>> GOOD MORNING, EVERYONE.
WELCOME BACK TO DAY TWO OF THE
186TH MEETING OF THE NICHD
ADVISORY COUNCIL.
I DID WANT TO POINT OUT
SOMETHING ABOUT THE MICROPHONES.
THESE MICROPHONES ARE DIFFERENT
FROM THE ONES WE WERE USING
YESTERDAY, SO NOW YOU WANT TO
SEE THE GREEN SIGNAL IF YOU'RE
SPEAKING, AND THEN TURN IT OFF
AFTER YOU'RE DONE.
TODAY WE'RE GOING TO HEAR A VERY
SPECIAL REPORT FROM A NEW
COUNCIL WORKING GROUP THAT WAS
FORMED RECENTLY, VERY RECENTLY,
IN FACT, IN AUGUST, ON
NECROTIZING ENTEROCOLITIS, ALSO
KNOWN AS INEQU NEC IN PREMATURE
INFANTS.
WE ESTABLISHED THIS GROUP LAST
MONTH IN RESPONSE TO A UNITED
STATES DEPARTMENT OF HEALTH AND
HUMAN SERVICES REQUEST TO
DEVELOP A SUMMARY OF THE STATE
OF THE SCIENCE AND
RECOMMENDATIONS FOR FUTURE AREAS
OF RESEARCH.
THE CO-CHAIRS, DR. YVONNE
MALDONADO AND DR. RAVI PATEL
WHO'S NOT A COUNCILMEMBER BUT A
NEONATOLOGIST AS YOU'LL HEAR
WILL PRESENT RESULTS OF THE
GROUP'S INTENSIVE WORK OVER THE
PAST SEVERAL WEEKS, AND WE'RE
VERY GRATEFUL TO THEM AND TO THE
NICHD STAFF AND ESPECIALLY TO
OUR DEPUTY DIRECTOR, DR. ALISON
CERNICH, WHO PULLED ALL THIS
TOGETHER IN A VERY SHORT TIME.
THE COUNCILMEMBERS KNOW
DR. BONNIE MALD MALDONADO WHO S
AS THE T OBY PROFESSOR OF GLOBAL
HEALTH AND INFECTIOUS DISEASES,
SENIOR ASSOCIATE DEAN, FACULTY
DEVELOPMENT AND DIVERSITY,
PROFESSOR OF PEDIATRICS AND
INFECTIOUS DISEASES AND
EPIDEMIOLOGY AND POPULATION
HEALTH.
DR. MALDONADO DIRECTS STANFORD'S
GLOBAL CHILD HEALTH PROGRAM AND
SERVES AS MEDICAL DIRECTOR OF
INFECTION PREVENTION AND CONTROL
AT THE LUCILE PACKARD CHILDREN'S
HOSPITAL.
SHE'S CURRENTLY SERVING AS
THE -- SHE DOESN'T HAVE ENOUGH
TO DO, SO NOW SHE'S CURRENTLY
SERVING AS THE INTERIM CHAIR OF
THE DEPARTMENT OF MEDICINE AND
LEADS A RESEARCH PROGRAM ON
EPIDEMIOLOGIC ASPECTS OF VIRAL
VACCINE DEVELOPMENT AND
PREVENTION OF PERINATAL HIV
TRANSMISSION.
ON VIDEO, WE'RE GRATEFUL
DR. PATEL FOR YOU JOINING US,
WE'VE GOT DR. RAVI PATEL, WHO'S
A NEONATOLOGIST AT CHILDREN'S
HEALTHCARE OF ATLANTA.
HE'S PROFESSOR OF PEDIATRICS AT
THE EMORY SCHOOL OF MEDICINE,
WHERE HE DIRECTS A RESEARCH
PROGRAM ON, NUMBER ONE,
NECROTIZING ENTEROCOLITIS,
INCLUDING ITS RELATIONSHIP WITH
NEONATAL TRANSFUSION PRACTICES,
NUMBER TWO, CAFFEINE THERAPY IN
PRETERM INFANTS.
DR. PATEL RECEIVED HIS
MEDICAL DEGREE FROM MEDICAL
COLLEGE OF GEORGIA AT AUGUSTA
UNIVERSITY, FOLLOWED BY A
MASTER'S OF SCIENCE IN CLINICAL
RESEARCH AND FELLOWSHIP TRAINING
IN NEONATOLOGY AT THE EMORY
UNIVERSITY SCHOOL OF MEDICINE.
SO THEY ARE GOING TO MAKE THEIR
PRESENTATIONS.
I'D ALSO LIKE TO ACKNOWLEDGE
DAVID ROICH, MEMBER OF OUR
ADVISORY COUNCIL, SERVED AS A
MEMBER OF THIS WORKING GROUP.
SO OVER TO DRS. MALDONADO AND
PATEL, WHO MOVED MOUNTAINS IN A
MATTER OF A FEW SHORT WEEKS, AND
WE ARE VERY GRATEFUL TO YOU.
>> THANK YOU, DIANE.
I WANT TO THANK MY CO-CHAIR, DRN
THIS AREA.
SO AS YOU
CAN YOU HEAR ME?
SO I WANT TO THANK MYCO-CHAIR,
DR. RA RAVI PATEL, AND ALSO WANY
EXPEDITED AND PUT THIS PROGRAM
TOGETHER VERY RAPIDLY, THEY DID
A REALLY AMAZING JOB AT PULLING
TOGETHER A LARGE GROUP OF
SUBJECT MATTER EXPERTS AND
YOU'LL SEE MORE ABOUT THAT.
CAN YOU HEAR ME?
IS THAT BETTER?
>> YES.
>> OKAY.
>> AS YOU CAN SEE HERE, THE
CHARGE -- IN AUGUST OF 2024, AT
THE REQUEST OF THE SECRETARY OF
THE DEPARTMENT OF HEALTH AND
HUMAN SERVICES, NACHHD CONVENED
A WORKING GROUP OF THE NATIONAL
ADVISORY COUNCIL OF CHILD HEALTH
AND HUMAN DEVELOPMENT.
SO THE CHARGE -- THE SPECIFIC
CHARGE TO THE WORKING GROUP
INCLUDED THE FOLLOWING: WE WERE
TO ASSESS THE SCIENTIFIC
EVIDENCE REGARDING THE ENTERAL
FEEDING PRACTICES IN PREMATURE
INFANTS AND FACTORS THAT MAY
PROTECT AGAINST OR INCREASE THE
RISK FOR NECROTIZING
ENTEROCOLITIS.
WE WERE ASKED TO IDENTIFY
IMPORTANT RESEARCH GAPS AND TO
MAKE RECOMMENDATIONS FOR
POTENTIAL FUTURE RESEARCH
DIRECTIONS.
NOW THE ACTUAL PROCESS ITSELF
WAS FAIRLY RAPID BUT IT WAS
QUITE THOROUGH CONSIDERING THE
TIME FRAME.
THE GROUP WAS COMPOSED OF
SUBJECT MATTERS IN NECROTIZING
ENTEROCOLITIS INCLUDING
LABORATORY SCIENTISTS AND
NEONATOLOGISTS, AS WELL AS
ADVOCACY LEADERS.
AS YOU CAN SEE HERE, THE GROUP
MET THREE TIMES OVER THE LAST
THREE WEEKS, ON AUGUST 15TH,
22ND AND 28TH.
AS PART OF THE STATE OF THE
SCIENCE ANALYSIS, NICHD
CONDUCTED AS WELL A PORTFOLIO
REVIEW, AND YOU CAN SEE THERE
FOR GRANTS ISSUED IN THE LAST
FIVE YEARS FROM FISCAL YEAR 2018
TO 2023, AND AS YOU CAN SEE,
THEY IDENTIFIED OVER
$101 MILLION IN NIH FUNDING
RELATED TO NECROTIZING
ENTEROCOLITIS.
I'M GOING TO CALL IT NEC FOR NOW
FORRESE OF SPEAKING.
INCLUDING OVER 340 UNIQUE
PROJECTS, 100 UNIQUE PIs AND
60 UNIQUE INSTITUTIONS, WITH 44%
OF THOSE FUNDS COMING FROM
NICHD, INCLUDING CLINICAL
TRIALS, 24% FROM NIDDK,
INCLUDING MANY MECHANISTIC
STUDIES, 40% OVERALL FOCUSED
PRIMARILY ON NEC VERSUS NEC AS
THE SECONDARY AIM OR OUT COME.
