DR. ASHLEY VARGAS: Good morning, afternoon, evening, depending on where you are. On behalf of NIH and
as part of the Workshop Organizing Committee, I'm so pleased to welcome you to day four in the very
first day of a two-day workshop that is going to focus on malnutrition in early life. Thank you
for those of you that attended the previous three days, and now we're going to move to a focus a little
closer to my heart. My name's Ashley Vargas, and I'm a registered dietician and a program
director at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Nutritional status and risk for malnutrition begins in early life and shapes developmental,
health, and disease outcomes throughout life and across generations. While pregnant and lactating
individuals and children are uniquely susceptible to malnutrition, this also makes this time point
pivotal in life. A small positive change can have an outsized, lifelong effect. Therefore, the
objectives of the next two days are to identify research gaps and opportunities that advance
malnutrition research in early life populations. Now it is my honor to introduce the NICHD Deputy
Director, Dr. Alison Cernich. Dr. Cernich is a board certified neuropsychologist with
expertise in cognitive neuroscience, and, in her role as deputy director, she works to
implement our recent NICHD strategic plan where nutrition has a prominent role. Dr. Cernich
DR. ALISON CERNICH: Thanks so much, Ashley, and thanks to all of you who are joining this focused part of
the workshop. On behalf of NICHD, and our partners at the Office of Nutrition Research, and the
National Heart, Lung, and Blood Institute, I would like to welcome you to the fourth day of this
workshop on malnutrition in clinical settings. Today and tomorrow you will have the opportunity
to take a closer look at the myriad factors influencing pediatric and family nutrition,
malnutrition risk, treatment, access to treatment, and the detrimental effects of
malnutrition in the U.S. health care setting. For the clinical practitioners in the audience, I
know many of you see malnutrition in your patients every day in the clinic, and there's a struggle
to provide the right care to the right patient at the right time to prevent and treat malnutrition.
While it's 2022, and I...I think we can do better for our youngest patients and their family.
Today and tomorrow, I implore this group of great minds to push boundaries and to
think outside of the box to discuss opportunities to advance the evidence
base we have for clinicians to address malnutrition seen every day across the U.S.,
build on the ideas from the first three days of this workshop, and discuss the science that
we will use to address the critical windows during pregnancy, lactation,
infancy, and childhood as levers to raise the nutritional health of our families.
In closing, I want to thank our visionary co-chairs, Doctors Mehta, Steiber, Seres, Cresci,
and Rice, along with our NIH organizing committee, Doctors Vargas, Lynch and Pratt, and certainly
our sponsor, the Office of Nutrition Research, for bringing this workshop together. While our
NICHD strategic plan emphasizes the importance of nutrition and lifelong health and is committed to
supporting early life nutrition research, we are so grateful for all the support we receive from
throughout the NIH, for the specific focus on lifespan nutrition. So thanks so much, Ashley.
DR. ASHLEY VARGAS: Thank you, Dr. Cernich, for your kind words and support.
Now I have the honor of turning the virtual microphone to our brilliant lead and our chair for
the early life part of this workshop. Dr. Nilesh Mehta of Harvard Medical School. Nilesh, to you.
DR. NILESH MEHTA: Thank you so much, Dr. Vargas. Dr. Cernich, thank you for introducing this session.
And welcome all to this exciting day four. We've had, as you heard, a very exciting adult
workshop session group on days one, two, and three. And I'm confident that the next
two days we will see equally stimulating discussions related to the early life.
I'm excited to bring you this session. My name is Nilesh Mehta. I'm a Professor of Anesthesia
Critical Care Medicine at Harvard Medical School. I work at Boston Children's Hospital.
In the session today, we will focus on early life malnutrition. This is an introductory session,
which will review some of the definitions, the burden, the epidemiology, and screening aspects
of pediatric malnutrition. I'm delighted that we are joined by a group of esteemed speakers
who have been at the forefront of pediatric malnutrition, advancing the field for years.
The session will begin with Dr. Corkins from the University of Tennessee Health Science Center,
who will speak to newer concepts of defining pediatric malnutrition.
It will be followed by Dr. Patricia Becker, who will speak on approaches to screening, assessing,
and diagnosing pediatric malnutrition. After that, Dr. Jimenez from the University of New
Mexico Health Sciences will speak of her experience with the application of recent
tool in diagnosing pediatric malnutrition in U.S. hospitals. And we will end the session with
Professor Fenton from University of Calgary, who will provide a unique perspective on
malnutrition as it relates to preterm infants and provide us with a bigger causal picture.
After that, we will break into a Q&A session. I'm delighted that I'll be joined by Dr. Todd Rice
from Vanderbilt University Medical Center and Dr. Vargas. And together, we will be delighted to take
your questions and, with the help of our speakers, have a lively discussion. This session goes on
until 10 past 1, after which we break. And then we move on to the next session, which is session eight.
And I'm excited at this point, without further ado, to once again welcome you all.
Thank you so much for joining us today. And I will now kick this off by moving
on to Dr. Corkin's presentation on defining pediatric malnutrition.
DR. MARK CORKINS: I was asked to talk about defining malnutrition, new concepts, and metrics.
So here's my disclosures. You know, our intestinal rehab clinic is a site for a Takeda-sponsored
study. I am the PI on that, but I get no direct income from that, so really have
no potential conflicts of interest with this presentation. So, when we're talking about
malnutrition, where have we been? Well, I'm just kind of giving the introduction and overview. First is marasmus,
and that's just basically not enough energy intake. This is your emaciated Third World kids,
who just don't get enough calories. The other one we learned when we were in school was kwashiorkor,
it's a Ghanaian word that means "the sickness when the new baby comes." And basically,
they're switched from breast milk, which contains protein, to carbohydrate-rich diets. And so,
they're protein deficient. And so, they have this edema that kinda of hides your malnutrition.
The one that we get that has been used for years in the developed world is failure to thrive. Now,
it was thought to be originally institutionalized orphans, and it's maternal deprivation.
It's not diagnostic, it's not descriptive. Parents don't like the term failure. And really,
more or less, it's been decided that probably this term should go away.
Now, but when you do a deep dive and you look at children, especially hospitalized children,
you find you that there are children who are malnourished. And this group, Joosten and Hulst,
in 2008, did a review. Now, when they looked at acute malnutrition, they found rates anywhere from
6.1 to 32%. But different nations had different methods. And so, it's kind of a hodgepodge.
So, there was a recognition that malnutrition in the developed world really happens in the
presence of disease. And it's a disease process. So the three mechanisms of malnutrition are you're
losing too many nutrients, you're using too many nutrients, or you're not taking in enough
nutrients. And when Grover and his group looked at the breakdown of kids who are malnourished,
they found out they had some sort of primary disease. And if you look at the bottom there
on the left, 44% of them had multiple diagnoses. So malnutrition is happening in the presence of
disease. And that sort of makes sense. So if you know that we have kids with these chronic diseases
now, that we're curing and treating, well, that sets them up to be malnourished. They have
inflammation, inflammation burns calories. They have all sorts of extra medical needs. In fact,
the U.S. Department of Health and Human Services defines kids with acute or chronic illnesses,
kids that have special health care needs. And they have an increased risk for chronic physical,
developmental, behavioral, and emotional conditions that require health and health-related
services beyond that of children generally. The thing is, in the US, that's 14%. 14% of kids are
those considered with special health care needs. That's a big group. And so, it was a recognition
that we needed a definition that worked in the developed world for malnutrition. And there was a
work group formed in April, 2010. Dieticians, physicians, (UNKNOWN) GI doc, yours truly,
actually, endocrinology, critical care, primary care, chronic care, nurses, pharmacists.
It was very multidisciplinary. And actually librarians, who helped pull literature. And
we actually published that in March 2013. It was endorsed by the American Society for Parenteral
and Enteral Nutrition, the Academy of Nutrition and Dietetics, and the American Academy of
Pediatrics. Now, when this group started looking at things, we looked at potential functional
measures. We really wanted functional measures to look at. Well, lean body mass measurement. Well,
that's not that easy to do in kids. Not even in a research setting is it that easy to do. Muscle
strength. Well, that depends on if you train or not, or you're male, or you're female, where you're
at in puberty. Neurocognitive outcomes. Well, that's great except that's also influenced by
a lot of other factors, socioeconomic factors. Some of it's genetic. Immune function, well,
how do you measure immune function? Duration of illness. Hey, that is a functional measure,
but are you going to give somebody an illness to measure how well their function works?
So, that's an ethical issue. Tanner Stages. And I will admit, I was in part of the group that
looked in depth at Tanner Stages, huge genetic input into Tanner Stages. There's a five-year
swing. If your mother went to puberty early, you're probably going to go into puberty early. If
your mother went late, it's late. And so, how can you use that as a nutrition marker? Well,
you really can't. So, when the group got really down to the brass tax, basically the only thing
that the literature put out that you could follow, that was very objective, was anthropometrics:
weight, height, length, body mass index, mid-upper arm circumference. And mid-upper arm circumference
is the one that surprised everybody that the literature showed that that was a very accurate
measure. It's primarily been used in Third World countries, and it's actually a very good predictor
of mortality and morbidity. The other thing that came out of the literature is that we should be
reporting this data as z-scores, how far they are from the median weight of the same reference data.
And actually, WHO has been recommending that we use z-scores since 1977. Our residents and
fellows love z-scores because it's continuous, and it's not a percentile. Less than the one
percentile is how far? Because that less than the one percentile is a big range sometimes.
Anthropometrics, obviously the problems are, of course, you need an accurate weight.
For up to two years of age, we're still using the 2006 WHO charts, and a supine
length measurement for kids age two to 20 years of age. We're using the CDC 2000 growth charts with
a standing height measurement for plotting. Now, ideally of course, we would use changes, weight,
length, velocity over time as opposed to a single measurement. But I'll tell you, the
work group that looked at this really recognized an ability that we needed to be able to make an
encounter diagnosis. Because you see kids, they're malnourished and you want to intervene, you need
to intervene, you shouldn't wait. Basically, created tables for both. Acute versus chronic,
well, NCHS defines chronic as anyone the last over three months, so that was defined for us.
Here is the single encounter chart, ok, and this'll be in your slide set. And here's the
multiple points. And this is basically looking at the changes in velocity with time. Again,
this is probably the ideal. Of course, what really falls out of this is when you start to talk about
malnutrition, it is an etiology-based diagnosis now. So, when you see a child,
they meet the parameters for malnourishment, you say, "Hey, is it acute or chronic? Is it mild,
moderate, or severe? Is it illness related or non illness related?" And state the illness and
you include the medical etiology as part of the diagnosis. This is a chronic, severe malnutrition
in the face of congenital heart disease. And you can say type of chronic congenital heart disease.
And that is the diagnosis, that's the malnutrition diagnosis in full. So that's kind of...a quick overview of the
new concepts in malnutrition now that we're approaching malnutrition with in children.
I was asked to talk about research gaps. Well, number one, based on this data we
have currently, number one, research gaps are accurate anthropometrics.
Now, weights aren't too bad, although they're currently not perfect.
Length and height though, are lots of issues with measuring those. And some kids can't be measured
in the standard length board or standing height, so there are proxy measures. Well, number one,
we can measure the distance if you're a golfer to the flag pole, so there should be good ways
to measure length in height better than just tape measure or length board. There should be
some sort of technologic approach to do that. The proxy measures, we need more studies on better
proxy measures and better tables and data on proxy measures. Functional measures, I talked about some
that didn't work, but we need studies on other functional measures, something that's measurable
over time in a predictable fashion that will correlate with the nutritional status. Now EHR,
good grief. There's a bunch of things that can be done there. We need to have some sort of a
system that can look at error measurements. "Oh, this height's too far, this length's too short.
This needs to be redone." And a smart system should be able to figure that out and do that. The
other thing is, special disease curves. We have some available, but they should be incorporated
into the EHRs. The EHR is a perfect place to do that. There's a Turner's growth curve. If
you have a child with Turner's, you should be able to go to a menu and select Turner's growth curves.
And some of the more common disorders, there should be growth curves for those children
that are available to help you track what normal growth is for them. Alright,
I appreciate your attention, and I'll look forward to discussing this later as a part of the group.
DR. PATRICIA BECKER: I am Patricia Becker and I am presenting on pediatric malnutrition risk
screening, assessment, and diagnosis. Malnutrition risk screening should utilize validated tools.
Those tools should have moderate to high user reliability and outcomes validity.
They should be usable in all patient care settings. Pediatric malnutrition
risk screening tools should be adaptable to both paper and electronic medical records.
Children should be screened for malnutrition risk in all patient care settings, within 24 hours of
admission in acute care, and upon presentation in the outpatient and primary care settings.
Tools that meet these criteria include the pediatric nutrition screening tool, PNST.
It is used by the Canadian health care system, the Australian health system,
Boston Children's Hospital, and by our hospital, Dayton Children's.
It is comprised of four questions. It is adaptable to both paper and electronic medical records.
It stratifies children into severe, moderate, or no risk. Children with severe or moderate
risk should be referred to a registered dietician nutritionist for further assessment.
This is the PNST. The URL for this tool is located at the bottom of this slide.
The screening tool for nutrition Risk of Nutritional status and Growth STRONGkids is in use by the Canadian
Healthcare System and the Academy/ASPEN Indicators of Malnutrition for Pediatrics Validation Study.
It is comprised of four questions. It is adaptable to both paper and electronic medical records.
It stratifies children into severe, moderate, or no risk. Children with severe or moderate
risk should be referred to a registered dietician nutritionist for further nutritional assessment.
Here are the screen questions for STRONGkids. They include questions related to the child's
medical condition, nutrition focused physical assessment, GI symptoms, nutrient intake,
and weight growth assessment. The URL for this tool is located at the bottom of this slide.
The screening tool for assessment of malnutrition and pediatrics, STAMP, is a five step malnutrition
risk screening tool that includes questions on height and weight measurement compared to
percentile tables and severity of medical diagnosis' impact on nutritional status.
The Electronic Health Record STAMP is the adapted tool for the electronic medical record that has
been validated and updated to include current criteria. The citations are included here.
This website provides information on its use in practice. This URL directs the user to the
percentile-based tool. Here is an example of that tool. The URL is provided below.
This information shows the adaptation of STAMP from the percentiles to the z-score
for use in the electronic medical record. For the assessment of malnutrition tools
for use include the Subjective Global Nutrition Assessment for pediatrics.
SGNA for pediatrics is currently the only validated tool for pediatric nutrition assessment.
It is often used as the reference standard for validation of other tools and criteria.
Concerns with the 2012 version are outdated and unvalidated measures, such as percentage of ideal
body weight for children, and changes in weight over a period of six months
plus weight loss percentage, and use of percentiles versus z-score data.
The highlighted areas here show the criteria that would benefit from updating to current standards
and validation. They include weight and weight change over the past six months and weight loss
percentage. Appropriateness of weight for height, as stated for ideal body weight greater than 90%,
75 to 90%, or less than 75%, and adequacy of intake with vague terms such as adequate,
somewhat adequate, and very inadequate starvation.
Highlighted areas include criteria that were updated to include the Academy/ASPEN Indicators of
Malnutrition for Pediatrics, which were validated for use by the Canadian Malnutrition Task Force.
The citations and website are indicated here as well.
The revised SGNA also includes more detailed assessment of adequacy of intake,
as well as a clearer description of functional capacity. For your information, I am also
presenting information on malnutrition diagnosis for pediatrics. The Academy of Nutrition and
Dietetics and ASPEN consensus derived Indicators of Malnutrition for Pediatrics, the AAIMP
have been in common use since their publication in December of 2014, with over 80 citations.
They are currently undergoing a multi-center research study to validate these criteria.
Criteria for mild, moderate, and severe malnutrition have been established for
children ages one month to 18 years. Documentation should include the criteria and be supported
by the modifiers of chronicity, the presence of inflammation, and their relationship to illness,
as well as inclusion of information on nutrition-focused physical examination findings.
Criteria for pre-term infants and neonates were not included in the AAIM for pediatrics.
These were proposed in the paper published in 2018.
These recommended indicators have been in use since that time. The indicators include weight,
length, gross velocity, and adequacy of intake-based criteria. In our NICU, we are
finding approximately 15% of the population meet the criteria with agreement from our providers.
To support practice, pathways for providing malnutrition care for children can be helpful for
the health care team. The following three slides show examples from the Canadian Malnutrition
Task Force, ASPEN, and the Children's Hospital of Philadelphia, all of which are open source.
They can be helpful in support nutrition care for children. The Canadian Malnutrition Task Force
Pathway outlines the steps in nutrition care, screening, assessment, diagnosis,
and treatment or nutrition care. The URL for this pathway is located at the bottom of this slide.
The ASPEN Pediatric Malnutrition Pathway for Children ages one month to 18 years is shown here.
The URL for the pathway is located at the bottom of this slide.
Here is an example of one of several malnutrition-related clinical pathways available
from the Children's Hospital of Philadelphia, and the URL is at the bottom of this slide as well.
Thank you for your attention. Please feel free to contact me at the email
addresses provided should you have questions or comments.
DR. ELIZABETH JIMENEZ: Hello, My name is Elizabeth Yakes Jiminez, and I'll be discussing application
of the Pediatric Academy and ASPEN Indicators to diagnose malnutrition in hospitalized patients,
otherwise known as the pediatric AAIM tool.
We know that malnutrition is associated with poor clinical outcomes and increased health care
utilization in hospitalized patients, but is likely underdiagnosed and undertreated.
A recent study found only a 6.4% prevalence of a coded diagnosis of malnutrition for U.S. pediatric
patients in 2019. One barrier to improving diagnostic practice is the lack of a systematic,
universally-accepted method of diagnosing malnutrition in the hospitalized pediatric
patients. As Patricia Becker explained in her presentation, the pediatric AAIM tool
was developed through a consensus process. More information is needed about the tool's predictive
validity and implementation before concluding that it should be widely used. To examine the
predictive validity of the pediatric AAIM tool, we are conducting a cohort study with U.S. hospitals.
For those interested in detailed information on the study design,
including inclusion and exclusion criteria, a published protocol paper is available.
At baseline, we are collecting some data for all patients enrolled in the study. This includes
sociodemographic information, medical history, a STRONGkids' malnutrition screener score,
duration and type of initial nutrition care, and an RDN-determined complexity measure.
If a physician orders biomarkers of inflammation, those are also captured.
From within this full study group, which will be used to examine study staffing aims,
we randomly selected a group of children for whom the pediatric AAIM tool and a nutrition-focused
physical exam are being completed. Children are randomly selected to be included in the
AAIM subgroup stratified approximately one-to-one as high or moderate versus
low-risk for malnutrition based on the STRONGkids' screener score. 90 days after discharge,
we pull information on dietician follow-up care, hospital readmissions, ER visits, and length of
stay from the medical record, along with ICD-10 Codes to calculate measures of disease severity,
including the MSDRG relative weight, the Charleston Comorbidity Index, and the Pediatric
Complex Chronic Conditions Measure. Thus far,
29 hospital sites have initiated data collection, and 23 sites have completed data collection.
I will be presenting data from 166 patients in the pediatric AAIM subgroup, from 22 hospital sites.
As data are still being collected for the study, all results included in this presentation should
be considered preliminary. Data collection for the study started in August 2019, and a
substantial proportion of the data were collected after the onset of the COVID-19 pandemic.
Hospital sites are located across 19 states and Washington D.C. Hospitals currently represented
in the analysis have a median of 187 licensed beds, a median average census of 154 patients,
and a median case mix index of 1.77. Almost all are affiliated with a medical school and
located in population-dense areas, and about a third are critical access hospitals. About
three-fourths of the dieticians collecting data for the study have advanced degrees, and about 40%
have additional advanced certifications related to pediatric nutrition or nutrition support.
Participating dieticians are experienced practitioners, with a median of nine years
of experience in dietetics, and seven and a half years of experience in inpatient nutrition care.
Patients currently enrolled in the study are about evenly divided between boys and girls,
and have a median age of 4 years. Overall, about a third of patients are less than 2,
half are 2 to 11.9 years, and about a fourth are adolescents. 61% of patients are White,
19% are Black, and 23% are Hispanic. Based on the STRONGkids screening tool,
about half of children are at moderate risk of malnutrition and about a third are at high risk.
A similar distribution is seen for dietician-assessed patient complexity, with about
half of patients rated by the dietician as medium complexity and a third rated as high complexity.
High complexity patients are defined as requiring nutrition interventions with frequent
reassessments, for example, patients with chronic or nutritionally complex diseases, new or modified
enteral or parenteral nutrition, or requiring new or complex comprehensive nutrition education.
Using the pediatric AAIM tool, the dieticians determined that 57% of patients have malnutrition,
about evenly divided between mild, moderate, and severe malnutrition.
This reflects the design of the study.
Dieticians reported spending a median of an hour on initial care for the children included in the
study, and frequently document nutrition diagnoses related to inadequate oral intake, malnutrition,
altered GI function, and inadequate energy intake. During the 90-day follow-up period, about half
of children did not have any contacts with the dietician related to oral nutrition supplements,
enteral nutrition, or parenteral nutrition. Another 19% had one contact, with about a
fourth of children having two or more nutrition support contacts during the three months after
discharge. About a third of patients spent some time in the ICU during their admission, while very
few were diagnosed with sepsis, had non-healing wounds, or died during the enrollment admission.
For the analysis, we used a composite 90-day outcome that adds together the number of
hospital readmissions and ER visits that the child had during the 90 days after discharge.
This ranged from zero to eight. The median length of stay was five days.
Finally, we calculated three different disease severity indices, all of which can be interpreted
as higher numbers indicating more severe disease or more intensive use of health care resources.
The study data analysis focuses on whether children and teens with the diagnosis of
malnutrition, based on the pediatric AAIM tool, have more ER visits and readmissions
and/or longer length of stay, compared to children without the diagnosis of malnutrition.
In our multilevel Poisson and generalized linear models, we controlled for disease severity,
ICU stays, and socio-demographics, since there is evidence that these factors may be related
both to malnutrition and health care outcomes, and also included a random effective site.
In addition, we examined the relationship between individual indicators, the STRONGkids screening
tool, RDN-assessed complexity, and the health care outcomes, controlling for the same factors.
As mentioned on the previous slide, all models controlled for a measure of disease severity,
ICU stay during admission, child age, and biological sex.
Overall, children who scored at high versus low risk on the STRONGkids screener,
or who were assessed as high versus low complexity by the dietician,
had higher incidents of ER visits and readmissions and longer length of stay. However, there was no
relationship between a pediatric AAIM diagnosis of malnutrition and health care outcomes. When we
examine the relationship between dietician's use of individual indicators and total ER visits and
readmissions, only dietician use of deceleration and weight for length or height z-score to support
a diagnosis of malnutrition, was significantly associated with a higher incidence of the outcome.
Deceleration and weight for length or height z-score is one of the longitudinal measures and
may be more useful to understand change in status, but it was unable to be assessed for 41 children.
