such as restriction and over exercising   1559 02:50:43,800 --> 02:50:50,160 that results in the loss of lean and fat mass. The  malnutrition of anorexia nervosa is considered to   1560 02:50:50,160 --> 02:50:55,920 be relatively uncomplicated because there usually  is no underlying infection, critical illness,   1561 02:50:55,920 --> 02:51:03,660 or cachexia. The numerous endocrine adaptations  that are directed toward extending life in this   1562 02:51:03,660 --> 02:51:08,700 state of starvation have been very well described  in patients with anorexia nervosa, such as low   1563 02:51:08,700 --> 02:51:14,639 leptin, resulting in an overall hypogonadal  hypo metabolic state, which we often describe   1564 02:51:14,640 --> 02:51:20,880 to parents as a state of hibernation. However, we  know children and adolescents are not there and   1565 02:51:20,880 --> 02:51:26,760 they are not equipped to withstand malnutrition  for long. Our patients quickly develop autonomic   1566 02:51:26,760 --> 02:51:32,880 dysfunction clinically indicated by vital sign  abnormalities that require hospitalization.   1567 02:51:34,020 --> 02:51:39,420 These are the most common vital sign abnormalities  in patients with anorexia nervosa when they   1568 02:51:39,420 --> 02:51:46,200 present for hospitalization. And we use these  as nutrition sensitive outcomes to measure the   1569 02:51:46,200 --> 02:51:52,920 efficacy of our refeeding protocols. So, you can  see here bradycardia hypotension or the stasis   1570 02:51:52,920 --> 02:51:59,580 hypothermia, we use these as a multifactorial  outcome to measure how well we are feeding these   1571 02:51:59,580 --> 02:52:06,420 patients. Of course, the greatest risk as in many  patients with malnutrition that can arise during   1572 02:52:06,420 --> 02:52:12,540 the course of the hospitalization is the refeeding  syndrome and unfortunately, since this was first   1573 02:52:12,540 --> 02:52:18,720 described among with prisoners of World War  II, all of the end organ complications of this   1574 02:52:18,720 --> 02:52:22,920 syndrome have been documented in patients  with anorexia nervosa during refeeding,   1575 02:52:22,920 --> 02:52:30,540 including cardiac arrhythmia, failure and arrest,  delirium, seizures, coma, and death. And so,   1576 02:52:30,540 --> 02:52:37,380 our approach to refeeding for many decades,  and all of the recommendations for refeeding   1577 02:52:37,380 --> 02:52:43,439 and patients with anorexia nervosa were extremely  conservative. In the U.S., published recommendations   1578 02:52:43,439 --> 02:52:50,460 began around 1,200 calories per day, advancing  slowly by 200 calories every other day. In Europe,   1579 02:52:50,460 --> 02:52:56,819 there were recommendations in place as starting  as low as 500 calories per day. And studies show   1580 02:52:56,819 --> 02:53:03,420 that using these conservative start low and go  slow approaches that it took weeks to restore   1581 02:53:03,420 --> 02:53:09,000 medical stability. And there are many studies  to show that protracted hospitalizations in   1582 02:53:09,000 --> 02:53:14,580 patients with eating disorders contribute to the  high cost of care for this illness, and they do   1583 02:53:14,580 --> 02:53:20,100 not improve outcomes. About half of patients are  readmitted within the first year of their first   1584 02:53:20,100 --> 02:53:27,540 hospitalization. Only one third are recovered at 12  months. And anorexia nervosa continues to have   1585 02:53:27,540 --> 02:53:34,260 the highest mortality rate of all psychiatric  disorders. So our research program is focused   1586 02:53:34,260 --> 02:53:40,920 on optimizing refeeding approaches for patients  with eating disorders. And we were fortunate to be   1587 02:53:40,920 --> 02:53:49,260 funded to do our first clinical trial by the NICHD  from 2015 to 2020 where performed the strong trial.   1588 02:53:49,260 --> 02:53:54,660 This was a very straightforward clinical trial  comparing the standard of care that I told you   1589 02:53:54,660 --> 02:54:04,139 about starting here at 1,400 calories and stepping  up slowly by 200 every other day, versus a more   1590 02:54:04,140 --> 02:54:10,319 aggressive refeeding protocol that we developed at  UCSF and others published preliminary findings to   1591 02:54:10,319 --> 02:54:16,620 support such as a group by Whitelion colleagues  and Melbourne. Patients were enrolled upon   1592 02:54:16,620 --> 02:54:21,660 admission to hospital. They were 12 to 24 year  olds with malnutrition evidenced by the vital sign   1593 02:54:21,660 --> 02:54:29,189 abnormalities that I showed. And we collected data  every day in hospital and over 12 months of follow   1594 02:54:29,189 --> 02:54:36,599 up. We also had a very tight electrolyte repletion  protocol. This is a Threshold Method, so unlike   1595 02:54:37,140 --> 02:54:44,700 the the new ASPEN recommendations that discuss  relative declines, this was repletion protocol   1596 02:54:44,700 --> 02:54:53,220 that only treated low electrolyte levels. So, a  potassium below 3.5, phosphorus, serum phosphorus   1597 02:54:53,220 --> 02:55:00,720 below three and magnesium below 1.8. So, to cut  right to the chase, here are the findings. We were   1598 02:55:00,720 --> 02:55:06,060 able to show that using high calorie refeeding  compared to the low calorie standard of care,   1599 02:55:06,060 --> 02:55:13,200 we could stabilize medical complications three  days earlier. Specifically heart rate normalized   1600 02:55:13,200 --> 02:55:20,580 four days earlier, weight gain was 0.8 kilos  higher. And importantly, hospital stay was   1601 02:55:20,580 --> 02:55:27,300 four days shorter, which translates into almost  a $20,000 healthcare savings per participant.   1602 02:55:27,840 --> 02:55:33,840 In terms of safety, we found no differences  in electrolyte shifting. So, only a handful   1603 02:55:33,840 --> 02:55:38,640 of patients developed hypophosphatemia. You  can see here. And there was no difference   1604 02:55:38,640 --> 02:55:43,380 in the proportion who needed electrolyte  correction. We did find that the nadir in  1605 02:55:43,380 --> 02:55:48,240 electrolytes occurred earlier with high calorie  refeeding, which has implications for monitoring,   1606 02:55:48,240 --> 02:55:51,660 meaning that if you're going to feed  high calories, you need to do more   1607 02:55:51,660 --> 02:55:58,139 monitoring upfront. And then in terms of long term  outcomes, no differences in clinical remission,   1608 02:55:58,140 --> 02:56:03,840 which is defined as a combination of both  cognitive and weight recovery. And what   1609 02:56:03,840 --> 02:56:08,460 this tells us if if the long term outcomes  were equally good with these two treatments,   1610 02:56:08,460 --> 02:56:14,100 that the upfront savings associated with high  calorie refeeding were sustained over 12 months.  1611 02:56:16,140 --> 02:56:23,220 We're very proud that we have worked hard too,  to rapidly translate these findings. So, the   1612 02:56:23,220 --> 02:56:28,920 new recommendations for refeeding in the US and  internationally reflect high calorie refeeding.   1613 02:56:30,600 --> 02:56:37,620 Now, about opportunities and gaps. One of the  serendipitous findings that came out of the   1614 02:56:37,620 --> 02:56:44,040 strong study is that 43% of the patients in fact,  were diagnosed with atypical anorexia nervosa. If   1615 02:56:44,040 --> 02:56:50,279 you're not familiar with this relatively new  diagnosis, it refers to patients who present   1616 02:56:50,279 --> 02:56:57,120 at or near the median BMI for their age and  sex. So, here's an example of a growth chart   1617 02:56:57,120 --> 02:57:03,359 of a young person with atypical AN, and you can  see that they technically have, quote, unquote,   1618 02:57:03,359 --> 02:57:10,139 normal weight. And in fact, in anorexia nervosa,  this would be considered a recovery weight. But   1619 02:57:10,140 --> 02:57:15,180 this is where these young people are presenting  for hospitalization. And what we showed is that   1620 02:57:15,180 --> 02:57:19,500 aside from their differences in presentation  weighed, there are no differences in medical   1621 02:57:19,500 --> 02:57:26,760 severity. Patients with atypical present with just  as likely Amenorrhea, similar percentage of weight   1622 02:57:26,760 --> 02:57:31,859 loss, and similar medical complications.  So, this is not anorexia nervosa light,   1623 02:57:31,859 --> 02:57:39,299 this is in fact a diagnosis associated with  malnutrition and medical complications. Now,   1624 02:57:39,300 --> 02:57:44,580 when we refed these patients, as I said, you  can see here in the red line, if you look at this   1625 02:57:44,580 --> 02:57:50,580 survival curve as patients step up to restored  medical stability, patients with anorexia did well   1626 02:57:50,580 --> 02:57:56,880 on high calorie feeding. However, patients with  atypical struggle behind and require two to three   1627 02:57:56,880 --> 02:58:04,140 more days of refeeding even on higher calorie  protocols. And so, we're now again fortunate to   1628 02:58:04,140 --> 02:58:10,020 be funded again by the NICHD to perform a second  clinical trial that is totally focused on atypical   1629 02:58:10,020 --> 02:58:17,340 anorexia nervosa. And looking at from more of a  precision medicine lens, how can we individualize   1630 02:58:17,340 --> 02:58:23,100 the refeeding protocols and optimize outcomes  in these patients who have diverse body weights? 1631 02:58:24,960 --> 02:58:31,859 An important gap associated with this study that  we are addressing is to develop biomarkers of   1632 02:58:31,859 --> 02:58:35,939 recovery. If weight is not informative in  these young people. And in fact, not only   1633 02:58:35,939 --> 02:58:40,379 is it non informative, it's highly controversial  because many of these patients became overweight,   1634 02:58:40,380 --> 02:58:45,120 some of them became obese. And there's  a lot of controversy about how high we   1635 02:58:45,120 --> 02:58:50,399 should go with recovery weights. So, as part  of this study, we are including biomarkers   1636 02:58:50,399 --> 02:58:55,439 to look at developing new benchmarks of  recovery, including the sex hormones,   1637 02:58:55,439 --> 02:59:02,939 T3 cortisol leptin and energy expenditure by  indirect calorimetry. We're also very interested   1638 02:59:02,939 --> 02:59:08,639 in developing body composition as a benchmark  of recovery in atypical AN. There's been some   1639 02:59:08,640 --> 02:59:15,420 very interesting talks during the course of this  workshop about sarcopenic obesity. And similarly,   1640 02:59:15,420 --> 02:59:21,240 these patients who are quote unquote normal  weight have highly altered body composition, and   1641 02:59:21,240 --> 02:59:27,479 that could be studied and used as a benchmark for  recovery. In collaboration with John Shepard and   1642 02:59:27,479 --> 02:59:35,639 Steven Heymsfield and support from NIDDK, we have  been studying the use of three dimensional optical   1643 02:59:35,640 --> 02:59:42,240 imaging to look at or as a use of a non invasive  measure of body composition and underweight   1644 02:59:42,240 --> 02:59:49,439 patients that I think has high potential for use  in our eating disorder patients, where other types   1645 02:59:49,439 --> 02:59:55,019 of anthropometrics would be highly inappropriate  and potentially psychologically triggering. And   1646 02:59:55,020 --> 03:00:00,720 we have a couple of papers already validating  beyond many papers validating this method.   1647 03:00:00,720 --> 03:00:07,140 There are a couple of specifically in children and  underweight patients. The final gap that I think   1648 03:00:07,140 --> 03:00:13,380 really deserves exploration here is the impact  of the gut microbiome on metabolic recovery in   1649 03:00:13,380 --> 03:00:18,779 patients with anorexia nervosa. We know that from  several studies now that patients with anorexia   1650 03:00:18,779 --> 03:00:25,080 nervosa have marked dysbiosis associated with  their malnutrition, that it does not fully recover   1651 03:00:25,080 --> 03:00:30,479 during the course of refeeding. And it has been  well characterized as including low production of   1652 03:00:30,479 --> 03:00:35,759 short chain fatty acids. But what is not known  is how this may modulate metabolic recovery,   1653 03:00:35,760 --> 03:00:40,560 or in fact, thwart response to refeeding  such as slowing down the weight gain.   1654 03:00:41,399 --> 03:00:47,759 I want to just take a moment to thank my  colleagues and collaborators and again, the NICHD for their support of this work. 1655 03:00:47,760 --> 03:00:56,880 ELENA LADAS: Hello, my name is Elena Ladas, and   1656 03:00:56,880 --> 03:00:57,540 I'm at Columbia University Irving  Medical Center, and here to talk   1657 03:00:57,540 --> 03:01:00,479 to you about the double burden of  malnutrition and childhood cancer.   1658 03:01:01,859 --> 03:01:05,819 So, childhood cancer is the second leading  cause of death among children. And in the   1659 03:01:05,819 --> 03:01:11,099 past 20 years, we have seen an increase both  nationally and globally in childhood cancer.   1660 03:01:11,760 --> 03:01:17,640 In terms of research and nutrition in  pediatric oncology, it really isn't until 2005,   1661 03:01:17,640 --> 03:01:25,380 where we started to get some well collected data  that documented both the role of under nutrition   1662 03:01:25,380 --> 03:01:32,160 and over nutrition in terms of its impact on  treatment related toxicities, as well as survival.   1663 03:01:33,720 --> 03:01:42,840 And so, here's two very common clinical situations  that we encounter. The first being a patient who   1664 03:01:42,840 --> 03:01:50,880 has acute lymphoblastic leukemia, had started  treatment at a healthy or ish weight. And if   1665 03:01:50,880 --> 03:01:56,279 you followed his, we would expect his weight to  kind of follow this red line. However, once he   1666 03:01:56,279 --> 03:02:02,040 starts treatment for leukemia, his weight starts  to decrease and increase, and then throughout   1667 03:02:02,040 --> 03:02:09,120 treatment which ends about here, he has a striking  increase in BMI and then into survivorship this   1668 03:02:09,120 --> 03:02:16,500 continues. On the other side, this is a patient  with a solid tumor. Five year old boy. Starts   1669 03:02:16,500 --> 03:02:22,800 again in the vicinity of a healthy to low weight.  Starts treatment. And again, if he would have   1670 03:02:22,800 --> 03:02:29,220 stayed in his weight category, we would have  anticipated this red line. But in fact, due to   1671 03:02:30,479 --> 03:02:35,040 conditions impacting his gut, as well as  another number a variety of other things,   1672 03:02:35,040 --> 03:02:40,500 he becomes severely malnourished to a point  where his Z-score is around a negative three. 1673 03:02:42,479 --> 03:02:49,259 Now, it's important to recognize that in childhood  cancer, malnutrition varies wildly by disease. So,   1674 03:02:49,260 --> 03:02:55,319 for those patients, for instance here that have  medulla blastoma, you can see a high incidence   1675 03:02:55,319 --> 03:03:01,620 of both under and over nutrition depending on the  phase of treatment. That's true for osteosarcoma,   1676 03:03:01,620 --> 03:03:07,979 and some other types of sarcomas. However, in  contrast, we have other diseases like Hodgkin's   1677 03:03:07,979 --> 03:03:16,740 disease, which the malnutrition both under and  over is smaller than for other cancers. But it   1678 03:03:16,740 --> 03:03:21,240 really the take home message is that this  is not one stop shopping that this really   1679 03:03:21,240 --> 03:03:25,559 requires a different approach depending  on the patient's pre existing condition.   1680 03:03:26,760 --> 03:03:32,580 And type of disease and therapy. So I'd like  to take childhood acute lymphoblastic leukemia   1681 03:03:32,580 --> 03:03:38,040 as an example, because it is the most common  childhood cancer. Survival is really outstanding   1682 03:03:38,040 --> 03:03:44,100 for patients who are standard risk ALL. They  have even over a 95% chance of survival,   1683 03:03:44,100 --> 03:03:52,140 overall is still 84% quite high. Treatment  consists of two years and it's either, you know,   1684 03:03:52,140 --> 03:03:57,720 vacillates between high and low dose therapy  and steroids are an important part of treatment.   1685 03:03:58,500 --> 03:04:03,240 However, there has been a price trial  of this success. About 60% of patients   1686 03:04:03,240 --> 03:04:06,779 that are healthy weight at diagnosis become  overweight or obese by the end of treatment.   1687 03:04:06,779 --> 03:04:14,399 And this continues into survivorship.Ten to 50%  of patients develop hypoglycemia and in turn,   1688 03:04:14,399 --> 03:04:20,639 this impacts their survival. And there's a number  of other morbidities, including pancreatitis, as   1689 03:04:20,640 --> 03:04:26,640 well as the risk of adult onset cancers, metabolic  disease, etc once they complete treatment.   1690 03:04:28,380 --> 03:04:35,220 Now ALL has been described as a pre-obese state  and this figure here on the right illustrates how   1691 03:04:35,220 --> 03:04:42,060 the three different weight groups, the green line  being obese, the red overweight, the blue healthy,   1692 03:04:42,060 --> 03:04:47,580 and how their weight trajectories change over  time. And clearly you can see that those patients   1693 03:04:47,580 --> 03:04:52,920 with a healthy weight at diagnosis become  overweight or obese by the end of treatment.   