ABOUT THREE QUARTERS INCLUDED
RESEARCH PROJECT GRANTS, 10%
WERE SBIR/STTRs AND 9% WERE
COOPERATIVE AGREEMENTS.
SO THE NEC WORKING GROUP
ACTIVITIES INCLUDED THE
FOLLOWING.
WE REVIEWED THE STATE OF THE
SCIENCE FOR RISK FACTORS FOR
NEC, NUTRITIONAL SUPPORT FOR
PRETERM INFANTS, AND
ASSOCIATIONS BETWEEN FEEDING
PRACTICES AND RISK OR SEVERITY
OF NEC.
WE THEN DEVELOPED
RECOMMENDATIONS TO IMPROVE THE
EVIDENCE BASE.
SO AS MANY OF YOU MAY BE AWARE,
NECROTIZING ENTEROCOLITIS IS A
COMMON SERIOUS GASTROINTESTINAL
ILLNESS IN WHICH THE TISSUE
LINING IN THE INTESTINES BECOME
INFLAMED, DIE, AND CAN SLOUGH
OFF.
SYMPTOMS INCLUDE BLOATING OR
SWELLING OF THE ABDOMEN, BLOODY
STOOL, BILE IN THE STOMACH AND
FOOD NOT MOVING THROUGH THE
INTESTINES.
ONE OF THE LEADING CAUSES OF
ILLNESS AND DEATH IN PRETERM
INFANTS OCCURS PRIMARILY IN
INFANTS BORN BEFORE 28 WEEKS
GESTATIONAL AGE, WITH 1 INFANT
DYING ALMOST EVERY DAY FROM NEC
IN THE UNITED STATES, WITH
APPROXIMATELY 356 DEATHS
RECORDED IN 2022 ACCORDING TO
CDC DATA.
NEC CAN APPEAR SUDDENLY AT
PROGRESS QUICKLY IN INFANTS WHO
OTHERWISE MAY SEEM TO BE GETTING
HEHEALTHIER.
FACTORS THAT MAY BE ASSOCIATED
WITH RISK FOR NEC INCLUDE
MATERNAL/ANTENATAL FACTORS.
FACTORS RELATED TO MOTHERS'
PREGNANCY, HEALTH AND TREATMENT
AND THE INFANTS' CHARACTERISTICS
AND TREATMENT.
FACTORS THAT APPEAR TO INCREASE
RISK INCLUDE MATERNAL
PREECLAMPSIA AND HYPERTENSION,
AND VERY LOW BIRTH WEIGHT OR
SMALL FOR GESTATIONAL AGE
INFANTS.
AND FACTORS THAT APPEAR TO BE
PROTECTIVE INCLUDE MATERNAL
ANTENATAL CORTICOSTEROID USE AND
EXPOSURE TO HUMAN MILK.
SO THE FOLLOWING ASSESSMENT IS
OF THE QUALITY OF THE RESEARCH
EVIDENCE AND DOES NOT REPRESENT
CLINICAL GUIDANCE.
PLEASE REFER TO PRACTICE
ORGANIZATIONS FOR SPECIFIC
CLINICAL MANAGEMENT
RECOMMENDATIONS.
AND AT THIS TIME, I'M GOING TO
TURN OVER THE DISCUSSION TO MY
CO-CHAIR, DR. RAVI PATEL.
THANK YOU.
>> THANK YOU, GOOD MORNING TO
EVERYONE.
WE'RE GOING TO START WITH SOME
FOUNDATIONAL STARTING POINTS
THAT THE WORKING GROUP BEGAN
WITH, AND ACKNOWLEDGED THESE
CONCEPTS THAT THEY MUST BE FED
AS SOON AS MEDICALLY FEASIBLE,
AND THAT NUTRITION IS VITAL FOR
THEIR BRAIN AND FEEDING SHOULD
BE DONE BY WHATEVER MEANS IS
AVAILABLE.
HOWEVER, INTRAVENOUS FEEDING CAN
INCREASE THE RISK OF DEVELOPING
BLOODSTREAM INFORECASTS.
THE AMERICAN ACADEMY OF
PEDIATRICS RECOMMENDS VERY LOW
BIRTH WEIGHT INFANTS, LESS THAN
1500 GRAMS, RECEIVE HUMAN MILK,
PREFERABLY FROM THEIR OWN
PARENT.
IF THIS IS NOT AVAILABLE,
PASTEURIZED DONOR MU HAN MILE
BEING IS RECOMMENDED AND HUMAN
MILK OFTEN NEEDS TO BE FORTIFIED
TO MEET THEIR NUTRITIONAL NEEDS.
SO THESE WERE SOME OF THE KIND
OF SHARED STARTING POINTS THAT
THE WORKING GROUP BEGAN WITH.
IN TERMS OF INITIATION OF
ENTERAL FEEDING, THERE HAVE BEEN
A NUMBER OF STUDIES FOR MANY
YEARS.
WE STARTED BY LOOKING AT
DIFFERENT APPROACHES TO FEEDING
AND LOOKING AT HOW SOON TO START
FEET FEEDING OR HOW QUICKLY TO
INCREASE FEEDING AND CLINICAL
TRIALS WITH DIFFERENT APPROACHES
FOR INITIATION OR ADVANCEMENT OF
FEEDING HAVE SHOWN NO CLEAR
EFFECTS ON THE RISK OF
DEVELOPING NEC.
WHEN WE LOOKED AT BASE DIETS AND
RESEARCH AS PART OF THE WORKING
GROUP'S CHARGE ON WHICH BASE
DIET TO FIELD FEED EARLY PRETERM
INFANTS, WHEN THE PARENTS' OWN
MILK IS INSUFFICIENT OR
INAVAILABLE, GIVING DONOR MILK
CAN LOWER THE RISK OF NEC.
RECENT CLINICAL TRIALS HAVE
FOCUSED ON INFANTS LESS THAN
1500 GRAMS AT BIRTH OR LESS THAN
1,000 GRAMS AT BIRTH.
NOW HUMAN MILK SOMETIMES NEEDS
TO BE FORTIFIED TO MEET THE
NUTRITIONAL NEEDS OF PRETERM
INFANTS SO RESEARCH ON HOW TO
FORTIFY THE BASE DIET BY ADDING
SPECIFIC COMPONENTS HAS SHOWN
MIXED RESULTS ON WHETHER TO USE
HUMAN MILK OR BOVINE MILK-BASED
FORTIFIERS.
THESE CLINICAL TRIALS HAVE
TENDED TO BE SMALL WITH TWO FEW
CASES OF NEC TO DRAW FIRM
CONCLUSIONS.
BASED ON THE EXPERIENCE OF THE
EXPERTS IN THE WORKING GROUP AND
PRESENTATIONS, THE WORKING GROUP
IDENTIFIED SEVERAL LIMITATIONS
OF THE EXISTING EVIDENCE ON NEC.
ONE LIMITATION WAS THAT OTHER
INTESTINAL CONDITIONS MAY MIMIC
NEC, WHICH CAN LIMIT SOME OF THE
SURVEILLANCE EVIDENCE FOR NEC.
FOR EXAMPLE, ICD CODES MAY
INCLUDE BOTH NEC AND A SEPARATE
ENTITY IN THE SAME CODE.
ADDITIONALLY MUCH OF THE
EVIDENCE SHOWS ASSOCIATIONS NOT
DIRECT OR INDIRECT CAUSATION,
AND THERE NEEDS TO BE A LINK TO
THE ASSOCIATED CLINICAL RISK
FACTORS FOR DEVELOPMENT AND/OR
PROGRESSION OF NEC FOR
BIOLOGICAL PATHWAYS FOR THE
UNDER DTS LYING MECHANISMS.
SOME OF THE RISK FACTORS HAVE
NOT BEEN CONFIRMED IN CLINICAL
TRIALS.
FOR EXAMPLE, RED CELL
TRANSFUSION AND EMPIRIC USE OF
ANTIBIOTIC TREATMENT WITH
ONGOING CLINICAL TRIALS
CURRENTLY.
ADDITIONALLY, MANY OF THE
EXISTING STUDIES HAVE BEEN SMALL
IN SIZE WITH TOO FEW NEC CASES
TO DRAW FIRM CONCLUSIONS.
NOW THE WORKING GROUP WORKED TO
GENERATE RECOMMENDATIONS TO
COUNCIL SO I'M GOING TO GO OVER
SOME OF THE RECOMMENDATIONS,
THESE ARE RESEARCH
RECOMMENDATIONS FROM THE WORKING
GROUP.
WE HAVE THREE OVERARCHING
RECOMMENDATIONS.
