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High-Risk Newborns and Nutrition Jatinder Bhatia, MD, FAAP

High-Risk Newborns and Nutrition Jatinder Bhatia, MD, FAAP Professor and Chief, Division of Neonatology Vice Chair, Clinical Research Department of Pediatrics Medical College of Georgia Augusta University Augusta, GA. Disclaimer.

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High-Risk Newborns and Nutrition Jatinder Bhatia, MD, FAAP

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  1. High-Risk Newbornsand Nutrition Jatinder Bhatia, MD, FAAP Professor and Chief, Division of Neonatology Vice Chair, Clinical Research Department of Pediatrics Medical College of Georgia Augusta University Augusta, GA

  2. Disclaimer • Statements and opinions expressed are those of the authors and not necessarily those of the American Academy of Pediatrics. • Mead Johnson sponsors programs such as this to give healthcare professionals access to scientific and educational information provided by experts. The presenter has complete and independent control over the planning and content of the presentation, and is not receiving any compensation from Mead Johnson for this presentation. The presenter’s comments and opinions are not necessarily those of Mead Johnson. In the event that the presentation contains statements about uses of drugs that are not within the drugs' approved indications, Mead Johnson does not promote the use of any drug for indications outside the FDA-approved product label.

  3. Objectives • At the end of the presentation participants will understand: • Global incidence of prematurity and morbidity and mortality • Long-term consequences of prematurity and low birthweight • Rationale for aggressive early and sustained nutritional goals • Choice of feeding • Post-discharge nutrition

  4. Title • Text

  5. Preterm Birth • Every year an estimated 15 million babies are born premature (<37 completed weeks of gestation), and this number is rising. • Preterm birth complications are a leading cause of death among children <5 years of age, and was responsible for nearly 1 million deaths in 2013. • Three-quarters of these deaths could have been prevented with current, cost effective interventions. • Across 184 countries, the rate of preterm birth ranges from 5% to 18% of babies born.

  6. Preterm birth is a risk factor for neonatal and postneonatal deaths. At least 50% of all neonatal deaths are preterm. Blencowe H, Cousens S, Chou D, et al. Born too soon: the global epidemiology of 15 million preterm births. Reprod Health. 2013;10(Suppl 1):S2

  7. ACN/SCN,WHO: IFPRI, 1992 Intergenerational Cycle of Growth Failure United Nations Administrative Committee on Coordination (ACC)/Subcommittee on Nutrition (SCN). 2nd Report on the World Nutrition Situation – Volume I: Global and Regional Results. Geneva, Switzerland: United Nations ACC/SCN; 1992

  8. Goals and Requirements • Optimal nutritional goal is to duplicate normal in utero fetal growth rates • Should have no negative impact on growth and development • Achieve maximal appropriate growth without adverse effects • In reality, extra uterine growth restriction is almost universal in small premature infants • Growth restriction or failure associated with adverse outcomes: neurocognitive effects and chronic lung disease • Accelerated growth associated with insulin resistance and cardiovascular disease Kleinman RE, Greer FR, eds. Pediatric Nutrition. 7th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2014; Ehrenkranz RA, Younes N, Lemons JA, et al. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics. 1999;104(2 Pt 1):280–289; SinghalA, Fewtrell M, Cole TJ, Lucas A. Low nutrient intake and early growth for later insulin resistance in adolescents born preterm. Lancet. 2003;361(9363):1089–1097; Singhal A, Cole TJ, Lucas A. Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials. Lancet. 2001;357(9254):413–419; and Singhal A, Lucas A. Early origins of cardiovascular disease: is there a unifying hypothesis? Lancet. 2004;363(9421):1642–1645

  9. Introduction • Over the past few decades, nutritional therapy for premature infants has improved • Human milk fortifiers and newer formulas have been developed • Early diet in preterm infants has both short- and long-term adverse consequences • Extraruterine growth restriction • Adult-onset hypertension, glucose intolerance, and obesity • Neurodevelopmental sequelae Lucas A, Gore SM, Cole TJ, et al. Multicentre trial on feeding low birthweight infants: effects of diet on early growth. Arch Dis Child. 1984;59(8):722–730; Singhal A, Cole TJ, Lucas A. Early nutrition in preterm infants and later blood pressure: two cohorts after randomised trials. Lancet. 2001;357(9254):413–419; and Lucas A, Morley R, Cole TJ. Randomised trial of early diet in preterm babies and later intelligence quotient. BMJ. 1998;317(7171):1481–1487