1694 03:04:55,740 --> 03:05:01,859 So here, figuratively, you can see this is a  meta analysis here on the left that compiled data   1695 03:05:01,859 --> 03:05:07,859 and had children with ALL and again found about  35% reduction in patients with poor nutrition   1696 03:05:07,859 --> 03:05:15,299 at diagnosis. And in turn, those patients also  are predisposed to hypoglycemia. And we see a   1697 03:05:15,300 --> 03:05:20,580 distinct difference in survival in those patients  who are hypoglycemic versus those that are not.   1698 03:05:21,240 --> 03:05:28,500 So we know that nutrition matters. We also know  that it can be remediated, meaning that the impact   1699 03:05:28,500 --> 03:05:36,720 of poor nutrition on outcome can be resolved.  So figure A here illustrates survival and the   1700 03:05:36,720 --> 03:05:41,040 yellow line of patients that are healthy  weight throughout the course of treatment.   1701 03:05:41,880 --> 03:05:46,859 And the other two lines are both patients that  are either undernourished or over nourished and   1702 03:05:46,859 --> 03:05:54,479 you can see their survival similar. Now, contrast  with, contrast that with figure B, and it's the   1703 03:05:54,479 --> 03:06:00,719 red line and the dotted black line that's slightly  above the yellow, the yellow line. And those are   1704 03:06:00,720 --> 03:06:07,140 patients that were in an at risk category either  under or over nutrition, and it was remediated.   1705 03:06:07,140 --> 03:06:13,020 So they did not spend a prolonged period of time  at an at risk weight group. And you can see their   1706 03:06:13,020 --> 03:06:16,980 survival is the same as those patients that remain  a healthy weight through the course of treatment. 1707 03:06:19,080 --> 03:06:25,500 So we've done a lot of work trying to understand  not only is this a matter of lifestyle or are   1708 03:06:25,500 --> 03:06:32,340 there biological factors that contribute. So  the ALL dataset, which is called DALLT,   1709 03:06:32,340 --> 03:06:37,740 is the largest dataset available, and it  looks at nutrition, genetics and diet over   1710 03:06:37,740 --> 03:06:45,120 the course of treatment for ALL. And the first  question that we wanted to ask this dataset is,   1711 03:06:45,120 --> 03:06:51,180 OK, this obesity, it must be related to access  eating, they are on steroids, they are sedentary.   1712 03:06:51,960 --> 03:06:57,240 You know, this just mean that's just explains why  they become obese. However, it does not explain   1713 03:06:57,240 --> 03:07:03,000 why they become obese and survivorship. But in  fact, that wasn't true because what we found was   1714 03:07:03,000 --> 03:07:09,000 that caloric increase intake decreases over time.  And again, you can contrast that decrease with   1715 03:07:09,000 --> 03:07:14,279 these patients. These are patients on different  regimens for ALL. But you can clearly see here's   1716 03:07:14,279 --> 03:07:19,019 where they start with BMI and here's where they  end. So this isn't really the entire story.   1717 03:07:20,939 --> 03:07:27,719 We've also looked at genetic factors  and determining if patients with a   1718 03:07:27,720 --> 03:07:33,300 poly genetic risk score or a predisposition  to obesity cannot explain it. And in fact,   1719 03:07:33,300 --> 03:07:42,359 both in non-Hispanic and Hispanic patients that  the a poly genetic risk score. So a propensity for   1720 03:07:42,359 --> 03:07:48,000 obesity does have some impact in those patients  that develop it over the course of treatment.   1721 03:07:49,260 --> 03:07:53,820 Now, what are the causal mechanisms? I  mean, quite frankly, we really don't know.   1722 03:07:55,080 --> 03:07:59,279 You know, there's really a lot of research that  needs to be done. We do know that this is disease   1723 03:07:59,279 --> 03:08:05,939 specific. I'm highlighting ALL, but malnutrition  and other diagnoses have also revealed similar   1724 03:08:05,939 --> 03:08:10,859 results. It may be a difference in terms of  the steroid. What prompts this more or less,   1725 03:08:12,540 --> 03:08:16,680 and certainly our pharmacodynamics, but  it's controversial and quite understudied.   1726 03:08:16,680 --> 03:08:23,700 There's also a factor of the leukemia microbiome  environment or other tumors that may be more or   1727 03:08:23,700 --> 03:08:28,920 less susceptible. And certainly the microbiome  has come into play in this, particularly with a   1728 03:08:28,920 --> 03:08:36,540 lot of the particularly with the increased use of  immunotherapy. And does that change the microbiota   1729 03:08:36,540 --> 03:08:43,680 in such a way to promote kind of deleterious  down downstream pathways that start in the gut. 1730 03:08:46,020 --> 03:08:52,140 So we are advancing towards interventional  studies, although slowly. One of the first   1731 03:08:52,140 --> 03:08:57,900 studies that looked at dietary intervention and  if it can even stave off obesity. So meaning   1732 03:08:58,439 --> 03:09:05,879 is the combination of factors overriding just  dietary education. And in this small pilot study,   1733 03:09:05,880 --> 03:09:13,080 we did find that nutrition education was effective  at improving diet. And most importantly, it staved   1734 03:09:13,080 --> 03:09:20,640 off weight gain. Again, this was not a weight  loss program. It was really just looking at if we   1735 03:09:20,640 --> 03:09:26,100 intervene aggressively and early, can we stave off  that weight gain? For the majority of patients,   1736 03:09:26,100 --> 03:09:30,840 again, in this small pilot we did, that there  is still a subset of patients, that subset of   1737 03:09:30,840 --> 03:09:36,480 patients that require more information about  the dietary intervention was not as effective.   1738 03:09:37,620 --> 03:09:44,819 To follow up on this, the Children's Oncology Group is launching a study. It's a multicenter   1739 03:09:44,819 --> 03:09:50,219 study that will look at not only dietary  intervention for the prevention of weight gain,   1740 03:09:50,220 --> 03:09:57,720 but is also going to look at the role of genetics  and socio demographic risk factors for obesity to   1741 03:09:57,720 --> 03:10:03,120 see if you know how these factors intertwine  with one another and may impact the increased   1742 03:10:03,120 --> 03:10:12,059 or decreased risk. So in closing, there are many  research opportunities in childhood cancer. You   1743 03:10:12,060 --> 03:10:20,100 know, we do know that both under and over  nutrition impacts, disease outcome as well   1744 03:10:20,100 --> 03:10:25,920 as treatment related toxicities. But in order  to effectively remediate this, we need more   1745 03:10:25,920 --> 03:10:32,880 understanding of the underlying mechanisms of  this. Existing research is limited to ALL. So   1746 03:10:32,880 --> 03:10:37,859 we really also need to understand how these  mechanisms, once understood, vary by disease,   1747 03:10:38,760 --> 03:10:44,399 and much of the existing data is really limited to  body, body mass index. And I didn't have time to   1748 03:10:44,399 --> 03:10:51,420 go into the other body of research that that has  looked at body composition, but body composition   1749 03:10:51,420 --> 03:10:57,180 certainly has played a role, a role both in  Hematologic as well as solid tumors, potentially   1750 03:10:57,180 --> 03:11:04,920 by altering pharmacokinetics or through other  factors that we don't know. Prevention is key   1751 03:11:04,920 --> 03:11:10,380 both for under and over and for undernutrition, we  know proactive intervention, and some ways that's   1752 03:11:10,380 --> 03:11:16,260 a little bit easier to resolve with the exception  of (UNKNOWN). However, the prevention of obesity   1753 03:11:16,260 --> 03:11:23,580 and the potential use of appetite inhibitors such  as GLP-1 agonists may be a clinical useful tool,   1754 03:11:23,580 --> 03:11:29,279 however, really needs more research, and the role  of dietary intake and quality is really virtually   1755 03:11:29,279 --> 03:11:36,719 unknown. There is some data to show that diet  quality does impact many of these mechanisms   1756 03:11:36,720 --> 03:11:41,640 and factors that we've talked about, certainly  especially as the microbiome becomes more into   1757 03:11:41,640 --> 03:11:48,240 play. But again, we need a lot more research in  this area. So thank you so much for your attention   1758 03:11:48,240 --> 03:11:53,819 and I look forward to the discussion.   1759 03:11:53,819 --> 03:11:59,460 DR. LORI BECHARD: Hello, I'm Lori Bechard and I'm pleased to present  during this important workshop among my esteemed   1760 03:11:59,460 --> 03:12:04,319 colleagues in the field today, I'll review  some of the aspects related to malnutrition   1761 03:12:04,319 --> 03:12:09,660 in pediatric critical care with a focus on the  consequences of nutrient intake inadequacy.   1762 03:12:11,040 --> 03:12:14,700 My disclosures are my employment at Boston  Children's, where my department supports   1763 03:12:14,700 --> 03:12:19,080 most of my work. And my research is partially  funded by the Pediatric Nutrition Practice Group,   1764 03:12:19,080 --> 03:12:25,080 and NIDDK grant that's awarded to Dr. Mehta and (UNKNOWN) for a multicenter trial.   1765 03:12:26,460 --> 03:12:30,000 The objectives of my talk  today are to describe the   1766 03:12:30,000 --> 03:12:33,840 unique barriers to nutrient delivery  in pediatric intensive care units,   1767 03:12:33,840 --> 03:12:38,520 to synthesize relationships between nutrition  practices and outcomes in PICUs use around   1768 03:12:38,520 --> 03:12:43,680 the world, and to explain research gaps and  future opportunities in this environment. 1769 03:12:45,840 --> 03:12:50,460 First, we'll review the commonly encountered  barriers to adequate nutrient delivery in   1770 03:12:50,460 --> 03:12:56,640 pediatric critical care patients. These barriers  can be thought of as stemming from three different   1771 03:12:56,640 --> 03:13:03,000 sources, the patient, him or herself, the provider  or care team taking care of the patient and the   1772 03:13:03,000 --> 03:13:07,800 published practice guidelines, pre-existing  nutritional status, as well as how that involves   1773 03:13:07,800 --> 03:13:13,200 the metabolic changes that occur with critical  illness or trauma and intolerance to enteral   1774 03:13:13,200 --> 03:13:18,300 or parenteral nutrients. All may challenge  the goal of achieving nutrient adequacy.   1775 03:13:18,300 --> 03:13:23,460 Furthermore, care team providers may be challenged  to best understand and prescribe the most   1776 03:13:23,460 --> 03:13:27,960 appropriate amount, type and route of nutrients.  Considering the diverse mix of patients who   1777 03:13:27,960 --> 03:13:33,359 present to a pediatric ICU. Feedings are often  interrupted for a variety of medical reasons,   1778 03:13:33,359 --> 03:13:38,700 preventing patients from achieving the intended  amounts. And finally, institutional algorithms,   1779 03:13:38,700 --> 03:13:44,460 national guidelines and other evidence will help  at a population level could inform practices   1780 03:13:44,460 --> 03:13:48,899 that might ultimately interfere with optimal  delivery of nutrients for some PICU patients.   1781 03:13:51,060 --> 03:13:55,859 About half of patients presenting to the PICU  with critical illness are of normal weight status   1782 03:13:55,859 --> 03:14:01,859 by BMI Z score, but a substantial proportion  are either underweight, overweight or obese, as   1783 03:14:01,859 --> 03:14:06,000 shown in this large cohort study of mechanically  ventilated patients from our PiNS studies.   1784 03:14:07,859 --> 03:14:12,899 And being underweight was associated with  a 1.5 times higher risk of mortality when   1785 03:14:12,899 --> 03:14:17,639 controlled for other important risk factors.  Both underweight and obesity were associated   1786 03:14:17,640 --> 03:14:20,701 with higher risk of infection and  longer life of stay in the hospital. 1787 03:14:23,040 --> 03:14:28,019 The metabolic sequelae of critical illness in  children is a unique scenario where an insult   1788 03:14:28,020 --> 03:14:33,120 such as trauma, sepsis, surgery or other critical  event triggers muscle breakdown to supply proteins   1789 03:14:33,120 --> 03:14:38,819 for the acute inflammatory response, along with  decreased utilization of glucose and resulting   1790 03:14:38,819 --> 03:14:45,960 hyperglycemia and lipolysis to provide ketone fuel  for the brain. This response leads to loss of lean   1791 03:14:45,960 --> 03:14:50,160 body mass and impaired tolerance to nutrients,  compounding the effect of the illness itself.   1792 03:14:50,760 --> 03:14:55,500 This often leads to nutritional deficits and  deterioration throughout the hospital stay. 1793 03:14:57,420 --> 03:15:01,920 In addition, there are several specific barriers  to receiving optimal nutrition delivery,   1794 03:15:01,920 --> 03:15:06,840 particularly by the favorite enteral route.  It's often difficult to prescribe the targeted   1795 03:15:06,840 --> 03:15:11,580 nutrition prescription accurately due to the  variability, volatility and heterogeneous   1796 03:15:11,580 --> 03:15:16,380 nature of critically ill children. Even with the  best feeding targets, interruptions to enteral   1797 03:15:16,380 --> 03:15:19,260 nutrition seem inevitable. Whether  for issues related to intolerance,   1798 03:15:19,260 --> 03:15:25,920 medical or surgical interventions or procedures.  Also, critically ill patients typically require   1799 03:15:25,920 --> 03:15:30,660 many medications and therapies then incur  additional volume, thereby limiting volume,   1800 03:15:30,660 --> 03:15:35,819 a lot of nutrition since excess fluids are  often poorly tolerated during critical illness. 1801 03:15:37,979 --> 03:15:42,000 The use of algorithms and protocols in the  PICU may help to reduce the barriers   1802 03:15:42,000 --> 03:15:47,399 and interruptions to nutrition adequacy in  critically ill children. This pre-post study   1803 03:15:47,399 --> 03:15:50,519 of the implementation of an internal  feeding algorithm at Boston Children's   1804 03:15:50,520 --> 03:15:54,899 shows how energy goals were achieved in a  significantly higher proportion of patients   1805 03:15:54,899 --> 03:15:59,700 and both a time to reach energy target and the  number of avoidable interruptions to enteral   1806 03:15:59,700 --> 03:16:03,840 nutrition were significantly reduced following  implementation of the algorithm in the (UNKNOWN).   1807 03:16:06,540 --> 03:16:12,300 While locally implemented protocols may improve  attainment of nutritional adequacy, there may be   1808 03:16:12,300 --> 03:16:17,520 gaps when interpreting national guidelines such as  these from ASPEN and SCCM, published in 2017.   1809 03:16:17,520 --> 03:16:23,041 Since many pragmatic questions around nutrition  delivery remain unanswered by research evidence.   1810 03:16:24,359 --> 03:16:30,000 These European guidelines were published in 2020  and are mostly aligned with the ASPEN guidelines,   1811 03:16:30,000 --> 03:16:35,100 concurring with early EN and energy provision  not to exceed resting energy expenditure in   1812 03:16:35,100 --> 03:16:39,540 the acute phase of critical illness. However,  there are two arguably important differences   1813 03:16:39,540 --> 03:16:43,680 with the European guidelines specifically  recommending withholding a PN during   1814 03:16:43,680 --> 03:16:47,520 the first week of critical illness for  all patients and limiting consideration   1815 03:16:47,520 --> 03:16:53,280 for the 1.5 grams of protein per kilo  guidance to enter early fed patients only.   1816 03:16:55,200 --> 03:17:00,300 So since we know there are barriers to enteral nutrition limitations to the guidelines,   1817 03:17:00,300 --> 03:17:04,859 let's take a look at a few of the larger studies  that suggest the need for more research on these   1818 03:17:04,859 --> 03:17:08,939 topics. These studies examined protein  and energy delivery and the timing of   1819 03:17:08,939 --> 03:17:13,319 nutrition delivery in the PICU and how it  relates to clinical and nutritional outcomes.   1820 03:17:14,880 --> 03:17:19,140 Our first international cohort study of  nutrition practices and outcomes showed   1821 03:17:19,140 --> 03:17:23,340 low energy and protein delivery of enteral nutrition through the first ten days of critical   1822 03:17:23,340 --> 03:17:28,319 illness and a significant relationship between  higher proportions of exclusively enteral energy   1823 03:17:28,319 --> 03:17:34,859 adequacy and lower 60 day mortality. In our second  PiNS study, we turn our attention to protein   1824 03:17:34,859 --> 03:17:39,899 specifically and continue to find low enteral delivery of protein and a significant relationship   1825 03:17:39,899 --> 03:17:43,920 between enteral protein adequacy, as defined  by percentage of the prescribed target that   1826 03:17:43,920 --> 03:17:48,540 was delivered in 60 day mortality, especially  among patients with the most severe illness. 