THE FIRST AND OBVIOUSLY THE BEST
WAY TO PREVENT MOST NEC CASES IS
TO PREVENT PRETERM BIRTH.
AND, THEREFORE, THE GROUP
RECOMMENDED THE CONTINUATION AND
EXPANSION OF RESEARCH INTO WAYS
TO PREVENT PRETERM BIRTH.
SECOND, THE WORKING GROUP FELT
WE NEEDED TO DEVELOP A MORE
SPECIFIC DEFINITION OF NEC AND
THE SEVERITY OF NECK NEC TO IME
EPIDEMIOLOGICAL STUDIES AND
DETERMINE ELIGIBILITY FOR TRIALS
AND TREATMENTS.
THIRD WE NEED TO UNDERSTAND THE
RESEARCH AND INCORPORATE THE
PERSPECTIVES OF AFFECTED
FAMILIES, TO BETTER INFORM THEM
ABOUT THE RISK OF NEC AND HOW WE
CAN SUPPORT THEM IN THE
INTENSIVE CARE UNIT.
RELATED TO THE EPIDEMIOLOGY OF
NEC, THE WORKING GROUP
RECOMMENDED THAT WE IMPROVE THE
TRACKING AND REPORTING OF NEC
CASES AS WELL AS DEATHS FROM NEC
TO BETTER QAWBT GUY THE TOTAL
BURDEN OF DISEASE.
AND THAT THIS NEEDS TO BE DONE
USING ICD10 CODES AND BY
STRATIFICATION TO UNDERSTAND THE
IMPACT ON DIFFERENT -- OR MORE
MATURE INFANTS.
ADDITIONALLY THE WORKING
GROUP -- THAT THIS COULD ALLOW
IDENTIFICATION OF DIAGNOSTIC,
PROGNOSTIC, PREDICTIVE
SUSCEPTIBILITY AND/OR SURROGATE
MARKERS FOR NEC.
IN ADDITION, RESEARCH NEEDS TO
EXPLORE INNOVATIVE METHODS FOR
COLLECTING AND ANALYZING DATA.
FOR EXAMPLE, CAN DATA BE USED TO
IMPROVE STIMENTSDZ FOR FACTORS
THAT CONTRIBUTE MOST FOR THE
DEVELOPMENT OF NEC.
WHAT'S THE -- NUTRITIONAL
APPROACHES OR BASELINE
CHARACTERISTICS, AND HOW
ACCURATE ARE THE DIAGNOSIS RATES
FOR NEC.
WERE WHAT TREATMENTS HAVE THE
MOST BENEFICIAL OUTCOMES, AND
CAN ARTIFICIAL INTELLIGENCE OR
MACHINE LEARNING BE USED TO LOOK
AT ELECTRONIC HEALTH RECORDS OR
ROUTINELY COLLECTED DATA OF
BABIES WITH AND WITHOUT NEC TO
IMPROVE THE DIAGNOSTIC CRITERIA.
BIOMARKERS OR SURROGATE MEASURES
TO HELP STUDY NEC GIVEN ITS
RELATIVELY LOW INCIDENCE.
IN TERMS OF MECHANISMS, WE
RECOMMEND EXPANDING RESEARCH
SUPPORT INTO THE MECHANISMS OF
NEC DEVELOPMENT.
WE NEED BIOMARKERS TO IMPROVE
EARLY DIAGNOSIS OF NEC AND TO
ENABLE EARLIER TREATMENT OF NEC
BEFORE THE DISEASE PROGRESSES,
AND UNDERSTANDING AND KNOWING
MORE ABOUT THE UNDERLYING
MECHANISMS OF THE DISEASE WILL
HELP US TO IDENTIFY POTENTIAL
PREVENTION TREATMENT TARGETS,
INCLUDING KNOWING MORE ABOUT THE
GENETIC AND EPIGENETIC PATHWAYS
OF NEC.
WE NEED ADDITIONAL LABORATORY
AND ANIMAL MODELS TO BETTER
MATCH THE DISEASE COMPLEXITY IN
LABORATORY EXPERIMENTS.
THE FIELD HAS DEVELOPED NEC IN A
DISH AND NEC ON A CHIP MODELS
AND ANIMAL MODELS MAINLY IN
MICE, RATS AND PIGS HAVE BEEN
UTILIZED, AND GASTROINTESTINAL
ORGANORGANOID SYSTEMS ARE BEING
DEVELOPED AND USED.
THESE MODELS NEED TO BE EXPANDED
TO INCLUDE THE MULTIFACTORIAL
COMPLEXITIES OF THE DISEASE.
MOVING ON TO THE FACTORS
AFFECTING THE RISK OF NEC.
THE WORKING GROUP RECOMMENDED
EXPLORING EXPOSURES THAT MAY BE
POSITIVELY OR NEGATIVELY
ASSOCIATED WITH THE RISK OF NEC
DEVELOPMENT, SEVERITY,
MORTALITY.
THE EMPHASIS ON SPECIFIC
NUTRITIONAL COMPONENTS, THE USE
OF ANTENATAL AND POSTNATAL
ANTIBIOTICS AND BACTERIAL
DYSBIOSIS AND VIRUSES.
ADDITIONALLY EXPANDING RESEARCH
ON FEEDING PRACTICES THAT MAY
AFFECT THE RISK OF NEC, THIS MAY
INCLUDE WHEN TO START AND HOW
FAST TO INCREASE FEEDINGS IN
VERY LOW BIRTH WEIGHT HUMANS AND
WHAT COMPONENTS OF HUMAN MILK,
FOR THE FIRES AND/OR FORMULA ARE
MOST BENEFICIAL.
RELATED TO NUTRITIONAL SUPPORT,
THE WORKING GROUP RECOMMENDED
SUPPORTING RESEARCH TO IDENTIFY
THE OPTIMAL NUTRITIONAL NEEDS OF
PREMATURE INFANTS.
WHAT DO THESE INFANTS REALLY
NEED TO THRIVE?
INCREASING RESEARCH ON HOW TO
HELP PARENTS INCREASE THEIR MILK
PRODUCTION AND IMPROVE LACTATION
TECHNIQUES.
THIS RESEARCH WOULD BE
BENEFICIAL NOT ONLY TO PRETERM
BUT ALL PRETERM AND TERM INFANTS
BROADLY.
AND SUPPORTING RESEARCH THAT
DETERMINED HOW TO IMPROVE THE
SAFETY OF HUMAN MILK,
PARTICULARLY DONOR MILK BY
COLLECTING, PROCESSING, STORAGE
AND DISPENSING, AND TO BETTER
UNDERSTAND WHAT ARE THE
BIOACTIVE COMPONENTS OF HUMAN
MILK THAT MAIN BE PROTECTED FOR
NEC AND HOW CAN WE PRESERVE
THESE WHILE STILL PROTECTING
AGAINST INFECTIOUS RISKS THAT
MAY BE PRESENT IN DONATED MILK.
AND TO DEVELOP POINT OF CARE
DIAGNOSTICS TO MEASURE MILK
COMPONENTS IN NICUs AND DONOR
BANKS.
ALSO RESEARCH POTENTIAL
STANDARDS FOR DONOR MILK, FOR
EXAMPLE, POSTPARTUM DONATION
TIMING, MILK COMPOSITION,
APPROACHES TO POOLING OF DONOR
MILK, AND OPTIMIZATION OF DONOR
MILK FOR SPECIFIC POPULATION
SUCH AS VERY LOW BIRTH WEIGHT
INFANTS.
THE WORKING GROUP RECOMMENDS TO
THE SECRETARY THAT WE SUPPORT
LARGE INDEPENDENT COMPARATIVE
EFFECTIVENESS CLINICAL TRIALS OF
FEEDING PRACTICES AND NEC RISK.
BECAUSE NEC IS A RELATIVELY RARE
OUTCOME, WE NEED LARGE TRIALS TO
HAVE ENOUGH POWER TO
DEFINITIVELY ANSWER QUESTIONS
ABOUT FEEDING PRACTICES.
THIS WOULD INCLUDE EVALUATION OF
DIFFERENT TYPES OF FORTIFIERS
AND METHODS OF FORTIFICATION
THAT ARE USED TO REDUCE THE RISK
OF NEC.
AS WELL AS HOW AND WHEN TO
TRANSITION BABIES THAT ARE
RECEIVING DONOR MILK OFF OF
DONOR MILK WHEN THE TIME COMES.