Only dietician use of length or height for age z-score to support a diagnosis of malnutrition
was significantly associated with longer length of stay. Interestingly, from an implementation
perspective, the same relationship with length of stay is not observed when using objective
length or height for age z-score cutoffs. And the dietician chose to use length or
height for age z-score as an indicator only about 30 to 40% of the time when the z-score was less
than negative two. So the dietician may be recognizing when linear growth restriction
is unrelated to chronic malnutrition and taking that into account during the diagnostic process.
While the findings from this work are preliminary, they identify the need for additional work to
determine the best tool to diagnose malnutrition in hospitalized pediatric patients.
Additional studies could consider relationships between a malnutrition diagnosis and other
outcomes, such as child development and quality of life, when identifying the best tool to use.
Once a validated tool is identified, it will be necessary to identify the level of
dietician staffing needed to provide nutrition care that improves outcomes. To determine if
diagnosed malnutrition resolves with nutrition intervention and to understand biological and
environmental factors that are associated with non-response to nutrition intervention.
Thank you very much for taking the time to listen to this presentation.
DR. TANIS FENTON: Today I've been asked to talk about malnutrition with respect to preterm infants and
the bigger malnutrition causal picture. So part one, preterm infants and malnutrition.
Preterm infants are challenging to nourish. At birth, they have limited nutrition stores
as well as no or limited oral feeding abilities. They're separated while they're
in intensive care from their families. Some have had poor growth in utero, and some have
limited tolerance of parenteral and/or enteral nutrition, so they are a challenge to nourish.
A concern I have about diagnosing malnutrition or poor infant growth
for preterm infants is that extrauterine growth restriction is a very popular categorization.
This graph shows the rise in the use of the term extrauterine growth restriction in Medline through
the PubMed search engine. Extrauterine growth restriction is usually defined as a weight less
than a 10th or a 3rd percentile at about 36 weeks post menstrual age. And you can see from
the pattern here that over the past 20 years, with a little bit of an exception, there's been
an approximate exponential rise in the use of this categorization.
The reason I don't value using this categorization is that extrauterine growth restriction is not
related to cognitive outcomes. Here are six studies that examine this question at
either the 3rd or 10th percentile, or seventh percentile at 36 to 40 weeks. We also looked at
continuous all percentiles at 36 weeks. And in all cases, this categorization was not associated with
low cognitive scores. We looked at both the Bayley and IQ scores at three years of age.
So a group of very smart dieticians have put together some malnutrition indicators led by
Dr. Dena Goldberg. These indicators are declines in weight for age z-scores,
and also relative to that needed to maintain expected growth rates,
a low weight gain velocity, and consecutive days of inadequate protein and energy.
These indicators have not yet been validated, so this is a good topic for a research project.
The reason why the X uterine growth restriction is probably not associated with
poor cognitive scores is the usual weight change pattern of preterm infants. This graph is showing
weekly cohorts of preterm infants and how weight loss is, is common amongst most preterm infants.
You can see that at the 10th percentile, the shaded area is, the bottom of the shaded area
is approximately equal to this 10th percentile on the growth chart. And this shaded area is
the interquartile range, which means it's the 25th to the 75th percentile. So, this graph is showing
that 25% of these preterm infants weighed less than the 25th percentile after their postnatal
weight loss. And these infants were selected to be the healthiest of preterm infants from
the healthiest of pregnancies, no morbidities, minimal respiratory support needed. And yet 25% of
them weighed less than the 10th percentile after the postnatal weight loss. The average of their Z
change, Z score changes was 0.8. But I proposed to you that we can't expect that all preterm infants
should only lose an average of 0.8 Z scores. And the actual range of Z score change for this
sample of preterm infants ranged from no change at all to a loss of two Z scores. So, what we
need for preterm infants are defined measures that are highly predictive of adverse outcomes.
So, the American Academy of Pediatrics and ESPGHAN have put forward some growth guidelines over the
years that have really passed the test of time. They both recommend that preterm infants grow
at approximately the rate of a normal fetus. And they don't recommend achievement of any particular
percentiles, but rather looking for a growth pattern that is approximately parallel to that
of the fetus. And what that looks like on growth charts is growth that approximately parallel to
growth chart curve. So, you can see this little girl on the left. She lost some weight and she
didn't keep up perfectly to intrauterine growth rates, but then she was able to maintain weight
gain that was approximately parallel, as well as length that was approximately parallel. Her head
did a little bit of catch up before her term. This little boy, on the other hand, was not
doing well. Both his weight and his length were continuing to fall off, fall away from the growth
chart curves. Even his head was falling off the, the growth chart curves. So, this is the
growth that is recommended as undesirable by the American Academy of Pediatrics and ESPGHAN and I
agree with them. So, this brings us to Part 2, the bigger malnutrition causal picture.
So, the problem is often assumed to be that poor nutrition leads to poor growth and malnutrition
leads to poor outcomes. But I propose to you that the actual causal relationships are much
more complex, and the factors that are important include the social determinants of health,
prenatal factors, inadequate nutrition is a factor. Also, stress in the NICU has been
associated with outcomes as well as morbidities. So, all of these factors lead directly to poor
outcomes. They can also lead to poor growth and malnutrition. But it's not really clear if there
is a causal link here as there was in the 1980s. But I'm hoping that in North America,
the nutritional care for the most part does not lead to poor outcomes
directly here. So, for pediatrics, the diagram is a little bit different because pediatrics are
removed somewhat from prenatal factors. Not to say that those factors aren't important at all,
but it's probably better to include the factor of environment for pediatrics.
And I proposed to you that there was some value in the traditional consideration for failure
to thrive, that there were organic causes, meaning medical causes, as well as non-organic
or non-medical etiologies. And this is true of malnutrition as well.
So, I proposed to you that what we need is, first of all,
we need malnutrition measures that are highly predictive of adverse outcomes.
And so that we can then work to improve the nutrition and the outcomes of, of the infants.
I think it's well established that the best malnutrition measures are based on
serial measurements to assess both growth and nutritional status and not one time measures.
And we need to consider several anthropometric measures and not only weight. And I think this
workshop is an opportunity that we could take to encourage the electronic medical record companies
to show several of the anthropometric measures simultaneously. For example,
for preterm infants, it's highly valuable to look at weight length and head circumference
at the same time on your screen, on your computer screen. For older infants, it's important to show
length or height with weight for age, or BMI, to be able to assess infants and and children well.
And then we need to consider the etiology, since it will help determine the solution.
That is, the etiology of malnutrition helps to determine the solution to the malnutrition.
So, I wish to thank you for your time and attention.
DR. NILESH MEHTA: For these excellent stimulating kickoffs to all of our speakers, Dr. Corkins, Dr. Backer,
Dr. Jimenez, Dr. Fenton, I truly appreciate it. At this point, I would like to welcome Dr.
Todd Rice, from Vanderbilt University, who will be joining me for the Q&A session.
Welcome, Todd. And, and once again, before we kick this off, a brief
temperature on what's happening. Well, on the other side, and we have over 70 participants
online right now, and it's really a big deal for us to have gathered in this forum. And to that end,
I truly wish to thank the NIH Office of Nutrition Research, our scientific program leadership from
Dr. Christopher Lynch, Dr. Charlotte Pratt, Dr. Ashley Vargas, on behalf of all the co-chairs,
we really thank you for this opportunity and giving both the adult and pediatric community
this platform. Thanks so much to Dr. Kimberly Barch, to Marc Dennis and today, Israel Gonzalez
for all the behind the scenes technical support that we've seen. And of course, thank you so
much to Dr. Cernich for being present here today and once again providing this platform.
So, with that said, I see many of our speakers already on here, and we can jump
right in. One of the beauties of this session is it follows the adult malnutrition research gaps
sessions over the last three days, last week. And I thought if Dr. Rice could kick us off by
some similarities, some themes that you saw in the adult sessions that you are hearing here in the pediatrics today. Dr. Rice.
DR. TODD RICE: Yeah. Thanks Nilesh, and great presentations to the panel. You know, the
adult sessions, many of the participants and, and current people watching may have actually watched
the adult sessions, too. But quickly, kind of some similarities in malnutrition is that I think we're
all looking for that elusive perfect marker. We don't have it yet in the adult world. And it
sounds like that's true in the pediatric world also. The scores are pretty good at predicting
malnutrition as defined by poor outcomes. But and this is something we spent some time talking about
on the, on the adult side is, but importantly, we haven't bridged the gap for predicting the
patients that we can actually intervene in and, and change the outcomes. And so, there's lots
of scores in the adult world that say, if your score is X on this or greater than X on this,
you're more likely to have a poor outcome. But what we don't have very much of is a marker
that says, if your score is this, you're likely to have a poor outcome. And if we intervene with the
nutrition therapy or nutritional support therapy, we can change that outcome and make it different.
One of the things, interestingly, and somebody in the panel, and maybe even you, Dr. Mehta,
can comment on it, that is becoming very popular in the adult world are imaging to try and diagnose
malnutrition. So, ultrasound of muscle bodies, or people love CT scans of kind of the L3-L4. So,
as muscle at that level to try and, and they reasonably predict, again, poor outcomes
and we think malnutrition. We didn't have a specific talk about that in the pediatric side,
but I'm intrigued to know if that's something that's truly different in the adult world. If
it's something in the pediatric world, you all have tried and said it doesn't work and
we've given up on it. Or if it's the, maybe that's all too common in the pediatric world.
DR. NILESH MEHTA: Thanks, Dr. Rice. Brilliant. I appreciate you giving
us a nice overview of how things are similar and how things are different, which, as you've heard,
surely imaging. And I will let our speakers jump in. I just wanted to remind everyone to use the
question box on your, on your platform and thank you for all the questions that you've put in. We'd
love to get more, and I will interrupt this discussion if I see new questions pouring in.
But we have plenty of questions that we could kick this off with. Alright. Dr. Corkins,
a couple of questions related to the low resource community that you alluded to.
And one of them is, it seems like and this is from Dr. Christopher Duggan from Boston Children's.
It seems like, seems like this approach assumes that malnutrition in the low resource countries
developing world is not generally associated with illnesses. But, but of course, many episodes
of severe and moderate acute malnutrition in children in resource poor countries are linked
with infectious or other inflammatory stresses. Does it make sense, Dr. Duggan asked to have
two definitions of malnutrition, one for, one for industrialized countries and another for other countries.
DR. MARK CORKINS: Yes, it does make sense. At least it makes sense to me. So, in the developing world,
it sometimes is a chicken and the egg. And are they malnourished? Does it lower their threshold
for infection? But infection certainly will worry, worrisomely, I think that's,
I think that's a word, make their malnutrition worse. And sometimes it is a vicious cycle.
In the U.S., for the most part, we believe most of our children are well-nourished. Again, that's a
supposition. That's a big supposition. But we see malnutrition in the US and developed world
in conjunction with disease and disease seems to be step one. So, now that not,
not every child in the U.S. and malnourished also has a disease, there are some social as well.
But a lot of the non-nutrition we see does start with disease. Like I said,
the special health care needs from the, from the government handbook, 14% of the kids in the U.S.
have a special health care need. And those are the ones that we tend to see developing malnutrition.
So, there, there does seem to be kind of a two, two categories here. Of course,
there's overlap. But I think one of the important things is that we recognize there is malnutrition.
And I can still remember when I was young and skinny and my hair was brown. And we'd see this
kid and they were underweight and they'd say, well, they have congenital heart disease. And
it was almost like it was accepted, Oh, well, this kid has cancer. And we would accept that.
And the value of this kind of approach in the developed world is we like, wait a minute,
yes, they have a disease, but they're malnourished and you don't ignore it. And we need to intervene.
You know, to talk to Dr. Rice's question, one of the biggest issues is, is the ethics
of intervention. Because if my kid's going to enter a study of malnutrition intervention,
I don't want them randomized to the non intervention group.
You know, don't put my kid in the non intervention group.
I want my kid in the intervention group, you know. And so, that is a problem as far
as outcomes because a lot of it becomes then, you know, retrospective studies, which are very weak.
Even observational again, is it, is it ethical to, to not intervene, even if you quote unquote,
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?
DR. NILESH MEHTA: Thanks Dr. Corkins, DR. TODD RICE: Let me come out really quickly that I agree,
I agree with you. That's, I suspect I don't do pediatrics, but I suspect that that's an even
bigger ethical problem in the ped side than it is in the adult side. And it's still a problem
that we have on the adult side. One of the ways potentially around that would be to try and come
up with different tailored interventions and then apply those as your two arms. So, everybody's
getting some intervention, but we're trying to differentiate, you know, what the, what the actual
details of the intervention are that may be either helpful or the most helpful, as opposed
to not providing any nutritional support to a group that clearly has markers of malnourishment.
DR. NILESH MEHTA: Thank you, Dr. Rice. A few questions for Miss Becker. One from Dr. Seres, David Seres from
Columbia University. STAMP and other tools are validated against SGA and each other and
our predictable overall outcome. But have they been validated to predict, which patients will
have improved outcomes if a nourishment based intervention is applied to the individual?
You might be muted.
Ms. Becker, we can't hear you. You might be muted. If you go to the top right,
there's a mute camera and a mute audio button there.
DR. MARK CORKINS: She's going high tech on us.
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
what are these markers or screening tools or diagnostic criteria being used for. I wonder if,
Dr. Jimenez, you want to take a crack at this confusion between screening tools and
diagnostic indicators, which require a more detailed assessment. For example,
STRONGkids being a screening tool will detect risk of malnutrition and the AIMP is a,
you know, suggesting a diagnostic criteria. Any comments on how it's being used currently
and how you chose STRONGkids in your paper to compare with AIMP? It's a really excellent
DR. ELIZABETH JIMENEZ: It's a really excellent question. I was actually discussing this with Dr. Steiber last week and also a little bit
with Ms. Becker and some other folks from the pediatric nutrition practice group. I think,
you know, we, we looked at trying to think about maybe next steps here, the overlap between the
pediatric subjective global nutrition assessment that Ms. Becker talked about in her presentation,
the AAIM indicators and the STRONGkids screening tool. And it's interesting because there's
some aspects that are included in the pediatric subjective global nutrition assessment that are
not in the AAIM indicators that are in the STRONGkids screener. And those are namely, GI symptoms,
kind of metabolic stress related to underlying disease or surgery and the nutrition focused
physical exam. And so, the distinction is, is maybe not as clear with the STRONGkids screener
as, as some other screening tools, which are much simpler, like the MST, for example, in adults.
And so, you know, I think it's a good question for us going forward. And we chose it because it had,
you know, the the academy of nutrition and dietetics has kind of done scoping reviews and
looking at screening tools in pediatrics. And it had good metrics for the study.
DR. MARK CORKINS: And I'm hoping, go ahead. I was going to comment. I was actually on that task force with Pat.
Part of it's statistical, screening is a broad net. Screening is designed to find it,
not miss it. And so, statistically, you want, you want a high
sensitivity, but low specificity. In other words, you're going to accept some false
positives when you're screening. You don't want to miss somebody when you're screening
them. With a diagnostic test, you're trying to get at high sensitivity, but you're also trying
to get a high specificity. If you say it's not, it's not. And so, in a way, the difference literally
is in the statistics and the nitty gritty. Again, when you're doing a screen, the goal is
anybody who is at risk, you're going to pick them up and then you're going to have to assess them.
And that, that's a different statistical approach. And then it's interesting because some parameters
are great screens, but terrible diagnostic criteria. In other words,
almost everybody who is malnourished is going to have this, but then there's also some folks who are
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.
DR. NILESH MEHTA: Thanks, (UNKNOWN). OK. Dr. Jimenez, you want to jump in?
I just want to comment a little bit further because I think we thought it was interesting
how the dieticians were using the anthropometric indicators in the study, particularly length for
age Z score. They were not using it in many cases, only about 40% of the cases when kids
had a score of less than negative two, did they use it to support a diagnosis of malnutrition? And
I think that's because, you know, linear growth restriction can have many causes that are kind
of nutrition and non-nutrition related. And so, they were using their clinical judgment to really
interpret when it was nutrition related. So, I think, you know, the anthropometric
measures can sometimes be too broad as well, when we're trying to think about nutrition related
causes. And I don't know if Dr. Fenton wants to comment further. DR. NILESH MEHTA: Go ahead, Dr. Fenton.
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
addressed the question, what are the effects of macronutrient supplementation for small,
for gestational age or preterm infants? There are two papers published just this year by Lynne and
Harding and other collaborators, and it's quite interesting. They called it the Essence study
and they looked for existing randomized trial data and then they requested the data. So,
they did individual participant meta-analyses, which is a nice complicated technique and, and the
strength of these studies. And the results are really interesting because they, they looked at
two sets of outcomes. One were cognitive outcomes and the other were metabolic risk outcomes,
and they found that there was no increase in metabolic risk in terms of higher BMIs or
other markers of metabolic risk after the macronutrient supplementation.
In terms of growth, they didn't see huge differences, but some differences in male
toddlers. But I think these studies are useful because, you know, as Dr. Corkins mentioned,
it's hard to randomize because parents might not want it. Dr. Mehta mentioned, you know,
we can compare, you know, essentially standard of care with a treatment or two treatments.
And so, people don't have to feel they're getting poor care. They're getting essentially
in the placebo group. But studies have been done. And I think these two meta-analyses,
you know, give us some guidance about what we already know and, and how we can go forward.
DR. NILESH MEHTA: Thanks Dr. Fenton. It appears that in addition to understanding which variables or parameters
you incorporate into the screening or diagnostic test, it's also crucial to understand what is
the outcome. What are you assessing them for? And as you alluded, is this related
to longer term functional outcomes? Is it related to, as Dr. Seres was asking,
response to nutritional interventions, or is it a risk predictor of subsequent malnutrition?
And those studies appear to be modelled together in the literature, and it's important to ask them.
Professor Fenton, there's a question from Suzanna Attia from University of Kentucky.
In the community screening for malnutrition, what's the utility of weight for length Z scores for term and preterm infants?
DR. TANIS FENTON: What a really good question. So, after an infant,
after a preterm birth, we can't use the WHO growth standard until they reach 40 weeks post
menstrual age because there's no space on those charts. So, there are preterm growth charts for
them. But once they've reached 40 weeks or 50 weeks, if they're using MyChart, then they
they do need to go to the accepted standard of the, you know, which the WHO growth standard.
So, to assess weight and to assess growth, we need to look beyond weight and a lot of
papers in the literature, a systematic review we published in 2017 found that
50% of studies that looked at preterm infant growth only looked at weight. And so, yes,
you're right. We need to look at length as well. In terms of weight for length, it is the accepted
recommended way to look at weight and length together, although it's not perfect because
when infants grow from term age to six months, whether they were preterm or term, there are
changes in body proportionality And yet the weight for length approach doesn't consider changes with
age. The same age is used from zero to 24 months. And actually I have a PhD student looking at
this question. We're looking at five million data points to see how well the distributions look for
weight, for length at various ages versus looking, using BMI at the younger ages. But anyway, I don't
have a firm answer about the best approach. Excuse me. But I think we need to consider both
weight and length in the early weeks, even just by making sure we're seeing both plotted at the same
time and then using at this point the recommended approach, which is to use weight through length.
DR. MARK CORKINS: And also, there's a little data on that upper arm circumference. Even in the preemie,
there was a study that looked at it and tracked it, and it did change appropriately with time.
They're just not normal for preterm infants. DR. NILESH MEHTA: Thank you both.
DR. TANIS FENTON: Once they reach, sorry, Doctor.
DR. NILESH MEHTA: Oh, go on, please.
DR. TANIS FENTON: Once they reach 40 to 50 weeks, post menstrual age or,
you know, term age, you know, the appropriate growth recommendations or growth references
to use are those that we use for non-term infants. We just need to make sure we're,
sorry, for term infants, we just need to make sure we're correcting the age for them. And then, yes. Thank you.
DR. NILESH MEHTA: In terms of the specific topic that we are trying to address in this seminar,
which is the gaps and future avenues for us, any responses to Dr. Rice's question about
imaging in our early life patients? Is it, is it beginning to be assessed adequately? Are we
going to see any imaging areas, ultrasound? And maybe we should throw in bio impedance into that?
DR. MARK CORKINS: To my knowledge, there's no literature at this point on any of that.
You know and I, you know, it's hard to know, like infants, it may not be affected. You know,
the we looked at handgrip strength in kids, but, you know, male and female was different.
How far they were along in puberty was different, where they, they did athletics that changed it.
You know, they train, in other words. But, you know, younger kids, does it make a difference?
Infants, would it make a difference? To my knowledge, nobody's looked at it.
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,
we have some tools that are additionally useful that, you know, are not exactly the same for,
for adults. And that is, you know, growth is normal. And for an adult, generally maintaining
weight is normal, but for infants and children, growth is normal. So, we can assess their growth
patterns, which gives us more information. Now, there is a tendency now for people to
look at body composition for preterm infants. And actually, I'm quite concerned about it because
we know that after birth, whether a baby's preterm or term, they put on body fat, they increase their
proportion of body fat. And that happens at a younger post menstrual age with preterm infants.
And there's been quite a few papers that in, especially in their introduction,
talk about this concern about the body fat at term age of preterm infants.
But if you look at any data for older ages, like for around three months of post term age, they the
preterm infants do not any longer have a higher body fat percentage. So, it's just a comparison.
At 40 weeks, we see it higher. So, I actually think that what's happening with body composition
assessment clinically and in research for preterm infants is raising alarm bells that should not be
raised. We need to look at the bigger picture and see what our expectations should be.
DR. NILESH MEHTA: That's a great point. Thank you. Along those lines, Professor Fenton, there's a question to you which
actually is relevant to all our speakers in terms of actual validation of these tools.
And this question specifically is from Austin Mikulski from University of Michigan at the CS Mart.
If, if we need NICU dieticians were to contribute towards a validation effort
for the proposed malnutrition indicators, and specifically for preterm neonatal population,
what do we validate against and what outcome measures should we focus on?
DR. TANIS FENTON: Yeah. The most common outcomes that are used for, especially preterm infants are cognitive
outcomes. And, you know, the Bayleyis a routine measure that's often used in a lot of studies
and then in a lot of just general care of, of preterm infants in follow up. And then some,
some places also have IQ data. And the older is usually better because, you know, you can
imagine a young infant, particularly if they're tired, probably don't do an excellent job of a
Bayley at 21 months of age. But when children get older, they can express their intelligence better.
But generally, it is cognitive outcomes that are used for, for, for validation of these measures.
DR. NILESH MEHTA: Dr. Corkins, Dr. Jiminez, Dr. Becker's trying to get her audio fixed, but anyone else jump in
for pediatrics in terms of outcomes? DR. MARK CORKINS: Outcomes are, are, you know, it is interesting
because there are some big population data that better nutrition interventions produce.
You know, like, for instance, higher IQ scores. We're talking like some of the
third world countries, some of the developing world studies certainly show higher IQ scores.
There is the the study out at Appalachia in the U.S. where they had, they intervene in the preschool
age group and they had better outcomes, less cardiovascular disease, less obesity later on.
It's the, you know, thrifty hypothesis. But it, the troubled IQ is there is a genetic component.