1827 03:17:49,620 --> 03:17:56,220 With regards to timing of nutrition  delivery, an analysis of the large cohort of  1828 03:17:56,220 --> 03:18:00,240 PICUs from the Virtual PICU Systems  database showed lower mortality among children   1829 03:18:00,240 --> 03:18:05,519 who received at least 25% of their prescribed goal  calories by enteral nutrition within the first two   1830 03:18:05,520 --> 03:18:11,399 days of PICU admission, suggesting the need  to start enteral feeds early with benefit even   1831 03:18:11,399 --> 03:18:18,000 when low proportions of delivery are achieved. We  looked at timing of delivery adequacy in our most   1832 03:18:18,000 --> 03:18:23,040 recent PiNS cohort study in this group  of over 1800 mechanically ventilated children   1833 03:18:23,040 --> 03:18:29,340 achieving 60% energy or protein adequacy either by  enteral or combination of enteral and parenteral   1834 03:18:29,340 --> 03:18:34,020 nutrition in the first seven days of PICU admission was associated with a significantly   1835 03:18:34,020 --> 03:18:39,180 lower risk of mortality. This suggests that  it may be important to deliver at least 60%   1836 03:18:39,180 --> 03:18:44,279 adequacy by four to seven days after PICU admission, but there may not be any additional   1837 03:18:44,279 --> 03:18:48,899 benefit to a more aggressive target within the  first days, first three days after admission. 1838 03:18:50,160 --> 03:18:55,260 While cohort studies are helpful, certainly a  large clinical trial is higher quality evidence,   1839 03:18:55,260 --> 03:18:59,700 and while rare in the PICU setting, there  is one well-known three center trial of early   1840 03:18:59,700 --> 03:19:05,040 versus late PN known as the PEPaNIC trial that has  informed many publications and discussion of this   1841 03:19:05,040 --> 03:19:12,540 topic in recent years. They randomized over 1400  patients to receive PN, either within 24 hours of   1842 03:19:12,540 --> 03:19:18,359 admission or if needed, on day eight, with early  enteral feedings provided per protocol and the   1843 03:19:18,359 --> 03:19:23,519 primary outcomes were ICU acquired infections  and readiness for discharge. Most patients in   1844 03:19:23,520 --> 03:19:28,201 the late group actually never needed PN since they  achieve their goal through enteral feeds alone.   1845 03:19:29,160 --> 03:19:33,599 Their analyses were adjusted for several  contributing factors such as diagnosis,   1846 03:19:33,600 --> 03:19:39,120 age, illness, severity, malnutrition and site,  and showed significantly lower odds of infection   1847 03:19:39,120 --> 03:19:45,120 and showing shorter length of stay in the late  PN group, suggesting benefit to withholding PN   1848 03:19:45,120 --> 03:19:51,420 in the first week of PICU admission. There  are important limitations to the PEPaNIC trial,   1849 03:19:51,420 --> 03:19:56,220 however. The intervention may not have been  a pragmatic approach to some critically ill   1850 03:19:56,220 --> 03:20:01,859 children, particularly in U.S. PICU. Since  the application of PN was to extreme extremes   1851 03:20:01,859 --> 03:20:07,500 of timing, the population may also be different  with most who are able to receive full or nearly   1852 03:20:07,500 --> 03:20:12,720 full enteral nutrition. And for those in the early  PN group, the high energy targets may have caused   1853 03:20:12,720 --> 03:20:18,240 them to be overfed, which could have influenced  their outcomes. So many questions still remain as   1854 03:20:18,240 --> 03:20:24,120 to the ideal approach to nutrition for critically  ill children, which brings us to the final section   1855 03:20:24,120 --> 03:20:30,420 where we can highlight some of the nutrition  research opportunities in this population. We   1856 03:20:30,420 --> 03:20:35,160 have seen the importance of the timing and route  of nutrients. However, in real life PICU 1857 03:20:35,160 --> 03:20:41,099 settings, more nuance is often needed to achieve  optimal nutrient delivery. More investigation of   1858 03:20:41,100 --> 03:20:45,300 pragmatic approaches to nutrition, perhaps  combined with elements of rehabilitation   1859 03:20:45,300 --> 03:20:51,479 and mobility, as in the PICU up protocol is  now included in many U.S. PICUs. Also, since   1860 03:20:51,479 --> 03:20:56,879 fortunately mortality is very low in PICUs,  but morbidities are common consideration for the   1861 03:20:56,880 --> 03:21:02,040 impact of nutrition strategies on other short term  and long term outcomes is increasingly important.   1862 03:21:02,700 --> 03:21:07,559 Refinement of advanced techniques to measure  nutritional mediators such as body composition   1863 03:21:07,560 --> 03:21:14,279 and energy expenditure measurements at the bedside  is needed for tools such as muscle, ultrasound or   1864 03:21:14,279 --> 03:21:20,040 indirect calorimetry, as shown on this slide. And  many PICU patients have multiple morbidities   1865 03:21:20,040 --> 03:21:24,244 and chronic diseases where the relationship  between nutrition delivery and more patient   1866 03:21:24,244 --> 03:21:29,580 centered outcomes such as functional status and  quality of quality of life could be very relevant.   1867 03:21:31,080 --> 03:21:34,859 So with that, I want to acknowledge the  important contributions of, of course,   1868 03:21:34,859 --> 03:21:38,759 our patients, but also many dietitians,  investigators, clinicians and research   1869 03:21:38,760 --> 03:21:43,740 staff that have assisted with our studies. Too  many to mention here. And I thank you for your   1870 03:21:43,740 --> 03:21:51,359 attention and look forward to the discussions. 1871 03:21:51,359 --> 03:21:59,399 DR. DAVID SUSKIND: It's a pleasure to be here today to talk about nutritional therapies in inflammatory bowel  disease, their implication on health and disease.   1872 03:22:00,359 --> 03:22:07,139 Nutrition is not only integral in terms  of the well-being of our patients,   1873 03:22:07,140 --> 03:22:16,260 but it also is intertwined with disease and  disease activity in inflammatory bowel disease.   1874 03:22:17,640 --> 03:22:24,420 Malnutrition is common in pediatric IBD.  It's interrelated to a number of factors,   1875 03:22:24,420 --> 03:22:31,380 including anorexia, secondary to  elevated cytokines such as TNF alpha.   1876 03:22:32,340 --> 03:22:39,960 Also decreased oral intake, secondary  to symptoms, increased nutrient losses,   1877 03:22:39,960 --> 03:22:48,480 increased catabolism, drug therapies such as  corticosteroids and surgical interventions.   1878 03:22:50,040 --> 03:22:55,920 So why focus on nutrition in inflammatory bowel  disease? Well, there are many really important   1879 03:22:55,920 --> 03:23:02,040 reasons. One is not only does nutrition  have an effect in the acute setting,   1880 03:23:02,040 --> 03:23:09,600 but it has long term effects as well. And you can  see here that stunting is not an uncommon issue   1881 03:23:09,600 --> 03:23:16,980 in pediatric IBD. It also has implications  on psychosocial well-being of our patients.   1882 03:23:17,819 --> 03:23:24,840 In addition, our medication therapies, while  effective, are not completely effective for   1883 03:23:24,840 --> 03:23:31,500 every patient all of the time. And you can see  here in the sonic trial, using two very potent   1884 03:23:31,500 --> 03:23:39,600 immunosuppressants, Infliximab and azathioprine  and there is still only a 56% efficacy rate   1885 03:23:39,600 --> 03:23:47,880 in the short term for these patients. And  finally, nutrition is interrelated to the   1886 03:23:47,880 --> 03:23:56,640 potentially idiopathic genesis of IBD itself.  And we see this by increasing incidence of IBD   1887 03:23:56,640 --> 03:24:04,500 over the last 20, 50 plus years, both  in the pediatric and the adult worlds. 1888 03:24:08,100 --> 03:24:14,700 So to understand how nutrition and IBD  are interrelated, it's really important   1889 03:24:14,700 --> 03:24:23,220 for us to understand the IBD paradigm. We know  that inflammatory bowel disease is an immune   1890 03:24:23,220 --> 03:24:30,420 dysregulation. So the immune system which is there  to protect us has gone awry and is now attacking   1891 03:24:30,420 --> 03:24:36,300 the intestines. And there are many reasons for  this. One, there's a genetic predisposition,   1892 03:24:36,300 --> 03:24:44,819 but as noted prior, the incidence has increased  over the last 50 plus years, suggesting that   1893 03:24:44,819 --> 03:24:52,500 while this is important, it's not the main driver  of IBD. We know that certain medications such as   1894 03:24:52,500 --> 03:24:59,760 antibiotics are associated with IBD and we  know that westernized diets high in sugars   1895 03:24:59,760 --> 03:25:10,680 and high in fat are also associated with IBD.  Now the foods that we eat impact the different   1896 03:25:10,680 --> 03:25:18,239 components of IBD. The foods that we eat changed  the microbiome to being eubi, from being eubiotic   1897 03:25:18,239 --> 03:25:27,660 to becoming dysbiotic or being pro-inflammatory.  The foods that we eat also break down the mucosa,   1898 03:25:27,660 --> 03:25:34,739 which keeps away the vast majority of  bacteria from the intestinal immune system.   1899 03:25:35,880 --> 03:25:45,540 And because the immune system can now interact  more easily with the microbiome, the immune system   1900 03:25:45,540 --> 03:25:53,279 becomes upregulated, causing inflammation  leading to inflammatory bowel disease.   1901 03:25:54,420 --> 03:26:00,840 Because nutrition is intertwined with the  etiopathogenesis of inflammatory bowel disease,   1902 03:26:01,500 --> 03:26:08,760 it can also be used as an intervention,  as a therapy for IBD as well. And there's   1903 03:26:08,760 --> 03:26:14,520 no better example of this than  exclusive enteral nutrition or EEN.   1904 03:26:15,479 --> 03:26:22,379 This has been designated a primary nutritional  intervention for pediatric Crohn's disease by the   1905 03:26:22,380 --> 03:26:30,899 North American Society of Pediatric Astrology,  Hepatology and Nutrition. With EEN patients go   1906 03:26:30,899 --> 03:26:41,099 on to any formula and formula alone for six to 12  weeks. No other foods or drinks outside of water   1907 03:26:41,100 --> 03:26:49,860 are taken in, and this is given either orally or  via nasogastric tube. And as you can see here,   1908 03:26:50,399 --> 03:26:57,719 our center is so supportive of this intervention  because it is such an important intervention that   1909 03:26:57,720 --> 03:27:08,220 we on IBD Day placed our own nasogastric tubes  and gave ourselves formula as a mechanism of   1910 03:27:08,220 --> 03:27:17,340 support for our patients. EEN Intervention  has two main roles. It not only corrects the   1911 03:27:17,340 --> 03:27:25,200 malnutrition seen in pediatric Crohn's disease,  but it also treats the primary disease itself.   1912 03:27:25,979 --> 03:27:32,459 With regards to correction of the malnutrition,  it provides the caloric needs for the patients   1913 03:27:32,460 --> 03:27:40,859 and allows for catch up growth. In addition, it  corrects for micronutrient deficiencies often   1914 03:27:40,859 --> 03:27:47,099 seen in pediatric Crohn's disease. With  regarding to treating the primary disease   1915 03:27:47,100 --> 03:27:54,000 itself is been shown to resolve inflammation  and get patients into clinical remission.   1916 03:27:54,899 --> 03:28:04,080 And importantly, it improves mucosal healing  rates and decreases the need for prednisone usage,   1917 03:28:04,080 --> 03:28:11,580 which is associated with worse outcomes in  pediatric Crohn's disease. But one of the   1918 03:28:11,580 --> 03:28:19,739 most interesting aspects of EEN is that the  mechanism by which it works is still unknown.   1919 03:28:20,819 --> 03:28:28,739 One of the most pivotal studies on the use of EEN  in Crohn's disease is this study by Borelli and   1920 03:28:28,739 --> 03:28:38,040 colleagues. What they did is enrolled patients  with Crohn's disease into a ten week randomized   1921 03:28:38,040 --> 03:28:45,060 controlled trial of steroids versus exclusive  enteral nutrition. And they looked at three   1922 03:28:45,060 --> 03:28:51,600 main outcomes. They looked at clinical remission.  They looked at biochemical remission and they also   1923 03:28:51,600 --> 03:28:59,399 looked at mucosal healing rates. And as you can  see here with the pictogram on the left that the   1924 03:28:59,399 --> 03:29:06,599 remission rates, the clinical remission rates were  similar between EEN and steroids. In addition,   1925 03:29:06,600 --> 03:29:14,820 biochemical remission, meaning laboratory  improvements were similar between the two groups.   1926 03:29:15,420 --> 03:29:21,720 But what was different was the mucosal healing  rates. As you can see in this pictographs,   1927 03:29:21,720 --> 03:29:30,060 EEN worked significantly better than steroids  in healing the bowels, and this has large   1928 03:29:30,060 --> 03:29:38,939 implications on short term and long term outcomes.  There are a number of postulated mechanisms by   1929 03:29:38,939 --> 03:29:45,419 which EEN works in Crohn's disease. It may  be interrelated to a reduced luminal antigen   1930 03:29:45,420 --> 03:29:52,739 exposure leading to antigenic monotony which  allows the immune system to downregulate.   1931 03:29:53,700 --> 03:29:59,819 It may be interrelated to food exclusions,  specifically those foods that break down   1932 03:29:59,819 --> 03:30:08,519 the mucosal layer and allow the microbiome to  interact more with the intestinal immune system.   1933 03:30:09,779 --> 03:30:14,700 It may also be interrelated to indirect  effects of nutritional supplementation,   1934 03:30:14,700 --> 03:30:19,979 such as modification of fat content,  which affects the bile acid synthesis.   1935 03:30:20,939 --> 03:30:29,160 It may also be interrelated to trophic amino  acids or modulation of the gut microbiome and   1936 03:30:29,160 --> 03:30:35,760 metabolome. It has also been postulated  that mechanical properties of food may be   1937 03:30:35,760 --> 03:30:44,880 also interrelated with the inflammatory process  itself. But to date, no conclusive evidence has   1938 03:30:44,880 --> 03:30:55,020 pointed to one or other mechanisms as the cause  of the improvements we see with EEN in IBD.   1939 03:30:56,520 --> 03:31:03,000 There have been some studies looking at  potential mechanisms by which EEN works.   1940 03:31:03,600 --> 03:31:13,140 This study by (UNKNOWN) replicated Borelli's  earlier study showing efficacy of EEN in   1941 03:31:13,140 --> 03:31:19,560 Crohn's disease. But they took it a step  further. They not only looked at clinical,   1942 03:31:19,560 --> 03:31:28,319 biochemical and histologic outcomes, but they also  looked at the intestinal microbiome. And what you   1943 03:31:28,319 --> 03:31:36,960 can see here is the shifts that occurred with the  intervention. On the left hand side of the screen,   1944 03:31:36,960 --> 03:31:45,000 you can see the principal coordinate analysis  prior to treatment of the patients with Crohn's   1945 03:31:45,000 --> 03:31:52,800 disease and after the intervention with EEN  versus steroids. And you see a significant   1946 03:31:52,800 --> 03:32:02,520 shift in different directions with the usage of  EEN versus steroids possibly interrelated to why   1947 03:32:02,520 --> 03:32:11,460 we see better mucosal healing with EEN. And on the  right hand side of the screen, you can actually   1948 03:32:11,460 --> 03:32:19,859 see a number of important species and the shifts  that occurred with the different interventions.   1949 03:32:21,840 --> 03:32:29,760 This study by (UNKNOWN) looked at mucosal  inflammation and cytokine levels in patients with   1950 03:32:29,760 --> 03:32:38,939 Crohn's disease undergoing EEN and therapy. And  what you can see, is prior to the intervention,   1951 03:32:38,939 --> 03:32:46,439 the cytokine levels in the mucosa were  significantly elevated as compared to controls.   1952 03:32:47,100 --> 03:32:55,020 But after the intervention with EEN, the  pro-inflammatory cytokines reduced significantly   1953 03:32:55,020 --> 03:33:04,680 and became on par with that of controls.  Understanding the mechanisms by which EEN   1954 03:33:04,680 --> 03:33:15,960 works is essential. But what's more powerful is  to see it work in action. And so I wanted to bring   1955 03:33:15,960 --> 03:33:22,620 this clinical case forward. And this is a 14 year  old patient that I saw a number of years ago with   1956 03:33:22,620 --> 03:33:29,460 a three month history of abdominal pain, diarrhea  and weight loss. The patient was anemic and had   1957 03:33:29,460 --> 03:33:37,800 elevated C-reactive protein, all consistent with  IBD. Patient underwent endoscopy and colonoscopy   1958 03:33:37,800 --> 03:33:46,800 and here you see his terminal ilium, which  is inflamed, ulcerated and angry. After the   1959 03:33:46,800 --> 03:33:53,340 procedure, talked with the family, and the family  wanted to see if there was an intervention where   1960 03:33:53,340 --> 03:34:01,260 they could avoid using medication therapy. We had  a long discussion about different interventions   1961 03:34:01,260 --> 03:34:08,100 and the pros and cons of those interventions for  the treatment of IBD and the family and patient   1962 03:34:08,100 --> 03:34:13,800 decided to move forward with exclusive enteral  nutrition and then transition to a Whole Foods   1963 03:34:13,800 --> 03:34:21,000 dietary treatment called the Specific Carbohydrate  Diet. He maintained clinical and laboratory   1964 03:34:21,000 --> 03:34:27,779 remission for over five years until I lost contact  with him as he moved to an adult GI provider.   1965 03:34:28,859 --> 03:34:36,359 And during that time he had a repeat endoscopy  and colonoscopy which revealed normal appearing   1966 03:34:36,359 --> 03:34:44,939 mucosa with normal histology, showing you the  impact that dietary interventions can have.   1967 03:34:46,020 --> 03:34:51,120 You would imagine an intervention which  not only improves the nutritional outcomes   1968 03:34:51,120 --> 03:34:57,540 of your patients, but also improves the  disease itself would be used extensively.   