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Trend of Nutritional Support in Preterm Infants

2016; Elsevier BV; Volume: 57; Issue: 5 Linguagem: Inglês

10.1016/j.pedneo.2015.10.006

2212-1692

Man-Yau Ho, Yu-Hsuan Yen,

Child Nutrition and Feeding Issues

Without appropriate nutritional support, preterm infants fail to grow after birth and have malnutrition. The main reason for delayed feeding is fear of immaturity of gastrointestinal function. The principles of nutritional practice should be as follows: (1) minimal early initiation of enteral feeding with breast milk (0.5–1 mL/h) to start on Day 1 if possible and gradual increase as tolerated; (2) early aggressive parenteral nutrition as soon as possible; (3) provision of lipids at rates that will meet the additional energy needs of about 2–3 g/kg/d; and (4) attempt to increase enteral feeding rather than parenteral nutrition. Without appropriate nutritional support, preterm infants fail to grow after birth and have malnutrition. The main reason for delayed feeding is fear of immaturity of gastrointestinal function. The principles of nutritional practice should be as follows: (1) minimal early initiation of enteral feeding with breast milk (0.5–1 mL/h) to start on Day 1 if possible and gradual increase as tolerated; (2) early aggressive parenteral nutrition as soon as possible; (3) provision of lipids at rates that will meet the additional energy needs of about 2–3 g/kg/d; and (4) attempt to increase enteral feeding rather than parenteral nutrition. Most preterm neonates fail to grow after birth, and they are often affected by respiratory distress and immaturity. Malnutrition may occur without appropriate nutritional support.1Hack M. Fanaroff A.A. Outcomes of extremely-low-birth-weight infants between 1982 and 1988.N Engl J Med. 1989; 321: 1642-1647Crossref PubMed Scopus (196) Google Scholar Preterm infants do not usually fully catch up to normal rates of growth, and it takes a mean of 14–17 days to regain birth weight in infants of <1000 g at birth.2Georgieff M.K. Mills M.M. Zempel C.E. Chang P.N. Catch-up growth, muscle and fat accretion, and body proportionality of infants one year after newborn intensive care.J Pediatr. 1989; 114: 288-292Abstract Full Text PDF PubMed Scopus (27) Google Scholar, 3Ehrenkranz R.A. Younes N. Lemons J.A. Fanaroff A.A. Donovan E.F. Wright L.L. et al.Longitudinal growth of hospitalized very low birth weight infants.Pediatrics. 1999; 104: 280-289Crossref PubMed Scopus (685) Google Scholar Very-low-birth-weight infants are characterized by significant weight loss in the initial days and weeks because of catabolic illness and insufficient protein energy supply.4de Boo H.A. Harding J.E. Protein metabolism in preterm infants with particular reference to intrauterine growth restriction.Arch Dis Child Fetal Neonatal Ed. 2007; 92: F315-F319Crossref PubMed Scopus (26) Google Scholar The most common reason is that mechanical ventilation and high oxygen concentrations cause pulmonary and systemic inflammatory processes.5Bose C.L. Laughon M.M. Allred E.N. O'Shea T.M. Van Marter L.J. Ehrenkranz R.A. et al.Systemic inflammation associated with mechanical ventilation among extremely preterm infants.Cytokine. 2013; 61: 315-322Crossref PubMed Scopus (75) Google Scholar In the traditional nutrition model, for preterm neonates with respiratory distress syndrome, enteral nutrition and parenteral nutrition (PN) were often delayed. The reasons for the preterm neonates to have delayed feeding are fear of (1) respiratory distress syndrome and mechanical ventilation, (2) immaturity of gastrointestinal function, (3) systemic hypoxia, (4) catabolic stage, and (5) necrotizing enterocolitis (NEC; Table 1). Consequently, enteral feeding may be delayed for several days, partly because of gastrointestinal immaturity to digest and absorb the complex nutrients in preterm neonates.6Skillman H.E. Wischmeyer P.E. Nutrition therapy in critically ill infants and children.JPEN J Parenter Enteral Nutr. 2008; 32: 520-534Crossref PubMed Scopus (59) Google Scholar, 7Tinckler L. Surgery and intestinal motility.Br J Surg. 1965; 52: 140-150Crossref PubMed Scopus (46) Google Scholar Often, intravenous (IV) amino acids are not given immediately after birth, and when provided they are given in low amounts. The dose of IV amino acids is usually <3 g/kg/d, and then it is increased slowly, taking several days to reach an appropriate amount.Table 1Frequent reasons for delayed feeding of preterm infants.Type of delayed feedingReason for