You know, if you're from Lake Wobegon, you know, all the children are above average. So, you know,
what is the norm? What is the IQ? Because IQ is a range. And so, you need a big group and again,
you'd have to compare a big group, you know, with some sort of intervention without,
with and without to see a difference because there is going to be the normal spread of IQ.
DR. ELIZABETH JIMENEZ: And I'll just agree that development is a really important outcome in pediatrics with the other speakers.
DR. TANIS FENTON: And as Dr. Corkins mentioned, the metabolic concerns, which,
you know, the Lynn and Harding meta-analyses indicated no concern. But you're right,
that is, those are other outcomes that need to be examined because people are concerned about them.
DR. NILESH MEHTA: Thank you all. Dr. Becker, can you hear us?
Sorry, I'm sorry that you're struggling with your audio. One question for the group. Do you know of
ready solutions for electronic health records where some of these tools have been adopted
that can be taken by other children's hospitals, where these applications can be put on to some of
the predominant EHRs in the country right now? Patricia Becker talked about the EHR STAMP.
And most children's hospitals are struggling, developing their own way to incorporate it.
DR. MARK CORKINS: It's funny because you have to ask them to switch disease scores, we had to ask them,
you know, hey, we want Z scores, not percentiles. You know, we still, it's in the queue supposedly
to get the drop, I'd like a dropdown to get some of the special curves. I would love to see some sort
of artificial intelligence. Look at this, you know, I talked about gaps, for instance. Now,
it's not their fault, but like orthopedics clinic, if you have a kid who goes to orthopedics clinic
and they have a cast on, the weight is out of line with the rest of them.
And there should be some sort of intelligence system to look at that and say that weight point
is not accurate. Now, again, they've got a cast on, so the orthopedics clinics,
somebody needs to realize that, you know, somehow the system needs to figure out that point needs
to have an asterisk by it. But again, some sort of smart system to look at the data and it should be
able to somehow be automatic that they're preterm as opposed to having to tell it it's preterm.
DR. NILESH MEHTA: Agreed. Dr. Jimenez, you had a comment?
DR. ELIZABETH JIMENEZ: Yeah. I just wanted to point out,
I think the research gap in this area is really the need for implementation science to figure
out best practices and how to do this across sites in terms of screening and referral and
diagnosis. I think we do a lot of multi-site studies and see lots and lots of variability
across sites and how it's done and what the capabilities are of the electronic medical record.
DR. TANIS FENTON: I have a point to add. Excuse me. So, I think as I mentioned in my talk, that
we really need to have the growth charts shown to us with more than one parameter every time.
And that's simple, and I think it's doable. And I've worked with medical record companies both
as a provider of a growth chart and also as a, a user in the system. And they, talking with them,
they can do these kind of things, but they say, they, they often say they can't, but they
can, you know, they can do that. And that's a simple thing. And we already have the intelligence
to do that. And it might mean, you know, the growth chart will be smaller, but you could
see the whole thing. I think that that really should be step one for pediatrics to, because
if you're not looking at the growth pattern, then what are you doing? You know, step one,
Dr. Becker talked about it. Dr. Corkins talked about, you know, the importance of
looking at some of these things. And I think that should be step one is that everybody contact their
representative for their EMR in their hospital and say, we want to see, you know, two or three growth
parameters at a time. And if there is enough request, I think the companies will, will bend
to it because they, they have been responding by putting growth charts into their system.
So, anyway, that that would be my suggestion, number one.
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
is a lot of important information that you've imparted, a lot of interesting discussion. It
sounds like variability is the, is the theme right now, both in adult and pediatrics in this concept
of how do we address or even diagnose or detect malnutrition. The vendor piece that you have all
alluded to is very relevant and I think together we might have a voice to try and influence some
of that. And then it comes to the validity of these. And when we talk about validation, we are
interested in important outcomes. No longer are hospital outcomes enough both in the community and
in hospital. The longer term outcomes, functional outcomes that so many were alluded to by you. And,
and that seems to be some of the take home points. The question we are asking from
these screening tools or diagnostic tools as to what we want them to do.
It's 18 past, I'm conscious that at 1:25 we start the next session. So, I want to give you at least
7 minutes to take a break. On behalf of Dr. Rice and myself and Dr. Vargas and the entire
ONR team at NIH, thank you to the speakers. I really appreciate it. Your talks were concise,
but stimulating. And thank you to all of you who have joined almost close to 100
folks online and enjoy the rest of the session. See you at session number eight soon. Thank you.
DR. GAIL CRESCI: Hello and welcome to Malnutrition in Clinical Settings, Research Gaps and Opportunities
for Early Life. This is Session eight on Early Life Research Considerations. My name is Gail
Cresci and I'm an associate professor at the Cleveland Clinic, Lerner College of Medicine of
Case Western Reserve University, and full staff in the departments of Pediatric Gastroenterology and
Information and Immunity at the Cleveland Clinic in Cleveland, Ohio. I am also the immediate past
president of the American Society for Parenteral and Enteral Nutrition. I will be your moderator
for this session. We have a phenomenal panel of experts presenting on this topic today.
For detailed information regarding their backgrounds, please refer to the Speaker
tab and the left hand column of this page, and you can also go to the main page of the Labroots under
the Speakers tab for their bios. This session is broken into two parts with three segments. The
first two segments will be presented in this Part one. In segment one, we will hear about the unique
challenges in early life research on malnutrition. Dr. Marie Revilla will discuss opportunities to
address challenges in conducting dietary assessment during infancy.
Dr. Barbara Medoff-Cooper will address the challenges of growth faltering after neonatal
surgery for complex congenital heart disease and Dr. Maureen Black will discuss complexities
of children being dependent on food systems and caregivers in research and malnutrition.
We will then transition into the second session when we will review a summary of evidence on
malnutrition in early life. Lisa Moloney will present on the Academy of Nutrition and Dietetics,
Systematic Reviews and Practice Guidelines for Pediatric Malnutrition and Dr. Sharon Irving will
discuss Pediatric Malnutrition and the Research Landscape with the use of the ASPEN guidelines.
The presentations will be followed by a live question and answer period with the speakers.
During the session, we would like you to please share your questions for the presenters in the
chat box. We will try to address as many as we can during the question and answer period.
So without further ado, here we go.
DR. MARIE KAINOA FIALKOWSKI REVILLA: (UNKNOWN) Hello, everyone, Mahalo. Thank you for including
me on this session focused on early life malnutrition research organized by the National
Institutes of Health. Before I begin, I would like to also Mahalo or thank the amazing team of
researchers spread across the United States and Australia for their work in using technology
to advance dietary assessment approaches. Listed on this slide is my disclosures for you to view.
Nutrition plays a significant role in the first 1,000 days of life, establishing the foundation
for optimum health, growth and neurodevelopment across the lifespan. In this presentation,
we're going to focus specifically on the period between birth and 12 months. Infant dietary
assessment is essential for monitoring adequate growth and development during this time period.
However, as infants are unable to report for themselves, it is a process reliant on surrogate
reporters such as parents, grandparents and other types of caregivers. There are significant burdens
that surrogates face, including the amount of time it takes to complete the assessment, having...not
having the information on the details of food that may have been prepared elsewhere, such as daycare,
the potential bias in the types of foods that surrogates may report, as well as the difficulty
to ascertain the amount that was eaten because of spillage or spit up as shown here on this image.
It has been found that the weighted food record provides the best estimate of energy,
but note this poses a significant amount of burden on surrogate reporters.
The 24 hour dietary recall has also been commonly done in the clinical setting,
but it has been found to overestimate energy and nutrient intake.
So given those challenges, what opportunities exist in technology to advance the field?
The incorporation of technology as a dietary assessment is an opportunity for the field as
we know that smartphone adoption is widespread, especially in adults of childbearing age.
With that, there are, simply put, two ways in which technology has been incorporated into
dietary assessment for infants. The first is with images and the second is with automation.
In regards to images, there are two approaches. The first is having images assist a traditional method
of dietary assessment, and the second is with images serving as the dietary assessment method.
Let's first examine image assisted methods.
A study by Johansson et al in 22 healthy infants in Sweden compared the energy estimated using an
image assisted record with regular food records. These estimates were also compared to total energy
expenditure determined by doubly labeled water. They had 38 reporters complete a five day record
in which two main meals included before and after images of the infant's food. These images
were taken on a standardized plate and emailed to researchers directly from the participants phone.
What they found was that estimated energy intake did not differ significantly between
image assisted records and regular records. The main difference in energy intake estimated from
food records with the active images substance and metabolizable energy calculated from doubly
labeled water was about 366 kilojoules, which translates to about a 10% overestimation. This
is a little bit on the high side, but within range of what has been found in
other validation studies. However, there are limits of agreement were narrower. However,
some notable points to make is that this study did not use image assistance for all meals and
snacks due to concerns regarding surrogate burden. There was also the subjectivity of the devices in
regards to lighting and angles that may have influenced the ability to evaluate the images
submitted. At the end of the article, the authors commented that a mobile phone application would
have improved the quality of data collected. So this segues us nicely into the following
approach to doing dietary assessment using images, which is the image based approach.
This approach was used in a feasibility study of the mobile food record in 70 infants in Hawaii.
The mobile food record is a part of the technology Assisted Dietary Assessment,
Technology Assisted Dietary Assessment System or TADA. The mobile food record has been used
almost across the entire lifespan. The advantages of the mobile food record is that it provides easy
access to dietary intake data, such as energy, nutrients, food groups or dietary patterns. It
also provides the context of eating such as on a highchair table shown in the before image.
It can give you a location via GPS, a date and [inaudible] time stamp for beginning and eating
occasions which provides duration of eating. And in addition, it can provide you food
waste as to what you can see on the after image of the food on the floor.
The mobile food record used in this feasibility, in this feasibility study
was designed specifically for use in infant. There was a before and after eating image
button with infant appropriate icon as well as a timer used to capture a breastfeeding duration.
Surrogate reporters were instructed to take before and after images of
their infants' meals, which included this additional marker which is the square
checkerboard that you see in the bottom images to help with image evaluation.
What we found was that over 90% of surrogate reporters found the mFR easier to use And
over three quarters of participants found the mFR enjoyable to use and would use it again.
Feedback received from the mFR center on the ease of its use and its user friendly nature.
Surrogate reporters were easily able to capture their infant meals, including the packaged one.
Surrogates also commented on the ability to complete
their assessments with the mFR being much easier than writing things down.
And it was easy to go wherever they went because their phone was always with them.
As you can see here, the images submitted by a surrogate reporter of an outing to Costco.
The other unique feature was the transferability of the mFR
to other caregivers, as reflected in this comment where the app was downloaded onto
the grandparents' device so they may record the infant participants intake.
As a result of this feasibility study, additional innovations for add to the mobile food report
such as the addition of a bottle button, the accessibility across more types of devices,
and the incorporation of food annotation and images that will soon become automated.
So the last approach to mentioned is the automated approach.
Specifically, the automated self-administered 24 hour or ASA24 dietary assessment tool is a
free web based dietary assessment tool. The ASA24 can do multiple automatically coded,
self-administered, 24 hour vehicle and or single or multiday food records. The ASA24 is
also accessible using current mobile devices. In the just released 2022 edition, the ASA24
now has an infant feeding option for meals and snacks to make it easier for surrogate reporters
to record the number of feedings especially early on when feeding is frequent throughout the day.
However, the field is still in need of further innovation. The validation of
these methods against biomarkers are needed, as well as determining an appropriate method
to estimate the contribution of human milk intake within infants.
Mahalo- Thank you for allowing me to share this information with you today.
DR. BARBARA MEDOFF-COOPER: Today, I'll be addressing the Challenges of Growth
Faltering after Neonatal Surgery for Complex Congenital Heart Disease.
I am the co-founder of the Neoneur LLC and we've received funds from National
Institute of Nursing Research and Saving Tiny Hearts Foundation.
Growth faltering is a major concern for infants with complex CHD. During this presentation,
topics will include a definition of growth faltering, factors contributing
to growth faltering, the role of feeding difficulties, and then some of the challenges.
There are many terms used in the literature to describe an infant who does not exhibit
the expected growth trajectory, their growth faltering, growth failure, failure to thrive
and of course malnutrition. In this graph, we see a typical example of Weight for Age Z score,
it's decreasing across to 2% tabs which is one definition of growth failure.
My work we use the definition of Weight for Age Z score of less than -2.
Infants with complex CHD are usually born full term, and within normal weight ranges.
Nutritional issues often emerge shortly after surgery, and often persist throughout the first
years of life. 20%-50% of infants are at risk for vocal cord paralysis, it's often related
the type of surgery and the growth failure is associated with an array of health problems.
There are both short term and long term consequences of growth faltering or
(UNKNOWN) failure. Short term includes prolonged length of stay, readmissions and oral aversion.
Long term includes poor growth, about 20%-30% of infants will have delayed motor and or cognitive
skills as well as behavioral problems. And the behavior problems include both ADHD and autism.
We do know also that decrease in Weight for Age Z score of more
than 0.67 is strongly associated with mortality during the first year of life.
These are just some of the factors have been hypothesized as contributing to growth faltering.
Depending on the publication list may vary. The true challenge is how to address these issues. For
infants with the most complex CHD, 89% are risk for failing to meet CDC standards for adequate
growth at some point in the first year of life. These are data from one of my studies,
the mean Weight for Age Z score change from surgery discharge was -1.5 for all the infants,
but the infants with most complex CHD given the HLHS if it was -1.7. Orally fed infants do
better than infants that were supported with a feeding tube. I think the histogram clearly
demonstrates a shift to the left in Weight for Age Z Score. To orient the slide, the x axis represents Z
scores and the y axis frequency. You can see at the top histogram that there was a normal
distribution Weight for Age Z score at birth. At surgery, not much of a change, but by 22 days,
you see that median Weight for Age Z score was -2. And so that was a significant shift to the left.
Publications for a wide array of cardiac centers have validated our findings. The discharge, 50% of
infants continued to be dependent to some degree of tube feedings. The discharge protocols varies.
However, some infants, sent infants home with feeding tubes and teach parents how to reinsert
them. Others sent infants home with feeding tubes, but the parents have to bring the babies
back to the ER to have the feeding tube inserted. Other centers sent babies home with gastric
tubes and other centers just keep the babies in the hospital until they can get the oral feed.
We do know the longer an infant is tube fed, the more difficult is to wean them. And
there are concerns about potential link between prolonged tube feeding and speech. Research has
confirmed that there is an association between neurologic compromise and poor feeding skills.
From imaging studies, we have come to realize that full term infants with the most complex
defects are more likely to have brain development that looks more like an infant born 35 weeks.
To complicate the picture, both periventricular leukomalacia and strokes are often present
before and during and after surgery. What is not associated with feeding disorders is birth weight,
gestational age, preoperative, hemodynamics, and environmental factors. Environmental factors
include age of mother, number of older siblings, and parental education. Safe feeding is not
about buying, but about the coordination of sucking and swallowing and breathing.
The ability to achieve full oral feeding is the most significant factor associated with
developmental outcomes. I don't want us to forget the fact that we have a newborn who has undergone
open heart surgery. This is a major insult, this tiny being. Stabilization of physiologic
systems needs to be take place. Many systems have been impacted by the surgery, including the GI
system. And on top of that, we give the infants plenty of pain medications, which decreases the
infant's ability to achieve an alert behavioral state which is needed for effective oral feeding.
And we have to remember that this is an infant, they are still recovering from the
birthing process. It's no wonder that feeding is a major concern.
Feeding protocols appear to be an important element in the fight to ameliorate GF.
This is a graphic representation of pediatric acute care cardiology collaborative pathway
that is being used in participating cardiac centers. This does not preclude the 150 pediatric
cardiac centers in developing their own pathways. As of 2021, only living clinical pathways have
been published, nine with positive outcomes. But we know there are many more out there
including the pathway that's been developed at the Children's Hospital Philadelphia, my home
institution. Developing a clinical pathway is not for the faint of heart, convincing a full care
team which was multidisciplinary that all infants should have both pre and post operative parenteral
nutrition was the first challenge I should say, battle. The next battle was trying to convince
everyone that we needed to have feeding tubes placed in every baby immediately after surgery.
But other elements were easy to incorporate, enteral feeding readiness assessments,
promotion of human milk especially considerations for breastfeeding and fortification guidelines,
infant driven feeding practices and feeding tolerance evaluations recommended by the SLPs.
Feeding assessments are crucial and should be part of every feeding protocol. There are
various ways to make these assessments clearly the bedside nurse and the parents are always
making assessments of how an infant is feeding. For centers with dedicated SLPs with speech and
language pathologist, frequent evaluations need to be routine. A tool used by some SLPs is the NOMAS
which is the Neonatal Oral Motor Assessment Scale. This is an observation tool that can be subjected
to interrater reliability issues, but has been used in research. In my work, we've been using a
feeding device which allows us to see the pattern of sucking and tracking behaviors over time.
The organization of feeding can serve as a proxy for an infant central nervous system integrity.
We look at the length of sucking bursts, type an infant needs to recover from one
burst and start sucking again which we believe is a measure of fatigue.
And you can see these two different of traces. On the left, we have an infant that's fairly
disorganized or I should say very disorganized, we have few sucks, low pause, and few more sucks. If
we look at the whole trace, we can see this baby's not ready for full oral feeding. On the right,
is a baby that's organized, is ready for full oral feeding, it is not already on oral for feeding.
And then we track them over time we'll see that again we'll have further improvement.
So just a reminder that addressing growth faltering does not stop at discharge. Rather,
the challenge continues sometimes for months and for years.
We need to increase a coordination with particular attention to feeding, virtual
home visits for feeding management, something that I did for five years we'll open it another
study from an NINR and we found that it made a big difference the way parents were
managing families, the babies in comorbidity management assisting families in managing
multiple visits and coordination between primary care and cardiology and speech.
So in summary, growth faltering has serious consequences. Adherence to feeding protocol
appears to ameliorate some loss in the Weight for Age Z score, the attention to feeding skills is
an essential component and interesting growth faltering. Thank you very much.
DR. MAUREEN BLACK: Greetings. My name is Maureen Black, and I have been asked to
discuss the Complexities of Children Being Dependent on Food Systems and Caregivers in
Research on Malnutrition. The operative word is malnutrition which may include underweight,
overweight, or nutritional deficiencies such as micronutrient deficiencies, not getting
the recommended amount of specific nutrients. To address the role of food systems and caregivers,
we turn to nutritional ecology, what is nutritional ecology? Nutritional ecology
represents the interactions between children and environments. This is how it works.
Children are complex internal biological systems that grow from conception through infancy,
childhood and adolescence. The environment, the rest of it represents complex external systems,
such as climate, geopolitical, social, food, home, and so on.
And food systems refer to the acquisition of food, it could be growing food, getting milk from cows,
plus processing and making food available. Caregivers are part of a family system,
and are the final common pathway in interactions with children.
Now the distal environment has a major impact on food systems. For example, if the climate is
too hot or dry, growing could be disrupted. If the event of a conflict, such as the conflict in
Ukraine could disrupt the distribution of food, or policies may dry up, drive up food prices.
Food Systems have a major impact on getting food to children and families through food availability
such as in stores, accessibility, the ability to get to the store, affordability, the ability to
pay for the food, and then acceptability, food that the family is able and willing to eat.
Caregivers are part of families and many aspects of family life influence food and play a role
in malnutrition. Food Security refers to the availability and access of enough food for a
family to live an active lifestyle. Among many children, food insecurity is invisible and not
associated with underweight or overweight, but it may be associated with poor health and development
and micronutrient deficiencies. Services such as SNAP and school feeding programs can assist
families and children and prevent food insecurity. Material hardships, primarily represented by
poverty pose a major threat to malnutrition. Families may have difficult choices to make,
eat or eat. Nutrition security and nutrition insecurity refers to foods that are needed in
terms to support health essential nutrients. The lack of these nutrients could lead to specific
nutritional deficiencies. Food skills are another aspect of nutritional ecology that are important
to consider. Caregivers who lack preparation skills are more likely to rely on heavily
processed foods that may be low in nutrients, and thus increase the likelihood for malnutrition.
How food is used in a family is critically important beyond response to hunger and
provision of nutrients and in celebratory occasions. When food is used to manage behavior or emotions,
it can increase the risk for malnutrition, and for eating disorders. Daily routines and chaos can
have an impact on children's nutrition. The daily routines will help children gauge their eating
but without a mealtime structure, children are likely to snack, often consuming food with little
nutritional value and a risk of malnutrition. So, food parenting then refers to the interaction
between children and caregivers' around food, often focused on issues of control
and caregivers response to children. This is a closer look at food parenting. This conceptual
map was developed by Vaughn and colleagues. You can see coercive control includes behaviors
such as pressuring the child to eat more, or restricting the child's food choices. Structure
refers to modeling and mealtime structure. And autonomy refers to the child gaining independence
in eating. A graduate student and I validated this conceptual model using the comprehensive
feeding practices questionnaire with mothers of preschoolers. We identified three patterns as
you can see. The most prevalent was controlling, that's the gray pattern that was high in coercive
control, and low in structure and autonomy. However, we identified the other two patterns
balancing and regulating that were high in structure and autonomy. What we found is that the
regulating pattern was associated with lower BMI in preschoolers than the controlling pattern was.
But we see that food systems and caregivers play important roles in the nutritional
ecology of malnutrition. They can certainly influence children's nutritional status,
so that's malnutrition, but they can also influence children's health both chronic
conditions as well as acute or infectious conditions. It can influence dietary choice,
it can influence eating attitudes, and then they can also influence physical activity,
children's school performance, cognition, socioemotional development and mental health.
So nutritional ecology, can play an important role in children's development beyond only looking at
malnutrition. But if we think about malnutrition, we see that the research requires a comprehensive
assessment of children's nutritional ecology including both distal and proximal components
such as the food system, and the household and family. In order to do this research needs to be
driven by at a theoretical model that hypothesizes the pathways linking the systems. So there are
many research gaps related to malnutrition and related to incorporating the nutritional ecology.
We'll give an example. So an example may be does the school feeding program protect
against malnutrition in communities with low food access? Well, this portrays children
and we can evaluate their nutritional status. And if we look at the response to the school program,
we will find that some children are doing well, some children are doing better than
other children. But looking at this alone is really a very incomplete picture, recognizing
what we now know about nutritional ecology. So we need a broader picture. So we start again
with the children. And maybe this time we look at the caregiver and the caregiver's interaction with
the child, some of those feeding patterns as well as availability of food in the household. So we
look at the family, and again, the availability of food and some of the feeding practices. And
then we think maybe we should consider the food systems, what is the availability of food within
the community and how is that related to the family? Do they have the resources to acquire
the food, and then we might look at the climate. Again, is it, is the climate impacting the systems
that's impacting that family and the caregiver? Now, when we look at the school feeding programs,
we can look at whether there's a moderating effect or whether the school feeding programs then can
protect the child from some of the challenges that may be happening at the caregiver level.