1969 03:34:58,319 --> 03:35:05,639 The opposite is actually true. In the U.S., only  12% of American pediatric gastroenterologists   1970 03:35:05,640 --> 03:35:14,940 use EEN regularly. The percent of patients  that use EEN is significantly less in the US   1971 03:35:15,660 --> 03:35:23,519 as compared to Western Europe, Canada and Israel.  There are a number of questions we need to answer   1972 03:35:23,520 --> 03:35:31,680 with regards to EEN in inflammatory bowel disease.  We need to understand the mechanism of action by   1973 03:35:31,680 --> 03:35:40,260 which EEN works. This will allow us to understand  the IDO pathogenesis of IBD much better.   1974 03:35:41,040 --> 03:35:50,160 In addition, it will allow us to understand how  we may use a Whole Foods diet to help treat IBD.   1975 03:35:51,300 --> 03:35:56,819 In addition to this, we need to understand  how to optimize the use of dietary therapy   1976 03:35:56,819 --> 03:36:09,334 for these patients. Increasing utilization as  well as identifying dietary responsive patients. Thank you very much. 1977 03:36:09,960 --> 03:36:13,500 DR. BRUNO CHUMPITAZI:  Hello, everyone. This is Bruno Chumpitazi  from Texas Children's Hospital and Baylor   1978 03:36:13,500 --> 03:36:15,660 College of Medicine. And it is  a pleasure to be with everyone,   1979 03:36:15,660 --> 03:36:20,220 albeit virtually. I'd like to thank the  organizers for the opportunity to speak to   1980 03:36:20,220 --> 03:36:26,340 you about carbohydrate malabsorption in irritable  bowel syndrome. This is my disclosure slide.  1981 03:36:30,060 --> 03:36:34,920 Irritable bowel syndrome is a disorder of  gut brain interaction, and these disorders   1982 03:36:34,920 --> 03:36:40,260 are extremely prevalent with 25% of all children  worldwide over the age of four are suffering from   1983 03:36:40,260 --> 03:36:46,380 one of these types of disorders. These disorders  can have several factors that are heterogeneous in   1984 03:36:46,380 --> 03:36:51,120 nature that can affect any one individual.  And this figure here tries to summarize   1985 03:36:51,120 --> 03:36:56,220 some of those potential factors. One can have  sensitizing medical events, including distension,   1986 03:36:56,220 --> 03:37:01,319 inflammation or delay disorder, combined with  genetic predisposition and early life events,   1987 03:37:01,319 --> 03:37:05,279 which then leads to changes in pain  processing and visceral hypersensitivity.   1988 03:37:06,120 --> 03:37:10,800 These changes, combined with sensitizing  psychosocial events, including those listed here   1989 03:37:10,800 --> 03:37:15,840 such as depression or anxiety, can then lead to  the phenotype that we see clinically of abdominal   1990 03:37:15,840 --> 03:37:20,520 pain and other gastrointestinal problems. In  the case of irritable bowel syndrome, this is   1991 03:37:20,520 --> 03:37:25,140 chronic abdominal pain associated with changes  in stool frequency or changes in stool form.   1992 03:37:28,380 --> 03:37:33,239 One of the common symptom culprits in those  with irritable bowel syndrome is diet. And   1993 03:37:33,239 --> 03:37:37,500 food is perceived to be a symptom culprit  by over 90% of children and adolescents   1994 03:37:37,500 --> 03:37:42,300 for the irritable bowel syndrome. You can  see that this is significantly higher than   1995 03:37:42,300 --> 03:37:46,800 healthy controls. For example, one study  showing 92 or almost 93% of children with   1996 03:37:46,800 --> 03:37:51,360 IBS versus 62% of healthy controls having at  least one self-perceived food intolerance.   1997 03:37:52,080 --> 03:37:57,960 But there are also a significantly higher number  of potential culprit foods identified by children   1998 03:37:57,960 --> 03:38:01,800 with irritable bowel syndrome as causing an  issue. There's significantly higher number   1999 03:38:01,800 --> 03:38:06,779 of avoided foods that children with IBS have from  their diets so that they do not have an issue. And   2000 03:38:06,779 --> 03:38:12,899 you can see similar prevalence data in adolescents  with irritable bowel syndrome identified, 92% of   2001 03:38:12,899 --> 03:38:17,279 them versus 20% of healthy children identifying  at least some type of food that causes an issue.   2002 03:38:18,300 --> 03:38:24,720 Now, perhaps one of the most studied GI symptom  culprits are FODMAP Carbohydrates. FODMAP is   2003 03:38:24,720 --> 03:38:30,479 an acronym that was coined by investigators at  Monash University, where F stands for fermentable,   2004 03:38:30,479 --> 03:38:34,319 meaning that bacterial metabolism is playing  a role. O stands for oligosaccharides,   2005 03:38:34,319 --> 03:38:38,939 including the fructans and galactans. D stands  for disaccharides, including lactose. M stands   2006 03:38:38,939 --> 03:38:43,739 for monosaccharides, including fructose. A  stands for and, and P stands for Polyols,   2007 03:38:43,739 --> 03:38:48,359 including sugar alcohols such as sorbitol  or mannitol. And taken together, these are   2008 03:38:48,359 --> 03:38:52,679 poorly absorbed, osmotic, reactive, and rapidly  fermented carbohydrates which can produce gas.   2009 03:38:53,700 --> 03:39:00,599 And this leads to the putative pathogenesis of  FODMAP carbohydrates in which these carbohydrates,   2010 03:39:00,600 --> 03:39:04,560 if they're not well absorbed, such as  lactose, the polyols, the fructose,   2011 03:39:04,560 --> 03:39:09,540 or fructose and galactose, can have increased  osmotic activity bringing water into the small   2012 03:39:09,540 --> 03:39:14,640 intestine. These carbohydrates then are  transported distally into the colon where   2013 03:39:14,640 --> 03:39:19,319 the bacteria will ferment them producing gas  such as hydrogen, methane and carbon dioxide,   2014 03:39:19,319 --> 03:39:22,380 and as well as other metabolites  such as short-chain fatty acids.   2015 03:39:22,920 --> 03:39:28,380 This in turn will lead to luminal distension, and  the luminal distention because of the visceral   2016 03:39:28,380 --> 03:39:34,080 hypersensitivity in those with IBS, will lead to  increased symptoms. But one of the challenges in   2017 03:39:34,080 --> 03:39:39,000 the field is that despite the fact that there  are these small bowel water content changes and   2018 03:39:39,000 --> 03:39:44,279 colonic gas production, it's not been possible,  for example, using MRI studies to predict who   2019 03:39:44,279 --> 03:39:50,219 will or will not respond to a low FODMAP diet. And  this is a diet in which these FODMAP carbohydrates   2020 03:39:50,220 --> 03:39:55,260 are actually significantly restricted. So  there's been a lot more attention actually   2021 03:39:55,260 --> 03:40:00,600 paid specifically to bacterial fermentation,  both in terms of looking at the overall gut   2022 03:40:00,600 --> 03:40:04,800 microbiome composition as well as metabolites,  and there've been several adult IBS studies.   2023 03:40:04,800 --> 03:40:10,200 We'll be focusing primarily on pediatric IBS  effort that our work as a group has been doing. 2024 03:40:11,460 --> 03:40:18,840 Now, just to summarize very briefly, the low  FODMAP diet summary evidence suggesting that low   2025 03:40:18,840 --> 03:40:22,380 FODMAP diet may be helpful, it's been growing. In  adults with irritable bowel syndrome, there's one   2026 03:40:22,380 --> 03:40:26,939 Double-blind placebo-controlled challenge study  and more than ten randomized controlled trials   2027 03:40:26,939 --> 03:40:32,339 which show that a low FODMAP diet is either as  efficacious as other interventions such as yoga,   2028 03:40:32,340 --> 03:40:36,840 or actually more efficacious in ameliorating  symptoms as compared to other dietary   2029 03:40:36,840 --> 03:40:40,979 interventions which have higher FODMAP content.  There are several uncontrolled studies which show   2030 03:40:40,979 --> 03:40:47,519 symptom improvement ranging from 56 to 94%. And  the data is also increasing in pediatric irritable   2031 03:40:47,520 --> 03:40:50,819 bowel syndrome and functional abdominal pain,  with one double-blind placebo-controlled challenge   2032 03:40:50,819 --> 03:40:54,840 study suggesting that fructans can play a role  in increasing symptoms, which we'll be going   2033 03:40:54,840 --> 03:40:59,640 into briefly. And then three randomized controlled  trials suggesting that low FODMAD diet is either   2034 03:40:59,640 --> 03:41:05,161 more efficacious than other interventions or  as efficacious as another dietary intervention.   2035 03:41:05,819 --> 03:41:11,399 And then uncontrolled studies showing  symptom improvement ranging from 50 to 77%. 2036 03:41:14,340 --> 03:41:19,439 Now, specifically regarding the Fructan Challenge  study, this is a randomized crossover study   2037 03:41:19,439 --> 03:41:24,540 of children with irritable bowel syndrome who  received either fructan or maltodextrin during the   2038 03:41:24,540 --> 03:41:30,000 dietary intervention periods. We identified that  children with IBS had increased abdominal pain,   2039 03:41:30,000 --> 03:41:35,819 bloating and flatulence when given the fructan, as  compared to when they were given the maltodextrin.   2040 03:41:36,779 --> 03:41:41,880 We also identified a specific subgroup  that we termed the fructan sensitive   2041 03:41:41,880 --> 03:41:47,040 subgroup. And these were children that had a  30% increase in abdominal pain frequency during   2042 03:41:47,040 --> 03:41:52,560 that fructan dietary challenge period versus  the Maltodextrin Challenge period. And 17 of   2043 03:41:52,560 --> 03:41:57,779 the 38 participants met this criteria. When  comparing fructan sensitive children versus   2044 03:41:57,779 --> 03:42:01,739 those that we termed fructan tolerant, which  is to say they did not develop this increase   2045 03:42:01,739 --> 03:42:05,639 in abdominal pain when given fructans, we  could not differentiate the two groups with   2046 03:42:05,640 --> 03:42:09,960 respect to several baseline clinical parameters,  including demographics such as age or gender,   2047 03:42:09,960 --> 03:42:14,819 diet, GI symptoms, or psychosocial  distress or overall gas production. 2048 03:42:18,359 --> 03:42:25,679 This led to further evaluation of the overall gut  microbiome. The subjects provided fecal samples   2049 03:42:25,680 --> 03:42:31,680 during the baseline period and during each dietary  intervention. And using 16s RRNA evaluation,   2050 03:42:31,680 --> 03:42:37,380 we're able to compare the overall alpha  diversity between those who were fructan   2051 03:42:37,380 --> 03:42:41,460 sensitive and tolerant. This figure shows these  results. Here in the blue you're seeing the median   2052 03:42:41,460 --> 03:42:46,500 and 25th and 75th percentile data of observed  OTUs and those who are fructan tolerant. And   2053 03:42:46,500 --> 03:42:50,819 in the orange, you're seeing the same data for  those who are fructan sensitive. And during the   2054 03:42:50,819 --> 03:42:55,019 baseline period and when the subjects were being  given the maltodextrin, there was a significant   2055 03:42:55,020 --> 03:42:59,940 overall decrease in alpha diversity in those who  are fructan sensitive versus fructan tolerant.   2056 03:43:01,260 --> 03:43:06,180 Further suggesting that there is a difference in  the microbiome composition was a data diversity   2057 03:43:06,180 --> 03:43:11,880 evaluation comparing the two groups. Here in the  blue again, you're seeing those data points in a   2058 03:43:11,880 --> 03:43:15,960 principal coordinate analysis plot for those who  are fructan tolerant, and then the orange here for   2059 03:43:15,960 --> 03:43:20,399 those who are fructan sensitive. And there was  a significant difference between the two groups   2060 03:43:20,399 --> 03:43:25,200 at baseline and also during the maltodextrin  period. And while we don't have enough time   2061 03:43:25,200 --> 03:43:29,819 to go into all the differences that we saw during  the interventions, I wanted to highlight. At least   2062 03:43:29,819 --> 03:43:35,399 during the baseline period, there were 14 taxa  within the Clostridia class that were enriched   2063 03:43:35,399 --> 03:43:39,779 and those who are fructan tolerant and those  who are listed here, ranging from Clostridia to   2064 03:43:39,779 --> 03:43:45,059 Ruminococcaceae to coprococcus, suggesting  that at least at baseline, those who were   2065 03:43:45,060 --> 03:43:50,220 fructan intolerant could be differentiated from  those who are fructan sensitive based on fecal   2066 03:43:50,220 --> 03:43:55,080 samples and evaluation of the gut microbiome.  And also suggesting potentially that those who   2067 03:43:55,080 --> 03:43:59,880 are fructan tolerate had an increased  ability... The bacteria had increased   2068 03:43:59,880 --> 03:44:05,040 (UNKNOWN) ability and were able to metabolize  and hydrolyze carbohydrates more easily. 2069 03:44:07,380 --> 03:44:12,120 And this is a summary of some preliminary data  taking a look at additional multi-omics beyond   2070 03:44:12,120 --> 03:44:16,500 16s RRNA, now looking at whole genome  sequencing as well as lipidomics and   2071 03:44:16,500 --> 03:44:21,180 metabolomics of the same fecal samples. We  use random forest modeling and we're able to   2072 03:44:21,180 --> 03:44:27,060 discriminate fructan sensitive versus tolerant  participants with a median value of 0.854 when   2073 03:44:27,060 --> 03:44:33,359 combining all this omics of the diets together.  And that can be seen in panel A and panel B,   2074 03:44:33,359 --> 03:44:40,019 we actually took a look at the different periods  of the baseline versus fructan versus maltodextrin   2075 03:44:40,020 --> 03:44:44,640 periods, and found that the baseline period was  actually contributing the greatest discrimination   2076 03:44:46,319 --> 03:44:51,779 in terms of... vs. the other dietary periods  to the overall mean, suggesting that where you   2077 03:44:51,779 --> 03:44:56,219 start from is actually very important in terms of  the gut microbiome and its activity in determining   2078 03:44:56,220 --> 03:45:03,120 fructan sensitivity. This leads to further  research opportunities, including increased   2079 03:45:03,120 --> 03:45:06,660 need for increased understanding of human  biology related to carbohydrate malabsorption   2080 03:45:06,660 --> 03:45:11,639 in both health and GI disorders such as IBS.  Need further information about transporters,   2081 03:45:11,640 --> 03:45:17,340 how they are regulated, as well as genetics and  epigenetics. When you further a non-invasive   2082 03:45:17,340 --> 03:45:21,120 assessments of intraluminal gut microbiome  throughout the GI tract, including the small   2083 03:45:21,120 --> 03:45:25,500 bowel in particular, so you gain greater  insight into the composition function,   2084 03:45:25,500 --> 03:45:31,319 and also need bioinformatic standardization  to be able to compare study results between   2085 03:45:31,319 --> 03:45:36,299 investigators and research groups. And finally,  integration of the host biology and microbiome   2086 03:45:36,300 --> 03:45:42,600 and luminal physiology will be the future in this  area as well. I'd like to end by acknowledging the   2087 03:45:42,600 --> 03:45:47,819 investigators listed on this slide, as well as the  support listed here on the bottom right. Thank you   2088 03:45:47,819 --> 03:45:50,200 so much for your attention today.   2089 03:45:52,800 --> 03:45:56,400 DR. ALEXANDRA CAREY: Thank you for this introduction. I am  honored to be able to speak to you today.   2090 03:45:58,080 --> 03:46:01,620 My disclosures are related to three  studies I am closely involved with,   2091 03:46:01,620 --> 03:46:06,540 the latter two related to therapies used in  pediatric short bowel syndrome with malabsorption. 2092 03:46:08,460 --> 03:46:12,720 To really understand malnutrition and short bowl  syndrome, you have to become familiar with the   2093 03:46:12,720 --> 03:46:16,920 different evidence based definitions related  to this chronic illness. The first of which   2094 03:46:16,920 --> 03:46:21,779 is intestinal failure. My favorite and most  broad definition of intestinal failure is a   2095 03:46:21,779 --> 03:46:27,719 reduction in GI function below what is necessary  for digestion and absorption of adequate nutrient,   2096 03:46:27,720 --> 03:46:33,779 fluid, and growth requirements. In a recent  manuscript, my colleagues doctors (UNKNOWN)  2097 03:46:33,779 --> 03:46:37,979 and (UNKNOWN) and former CCO fellow Dr. Galloway,  along with other notable members of this field,   2098 03:46:37,979 --> 03:46:45,779 define intestinal failure as a need for chronic  parenteral nutrition dependence for 60 days within   2099 03:46:45,779 --> 03:46:51,179 a 74 consecutive day interval. Intestinal  failure from short bowel syndrome includes   2100 03:46:51,180 --> 03:46:57,180 surgical resections and/or congenital defects  that decreases the total GI mass and absorptive   2101 03:46:57,180 --> 03:47:02,820 capacity of the GI system, and represents  the condition that we will focus on today.   2102 03:47:03,660 --> 03:47:08,099 Now, there are many causes of short bowel  syndrome, but a common theme remains that all   2103 03:47:08,100 --> 03:47:12,840 patients, whether on oral supplements,  enteral tube feedings or parenteral   2104 03:47:12,840 --> 03:47:18,540 support through a central venous catheter,  remain at risk for malnutrition. As such,   2105 03:47:18,540 --> 03:47:23,640 it is crucial that we understand how to now  define, diagnose, and treat malnutrition.   