S102- Neonatal Nutrition: Maximizing the Nutrition of the NICU Grad

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1 S102- Neonatal Nutrition: Maximizing the Nutrition of the NICU Grad David H Adamkin, MD Professor of Pediatrics Director, Division of Neonatology Director of Nutritional Research Rounsavall Chair of Neonatal Medicine Co-Director of Neonatal Fellowship University of Louisville Louisville, Kentucky

2 Disclosure of Relevant Relationship Dr. Adamkin (or spouse/partner) has disclosed the following commercial industry affiliation and/or financial relationship in the past 12 months: Company/Organizati on Individual with COI All COIs have been resolved prior to this presentation Dr. Adamkin will support this presentation and clinical recommendations with the best available evidence from medical literature. Dr. Adamkin does not intend to discuss an unapproved/investigative use of a commercial product/device in this presentation. Role Medolac Self Consulting Fee, Ownership interest

3 Neonatal Nutrition:Maximizing the Nutrition of the NICU Grad 50 th Pediatric Postgraduate Course: Perspectives in Pediatrics Miami, Florida March 2015 David H Adamkin Professor Of Pediatrics Director of Division of Neonatology Director of Nutritional Research Rounsavall Chair of Neonatal Medicine Co-Director of Neonatal Fellowship University of Louisville September 2014

4 Disclosures Consultant and Investor in Medolac Laboratories I will not discuss any off-label use and/or investigational use in my presentation I have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and / or provider(s) of commercial services discussed in thie CME activity

5 VLBW

6 Asymmetric EUGR with head sparing POSTNATAL GROWTH FAILURE 6

7 Protein Intake gm/kg/day The Cumulative Protein Deficit and 4.5 Growth Failure* Reference Requirement* Protein Deficit Infants <750 gm 2 Infants gm Typical Protein Intake Week 1 Week 2 Weeks 3-12 Weeks after preterm birth *Graphic adapted from Ernst 2003 with reference requirement based on intrauterine protein accretion rate from Ziegler 1994 Ernst J of Peri 2003

8 TOO FAT? TOO THIN?

9 Preterm Birth and Body Equivalent Age (TEA): A Systematic Review and Meta Analysis 8 studies N=733 30wks gest, 1180gms BW. Term Controls 39.6wks 3410gms Preterm@TEA vs Term Mean Diff 1) Increase % body fat 3% 2) Less Fat Mass 50g 3) Much less Fat Free Mass 460g 4) HC -1.03cm Less Lean with more similar Fat. Significant constraint on acquisition of lean tissue Johnson et al Peds 2012

10 Altered Adiposity After Extremely Preterm Birth n = 38 n = 29 <32weeks Term whole body MR adipose tissue HYPOTHESIS: Quantity and distribution of adipose tissue are markers of morbidity risk Third trimester is a period of rapid adipose tissue deposition Preterm infants may be at risk of altered adiposity Uthaya et al Ped Res 2005

11 BODY COMPOSITION FETUS vs EXTREME PRETERM POSTNATAL reference fetus Wt Water Protein Lipid Glycogen Energy Weeks (g) (%) (%) (%) (g) (kcal) (1gm) (13gm) (38gm) (386gm) mo Reference fetus: Ziegler, Growth, 1976.

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13 Altered Adiposity Extremely RESULTS Preterm Birth 1) PT infants at term were significantly lighter and shorter, but no difference in HC vs Term born infants 2) PT had highly significant decrease in subcutaneous adipose tissue and significantly increased intraabdominal adipose tissue 3) Illness severity (days of level 1 and 2 ICU days, British Perinatal Med, criteria) was the principal determinant of increased intraabdominal adiposity. Growth restriction with head sparing and preferential visceral fat deposition short and fat Uthaya, Ped Res 2005

14 Growth in VLBW Infants Is Associated With: Cummulative losses by hospital discharge of protein and energy Reduced body stores of nutrients (eg, Fe, DHA ARA) Reduced bone density Altered Adiposity ( short and fat?) Embleton Ped 2001

15 Post Discharge Period Programming Growth and Improving Outcomes First year of life provides an important opportunity for human somatic and brain growth to compensate for earlier deprivation Opportunity to promote lean body mass Catch up growth to enhance neurodevelopment Protein is the Key!!!! Hack M, et al. Am J Obstet Gyn. 1982;143:

16 RANGE of PROTEIN INTAKES g protein/kg/d at150 ml/kg/d Human milk provides ~1.5 g/kg/d of protein 4.0 Requirement g/k/d Term formula Nutrient-enriched formula 22 cal Preterm formula 24 High-protein preterm formula 24 Adamkin J of Peri

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18 Not just a 22 calorie formula Please note: All values are per 100 calories

19 Nutrient-Enriched Formula or Post-Discharge Formula (PDF) Contains Predominantly an increase in protein with extra energy Extra calcium, phosphorus, and zinc Additional vitamins and trace elements Post-Discharge Strategy Replenish accumulated nutrient deficiencies Catch-up growth Promote lean body mass Bone Mineralization Enhance Neurodevelopment 21

20 Weight (g) Length (cm) Preterm Infants Gained More Weight and Length When Fed Post Discharge Formula the First Year P= P= P= months 12 months 55 6 months Postdischarge formula. (n=67) Standard-term formula (n=57) Carver JD, et al. Pediatrics. 2001;107:

21 Head Circumference (cm) Preterm Infants Larger HC on PDF <1250g PDF 30 0 Term *Weighing less than 1250 g. HC = head circumference Carver JD, et al. Pediatrics. 2001;107: Months Post Term 23

