2. Nutrition in NICU (1) for preterm as well as term babies

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1. Higher Growth Rates and Low Nutrient Stores Role of Optimal Nutrition in Preterm Infants

2. Breastfeeding is the best Start Breastfeeding ASAP, within first hour of birth. Exclusive breastfeeding till 6 months. Continue breastfeeding 2 years and beyond…..

3. Infants born prematurely miss several weeks of fastest growth period in utero Growth rate is the highest during the last trimester of pregnancy 1 4-fold increase 2 6-fold increase 3 Tudehope , D. et al. Journal of Paediatrics and Child Health . 2012; 48(9):759–767.   Konkel , L. Environmental Health Perspectives . 2018; 126(11), 112001.   Fenton and Kim. BMC Pediatrics 2013, 13:59 Brain growth Body weight 24 to 40 weeks of pregnancy 24 to 40 weeks of pregnancy

4. Delay in providing adequate nutrition increases risk of growth failure Embleton NE et al. Pediatrics . 2001 Feb;107(2):270-3.  By two weeks of age , a preterm infant receives only 70% of requirements Cumulative calorie deficit increases from first to the end of the fift h week of life Actual amount of energy received Recommended energy intakes Actual amount of energy received Daily calorie deficit

5. Degree of prematurity correlates with degree of nutrient deficiency Premature infants have lower plasma levels of certain nutrients Shah, Malika D.; Shah, Shilpa R. (2009).  Nutrient Deficiencies in the Premature Infant. Pediatric Clinics of North America, 56(5), 1069–1083.  doi:10.1016/j.pcl.2009.08.001  Increased nutrition particularly protein is required for developmental outcome

6. Failure of catch-up growth may have long-term consequences Euser , et al. Hormone Research in Paediatrics , 70(6), 319–328.   Ong KK. Curr Opin Endocrinol Diabetes Obes 2007;14:30–34 Victora CG, et al. Int J Epidemiol 2001;30:1325-30 Adair LS,et al. Lancet 2013;382:525-34. Brandt I, et al. J Pediatr 2005;147:662-8. Pylipow M, et al. J Pediatr 2009;154:201-6. Longo S, et al. J Maternal Fetal Neonat Med 2013;26:222-5 Optimum catch-up growth ↑ in linear Growth ↑ in body Mass ↑ in Fat mass ↑ Central adiposity F requent infection 3 Short stature 4,5 Impaired cognitive development 6,7 Persistent poor postnatal growth Too-rapid catch-up growth 2 ↑ Insulin resistance

7. Delayed feeding for several days can lead to malnutrition Ho,et al . Pediatrics & Neonatology, 57(5), 365–370.  doi:10.1016/j.pedneo.2015.10.006 Immaturity of gastrointestinal function Respiratory conditions Inadequate oxygen supply Severe intestinal inflammatory disease Catabolic state: Breakdown molecules Reasons for Delayed Feeding

8. Optimal Nutrition for Preterm Infants Importance and Need of Macronutrients

9. Preterm infants have increased calorie requirements Reasons for Increased Calorie requirements Camelo Jr., J. S., & Martinez, F. E. (2005). Dilemas nutricionais no pré-termo extremo e repercussões na infância, adolescência e vida adulta. Jornal de Pediatria, 81(1), S33–S42. doi:10.1590/s0021-75572005000200005 ↑ Energy expenditure Larger body surface area Greater heat loss due to the thin skin ↑ Energy required for growth

10. Premature infants are in an energy-deficit state Causes of energy deficiency in the premature infant 1 Tan J et al.(2018).  The Energy Costs of Prematurity and the Neonatal Intensive Care Unit (NICU) Experience. Antioxidants, 7(3), 37.   American Academy of the Pediatric (AAP) Committee on Nutrition: Nutritional needs of the preterm infant; in Kleinman RE (ed): Pediatric Nutrition Handbook, ed 6. Elk Grove Village/IL, AAP, 2009, pp 79–112. Agostoni , et al. J Pediatr Gastroenterol Nutr , 2010;50(1):85-91 Energy deficit state Recommendations for Energy

11. Glucose is the major source of energy to the preterm infants early in life Camelo Jr., J. S., & Martinez, F. E. (2005). Dilemas nutricionais no pré-termo extremo e repercussões na infância, adolescência e vida adulta. Jornal de Pediatria, 81(1), S33–S42. doi:10.1590/s0021-75572005000200005 Glucose Glycogen deposits are limited Preterm infants need a continuous glucose source A 24-week-old preterm infant has energy for less than a day