2106 03:47:25,620 --> 03:47:31,200 In this group, I am willing to bet we can all  appreciate that malnutrition is common in short   2107 03:47:31,200 --> 03:47:36,479 bowel syndrome. And I'm also willing to bet, and  it's easy to deduce that malnutrition is often the   2108 03:47:36,479 --> 03:47:43,439 result of malabsorption, given the reduction in  gastrointestinal mass and function. But then why   2109 03:47:43,439 --> 03:47:48,719 can it be so hard at times to identify and correct  it, or to know how to manage and prevent it?   2110 03:47:49,500 --> 03:47:55,380 Well, first we diagnose malnutrition using  standardized anthropometric Z scores. However,   2111 03:47:55,380 --> 03:48:01,560 these patients don't typically follow the  rules of typical anthropometry. Furthermore,   2112 03:48:01,560 --> 03:48:06,960 there are variable ways to manage and treat. Some  of these are evidence based, some of these are   2113 03:48:06,960 --> 03:48:12,120 based on expert opinion and experience. Treatment  is also going to be based on the capabilities   2114 03:48:12,120 --> 03:48:16,920 of your center and the resource allocation  that exists, including the funding potential. 2115 03:48:21,479 --> 03:48:26,459 It is also clear that similar to some of the  other conditions discussed today, that this rare,   2116 03:48:26,460 --> 03:48:32,580 complex and heterogeneous pediatric condition  carries with it significant research gaps.   2117 03:48:32,580 --> 03:48:38,700 But in any field, significant research gaps like  these stimulate clinicians and researchers like   2118 03:48:38,700 --> 03:48:44,939 yourselves to work hard to create future research  opportunities. So now let's discuss an example of   2119 03:48:44,939 --> 03:48:48,899 a patient we recently saw in our CAIR clinic,  which is the Center for Advanced Intestinal   2120 03:48:48,899 --> 03:48:54,059 Rehabilitation, to help us understand  how malnutrition can be hard to diagnose. 2121 03:48:57,300 --> 03:49:01,620 This is the case of an eight year old male with  jejunal regional atresia. He presents to clinic   2122 03:49:01,620 --> 03:49:07,260 for standard follow up without any GI complaints.  He was weaned from parental support about a year   2123 03:49:07,260 --> 03:49:12,600 ago and remains on nightly IV fluids due to  inability to maintain his hydration and relies   2124 03:49:12,600 --> 03:49:19,620 heavily on enteral tube feedings with an elemental  formula. On exam, his weight and BMI for age are   2125 03:49:19,620 --> 03:49:25,559 reassuring, as you can see on the left, but  his weight velocity on the right is decreased,   2126 03:49:25,560 --> 03:49:31,680 and his mid upper arm circumference is actually  down. He has a distended abdomen with thin arms   2127 03:49:31,680 --> 03:49:38,700 and legs. So I ask you, does this patient have  malnutrition? I would say so. But if you base it   2128 03:49:38,700 --> 03:49:43,920 on his weight and BMI for age trends, you may  miss this very subtle trend. I'm also worried   2129 03:49:43,920 --> 03:49:48,300 that as he approaches puberty, he's going to  require more nutritional support in the form   2130 03:49:48,300 --> 03:49:55,560 of IV calories. So this patient therefore warrants  very close follow up with nutritional titrations   2131 03:49:56,939 --> 03:50:03,120 to help improve his growth. Malabsorption can  present by subtle changes in growth patterns,   2132 03:50:03,120 --> 03:50:08,099 as demonstrated on the previous slide, as well as  intolerances of enteral and parenteral regimens   2133 03:50:09,180 --> 03:50:13,859 can manifest as diarrhea above the  patient's baseline. Additionally,   2134 03:50:13,859 --> 03:50:19,259 dysbiosis and inflammation can lead to  malabsorption and then malnutrition. This   2135 03:50:19,260 --> 03:50:23,340 image on the right was taken during endoscopy of  a five year old male with short bowel syndrome   2136 03:50:23,340 --> 03:50:29,520 for history of poor growth and chronic diarrhea.  Intestinal biopsy and duodenal aspirate confirmed   2137 03:50:29,520 --> 03:50:33,899 small bowel bacterial overgrowth with chronic  inflammation. So this patient was started on   2138 03:50:33,899 --> 03:50:39,120 cycled antibiotics and anti-inflammatories and  his experience dramatically improved growth and   2139 03:50:39,120 --> 03:50:45,899 decreased symptomatology. Now, intestinal failure  associated. Liver disease is also common and can   2140 03:50:45,899 --> 03:50:50,700 increase the risk of malabsorption related  at times to fat soluble vitamin deficiencies.   2141 03:50:53,819 --> 03:50:59,939 Systematic evaluation and diagnostic protocols,  including imaging and panendoscopy when indicated   2142 03:50:59,939 --> 03:51:06,000 or when able, is key when patients are  thriving as it can lead to clear nutritional,   2143 03:51:06,000 --> 03:51:11,520 medical and/or surgical treatment plans, which  can directly improve the morbidity and mortality   2144 03:51:11,520 --> 03:51:17,640 of these vulnerable patients. As we alluded to,  anthropometry and short bowel syndrome can be   2145 03:51:17,640 --> 03:51:21,960 challenging. Typically, we base our nutritional  status on serial weight and height measurements,   2146 03:51:21,960 --> 03:51:26,700 but are these accurate in short bowel syndrome?  I would advocate that they are often inaccurate   2147 03:51:26,700 --> 03:51:31,739 due to fluid shifts, abdominal distention, timing  of the last stool, and measurement discrepancies   2148 03:51:31,739 --> 03:51:37,800 in part related to increased home measurements  following the COVID-19 pandemic. Less commonly,   2149 03:51:37,800 --> 03:51:45,359 we use other methods such as skin folds, mid upper  arm circumferences, BIA, DXA, or air displacement   2150 03:51:45,359 --> 03:51:50,279 plethysmography or ADP. These methods have been  shown to hold some weight in short bowel syndrome,   2151 03:51:50,279 --> 03:51:55,019 but are underutilized for a variety of reasons.  For example, many centers do not even have ADP   2152 03:51:55,020 --> 03:52:00,359 clinically available. I am particularly  excited about ADP in short bowel syndrome,   2153 03:52:00,359 --> 03:52:05,639 as I believe it complements our interpretation of  nutritional status by more accurately measuring   2154 03:52:05,640 --> 03:52:10,979 body composition and lean body mass. It is  validated in healthy children, but more research   2155 03:52:10,979 --> 03:52:14,759 is needed to apply to subpopulations  like pediatric short bowel syndrome.   2156 03:52:15,960 --> 03:52:20,160 Without a doubt, the key to the successful  nutritional management of children with   2157 03:52:20,160 --> 03:52:24,779 malnutrition due to short bowel syndrome remains  with the concept of the interdisciplinary   2158 03:52:24,779 --> 03:52:30,120 intestinal rehabilitation program. This approach  is well documented in the literature. Together,   2159 03:52:30,120 --> 03:52:35,279 we can predict the degree of malabsorption  occurring in patients so we can better tailor   2160 03:52:35,279 --> 03:52:40,439 and apply comparative standards such as basal  or resting energy expenditure, protein and total   2161 03:52:40,439 --> 03:52:45,000 fluid goals. For example, say you have a one year  old female with 30 centimeters of small bowel,   2162 03:52:45,000 --> 03:52:50,399 ending in Jejunostomy who is advancing  nicely on feeds. But you learn that ostomy output   2163 03:52:50,399 --> 03:52:56,160 is watery and 3mls per kilo per hour. Family's  excited the baby is seemingly weaning from PN.   2164 03:52:56,160 --> 03:52:59,939 However, I'm willing to bet that this infant  is moderately malnourished and would benefit   2165 03:52:59,939 --> 03:53:04,679 actually from increasing parental support and  backing down significantly on enteral support   2166 03:53:04,680 --> 03:53:11,220 due to evidence of malabsorption. Expectations  setting from the get go is crucial. Often,   2167 03:53:11,220 --> 03:53:15,720 it is slow and steady that wins the enteral  autonomy or race short bowel syndrome.   2168 03:53:16,739 --> 03:53:21,479 We are in an era of limited resources,  therefore having a team work together to select   2169 03:53:21,479 --> 03:53:27,239 the appropriate formula and route can improve  absorption and reduce malabsorption. Understanding   2170 03:53:27,239 --> 03:53:32,219 the complexity of parental support, especially  strategies in advancing and weaning support, can   2171 03:53:32,220 --> 03:53:37,859 also help with energy utilization. For example,  close examination and titration of the sodium dose   2172 03:53:37,859 --> 03:53:42,660 or the glucose infusion rate and parental support  can be the difference between normal and stunted   2173 03:53:42,660 --> 03:53:48,660 growth. Lastly, having access to complementary  medical therapies and research protocols such as   2174 03:53:48,660 --> 03:53:54,599 GLP-2 analogues and immobilized lipase cartridges  can also help improve nutritional status. 2175 03:53:57,300 --> 03:54:02,520 I want to conclude by discussing the research gaps  and opportunities that I think we should focus   2176 03:54:02,520 --> 03:54:07,980 on next to as a field. We know that predictive  energy equations are fraught with inaccuracies.   2177 03:54:08,700 --> 03:54:13,679 Therefore, using better methods to predict energy  requirements to tailor nutrition is needed. One   2178 03:54:13,680 --> 03:54:18,720 such test could be using indirect calorimetry,  which is the standard of care in the ICU setting,   2179 03:54:18,720 --> 03:54:22,860 but is definitely underutilized in the  outpatient and short bowel syndrome setting.   2180 03:54:23,880 --> 03:54:28,319 Next, we discussed how difficult it can be  to predict lean body mass and growth based   2181 03:54:28,319 --> 03:54:34,380 on standard anthropometry. So perhaps using  serial ADP clinically can be part of the new   2182 03:54:34,380 --> 03:54:41,100 standard of care. It also dawned on me a few years  back that each center manages parenteral support   2183 03:54:41,100 --> 03:54:45,780 differently. We all cycle the PN according to  different protocols and use different standards.   2184 03:54:46,319 --> 03:54:50,939 So employing something like continuous  glucose monitoring in our patients on   2185 03:54:50,939 --> 03:54:56,040 parenteral nutrition may be a great way to  understand glucose utilization and disglycemia,   2186 03:54:56,040 --> 03:55:01,739 which can lead to poor growth. In fact, one  such study is underway with our endocrine   2187 03:55:01,739 --> 03:55:04,920 colleagues at Boston Children's Hospital,  which I'm very much looking forward to.   2188 03:55:05,520 --> 03:55:10,680 And lastly, we have a long way to go before we  understand the microbiota signature in short   2189 03:55:10,680 --> 03:55:15,779 bowel syndrome. If we can develop better ways to  characterize the microbiome and identify bacterial   2190 03:55:15,779 --> 03:55:21,300 overgrowth that are clinically available, valid,  reproducible and non-invasive, we can better treat   2191 03:55:21,300 --> 03:55:27,779 inflammation and therefore improve enteral  autonomy and decrease risk of malnutrition.   2192 03:55:28,560 --> 03:55:33,180 And with that, I would like to thank you as  well as my many mentors and colleagues at   2193 03:55:33,180 --> 03:55:36,926 Boston Children's Hospital. Thank you. 2194 03:55:36,926 --> 03:55:42,060 DR. JALAL ABU-SHAWEESH: I would like to thank the organizing committee on their invite to  participate in this important workshop.   2195 03:55:42,060 --> 03:55:47,640 It is truly an honor and a privilege to be  part of this esteemed group of colleagues,   2196 03:55:49,859 --> 03:55:56,519 I have no conflict of interest to. By  the end of this talk, I hope that you   2197 03:55:56,520 --> 03:56:01,500 will be able to understand the challenges of  providing adequate nutrition and preventing   2198 03:56:01,500 --> 03:56:08,220 necrotizing enterocolitis, identify factors that  improve nutrition and help decrease necrotizing   2199 03:56:08,220 --> 03:56:13,979 enterocolitis in preterm infants, recognize  the value of establishing a feeding protocol,   2200 03:56:13,979 --> 03:56:22,019 and appreciate the importance of evaluating your  own practices. Necrotizing Enterocolitis remains   2201 03:56:22,020 --> 03:56:27,660 the major gastrointestinal disorder affecting  preterm infants. Its incidence is quite variable   2202 03:56:27,660 --> 03:56:34,319 among different in ICUs, and has been reported  to range between 2 to 20% with an average of 5   2203 03:56:34,319 --> 03:56:41,099 to 10%. The incidence and severity of the disease  are inversely proportional to gestational age and   2204 03:56:41,100 --> 03:56:47,580 birth weight, with the most immature infants being  most likely to be affected by the severe disease.   2205 03:56:48,479 --> 03:56:54,959 Pathophysiology of necrotizing enterocolitis  is multifactorial, and as currently reported,   2206 03:56:54,960 --> 03:57:00,300 probably represent multiple diseases rather  than a single entity. The origin of the   2207 03:57:00,300 --> 03:57:06,600 disease stems from a complex interaction between  immature host defences and normal development of   2208 03:57:06,600 --> 03:57:13,920 commensal flora, resulting in a combination of  ischemia, hypoxia, inflammation and/or necrosis. 2209 03:57:15,720 --> 03:57:22,020 Necrotizing enterocolitis has been staged  based on Modified Bell's criteria into three   2210 03:57:22,020 --> 03:57:27,899 stages. Stage one constitutes signs and  symptoms concerning for NEC, in which in   2211 03:57:27,899 --> 03:57:34,080 almost always nonspecific and may be related to  other (INAUDIBLE) illnesses, immature responses   2212 03:57:34,080 --> 03:57:42,120 including poor gut motility, constipation, CPAP  therapy, or milk protein allergy, or intolerance.   2213 03:57:42,120 --> 03:57:49,019 Stage two is diagnosed medical NEC with the  hallmark of pneumatosis intestinalis or air   2214 03:57:49,020 --> 03:57:54,420 in the wall of the gut, or portal venous  gas. Stage three is complicated surgical   2215 03:57:54,420 --> 03:58:01,080 NEC associated with perforation, gangrene  and/or necrosis of parts or all of the bowel.   2216 03:58:02,819 --> 03:58:07,139 Necrotizing enterocolitis is associated  with very high mortality, ranging from   2217 03:58:07,140 --> 03:58:14,340 20% for medical NEC to as high as 50% in  surgical NEC. It is also associated with   2218 03:58:14,340 --> 03:58:20,580 high rate of morbidity, both short and long  term, including short gut syndrome, stricture,   2219 03:58:20,580 --> 03:58:26,640 repeated surgeries, neurodevelopmental delay,  poor growth, cholestasis, and liver failure.   2220 03:58:27,720 --> 03:58:33,420 The impact of necrotizing enterocolitis and  nutritional status of the preterm mirrors   2221 03:58:33,420 --> 03:58:39,960 that of the different stages of necrotizing  enterocolitis. Stage one truly affects the vast   2222 03:58:39,960 --> 03:58:45,779 majority of preterm infants and results in feeding  restrictions and interruption of feeding advanced   2223 03:58:45,779 --> 03:58:55,199 secondary to feeding tolerance in fear that this  might be early necrotizing enterocolitis Stage   2224 03:58:55,199 --> 03:59:02,220 two and three affects the 5 to 10% of preterm  infants affected by necrotizing enterocolitis,   2225 03:59:02,220 --> 03:59:06,720 and results in altered nutritional  support during the acute illness.   2226 03:59:06,720 --> 03:59:12,359 And even a smaller percentage of infants inflicted  with post necrotizing enterocolitis complications,   2227 03:59:12,359 --> 03:59:20,219 nutritional deficits are assessed beyond the acute  ailment. We have seen necrotizing enterocolitis   2228 03:59:20,220 --> 03:59:26,340 is a very serious and devastating illness, and  its management is based on early recognition and   2229 03:59:26,340 --> 03:59:32,100 intervention. The problem is, early necrotizing  enterocolitis presents with feeding intolerance,   2230 03:59:32,100 --> 03:59:38,220 which is very common in preterm infants, affecting  30 to 50% of extremely low birth weight infants.   2231 03:59:38,760 --> 03:59:44,460 The presentation of which mimics that of early  necrotizing enterocolitis, and might include   2232 03:59:46,500 --> 03:59:49,199 abdominal distention, gastric residuals,   2233 03:59:49,199 --> 03:59:54,479 bilious aspirate, vomiting, or simply  what's described as low PPEP abdomen.   2234 03:59:55,199 --> 04:00:02,519 Often the medical response is to stop feeds and  reassess with multiple X-rays and blood tests. 2235 04:00:04,680 --> 04:00:09,239 Often the presentation occurs in  off hours and thus TPN might not   2236 04:00:09,239 --> 04:00:11,939 be available to compensate  for the loss of calories.   