AS PART OF THAT, WE NEED TO
DEVELOP INNOVATIVE CLINICAL
TRIALS THAT CAN TEST THE SAFETY
AND EFFICACY OF PROMISING
NUTRITIONAL ADDITIVES TO PREVENT
AND/OR TREAT NEC.
FOR EXAMPLE, PROBIOTICS THAT
SHOW PROMISE, WE NEED WAYS TO
DEVELOP AND MANUFACTURE THESE
PRODUCTS CONSISTENTLY SO THAT
THEY CAN BE TESTED AND EVALUATED
IN NEONATES.
WE NEED WAYS TO TEST MULTIPLE
COMPONENTS WORKING TOGETHER, WE
MAY FIND WE NEED ONE OR MORE
INGREDIENT TO OPTIMIZE
PREVENTION IN OUR TREATMENT OF
NEC.
FINALLY WE RECOMMEND EXPANDING
IMPLEMENTATION SCIENCE RESEARCH
TO REDUCE DISPARITIES IN ACCESS
TO DONOR MILK.
ARE THERE BARRIERS TO ACCESSING
DONOR MILK IN RURAL COMMUNITIES,
HOSPITALS OR IN MINORITY MOP
LAITIPOPULATIONS AND HOW CAN WE
BETTER SUPPORT RESEARCH AND HOW
CAN WE IMPROVE LACTATION SUPPORT
FOR NEW MOTHERS?
LASTLY, WE NEED SUPPORT ON
RESEARCH ON PARENT EDUCATION,
HOW CAN WE BEST INFORM PARENTS
IN THE NICU ABOUT OPTIMAL
FEEDING PRACTICES AND THE RISK
OF PRETERM CONDITIONS SUCH AS
NEC.
THE NEXT STEPS FOR THIS WORKING
GROUP ARE TO FINALIZE A REPORT
OF OUR FINDINGS AND
RECOMMENDATIONS AND SUBMIT THIS
REPORT TO THE SECRETARY OF
HEALTH AND HUMAN SERVICES BY
SEPTEMBER 16TH OF THIS YEAR.
I WANT TO FINISH BY REALLY
THANKING THE WORKING GROUP
MEMBERS FOR THEIR DEDICATION AND
WILLINGNESS TO COME TOGETHER ON
SUCH SHORT NOTICE, MY CO-CHAIR,
DR. MALDONADO AND MY COLLEAGUES
AT NIH AND NICHD ON MOVING THIS
PROCESS FORWARD.
SO THANK YOU TO ALL THAT HAVE
BEEN INVOLVED AND I THINK WE
HAVE SOME TIME FOR QUESTIONS AND
FEEDBACK.
>> THANK YOU, DRS. PATEL AND
MALDONADO FOR SUCH AN
INFORMATIVE REPORT.
NOW IS THE CHANCE FOR THE
COUNCIL TO PROVIDE FURTHER
DISCUSSION.
SO THE FLOOR IS OPEN, AND WE
REALLY ENCOURAGE YOUR QUESTIONS
AND ADDITIONAL THOUGHTS BECAUSE
WE WILL INCORPORATE THEM INTO
THE REPORT.
>> THAT WAS REALLY EXCELLENT.
THANK YOU BOTH AND THE
COMMITTEE.
BUT I HAD A QUESTION, MAYBE THIS
IS -- IT'S GREEN.
SO THIS IS -- PROBABLY REFLECTS
MY OWN IGNORANCE AND MAYBE SEEMS
SIMPLISTIC AND MAYBE IT'S BEEN
DONE, BUT IF HUMAN MILK IS BEST,
HAVE PEOPLE, WHETHER IT'S SOME
SEPARATION TECHNIQUE, HPLC,
WHATEVER IT IS, HAS SOMEBODY
LOOKED AT HUMAN MILK VERSUS
FORMULA TO SEE WHAT IT IS THAT'S
EITHER GOOD IN HUMAN MILK OR BAD
IN FORMULA SO THAT YOU CAN BE,
WHEN HUMAN MILK IS NOT
AVAILABLE, HAVE -- EXCUSE ME --
A BETTER ALTERNATIVE?
DO WE KNOW WHY HUMAN MILK IS
GOOD?
>> I CAN TAKE THAT.
THAT'S A GREAT QUESTION.
THERE WERE SPECIFIC
PRESENTATIONS BY -- AS PART OF
THIS WORKING GROUP SPECIFICALLY
ON THAT IMPORTANT QUESTION.
THERE ARE A NUMBER FACTORS THAT
WERE REVIEWED INCLUDING
OLIGOSACCHARIDES, GROWTH FACTOR,
A NUMBER OF OTHER COMPONENTS
THAT MAY EXPLAIN THE BENEFITS ON
INTESTINAL HEALTH, INTESTINAL
MATURATION, AND SO THOSE ARE
THINGS THAT HAVE BEEN LOOKED AT.
IT MAY BE THAT THE ABSENCE OF
THOSE FACTORS OR THE LACK OF
THOSE BENEFICIAL FACTORS MIGHT
INFLUENCE THE RISK OF KIND OF
SOME OF THE RISK THAT'S
ATTRIBUTABLE TO NEC AS IT
RELATES TO FEEDING PRACTICES.
I DON'T KNOW IF DR. MALDONADO
HAS ANYTHING SHE'D LIKE TO ADD.
>> WE HAD A SERIES OF EXPERTS
WHO DID COME IN AND TALK TO US
ABOUT ALL OF THE DIFFERENT
STUDIES AND COMPONENTS IN VITRO
AND IN VIVO LOOKING AT
INDIVIDUAL COMPONENTS BUT TAKEN
TOGETHER, THERE'S STILL A DERTH
OF INFORMATION ABOUT WHICH
INDIVIDUAL FACTORS ARE REALLY
GOOD AT PROMOTING GUT HEALTH,
NUTRITION, ET CETERA.
SO THERE ARE SOME INDIVIDUAL
COMPONENTS THAT DR. PATEL
MENTIONED AND OTHERS, BUT IT'S
NOT CLEAR WHICH ONES ARE BEST IN
HUMAN MILK AND WHAT'S MISSING IN
FORMULA MILK, OR IS FORMULA
ACTUALLY -- DOES FORMULA HAVE
COMPONENTS THAT ARE DETRIMENTAL.
SO THAT'S STILL NOT CLEAR.
>> BUT I DIDN'T SEE THAT AS A
RECOMMENDED RESEARCH AREA, WHICH
SEEMS LIKE THAT WOULD BE VERY
FRUITFUL, TO EITHER FIND OUT
WHAT'S BAD IN FORMULA OR FIND
OUT WHAT'S GOOD IN HUMAN MILK.
SEEMS LIKE THAT WOULD BE
SOMETHING THAT WOULD BE
IMPORTANT TO DO BECAUSE YOU MAY
END UP HAVING TO CREATE SOME
ALTERNATIVE BUT WITHOUT KNOWING
WHAT INGREDIENTS YOU NEED,
YOU'RE IN TROUBLE.
>> SO INDIRECTLY, ONE OF THE
AREAS THAT WE LOOKED AT IS
SUPPORTING RESEARCH TO IDENTIFY
THE OPTIMAL NUTRITIONAL NEEDS OF
PREMATURE INFANTS, AND THEN THE
OTHER AREA WAS LOOKING AT
SPECIFIC MODELS, FOR EXAMPLE,
NEC ON A CHIP OR NEC
ORGANOID-TYPE MODEL, SO TRYING
TO IDENTIFY WAYS TO PULL APART
THOSE PARTICULAR COMPONENTS.
>> THANK YOU.
SO WE HAVE A QUESTION ONLINE
FROM DR. BARKIN, THEN WE'LL GO
TO DRS. NEIL PERI --
>> THANK YOU, GOOD MORNING,
EVERYONE CH AND THANKS TO
DR. PATEL AND MALDONADO FOR THIS
IMPORTANT WORK AND THE LARGE
TEAM THAT SUPPORTED YOU.
JUST TWO COMMENTS, AND I THINK
APROPOS OF THE FIRST COMMENT, WE
KNOW THE MICROBIOME REALLY MAKES
A DIFFERENCE THERE, AND WE NOW
HAVE EMERGING TECHNOLOGY SO WE
CAN ASK AND ANSWER DIFFERENT
QUESTIONS TO TRY TO BETTER
ARTICULATE AND IDENTIFY WHAT
THOSE ELEMENTS ARE RELATED TO
THE MICROBIOME.