  10. Data from the United Kingdom on Percentage of Infants <1 kg with Weight <10th Percentile Fewtrell MS. Growth and nutrition after discharge. Sem Perinatol. 2003;8(2):169–176

  11. Extremely-Low-Birthweight Infants Grow Poorly Average body weight compared to intrauterine growth Ehrenkranz RA, Younes N, Lemons JA, et al. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics. 1999;104(2 Pt 1):280–289

  12. Weight Gain Patterns at 23-25 Weeks Fenton TR, Nasser R, Eliasziw M, Kim JH, Blan D, Sauve R. Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant. BMC Pediatr. 2013;13:92

  13. Weight Gain Velocity of Preterm Infants with the Reference Fetus and Infant Fenton TR, Nasser R, Eliasziw M, Kim JH, Blan D, Sauve R. Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant. BMC Pediatr. 2013;13:92

  14. Rationale for Aggressive Nutrition • Last Trimester Active amino acid transport Calcium, iron, magnesium, lipid transfer present; docosahexaenoic acid (DHA) transported Glucose, facilitated diffusion Higher energy expenditure Inadequate protein and energy intake Delivery of premature infant Negative Nitrogen Balance Adapted from Bhatia J. Human milk and the premature infant. Ann NutrMetab. 2013;62(Suppl 3):8–14

  15. Prevention of Growth Restriction Adapted from Adamkin DH. Feeding the Preterm Infant. In: Bhatia J, ed. Perinatal Nutrition: Optimizing Infant Health and Development. New York, NY: Marcel Dekker; 2005:165–190

  16. Principles of Early Nutrition • Early total parenteral nutrition • Amino acids 3.5 g/kg/d • Lipids 1-2 g/kg/d • Carbohydrate (glucose): as per clinical use • If the gut works, use it • Colostrum swabbing • Minimal enteral feeding • Feeding protocols • Mother’s own milk • Donor human milk • Appropriate fortification • Reduce the time to return to birthweight • Reduces extra uterine growth restriction

  17. Goals • Minimize time to regain birthweight • Suggested fluid, protein, and energy intakes • Fluid: 135-150 mL/kg/d • Protein: 3.5-4 g/kg/d (4-4.5 g/kg <1000 g) • Energy: 110-135 kcal/kg/d • Expected growth after return to birthweight • Weight: 15-20 g/kg/d • Length: 0.75-1.0 cm/week • Head circumference: 0.75-1.0 cm/week

  18. Feeding Strategies • Total parenteral nutrition • Mother’s own milk (with appropriate fortification) • Donor human milk (with appropriate fortification) • Premature infant formulas • Transition to 22 kcal/oz formula or remain on fortified human milk >1800 g • Appropriate follow-up of growth after discharge

  19. Specific Nutrient Requirements • Limited data on requirements following hospital discharge • Hospital discharge occurring earlier and earlier • Post-discharge practices vary by country, neonatal intensive care units (NICUs), and neonatologists • Pre- and post-discharge nutritional strategies should be a continuum • Type and volume of feedings vary; lower energy dense feedings have been demonstrated to result in increased intake • Extrauterine growth restriction widely reported • Altered body composition, especially increased fat mass observed • Rate of weight gain similar to intrauterine may be achieved, but “catch up” is not Greer FR. Post-discharge nutrition: what does the evidence support? Sem Perinatol. 2007;31(2):89–95; Lapillonne A. Feeding the preterm infant after discharge. World Rev Nutr Diet. 2014;110:264–277; Cooke, McCormick K, Griffin IJ, et al. Feeding preterm infants after hospital discharge: effect of diet on body composition. Pediatr Res. 1999;46(4):461–464; Bertino, Coscia A, Mombrò M, et al. Postnatal weight increase and growth velocity of very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2006;91(5):F349–F356; Roggero P, Giannì ML, Amato O, et al. Postnatal growth failure in preterm infants: recovery of growth and body composition after term. Early Hum Dev. 2008;84(8):555–559; Sakurai M, Itabashi K, Sato Y, Hibino S, Mizuno K. Extrauterine growth restriction in preterm infants of gestational age < or =32 weeks. Pediatr Int. 2008;50(1):70–75; Bertino E, Coscia A, Boni L, et al. Weight growth velocity of very low birth weight infants: role of gender, gestational age and major morbidities. Early Hum Dev. 2009;85(6):339–347; and DusickAM, Poindexter BB, Ehrenkranz RA, Lemons JA. Growth failure in the preterm infant: can we catch up? Sem Perinatol. 2003;27(4):302–310