2237 04:00:13,199 --> 04:00:18,779 This graph perfectly summarizes the effect of  feeding intolerance in advancing feeds in very   2238 04:00:18,779 --> 04:00:26,040 low birth weight infants. X axis represents days  taken to full feeds, and the Y axis represent   2239 04:00:26,040 --> 04:00:30,779 the percent of infants reaching full feeds in  multiple different units across the world, both   2240 04:00:30,779 --> 04:00:37,979 in China designated by the GED, and outside of it  there are non GED graphs. The feeding protocols   2241 04:00:37,979 --> 04:00:45,540 utilized would reach full feeds between 7 to 15  days according to how they were established. While   2242 04:00:45,540 --> 04:00:52,260 some units were able to achieve this duration in  the majority of their infants, I'll look at the   2243 04:00:52,260 --> 04:00:58,319 tail of these curves as even the most aggressive  units needed up to 30 days to get all of their   2244 04:00:58,319 --> 04:01:06,239 infants up to full feeds, and some slower units  needed as long as 60 days to achieve the same.   2245 04:01:06,239 --> 04:01:14,219 The usual practice of starting and stopping feeds  is what usually causes this delay. Stages two and   2246 04:01:14,220 --> 04:01:21,060 three are usually managed by cessation of feeds  for variable duration, antibiotics and TPN. It   2247 04:01:21,060 --> 04:01:26,040 has been shown that prolonged duration of feed  cessation is associated with atrophy of intestinal   2248 04:01:26,040 --> 04:01:32,279 line and interruption of hormonal and trophic  intestinal function. This also might be associated   2249 04:01:32,279 --> 04:01:39,000 with cholestasis and liver failure secondary to  prolonged NPO, TPN, and lipid administration. 2250 04:01:40,080 --> 04:01:46,859 Improved nutrition in stages two and three  should concentrate on aggressive nutritional   2251 04:01:46,859 --> 04:01:53,759 support using TPN, and perhaps non soy lipid  formulation. Our unit has moved to the use of   2252 04:01:53,760 --> 04:02:04,199 SMOF, which is a combination of soy, lipids, olive  oil, triglycerides and fish oil in all babies,   2253 04:02:04,199 --> 04:02:09,179 to successfully decrease the incidence  of cholestasis. Further management should   2254 04:02:09,180 --> 04:02:14,279 concentrate on introduction of feeds as soon  as possible. There are no randomized controlled   2255 04:02:14,279 --> 04:02:20,040 trials to identify the earliest possible  feeds can be safely restarted. However,   2256 04:02:20,040 --> 04:02:27,120 two studies looked at this question, both  implied small number of infants 47 and 44.   2257 04:02:27,120 --> 04:02:34,019 One was a retrospective review and the other was  a comparison of a new protocol to historic data.   2258 04:02:34,020 --> 04:02:39,720 The comparison was between starting feeds  before and after five days in one study,   2259 04:02:39,720 --> 04:02:45,660 and four versus ten days in the second. Both  studies showed no effect on recurrence of   2260 04:02:45,660 --> 04:02:51,420 necrotizing enterocolitis. However, neither  study was powered to find a difference.   2261 04:02:52,620 --> 04:03:01,140 There was also lower incidence of related  infection, as well as faster reaching full feeds. 2262 04:03:04,380 --> 04:03:10,199 There are two studies that have evaluated the  long term effects of necrotizing enterocolitis   2263 04:03:10,199 --> 04:03:14,519 on nutrition. The first looked at  the impact of having an enterostomy 2264 04:03:14,520 --> 04:03:21,180 post necrotizing enterocolitis in growth. This  slide represent the c-score at birth before stoma   2265 04:03:21,180 --> 04:03:29,699 formation and stoma closure in infants who  were cared for in ICU in the black columns,   2266 04:03:29,699 --> 04:03:36,000 those who were cared for at the local hospital  or at home in the gray columns. As you can see,   2267 04:03:36,000 --> 04:03:43,680 the z-scores decreased significantly in both  groups between stoma formation and stoma closure.   2268 04:03:45,120 --> 04:03:51,660 The second study looked at long term nutritional  complications in Sweden in all survivors of   2269 04:03:51,660 --> 04:03:58,559 necrotizing enterocolitis, and found that NEC  patients were at significant risk of rickets in   2270 04:03:58,560 --> 04:04:08,460 the first year of life, as well as a significant  risk of non-specific malabsorption syndrome.   2271 04:04:08,460 --> 04:04:15,720 However, there was no effect on incidence of short  stature, malnutrition, or failure to survive. 2272 04:04:17,580 --> 04:04:22,080 In the last part of the talk, we will  concentrate on nutritional approaches   2273 04:04:22,080 --> 04:04:28,739 to preventing necrotizing enterocolitis. Some of  these proven strategies include feeding maternal   2274 04:04:28,739 --> 04:04:34,260 breast milk. While donor breast milk hasn't  been associated with increased incidence of   2275 04:04:34,260 --> 04:04:41,160 necrotizing enterocolitis, it is not settled if  its use can prevent necrotizing enterocolitis. The   2276 04:04:41,160 --> 04:04:48,420 use of trophic feeds or minimal enteral feeds  at 10 to 20mls per kilo per day has not been   2277 04:04:48,420 --> 04:04:53,520 associated with necrotizing enterocolitis, and  might decrease villous atrophy associated with   2278 04:04:53,520 --> 04:05:01,439 being (INAUDIBLE). However, the optimum duration  of trophic feeds is not established. Establishing   2279 04:05:01,439 --> 04:05:06,899 a feeding protocol has also been associated with  decreasing incidence of necrotizing enterocolitis.   2280 04:05:07,560 --> 04:05:12,660 Gastric residuals on the other hand, have long  been advocated for early detection of eating   2281 04:05:12,660 --> 04:05:18,120 intolerance. However, volume and significance of  these residuals is very debated and contribute   2282 04:05:18,120 --> 04:05:24,120 significantly to delay in feeding advance. We and  many other units across the country have stopped   2283 04:05:24,120 --> 04:05:31,439 checking residuals in all preterm infants.  Non settle issues regarding the occurrence   2284 04:05:31,439 --> 04:05:37,199 of necrotizing enterocolitis include continuous  versus bolus feeds, how fast to advance feeds,   2285 04:05:37,199 --> 04:05:43,199 and the use of (INAUDIBLE). This study summarizes  a meta analysis for the evidence that standardized   2286 04:05:43,199 --> 04:05:49,199 feeding protocol does decrease the incidence  of necrotizing colitis by an average of 80%,   2287 04:05:50,340 --> 04:05:55,319 with a confidence interval that is narrow and  does not cross one, indicating significance.   2288 04:05:56,819 --> 04:06:01,559 However, which feeding protocol to choose. A  Cochrane review summarized the results of ten   2289 04:06:01,560 --> 04:06:07,500 randomized controlled trials comparing fast  versus slow feeding advance. Slow was defined   2290 04:06:07,500 --> 04:06:15,239 as advancing by 15 to 20mls per kilo per day,  and fast as 30 to 40mls per kilo per day. The   2291 04:06:15,239 --> 04:06:22,260 study included over 3,700 infants, about 2,800  of which came from one study. One third of the   2292 04:06:22,260 --> 04:06:29,279 infants were extremely low birth weight, and 20%  were SGA or compromised (INAUDIBLE). Analysis   2293 04:06:29,279 --> 04:06:35,580 found no difference in incidence of necrotizing  enterocolitis or mortality, no effect on discharge   2294 04:06:35,580 --> 04:06:40,019 weight or head circumference between the two  groups. However, slow protocols were associated   2295 04:06:40,020 --> 04:06:46,260 with delayed establishment of full feeds by one to  five days, and borderline increase in infection.   2296 04:06:46,979 --> 04:06:54,120 Also, the incidence of feeding intolerance causing  interruption was 29 and 35% in both groups,   2297 04:06:56,340 --> 04:07:02,819 six to nine days. This emphasizes the importance  of choosing a feeding protocol that is acceptable   2298 04:07:02,819 --> 04:07:09,059 by all stakeholders in your unit, including  nurses, nurse practitioners, nutritionists   2299 04:07:09,060 --> 04:07:14,460 and physicians, as well as continuous review  of your feeding data to decrease protocol   2300 04:07:14,460 --> 04:07:21,180 violations secondary to feeding and (INAUDIBLE).  While initial studies and probiotics were very   2301 04:07:21,180 --> 04:07:27,779 promising in respect to decreasing necrotizing  enterocolitis, they employed different protocols,   2302 04:07:27,779 --> 04:07:33,960 population and small number of extremely low  birth weight infants. Most recent studies and   2303 04:07:33,960 --> 04:07:40,319 meta analysis fail to show protective effect  of probiotics on necrotizing enterocolitis.   2304 04:07:40,319 --> 04:07:45,599 This prompted the Committee on Fetus and Newborn  to come up with the following statement, current   2305 04:07:45,600 --> 04:07:51,120 evidence does not support the routine universal  administration of probiotics for preterm infants,   2306 04:07:51,120 --> 04:07:56,220 particularly those with a birth weight  of less than a thousand grams. 2307 04:07:56,220 --> 04:08:01,199 In conclusion, the best approach to improving  nutrition in preterm infants is the prevention   2308 04:08:01,199 --> 04:08:07,439 of necrotizing enterocolitis. Proved strategies  to achieving that include trophic feeds,   2309 04:08:07,439 --> 04:08:13,259 early feeding advance, establishment of a feeding  protocol, and the use of antenatal steroids. The   2310 04:08:13,260 --> 04:08:18,479 best feeding protocol is associated with minimal  feeding interruptions and steady advance,   2311 04:08:18,479 --> 04:08:25,379 need for ongoing evaluation of growth, adherence  to feeding protocol, and other outcome measures.  2312 04:08:44,040 --> 04:08:51,300 DR. GAIL CRESI: Thank you everyone. Wow, that was just as  the wealth of knowledge that we're just exposed   2313 04:08:51,300 --> 04:08:57,180 to. I'm so excited to begin our Q&A session. But  before we do that, I just want to take a brief   2314 04:08:57,180 --> 04:09:04,380 moment to thank again everyone that was involved  with putting this session together. That includes   2315 04:09:04,380 --> 04:09:13,020 our NIH scientific program contacts, including  doctors Ashley Vargas, Dr. Charlotte Pratt and   2316 04:09:13,020 --> 04:09:19,979 Christopher Lynch, as well as our working group  members, which in addition to myself includes   2317 04:09:19,979 --> 04:09:27,059 Nilesh Mehta, Dr. Todd Rice, Dr. David Seres, and  Alison Steiber. And of course, we couldn't do all   2318 04:09:27,060 --> 04:09:33,479 of this work without logistical support, which  comes from Kimberly Barch and Mark Dennis,   2319 04:09:33,479 --> 04:09:41,279 as well as our lab roots gurus, which include Israel Gonzalez and Bret Long. So thank you   2320 04:09:41,279 --> 04:09:47,880 so much for your support. And now let's get  into our question and answers, which I know   2321 04:09:47,880 --> 04:09:53,340 is going to be exciting, so I'm just going to  dive right in. So the first question is for   2322 04:09:54,060 --> 04:10:04,260 Dr. Hannon. And you talked about early  feeding of the infant (INAUDIBLE) of diabetes,   2323 04:10:04,260 --> 04:10:10,320 and you mentioned about the infant formulas, and  that the different components in the formulas   2324 04:10:12,600 --> 04:10:19,680 compared to human milk. So acknowledging that  not all children have access to human milk,   2325 04:10:19,680 --> 04:10:25,439 and that infant formula is necessary, are  there any other common formula ingredients   2326 04:10:25,439 --> 04:10:31,319 that produce different outcomes besides the corn  syrup solids that might warrant further research?  2327 04:10:36,899 --> 04:10:43,979 DR. TAMARA HANNON: This is a very active area of  research, the study of human milk and how we can   2328 04:10:45,000 --> 04:10:50,460 make the product formulas  bioidentical as we possibly can   2329 04:10:51,779 --> 04:10:55,380 be. In general, things that  are not found in nature   2330 04:10:57,600 --> 04:11:06,180 need to be studied. In my opinion and the opinion  of others before, they are routinely fed to   2331 04:11:08,279 --> 04:11:18,660 infants and children. Many of the food products  that we eat ourselves and feed our children are   2332 04:11:18,660 --> 04:11:30,180 not substances that are found naturally, and are  created in factories by manipulating naturally   2333 04:11:30,180 --> 04:11:36,720 occurring substances. And more research would  be needed to determine the long term outcomes   2334 04:11:36,720 --> 04:11:43,800 of humans consuming those substances. Did that  answer the question? So I think what I'm saying   2335 04:11:43,800 --> 04:11:49,680 is the field is still wide open and more work  needs to be done. Yes, there's the formula,   2336 04:11:49,680 --> 04:12:00,432 but we also need to continue to work to  figure out what we're feeding babies and how that's contributing to (UNKNOWN) disease. 2337 04:12:00,432 --> 04:12:03,060 DR. GAIL CRESI: Yeah, no, I think you're absolutely right   2338 04:12:03,060 --> 04:12:09,060 there, work is still in progress. So I have  another question. This one is actually for   2339 04:12:09,060 --> 04:12:15,000 both you and Dr. Wickham, in your perspective,  disease conditions that you're working with.   2340 04:12:15,660 --> 04:12:22,979 So we know you both mentioned gut microbiome  as a potential link with some of the diabetes   2341 04:12:22,979 --> 04:12:32,339 as well as pediatric obesity. And we know that in  utero now and then with first delivery, that's how   2342 04:12:32,340 --> 04:12:37,380 the infant first starts to become colonized. And  then of course, if the infants being breastfed,   2343 04:12:37,979 --> 04:12:43,379 they can also get some of these components from  the microbiome, from the mom through the breast   2344 04:12:43,380 --> 04:12:51,540 milk. So my question is, is there anything...if  you know of any research regarding the maternal   2345 04:12:51,540 --> 04:13:01,080 diet and the onset in either pediatric diabetes  or pediatric obesity, and this is, you know,   2346 04:13:01,080 --> 04:13:08,160 going to be, you know, realized a little bit later  in life for the infant. But is there any links...   2347 04:13:08,160 --> 04:13:11,260 are any links been identified?   2348 04:13:11,260 --> 04:13:14,699 DR. TREY WICKHAM: So you want me to go for it or you want to? 2349 04:13:14,699 --> 04:13:19,920 DR. GAIL CRESCI: Dr. Hannon, if you want to go first.  2350 04:13:19,920 --> 04:13:27,420 DR. TAMARA HANNON: Sure the research  was much more robust in primates  2351 04:13:27,420 --> 04:13:36,180 and rodents that it is in humans. I mean those studies are  long and difficult, especially keeping track of   2352 04:13:36,180 --> 04:13:44,280 maternal diets. It's incredibly tedious and hard.  We do know that the metabolic state of the mother,   2353 04:13:45,000 --> 04:13:54,239 which is related to her diet will  directly impact the fetus and the infant,   2354 04:13:55,380 --> 04:14:02,520 not only in response to how the fetus grows  and its exposure to glucose and its resulting   2355 04:14:02,520 --> 04:14:06,840 (INAUDIBLE) response (INAUDIBLE) response that the fetus has.   2356 04:14:07,439 --> 04:14:18,419 But then, however, that metabolic programming  carries on post delivery and as the infant grows   2357 04:14:18,420 --> 04:14:27,540 and then there's a relationship between what the  infant is fed after the infant is born and so it's really complex. 2358 04:14:27,540 --> 04:14:31,979 DR. GAIL CRESI: Yes. What about you Dr. Wickham, what are your thoughts?  2359 04:14:31,979 --> 04:14:37,559 DR. TREY WICKHAM: I would just add that I think, well,   2360 04:14:37,560 --> 04:14:42,899 certainly to answer your initial question. I mean,  there are studies that show an association between   2361 04:14:42,899 --> 04:14:51,059 kind of maternal dietary intake during pregnancy  and the prevalence of obesity in offspring.   2362 04:14:52,199 --> 04:14:57,960 And maybe that's needed some by the microbiome.  But I guess my point would be there's a lot of   2363 04:14:57,960 --> 04:15:03,600 other kind of confounding variables there that  are really difficult to tease out. Right? So   2364 04:15:03,600 --> 04:15:10,739 you can't... we know that maternal BMI during  pregnancy is a risk factor. And so how can you   2365 04:15:10,739 --> 04:15:18,120 separate that out from kind of dietary, you know,  dietary patterns as well as for many individuals,   2366 04:15:19,020 --> 04:15:28,800 dietary patterns kind of persist over a longer  period of time. And for many, many individuals,   2367 04:15:28,800 --> 04:15:34,680 their dietary pattern, while they're pregnant  will persist after delivery as well. This is   2368 04:15:34,680 --> 04:15:40,260 gonna further kind of impacts the offspring's  kind of risk. So certainly there's an association   2369 04:15:40,260 --> 04:15:46,920 there, but it's very difficult to have a lot  of scientific rigor that establish causation.  2370 04:15:46,920 --> 04:15:52,440 DR. GAIL CRESI: Yeah, I could ask so many more  questions in that area, but I think   2371 04:15:53,040 --> 04:15:56,939 I'm going to move on, unless someone, did  someone else had a comment about that.  2372 04:15:56,939 --> 04:16:06,540 DR. JALAL ABU-SHAWEESH: I was just going to mention I agree with  both that it's very difficult to do these types   2373 04:16:06,540 --> 04:16:14,220 of studies in the world of inflammatory bowel  disease, which is not only having a genetic   2374 04:16:14,220 --> 04:16:24,540 but also environmental link. There is a ongoing  study called meconium, where mothers who have IBD   2375 04:16:25,859 --> 04:16:34,620 are going into the study and doing a dietary  intervention to see if that impacts the   2376 04:16:34,620 --> 04:16:45,540 development of IBD in their offspring. And it's  not yet done, it's long-term, but I think those   2377 04:16:45,540 --> 04:16:54,660 are the types of studies that will really help us  better define what diets will improve and decrease   2378 04:16:54,660 --> 04:17:02,220 the etiology of all these conditions that are  increasing so significantly within our society.  