So in conclusion, we know that we need to look at the food ecology to understand
malnutrition and other aspects of children's development. And OK, and I would like to end
by thanking the colleagues that I'm working with, and an NICHD sponsored program called
BOND-KIDS. We're focused on the environmental aspect. BOND-KIDS stands for Biological Origins
of Nutrition and Diet, Knowledge Indicating Dietary Sufficiency. Thank you very much.
DR. SHARON Y IRVING: Hello, and thank you to the organizing committee for inviting me to be a part
of this workshop. My name is Sharon Irving, and I will talk to you today about pediatric
malnutrition, the research landscape, where are we, what are we learned, all in relation to the use
of the ASPEN guidelines. I have no financial disclosures pertinent to this presentation.
The guidelines that I'm going to discuss are those that were published in 2017 between the
Society of Critical Care Medicine and the American Society for parenteral and enteral nutrition.
This publication marked the first collaboration of these two very large important organizations
on to discuss nutrition therapy for critically ill children. It is not the
first guidelines that were published for this population as that occurred in 2009. However,
it was the first time for these two organizations. The target population was truly that pediatric
population of greater than one month and less than or equal to 18 years of age.
They also had to have a presumed intensive care stay of greater than two days.
Since its publication which was done both in the Journal of parenteral and enteral
nutrition and pediatric critical care medicine, those two publications, these
guidelines have enjoyed more than 225 citations worldwide. And when I say worldwide, the global
reach of these guidelines has been European countries, countries on the African continent,
throughout the Middle East, Central and South America, East Asia and Australia.
When we talk about pediatric malnutrition, and I know my colleague, Dr. Corkins has talked about
this earlier today, we need to truly understand what we're talking about. And so I'm just going to
quickly summarize here what I am talking about in terms of this. It's that imbalance that occurs
between nutrient intake and requirement and that imbalance so it results in deficiencies
or excesses, excesses in energy, protein, or micronutrients that encompass the underweight,
the overweight and micronutrient deficiencies. And that definition that I've provided for
you here is a combination of the one from ASPEN and from World Health Organization.
So when we go back to the guidelines, we have to look at what impact does nutrition
status have on outcomes in these children? And what are the best practices to screen
and identify those patients most at risk? So then, of course, you go to the literature.
So I looked at systematic reviews. The first one I will present for you here is by Toh and
colleagues and it's looking at the association between admission body mass index and outcomes
in this population. They define nutrition status which I have for you here. Their overall aim was
to compare the outcomes that are typical when you look at this population of critically ill
children. And that is mortality, their length of stay, their duration of mechanical ventilation,
and they based it all on nutrition status as they had defined it. Their primary outcome was
mortality. They looked across randomized control trials, retro and prospective
observational studies, and their population was less than 18 years of age with a PICU admission.
They reviewed 20 studies, only one of which was a randomized controlled trial.
The studies were across income categories and were mixed patient populations.
What did they find? Underweight and obese patients did not have increased risk of mortality. They had
no difference in mechanical ventilation, length of stay across the weight categories by either
Z score or percentiles. However, in studies that use BMI Z scores, there was an increased
risk of mortality in the underweight patients. They did find an increased length of stay for
these underweight patients and also for the overweight or the obese patient. They had to
do a sensitivity analysis in this systematic review and meta-analysis because of mixed PICU
populations in some of the studies. And they want their results to be as clean as possible.
And they found that there was an increased odds of mortality for underweight and overweight in
these mixed studies. And so what I've presented for you here are two of their forest plots that
defining their or describing their results. In Fig. A, the underweight significantly
increased odds for mortality by these z scores, but not so in using percentiles. Figure B in the
overweight and obese population did not have significant differences in odds for mortality
with poor Z scores or percentiles. So what did they conclude? They found no differences in
clinical outcomes comparing underweight, normal or typical weight or overweight obese patients.
However, the studies that use BMI z-scores demonstrated increased risk of mortality
in the underweight patients. They found differences in classification of weight
categories and that different studies used different growth reference standards.
They identified a need for standardization of classification of nutrition status in the
critically ill child. And the methodology was very heterogeneric across the studies.
So then, of course, you have to look at the obese. And so in 2019, Alipoor and colleagues
published a systematic review with meta analysis of the association of obesity with
morbidity and mortality in this population. They defined obesity as I have for you here.
Their primary aim was to examine the association of obesity across outcomes
of interest in critically ill children. They looked at observational studies,
prospective or retrospective. And mortality, again, was their primary outcome. However, they
did identify secondary outcomes to include length of stay and duration of mechanical ventilation.
What did they find? That obese children had increased mortality. There was an increase of
hospital length of stay, there was a longer duration that they needed to be mechanically
ventilated and therefore had a longer PICU length of stay. They also identified
different cutoffs for the determination of obesity and the presence of a mass amount of heterogeneity
between the studies and their findings, one of the graphs that they had, their forest plot
I've put for you here demonstrates that the meta analysis of the studies investigating mortality
showed that they had a lot of congruence around the centrality of these studies.
But again, how things were described was very heterogenetic.
So what about screening? What do we do with that? So Ventura and colleagues published in 2022
screening tool, a nutritional screening tool for critically ill children in a systematic review.
They defined screening tool as that what was used to assess from malnutrition, risk of
undernutrition and the associated outcomes. Their primary aim was the use of nutritional screening
tools in hospitalized children, and they focused to see methodology of tool development, tool
application and tool validity. They had the same targeted population of greater than one month and
less than 18 years of age. Their secondary aim was relevance of the tool in critically ill children.
They found 103 studies and 25 of which were cohort studies. Only three of the studies, however,
included PICU patients, and the validation of the tools was performed on ten. So what did they find?
Two of the three studies successfully tested prediction of nutrition status deterioration.
Only one of the three studies was able to identify hospital length of stay. 91 of the
studies assessed one or more nutritional outcomes. However, there was no standardization in what that
definition was. And in one of their charts that I thought was of interest here, they identified
the variables that they looked at for screening tools for nutritional outcomes, and they broke it
down into clinical nutrition status, laboratory, and dietary intake. And what I thought was of
interest here is that only one study identified severity of illness as a variable of interest.
Why does this matter and what is the importance? Because we identify and we define malnutrition
based on anthropometric measures for the most part, which I've shown you in both of these systematic
reviews, we have to take into consideration are there differences in anthropometrics? And so I
will present for you now a couple of studies that do define that. So Morisaki looked at
social and anthropometric factors across races and ethnicity based on birth weight.
They looked at 14 different races and ethnicities and they found that the average birth weight
differed by greater than 100g in most races, with the exception of those that I've identified here.
Their z-score comparison by gestational age of 34 to 41 weeks differed by 0.1 standard
deviations and again, with these exceptions. Once they adjusted all factors that minimally change
birth weight discrepancy for Black infants, and national birth weight reference charts that we
currently use may not be inclusive of all of the races and ethnicities. Further exploration
of maternal characteristics may be necessary to better explain variability of birth weight in U.S.
infants. So there is some discrepancy. Taking it to an older population, Hawkes and colleagues in
2020 looked at sitting height to standing height ratio reference charts for children in the US.
They used NHANES data and looked at more than 9,500 children with an aim to really develop
these reference charts for sitting height to standing height ratio of children in the U.S.
Their age range was a little bit different than all of the previous studies, and it was greater
than or equal to two years of age to less than 18 years of age. They looked at non-Hispanic Black,
non-Hispanic white, and Mexican-American as the demographic ancestry of their populations. And in
the U.S., non-Hispanic Black children have a lower sitting height to height ratio across all age
groups. And this is something for us to consider in terms of interpretation of our anthropometric.
So when we go back to the guidelines and malnutrition, the impact on the nutrition
status, how is that addressed? So we found one randomized controlled trial
that there was a heterogeneity of measures and classifications of nutrition status. However,
when we looked at BMI z-scores, it did identify an increased risk of mortality in underweight
patients. When we look at best practices on screening and nutritional status of these
children and who's at risk, the systematic review of the screening tools found no standardization
of definition of nutritional outcomes. None were validated in critically ill children,
and the severity of illness is a factor to consider. So where are we and what's missing?
We need to consider demographic ancestry and anthropometric measurements. There are age
related differences that we also need to think about. We need a uniform strategy for nutrition
status assessment that is applicable across all populations of children from critically ill and
hospitalized children. We need to standardize our definitions for nutritional outcomes. There's a
role of obesity in outcomes and all of the associated corollaries, and we need to peel
back the onion on that. Reliable tools are needed to predict risk of nutrition status deterioration.
We need to standardize our methods and measures to monitor efficacy of nutrition therapy, and
the identification of novel biomarkers to track status during critical illness is badly needed.
I thank you so...thank you so much. Here are a list of references that I use for this presentation. I
appreciate your time and your attention. Thank you.
LISA MOLONEY: Hello, my name is Lisa Moloney and I'm a nutrition researcher at the Academy of
Nutrition and Dietetics. Today I'll be discussing the Academy's systematic reviews and practice
guidelines for pediatric malnutrition. I have no conflicts of interest to disclose other than that
I am an employee of the Academy of Nutrition and and Dietetics. So for today's learning objectives,
we will describe the evidence analysis library, nutrition screening for pediatric
systematic reviews, validity and reliability of nutrition screening tools for identifying risk of
malnutrition related to under or over nutrition in the pediatric population, provide an overview
of the very low birth weight, preterm infant evidence based nutrition practice guideline and
identify limitations in research, applications to practice and areas for further research.
So the Academy follows a standard process for conducting systematic
reviews. They are conducted by a panel of volunteer experts. A systematic search is
conducted within multiple electronic databases. Each of the included articles are evaluated for
risk of bias, and we evaluate the certainty of evidence following the grade process.
The guideline development process that is also conducted by that same as our panel
will utilize the evidence and decision framework that takes evidence, harms
benefits, cost and implementation factors into consideration when developing the recommendation,
and each of our guidelines go for external review with content experts who use the Agreed II tool.
So here is our malnutrition screening systematic review team our volunteer panel members,
Project manager, Lead analyst, Medical Librarian, Academy Staff and Evidence Analyst. Pediatric
malnutrition screening is a process to identify a child under 18 years of age who is at nutritional
risk for a nutrition related problems and should be referred to a dietitian or nutrition assessment.
Malnutrition screening may be conducted in any practice setting. Tools should be quick,
easy to use, valid and reliable for the patient population and setting, process and parameters
established by the institution should be developed by a multidisciplinary team, including dietitians.
It should be performed by medical professionals who have been trained in the screening process,
and screening should occur within a designated appropriate time frame.
So what does it mean to say a tool is valid? The ability of nutrition screening
tools to identify those at malnutrition risk versus those who are not at risk.
Validity should compare the results of a screening tool with a reference standard,
reference standards could include anthropometrics at a given time or changes over time,
the Pediatric Subjective Global Nutrition Assessment Tool or full dietitian assessment.
Seven tools for screening for malnutrition risk in the in-patient hospital setting
were identified in the literature. STAMP, STRONGkids, Pediatric Yorkhill Malnutrition
Score, a Pediatric Malnutrition Screening Tool, the Pediatric Nutrition Screening Tool,
Pediatric Nutrition Risk Score, Integrated Management of Childhood Screening, Pediatric
Digital Scale, Malnutrition Risk Screening Tool. All tools except PeDiSMART had moderate validity,
STAMP had the oral highest quality evidence. No evidence meaning inclusion criteria was found
to evaluate the validity and reliability of the PeDiSMART for identifying risk of
malnutrition related to under or over nutrition in the pediatric population. Three tools were
designated for use in the community setting. The Electronic Kids, E-KINDEX Nutrition Screening tool
for every preschooler NutriSTEP and the toddler NutriSTEP. E-KINDEX, a NutriSTEP had low validity,
NutriSTEP that for toddlers had moderate validity. Available evidence for all tools was limited.
Tools used to identify malnutrition risk should be valid and reliable for the target population
and setting. While no screening tool can be 100% accurate, pediatric nutrition screening tools
should have at least moderate to high validity and reliability based on strong or fair evidence.
The systematic review concluded that tools meeting this goal were STAMP,
STRONGkids and PYMS and the inpatient setting and
NRST CF in the specialty setting, though none of these tools had high validity.
Limitation to these nutrition screening tools include a few studies examining each tool,
heterogeneity among studies examining a common tool and lack of tools that included indicators
that are currently recommended to identify pediatric malnutrition. Future studies are needed
that include malnutrition screening tools that use academy ASPEN indicators for identification and
documentation of pediatric malnutrition. Multiple studies are needed for commonly used tools as well
as additional information on how training for and user of the tools affect validity and reliability.
So next I will cover the very low birth weight preterm infant until nutrition
evidence based nutrition practice guideline. So the preterm project was a collaboration
of the National Institute of Health and the Academy of Nutrition and Dietetics. So the
goal was to evaluate available evidence to support guidelines for nutrition care.
So this project had two phases. Phase 1 was led by the NIH and Phase 2 was led by the Academy.
So here is our pre-term infant expert panel. So the same setup as the malnutrition screening
panel. So with our panel members, we had a patient advocate, project manager,
lead analyst and a librarian. So multiple systematic reviews were conducted to support
the guideline including systematic reviews that compared to fortifiers, protein amount,
calorie and fat intake and SRs compared milk to formula and human milk with donor milk.
So here are the recommendations that were developed based on the evidence, the decision
framework and the conducted SRs. So for protein amount, health care practitioners should provide
3.5g-4.0g of protein per kilogram of body weight. For type of fat, health care practitioners should
not routinely supplement additional enteral long chain fatty acids. Formula enrichment is
recommended compared to standard formula for the preterm very low birth weight preterm population.
Human milk should be fortified when possible. Mother,
fortified mother's milk should be provided. Health care practitioners should provide fortified
human milk regardless of source of maternal or donor. And when quantity of maternal milk
is insufficient, health care practitioners should supplement very low birth weight preterm infants
with donor milk during the time that infants are at high risk for necrotizing enterocolitis.
So implementation considerations for the protein amount are the lack of the ability to measure
specific nutrition composition of human milk. If practitioners lack access to human milk analysis,
practitioners must rely on estimated intake. For human milk fortification,
this will require suitable area and staff education for safe preparation
and an acceptable feeding protocol that indicates when fortification has started, advanced and
stopped. As far as maternal milk recommendation, this will require a multidisciplinary approach
to educate patients of very low birth weight, preterm infants and the benefits of human milk,
how to effectively initiate milk production and how to maintain milk supply throughout
hospital stay and post-discharge period. So support may include educational materials
and access to high quality pumping equipment and ongoing lactation services. Implementation of the
maternal milk supplementation recommendation also will require a multidisciplinary team approach
when implementing donor milk programs in NICUs. It will require policies and protocols to track
donor milk, and the FDA recommends against acquiring donor milk directly from individuals
or online. Donor milk should be obtained from a source that has screened milk donors.
As far as research and research gaps and future research, more research is needed
on all investigated topics for very low birth weight, preterm infants for our protein systematic
reviews, the amount of protein provided, how it was provided and how it was reported had a
very high heterogeneity, and there was a lack of isocaloric studies that evaluated greater than
versus less than 4g/kg of body weight per day. The fat SRs only found studies that evaluated
omega three fatty acids and there was very little evidence found a non protein energy intake.
As far as the human milk studies, of course these were limited to observational studies. They did
not identify or control over known confounding socio and economic factors. Additional information
is needed on the amount and type afforded bias, as well as access to the nutrient
composition of mothers' milk in real time. And that concludes today's presentation. Thank you.
DR. GAIL CRESCI: Wow, thank you so much to our fabulous team of presenters.
That was really a wealth of information. Before we get started with the Q&A, I, of course,
need to thank our NIH scientific program contacts for assisting with this wonderful event, Ashley
Vargas, Charlotte Pratt and Christopher Lynch, as well as our working group members that have
helped with this, including Nilesh Mehta, Dr. Todd Rice, David Seres, Alison Steiber and
myself. And of course we couldn't do this without our logistical support. Kimberly Barch has
been amazing in helping with everything. Mark Dennis and of course our colleagues at Labroots,
including Brett Long, you've been fabulous in keeping us on track and moving forward. We
really have some really amazing questions here for our presenters, so I'm just going to dive right
in. And as I was sifting through these questions that were coming in, I was trying to think about
a sequential way to ask them. So I'm going to do whatever worked in my mind for this. And so
the first question goes off to Dr. Medoff-Cooper. At your center, what is the earliest time point
when an infant admitted for open heart surgery is assessed by the SLP and has intervention?
DR. BARBARA MEDOFF-COOPER: Thank you for that question. It really depends on the infant obviously. We have
some infants that are being fed before surgery and those infants are commonly assessed from with
SLPs. Infants that are not being fed pre-surgery that as soon as oral feeding is being initiated,
the SLPs will start working with these infants. Almost all of our infants
have the speech language pathologist referral just as feeding as beginning.
DR. GAIL CRESCI: That's great. Thank you. So you know how transition from inpatient,
outpatient, particularly in this early life population is so important because as
these infants and children can bounce back and forth through both environments. So having
that continuity of nutritional support is so important. So these questions go out to Dr. Black.
And the first one is are there specific questions about the nutritional ecology in which a child
lives that would help improve the screening or the choice of treatment for pediatric malnutrition
that could be incorporated into the electronic health record or the clinical care process?
DR. MAUREEN BLACK: Thank you very much for the question and the answer to that is yes, with the electronic medical
record, for example, there's a two-item screen for food security, sometimes referred to as the
hunger vital sign that has been incorporated into a number of electronic medical records. What this
does then is alert the clinician about the food security status of the household under really,
ideal conditions, there are examples of that information in the food, in the electronic medical
record then being transmitted either to with permission, of course, either to work or to a
food bank so that it's not only learning about the family, but it's connecting them with some
resources to improve their food security status. So that's the most obvious example of
one that I can think of. It's just very helpful to understand what's going on at a family level to be
able to move forward and come up with some rest of the evaluation and some interventions that can be
implemented within the family. Excellent. And so a continuation of that. So you have those type of
resources, then what about maybe those that don't get into that resource system or that do even,
how would you address food deserts and food swamps in this context and how to help families navigate through these challenges?
DR. MAUREEN BLACK: Thank you. These are very interesting questions and illustrate how
important it is to understand the contexts in where families live. It also illustrates the
role that nutrition can play beyond a single family, and that is advocating in a community
that there be more resources available for families who are living in a food desert or
a food swamp and who don't have transportation. It's very, very difficult that even if they're
aware of the interventions and want to follow through, that it can be very difficult to do.
So I would say that the nutrition community has a wonderful opportunity to work with
existing municipalities or existing services beyond individual families and children,
really to try and help them so that the...the onus is not always on the families, but on the broader
community to sort out how to provide services for their communities. Also, there are examples of
the communities that have done some innovative things, either working through libraries.
There's online grocery shopping to try and help families who are living in very difficult places.
DR. GAIL CRESCI: Thank you, thank you for that response. So in thinking a little bit more now,
so we have our patient identified to need some nutritional assistance. The patient is getting
assistance. How do we monitor that? So this question is for Dr. Revilla and was the mFR easy to
use when children had care outside of their home, like were daycare providers, for example, easily
able to adhere to taking the photos with the marker. And then were the parents able to verify
the foods in the photos at the end of the day? Then that gets translated back to the clinician
to have a better understanding of what might be going on nutritionally with the patient.
DR. MARIE KAINOA FIALKOWSKI REVILLA: Yeah, mahalo for the question. Thank you. It was actually something that
was unexpected that we found in our pilot study. It was actually the impetus of the parents that
they just went and downloaded it on grandma's phone or auntie's phone or the sitter's phone
when the child wasn't with them. And for some of the parents, we collected data for four days and
it was three out of the four days that there was some meal that was reported by another caregiver.
And so based on our,
we had surveys and things with the parents and based on what they told us, it worked out great
and it helped them. And we were still able to do content verification with the parents,
with the images that were submitted. However, we do need to do further research to kind of examine
if that wasn't necessarily at the onset what we were planning on doing. And so now that we found
that this occurs, because this was the first time that the mFR, the mobile food record had been used
in infants, we thought: Oh, we need to examine this further to see if there are any differences
and if there's differences in quality of images. But it was at the impetus of the parents and
they would train the other caregivers. So I guess it does also speak to the utility
of the technology to hopefully reduce one of the burdens of dietary assessment. So
hopefully we'll have more to come to address that question. That was a great question. Thank you.
DR. GAIL CRESCI: Yeah, it's definitely a needed area of research and but what part of your research,
have you been able to identify if addressing these feeding behaviors
using this...the mFR, has it been able to show ability to impact growth failure for these
vulnerable infants or any children with complex physiologic challenges?
DR. MARIE REVILLA: Yeah, I put in the response to that one. You know,
that's not something that we've actually explored yet. So I don't really have
much to clarify on that response. Maybe some of my colleagues might be able
to add further. Not at this time, though. That's a very important question, though. Thank you.
DR. GAIL CRESCI: So that's a future direction we need to go, is try to move to that stage. So let's now
move to our guidelines. Our systematic reviews and guidelines conversations because what guidelines
tend to do because we're reviewing the literature, they really identify gaps,
that...what we we are missing. And so I'm just curious between Dr. Irving and Dr. Moloney,
this question for both of you because you both listed several gaps,
future directions. If you had to pick one to start with, what would it be?
DR. SHARON IRVING: I'll jump in.
DR. GAIL CRESCI: Yeah, sure.
DR. SHARON IRVING: I would say definitions. One of the things that I've found consistently in looking
at guidelines and looking at even the systematic reviews and how they evaluated the guidelines
that they included was that there was such heterogeneity in definitions, definitions
about nutrition status, definition about when do you hit that cutoff. So I would say that
some common definitions to address this across age groups would be for, in my mind, an important
first step so that as people are engaging in research and even in QI projects, you know what
you're dealing with and you are measuring apples to apples and oranges to oranges. Dr. Moloney.
DR. GAIL CRESCI: Dr. Moloney may be...
DR. SHARON IRVING: Frozen. That would be number one for me would be those to standardised definitions. I
think that's one of the biggest challenges that we have. And so it makes for very difficult
assessments, but it also makes for difficult comparisons.
DR. GAIL CRESCI: Well, another question for you, Dr. Irving, with all the guidelines in the scoring
systems, do any of these predict poor outcomes? Did any of the research help to clarify whether
any of these definition or guidelines predicts an individual patients to help us identify
who will need or respond to nutritional nourishment based on their interventions?
DR. SHARON IRVING: Well, that's a great question. Excuse me. And, you know, the guidelines that I used as
my base to do my comparison is in critically ill infants and children, right. And so none
of the tools out there have been validated in that group. So that's the first thing to recognize. So
therefore, when you talk about predicting what populations or subpopulations and subgroups will
benefit from nutrition and can these tools identify that, that's a really tough place
to be because of what I said previously. One, the definitions are so variable and two, none of them
have been really validated in pediatric critical care. The third component of that is there's only
three of the tools that are out there that were even in their original development,
even included some critically ill children. So it makes it really difficult to overlay that onto
this population. And then the last point that I'll make there, that those of us that work in
the critical care environment and actually even in the inpatient environment, severity
of illness is such a large component of this. And there's only one of those tools that even
included that. So I think we have lots of work to do and lots of area for research and development.