  20. Current Guidelines • Preferred feeding is human milk; rate of human milk feedings may be only 50% at discharge. • Due to variability between and among mothers and the decline in protein content over time, is exclusive human milk suitable for all? • Human milk alone may not be sufficient in energy, protein, and minerals. • Existing data on post-discharge fortification of human milk are conflicting. Saarela T, Kokkonen J, Koivisto M. Macronutrient and energy contents of human milk fractions during the first six months of lactation. ActaPaediatr. 2005;94(9):1176–1181; Aimone A, Rovet J, Ward W, et al. Growth and body composition of human milk-fed premature infants provided with extra energy and nutrients early after hospital discharge: 1-year follow-up. J PediatrGastroenterolNutr. 2009;49(4):456–466; and Zachariassen G, Faerk J, Grytter C, et al. Nutrient enrichment of mother's milk and growth of very preterm infants after hospital discharge. Pediatrics. 2011;127(4):e995–e1003

  21. Growth with Preterm Formulas Heird W, Wu C. Are We Discharging Preterm Infants in a Suboptimal Nutritional State? Nutrition, Growth, and Body Composition. In: Hay WW Jr, Lucas A, eds. Posthospital Nutrition in the Preterm Infant. Report of the 106th Ross Conference on Pediatric Research. Columbus, OH: Ross Products Division, Abbott Laboratories; 1996:13

  22. Other Studies • 2001, multicenter study, 9 month post-intervention, n=229, <1750 g • Significant differences in weight and length at 9 months • At 18 months, length difference persisted (1.5 cm, 95% confidence interval [CI] 0.3-2.7) • No differences in neurodevelopmental outcome Lucas A, Fewtrell MS, Morley R, et al. Randomized trial of nutrient-enriched formula versus standard formula for postdischarge preterm infants. Pediatrics. 2001;108(3):703–711

  23. Preterm or Term Formula After Hospital Discharge • Multicenter, 125 infants; post-discharge formula (22 kcal/oz) vs term (20 kcal/oz) • ~50% of subjects lost to follow up at 12 months • Mean gestational age 30 weeks, birthweight 1250-1300 g • Significant differences in weight at both 1 month (4092 vs 3825 g, p<0.02) and 2 months (4968 vs 4724, p<0.05) • No significant differences at 6 and 12 months, but study lost power due to loss of subjects • Subgroup analysis of infants <1250 g suggested that infants may have benefited from the discharge formula (increased weight and head circumference), but number of infants is small Carver JD, Wu PY, Hall RT, et al. Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge. Pediatrics. 2001;107(4):583–689

  24. Post-Discharge or Term Formula • 89 infants, discharge formula vs term • Anthropometry plus dual-energy x-ray absorptiometry (DEXA) at 12 months • Term formula fed infants were significantly heavier and longer than those fed post-discharge formulas. Differences in intake? • Large improvement in z-scores over the first 9 months for ALL measures regardless of feeding type • Suggests that catch up growth occurs after discharge and the period is important to provide appropriate nutrients Koo WW, Hockman EM. Posthospital discharge feeding for preterm infants: effects of standard compared with enriched milk formula on growth, bone mass and body composition. Am J ClinNutr. 2006;84(6):1357–1364

  25. Double blind study • 3 groups: • Control • Algal DHA • Fish DHA • Term, breastfed reference group • Fed, preterm, discharge, and term formulas • Weight of algal > control, 66-118 weeks post-menstrual age (PMA) • No difference from term at 118 weeks • Algal significantly longer than control and fish at 57, 79, and 92 weeks • Supplemented groups had higher Bayley Scores, Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI), at 118 weeks than control Clandinin MT, Van Aerde JE, Merkel KL, et al. Growth and development of preterm infants fed infant formulas containing docasohexanoic acid and arachidonic acid. J Pediatr. 2005;146(4):461–468