12. Premature infants require high protein supplementation Dallas, D. (2012). Digestion of Protein in Premature and Term Infants. Journal of Nutritional Disorders & Therapy, 02(03). doi:10.4172/2161-0509.1000112 Hay WW et al.   Pediatr Neonatol 2010;51(4):198−207. 3. Denne, S. C. (2001). Seminars in Neonatology, 6(5), 377–382. doi:10.1053/siny.2001.0059  Reasons for Increased Protein requirements More protein required to achieve normal intrauterine growth rates Low capacity for protein synthesis Low protein digestive capacity Immature gastrointestinal tract Rate of protein loss is two-fold higher in preterm than in normal term infants 3

13. Protein supplementation of human milk may promote growth Protein supplementation of human milk in preterm infants results in increases in: Kuschel , C. A., & Harding, J. E. (2000).  Protein supplementation of human milk for promoting growth in preterm infants. Cochrane Database of Systematic Reviews.  doi:10.1002/14651858.cd000433  Weight Gain H eight Gain Head Growth

14. Types of protein for preterm: Whey or Casein Hay, W. W., & Hendrickson, K. C. (2017). Preterm formula use in the preterm very low birth weight infant. Seminars in Fetal and Neonatal Medicine, 22(1), 15–22. Whey Predominant Feed Slower digestible Slower gastric emptying Better digestible Faster gastric emptying Casein Predominant Feed

15. Whey-predominant protein maintains acid base balance 1 Insufficient availability of essential amino acids 3 Catabolic state : Increased protein breakdown Increased burden on the preterm infant’s immature kidney Overabundance of amino acids 3 Optimum quantity and quality of protein supply is crucial Amino acids maintain positive protein balance 2 Amino acids are building blocks of protein 1. Shenai , J. P et al . (1986) . Journal of Pediatric Gastroenterology and Nutrition, 5(3), 428–433. 2. Denne, S. C. (2001). Seminars in Neonatology, 6(5). 3. Bonsante F, et al. PLoS ONE 8(8): e72880. M aintain the infants' body in an anabolic state where the body builds and repairs 3

16. Lipids: Important Components to meet the requirements for Essential Fatty Acids (EFA) 1. Martin, C. R. (2015). Lipids and Fatty Acids in the Preterm Infant, Part 2: Clinical Considerations. NeoReviews , 16(3), e169–e180. doi:10.1542/neo.16-3-e169 2. Vlaardingerbroek H et al.. J Pediatr 2013;163:638e44. e1e5 3. D.T. Robinson, C.R. Martin / Seminars in Fetal & Neonatal Medicine 22 (2017) 8-14 Lipids for preterm infants 2 Essential for glucose synthesis Required for ongoing development and function of cells and organs Required for normal development of the central nervous system Prevent deficiency of essential fatty acid

17. Immature GI system affects leads to impaired digestion & absorption of fats 1. Martin, C. R. (2015). . NeoReviews , 16(3), e160–e160=8. doi:10.1542/neo.16-3-e169 2. Burge, K et al. . Nutrients 2021 , 13 , 550. 3. D.T. Robinson, C.R. Martin / Seminars in Fetal & Neonatal Medicine 22 (2017) 8-14 DHA: Docosahexaenoic acid AA: arachidonic acid Immature GI system Decreased absorption of total dietary fat Decreased absorption of DHA and AA Accumulation of incompletely digested lipids Inflammation of the intestinal epithelium 2

18. Need for lipid supplementation in preterm infants D.T. Robinson, C.R. Martin / Seminars in Fetal & Neonatal Medicine 22 (2017) 8-14 Preterm infant Early cessation of placental transfer of LCPUFA from mother to preterm infant Insufficient synthesis of LCPUFAs Gastrointestinal immaturity impair absorption of lipids Liver immaturity impair absorption of total fat and specific fatty acids LCPUFA- Long chain poly unsaturated fatty acids

19. Enteral provision of lipids should be started soon in preterm infants D.T. Robinson, C.R. Martin / Seminars in Fetal & Neonatal Medicine 22 (2017) 8-14 Importance of beginning enteral feeding as early as possible Promote Gastrointestinal system development Prevents bone loss Promote formation of stool Decrease risk of liver disease