MY QUESTION IS, I'M REALLY
STRUCK BY THE FACT THAT ONLY 356
CHILDREN DIE A YEAR OF NEC, AND
EVERY DEATH IS A TRAGEDY, SO 356
IS STILL TOO LARGE OF A NUMBER.
AND YET IF YOU COMPARE THE
NUMBER OF NEONATES THAT HAVE ALL
OF THE RISK FACTORS THAT YOU ALL
AR TAXICAB LATED TO THOSE WHO
DON'T, AND THOSE WHO HAVE THE
SAME RISK FACTORS AND DON'T GET
NEC, VERSUS THOSE THAT DO, THERE
IS A LOT OF GOOD DATA TO BE
FOUND IN THOSE THAT DON'T GET
NEC.
I JUST WANTED TO UNDERSTAND IF
THE COMMITTEE PULLED THAT
FORWARD TO LOOK AT SORT OF THE
FOUND PILOTS, THE POSITIVE
OUTLIERS, TO LEARN FROM THEM AS
WELL.
THANK YOU.
>> WELL, I'LL LET DR. PATEL TAKE
THE FIRST ANSWER -- FIRST STEP
IN ANSWERING THAT AND THEN I
HAVE MY OWN COMMENTS.
>> THAT'S A GREAT POINT.
YOU KNOW, WE KNOW THAT BABIES
WHO, FOR EXAMPLE, RECEIVE ONLY
HUMAN MILK STILL ARE AT RISK OF
NEC AND WE DON DON'T UNDERSTANDY
THAT IS, SOME OF THE -- WHAT ARE
THE FACTORS THAT WE UNDERSTAND
THAT CAN EXPLAIN NEC AND MAYBE
THERE'S SOME RESIDUAL
UNCERTAINTY AND I THINK TRYING
TO UNDERSTAND WHY SO THAT EVEN
IN INFANTS WHO SEEMINGLY MAY NOT
HAVE SOME OF THOSE RISK FACTORS
THAT DEVELOP IT OR EXPERIENCE
THOSE, I THINK THAT THERE IS
TOONT TO BETTER UNDERSTAND THAT
BECAUSE IT IS RELATIVELY
UNCOMMON WHEN YOU THINK OF THE
VERY LOW BIRTH WEIGHT POPULATION
AND OVERALL INCIDENCE.
AND TO THE POINT ABOUT THE
MICROBIOME, THAT WAS IMPORTANT
PART, ONE OF THE RECOMMENDATIONS
ABOUT UNDERSTANDING DYSBIOSIS AS
WELL AS INFECTIONS HAVE BEEN
ASSOCIATED WITH KIND OF AN
IMBALANCE AND ABUNDANCE OF
SPECIFIC TYPES OF INTESTINAL
BACTERIA LIKE PROTEOBACTERIA
HAVE BEEN ASSOCIATED WITH THE
RISK AND IT'S STILL NOT CLEAR
WHAT'S DRIVING THAT CHANGE IN
THE MICROBIOME AND I THINK
OPPORTUNITIES TO BETTER
UNDERSTAND THAT.
>> SO DR. BARKIN, TO YOUR POINT,
WE'VE TALKED ABOUT THIS FROM AN
EPIDEMIOLOGIC PERSPECTIVE AS
WELL, SO GIVEN THE ALMOST
4 MILLION BIRTHS A YEAR, WE
THINK THAT THERE ARE ABOUT
ALMOST 60 FOW PREMATURE BIRTHS
AND AMONG THOSE, THE HIGHEST
RISKS ARE THE VERY LOW BIRTH
WEIGHT INFANTS AND THE QUESTION
WOULD BE THEN, THE MORTALITY
THAT YOU SEE REALLY AS YOU
MENTIONED IS THE TIP OF THE
ICEBERG, BUT ARE THERE -- OF
NEC, IS THERE A PROGRESSION OF
DISEASE AND WHAT HAPPENS TO
CHILDREN IN THE INTENSIVE CARE
NURSERY, FOR EXAMPLE, THAT ARE
PUT ON NEC PROPHYLAXIS OR NEC
PREVENTIVE MEASURES AND WHAT ARE
THOSE FACTORS AND HOW DO THEY
COMPARE TO, SAY, THE CHILDREN
WHO ULTIMATELY DEVELOP FULL
BLOWN DISEASE AND/OR DIE, AN
WHAT CAN WE -- HOW CAN WE PULL
OUT ANY OF THOSE VARIABLES AND
UNDERSTAND THAT.
SO THAT WAS ONE OF THE
RECOMMENDATIONS, IS
UNDERSTANDING MORE ABOUT THE
PREVALENCE OF DISEASE OVERALL,
LOOKING AT END POINTS, AND
FINALLY LOOKING AT, SAY, DEEP
DIVES INTO ELECTRONIC HEALTH
RECORDS TO TRY TO UNDERSTAND THE
BIGGER DENOMINATOR OF CHILDREN
WHO MAY HAVE SOME EARLIER
VERSIONS OF THIS AND HOW THEY
MIGHT BE DIFFERENT, FOR EXAMPLE,
FROM THE CHILDREN WHO ULTIMATELY
SUCCUMB TO THE DISEASE.
>> I REALLY LIKE THIS MOTION,
WHICH IS WE ARE PROBABLY
UNDERDIAGNOSING MANY DIFFERENT
PHENOTYPES OF NEC SO I THINK
THAT'S SUCH AN IMPORTANT
RECOMMENDATION.
I JUST WOULD ENCOURAGE THE
COMMITTEE TO PULL OUT AS A
RECOMMENDATION UNDERSTANDING
CHILDREN WHO HAVE THE SAME RISK
FACTORS BUT DON'T GO ON TO HAVE
NEC.
THAT'S A REALLY RICH GROUP TO
LEARN FROM AS WELL.
THANK YOU.
>> THANK YOU.
>> CAN YOU HEAR ME OKAY?
ACTUALLY, SHARI ACTUALLY ASKED
SOME OF THE QUESTIONS THAT I
HAD.
THE OTHER THING I GUESS I WOULD
ADD TO THAT IS, ONE OF THE
THINGS THAT YOU IDENTIFY AS A
PROTECTIVE FACTOR IS STEROIDS.
AND JUST UNDERSTANDING A LITTLE
BIT MORE ABOUT STEROIDS ACTUALLY
MAY MODIFY THE GUT MICROBIOME
AND WHY THAT'S PROTECTIVE,
BECAUSE ONE WOULD THINK THAT
STEROIDS, YOU KNOW, DO SPECIFIC
THINGS TO THE GUT MICROBIOME.
AND THIS IS A SEPARATE QUESTION
BUT DO YOU HAVE ANY LONG-TERM
HEALTH OUTCOMES FOR KIDS WHO DID
NOT QUITE GET FULL BLOWN NEC BUT
HAVE HAD SOME VERY SERIOUS
ILLNESS IN TERMS OF WHAT THEIR
HEALTH STATUS HAS BEEN AS
THEY'VE DEVELOPED?
ARE THEY AT INCREASED RISK FOR
OTHER DISEASES?
>> SO THE FIRST QUESTION WAS
ABOUT CORTICOSTEROID USE AND
RISK AND THE SECOND QUESTION WAS
CHILDREN WHO --
>> UNDERSTANDING THE LIFECOURSE
OF CHILDREN WHO DID NOT HAVE
FULL BLOWN NEC BUT THEY HAD BEEN
SICK AND HOSPITALIZED FOR A LONG
TIME, DO YOU KNOW WHETHER
THEY'RE AT ANY INCREASED RISK
FOR OTHER DISORDERS IN LIFE?
>> RAVI, DO YOU WANT TO TAKE THE
FIRST --
>> IN TERMS OF -- STEROID
ADMINISTRATION PARTICULARLY IN
THE EARLY PRETERM INFANTS HAS A
NUMBER OF EFFECTS BROADLY IN
TERMS OF IMPROVEMENT IN
SURVIVAL, IN TERMS OF PRODUCTION
IN A NUMBER OF OUTCOMES --
REDUCTION IN A NUMBER OF
OUTCOMES INCLUDING NEC.
IN TERMS OF LONG TERM OUTCOMES,
MOST OF THE STUDIES HAVE FOCUSED
ON TWO-YEAR OUTCOMES.
MOST HAVE BEEN FOCUSED ON THOSE
INFANTS WHO HAVE MORE
SIGNIFICANT DISEASE SUCH AS
SURGERY, REQUIRES SURGERY WHERE
WE KNOW THERE'S A SUBSTANTIAL
LONG TERM BURDEN OF DISEASE.