2379 04:17:02,220 --> 04:17:09,479 DR. GAIL CRESI: Yeah. As a dietitian, I just think about,  you know, how we focus on gestational diabetes   2380 04:17:09,479 --> 04:17:14,699 and how to educate the mom who's identified to  have gestational diabetes. But we're not really   2381 04:17:14,699 --> 04:17:21,300 paying attention to her microbiome. And, you know,  should we be doing that? Because this could have,   2382 04:17:21,300 --> 04:17:28,319 you know, a relationship later on in that infant's  life and their outcomes. So I think this is,   2383 04:17:28,319 --> 04:17:35,219 in my opinion, a good area of future research  to try to figure out how to do that and see if   2384 04:17:35,220 --> 04:17:39,180 we... with all of these different diseases  that we've been talking about related to   2385 04:17:39,180 --> 04:17:46,319 early colonization of the gut and the immune  function in the gut and how much that impacts   2386 04:17:46,319 --> 04:17:52,319 many of these conditions. But I'm going to  move on to the next question for Dr. Wickham.   2387 04:17:53,160 --> 04:18:03,161 Are there any data on the relationship between  provider bias in obesity outcomes and outcomes in obese children with complicated health conditions? 2388 04:18:03,161 --> 04:18:06,120 DR. TREY WICKHAM: Yeah, Gail, I can answer that question.   2389 04:18:06,120 --> 04:18:10,019 One of the things I would refer  people to is that several years ago,   2390 04:18:10,020 --> 04:18:15,779 the American Academy of Pediatrics came up with  a policy statement about stigma experienced by   2391 04:18:15,779 --> 04:18:20,040 children and adolescents with obesity, which  is a great kind of review on this topic.   2392 04:18:21,060 --> 04:18:23,700 So the few things that I would kind  of highlight to answer that question   2393 04:18:24,779 --> 04:18:30,359 is that the vast majority of our youth with  obesity experienced some form of stigma and   2394 04:18:30,359 --> 04:18:36,719 discrimination. And unfortunately, the health care  setting is a place where that is not uncommon.   2395 04:18:37,439 --> 04:18:43,799 It's a little bit more difficult to tease out  specifically kind of the impact of bias, stigma,   2396 04:18:43,800 --> 04:18:48,479 and discrimination within the health care with  that... within kind of that larger context. But   2397 04:18:48,479 --> 04:18:55,139 I think things that we know and is that evidence  would suggest that patients feeling stigma and we   2398 04:18:55,140 --> 04:19:00,779 were talking about the pediatric population that  includes kind of their family overall are less   2399 04:19:00,779 --> 04:19:06,479 likely potentially to seek follow-up care. There's  some evidence that stigmatized youth are more   2400 04:19:06,479 --> 04:19:13,859 likely to engage in behaviors that we feel like  are less healthy. So increased binge eating, more   2401 04:19:13,859 --> 04:19:19,679 unsupervised kind of dieting, which again, have  been linked with kind of worse, worse outcomes,   2402 04:19:19,680 --> 04:19:26,520 less likely to participate in regular physical  activity. And there's some data that suggests   2403 04:19:26,520 --> 04:19:32,581 that kind of that burden of stigmatization that  is associated with subsequent weight gain. So   2404 04:19:33,540 --> 04:19:38,460 I think that there again, there's certainly  places where we need to have that clarified.  2405 04:19:41,340 --> 04:19:45,359 But I think data supports that, that it  does have adverse outcomes for our youth.  2406 04:19:45,359 --> 04:19:51,599 DR. GAIL CRESI: Oh, thank you for that. For that  nice answer. I'm going to move now to   2407 04:19:51,600 --> 04:19:59,100 Dr. Garber. So I'm wondering, are there any  opportunities for appetite, stimulation, or other   2408 04:19:59,100 --> 04:20:05,100 modulation of diet-related sensation to address  malnutrition in children with eating disorders?  2409 04:20:05,100 --> 04:20:12,000 DR. ANDREA GARBER: That certainly is an area of  interest. But so far, no, they have not been   2410 04:20:12,000 --> 04:20:19,260 successful. So any kind of appetite stimulant  medications, sometimes are used to increase   2411 04:20:22,080 --> 04:20:27,479 the rapidity of kind of movement or gastric  movement. And nothing like that has been   2412 04:20:27,479 --> 04:20:32,939 successful. Really, all of the studies in  clinical practice just points to re-nutrition   2413 04:20:33,840 --> 04:20:39,960 and re-feeding as quickly as possible to stimulate  all of those processes. So as far as I know,   2414 04:20:39,960 --> 04:20:46,260 there are right now there is no approved  pharmacotherapy specifically for anorexia nervosa.   2415 04:20:46,260 --> 04:20:50,699 All of the medications that are used are geared  toward the co-morbidities like the depression   2416 04:20:50,699 --> 04:21:00,000 that occurs and the anxiety that occurs. But in  terms of treating the malnutrition, it's alright now only we only have food as the medicine. 2417 04:21:00,000 --> 04:21:03,540 DR. GAIL CRESI: So again, along the lines of gut   2418 04:21:03,540 --> 04:21:09,960 microbiome, you have to know that that's my  area of research so interest, but there's so   2419 04:21:09,960 --> 04:21:16,979 much growing with the gut-brain axis and knowing  how their gut microbiome signals to the brain,   2420 04:21:16,979 --> 04:21:22,319 particularly with a lot of these neurological  disorders. So with the success of the re-feeding,   2421 04:21:22,319 --> 04:21:30,420 has that been ever investigated to look to target  the microbiome as well as targeting the host in   2422 04:21:30,420 --> 04:21:40,239 that re-feeding and that you're providing the food  source for what may go awry with the gut dysbiosis that you noted occurs with anorexia nervosa? 2423 04:21:40,239 --> 04:21:43,019 DR. ANDREA GARBER: That's really so you're   2424 04:21:43,020 --> 04:21:46,440 light years ahead of me. I'm just  proposing a pilot study right now   2425 04:21:46,979 --> 04:21:52,859 to look at that, but certainly, other people have  it's a really ripe area of investigation because,   2426 04:21:52,859 --> 04:21:58,380 as you said, the gut-brain axis has been  elucidated in so many other conditions. And   2427 04:21:58,380 --> 04:22:02,460 this is a condition where we know that  in the state of malnutrition when they   2428 04:22:02,460 --> 04:22:07,439 come in to us and they are low weight, their  depression is worse, their anxiety is worse,   2429 04:22:08,340 --> 04:22:19,500 and all of those other psychiatric features.  So right now the state of the evidence is that   2430 04:22:19,500 --> 04:22:25,500 patients with anorexia nervosa do have (UNKNOWN)  gut dysbiosis, and it's been well characterized.   2431 04:22:26,460 --> 04:22:32,160 Three or four studies only have looked at  improvements during the course of re-feeding. And   2432 04:22:32,160 --> 04:22:40,260 they've all shown that yes, that the gut, the the  the microbiota do respond to re-feeding, but they   2433 04:22:40,260 --> 04:22:47,460 don't fully recover. So then the next question  and as far as I know, only one or maybe two groups   2434 04:22:48,180 --> 04:22:56,819 have tried to look at this is if the gut does not  fully recover, what does that mean in terms of the   2435 04:22:56,819 --> 04:23:03,960 long-term prognosis for these patients? So Kleiman  and colleagues, for example, have shown that   2436 04:23:05,699 --> 04:23:12,720 gut dysbiosis, the persistent dysbiosis, is  related to perpetuation of the depression   2437 04:23:12,720 --> 04:23:18,120 and the eating disorder psychopathology. Nobody  that I know has really gotten to the point that   2438 04:23:18,120 --> 04:23:26,279 you're asking about, which is microbiota-directed  therapies. So is there some level of medium chain   2439 04:23:26,279 --> 04:23:33,120 triglycerides or lactobacillus or something that  could be directed at microbiome recovery, anorexia   2440 04:23:33,120 --> 04:23:39,059 nervosa? I think that's pretty far off given the  state of the evidence in this population. But I think it's fascinating. I hope we get there. 2441 04:23:39,060 --> 04:23:44,040 DR. GAIL CRESCI: Excellent. Thank you. OK. I'm going to   2442 04:23:44,040 --> 04:23:50,160 need to move on to ask some other  of the speakers some questions. So,   2443 04:23:50,160 --> 04:23:59,279 Dr. Ladas, I wonder if you could... ..add to this  question. So it seems that all ALL is relatively   2444 04:23:59,279 --> 04:24:05,040 well studied and frequent enough in pediatrics  that it might serve as a good model for disease,   2445 04:24:05,040 --> 04:24:13,691 for studying the malnutrition pediatrics in  general. Do you think this is an opportunity or is ALL really too specialized to serve as a model? 2446 04:24:13,691 --> 04:24:18,359 DR. ELENA LADAS: And in the model you're talking about   2447 04:24:18,359 --> 04:24:21,828 childhood cancer at large or just in general? 2448 04:24:21,828 --> 04:24:31,080 DR. GAIL CRESCI: I think just in general. Is it too specialized to that or either in oncology model  or just a general kind of malnutrition model.  2449 04:24:31,080 --> 04:24:38,340 DR. ELENA LADAS: So, you know, we do use it in  oncology and in part because it is the most   2450 04:24:38,340 --> 04:24:45,899 common type of cancer. And you know historically  when I first started, there was a lot of   2451 04:24:45,899 --> 04:24:53,759 undernutrition now the landscape has completely  changed where that's very, I wouldn't say rare,   2452 04:24:53,760 --> 04:25:01,500 but it's below like 3%. So it's it's not common.  But obesity, as I presented, is quite common.   2453 04:25:02,399 --> 04:25:09,179 I don't know that you could really apply what we  know in ecology to other pediatric illnesses. I   2454 04:25:09,180 --> 04:25:17,340 mean, sometimes we've drawn parallels  in children with hypothalamic obesity   2455 04:25:18,359 --> 04:25:24,899 unrelated to a tumor or radiation to the brain.  And we do have some ongoing work at Columbia   2456 04:25:24,899 --> 04:25:35,519 looking at appetite suppressants for that.  But I think, really, even within an ecology,   2457 04:25:35,520 --> 04:25:42,720 it's so vastly different. Just the duration  of treatment, the types of treatment they get,   2458 04:25:42,720 --> 04:25:50,950 and how they vacillate between under and  over-nutrition that it's really hard unfortunately to kind of then take that and apply it elsewhere. 2459 04:25:50,950 --> 04:25:54,540 DR. GAIL CRESCI: Yeah, that makes sense. Along the lines of   2460 04:25:54,540 --> 04:26:01,920 that, to prevent the weight gain that happens  in pediatric ALL, have you used any other type   2461 04:26:01,920 --> 04:26:08,399 of treatments besides dietary interventions  such as physical activity or family support,   2462 04:26:10,080 --> 04:26:14,819 parenting skills, or anything like that?   2463 04:26:15,359 --> 04:26:19,559 DR. ELENA LADAS: Sure. So that's a great point. So there's two  diseases where we look at obesity,   2464 04:26:19,560 --> 04:26:26,700 ALL is one of them, and the other is in  children with brain tumors. And you know,   2465 04:26:27,540 --> 04:26:33,239 because there is not a uniform  recommendation for exercise during treatment,   2466 04:26:34,859 --> 04:26:41,939 you know, some individuals think it's fine.  Others think it really has to be limited. And   2467 04:26:41,939 --> 04:26:47,639 all of these children have ports, so they can't  have any you know, if they were soccer players or   2468 04:26:47,640 --> 04:26:52,800 football or whatever, they can't have any contact  sports. They can't do weightlifting. So there's   2469 04:26:52,800 --> 04:27:01,920 already just limitations there. I think that we  have been focused on weight prevention, where a   2470 04:27:01,920 --> 04:27:07,380 lot of the data shows that dietary counseling,  inclusive of family, inclusive of parental   2471 04:27:07,380 --> 04:27:15,600 practices, can prevent weight gain. And that's  kind of where we're focused on. We realize that   2472 04:27:15,600 --> 04:27:22,439 we need to focus on weight loss as well because  there's about a 30% increased risk of death in   2473 04:27:22,439 --> 04:27:30,359 patients that are obese. So it's not trivial at  all. It's just a matter of how to embark on a   2474 04:27:30,359 --> 04:27:36,659 weight loss program while a patient's being told,  a child's being told they have cancer, it's hard,   2475 04:27:38,399 --> 04:27:44,759 you know. So I think that we haven't quite  figured out yet. We are starting to explore   2476 04:27:44,760 --> 04:27:54,120 the use of GLP-1 agonist. It is like six  months old. We are trying this. So it's really   2477 04:27:54,899 --> 04:28:00,000 and it's been in the extreme cases,  particularly kids with damage to the   2478 04:28:00,000 --> 04:28:08,220 hypothalamus or kids with craniopharyngioma  that just have wildly excess eating. So I mean,   2479 04:28:08,220 --> 04:28:15,239 it's that is think is a very, very fertile  area for research, really fertile. And we're   2480 04:28:15,239 --> 04:28:19,739 particularly excited about it here at Columbia. GAIL: Oh, that's great. Well, we look forward to   2481 04:28:19,739 --> 04:28:27,479 that future research. So I'm going to move on now  to Dr. Bechard. You talked to us about malnutrition   2482 04:28:27,479 --> 04:28:32,819 in that critical care setting and that there's  a causal relationship between getting closer to   2483 04:28:32,819 --> 04:28:39,479 the enteral nutrition prescription and improved  outcomes. Or do you think this might just be that   2484 04:28:39,479 --> 04:28:43,799 the patients are getting closer to the enteral  nutrition prescription because they're healthier,   2485 04:28:43,800 --> 04:28:49,380 they're getting better and they're more  responsive to the therapy or they need less   2486 04:28:49,380 --> 04:28:52,644 other interventions? Any thoughts on that? 2487 04:28:52,644 --> 04:29:01,200 DR. LORI BECHARD: Yeah, absolutely. Thanks,  Gail, for that question. And I misspoke. If I  said there was a causal relationship between   2488 04:29:02,939 --> 04:29:11,339 enteral nutrition and outcomes in the studies that  I spoke about. But I think what this question gets   2489 04:29:11,340 --> 04:29:18,239 me to think about is one of the sort of underlying  themes among all these talks is that in order to   2490 04:29:18,239 --> 04:29:26,099 really study nutrition, we need larger trials.  We need prospective interventional trials that   2491 04:29:26,100 --> 04:29:33,479 are designed to pragmatically address these  kinds of questions. And they are difficult,   2492 04:29:33,479 --> 04:29:40,439 they are expensive, they're complex. Nutrition is  notoriously hard to kind of isolate. It's not like   2493 04:29:40,439 --> 04:29:46,979 a drug where you can just give a placebo. So I  think, you know, it's it's a complicated question,   2494 04:29:46,979 --> 04:29:54,419 and there certainly is a possibility that this  is just a relationship that is not causal.   2495 04:29:55,140 --> 04:30:01,200 I don't think we truly know the answer to  that. And we need a lot more investigation   2496 04:30:03,000 --> 04:30:10,020 into some more pragmatic trials. But of course,  these things are confounded by many covariates,   2497 04:30:10,020 --> 04:30:18,060 particularly in critically ill children. There  are so many different cofactors and elements   2498 04:30:18,060 --> 04:30:24,720 related to the child, as well as the environment  that could contribute to outcomes that it's tough   2499 04:30:24,720 --> 04:30:30,840 to sort these things out. But we're getting there.  We're starting an interventional trial very soon,   2500 04:30:31,800 --> 04:30:40,910 looking at a couple of these factors and  I think hopefully with more interest in this will be able to move, move the needle. 2501 04:30:40,910 --> 04:30:48,059 DR. GAIL CRESCI: Oh, excellent. Yeah, good luck with that.  I look forward to that work as well. We have the  same problems in the adult population, of course.   2502 04:30:48,960 --> 04:30:56,220 So I'm going to move on now to Dr. Suskind. You  talked a lot about EEN and how successful it is   2503 04:30:56,220 --> 04:31:04,500 with inducing remission in pediatric IBD. And, you  know, I can't help but think that why is this you   2504 04:31:04,500 --> 04:31:10,560 know, you gave your, you know, different potential  mechanisms of why that might be occurring. And   2505 04:31:11,100 --> 04:31:16,319 you know, what that that comes to me is that these  formulas are immunosuppressive, that we know that   2506 04:31:16,319 --> 04:31:20,939 we've been talking about that for years in the  adult population because of their components.   2507 04:31:22,020 --> 04:31:26,279 We don't like to feed them to our critically  ill people and things like that because they   2508 04:31:26,279 --> 04:31:31,019 are immunosuppressive. And it makes me think too,  you know, another two parts of this question,   2509 04:31:31,020 --> 04:31:37,800 do you think that might be a mechanism?  And then the fact that we don't see that   2510 04:31:37,800 --> 04:31:43,199 these EEN randomized controlled trials,  they're not very successful in adults.   2511 04:31:43,800 --> 04:31:50,040 So why, why could that be? Could it be related  to microbiome and the different ages of the life   2512 04:31:50,040 --> 04:31:55,439 cycle or the gut immune response at different  parts of the life cycle? I just want to get   2513 04:31:55,439 --> 04:31:58,403 your input on that? Loaded question, I know. 2514 04:31:58,403 --> 04:32:08,340 DR. DAVID SUSKIND: Definitely. Well, actually, fantastic  questions. And I think, you know, the answer  is always complex. So to take the first or the   2515 04:32:08,340 --> 04:32:17,699 last question first. The question of why there is  such significant positive studies in the pediatric   2516 04:32:17,699 --> 04:32:27,540 realm and the adult studies are less positive.  