  26. Approaches to Intervention • ≤1750 g, ≤34 weeks gestation • Randomized to preterm formula from discharge to 6 months post conception OR term formula (discharge to 6 months), OR preterm formula (discharge to term), OR term formula (term to 6 months) • Down regulated intake to achieve similar energy intakes • Boys: weight, length, and head circumference were greater in preterm formula group and persisted at 18 months; no differences in MDI or PDI Cooke RJ, Embleton ND, Griffin IJ, Wells JC, McCormick KP. Feeding preterm infants after hospital discharge: growth and development at 18 months of age. Pediatr Res. 2001;49(5):719–722

  27. Body weight, crown-heel length, and OFC in the three study groups. Results are mean ± SD. Closed circles, open circles, and crosses indicate infants fed the preterm (A), term (B), and preterm followed by term (C) formulas, respectively. Data were analyzed using ANOVA. *p < 0.0001 for differences between A and B/C. Cooke RJ, Embleton ND, Griffin IJ, Wells JC, McCormick KP. Feeding preterm infants after hospital discharge: growth and development at 18 months of age. Pediatr Res. 2001;49(5):719–722

  28. Approaches to Intervention • Infants fed preterm formula had better growth compared to fortified human milk-fed infants • No differences in developmental outcome • Breastfed after discharge: lower serum PO4, alkaline phosphatase, transferrin • Lower bone mineral mass, poorer growth, and higher fat mass in the first year

  29. Cochrane Database Syst Rev. 2012;3:CD004696

  30. Nutrient-Enriched Formula • 15 eligible trials, n=1128 • 10 trials compared post-discharge formula vs standard infant formula • No consistent effect on growth parameters up to 12-18 months of age • 5 trials compared preterm formula vs term infant formula • Higher rates of growth through infancy • 500 g weight difference between 12-18 months • 0.5-1.0 cm difference in length • 0.5 cm difference in head circumference • Few trials assessed neurodevelopmental outcome

  31. Post-Discharge Formula vs Standard Term Formula: Weight Weight greater Young L, Morgan J, McCormick FM, McGuire W. Nutrient-enriched formula versus standard term formula for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2012;3:CD004696

  32. Post-Discharge Formula vs Standard Term Formula: Length Significantly longer at 12 months Young L, Morgan J, McCormick FM, McGuire W. Nutrient-enriched formula versus standard term formula for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2012;3:CD004696

  33. Preterm Formula vs Standard Term Formula: Weight Young L, Morgan J, McCormick FM, McGuire W. Nutrient-enriched formula versus standard term formula for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2012;3:CD004696

  34. Preterm Formula vs Standard Term Formula:Crown Heel Length Young L, Morgan J, McCormick FM, McGuire W. Nutrient-enriched formula versus standard term formula for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2012;3:CD004696

  35. Preterm Formula vs Standard Term Formula:Head Circumference Young L, Morgan J, McCormick FM, McGuire W. Nutrient-enriched formula versus standard term formula for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2012;3:CD004696

  36. Implications for Practice • Do not support recommendations that formula-fed preterm infants should receive a post-discharge formula for up to 12 months post-discharge • In contrast, feeding with a “preterm formula” may increase weight, length, and head circumference growth up to 12-18 months corrected age

  37. Human Milk-Fed Infants • Of particular concern • Evidence is clear that despite non-nutritional and important advantages of human milk, growth of these infants is poorer than those given standard infant formula • Limited data suggest that feeding non-fortified human milk after discharge leads to calcium and phosphorus deficiency and lower bone mineral content (BMC) • However, this disappears by 2 years of age Griffin IJ. Postdischarge nutrition for high risk neonates. ClinPerinatol. 2002;29(2):327–344; Abrams SA, Schanler RJ, Garza C. Bone mineralization in former very low birth weight infants fed either human milk or commercial formula. J Pediatr. 1988;112(6):956–960; and Schanler RJ, Burns PA, Abrams SA, Garza C. Bone mineralization outcomes in human milk-fed preterm infants. Pediatr Res. 1992;31(6):583–586