I THINK WE KNOW LESS ABOUT THE
MILDER CASES, THOSE INFANTS WHO
MIGHT BE MEDICALLY MANAGED AND
RECOVER WITHOUT NEED FOR
SURGERY, AND WHAT THE IMPACT OF
THAT IS, BUT WE'VE HEARD FROM
FAMILIES AND SURVIVORS WHO ARE
IN ADULTHOOD THAT DEVELOP NEC
AND SOME OF THE LONG-LASTING
EFFECTS OF THE DISEASE, BUT I
THINK AN AREA THAT WASN'T
SPECIFICALLY CALLED OUT BUT --
BECAUSE IT'S MAYBE LESS SPECIFIC
TO ENTERAL FEEDING BUT I THINK
AN IMPORTANT AREA FOR
UNDERSTANDING.
>> CAN YOU ALL HEAR ME OKAY?
THANK YOU FOR THE LOVELY
PRESENTATION.
AND FOR COVERING THIS IMPORTANT
TOPIC IN SUCH A SHORT TIME.
I WAS PARTICULARLY ENTHUSED THAT
YOU CALLED OUT PRETERM BIRTH AND
THAT ONE OF THE PRIMARY, I
THINK, WAS YOUR FIRST BULLET IN
A WAY TO PREVENT NEC WOULD BE TO
IDENTIFY STRATEGIES TO PREVENT
PRETERM BIRTH.
YOU KNOW, AS I THINK MANY FOLKS
KNOW, THE PRIMARY PREVENTIVE
STRATEGY WE'VE USED FOR OVER 20
YEARS IN MATERNAL FETAL MEDICINE
WAS RECENTLY PULLED FROM THE
MARKET, AND WITH NOTHING TO
REPLACE IT.
I THINK THERE'S AN URGENT NEED
FOR US TO IDENTIFY STRATEGIES TO
PREVENT PRETERM BIRTH.
IN FACT, COMING UP AT S THE
PRESIDENT'S WORKSHOP IS GOING TO
BE ON PRETERM BIRTH PREVENTION
BECAUSE THERE'S SEEMINGLY BEEN A
PAUSE IN OUR STRATEGIES AND A
PAUSE IN THE RESEARCH AND I
THINK WE NEED TO REINVIGORATE
OURSELVES TO REALLY FOCUS ON
PRETERM BIRTH AND HOW TO PREVENT
THAT.
SO THANK YOU FOR CALLING THAT
OUT.
IF THE WORKING GROUP CONTINUES
TO MOVE FORWARD I THINK IT WOULD
BE GREAT TO HAVE MAYBE MORE
REPRESENTATION OF MATERNAL FETAL
MEDICINE DOCS AND OBSTETRICIANS
TO KIND OF HELP WITH THAT JUST
BECAUSE IT WAS THE NUMBER ONE
STRATEGY YOU CALLED OUT.
>> I WAS ACTUALLY IMPRESSED BY
HOW MUCH CURRENT FUNDING IS
GOING INTO NEC.
AND I'M TRYING TO UNDERSTAND OF
THAT FUNDING HOW MUCH OF THAT
ACTUALLY MAY BE ADDRESSING SOME
OF THESE AREAS THAT YOU WANT TO
ENHANCE.
AND HOW MUCH IS REALLY LACKING.
>> THAT'S A GOOD POINT.
SO REGARDING THE $101 MILLION
THAT ARE CURRENTLY BEING
UTILIZED, WE DIDN'T HAVE A
CHANCE TO REALLY LOOK AT THE
PORTFOLIO, BUT THAT WOULD BE
SOMETHING THAT WE COULD TAKE A
LOOK AT BEFORE OUR FINAL REPORT
TO THE SECRETARY TO UNDERSTAND
WHAT AREAS ARE ALREADY BEING
ADDRESSED.
GREAT POINT.
>> AND ALSO, ARE THERE PREMATURE
COHORTS THAT COULD EASILY BE
PIVOTED TO TRY TO ENHANCE THEIR
FUNDING, YOU KNOW, TO DEVELOP AN
ARM THAT WOULD ADDRESS THESE
ISSUES ON NEC?
>> RAVI, DO YOU KNOW OF ANY
EXISTING PREMATURE COHORTS OR
COHORTS THAT ARE ENROLLING
INFANTS AT RISK?
>> THERE'S ONGOING WORK BY
GROUPS LOOKING AT AND DEVELOPING
A BIOREPOSITORY ACROSS A KIND OF
SELECT NUMBER OF CENTERS LED BY
ONE OF THE PRESENTERS OF THE
WORKING GROUP, MISTY GOOD.
THE NEONATAL RESEARCH NETWORK
ENROLLS A NUMBER OF COHORTS THAT
INVOLVE THE MOST IMMATURE
INFANTS AND COLLECTS
EPIDEMIOLOGIC DATA ROUTINELY
ACROSS 15 PARTICIPATING CENTERS,
THAT THAT'S PART OF NICHD ACROSS
THE U.S. THAT DO COLLECT IT, BUT
THAT COHORT IS, I THINK, MORE
BROAD AND COULD BE ENHANCED WITH
MORE SPECIFIC MEASURES IF THAT
WAS A PROCESS THAT WENT FORWARD.
>> THANK YOU FOR THIS GREAT
PRESENTATION AND THE WORK.
MY QUESTION IS RELATED TO THE
IMPACT OF CO-OCCURRING OTHER
MORBIDITIES THAT AFFECT PRETERM
INFANTS AND HOW THOSE ARE
TREATED, AND THE IMPACT OF THAT
ON NEC.
HOW WILL THAT BE INTEGRATED IN
YOUR RECOMMENDATIONS?
>> THAT'S A GREAT COMMENT AROUND
WHAT ARE COFACTORS AND WHAT DO
WE KNOW ABOUT THE COFACTORS.
ONE OF THE AREAS THAT WE
DISCUSSED, PARTICULARLY AT ONE
OF THE MEETINGS --
>> DR. MALDONADO, I THINK WE
LOST YOUR AUDIO.
>> CAN YOU HEAR ME, RAVI?
>> YEP.
>> OKAY.
SO JUST LOOKING AT ATTRIBUTABLE
FACTORS, SO GIVEN UNDERLYING
CONDITIONS, HOW MUCH DO THEY
WEIGH IN ON RISK FOR NEC.
AND I THINK THAT GOES BACK TO
DR. BARKIN'S QUESTION AS WELL
AROUND WHAT DO KIDS HAVE THAT
DEVELOP NEC VERSUS THOSE WHO
DON'T.
SO LOOKING MORE DEEPLY AT THAT.
I DON'T KNOW, RAVI, HAVE YOU IF
COMMENTS.
>> THERE HAS BEEN SOME WORK,
BABIES WHO DEVELOP PARTICULARLY
REQUIRE SURGERY FOR NEC HAVE A
HIGH RISK OF NEURODEVELOPMENTAL
IMPAIRMENT, RISK OF CEREBRAL
PALSY, AND THAT RISK MIGHT BE
INCREASING.
THERE HAS BEEN WORK AT
UNDERSTANDING THE MECHANISM OF
GUT INJURY RELATED TO BRAIN AND
SPECIFIC TARGETS THAT MIGHT BE
OPPORTUNITIES FOR THERAPY, AND
THERE ARE A COUPLE OF GROUPS
THAT ARE WORKING ON THOSE AREAS
TO TRY TO MINIMIZE SOME OF THE
NEC-ASSOCIATED MORBIDITY AMONG
THOSE WHO DEVELOP DISEASE.
OF COURSE THE BEST WAY TO
PREVENT THAT MORBIDITY IS TO
PREVENT NEC OR TO REDUCE THE
SEVERITY INITIALLY, BUT ONCE
BABIES DEVELOP IT OR REQUIRE
SURGERY, I THINK THERE'S EFFORT
TO TRY TO DETERMINE SOME OF THE
PATHWAYS THAT MIGHT BE
RESPONSIBLE FOR BRAIN INJURY AND
CEREBRAL PALSY FROM THE DEGREE
OF GUT INJURY AND INFLAMMATION
THAT GOES ON.
>> I HAD A QUESTION ACTUALLY, A
SCIENTIFIC QUESTION.
I WAS ABLE TO ATTEND TWO OF THE
THREE MEETINGS, SO MAYBE THIS
WAS DISCUSSED IN THE THIRD.
BUT AS WE KNOW, THERE ARE
MATERNAL CELLS IN BREAST MILK.
AND THEY PLAY A ROLE IN
EDUCATING THE INFANTS' IMMUNE
SYSTEM.