delayed feedingSource of fearEnteral feedingAbdominal distensionNECGERApneaHyperglycemia &/or rebound hypoglycemiaPoor metabolism & infectionsLow SPO2Slow metabolism of nutrientsOn CPAPAir entering the stomachOn ventilatorSlow digestion & absorptionParenteral nutritionUA &/or UV cathetersGut ischemia & NECHigh BUNUrea & amino acid toxicityHypo or hyperkalemiaInterfere with poor gut functionLipid emulsionHigh bilirubinInterfere with bilirubin bindingHyperlipidemiaAccumulation in reticuloendothelial system & in lungsBUN = blood urea nitrogen; CPAP = continuous positive airway pressure; GER = gastroesophageal reflux; NEC = necrotizing enterocolitis; SPO2 = saturation of peripheral oxygen; UA = umbilical artery; UV = umbilical vein.Note. From "Aggressive nutrition of the very low birthweight infant," by E.E. Ziegler, P.J. Thureen, and S.J. Carlson, 2002, Clin Perinatol, 29, p. 225–44. Copyright 2002, Elsevier Inc. Reproduced with permission. Open table in a new tab BUN = blood urea nitrogen; CPAP = continuous positive airway pressure; GER = gastroesophageal reflux; NEC = necrotizing enterocolitis; SPO2 = saturation of peripheral oxygen; UA = umbilical artery; UV = umbilical vein. Note. From "Aggressive nutrition of the very low birthweight infant," by E.E. Ziegler, P.J. Thureen, and S.J. Carlson, 2002, Clin Perinatol, 29, p. 225–44. Copyright 2002, Elsevier Inc. Reproduced with permission. How early should enteral feeding be given? Should it commerce within the first 24 hours or 48 hours? Early feeding within the first 24 hours after birth can induce the release of trophic endogenous agents and inhibit the effects of inflammatory mediators and cytokines released in critically ill children.8Marik P.E. Zaloga G.P. Early enteral nutrition in acutely ill patients: a systematic review.Crit Care Med. 2001; 29: 2264-2270Crossref PubMed Scopus (713) Google Scholar, 9Sánchez C. López-Herce J. Carrillo A. Mencía S. Vigil D. Early transpyloric enteral nutrition in critically ill children.Nutrition. 2007; 23: 16-22Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar The first option is early minimal enteral feeding after birth, namely, trophic or priming feeding. Early and gradual advancement of enteral feeding can promote release of gastrin and then full breast-feeding can be achieved.10Meetze W.H. Valentine C. McGuigan J.E. Conlon M. Sacks N. Neu J. Gastrointestinal priming prior to full enteral nutrition in very low birth weight infants.J Pediatr Gastroenterol Nutr. 1992; 15: 163-170Crossref PubMed Scopus (123) Google Scholar Early feeding can help develop intestinal villi and activate enzymes, improving digestion, absorption, and motility. Early feeding can also help develop gut microbiota, thereby preventing infection and NEC, and it can also help reduce local and systemic inflammation.11Berseth C.L. Nordyke C. Enteral nutrients promote postnatal maturation of intestinal motor activity in preterm infants.Am J Physiol. 1993; 264: G1046-G1051PubMed Google Scholar, 12Leaf A. Dorling J. Kempley S. McCormick K. Mannix P. Linsell L. et al.Early or delayed enteral feeding for preterm growth-restricted infants: a randomized trial.Pediatrics. 2012; 129: e1260-e1268Crossref PubMed Scopus (106) Google Scholar Human milk is preferred in feeding, particularly for preterm and sick infants. If the mother's breast milk is insufficient, donor breast milk from the milk bank may be used. Preterm infants should receive breast milk as soon as possible after birth. Breast milk consumption can stimulate the release of endocrine and metabolic factors such as gastrin, enteroglucagon, motilin, neurotensin, gastro-inhibiting peptide, and pancreatic polypeptide. Using breast milk with the growth of Bifidobacteriae and Lactobacillus strains can help gastrointestinal absorption and motility.13Henderson G. Anthony M.Y. McGuire W. Formula milk versus maternal breast milk for feeding preterm or low birth weight infants.Cochrane Database Syst Rev. 2007; : CD002972PubMed Google Scholar The fat content of breast milk is important to infant development when it comes to the omega-3 fatty acid docosahexaenoic acid, and the omega-6 fatty acid metabolite arachidonic acid, which are both concentrated in the infant brain during the last trimester and in the 1st year of life.14Helland I.B. Smith L. Saarem K. Saugstad O.D. Drevon C.A. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age.Pediatrics. 