22 mg/cm Nutrient Enriched Formulas Increased Bone Mineral Content to 9 mo CA * * Enriched Formula Term Formula 0 Discharge 3 Months 9 Months *Enriched versus term 24 Bishop NJ, et al. Arch Dis Child. 1993;68:

23 Nutrient-Enriched Formula to 12 Months Corrected Age (CA) Improved Proportional Growth ( Summary of many studies) Gained more weight through 1 and 2 mo CA Longer at 3 mo CA Early <1250 g at birth Weighed more at 6 and 12 mo CA Longer at 6 mo CA Larger HC at term and 1, 3, 6, 12 mo CA VLBW Appeared to be of particular benefit for growth of infants <1250 g and male infants Male Compared with the infants fed term formula, those fed the nutrientenriched formula consumed Less formula More protein Similar kcal Carver JD, et al. Pediatrics 2001;107:

24 Differences in mean weight between male infants assigned to a preterm formula (even higher protein) and males assigned to a standard term formula from discharge to 6 months of age Age Critical Growth Epochs Difference in Weight, g Birth -9 Enrollment 118 Term weeks weeks weeks months months 700 Increased Lean Body Mass 6 months months to 48 weeks 18 months 1000 Cooke RJ, et al. J Pediatr

25 Growth and Fat Free Mass Gain in Infants After Discharge RCT Term Formula (TF) vs Post Discharge Formula (PDF) Human milk < 20% of diet Protein 2.0g/dl vs 1.4 ; P/E 2.6 vs 2.0 Diets through 6 mos Corrected age (CA) Body Composition Air Displacement Plethysmography Anthropometrics Term,1,3,6,12 mos CA Roggerro et al Peds

26 RESULTS Protein Intakes greater but less volume consumed with Post Discharge Formula. No Differences in weight or length gain despite more protein All AGA demonstrated Catch Up growth Mean HC larger for AGA infants fed Post Discharge Formula 6/12 mos Fat Free Mass 6 mos for AGA fed (LEAN) 29 Roggerro et al Peds 2012

27 Potential Benefits of Nutrient Enriched Formula Post Discharge for AGA Preterm Infants INCREASED HEAD CIRCUMFERENCE GROWTH INCREASED FAT FREE MASS GAIN Increased Brain Growth and Lean Body Mass.. 30

28 Growth: Catch-Up Growth and Cognition

29 Brain Growth and Neurodevelopment Neuro/Intellectual Function at School Age With Subnormal Head Circumference at 8 Months Total Population Neurologically Intact Condition (criteria) (8 years) HC (nl) (216) HC (subnl) (33) 13% RR HC (nl) (199) HC (subnl) (26) RR Neurological Impairment (major neurological abnormality) ~8% 21% 2.69* Low IQ IQ <70 IQ <85 3% 27% 24% 52% % 26% 12% 46% Limited Academic Skills (read/math/spell std score <80) * P<.05 by chi square test P<.01 31% 56% % 54% 1.88 HC subnormal; 1.1 versus 1.2 kg, higher neonatal risk scores ( ) Hack. N Eng J Med

30 Subnormal HC in VLBW Infants at 8 Months of Age Predicted Poorer Outcomes at 8 Years of Age N=249 Neurological Impairment Lower IQ Limited Academic Skills Hack. N Eng J Med. 1991

31 Summary of Neurodevelopmental Outcomes in appropriate-for-gestational-age (AGA) and smallfor-gestaional-age (SGA) Infants who attained adequate vs delayed extrauterine growth* Neurodevelopmental Adequate Delayed extrauterine Outcomes in subgroups catch-up growth growth (EUGR) Of VLBW premature infants AGA good neurodevelopmental decreased mental and (28wks/1050g) outcome motor function SGA good neurodevelopmental decreased motor function (31wks/950g) outcome (similar to AGA with adequate catch-up growth Catch - down Catch - up VLBW, very low birthweight predominantly SSGA *9 and 24 months Latal-Hajnal et al J pediatr 2003;143(2):163-70

32 Treatment Recommendations Formula-fed preterm infants should be fed nutrient-enriched discharge formula in the first year of life to replenish nutrient deficits and promote growth Duration of use varies depending on Clinical history Degree of postnatal growth failure Bone health Proportional growth Growth in breast-fed premature infants should be closely monitored Employ individual feeding strategies as needed to optimize proportional growth

33 Post-discharge Nutrition Choices with Human Milk Human milk Alone Supplemental Post- Discharge Formula (4 6 feeds per day) Liquid Fortifier Reasons for Fortification 1) Postnatal Growth Failure < 10 th percentile 2) Metabolic Bone Disease (serum phosphorous < 4.3)

34 Head Circumference (cm) Fortified Human Milk Improves Head Circumference in the First Year of Life (<1250g) Head Circumference (cm) 50 Group x time P= ± ± ± ± ± ± ± 1.8 Fortified human milk Human milk Study Day 1 4 mo CA 6 mo CA 12 mo CA Aimone A, et al. J Pediatr Gastroenterol Nutr. 2009;49:

35 TAKE HOME POINTS For Your Practice VLBW infants maybe be growth restricted at discharge and nearly always have accumulated nutrient deficiencies when they are discharged Using growth curves for these infants to guide you promote catch-up growth that is characterized by increasing head circumference growth and lean body mass (WT/L ratio) Using Post Discharge Formulas or Human Milk with supplementation for those VLBW infants with growth failure provides extra protein, energy, calcium, phosphorous and vitamins to replenish accumulated deficiencies and promote catch-up growth. 43