SO DID ANYBODY BRING UP THE
ISSUE OF CELLS IN BREAST MITT
BEING AND WHAT COULD BE THE
CONSEQUENCES OF GIVEN FOREIGN
CELLS IN BREAST MILK VIA DONOR
MILK?
>> I DON'T RECALL THAT THAT CAME
UP IN THE CONVERSATION.
DO YOU RECALL IT, RAVI, IF THAT
WAS ADDRESSED?
>> NO, THE CELLS SPECIFICALLY
WEREN'T TALKED ABOUT.
THERE WERE DISCUSSIONS FROM --
ON KIND OF A HUMAN MILK SIGH
EBBS ASPECT ABOUT SPECIFIC --
VARIABILITY IN SPECIFIC
COMPONENTS IN MILK, A HUMAN MILK
OLIGOSACCHARIDE THAT'S NOT
PRESENT IN ALL LACTATING PEOPLE,
AND THAT THAT AMOUNT OR
ABUNDANCE OF THAT SPECIFICALLY
COMPONENT MIGHT VARY IN, FOR
EXAMPLE, DONATED MILK, SO THAT
WAS DISCUSSED BUT NOT
SPECIFICALLY CELLS AND WHETHER
THAT'S AN IMPACT OR DIFFERENTIAL
BETWEEN DONATED MILK AND MILK
FROM A PARENT.
>> I WILL SAY ONE OF THE OTHER
AREAS -- SORRY.
ONE OF THE OTHER AREAS THAT WAS
REALLY -- THAT'S ALWAYS BEEN
REALLY STRIKING ABOUT NEC IS
THAT IT DOES HAVE A FAIRLY
TIME-LIMITED PERIOD OF RISK, SO
TO THE EXTENT THERE'S AN
EVOLVING GUT MAYBE WITH MATERNAL
CELLS, ON THEGENIC ISSUES AROUND
INFANT GUT IMMUNITY, ALL OF
THOSE FACTORS SEEM TO PLAY A
ROLE IN VERY CRITICAL EARLY
PERIOD IN THE PRETERM INFANT BUT
ALSO SOME CASES IN THE -- SO
THOSE ARE AREAS OF INTEREST AS
WELL.
>> I'M JUST TRYING TO
UNDERSTAND, AGAIN, A LITTLE BIT
MORE, BECAUSE I THINK THAT GOES
BACK TO MARCEL'S QUESTION ABOUT
UNDERSTANDING KIND OF WHAT'S IN
MATERNAL MILK VERSUS WHAT'S IN
FORMULA, AND JUST KIND OF TRYING
TO UNDERSTAND SOME OF THOSE
DIFFERENCES AS A WAY TO HELP US
IDENTIFY FACTORS.
WHEN USING DONOR MILK, DO YOU
SEE DIFFERENCES IN TERMS OF
BENEFIT?
SO IF YOU'RE USING FROZEN
SLOBODAN MILOSEVIMILKVERSUS FREE
DIFFERENCES?
>> I'LL LET RAVI EXPAND MORE BUT
SO IN STUDIES WHERE PARENTS'
MILK VERSUS DONOR MILK VERSUS
FORMULA, THERE IS A DIFFERENCE,
THERE'S A STATISTICALLY
SIGNIFICANT DIFFERENCE BETWEEN
GIVING DONOR MILK, SO THERE'S A
BENEFIT TO DONOR MILK COMPARED
TO FORMULA.
I DON'T KNOW, RAVI, IF YOU HAVE
ANY FURTHER --
>> THERE WERE SOME DISCUSSIONS
AND PRESENTATIONS ON KIND OF THE
DIFFERENCES BETWEEN PARENTS' OWN
MILK AND DONOR MILK BECAUSE
DONOR MILK GOES THROUGH
PASTEURIZATION THAT ALTERS SOME
OF THE FOR EXAMPLE SOME OF THE
MICROBIOME GETS CHANGED AND
THERE'S SOME OTHER COMPONENTS
THAT ARE ALTERED WHEREAS OTHERS
PRESERVE, THERE'S STILL A
PROTECTIVE EFFECT.
IN TERMS OF FREEZING AND
PROCESSING, THAT ALSO MIGHT HAVE
SOME ALTERATIONS.
THERE HAVEN'T -- YOU KNOW,
BECAUSE OUR GOAL IS FOR FEEDING
A PARENTS' ONLY MILK WHEN
POSSIBLE, THERE'S NOT BEEN ANY
CLINICAL COMPARATIVE TRIALS
AGAINST DONOR MILK AND PARENTS'
OWN MILK.
MOST HAVE BEEN IF THE PARENTS'
OWN MILK IS INSUFFICIENT.
THERE HAVE BEEN STUDIES
COMPARING PARENTS 18 OWN MILK
VERSUS DONOR MILK AND SOME
SUGGEST POTENTIAL DIFFERENCES
ALTHOUGH THERE'S LIMITED
RESEARCH IN THAT AREA OF HOW
THEY MIGHT IMPACT THAT, BUT
THERE ARE KNOWN CHANGES THAT
OCCUR WITH PASTEURIZATION OF
DONOR MILK COMPARED TO PARENTS'
OWN MILK THAT HAVE BEEN
EVALUATED AND STUDIED.
>> I WANTED TO COMMENT ON THE
SAME POINT.
IN THE CONVERSATIONS ON THE
CALLS, THERE WAS EVIDENCE
PRESENTED THAT RATES OF NEC WERE
APPROXIMATELY HALVED WHEN USING
HUMAN MILK VERSUS FORMULA.
SO THAT'S A MAJOR INSIGHT INTO,
I GUESS, PATHOGENESIS BY
IMPLICATION.
IT HAS PRACTICE IMPLICATIONS
ALTHOUGH THE GROUP WASN'T
SUPPOSED TO BE TALKING ABOUT
BEST PRACTICE.
I THINK WHAT HOPEFULLY WILL COME
ACROSS IN THE REPORT IS, HUMAN
MILK IS PREFERRED.
PARENTS' OWN MILK, I GUESS,
NUMBER ONE OR DONOR MILK.
DONOR MILK ACTUALLY SHOULD BE
INCREASED.
AND THE QUESTIONS SCIENTIFICALLY
ARE WHAT IS IT ABOUT HUMAN MILK
THAT IS PROTECTIVE, AND IT
REALLY HELPS TO FRAME WHERE I
THINK THE FURTHER RESEARCH COULD
GO, LOOKING FOR THOSE SPECIFIC
FACTORS, CELLULAR OR BIOCHEMICAL
IN EVEN MILK.
BUT IT WAS A VERY IMPRESSIVE SET
OF DATA WE HEARD FROM NICHD
NETWORK.
>> MAYBE AN OPPORTUNITY TO
UNDERSTAND HOW BEST TO PRESERVE
HUMAN MILK SO YOU HAVE OPTIMAL
EFFECTIVENESS AND BENEFIT.
>> THAT DISCUSSION CAME UP AS
WELL AND WE TRIED TO SHOWCASE IT
IN ONE OF THE SLIDES, BUT IT
BECAME CLEAR THAT THE
STANDARDIZING PROTOCOLS FOR
HANDLING STORAGE, ALL OF THE
OPERATIONAL ELEMENTS THAT
REQUIRE BANKING AND DISTRIBUTION
OF DONOR MILK ARE REALLY NOT
QUITE AS WELL DEVELOPED AS ONE
WOULD LIKE, AND SO THAT WAS AN
AREA OF OPPORTUNITY AS WELL.
>> SO WE'LL GO TO ENYA AND THEN
PEPE.
>> I JUST HAVE A SHORT FOLLOW-UP
QUESTION ON THAT, AND THAT IS
THE GESTATIONAL AGE AT THE TIME
OF DELIVERY, WHEN THE DONOR MILK
IS OBTAINED IS POTENTIALLY MUCH
MORE ADVANCED MOST OF THE TIME
THAN THE GESTATIONAL AGE OF THE
PARENT WHO PROVIDES THE MILK.
SO IS THAT TAKEN INTO ACCOUNT IN
STUDIES TO LOOK AT -- IS THERE A
DIFFERENCE WHEN YOU GET HUMAN
MILK AT 24, 25 OR BEFORE 28
WEEKS AND LATER ON?
>> RAVI, DO YOU WANT TO TAKE
THAT ONE?
>> YEAH, THAT WAS ONE OF THE
PRESENTATIONS THAT TOUCHED ON
THAT WHICH IS THE DONORS THAT
PROVIDE DONATED MILK VARY IN
GESTATIONAL AGE.