DR. GAIL CRESCI: Thank you. Oh, yeah, yeah, please. We have time for one more. So yeah, Lisa,
we're waiting to hear from you.
DR. LISA MOLONEY: Sorry, I had a little bit of technology issue. Yes,
I would definitely concur that we had a lot of trouble. So when we try to aggregate the data,
the definitions are certainly a huge concern. A lot of nutrition screening
and nutrition assessment using being used interchangeably as far as the tools went. Also,
when it came to trying to aggregate the data, just the way that things were reported. So we didn't
have enough raw data that we needed to truly aggregate all of the available evidence. But
right out of the gate, the first issue that we did have was the definitions and the lack
of standardization between screening and assessment and what outcomes were reported.
DR. GAIL CRESCI: And would you say that is what contributes to the heterogeneity
that you had noticed amongst the evidence base?
DR. LISA MOLONEY: Yeah. So, I mean, as far as the screening and the assessment systematic reviews
we've been conducting that we had heterogeneity and difference in...different reference standards that were being
used that the tools were compared to. And then as far as the intervention studies, the interventions
might have been fairly similar, but what they were compared to were rigorously different. So it was
just the overall study design was hard to compare apples to apples with most of these studies.
DR. GAIL CRESCI: So in 30 seconds, can you tell us how would we design
a study to get around this heterogeneity issue?
DR. LISA MOLONEY: I think it would be, I think a multidisciplinary approach would definitely be
helpful when it came with screening and assessment for everyone to provide what exactly is that gold
standard in nutrition research? It's not exactly easy...30 seconds is a tough one to do.
I think it's also referral back to these systematic reviews would also be helpful.
But yeah, we had heterogeneity not just in the outcome, but then also in these interventions.
DR. GAIL CRESCI: OK.
DR. LISA MOLONEY: Sorry, it's probably not, I don't know gold standard answer.
DR. GAIL CRESCI: No, I know the magic ball. So, okay, well, I want to thank everyone for your participation.
We had up to 86 participants, and thank you to our presenters for such an engaging discussion.
We will now take a quick break before the second part of this Session 8 will begin at 2:50pm.
Thank you.
DR. GAIL CRESCI: Hello, and welcome to Malnutrition in Clinical Settings,
Research Gaps and Opportunities. And this is part two of session eight on Early Life
Research Considerations. My name is Gail Cresci, and I'm an associate professor in the Cleveland
Clinic Lerner College of Medicine of the Case Western Reserve University,
and full staff in the Department of Pediatric Gastroenterology and Inflammation and Immunity
at the Cleveland Clinic in Cleveland, Ohio. I am also the immediate past president of the American
Society for Parenteral and Enteral Nutrition. I will be your moderator for this session.
We have a phenomenal panel of experts presenting on this topic today. For detailed information
regarding their backgrounds, please refer to the speaker tab on the left column of this screen,
or you can go to the main page under the speaker tab and also find their bios. This session focuses
on disease and condition-specific malnutrition in early life. There are many disease conditions that
impact nutritional status in early life. Unfortunately, due to time limitations,
we are not able to cover every disease state, but we certainly have many to discuss.
Dr. Tamara S. Hannon will discuss changes in metabolism focusing on gestational diabetes.
Dr. Edmond Wickman will discuss a unique form of malnutrition in pediatric obesity.
Dr. Andrea Garber will discuss the inability to meet nutrient needs in anorexia nervosa.
Dr. Elena Ladas will discuss the double burden of malnutrition in childhood cancer.
Dr. Lori Bechard will discuss the inability to meet nutrient needs in pediatric critically ill.
Dr. David Sasken will discuss nutritional therapies and inflammatory bowel disease
and implications of malnutrition and disease. Dr. Bruno Chumpitazi will discuss carbohydrate
malabsorption in irritable bowel syndrome. Alexandra Carey will discuss nutritional
strategies in the malnutrition child with short bowel syndrome.
And lastly, Dr. Jalal Abu-Shaweesh will discuss malnutrition in immune related necrotizing enterocolitis.
The presentations will be followed by a live question and answer period with the speakers. I
encourage you as the sessions are being presented to please submit your questions in the question
and answer box. We will try to address as many questions as we can during the live q&a session.
So, without further ado, here we go.
DR. TAMARA S HANNON: Thank you for the invitation to present on type 2 diabetes in youth and gestational diabetes.
I would like to disclose that I am a consultant and serve on a pediatric
clinical trials advisory board for Eli Lilly Incorporated, but we will
not be discussing pharmaceutical products or clinical trials here.
I would like to start with a case history of 12 year old Mariah who presents with increasing body
mass index. Her mother had gestational diabetes but does not know her current diabetes status.
Her maternal grandparents have diabetes, eye, and kidney disease and cardiovascular disease.
Mariah has (INAUDIBLE) indicative of insulin resistance and her hemoglobin a1c is 6.3% just below the cutoff
point for diabetes. How do we intervene in the generational cycle of diabetes?
It is well known that type two diabetes is increasing in youth. The search for diabetes in
youth multicenter study has reported a continued increase since the study began in the year 2000,
particularly among minority race and ethnic groups. The incidence rates for
type two diabetes in youth show a dramatic increase in non Hispanic black youth. This
has further increased during the COVID pandemic as rates increased by 77% between March 2020 and
March 2021, as determined by a multicenter hospital base case ascertainment study.
Is there an ideal intervention for 12 year old Mariah?
Effective prevention strategies for type 2 diabetes have not been determined.
Treatment of impaired glucose tolerance for pre diabetes with diabetes medications including
Metformin or insulin does not stop the progressive beta cell dysfunction in this age group.
So, early recognition and intensive treatment are recommended but patients often have gaps in care.
There are barriers to seeking care. Diabetes is a stigmatized disease.
Failing and OGTT feels bad whether you're a child or an adult. Moreover, the reality
for families living with type two diabetes is often trying to make ends meet due to poverty,
lack of basic needs, and lack of access to medical, social and community support.
Mariah is now 21 years old, and presents during the second trimester of her first pregnancy.
Her diabetes status is unknown. She has never had prenatal counseling or
reproductive health care. And given her family and past medical history,
it is likely that her pregnancy has already been impacted by hyperglycemia.
According to the International Diabetes Federation in 2019 20 million or 16% of live births had
hyperglycemia in pregnancy. One in six births was affected by gestational diabetes. Most cases of
hyperglycemia in pregnancy were in low and middle income countries or areas of the United States.
We learned through the today's study pregnancy outcomes
study of young women who were diagnosed with type 2 diabetes during adolescence,
over 15 years of the combined today's study data collection 260 pregnancies were reported
by 141 young women. Those reporting of pregnancy have lower household incomes at baseline with a
higher proportion of non Hispanic black race ethnicity. The average age at first pregnancy
was 20.5 years with an average duration of diabetes prior to the pregnancy of 7.3 years.
Approximately one third had chronic hypertension, one third had glycemic failure and a quarter had diabetes
neuropathy before pregnancy. There were high rates of pregnancy loss, stillbirth,
preterm birth, maternal complications, SGA and LGA, and neonatal hypoglycemia.
Antenatal glycemia predicts poor outcomes in young women.
The demographics and increased incidence rates of type 2 diabetes in youth in the U.S. will be
associated with increased high risk pregnancies in the U.S. In the near future, even more youth
will be at both genetic and metabolic risk for type 2 diabetes or have type 2 diabetes.
Mariah is now back with her three month old infant. Her baby is growing well on breast milk,
and she can no longer breastfeed due to work obligations. She and her baby are eligible for
WIC, the special Supplemental Nutrition Program for Women, Infants and Children.
She would like information on how to feed her baby with formula.
A very recent publication out just last week has highlighted potential increased risk for rapid
weight gain in infants receiving lactose reduced formula that is made with corn syrup solids.
This formula is glucose rich, rather than galactose rich.
WIC data from more than 15,000 children who stopped breastfeeding by three months
of age were analyzed to compare weights and links of children grouped as those
who were ever issued formula with corn syrup solids 23% of the children versus
those who were never issued formula with corn syrup solids, most of the children.
As you see here, both males and females who were issued formula with corn syrup solids
had steeper trajectories of increase for weight for length Z score up until two years of age.
The difference between those who ever received formula with
corn syrup solids and those who had not remained at age four.
The association's remained significant, independent of maternal weight status,
total formula issued and breastfeeding duration, and were not modified by child race or sex.
This study provides additional formula, if you will, for thought about how to feed children
who cannot breastfeed.
There are many research gaps that should be evident from my presentation,
including how can generations of women with diabetes help us learn more? When
and how should young women with multiple risk factors for diabetes be treated?
And how should infants and young children be fed to decrease the risk for diabetes?
There are many in targets for research across the spectrum of research to address these questions.
I will leave the rest for discussion. Thank you.
DR. TREY WICKHAM: Good afternoon. I'm Trey Wickham from Virginia Commonwealth University and it's my honor to
present at the NIH malnutrition and clinical settings workshop.
I receive funding support from the National Institutes of Health as well as WW International.
The World Health Organization considers your obesity disease and places it on the spectrum
of malnutrition in children. Let's explore how pediatric obesity may represent a unique form
of malnutrition. Both malnutrition and obesity result from significant perturbations in energy
metabolism, are associated with increased risk of disease, affect children's physical, emotional,
and social development, and are significantly influenced by social determinants of health
including poverty and food insecurity. Moreover, youth with obesity may be at increased risk of
other forms of malnutrition including fiber, protein, vitamin, and mineral deficiencies.
As such, obesity is a highly prevalent form of malnutrition, affecting approximately one out of
four to five youth in the United States with higher rates among marginalized populations.
Consistent with the WHO definition of malnutrition as an imbalance in energy metabolism, long term
positive energy balance where energy intake exceeds energy expenditure is central to the
development of obesity. Yet this paradigm has been used to inappropriately and detrimentally
oversimplify the pathogenesis of obesity, suggesting that the condition is solely the
results of apparent behaviors, including poor dietary choices and limited physical activity.
In contrast, robust data supports the role of complex neuro humoral pathways in the regulation
of energy intake and expenditure. Moreover, alterations in these pathways that lead to a
positive energy balance are well described in patients with obesity, providing a biologic
basis for many observed behaviors. Moreover, weight loss triggers compensatory changes in
these pathways that push the patient to regain weight, leading to increased energy intake and
reduced energy expenditure. Thus, obesity results from not only sustained positive energy balance,
but a resetting of the body weight setpoint and an increased level. In summary, obesity
is a complex chronic disease that frequently emerges during childhood and adolescence and
results from an interplay of a myriad of genetic, environmental, metabolic and behavioral factors.
Clearly, genetics plays a prominent role in the regulation of body weights and pathogenesis of
obesity. Moreover, as highlighted by other speakers already today, epigenetic changes,
including those resulted from factors in the fetal environment and early postnatal life appear to
influence the risk of obesity as well as other metabolic disorders. Lastly, the gut microbiome
which we know is established early during childhood and plays a prominent role of health
has also been implicated in the development of obesity. Yet data regarding the role of epigenetic
and microbiome changes have largely been derived from animal studies, and the role in human
physiology is less clear, representing one area for further research. Relevant to our focus today
on early life, we know that certain behavioral factors including breastfeeding, sugared beverage
intake, and impaired sleep appear to contribute to obesity. I also wish to highlight the role of
environmental and social factors in this complex disease, including contributions from agricultural
policy, food industry, factors within the built environment, socio economic factors and the
potential role of endocrine disrupting chemicals. To further highlight research opportunities in the
field we do need to rigorously investigates how even well intentioned policy changes and impacts
obesity and other components of health. We further also need to clarify the biologic pathways
by which endocrine disrupting chemicals may contribute to energy imbalance and obesity risk.
Behavioral weight management including and components dietary modification, increased physical
activity, and behavior change in support are at the core foundation of the treatment of pediatric
obesity. Extensive research has failed to demonstrate that a dietary approach that targets
any specific macronutrient category is superior to others in regards to weight loss. However,
there are interesting data regarding the potential impact of ultra processed foods on the previously
outlined feedback pathways controlling energy metabolism. Evidence supported recommendations
highlight that parental involvement is essential component of pediatric weight management.
In fact, results show that in youth younger than age 11 exclusively targeting parents or
caregivers results in similar clinical responses to those interventions that include youth as well.
Although parental engagement and adolescent weight management is still recommended the most effective
approach during this unique developmental period is not well defined and warrants
further investigation as our group is currently doing. I also wish to address concerns based
on observational studies that have been proposed linking unsupervised dieting to increase dieting,
or eating disorder risk among youth. Yet, evidence does not suggest that supervised
empirically supported behavioral weight management treatment increases eating disorder risk. Indeed,
family based behavioral weight management has the potential to buffer eating disorder risk given its
focus on healthy sense of self regulation of energy balance and weights. Another research
gap is determining which youth will respond to behavioral weights management most effectively
data like these from Danielson and colleagues suggest that behavioral weight management
responses are greatest in youth when initiated early in life and among those with less severe
obesity. Moreover, we need research to identify the minimal amount of BMI or weight change that
results in clinically significant improvements among the pediatric population and adults mild
to moderate weight losses of three to 5% have been shown to result consistently and metabolic
improvements, yet a similar threshold has not been robustly and clearly defined in the pediatric
population. For older youth with severe obesity is it is unlikely that lifestyle modification
alone will adequately treat that patient's obesity and consideration of pharmacotherapy as well as
Metabolic and Bariatric surgery is recommended. Four pharmacologic agents are currently approved
for the treatment of obesity and youth younger than age 18. Although newer agents demonstrate
more robust weight losses studies clearly show that patients typically experience weight regain
when these medications are discontinued. Thus, although pharmacotherapy law does likely represent
an important treatment modality in severe pediatric obesity, it is essential to continue
to follow youth on these medications longer term to more fully assess risks and benefits.
In contrast to the limited data regarding pediatric obesity pharmacotherapy, they are
increasingly robust data regarding the clinical efficacy, safety and durability of Metabolic and
Bariatric Surgery among youth with severe obesity. In fact, the results of Teen-LABS as well as other
studies have demonstrated weight losses among youth after weight bariatric surgery that are
comparable to adult counterparts with likely even higher rates of comorbidity resolution.
In light of this robust data, the American Academy of Pediatrics recently issued a policy statement
emphasizing the potential role of bariatric surgery in the care of youth with obesity,
as well as a call to action to reduce barriers and enhance access for eligible youths.
Research unfortunately confirms that individuals with obesity including youth frequently face
stigma, bias and discrimination across multiple social domains, including healthcare. Moreover,
evidence suggests that patients experiencing stigma during health care are less likely to
follow up and more likely to engage in unhealthy behaviors such as unsupervised dieting.
In summary, I've attempted to highlight multiple research gaps that impair understanding regarding
the pathogenesis and treatment of pediatric obesity, a unique form of malnutrition. In brief,
these include the lack of understanding of the risk of new nutritional deficiencies among
affected youth mechanisms by which the prenatal environment and the microbiome potentially
impact energy homeostasis, establishing thresholds that define clinically significant
weight loss in this younger population. The potential impact and supervise family based
behavioral weight management on disordered patterns of eating. The long term metabolic
benefits and risk of both pharmacotherapy and bariatric surgery, as well as interventions
that effectively address provider bias and reduce stigma towards patients with obesity.
DR. ANDREA GARBER: Hello, I'm Andrea Garber. I'm a Professor of Pediatrics at the University of
California, San Francisco, and Director of Nutrition for Our Eating Disorders
Program. Very pleased to be part of this conference on malnutrition, and to speak
to you today about our advances in the treatment of malnutrition in patients with anorexia nervosa.
Anorexia nervosa is a psychiatric diagnosis with behaviors such as restriction and over exercising
that results in the loss of lean and fat mass. The malnutrition of anorexia nervosa is considered to
be relatively uncomplicated because there usually is no underlying infection, critical illness,
or cachexia. The numerous endocrine adaptations that are directed toward extending life in this
state of starvation have been very well described in patients with anorexia nervosa, such as low
leptin, resulting in an overall hypogonadal hypo metabolic state, which we often describe
to parents as a state of hibernation. However, we know children and adolescents are not there and
they are not equipped to withstand malnutrition for long. Our patients quickly develop autonomic
dysfunction clinically indicated by vital sign abnormalities that require hospitalization.
These are the most common vital sign abnormalities in patients with anorexia nervosa when they
present for hospitalization. And we use these as nutrition sensitive outcomes to measure the
efficacy of our refeeding protocols. So, you can see here bradycardia hypotension or the stasis
hypothermia, we use these as a multifactorial outcome to measure how well we are feeding these
patients. Of course, the greatest risk as in many patients with malnutrition that can arise during
the course of the hospitalization is the refeeding syndrome and unfortunately, since this was first
described among with prisoners of World War II, all of the end organ complications of this
syndrome have been documented in patients with anorexia nervosa during refeeding,
including cardiac arrhythmia, failure and arrest, delirium, seizures, coma, and death. And so,
our approach to refeeding for many decades, and all of the recommendations for refeeding
and patients with anorexia nervosa were extremely conservative. In the U.S., published recommendations
began around 1,200 calories per day, advancing slowly by 200 calories every other day. In Europe,
there were recommendations in place as starting as low as 500 calories per day. And studies show
that using these conservative start low and go slow approaches that it took weeks to restore
medical stability. And there are many studies to show that protracted hospitalizations in
patients with eating disorders contribute to the high cost of care for this illness, and they do
not improve outcomes. About half of patients are readmitted within the first year of their first
hospitalization. Only one third are recovered at 12 months. And anorexia nervosa continues to have
the highest mortality rate of all psychiatric disorders. So our research program is focused
on optimizing refeeding approaches for patients with eating disorders. And we were fortunate to be
funded to do our first clinical trial by the NICHD from 2015 to 2020 where performed the strong trial.
This was a very straightforward clinical trial comparing the standard of care that I told you
about starting here at 1,400 calories and stepping up slowly by 200 every other day, versus a more
aggressive refeeding protocol that we developed at UCSF and others published preliminary findings to
support such as a group by Whitelion colleagues and Melbourne. Patients were enrolled upon
admission to hospital. They were 12 to 24 year olds with malnutrition evidenced by the vital sign
abnormalities that I showed. And we collected data every day in hospital and over 12 months of follow
up. We also had a very tight electrolyte repletion protocol. This is a Threshold Method, so unlike
the the new ASPEN recommendations that discuss relative declines, this was repletion protocol
that only treated low electrolyte levels. So, a potassium below 3.5, phosphorus, serum phosphorus
below three and magnesium below 1.8. So, to cut right to the chase, here are the findings. We were
able to show that using high calorie refeeding compared to the low calorie standard of care,
we could stabilize medical complications three days earlier. Specifically heart rate normalized
four days earlier, weight gain was 0.8 kilos higher. And importantly, hospital stay was
four days shorter, which translates into almost a $20,000 healthcare savings per participant.
In terms of safety, we found no differences in electrolyte shifting. So, only a handful
of patients developed hypophosphatemia. You can see here. And there was no difference
in the proportion who needed electrolyte correction. We did find that the nadir in
electrolytes occurred earlier with high calorie refeeding, which has implications for monitoring,
meaning that if you're going to feed high calories, you need to do more
monitoring upfront. And then in terms of long term outcomes, no differences in clinical remission,
which is defined as a combination of both cognitive and weight recovery. And what
this tells us if if the long term outcomes were equally good with these two treatments,
that the upfront savings associated with high calorie refeeding were sustained over 12 months.
We're very proud that we have worked hard too, to rapidly translate these findings. So, the
new recommendations for refeeding in the US and internationally reflect high calorie refeeding.
Now, about opportunities and gaps. One of the serendipitous findings that came out of the
strong study is that 43% of the patients in fact, were diagnosed with atypical anorexia nervosa. If
you're not familiar with this relatively new diagnosis, it refers to patients who present
at or near the median BMI for their age and sex. So, here's an example of a growth chart
of a young person with atypical AN, and you can see that they technically have, quote, unquote,
normal weight. And in fact, in anorexia nervosa, this would be considered a recovery weight. But
this is where these young people are presenting for hospitalization. And what we showed is that
aside from their differences in presentation weighed, there are no differences in medical
severity. Patients with atypical present with just as likely Amenorrhea, similar percentage of weight
loss, and similar medical complications. So, this is not anorexia nervosa light,
this is in fact a diagnosis associated with malnutrition and medical complications. Now,
when we refed these patients, as I said, you can see here in the red line, if you look at this
survival curve as patients step up to restored medical stability, patients with anorexia did well
on high calorie feeding. However, patients with atypical struggle behind and require two to three
more days of refeeding even on higher calorie protocols. And so, we're now again fortunate to
be funded again by the NICHD to perform a second clinical trial that is totally focused on atypical
anorexia nervosa. And looking at from more of a precision medicine lens, how can we individualize
the refeeding protocols and optimize outcomes in these patients who have diverse body weights?
An important gap associated with this study that we are addressing is to develop biomarkers of
recovery. If weight is not informative in these young people. And in fact, not only
is it non informative, it's highly controversial because many of these patients became overweight,
some of them became obese. And there's a lot of controversy about how high we
should go with recovery weights. So, as part of this study, we are including biomarkers
to look at developing new benchmarks of recovery, including the sex hormones,
T3 cortisol leptin and energy expenditure by indirect calorimetry. We're also very interested
in developing body composition as a benchmark of recovery in atypical AN. There's been some
very interesting talks during the course of this workshop about sarcopenic obesity. And similarly,
these patients who are quote unquote normal weight have highly altered body composition, and
that could be studied and used as a benchmark for recovery. In collaboration with John Shepard and
Steven Heymsfield and support from NIDDK, we have been studying the use of three dimensional optical
imaging to look at or as a use of a non invasive measure of body composition and underweight
patients that I think has high potential for use in our eating disorder patients, where other types
of anthropometrics would be highly inappropriate and potentially psychologically triggering. And
we have a couple of papers already validating beyond many papers validating this method.
There are a couple of specifically in children and underweight patients. The final gap that I think
really deserves exploration here is the impact of the gut microbiome on metabolic recovery in
patients with anorexia nervosa. We know that from several studies now that patients with anorexia
nervosa have marked dysbiosis associated with their malnutrition, that it does not fully recover
during the course of refeeding. And it has been well characterized as including low production of
short chain fatty acids. But what is not known is how this may modulate metabolic recovery,
or in fact, thwart response to refeeding such as slowing down the weight gain.
I want to just take a moment to thank my colleagues and collaborators and again, the NICHD for their support of this work.
ELENA LADAS: Hello, my name is Elena Ladas, and
I'm at Columbia University Irving Medical Center, and here to talk
to you about the double burden of malnutrition and childhood cancer.
So, childhood cancer is the second leading cause of death among children. And in the
past 20 years, we have seen an increase both nationally and globally in childhood cancer.