20. Current recommendations for lipid supplementation No evidence to support the provision of DHA without ARA 1. Agostoni C, et al. . J Pediatr Gastroenterol Nutr 2010;50:85-91. 2. Koletzko B, et al. In: Koletzko B, Poindexter B, Uauy R, editors. Nutritional care of preterm infants: scientific basis and practical guidelines. Karger; 2014. p. 297e9 AA: arachidonic acid; ] DHA: docosahexaenoic acid

21. Micronutrient Deficiencies in Preterm Infants Micronutrient deficiencies and its Association with Growth Failure

22. Preterm infants are at high risk of micronutrient deficiencies Powers, H. (1993). Proceedings of the Nutrition Society,   52 (2), 285-291. doi:10.1079/PNS19930064 Neonatally Low nutrient stores at birth Immaturity of organs Risk of infections Postnatal care Delayed introduction of feeds Loss of vitamins In utero Poor maternal status Poor placental transfer

23. Specific nutrients support brain growth, development and function Barbara et al. Nutrients  2019,  11 (9), 2029;  https://doi.org/10.3390/nu11092029 Brain growth and development is effected by neuronutrients ’ deficiency Inadequate energy Protein Deficiency Thiamine Deficiency Deficiencies of: Fe, Zn, Vit. A, B6, B12, C, D, I, Cu, Se, Choline, Taurine

24. Iron: Risk of deficiency & overload in preterm infants The effects of iron deficiency involve multiple organ systems Iron Deficiency Poor physical growth Gastrointestinal disturbances Thyroid dysfunction Altered Immunity Temperature instability Rao R, Georgieff MK. Iron therapy for preterm infants. Clin Perinatol . 2009;36(1):27-42. doi:10.1016/j.clp.2008.09.013

25. Vitamin A: Preterm infants have inadequate stores of Vitamin A Cellular retinol binding protein type 2 (CRBP) is limited in the preterm infant Mactier, H. (2005).  Vitamin A and preterm infants: what we know, what we don’t know, and what we need to know. Archives of Disease in Childhood - Fetal and Neonatal Edition, 90(2), F103–F108.  doi:10.1136/adc.2004.057547  Retinal sensitivity is less in preterm infants Preterm infants are prone to altered visual acuity & retinopathy of prematurity CRBP II is required for metabolism of Vit A Retinal sensitivity correlates with stores of vitamin A in the liver CRBP

26. Biological effects of Vitamin A supplementation Mactier, H. (2005).  Vitamin A and preterm infants: what we know, what we don’t know, and what we need to know. Archives of Disease in Childhood - Fetal and Neonatal Edition, 90(2), F103–F108.  doi:10.1136/adc.2004.057547  Sun, H., Cheng, R., & Wang, Z. (2019).  Retina, 1.  doi:10.1097/iae.0000000000002543

27. Optimal Vitamin D supplementation is crucial for preterm infants 1. Taylor, S. N., Hollis, B. W., & Wagner, C. L. (2009).  Vitamin D Needs of Preterm Infants. NeoReviews , 10(12), e590–e599.  doi:10.1542/neo.10-12-e590  2. Natarajan, et al. (2014).  Trial of Daily Vitamin D Supplementation in Preterm Infants. PEDIATRICS, 133(3), e628–e634.  doi:10.1542/peds.2012-3395  PMA: Post menstrual age; VDD: Vitamin D deficiency; CA: Corrected age Daily supplementation with 800 IU of vitamin D reduces the prevalence of Vitamin D deficiency in preterm infants 2

28. ESPGHAN Recommendations Vitamin ESPGHAN 2010 recommendation A 400–1,000 μ g/kg E 2.2–11 mg K 4.4–28 µg D 800-1000 IU /day Thiamine (B1) 140–300 µg/kg/day Riboflavin (B2) 200-400 µg/kg/day Niacin (B3) 380-5500 µg/kg/day Pyridoxine (B6) 45 - 300 µg/kg/d Biotin 1.7-16.5 µg/kg/d Folic acid 35-100 µg/kg/day Agostoni C,et al . J Pediatr Gastroenterol Nutr 2010;50:85-91. Expanded reference material available at http://links.lww.com/A1480.

29. Summary