SOME ARE AFTER DELIVERY, INFANT
BORN AT TERM, SO THE NUTRITIONAL
CONTENT OF THAT MILK IS
DIFFERENT THAN, FOR EXAMPLE, THE
NUTRITIONAL CONTENT OF MILK FROM
A PARENT WHO MIGHT BE
IMMEDIATELY POSTPARTUM.
AND ALSO SOME OF THE COMPONENTS
DO DIFFER OVER THE WEEKS AND
MONTHS POSTPARTUM IN TERMS OF
THE CHARACTERISTICS OF THE DONOR
MILK.
THERE WAS SOME DISCUSSION ABOUT
BETTER UNDERSTANDING THAT TO
POTENTIALLY OPTIMIZE THE
DELIVERY OF DONOR MILK THAT
MIGHT MAXIMIZE ITS KIND OF
BENEFICIAL CONTENT OF SPECIFIC
COMPONENTS BY SELECTION OF
DONORS WITHIN, FOR EXAMPLE, A
CERTAIN AMOUNT OF MONTHS
POSTPARTUM THAT MIGHT ALLOW
THAT, ALTHOUGH THAT'S AN AREA
WHERE THERE STILL NEEDS MORE
DATA TO KIND OF GUIDE THAT
ASPECT, BUT THERE ARE
DIFFERENCES IN DONORS AND THOSE
DONORS, MANY OF THEM ARE BORN
AT -- DELIVERED AT TERM JETION
TAIGESTATION SO THE CHARACTERISS
OF THAT MILK IS GOING TO BE
DIFFERENT THAN A BABY THAT'S
BORN, FOR EXAMPLE, AT 24 WEEKS
GESTATION.
>> THE OTHER ISSUE THAT CAME UP
IS THE FACT THAT THERE ARE
REALLY NO POINT OF CARE
DIAGNOSTICS FOR DETERMINING THE
COMPOSITION OF MILK WHEN IT'S
GIVEN, SO AGAIN, WHETHER OR NOT
YOU CAN EVEN TRY TO MATCH
CHRONOLOGICAL AND GESTATIONAL
AGE EVEN BEYOND THAT IS JUST
UNDERSTANDING THE CONTENT EVEN
AT THE SAME CHRONOLOGICAL OR
GESTATIONAL AGE, THERE'S A
GOOD DEGREE OF VARIABILITY AMONG
DONORS AND IT WOULD BE -- THE
DIFFERENT MEMBERS OF THE GROUP
WORKING GROUP THOUGHT IT WOULD
BE HELPFUL TO HAVE RAPID
DIAGNOSTICS TO BE ABLE TO
DETERMINE THAT CONTENT AND THE
COMPOSITION.
>> WE'LL TAKE ONE LAST QUESTION.
>> THANK YOU.
SO ONE OF THE RECOMMENDATIONS
WAS ON HARNESSING OPEN AI AND
MACHINE LEARNING AND THAT MAKES
SENSE GIVEN THE NUMBER OF
STUDIES, BUT DO YOU THINK WHAT'S
READINESS OF THE DATASETS?
DO YOU THINK WE NEED SOME
HARMONIZING OR -- THEY NEED
INFRASTRUCTURE THAT NEEDS TO BE
DONE IF BEFORE WE GO THERE?
MY SECOND QUESTION IS, HOW WOULD
YOU PRIORITIZE AIL THESE
REPRESENTATIONS, OR DO WE NEED
TO?
>> GREAT POINT.
I DON'T KNOW, RAVI, IF YOU
HAVE -- WE TALKED A BIT AND I
KNOW WITH DAVID ROWCH AS WELL WE
TALKED ABOUT THE AVAILABILITY OF
ELECTRONIC HEALTH RECORDS
DATASETS AND I THINK MORE AND
MORE THEY ARE BECOMING
AVAILABLE, I DON'T KNOW
SPECIFICALLY FOR THIS PARTICULAR
INDICATION BUT CAPACITY IS BEING
BUILT AT A NUMBER OF
INSTITUTIONS.
THE QUESTION WOULD BE, AGAIN,
THE ABILITY TO HAVE THE
COMPUTING POWER TO BE ABLE TO
STORE THAT --
>> I THINK THERE'S OPPORTUNITY,
THE CHALLENGE FOR A LOT OF THE
MACHINE LEARNING AND THE AI
MODELS IS TRAINING WHAT'S THE
GOLD STANDARD DEFINITION AND
THAT'S A LIMITATION OF KIND OF
WHAT YOU USE AS THE GOLD
STANDARD DEFINITION TO LEARN ON
THOSE MODELS.
THE OTHER CHALLENGE IS NEC CAN
BE AN ACUTE DISEASE THAT OFTEN
IS VERY SUDDEN ONSET, SO THE
KIND OF DOCUMENTATION FOR
CLINICAL SYMPTOMATOLOGY, TIME OF
ONSET MAY NOT BE CONSISTENT, AND
SO SOME OF THE FEATURES THAT
MIGHT BE RECORDED ON A DAILY
BASIS ON FOR EXAMPLE A DAILY
NOTE MAY NOT CAPTURE THE
GRANULARITY THAT MIGHT BE NEEDED
AT TIME OF ONSET, WHICH CAN BE
VERY ACUTE AND PROGRESS QUICKLY,
SO THERE ARE OTHER DATA IN THE
ELECTRONIC HEALTH RECORD THAT
CAN BE EXTRACTED BUT SOME OF THE
CLINICAL DATA IS LIMITED IN THAT
REGARD.
>> YOU ALSO MENTIONED
PRIORITIZING.
WE COULDN'T GET TO THAT POINT
YET.
I DON'T KNOW IF IN THE NEXT WEEK
WE'LL BE ABLE TO DO THAT.
IT'S A PRETTY BROAD ARRAY OF
QUESTIONS, BUT I THINK WE'LL
HAVE TO THINK ABOUT MAYBE A
SECOND SET OF MEETINGS TO TRY TO
THINK ABOUT PRIORITIZATION, BUT
I THINK THIS WAS AT LEAST A
PRELIMINARY STAB AT SOME OF THE
HIGH LEVEL QUESTIONS THAT
HAVEN'T REALLY BEEN ADDRESSED.
>> OKAY.
IN THE INTEREST OF TIME,
REGRETFULLY I HAVE TO LIMIT THE
DISCUSSION, AND AGAIN, I WANT TO
THANK EVERYONE INVOLVED AND THE
COUNCILMEMBERS FOR THEIR VERY
INTERESTING AND RELEVANT
QUESTIONS.
WE ARE NOW GOING TO ASK FOR A
MOTION FOR APPROVAL OF THE
WORKING GROUP'S REPORT.
WE'RE GOING TO DO DOUBLE DUTY
AND ASK YOU TO ENDORSE THE
RECOMMENDATIONS FOR FUTURE
RESEARCH.
SO WE'LL USE IT ALSO AS AN OPEN
CLEARANCE OF THE CONCEPT.
SO WE NEED A MOTION TO APPROVE
THE WORKING GROUP'S REPORT AND
AT THE SAME TIME, PROVIDE
CONCEPT CLEARANCE.
SO DOES SOMEONE WANT TO PROVIDE
A MOTION?
>> SO MOVED.
>> THANK YOU, MARCEL.
IS THERE A SECONDER?
>> SECOND.
>> THANK YOU, ENYA.
NOW WE'RE GOING TO ASK YOU TO
VOTE BY RAISING YOUR HANDS AND
THOSE -- I SEE DR. BARKIN, I
DON'T KNOW IF DR. --
>> PROFESSOR BROOKS AND
DR. FAIR.
>> OKAY, THANK YOU VERY MUCH.
SO THE WORKING GROUP'S REPORT IS
APPROVED.
AGAIN, WE THANK YOU FOR YOUR
OUTSTANDING WORK AT THIS TIME,
THE OPEN SESSION IS GOING TO
CONCLUDE.
WE ARE GOING TO TAKE A 15-MINUTE
BREAK NOW TO SWITCH OVER TO THE
CLOSED SESSION.
I REALIZE SOME OF YOU HAVE TIGHT
FLIGHT CONNECTIONS, SO WE MAY
NEED TO SACRIFICE THE BREAK
LATER ON IN THE MEETING.
I'M VERY AWARE OF THE FACT THAT
PEOPLE NEED TO GET TO THE
AIRPORT.
SO LET'S TAKE A BREAK NOWM, ANDD
WE WILL RESUME AT 10:00.