In terms of research and nutrition in pediatric oncology, it really isn't until 2005,
where we started to get some well collected data that documented both the role of under nutrition
and over nutrition in terms of its impact on treatment related toxicities, as well as survival.
And so, here's two very common clinical situations that we encounter. The first being a patient who
has acute lymphoblastic leukemia, had started treatment at a healthy or ish weight. And if
you followed his, we would expect his weight to kind of follow this red line. However, once he
starts treatment for leukemia, his weight starts to decrease and increase, and then throughout
treatment which ends about here, he has a striking increase in BMI and then into survivorship this
continues. On the other side, this is a patient with a solid tumor. Five year old boy. Starts
again in the vicinity of a healthy to low weight. Starts treatment. And again, if he would have
stayed in his weight category, we would have anticipated this red line. But in fact, due to
conditions impacting his gut, as well as another number a variety of other things,
he becomes severely malnourished to a point where his Z-score is around a negative three.
Now, it's important to recognize that in childhood cancer, malnutrition varies wildly by disease. So,
for those patients, for instance here that have medulla blastoma, you can see a high incidence
of both under and over nutrition depending on the phase of treatment. That's true for osteosarcoma,
and some other types of sarcomas. However, in contrast, we have other diseases like Hodgkin's
disease, which the malnutrition both under and over is smaller than for other cancers. But it
really the take home message is that this is not one stop shopping that this really
requires a different approach depending on the patient's pre existing condition.
And type of disease and therapy. So I'd like to take childhood acute lymphoblastic leukemia
as an example, because it is the most common childhood cancer. Survival is really outstanding
for patients who are standard risk ALL. They have even over a 95% chance of survival,
overall is still 84% quite high. Treatment consists of two years and it's either, you know,
vacillates between high and low dose therapy and steroids are an important part of treatment.
However, there has been a price trial of this success. About 60% of patients
that are healthy weight at diagnosis become overweight or obese by the end of treatment.
And this continues into survivorship.Ten to 50% of patients develop hypoglycemia and in turn,
this impacts their survival. And there's a number of other morbidities, including pancreatitis, as
well as the risk of adult onset cancers, metabolic disease, etc once they complete treatment.
Now ALL has been described as a pre-obese state and this figure here on the right illustrates how
the three different weight groups, the green line being obese, the red overweight, the blue healthy,
and how their weight trajectories change over time. And clearly you can see that those patients
with a healthy weight at diagnosis become overweight or obese by the end of treatment.
So here, figuratively, you can see this is a meta analysis here on the left that compiled data
and had children with ALL and again found about 35% reduction in patients with poor nutrition
at diagnosis. And in turn, those patients also are predisposed to hypoglycemia. And we see a
distinct difference in survival in those patients who are hypoglycemic versus those that are not.
So we know that nutrition matters. We also know that it can be remediated, meaning that the impact
of poor nutrition on outcome can be resolved. So figure A here illustrates survival and the
yellow line of patients that are healthy weight throughout the course of treatment.
And the other two lines are both patients that are either undernourished or over nourished and
you can see their survival similar. Now, contrast with, contrast that with figure B, and it's the
red line and the dotted black line that's slightly above the yellow, the yellow line. And those are
patients that were in an at risk category either under or over nutrition, and it was remediated.
So they did not spend a prolonged period of time at an at risk weight group. And you can see their
survival is the same as those patients that remain a healthy weight through the course of treatment.
So we've done a lot of work trying to understand not only is this a matter of lifestyle or are
there biological factors that contribute. So the ALL dataset, which is called DALLT,
is the largest dataset available, and it looks at nutrition, genetics and diet over
the course of treatment for ALL. And the first question that we wanted to ask this dataset is,
OK, this obesity, it must be related to access eating, they are on steroids, they are sedentary.
You know, this just mean that's just explains why they become obese. However, it does not explain
why they become obese and survivorship. But in fact, that wasn't true because what we found was
that caloric increase intake decreases over time. And again, you can contrast that decrease with
these patients. These are patients on different regimens for ALL. But you can clearly see here's
where they start with BMI and here's where they end. So this isn't really the entire story.
We've also looked at genetic factors and determining if patients with a
poly genetic risk score or a predisposition to obesity cannot explain it. And in fact,
both in non-Hispanic and Hispanic patients that the a poly genetic risk score. So a propensity for
obesity does have some impact in those patients that develop it over the course of treatment.
Now, what are the causal mechanisms? I mean, quite frankly, we really don't know.
You know, there's really a lot of research that needs to be done. We do know that this is disease
specific. I'm highlighting ALL, but malnutrition and other diagnoses have also revealed similar
results. It may be a difference in terms of the steroid. What prompts this more or less,
and certainly our pharmacodynamics, but it's controversial and quite understudied.
There's also a factor of the leukemia microbiome environment or other tumors that may be more or
less susceptible. And certainly the microbiome has come into play in this, particularly with a
lot of the particularly with the increased use of immunotherapy. And does that change the microbiota
in such a way to promote kind of deleterious down downstream pathways that start in the gut.
So we are advancing towards interventional studies, although slowly. One of the first
studies that looked at dietary intervention and if it can even stave off obesity. So meaning
is the combination of factors overriding just dietary education. And in this small pilot study,
we did find that nutrition education was effective at improving diet. And most importantly, it staved
off weight gain. Again, this was not a weight loss program. It was really just looking at if we
intervene aggressively and early, can we stave off that weight gain? For the majority of patients,
again, in this small pilot we did, that there is still a subset of patients, that subset of
patients that require more information about the dietary intervention was not as effective.
To follow up on this, the Children's Oncology Group is launching a study. It's a multicenter
study that will look at not only dietary intervention for the prevention of weight gain,
but is also going to look at the role of genetics and socio demographic risk factors for obesity to
see if you know how these factors intertwine with one another and may impact the increased
or decreased risk. So in closing, there are many research opportunities in childhood cancer. You
know, we do know that both under and over nutrition impacts, disease outcome as well
as treatment related toxicities. But in order to effectively remediate this, we need more
understanding of the underlying mechanisms of this. Existing research is limited to ALL. So
we really also need to understand how these mechanisms, once understood, vary by disease,
and much of the existing data is really limited to body, body mass index. And I didn't have time to
go into the other body of research that that has looked at body composition, but body composition
certainly has played a role, a role both in Hematologic as well as solid tumors, potentially
by altering pharmacokinetics or through other factors that we don't know. Prevention is key
both for under and over and for undernutrition, we know proactive intervention, and some ways that's
a little bit easier to resolve with the exception of (UNKNOWN). However, the prevention of obesity
and the potential use of appetite inhibitors such as GLP-1 agonists may be a clinical useful tool,
however, really needs more research, and the role of dietary intake and quality is really virtually
unknown. There is some data to show that diet quality does impact many of these mechanisms
and factors that we've talked about, certainly especially as the microbiome becomes more into
play. But again, we need a lot more research in this area. So thank you so much for your attention
and I look forward to the discussion.
DR. LORI BECHARD: Hello, I'm Lori Bechard and I'm pleased to present during this important workshop among my esteemed
colleagues in the field today, I'll review some of the aspects related to malnutrition
in pediatric critical care with a focus on the consequences of nutrient intake inadequacy.
My disclosures are my employment at Boston Children's, where my department supports
most of my work. And my research is partially funded by the Pediatric Nutrition Practice Group,
and NIDDK grant that's awarded to Dr. Mehta and (UNKNOWN) for a multicenter trial.
The objectives of my talk today are to describe the
unique barriers to nutrient delivery in pediatric intensive care units,
to synthesize relationships between nutrition practices and outcomes in PICUs use around
the world, and to explain research gaps and future opportunities in this environment.
First, we'll review the commonly encountered barriers to adequate nutrient delivery in
pediatric critical care patients. These barriers can be thought of as stemming from three different
sources, the patient, him or herself, the provider or care team taking care of the patient and the
published practice guidelines, pre-existing nutritional status, as well as how that involves
the metabolic changes that occur with critical illness or trauma and intolerance to enteral
or parenteral nutrients. All may challenge the goal of achieving nutrient adequacy.
Furthermore, care team providers may be challenged to best understand and prescribe the most
appropriate amount, type and route of nutrients. Considering the diverse mix of patients who
present to a pediatric ICU. Feedings are often interrupted for a variety of medical reasons,
preventing patients from achieving the intended amounts. And finally, institutional algorithms,
national guidelines and other evidence will help at a population level could inform practices
that might ultimately interfere with optimal delivery of nutrients for some PICU patients.
About half of patients presenting to the PICU with critical illness are of normal weight status
by BMI Z score, but a substantial proportion are either underweight, overweight or obese, as
shown in this large cohort study of mechanically ventilated patients from our PiNS studies.
And being underweight was associated with a 1.5 times higher risk of mortality when
controlled for other important risk factors. Both underweight and obesity were associated
with higher risk of infection and longer life of stay in the hospital.
The metabolic sequelae of critical illness in children is a unique scenario where an insult
such as trauma, sepsis, surgery or other critical event triggers muscle breakdown to supply proteins
for the acute inflammatory response, along with decreased utilization of glucose and resulting
hyperglycemia and lipolysis to provide ketone fuel for the brain. This response leads to loss of lean
body mass and impaired tolerance to nutrients, compounding the effect of the illness itself.
This often leads to nutritional deficits and deterioration throughout the hospital stay.
In addition, there are several specific barriers to receiving optimal nutrition delivery,
particularly by the favorite enteral route. It's often difficult to prescribe the targeted
nutrition prescription accurately due to the variability, volatility and heterogeneous
nature of critically ill children. Even with the best feeding targets, interruptions to enteral
nutrition seem inevitable. Whether for issues related to intolerance,
medical or surgical interventions or procedures. Also, critically ill patients typically require
many medications and therapies then incur additional volume, thereby limiting volume,
a lot of nutrition since excess fluids are often poorly tolerated during critical illness.
The use of algorithms and protocols in the PICU may help to reduce the barriers
and interruptions to nutrition adequacy in critically ill children. This pre-post study
of the implementation of an internal feeding algorithm at Boston Children's
shows how energy goals were achieved in a significantly higher proportion of patients
and both a time to reach energy target and the number of avoidable interruptions to enteral
nutrition were significantly reduced following implementation of the algorithm in the (UNKNOWN).
While locally implemented protocols may improve attainment of nutritional adequacy, there may be
gaps when interpreting national guidelines such as these from ASPEN and SCCM, published in 2017.
Since many pragmatic questions around nutrition delivery remain unanswered by research evidence.
These European guidelines were published in 2020 and are mostly aligned with the ASPEN guidelines,
concurring with early EN and energy provision not to exceed resting energy expenditure in
the acute phase of critical illness. However, there are two arguably important differences
with the European guidelines specifically recommending withholding a PN during
the first week of critical illness for all patients and limiting consideration
for the 1.5 grams of protein per kilo guidance to enter early fed patients only.
So since we know there are barriers to enteral nutrition limitations to the guidelines,
let's take a look at a few of the larger studies that suggest the need for more research on these
topics. These studies examined protein and energy delivery and the timing of
nutrition delivery in the PICU and how it relates to clinical and nutritional outcomes.
Our first international cohort study of nutrition practices and outcomes showed
low energy and protein delivery of enteral nutrition through the first ten days of critical
illness and a significant relationship between higher proportions of exclusively enteral energy
adequacy and lower 60 day mortality. In our second PiNS study, we turn our attention to protein
specifically and continue to find low enteral delivery of protein and a significant relationship
between enteral protein adequacy, as defined by percentage of the prescribed target that
was delivered in 60 day mortality, especially among patients with the most severe illness.
With regards to timing of nutrition delivery, an analysis of the large cohort of
PICUs from the Virtual PICU Systems database showed lower mortality among children
who received at least 25% of their prescribed goal calories by enteral nutrition within the first two
days of PICU admission, suggesting the need to start enteral feeds early with benefit even
when low proportions of delivery are achieved. We looked at timing of delivery adequacy in our most
recent PiNS cohort study in this group of over 1800 mechanically ventilated children
achieving 60% energy or protein adequacy either by enteral or combination of enteral and parenteral
nutrition in the first seven days of PICU admission was associated with a significantly
lower risk of mortality. This suggests that it may be important to deliver at least 60%
adequacy by four to seven days after PICU admission, but there may not be any additional
benefit to a more aggressive target within the first days, first three days after admission.
While cohort studies are helpful, certainly a large clinical trial is higher quality evidence,
and while rare in the PICU setting, there is one well-known three center trial of early
versus late PN known as the PEPaNIC trial that has informed many publications and discussion of this
topic in recent years. They randomized over 1400 patients to receive PN, either within 24 hours of
admission or if needed, on day eight, with early enteral feedings provided per protocol and the
primary outcomes were ICU acquired infections and readiness for discharge. Most patients in
the late group actually never needed PN since they achieve their goal through enteral feeds alone.
Their analyses were adjusted for several contributing factors such as diagnosis,
age, illness, severity, malnutrition and site, and showed significantly lower odds of infection
and showing shorter length of stay in the late PN group, suggesting benefit to withholding PN
in the first week of PICU admission. There are important limitations to the PEPaNIC trial,
however. The intervention may not have been a pragmatic approach to some critically ill
children, particularly in U.S. PICU. Since the application of PN was to extreme extremes
of timing, the population may also be different with most who are able to receive full or nearly
full enteral nutrition. And for those in the early PN group, the high energy targets may have caused
them to be overfed, which could have influenced their outcomes. So many questions still remain as
to the ideal approach to nutrition for critically ill children, which brings us to the final section
where we can highlight some of the nutrition research opportunities in this population. We
have seen the importance of the timing and route of nutrients. However, in real life PICU
settings, more nuance is often needed to achieve optimal nutrient delivery. More investigation of
pragmatic approaches to nutrition, perhaps combined with elements of rehabilitation
and mobility, as in the PICU up protocol is now included in many U.S. PICUs. Also, since
fortunately mortality is very low in PICUs, but morbidities are common consideration for the
impact of nutrition strategies on other short term and long term outcomes is increasingly important.
Refinement of advanced techniques to measure nutritional mediators such as body composition
and energy expenditure measurements at the bedside is needed for tools such as muscle, ultrasound or
indirect calorimetry, as shown on this slide. And many PICU patients have multiple morbidities
and chronic diseases where the relationship between nutrition delivery and more patient
centered outcomes such as functional status and quality of quality of life could be very relevant.
So with that, I want to acknowledge the important contributions of, of course,
our patients, but also many dietitians, investigators, clinicians and research
staff that have assisted with our studies. Too many to mention here. And I thank you for your
attention and look forward to the discussions.
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.
Nutrition is not only integral in terms of the well-being of our patients,
but it also is intertwined with disease and disease activity in inflammatory bowel disease.
Malnutrition is common in pediatric IBD. It's interrelated to a number of factors,
including anorexia, secondary to elevated cytokines such as TNF alpha.
Also decreased oral intake, secondary to symptoms, increased nutrient losses,
increased catabolism, drug therapies such as corticosteroids and surgical interventions.
So why focus on nutrition in inflammatory bowel disease? Well, there are many really important
reasons. One is not only does nutrition have an effect in the acute setting,
but it has long term effects as well. And you can see here that stunting is not an uncommon issue
in pediatric IBD. It also has implications on psychosocial well-being of our patients.
In addition, our medication therapies, while effective, are not completely effective for
every patient all of the time. And you can see here in the sonic trial, using two very potent
immunosuppressants, Infliximab and azathioprine and there is still only a 56% efficacy rate
in the short term for these patients. And finally, nutrition is interrelated to the
potentially idiopathic genesis of IBD itself. And we see this by increasing incidence of IBD
over the last 20, 50 plus years, both in the pediatric and the adult worlds.
So to understand how nutrition and IBD are interrelated, it's really important
for us to understand the IBD paradigm. We know that inflammatory bowel disease is an immune
dysregulation. So the immune system which is there to protect us has gone awry and is now attacking
the intestines. And there are many reasons for this. One, there's a genetic predisposition,
but as noted prior, the incidence has increased over the last 50 plus years, suggesting that
while this is important, it's not the main driver of IBD. We know that certain medications such as
antibiotics are associated with IBD and we know that westernized diets high in sugars
and high in fat are also associated with IBD. Now the foods that we eat impact the different
components of IBD. The foods that we eat changed the microbiome to being eubi, from being eubiotic
to becoming dysbiotic or being pro-inflammatory. The foods that we eat also break down the mucosa,
which keeps away the vast majority of bacteria from the intestinal immune system.
And because the immune system can now interact more easily with the microbiome, the immune system
becomes upregulated, causing inflammation leading to inflammatory bowel disease.
Because nutrition is intertwined with the etiopathogenesis of inflammatory bowel disease,
it can also be used as an intervention, as a therapy for IBD as well. And there's
no better example of this than exclusive enteral nutrition or EEN.
This has been designated a primary nutritional intervention for pediatric Crohn's disease by the
North American Society of Pediatric Astrology, Hepatology and Nutrition. With EEN patients go
on to any formula and formula alone for six to 12 weeks. No other foods or drinks outside of water
are taken in, and this is given either orally or via nasogastric tube. And as you can see here,
our center is so supportive of this intervention because it is such an important intervention that
we on IBD Day placed our own nasogastric tubes and gave ourselves formula as a mechanism of
support for our patients. EEN Intervention has two main roles. It not only corrects the
malnutrition seen in pediatric Crohn's disease, but it also treats the primary disease itself.
With regards to correction of the malnutrition, it provides the caloric needs for the patients
and allows for catch up growth. In addition, it corrects for micronutrient deficiencies often
seen in pediatric Crohn's disease. With regarding to treating the primary disease
itself is been shown to resolve inflammation and get patients into clinical remission.
And importantly, it improves mucosal healing rates and decreases the need for prednisone usage,
which is associated with worse outcomes in pediatric Crohn's disease. But one of the
most interesting aspects of EEN is that the mechanism by which it works is still unknown.
One of the most pivotal studies on the use of EEN in Crohn's disease is this study by Borelli and
colleagues. What they did is enrolled patients with Crohn's disease into a ten week randomized
controlled trial of steroids versus exclusive enteral nutrition. And they looked at three
main outcomes. They looked at clinical remission. They looked at biochemical remission and they also
looked at mucosal healing rates. And as you can see here with the pictogram on the left that the
remission rates, the clinical remission rates were similar between EEN and steroids. In addition,
biochemical remission, meaning laboratory improvements were similar between the two groups.
But what was different was the mucosal healing rates. As you can see in this pictographs,
EEN worked significantly better than steroids in healing the bowels, and this has large
implications on short term and long term outcomes. There are a number of postulated mechanisms by
which EEN works in Crohn's disease. It may be interrelated to a reduced luminal antigen
exposure leading to antigenic monotony which allows the immune system to downregulate.
It may be interrelated to food exclusions, specifically those foods that break down
the mucosal layer and allow the microbiome to interact more with the intestinal immune system.
It may also be interrelated to indirect effects of nutritional supplementation,
such as modification of fat content, which affects the bile acid synthesis.
It may also be interrelated to trophic amino acids or modulation of the gut microbiome and
metabolome. It has also been postulated that mechanical properties of food may be
also interrelated with the inflammatory process itself. But to date, no conclusive evidence has
pointed to one or other mechanisms as the cause of the improvements we see with EEN in IBD.
There have been some studies looking at potential mechanisms by which EEN works.
This study by (UNKNOWN) replicated Borelli's earlier study showing efficacy of EEN in
Crohn's disease. But they took it a step further. They not only looked at clinical,
biochemical and histologic outcomes, but they also looked at the intestinal microbiome. And what you
can see here is the shifts that occurred with the intervention. On the left hand side of the screen,
you can see the principal coordinate analysis prior to treatment of the patients with Crohn's
disease and after the intervention with EEN versus steroids. And you see a significant
shift in different directions with the usage of EEN versus steroids possibly interrelated to why
we see better mucosal healing with EEN. And on the right hand side of the screen, you can actually
see a number of important species and the shifts that occurred with the different interventions.
This study by (UNKNOWN) looked at mucosal inflammation and cytokine levels in patients with
Crohn's disease undergoing EEN and therapy. And what you can see, is prior to the intervention,
the cytokine levels in the mucosa were significantly elevated as compared to controls.
But after the intervention with EEN, the pro-inflammatory cytokines reduced significantly
and became on par with that of controls. Understanding the mechanisms by which EEN
works is essential. But what's more powerful is to see it work in action. And so I wanted to bring
this clinical case forward. And this is a 14 year old patient that I saw a number of years ago with
a three month history of abdominal pain, diarrhea and weight loss. The patient was anemic and had
elevated C-reactive protein, all consistent with IBD. Patient underwent endoscopy and colonoscopy
and here you see his terminal ilium, which is inflamed, ulcerated and angry. After the
procedure, talked with the family, and the family wanted to see if there was an intervention where
they could avoid using medication therapy. We had a long discussion about different interventions
and the pros and cons of those interventions for the treatment of IBD and the family and patient
decided to move forward with exclusive enteral nutrition and then transition to a Whole Foods
dietary treatment called the Specific Carbohydrate Diet. He maintained clinical and laboratory
remission for over five years until I lost contact with him as he moved to an adult GI provider.
And during that time he had a repeat endoscopy and colonoscopy which revealed normal appearing
mucosa with normal histology, showing you the impact that dietary interventions can have.
You would imagine an intervention which not only improves the nutritional outcomes
of your patients, but also improves the disease itself would be used extensively.
The opposite is actually true. In the U.S., only 12% of American pediatric gastroenterologists
use EEN regularly. The percent of patients that use EEN is significantly less in the US
as compared to Western Europe, Canada and Israel. There are a number of questions we need to answer
with regards to EEN in inflammatory bowel disease. We need to understand the mechanism of action by
which EEN works. This will allow us to understand the IDO pathogenesis of IBD much better.
In addition, it will allow us to understand how we may use a Whole Foods diet to help treat IBD.
In addition to this, we need to understand how to optimize the use of dietary therapy
for these patients. Increasing utilization as well as identifying dietary responsive patients. Thank you very much.
DR. BRUNO CHUMPITAZI: Hello, everyone. This is Bruno Chumpitazi from Texas Children's Hospital and Baylor
College of Medicine. And it is a pleasure to be with everyone,
albeit virtually. I'd like to thank the organizers for the opportunity to speak to
you about carbohydrate malabsorption in irritable bowel syndrome. This is my disclosure slide.
Irritable bowel syndrome is a disorder of gut brain interaction, and these disorders
are extremely prevalent with 25% of all children worldwide over the age of four are suffering from
one of these types of disorders. These disorders can have several factors that are heterogeneous in
nature that can affect any one individual. And this figure here tries to summarize
some of those potential factors. One can have sensitizing medical events, including distension,
inflammation or delay disorder, combined with genetic predisposition and early life events,
which then leads to changes in pain processing and visceral hypersensitivity.