  38. Long-Term Bone Health • Whole body and regional BMC and bone mineral density (BMD) and bone turnover at 8-12 years of age • Previously participated in studies where they were randomized to banked breast milk (BBM) vs preterm formula (PTF) or as a supplement to expressed breast milk (EBM) vs PTF Fewtrell MS, Prentice A, Jones SC, et al. Bone mineralization and turnover in preterm infants at 8-12 years of age: the effect of early diet. J Bone and Miner Res. 1999;14(5):810–820

  39. Results • Preterm children were shorter and “lighter” than term children • Significantly lower BMC • Differences disappeared after adjusting for bone area, body size, and pubertal status • BBM vs PTF or term formula vs PTF: no differences in anthropometry, BMC, BMD, or osteocalcinin • Early diet did not affect bone mass in preterm children; fresh human milk had no specific effect • Higher bone formation in childhood may be seen Fewtrell MS, Prentice A, Jones SC, et al. Bone mineralization and turnover in preterm infants at 8-12 years of age: the effect of early diet. J Bone and Miner Res. 1999;14(5):810–820

  40. Human Milk Studies • <1800 g, fortified to 22 kcal/oz after discharge or human milk alone (800-1800 g at birth) • Greater whole body BMC (p=0.02) and longer (p<0.001) at 12 months than controls • <1250 g infants had greater head circumference through 12 months (p<0.0001) • No difference in Bayley scores at 18 months corrected age Aimone A, Rovet J, Ward W, et al. Growth and body composition of human milk-fed premature infants provided with extra energy and nutrients early after hospital discharge: 1-year follow up. J PediatrGastroenterolNutr. 2009;49(4):456–466

  41. Fortification After Hospital Discharge • 2 trials, n=246 • No differences in growth outcomes during the first year of life due to multinutrient fortified breast milk vs unfortified human milk • In one study, only half the intake was fortified human milk; the other study included infants from 535-2255 g • “Limited data do not provide convincing evidence” Young L, Embleton ND, McCormick FM, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2013;2:CD004866 and O’Connor DL, Khan S, Weishuhn K, et al. Growth and nutrient intakes of human milk-fed preterm infants provided with extra energy and nutrients after hospital discharge. Pediatrics. 2008;121(4):766–776

  42. Fortified Human Milk during Hospitalization • 217 very-low-birthweight (VLBW) infants; 136 eligible for study • 127 studied • Part of a study on long-chain polyunsaturated fatty acid (LCPUFA) supplementation on cognitive development • All infants received fortified human milk—mother’s or donor • At an enteral intake of 120 mL/kg/d, human milk was fortified with energy, protein, and minerals or a human milk fortifier • At discharge, 76% of infants received only human milk Henriksen C, Westerberg AC, Rønnestad A, et al. Growth and nutrient intake among very-low-birth-weight infants fed fortified human milk during hospitalization. Br J Nutr. 2009,102(8):1179–1186

  43. Henriksen C, Westerberg AC, Rønnestad A, et al. Growth and nutrient intake among very-low-birth-weight infants fed fortified human milk during hospitalization. Br J Nutr. 2009,102(8):1179–1186

  44. Multinutrient vs No Fortification of Human Breast Milk: Weight at 12 Weeks Post-Discharge McCormick FM, Henderson G, Fahey T, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2010;7:CD004866

  45. Multinutrient vs No Fortification of Human Breast Milk: Length at 12 Weeks Post-Discharge McCormick FM, Henderson G, Fahey T, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2010;7:CD004866

  46. Multinutrient vs No Fortification of Human Breast Milk: Length at 12 Months Post-Menstrual Age McCormick FM, Henderson G, Fahey T, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2010;7:CD004866

  47. Multinutrient Fortification vs No Fortification: Length at 3-4 and 12 Months Young L, Embleton ND, McCormick FM, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2013;2:CD004866

  48. Multinutrient Fortification vs No Fortification: Head Circumference at 12 Weeks McCormick FM, Henderson G, Fahey T, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2010;7:CD004866

  49. Multinutrient Fortification vs No Fortification: Visual Acuity (Cycles/Degree) Young L, Embleton ND, McCormick FM, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2013;2:CD004866

  50. Multinutrient Fortification vs No Fortification: Bone Mineral Content Young L, Embleton ND, McCormick FM, McGuire W. Multinutrient fortification of human breast milk for preterm infants following hospital discharge. Cochrane Database Syst Rev. 2013;2:CD004866

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