Well, you know, when we do a study, I think we   2517 04:32:27,540 --> 04:32:34,560 are looking at many questions of why something  works and something doesn't work. And in the adult   2518 04:32:34,560 --> 04:32:41,699 population, it may not be that it doesn't work.  It just may be that adults are less compliant.   2519 04:32:41,699 --> 04:32:56,040 So it doesn't work from a client issue, but it  may actually work from a biochemical effect.  2520 04:32:56,040 --> 04:33:01,500 And the reason I say that is that there are  actually three studies that stand apart from   2521 04:33:01,500 --> 04:33:09,000 the other adult studies that have been done on  EEN on adults. Where patients were required to   2522 04:33:09,000 --> 04:33:18,719 have a nasogastric tube placed for 8 to 10 weeks.  And in these three studies, the efficacy was the   2523 04:33:18,719 --> 04:33:24,539 same or very similar to the pediatric data. And  actually one of those studies was the study by   2524 04:33:24,539 --> 04:33:33,959 Yamamoto where he not only put them on to EEN  but then did a biopsy, then actually saw that   2525 04:33:33,959 --> 04:33:38,699 significant decrease in cytokine levels. So I think the adult studies,   2526 04:33:39,420 --> 04:33:45,539 why they don't show efficacy may be more a  question of compliance than actually not working.   2527 04:33:45,539 --> 04:33:52,439 And I actually know a number of adult colleagues  who have started to integrate EEN into their   2528 04:33:53,520 --> 04:34:01,740 therapeutic practice and getting very positive  responses because they talk about the pitfalls,   2529 04:34:01,740 --> 04:34:09,599 the formula fatigue upfront with these patients  versus just giving them the formula and saying,   2530 04:34:09,600 --> 04:34:17,520 OK, this is what you have to do. The question  about efficacy is also fascinating, and I think   2531 04:34:17,520 --> 04:34:24,119 this is why EEN really needs to be studied  much more from not only a clinical but a   2532 04:34:24,119 --> 04:34:31,320 basic science point of view. The fact that  we are getting patients with mucosal healing   2533 04:34:32,520 --> 04:34:35,280 without any other medication intervention   2534 04:34:36,539 --> 04:34:44,519 really points to etiopathogenesis, the question  of immunosuppressant, and the components of the   2535 04:34:44,520 --> 04:34:50,760 formula. is a really good question, and I wish  I could say this is why EEN works, but I can't do   2536 04:34:50,760 --> 04:34:59,400 that. We use multiple different formulas and  it doesn't matter what formula you use. They   2537 04:34:59,400 --> 04:35:06,900 all seem to work equally as well. And we actually  just completed a study here at Seattle Children's   2538 04:35:06,900 --> 04:35:14,039 where we utilize a Whole Foods formula. Not only  a Whole Foods formula, we actually gave families   2539 04:35:14,039 --> 04:35:24,119 blenders and Amazon gift cards to buy  predetermined foods to make a formula at home. So   2540 04:35:24,119 --> 04:35:31,980 no other additives, all fresh. And the efficacy  seems equal to those of the standard formulas   2541 04:35:31,980 --> 04:35:39,119 we use. So there are a lot of fascinating  questions of why something like that works.   2542 04:35:39,119 --> 04:35:46,920 And the other interesting aspect is that the  microbiome data coming from this initial pilot   2543 04:35:46,920 --> 04:35:54,061 study actually shows a different direction than  the standard formulas, and that is likely due to   2544 04:35:54,061 --> 04:36:03,540 the differences in components of the formula as we  don't have a lot of additives such as maltodextrin   2545 04:36:04,561 --> 04:36:12,299 and corn starch, etc., and the homemade formulas.  But I think, again, it brings to question, you   2546 04:36:12,299 --> 04:36:23,580 know, the impact of diet on the microbiome, on the  metabolome, on the mucosal layer, and points to a   2547 04:36:23,580 --> 04:36:32,340 potential etiopathogenesis or cause of why we're  seeing such an increase in IBD in the world today.  2548 04:36:32,340 --> 04:36:38,641 DR. GAIL CRESCI: Thank you. Yeah, lots more work to be  done on that for sure. I'm going to move now   2549 04:36:38,641 --> 04:36:46,740 to Dr. Chumpitazi, and you gave us such a nice  review and new data on the role of carbohydrate,   2550 04:36:46,740 --> 04:36:53,760 fermentation, and carbohydrate malabsorption in  irritable bowel syndrome. If there were no limits,   2551 04:36:53,760 --> 04:36:57,412 what would you like to see studied in this area?   2552 04:36:57,412 --> 04:37:03,480 DR. BRUNO CHUMPITAZI: Oh, my goodness. No limits. Wow, That's incredible. Well, hello,  everyone, and thanks again Dr. Cresi 2553 04:37:03,480 --> 04:37:09,480 for the opportunity to be a part of this panel.  I think it's been mentioned by the panelists   2554 04:37:09,480 --> 04:37:15,660 before in terms of trying to have pragmatic  trials and having an intervention. Now,   2555 04:37:15,660 --> 04:37:21,000 what's interesting in this irritable bowel  syndrome space is that that trial could either   2556 04:37:21,000 --> 04:37:26,820 be one where you're actually restricting those  fermentable carbohydrates and trying to determine   2557 04:37:26,820 --> 04:37:32,580 the mechanisms by which it may work. Or on the  flip side, there may actually be one in which you   2558 04:37:32,580 --> 04:37:37,260 are going to be challenging patients, you know,  with certain fermentable carbohydrates and trying   2559 04:37:37,260 --> 04:37:42,600 to understand the mechanism by which they work.  And, you know, I don't know if our field has quite   2560 04:37:42,600 --> 04:37:48,959 figured out which way to go. You know, that last  information that I presented was related to, you   2561 04:37:48,959 --> 04:37:53,400 know, a specific carbohydrate fructans that are  commonly found in wheat and onions in our diet.   2562 04:37:54,000 --> 04:38:00,959 And there's a part of me that likes that idea of  really trying to get at the pathogenesis of why   2563 04:38:00,959 --> 04:38:06,660 these fermentable carbohydrates may actually be  causing the symptoms. So that perhaps if we were   2564 04:38:06,660 --> 04:38:11,039 to, you know, fast forward a few years from now,  if we understand those mechanisms will actually be   2565 04:38:11,039 --> 04:38:16,560 able to do interventions that don't require, you  know, restricting the diet for these patients.   2566 04:38:17,699 --> 04:38:22,439 So, you know, quickly, it would be  a pragmatic trial in which we are   2567 04:38:23,219 --> 04:38:30,539 challenging patients long term. Looking at  both host factors, perhaps, you know, whether   2568 04:38:30,539 --> 04:38:34,740 or not be underlying low-grade inflammation  or visceral hypersensitivity, which tend to   2569 04:38:34,740 --> 04:38:38,760 be factors that occur in those with irritable  bowel syndrome, and how that may be modulated   2570 04:38:39,359 --> 04:38:46,019 while also concurrently looking at the gut  microbiome in terms of its composition and also in   2571 04:38:46,020 --> 04:38:52,740 terms of its, what it's producing from a metabolic  standpoint. So we can really understand, you know,   2572 04:38:52,740 --> 04:38:56,219 long-term exposure of these carbohydrates  and how it may be relating to symptoms.  2573 04:38:56,219 --> 04:39:02,820 DR. GAIL CRESCI: Yeah, I mean, I like that study  and that mindset, that approach. And I   2574 04:39:02,820 --> 04:39:08,218 see how that could really move us forward to a  personalized approach to caring for all these   2575 04:39:08,219 --> 04:39:14,340 different disease conditions we've been talking  about today. If we can find some biomarker that   2576 04:39:14,340 --> 04:39:19,859 at baseline will tell us, Oh, this person will  be able to digest this or respond to this and   2577 04:39:19,859 --> 04:39:27,480 this person may not. And that leads me to my  next question for Dr. Carey regarding short   2578 04:39:27,480 --> 04:39:34,378 bowel syndrome. And are any thoughts in any  routine use of biomarkers such as citrulline   2579 04:39:34,379 --> 04:39:37,912 or fecal fat or any in this patient population? 2580 04:39:37,912 --> 04:39:47,820 DR. ALEXANDRA CAREY: Yes, I think that's a great segue and an excellent question. I work with Dr. Tom  Jackson, who published on The use of citrulline   2581 04:39:47,820 --> 04:39:56,400 in 2009 and has published since then as well. As  you all probably know or don't know, citrulline is   2582 04:39:56,400 --> 04:40:03,539 it's an amino acid in the plasma and it's  produced by metabolism of glutamine, of glutamine,   2583 04:40:03,539 --> 04:40:10,740 and proline. And it can be a marker of intestinal  length. So we use it in our clinic, I would say   2584 04:40:10,740 --> 04:40:17,279 pretty routinely in patients who are on parenteral  nutrition or who are struggling from weaning from   2585 04:40:17,279 --> 04:40:26,160 PN. We use them a cut-off of around 15 to 20 to  predict if they have a good chance at tolerating   2586 04:40:26,160 --> 04:40:32,519 advancement of enteral feeds and weaning from  parenteral nutrition. As many of you may also   2587 04:40:32,520 --> 04:40:38,219 know, there's a medication called Teduglutide  or Gattex. And we do measure sertraline before   2588 04:40:38,760 --> 04:40:45,779 starting that medication. Then six months and  one year after starting this medication as a   2589 04:40:45,779 --> 04:40:52,439 marker for intestinal mass. So the higher the  citrulline level, the higher, it's thought that   2590 04:40:52,439 --> 04:40:58,259 the higher the intestinal mass. So, yes, we do use  citrulline in our patients on parental nutrition,   2591 04:40:58,260 --> 04:41:03,660 especially those who are struggling to wean off  of parental nutrition or if we want to try to   2592 04:41:03,660 --> 04:41:08,640 predict if they'll be successful in weaning off  of parental nutrition. But like any biomarker,   2593 04:41:10,020 --> 04:41:14,400 it may not always be accurate in your patient.  And there are certain things that can falsely   2594 04:41:14,400 --> 04:41:20,218 increase or decrease this level. Well, it's just  another marker that we can use to help us guide   2595 04:41:20,219 --> 04:41:28,320 our nutritional decisions. The other comment was  about fecal fat, and we do use fecal fat at times   2596 04:41:28,320 --> 04:41:33,900 in patients who are on parenteral or enteral  nutrition or both. If they are struggling with   2597 04:41:33,900 --> 04:41:40,439 malnutrition or signs of malabsorption to help  us (UNKNOWN) nutrition. So again, if you see   2598 04:41:40,439 --> 04:41:47,039 high levels of fat in a fecal fat sample, it could  suggest that you're having difficulties absorbing   2599 04:41:47,939 --> 04:41:51,599 fat, but also may be inaccurate.  We don't frequently use   2600 04:41:52,379 --> 04:41:59,879 the 24-hour fecal fat study or 72-hour fecal fat  studies, but sometimes we will use spot fecal fat   2601 04:41:59,879 --> 04:42:05,031 analysis to help guide our nutritional decisions. 2602 04:42:05,031 --> 04:42:09,056 DR. GAIL CRESCI: So it sounds like you have some biomarkers,  but there's still room for growth.   2603 04:42:09,056 --> 04:42:11,895 DR. ALEXANDRA CAREY: Absolutely. I'll definitely agree with that.   2604 04:42:11,895 --> 04:42:21,539 DR. GAIL CRESCI: Yeah. My last question is for Dr. Abu-Shaweesh. You know, you gave us a really  nice presentation on the immune   2605 04:42:21,539 --> 04:42:25,619 status in the gut and premature  infants and necrotizing enterocolitis   2606 04:42:26,820 --> 04:42:32,580 and, you know, ideal care for these  patients, But probably some future   2607 04:42:32,580 --> 04:42:38,699 research is still needed. And in thinking about  that, what specific studies do you think still   2608 04:42:38,699 --> 04:42:41,932 need to be done in this patient population?   2609 04:42:41,932 --> 04:42:49,199 DR. JALAL ABU-SHAWEESH: So I hope my presentation did not come through as we've solved everything that  we need to solve about necrotizing enterocolitis,   2610 04:42:49,199 --> 04:42:52,920 especially with regard to malnutrition.  It's completely the contrary. I think   2611 04:42:52,920 --> 04:42:57,660 what I presented is some of the things that we  know that might work. There's quite a bit of it   2612 04:42:57,660 --> 04:43:02,879 that we still don't know, and we could start  with that. Even the definition and diagnosis   2613 04:43:02,879 --> 04:43:08,100 of necrotizing enterocolitis, there's quite  a bit of evolving evidence that what we have   2614 04:43:08,100 --> 04:43:12,959 called historically necrotizing enterocolitis  is not just one disease, is multiple different   2615 04:43:12,959 --> 04:43:18,840 diseases that might be related to (UNKNOWN) allergy might be related to just feeding   2616 04:43:18,840 --> 04:43:24,840 intolerance, simple perforation and the  usual diagnosis that we do it. So, you know,   2617 04:43:24,840 --> 04:43:31,320 more research and more studies on how we truly  diagnose necrotizing enterocolitis is separated   2618 04:43:31,320 --> 04:43:38,580 from the large majority of our babies who just  have, you know, feeding intolerance. So that we do   2619 04:43:38,580 --> 04:43:43,859 not prevent them from advancing on their feeds and  stopping their feeds and all that impact that's   2620 04:43:43,859 --> 04:43:49,199 going to help malnutrition. But even once we  diagnose necrotizing enterocolitis, there is very   2621 04:43:49,199 --> 04:43:55,560 little evidence about when to start feeding these  babies and how fast to advance these feeds and how   2622 04:43:55,561 --> 04:44:01,680 soon can you get to full feeds on these kids. I  presented two very small retrospective studies   2623 04:44:01,680 --> 04:44:07,740 that we only looked at a few babies and we need  many more studies and many large number of babies   2624 04:44:07,740 --> 04:44:14,939 to see a difference and, you know, a significant  impact of how soon can we start feeding. Everybody   2625 04:44:14,939 --> 04:44:22,679 is very hesitant to start feeds and some babies  are being (UNKNOWN), you know, 10 to 14 days after   2626 04:44:22,680 --> 04:44:28,980 the initial diagnosis. And then the last question  of probiotics, I don't think that's settled yet.   2627 04:44:28,980 --> 04:44:34,740 I know the fetus and newborn community, came up  with that strong recommendation, but it's because   2628 04:44:34,740 --> 04:44:40,560 of lack of evidence. We still need to do a lot  of research, especially in extremely low birth,   2629 04:44:40,561 --> 04:44:46,680 with infants, to try to figure out if probiotics  truly work or not. The problem with necrotizing   2630 04:44:46,680 --> 04:44:50,939 enterocolitis is the low incidence, which  is a good thing for our premature babies,   2631 04:44:50,939 --> 04:44:58,619 but it then puts the onus on multiple centers to  come together and be able to study the disease   2632 04:44:58,619 --> 04:45:04,320 because one or two or even five centers are  not going to have enough babies population   2633 04:45:04,320 --> 04:45:12,539 to be able to study it in adequate time. You need  to have multiple different centers come together,   2634 04:45:12,539 --> 04:45:17,939 the NICHD will be a good place to start.  But you might even need a bigger consortium   2635 04:45:17,939 --> 04:45:21,113 than that to be able to address these questions.   2636 04:45:21,113 --> 04:45:27,959 DR. GAIL CRESCI: Yeah. Thank you so much for that overview. You're absolutely right. I mean, so many of  these conditions and it just proves validity   2637 04:45:27,959 --> 04:45:34,920 of the data if it can be multicenter  and have different interventions. So   2638 04:45:35,820 --> 04:45:41,580 we are actually over time. But I let it go over  time because this was such a great session. And   2639 04:45:41,580 --> 04:45:48,060 I really thank you all for participating and  giving us the latest in what's going on in your   2640 04:45:48,061 --> 04:45:55,619 particular area. There's a lot of overlap, as  you know, and I hope that this was fruitful for   2641 04:45:55,619 --> 04:46:01,920 everyone and really gets our brains thinking  for future research opportunities. I'm going   2642 04:46:01,920 --> 04:46:09,660 to turn now to wrap up day number four. Today, we  heard about our first session for today was about   2643 04:46:09,660 --> 04:46:15,599 early life malnutrition. With introductions  to its definition, burden, epidemiology, and   2644 04:46:15,600 --> 04:46:21,660 screening. We then discussed early life research  considerations with unique challenges in early   2645 04:46:21,660 --> 04:46:27,539 life research and malnutrition. This included a  summary of the evidence on malnutrition in early   2646 04:46:27,539 --> 04:46:33,719 life with systematic reviews and guidelines, then  the Academy of Nutrition and Dietetics in ASPEN.   2647 04:46:33,719 --> 04:46:38,820 Lastly, we just heard from this  esteemed group of clinicians and   2648 04:46:38,820 --> 04:46:43,920 researchers where we heard about disease and  condition-specific malnutrition in early life,   2649 04:46:43,920 --> 04:46:48,840 covering a multitude of clinical conditions  and diseases that impact nutritional status   2650 04:46:48,840 --> 04:47:08,200 in early life. We look forward to you all joining  us tomorrow for continued discussion with an update on malnutrition related measures in pediatrics with presentations on disparities, family, and system level determinants of early life malnutrition risks, access, and treatment. Thank you so much.