These changes, combined with sensitizing psychosocial events, including those listed here
such as depression or anxiety, can then lead to the phenotype that we see clinically of abdominal
pain and other gastrointestinal problems. In the case of irritable bowel syndrome, this is
chronic abdominal pain associated with changes in stool frequency or changes in stool form.
One of the common symptom culprits in those with irritable bowel syndrome is diet. And
food is perceived to be a symptom culprit by over 90% of children and adolescents
for the irritable bowel syndrome. You can see that this is significantly higher than
healthy controls. For example, one study showing 92 or almost 93% of children with
IBS versus 62% of healthy controls having at least one self-perceived food intolerance.
But there are also a significantly higher number of potential culprit foods identified by children
with irritable bowel syndrome as causing an issue. There's significantly higher number
of avoided foods that children with IBS have from their diets so that they do not have an issue. And
you can see similar prevalence data in adolescents with irritable bowel syndrome identified, 92% of
them versus 20% of healthy children identifying at least some type of food that causes an issue.
Now, perhaps one of the most studied GI symptom culprits are FODMAP Carbohydrates. FODMAP is
an acronym that was coined by investigators at Monash University, where F stands for fermentable,
meaning that bacterial metabolism is playing a role. O stands for oligosaccharides,
including the fructans and galactans. D stands for disaccharides, including lactose. M stands
for monosaccharides, including fructose. A stands for and, and P stands for Polyols,
including sugar alcohols such as sorbitol or mannitol. And taken together, these are
poorly absorbed, osmotic, reactive, and rapidly fermented carbohydrates which can produce gas.
And this leads to the putative pathogenesis of FODMAP carbohydrates in which these carbohydrates,
if they're not well absorbed, such as lactose, the polyols, the fructose,
or fructose and galactose, can have increased osmotic activity bringing water into the small
intestine. These carbohydrates then are transported distally into the colon where
the bacteria will ferment them producing gas such as hydrogen, methane and carbon dioxide,
and as well as other metabolites such as short-chain fatty acids.
This in turn will lead to luminal distension, and the luminal distention because of the visceral
hypersensitivity in those with IBS, will lead to increased symptoms. But one of the challenges in
the field is that despite the fact that there are these small bowel water content changes and
colonic gas production, it's not been possible, for example, using MRI studies to predict who
will or will not respond to a low FODMAP diet. And this is a diet in which these FODMAP carbohydrates
are actually significantly restricted. So there's been a lot more attention actually
paid specifically to bacterial fermentation, both in terms of looking at the overall gut
microbiome composition as well as metabolites, and there've been several adult IBS studies.
We'll be focusing primarily on pediatric IBS effort that our work as a group has been doing.
Now, just to summarize very briefly, the low FODMAP diet summary evidence suggesting that low
FODMAP diet may be helpful, it's been growing. In adults with irritable bowel syndrome, there's one
Double-blind placebo-controlled challenge study and more than ten randomized controlled trials
which show that a low FODMAP diet is either as efficacious as other interventions such as yoga,
or actually more efficacious in ameliorating symptoms as compared to other dietary
interventions which have higher FODMAP content. There are several uncontrolled studies which show
symptom improvement ranging from 56 to 94%. And the data is also increasing in pediatric irritable
bowel syndrome and functional abdominal pain, with one double-blind placebo-controlled challenge
study suggesting that fructans can play a role in increasing symptoms, which we'll be going
into briefly. And then three randomized controlled trials suggesting that low FODMAD diet is either
more efficacious than other interventions or as efficacious as another dietary intervention.
And then uncontrolled studies showing symptom improvement ranging from 50 to 77%.
Now, specifically regarding the Fructan Challenge study, this is a randomized crossover study
of children with irritable bowel syndrome who received either fructan or maltodextrin during the
dietary intervention periods. We identified that children with IBS had increased abdominal pain,
bloating and flatulence when given the fructan, as compared to when they were given the maltodextrin.
We also identified a specific subgroup that we termed the fructan sensitive
subgroup. And these were children that had a 30% increase in abdominal pain frequency during
that fructan dietary challenge period versus the Maltodextrin Challenge period. And 17 of
the 38 participants met this criteria. When comparing fructan sensitive children versus
those that we termed fructan tolerant, which is to say they did not develop this increase
in abdominal pain when given fructans, we could not differentiate the two groups with
respect to several baseline clinical parameters, including demographics such as age or gender,
diet, GI symptoms, or psychosocial distress or overall gas production.
This led to further evaluation of the overall gut microbiome. The subjects provided fecal samples
during the baseline period and during each dietary intervention. And using 16s RRNA evaluation,
we're able to compare the overall alpha diversity between those who were fructan
sensitive and tolerant. This figure shows these results. Here in the blue you're seeing the median
and 25th and 75th percentile data of observed OTUs and those who are fructan tolerant. And
in the orange, you're seeing the same data for those who are fructan sensitive. And during the
baseline period and when the subjects were being given the maltodextrin, there was a significant
overall decrease in alpha diversity in those who are fructan sensitive versus fructan tolerant.
Further suggesting that there is a difference in the microbiome composition was a data diversity
evaluation comparing the two groups. Here in the blue again, you're seeing those data points in a
principal coordinate analysis plot for those who are fructan tolerant, and then the orange here for
those who are fructan sensitive. And there was a significant difference between the two groups
at baseline and also during the maltodextrin period. And while we don't have enough time
to go into all the differences that we saw during the interventions, I wanted to highlight. At least
during the baseline period, there were 14 taxa within the Clostridia class that were enriched
and those who are fructan tolerant and those who are listed here, ranging from Clostridia to
Ruminococcaceae to coprococcus, suggesting that at least at baseline, those who were
fructan intolerant could be differentiated from those who are fructan sensitive based on fecal
samples and evaluation of the gut microbiome. And also suggesting potentially that those who
are fructan tolerate had an increased ability... The bacteria had increased
(UNKNOWN) ability and were able to metabolize and hydrolyze carbohydrates more easily.
And this is a summary of some preliminary data taking a look at additional multi-omics beyond
16s RRNA, now looking at whole genome sequencing as well as lipidomics and
metabolomics of the same fecal samples. We use random forest modeling and we're able to
discriminate fructan sensitive versus tolerant participants with a median value of 0.854 when
combining all this omics of the diets together. And that can be seen in panel A and panel B,
we actually took a look at the different periods of the baseline versus fructan versus maltodextrin
periods, and found that the baseline period was actually contributing the greatest discrimination
in terms of... vs. the other dietary periods to the overall mean, suggesting that where you
start from is actually very important in terms of the gut microbiome and its activity in determining
fructan sensitivity. This leads to further research opportunities, including increased
need for increased understanding of human biology related to carbohydrate malabsorption
in both health and GI disorders such as IBS. Need further information about transporters,
how they are regulated, as well as genetics and epigenetics. When you further a non-invasive
assessments of intraluminal gut microbiome throughout the GI tract, including the small
bowel in particular, so you gain greater insight into the composition function,
and also need bioinformatic standardization to be able to compare study results between
investigators and research groups. And finally, integration of the host biology and microbiome
and luminal physiology will be the future in this area as well. I'd like to end by acknowledging the
investigators listed on this slide, as well as the support listed here on the bottom right. Thank you
so much for your attention today.
DR. ALEXANDRA CAREY: Thank you for this introduction. I am honored to be able to speak to you today.
My disclosures are related to three studies I am closely involved with,
the latter two related to therapies used in pediatric short bowel syndrome with malabsorption.
To really understand malnutrition and short bowl syndrome, you have to become familiar with the
different evidence based definitions related to this chronic illness. The first of which
is intestinal failure. My favorite and most broad definition of intestinal failure is a
reduction in GI function below what is necessary for digestion and absorption of adequate nutrient,
fluid, and growth requirements. In a recent manuscript, my colleagues doctors (UNKNOWN)
and (UNKNOWN) and former CCO fellow Dr. Galloway, along with other notable members of this field,
define intestinal failure as a need for chronic parenteral nutrition dependence for 60 days within
a 74 consecutive day interval. Intestinal failure from short bowel syndrome includes
surgical resections and/or congenital defects that decreases the total GI mass and absorptive
capacity of the GI system, and represents the condition that we will focus on today.
Now, there are many causes of short bowel syndrome, but a common theme remains that all
patients, whether on oral supplements, enteral tube feedings or parenteral
support through a central venous catheter, remain at risk for malnutrition. As such,
it is crucial that we understand how to now define, diagnose, and treat malnutrition.
In this group, I am willing to bet we can all appreciate that malnutrition is common in short
bowel syndrome. And I'm also willing to bet, and it's easy to deduce that malnutrition is often the
result of malabsorption, given the reduction in gastrointestinal mass and function. But then why
can it be so hard at times to identify and correct it, or to know how to manage and prevent it?
Well, first we diagnose malnutrition using standardized anthropometric Z scores. However,
these patients don't typically follow the rules of typical anthropometry. Furthermore,
there are variable ways to manage and treat. Some of these are evidence based, some of these are
based on expert opinion and experience. Treatment is also going to be based on the capabilities
of your center and the resource allocation that exists, including the funding potential.
It is also clear that similar to some of the other conditions discussed today, that this rare,
complex and heterogeneous pediatric condition carries with it significant research gaps.
But in any field, significant research gaps like these stimulate clinicians and researchers like
yourselves to work hard to create future research opportunities. So now let's discuss an example of
a patient we recently saw in our CAIR clinic, which is the Center for Advanced Intestinal
Rehabilitation, to help us understand how malnutrition can be hard to diagnose.
This is the case of an eight year old male with jejunal regional atresia. He presents to clinic
for standard follow up without any GI complaints. He was weaned from parental support about a year
ago and remains on nightly IV fluids due to inability to maintain his hydration and relies
heavily on enteral tube feedings with an elemental formula. On exam, his weight and BMI for age are
reassuring, as you can see on the left, but his weight velocity on the right is decreased,
and his mid upper arm circumference is actually down. He has a distended abdomen with thin arms
and legs. So I ask you, does this patient have malnutrition? I would say so. But if you base it
on his weight and BMI for age trends, you may miss this very subtle trend. I'm also worried
that as he approaches puberty, he's going to require more nutritional support in the form
of IV calories. So this patient therefore warrants very close follow up with nutritional titrations
to help improve his growth. Malabsorption can present by subtle changes in growth patterns,
as demonstrated on the previous slide, as well as intolerances of enteral and parenteral regimens
can manifest as diarrhea above the patient's baseline. Additionally,
dysbiosis and inflammation can lead to malabsorption and then malnutrition. This
image on the right was taken during endoscopy of a five year old male with short bowel syndrome
for history of poor growth and chronic diarrhea. Intestinal biopsy and duodenal aspirate confirmed
small bowel bacterial overgrowth with chronic inflammation. So this patient was started on
cycled antibiotics and anti-inflammatories and his experience dramatically improved growth and
decreased symptomatology. Now, intestinal failure associated. Liver disease is also common and can
increase the risk of malabsorption related at times to fat soluble vitamin deficiencies.
Systematic evaluation and diagnostic protocols, including imaging and panendoscopy when indicated
or when able, is key when patients are thriving as it can lead to clear nutritional,
medical and/or surgical treatment plans, which can directly improve the morbidity and mortality
of these vulnerable patients. As we alluded to, anthropometry and short bowel syndrome can be
challenging. Typically, we base our nutritional status on serial weight and height measurements,
but are these accurate in short bowel syndrome? I would advocate that they are often inaccurate
due to fluid shifts, abdominal distention, timing of the last stool, and measurement discrepancies
in part related to increased home measurements following the COVID-19 pandemic. Less commonly,
we use other methods such as skin folds, mid upper arm circumferences, BIA, DXA, or air displacement
plethysmography or ADP. These methods have been shown to hold some weight in short bowel syndrome,
but are underutilized for a variety of reasons. For example, many centers do not even have ADP
clinically available. I am particularly excited about ADP in short bowel syndrome,
as I believe it complements our interpretation of nutritional status by more accurately measuring
body composition and lean body mass. It is validated in healthy children, but more research
is needed to apply to subpopulations like pediatric short bowel syndrome.
Without a doubt, the key to the successful nutritional management of children with
malnutrition due to short bowel syndrome remains with the concept of the interdisciplinary
intestinal rehabilitation program. This approach is well documented in the literature. Together,
we can predict the degree of malabsorption occurring in patients so we can better tailor
and apply comparative standards such as basal or resting energy expenditure, protein and total
fluid goals. For example, say you have a one year old female with 30 centimeters of small bowel,
ending in Jejunostomy who is advancing nicely on feeds. But you learn that ostomy output
is watery and 3mls per kilo per hour. Family's excited the baby is seemingly weaning from PN.
However, I'm willing to bet that this infant is moderately malnourished and would benefit
actually from increasing parental support and backing down significantly on enteral support
due to evidence of malabsorption. Expectations setting from the get go is crucial. Often,
it is slow and steady that wins the enteral autonomy or race short bowel syndrome.
We are in an era of limited resources, therefore having a team work together to select
the appropriate formula and route can improve absorption and reduce malabsorption. Understanding
the complexity of parental support, especially strategies in advancing and weaning support, can
also help with energy utilization. For example, close examination and titration of the sodium dose
or the glucose infusion rate and parental support can be the difference between normal and stunted
growth. Lastly, having access to complementary medical therapies and research protocols such as
GLP-2 analogues and immobilized lipase cartridges can also help improve nutritional status.
I want to conclude by discussing the research gaps and opportunities that I think we should focus
on next to as a field. We know that predictive energy equations are fraught with inaccuracies.
Therefore, using better methods to predict energy requirements to tailor nutrition is needed. One
such test could be using indirect calorimetry, which is the standard of care in the ICU setting,
but is definitely underutilized in the outpatient and short bowel syndrome setting.
Next, we discussed how difficult it can be to predict lean body mass and growth based
on standard anthropometry. So perhaps using serial ADP clinically can be part of the new
standard of care. It also dawned on me a few years back that each center manages parenteral support
differently. We all cycle the PN according to different protocols and use different standards.
So employing something like continuous glucose monitoring in our patients on
parenteral nutrition may be a great way to understand glucose utilization and disglycemia,
which can lead to poor growth. In fact, one such study is underway with our endocrine
colleagues at Boston Children's Hospital, which I'm very much looking forward to.
And lastly, we have a long way to go before we understand the microbiota signature in short
bowel syndrome. If we can develop better ways to characterize the microbiome and identify bacterial
overgrowth that are clinically available, valid, reproducible and non-invasive, we can better treat
inflammation and therefore improve enteral autonomy and decrease risk of malnutrition.
And with that, I would like to thank you as well as my many mentors and colleagues at
Boston Children's Hospital. Thank you.
DR. JALAL ABU-SHAWEESH: I would like to thank the organizing committee on their invite to participate in this important workshop.
It is truly an honor and a privilege to be part of this esteemed group of colleagues,
I have no conflict of interest to. By the end of this talk, I hope that you
will be able to understand the challenges of providing adequate nutrition and preventing
necrotizing enterocolitis, identify factors that improve nutrition and help decrease necrotizing
enterocolitis in preterm infants, recognize the value of establishing a feeding protocol,
and appreciate the importance of evaluating your own practices. Necrotizing Enterocolitis remains
the major gastrointestinal disorder affecting preterm infants. Its incidence is quite variable
among different in ICUs, and has been reported to range between 2 to 20% with an average of 5
to 10%. The incidence and severity of the disease are inversely proportional to gestational age and
birth weight, with the most immature infants being most likely to be affected by the severe disease.
Pathophysiology of necrotizing enterocolitis is multifactorial, and as currently reported,
probably represent multiple diseases rather than a single entity. The origin of the
disease stems from a complex interaction between immature host defences and normal development of
commensal flora, resulting in a combination of ischemia, hypoxia, inflammation and/or necrosis.
Necrotizing enterocolitis has been staged based on Modified Bell's criteria into three
stages. Stage one constitutes signs and symptoms concerning for NEC, in which in
almost always nonspecific and may be related to other (INAUDIBLE) illnesses, immature responses
including poor gut motility, constipation, CPAP therapy, or milk protein allergy, or intolerance.
Stage two is diagnosed medical NEC with the hallmark of pneumatosis intestinalis or air
in the wall of the gut, or portal venous gas. Stage three is complicated surgical
NEC associated with perforation, gangrene and/or necrosis of parts or all of the bowel.
Necrotizing enterocolitis is associated with very high mortality, ranging from
20% for medical NEC to as high as 50% in surgical NEC. It is also associated with
high rate of morbidity, both short and long term, including short gut syndrome, stricture,
repeated surgeries, neurodevelopmental delay, poor growth, cholestasis, and liver failure.
The impact of necrotizing enterocolitis and nutritional status of the preterm mirrors
that of the different stages of necrotizing enterocolitis. Stage one truly affects the vast
majority of preterm infants and results in feeding restrictions and interruption of feeding advanced
secondary to feeding tolerance in fear that this might be early necrotizing enterocolitis Stage
two and three affects the 5 to 10% of preterm infants affected by necrotizing enterocolitis,
and results in altered nutritional support during the acute illness.
And even a smaller percentage of infants inflicted with post necrotizing enterocolitis complications,
nutritional deficits are assessed beyond the acute ailment. We have seen necrotizing enterocolitis
is a very serious and devastating illness, and its management is based on early recognition and
intervention. The problem is, early necrotizing enterocolitis presents with feeding intolerance,
which is very common in preterm infants, affecting 30 to 50% of extremely low birth weight infants.
The presentation of which mimics that of early necrotizing enterocolitis, and might include
abdominal distention, gastric residuals,
bilious aspirate, vomiting, or simply what's described as low PPEP abdomen.
Often the medical response is to stop feeds and reassess with multiple X-rays and blood tests.
Often the presentation occurs in off hours and thus TPN might not
be available to compensate for the loss of calories.
This graph perfectly summarizes the effect of feeding intolerance in advancing feeds in very
low birth weight infants. X axis represents days taken to full feeds, and the Y axis represent
the percent of infants reaching full feeds in multiple different units across the world, both
in China designated by the GED, and outside of it there are non GED graphs. The feeding protocols
utilized would reach full feeds between 7 to 15 days according to how they were established. While
some units were able to achieve this duration in the majority of their infants, I'll look at the
tail of these curves as even the most aggressive units needed up to 30 days to get all of their
infants up to full feeds, and some slower units needed as long as 60 days to achieve the same.
The usual practice of starting and stopping feeds is what usually causes this delay. Stages two and
three are usually managed by cessation of feeds for variable duration, antibiotics and TPN. It
has been shown that prolonged duration of feed cessation is associated with atrophy of intestinal
line and interruption of hormonal and trophic intestinal function. This also might be associated
with cholestasis and liver failure secondary to prolonged NPO, TPN, and lipid administration.
Improved nutrition in stages two and three should concentrate on aggressive nutritional
support using TPN, and perhaps non soy lipid formulation. Our unit has moved to the use of
SMOF, which is a combination of soy, lipids, olive oil, triglycerides and fish oil in all babies,
to successfully decrease the incidence of cholestasis. Further management should
concentrate on introduction of feeds as soon as possible. There are no randomized controlled
trials to identify the earliest possible feeds can be safely restarted. However,
two studies looked at this question, both implied small number of infants 47 and 44.
One was a retrospective review and the other was a comparison of a new protocol to historic data.
The comparison was between starting feeds before and after five days in one study,
and four versus ten days in the second. Both studies showed no effect on recurrence of
necrotizing enterocolitis. However, neither study was powered to find a difference.
There was also lower incidence of related infection, as well as faster reaching full feeds.
There are two studies that have evaluated the long term effects of necrotizing enterocolitis
on nutrition. The first looked at the impact of having an enterostomy
post necrotizing enterocolitis in growth. This slide represent the c-score at birth before stoma
formation and stoma closure in infants who were cared for in ICU in the black columns,
those who were cared for at the local hospital or at home in the gray columns. As you can see,
the z-scores decreased significantly in both groups between stoma formation and stoma closure.
The second study looked at long term nutritional complications in Sweden in all survivors of
necrotizing enterocolitis, and found that NEC patients were at significant risk of rickets in
the first year of life, as well as a significant risk of non-specific malabsorption syndrome.
However, there was no effect on incidence of short stature, malnutrition, or failure to survive.
In the last part of the talk, we will concentrate on nutritional approaches
to preventing necrotizing enterocolitis. Some of these proven strategies include feeding maternal
breast milk. While donor breast milk hasn't been associated with increased incidence of
necrotizing enterocolitis, it is not settled if its use can prevent necrotizing enterocolitis. The
use of trophic feeds or minimal enteral feeds at 10 to 20mls per kilo per day has not been
associated with necrotizing enterocolitis, and might decrease villous atrophy associated with
being (INAUDIBLE). However, the optimum duration of trophic feeds is not established. Establishing
a feeding protocol has also been associated with decreasing incidence of necrotizing enterocolitis.
Gastric residuals on the other hand, have long been advocated for early detection of eating
intolerance. However, volume and significance of these residuals is very debated and contribute
significantly to delay in feeding advance. We and many other units across the country have stopped
checking residuals in all preterm infants. Non settle issues regarding the occurrence
of necrotizing enterocolitis include continuous versus bolus feeds, how fast to advance feeds,
and the use of (INAUDIBLE). This study summarizes a meta analysis for the evidence that standardized
feeding protocol does decrease the incidence of necrotizing colitis by an average of 80%,
with a confidence interval that is narrow and does not cross one, indicating significance.
However, which feeding protocol to choose. A Cochrane review summarized the results of ten
randomized controlled trials comparing fast versus slow feeding advance. Slow was defined
as advancing by 15 to 20mls per kilo per day, and fast as 30 to 40mls per kilo per day. The
study included over 3,700 infants, about 2,800 of which came from one study. One third of the
infants were extremely low birth weight, and 20% were SGA or compromised (INAUDIBLE). Analysis
found no difference in incidence of necrotizing enterocolitis or mortality, no effect on discharge
weight or head circumference between the two groups. However, slow protocols were associated
with delayed establishment of full feeds by one to five days, and borderline increase in infection.
Also, the incidence of feeding intolerance causing interruption was 29 and 35% in both groups,
six to nine days. This emphasizes the importance of choosing a feeding protocol that is acceptable
by all stakeholders in your unit, including nurses, nurse practitioners, nutritionists
and physicians, as well as continuous review of your feeding data to decrease protocol
violations secondary to feeding and (INAUDIBLE). While initial studies and probiotics were very
promising in respect to decreasing necrotizing enterocolitis, they employed different protocols,
population and small number of extremely low birth weight infants. Most recent studies and
meta analysis fail to show protective effect of probiotics on necrotizing enterocolitis.
This prompted the Committee on Fetus and Newborn to come up with the following statement, current
evidence does not support the routine universal administration of probiotics for preterm infants,
particularly those with a birth weight of less than a thousand grams.
In conclusion, the best approach to improving nutrition in preterm infants is the prevention
of necrotizing enterocolitis. Proved strategies to achieving that include trophic feeds,
early feeding advance, establishment of a feeding protocol, and the use of antenatal steroids. The
best feeding protocol is associated with minimal feeding interruptions and steady advance,
need for ongoing evaluation of growth, adherence to feeding protocol, and other outcome measures.
DR. GAIL CRESI: Thank you everyone. Wow, that was just as the wealth of knowledge that we're just exposed
to. I'm so excited to begin our Q&A session. But before we do that, I just want to take a brief
moment to thank again everyone that was involved with putting this session together. That includes
our NIH scientific program contacts, including doctors Ashley Vargas, Dr. Charlotte Pratt and
Christopher Lynch, as well as our working group members, which in addition to myself includes
Nilesh Mehta, Dr. Todd Rice, Dr. David Seres, and Alison Steiber. And of course, we couldn't do all
of this work without logistical support, which comes from Kimberly Barch and Mark Dennis,
as well as our lab roots gurus, which include Israel Gonzalez and Bret Long. So thank you
so much for your support. And now let's get into our question and answers, which I know
is going to be exciting, so I'm just going to dive right in. So the first question is for
Dr. Hannon. And you talked about early feeding of the infant (INAUDIBLE) of diabetes,
and you mentioned about the infant formulas, and that the different components in the formulas
compared to human milk. So acknowledging that not all children have access to human milk,
and that infant formula is necessary, are there any other common formula ingredients
that produce different outcomes besides the corn syrup solids that might warrant further research?
DR. TAMARA HANNON: This is a very active area of research, the study of human milk and how we can
make the product formulas bioidentical as we possibly can
be. In general, things that are not found in nature
need to be studied. In my opinion and the opinion of others before, they are routinely fed to
infants and children. Many of the food products that we eat ourselves and feed our children are
not substances that are found naturally, and are created in factories by manipulating naturally
occurring substances. And more research would be needed to determine the long term outcomes
of humans consuming those substances. Did that answer the question? So I think what I'm saying
is the field is still wide open and more work needs to be done. Yes, there's the formula,
but we also need to continue to work to figure out what we're feeding babies and how that's contributing to (UNKNOWN) disease.
DR. GAIL CRESI: Yeah, no, I think you're absolutely right
there, work is still in progress. So I have another question. This one is actually for
both you and Dr. Wickham, in your perspective, disease conditions that you're working with.
So we know you both mentioned gut microbiome as a potential link with some of the diabetes
as well as pediatric obesity. And we know that in utero now and then with first delivery, that's how
the infant first starts to become colonized. And then of course, if the infants being breastfed,
they can also get some of these components from the microbiome, from the mom through the breast
milk. So my question is, is there anything...if you know of any research regarding the maternal
diet and the onset in either pediatric diabetes or pediatric obesity, and this is, you know,
going to be, you know, realized a little bit later in life for the infant. But is there any links...
are any links been identified?
DR. TREY WICKHAM: So you want me to go for it or you want to?
DR. GAIL CRESCI: Dr. Hannon, if you want to go first.
DR. TAMARA HANNON: Sure the research was much more robust in primates
and rodents that it is in humans. I mean those studies are long and difficult, especially keeping track of
maternal diets. It's incredibly tedious and hard. We do know that the metabolic state of the mother,
which is related to her diet will directly impact the fetus and the infant,
not only in response to how the fetus grows and its exposure to glucose and its resulting
(INAUDIBLE) response (INAUDIBLE) response that the fetus has.
But then, however, that metabolic programming carries on post delivery and as the infant grows
and then there's a relationship between what the infant is fed after the infant is born and so it's really complex.
DR. GAIL CRESI: Yes. What about you Dr. Wickham, what are your thoughts?
DR. TREY WICKHAM: I would just add that I think, well,
certainly to answer your initial question. I mean, there are studies that show an association between
kind of maternal dietary intake during pregnancy and the prevalence of obesity in offspring.
And maybe that's needed some by the microbiome. But I guess my point would be there's a lot of
other kind of confounding variables there that are really difficult to tease out. Right? So
you can't... we know that maternal BMI during pregnancy is a risk factor. And so how can you
separate that out from kind of dietary, you know, dietary patterns as well as for many individuals,
dietary patterns kind of persist over a longer period of time. And for many, many individuals,
their dietary pattern, while they're pregnant will persist after delivery as well. This is
gonna further kind of impacts the offspring's kind of risk. So certainly there's an association
there, but it's very difficult to have a lot of scientific rigor that establish causation.
DR. GAIL CRESI: Yeah, I could ask so many more questions in that area, but I think
I'm going to move on, unless someone, did someone else had a comment about that.
DR. JALAL ABU-SHAWEESH: I was just going to mention I agree with both that it's very difficult to do these types
of studies in the world of inflammatory bowel disease, which is not only having a genetic
but also environmental link. There is a ongoing study called meconium, where mothers who have IBD
are going into the study and doing a dietary intervention to see if that impacts the
development of IBD in their offspring. And it's not yet done, it's long-term, but I think those
are the types of studies that will really help us better define what diets will improve and decrease
the etiology of all these conditions that are increasing so significantly within our society.
DR. GAIL CRESI: Yeah. As a dietitian, I just think about, you know, how we focus on gestational diabetes
and how to educate the mom who's identified to have gestational diabetes. But we're not really
paying attention to her microbiome. And, you know, should we be doing that? Because this could have,
you know, a relationship later on in that infant's life and their outcomes. So I think this is,
in my opinion, a good area of future research to try to figure out how to do that and see if
we... with all of these different diseases that we've been talking about related to
early colonization of the gut and the immune function in the gut and how much that impacts
many of these conditions. But I'm going to move on to the next question for Dr. Wickham.
Are there any data on the relationship between provider bias in obesity outcomes and outcomes in obese children with complicated health conditions?
DR. TREY WICKHAM: Yeah, Gail, I can answer that question.
One of the things I would refer people to is that several years ago,
the American Academy of Pediatrics came up with a policy statement about stigma experienced by
children and adolescents with obesity, which is a great kind of review on this topic.
So the few things that I would kind of highlight to answer that question
is that the vast majority of our youth with obesity experienced some form of stigma and
discrimination. And unfortunately, the health care setting is a place where that is not uncommon.
It's a little bit more difficult to tease out specifically kind of the impact of bias, stigma,
and discrimination within the health care with that... within kind of that larger context. But
I think things that we know and is that evidence would suggest that patients feeling stigma and we
were talking about the pediatric population that includes kind of their family overall are less
likely potentially to seek follow-up care. There's some evidence that stigmatized youth are more
likely to engage in behaviors that we feel like are less healthy. So increased binge eating, more
unsupervised kind of dieting, which again, have been linked with kind of worse, worse outcomes,
less likely to participate in regular physical activity. And there's some data that suggests
that kind of that burden of stigmatization that is associated with subsequent weight gain. So
I think that there again, there's certainly places where we need to have that clarified.
But I think data supports that, that it does have adverse outcomes for our youth.
DR. GAIL CRESI: Oh, thank you for that. For that nice answer. I'm going to move now to
Dr. Garber. So I'm wondering, are there any opportunities for appetite, stimulation, or other
modulation of diet-related sensation to address malnutrition in children with eating disorders?
DR. ANDREA GARBER: That certainly is an area of interest. But so far, no, they have not been
successful. So any kind of appetite stimulant medications, sometimes are used to increase
the rapidity of kind of movement or gastric movement. And nothing like that has been
successful. Really, all of the studies in clinical practice just points to re-nutrition
and re-feeding as quickly as possible to stimulate all of those processes. So as far as I know,
there are right now there is no approved pharmacotherapy specifically for anorexia nervosa.
All of the medications that are used are geared toward the co-morbidities like the depression
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.
DR. GAIL CRESI: So again, along the lines of gut
microbiome, you have to know that that's my area of research so interest, but there's so
much growing with the gut-brain axis and knowing how their gut microbiome signals to the brain,
particularly with a lot of these neurological disorders. So with the success of the re-feeding,
has that been ever investigated to look to target the microbiome as well as targeting the host in
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?
DR. ANDREA GARBER: That's really so you're
light years ahead of me. I'm just proposing a pilot study right now
to look at that, but certainly, other people have it's a really ripe area of investigation because,
as you said, the gut-brain axis has been elucidated in so many other conditions. And
this is a condition where we know that in the state of malnutrition when they
come in to us and they are low weight, their depression is worse, their anxiety is worse,
and all of those other psychiatric features. So right now the state of the evidence is that
patients with anorexia nervosa do have (UNKNOWN) gut dysbiosis, and it's been well characterized.
Three or four studies only have looked at improvements during the course of re-feeding. And
they've all shown that yes, that the gut, the the the microbiota do respond to re-feeding, but they
don't fully recover. So then the next question and as far as I know, only one or maybe two groups
have tried to look at this is if the gut does not fully recover, what does that mean in terms of the
long-term prognosis for these patients? So Kleiman and colleagues, for example, have shown that
gut dysbiosis, the persistent dysbiosis, is related to perpetuation of the depression
and the eating disorder psychopathology. Nobody that I know has really gotten to the point that
you're asking about, which is microbiota-directed therapies. So is there some level of medium chain
triglycerides or lactobacillus or something that could be directed at microbiome recovery, anorexia
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.
DR. GAIL CRESCI: Excellent. Thank you. OK. I'm going to
need to move on to ask some other of the speakers some questions. So,
Dr. Ladas, I wonder if you could... ..add to this question. So it seems that all ALL is relatively
well studied and frequent enough in pediatrics that it might serve as a good model for disease,
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?
DR. ELENA LADAS: And in the model you're talking about
childhood cancer at large or just in general?
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.
DR. ELENA LADAS: So, you know, we do use it in oncology and in part because it is the most
common type of cancer. And you know historically when I first started, there was a lot of
undernutrition now the landscape has completely changed where that's very, I wouldn't say rare,
but it's below like 3%. So it's it's not common. But obesity, as I presented, is quite common.
I don't know that you could really apply what we know in ecology to other pediatric illnesses. I
mean, sometimes we've drawn parallels in children with hypothalamic obesity
unrelated to a tumor or radiation to the brain. And we do have some ongoing work at Columbia
looking at appetite suppressants for that. But I think, really, even within an ecology,
it's so vastly different. Just the duration of treatment, the types of treatment they get,
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.
DR. GAIL CRESCI: Yeah, that makes sense. Along the lines of
that, to prevent the weight gain that happens in pediatric ALL, have you used any other type
of treatments besides dietary interventions such as physical activity or family support,
parenting skills, or anything like that?
DR. ELENA LADAS: Sure. So that's a great point. So there's two diseases where we look at obesity,
ALL is one of them, and the other is in children with brain tumors. And you know,
because there is not a uniform recommendation for exercise during treatment,
you know, some individuals think it's fine. Others think it really has to be limited. And
all of these children have ports, so they can't have any you know, if they were soccer players or
football or whatever, they can't have any contact sports. They can't do weightlifting. So there's
already just limitations there. I think that we have been focused on weight prevention, where a
lot of the data shows that dietary counseling, inclusive of family, inclusive of parental
practices, can prevent weight gain. And that's kind of where we're focused on. We realize that
we need to focus on weight loss as well because there's about a 30% increased risk of death in
patients that are obese. So it's not trivial at all. It's just a matter of how to embark on a
weight loss program while a patient's being told, a child's being told they have cancer, it's hard,
you know. So I think that we haven't quite figured out yet. We are starting to explore
the use of GLP-1 agonist. It is like six months old. We are trying this. So it's really
and it's been in the extreme cases, particularly kids with damage to the
hypothalamus or kids with craniopharyngioma that just have wildly excess eating. So I mean,
it's that is think is a very, very fertile area for research, really fertile. And we're
particularly excited about it here at Columbia. GAIL: Oh, that's great. Well, we look forward to
that future research. So I'm going to move on now to Dr. Bechard. You talked to us about malnutrition
in that critical care setting and that there's a causal relationship between getting closer to
the enteral nutrition prescription and improved outcomes. Or do you think this might just be that
the patients are getting closer to the enteral nutrition prescription because they're healthier,
they're getting better and they're more responsive to the therapy or they need less
other interventions? Any thoughts on that?
DR. LORI BECHARD: Yeah, absolutely. Thanks, Gail, for that question. And I misspoke. If I said there was a causal relationship between
enteral nutrition and outcomes in the studies that I spoke about. But I think what this question gets
me to think about is one of the sort of underlying themes among all these talks is that in order to
really study nutrition, we need larger trials. We need prospective interventional trials that
are designed to pragmatically address these kinds of questions. And they are difficult,
they are expensive, they're complex. Nutrition is notoriously hard to kind of isolate. It's not like
a drug where you can just give a placebo. So I think, you know, it's it's a complicated question,
and there certainly is a possibility that this is just a relationship that is not causal.
I don't think we truly know the answer to that. And we need a lot more investigation
into some more pragmatic trials. But of course, these things are confounded by many covariates,
particularly in critically ill children. There are so many different cofactors and elements
related to the child, as well as the environment that could contribute to outcomes that it's tough
to sort these things out. But we're getting there. We're starting an interventional trial very soon,
looking at a couple of these factors and I think hopefully with more interest in this will be able to move, move the needle.
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.
So I'm going to move on now to Dr. Suskind. You talked a lot about EEN and how successful it is
with inducing remission in pediatric IBD. And, you know, I can't help but think that why is this you
know, you gave your, you know, different potential mechanisms of why that might be occurring. And
you know, what that that comes to me is that these formulas are immunosuppressive, that we know that
we've been talking about that for years in the adult population because of their components.
We don't like to feed them to our critically ill people and things like that because they
are immunosuppressive. And it makes me think too, you know, another two parts of this question,
do you think that might be a mechanism? And then the fact that we don't see that
these EEN randomized controlled trials, they're not very successful in adults.
So why, why could that be? Could it be related to microbiome and the different ages of the life
cycle or the gut immune response at different parts of the life cycle? I just want to get
your input on that? Loaded question, I know.
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
last question first. The question of why there is such significant positive studies in the pediatric
realm and the adult studies are less positive. Well, you know, when we do a study, I think we
are looking at many questions of why something works and something doesn't work. And in the adult
population, it may not be that it doesn't work. It just may be that adults are less compliant.
So it doesn't work from a client issue, but it may actually work from a biochemical effect.
And the reason I say that is that there are actually three studies that stand apart from
the other adult studies that have been done on EEN on adults. Where patients were required to
have a nasogastric tube placed for 8 to 10 weeks. And in these three studies, the efficacy was the
same or very similar to the pediatric data. And actually one of those studies was the study by
Yamamoto where he not only put them on to EEN but then did a biopsy, then actually saw that
significant decrease in cytokine levels. So I think the adult studies,
why they don't show efficacy may be more a question of compliance than actually not working.
And I actually know a number of adult colleagues who have started to integrate EEN into their
therapeutic practice and getting very positive responses because they talk about the pitfalls,
the formula fatigue upfront with these patients versus just giving them the formula and saying,
OK, this is what you have to do. The question about efficacy is also fascinating, and I think
this is why EEN really needs to be studied much more from not only a clinical but a
basic science point of view. The fact that we are getting patients with mucosal healing
without any other medication intervention
really points to etiopathogenesis, the question of immunosuppressant, and the components of the
formula. is a really good question, and I wish I could say this is why EEN works, but I can't do
that. We use multiple different formulas and it doesn't matter what formula you use. They
all seem to work equally as well. And we actually just completed a study here at Seattle Children's
where we utilize a Whole Foods formula. Not only a Whole Foods formula, we actually gave families
blenders and Amazon gift cards to buy predetermined foods to make a formula at home. So
no other additives, all fresh. And the efficacy seems equal to those of the standard formulas
we use. So there are a lot of fascinating questions of why something like that works.
And the other interesting aspect is that the microbiome data coming from this initial pilot
study actually shows a different direction than the standard formulas, and that is likely due to
the differences in components of the formula as we don't have a lot of additives such as maltodextrin
and corn starch, etc., and the homemade formulas. But I think, again, it brings to question, you
know, the impact of diet on the microbiome, on the metabolome, on the mucosal layer, and points to a
potential etiopathogenesis or cause of why we're seeing such an increase in IBD in the world today.
DR. GAIL CRESCI: Thank you. Yeah, lots more work to be done on that for sure. I'm going to move now
to Dr. Chumpitazi, and you gave us such a nice review and new data on the role of carbohydrate,
fermentation, and carbohydrate malabsorption in irritable bowel syndrome. If there were no limits,
what would you like to see studied in this area?
DR. BRUNO CHUMPITAZI: Oh, my goodness. No limits. Wow, That's incredible. Well, hello, everyone, and thanks again Dr. Cresi
for the opportunity to be a part of this panel. I think it's been mentioned by the panelists
before in terms of trying to have pragmatic trials and having an intervention. Now,
what's interesting in this irritable bowel syndrome space is that that trial could either
be one where you're actually restricting those fermentable carbohydrates and trying to determine
the mechanisms by which it may work. Or on the flip side, there may actually be one in which you
are going to be challenging patients, you know, with certain fermentable carbohydrates and trying
to understand the mechanism by which they work. And, you know, I don't know if our field has quite
figured out which way to go. You know, that last information that I presented was related to, you
know, a specific carbohydrate fructans that are commonly found in wheat and onions in our diet.
And there's a part of me that likes that idea of really trying to get at the pathogenesis of why
these fermentable carbohydrates may actually be causing the symptoms. So that perhaps if we were
to, you know, fast forward a few years from now, if we understand those mechanisms will actually be
able to do interventions that don't require, you know, restricting the diet for these patients.
So, you know, quickly, it would be a pragmatic trial in which we are
challenging patients long term. Looking at both host factors, perhaps, you know, whether
or not be underlying low-grade inflammation or visceral hypersensitivity, which tend to
be factors that occur in those with irritable bowel syndrome, and how that may be modulated
while also concurrently looking at the gut microbiome in terms of its composition and also in
terms of its, what it's producing from a metabolic standpoint. So we can really understand, you know,
long-term exposure of these carbohydrates and how it may be relating to symptoms.
DR. GAIL CRESCI: Yeah, I mean, I like that study and that mindset, that approach. And I
see how that could really move us forward to a personalized approach to caring for all these
different disease conditions we've been talking about today. If we can find some biomarker that
at baseline will tell us, Oh, this person will be able to digest this or respond to this and
this person may not. And that leads me to my next question for Dr. Carey regarding short
bowel syndrome. And are any thoughts in any routine use of biomarkers such as citrulline
or fecal fat or any in this patient population?
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
in 2009 and has published since then as well. As you all probably know or don't know, citrulline is
it's an amino acid in the plasma and it's produced by metabolism of glutamine, of glutamine,
and proline. And it can be a marker of intestinal length. So we use it in our clinic, I would say
pretty routinely in patients who are on parenteral nutrition or who are struggling from weaning from
PN. We use them a cut-off of around 15 to 20 to predict if they have a good chance at tolerating
advancement of enteral feeds and weaning from parenteral nutrition. As many of you may also
know, there's a medication called Teduglutide or Gattex. And we do measure sertraline before
starting that medication. Then six months and one year after starting this medication as a
marker for intestinal mass. So the higher the citrulline level, the higher, it's thought that
the higher the intestinal mass. So, yes, we do use citrulline in our patients on parental nutrition,
especially those who are struggling to wean off of parental nutrition or if we want to try to
predict if they'll be successful in weaning off of parental nutrition. But like any biomarker,
it may not always be accurate in your patient. And there are certain things that can falsely
increase or decrease this level. Well, it's just another marker that we can use to help us guide
our nutritional decisions. The other comment was about fecal fat, and we do use fecal fat at times
in patients who are on parenteral or enteral nutrition or both. If they are struggling with
malnutrition or signs of malabsorption to help us (UNKNOWN) nutrition. So again, if you see
high levels of fat in a fecal fat sample, it could suggest that you're having difficulties absorbing
fat, but also may be inaccurate. We don't frequently use
the 24-hour fecal fat study or 72-hour fecal fat studies, but sometimes we will use spot fecal fat
analysis to help guide our nutritional decisions.
DR. GAIL CRESCI: So it sounds like you have some biomarkers, but there's still room for growth.
DR. ALEXANDRA CAREY: Absolutely. I'll definitely agree with that.
DR. GAIL CRESCI: Yeah. My last question is for Dr. Abu-Shaweesh. You know, you gave us a really nice presentation on the immune
status in the gut and premature infants and necrotizing enterocolitis
and, you know, ideal care for these patients, But probably some future
research is still needed. And in thinking about that, what specific studies do you think still
need to be done in this patient population?
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,
especially with regard to malnutrition. It's completely the contrary. I think
what I presented is some of the things that we know that might work. There's quite a bit of it
that we still don't know, and we could start with that. Even the definition and diagnosis
of necrotizing enterocolitis, there's quite a bit of evolving evidence that what we have
called historically necrotizing enterocolitis is not just one disease, is multiple different
diseases that might be related to (UNKNOWN) allergy might be related to just feeding
intolerance, simple perforation and the usual diagnosis that we do it. So, you know,
more research and more studies on how we truly diagnose necrotizing enterocolitis is separated
from the large majority of our babies who just have, you know, feeding intolerance. So that we do
not prevent them from advancing on their feeds and stopping their feeds and all that impact that's
going to help malnutrition. But even once we diagnose necrotizing enterocolitis, there is very
little evidence about when to start feeding these babies and how fast to advance these feeds and how
soon can you get to full feeds on these kids. I presented two very small retrospective studies
that we only looked at a few babies and we need many more studies and many large number of babies
to see a difference and, you know, a significant impact of how soon can we start feeding. Everybody
is very hesitant to start feeds and some babies are being (UNKNOWN), you know, 10 to 14 days after
the initial diagnosis. And then the last question of probiotics, I don't think that's settled yet.
I know the fetus and newborn community, came up with that strong recommendation, but it's because
of lack of evidence. We still need to do a lot of research, especially in extremely low birth,
with infants, to try to figure out if probiotics truly work or not. The problem with necrotizing
enterocolitis is the low incidence, which is a good thing for our premature babies,
but it then puts the onus on multiple centers to come together and be able to study the disease
because one or two or even five centers are not going to have enough babies population
to be able to study it in adequate time. You need to have multiple different centers come together,
the NICHD will be a good place to start. But you might even need a bigger consortium
than that to be able to address these questions.
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
of the data if it can be multicenter and have different interventions. So
we are actually over time. But I let it go over time because this was such a great session. And
I really thank you all for participating and giving us the latest in what's going on in your
particular area. There's a lot of overlap, as you know, and I hope that this was fruitful for
everyone and really gets our brains thinking for future research opportunities. I'm going
to turn now to wrap up day number four. Today, we heard about our first session for today was about
early life malnutrition. With introductions to its definition, burden, epidemiology, and
screening. We then discussed early life research considerations with unique challenges in early
life research and malnutrition. This included a summary of the evidence on malnutrition in early
life with systematic reviews and guidelines, then the Academy of Nutrition and Dietetics in ASPEN.
Lastly, we just heard from this esteemed group of clinicians and
researchers where we heard about disease and condition-specific malnutrition in early life,
covering a multitude of clinical conditions and diseases that impact nutritional status
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.