2003; 111: e39-e44Crossref PubMed Scopus (726) Google Scholar The omega-3 fatty acid is alpha-linoleic acid from the production of essential long-chain polyunsaturated fatty acids, docosahexaenoic acids, and arachidonic acids. Omega-3 fatty acids play an important role in retinal and neurologic development.15Innis S.M. Human milk: maternal dietary lipids and infant development.Proc Nutr Soc. 2007; 66: 397-404Crossref PubMed Scopus (210) Google Scholar The use of human milk fortifier (HMF) helps to meet the high nutritional requirements of the human milk-fed premature infant.16Thoene M. Hanson C. Lyden E. Dugick L. Ruybal L. Anderson-Berry A. Comparison of the effect of two human milk fortifiers on clinical outcomes in premature infants.Nutrients. 2014; 6: 261-275Crossref PubMed Scopus (35) Google Scholar Some studies have shown that the addition of HMF is associated with short-term improvements in weight, height, bone mineralization, neurologic outcome, and head growth.17Faerk J. Petersen S. Peitersen B. Michaelsen K.F. Diet and bone mineral content at term in premature infants.Pediatr Res. 2000; 47: 148-156Crossref PubMed Scopus (70) Google Scholar, 18Gross S.J. Bone mineralization in preterm infants and fed human milk with and without mineral supplementation.J Pediatr. 1987; 111: 450-458Abstract Full Text PDF PubMed Scopus (56) Google Scholar, 19Nicholl R.M. Gamsu H.R. Changes in growth and metabolism in very low birth weight infants fed with fortifier breast milk.Acta Paediatr. 1999; 88: 1056-1061Crossref PubMed Google Scholar, 20Pettifor J.M. Rajah R. Venter A. Moodley G.P. Opperman L. Cavaleros M. et al.Bone mineralization and mineral homeostasis in very low-birth-weight infants fed either human milk or fortifier human milk.J Pediatr Gastroenterol Nutr. 1989; 8: 217-224Crossref PubMed Scopus (33) Google Scholar, 21Martins E.C. Krebs V.L. Effects of the use of fortified raw maternal milk on very low birth weight infants.J Pediatr (Rio J). 2009; 85 ([Article in English, Portuguese]): 157-162PubMed Google Scholar However, HMF showed an increase in osmolarity of breast milk.22De Curtis M. Candusso M. Pieltain C. Rigo J. Effect of fortification on the osmolality of human milk.Arch Dis Child Fetal neonatal Ed. 1999; 81: F141-F143Crossref PubMed Scopus (63) Google Scholar Some studies showed that the addition of HMF temporarily delayed gastric emptying and caused a short-term increase in gastric residuals and emesis.21Martins E.C. Krebs V.L. Effects of the use of fortified raw maternal milk on very low birth weight infants.J Pediatr (Rio J). 2009; 85 ([Article in English, Portuguese]): 157-162PubMed Google Scholar, 23Ewer A.K. Yu V.Y. Gastric emptying in pre-term infants: the effect of breast milk fortifier.Acta Paediatr. 1996; 85: 1112-1115Crossref PubMed Scopus (65) Google Scholar, 24McClure R.J. Newell S.J. Effect of fortifying breast milk on gastric emptying.Arch Dis Child Fetal Neonatal Ed. 1996; 74: F60-F62Crossref PubMed Google Scholar, 25Moody G.J. Schanler R.J. Lau C. Shulman R.J. Feeding tolerance in premature infants fed fortified human milk.J Pediatr Gastroenterol Nutr. 2000; 30: 408-412Crossref PubMed Scopus (38) Google Scholar Another study showed increased infections and NEC in infants who were fed fortifier versus nonfortifier human milk.26Lucas A. Fewtrell M.S. Morley R. Lucas P.J. Baker B.A. Lister G. et al.Randomized outcome trial of human milk fortification and developmental outcome in preterm infants.Am J Clin Nutr. 1996; 64: 142-151PubMed Google Scholar The American Society for Parenteral and Enteral Nutrition suggested in 2009 that extremely-low-birth-weight and very-low-birth-weight infants might benefit from minimal enteral feeding, stating very slowly at 0.5–1 mL/kg/d and increasing to 20 mL/kg/d.27Bankhead R. Boullata J. Brantley S. Corkins M. Guenter P. Krenitsky J. et al.Enteral nutrition practice recommendations.JPEN J Parenter Enteral Nutr. 2009; 33: 122-167Crossref PubMed Scopus (403) Google Scholar Feeding volumes are to be kept low regardless of the size of gastric residuals, and are then gradually increased when gastric emptying is improved.28Ziegler E.E. Carlson S.J. Early nutrition of very low birth weight infants.J Matern Fetal Neonatal Med. 2009; 22: 191-197Crossref PubMed Scopus (25) Google Scholar In summary, small amounts of enteral feeding through nasogastric tube to supplement PN are given as early as the 1st day of life at birth in preterm infants. In the past 20 years, the practice in PN is to gradually increase the amount of amino acid intake and to shorten the time after birth to start parenteral alimentation.29Thureen P.J. Melara D. Fennessey P.V. Hay Jr., W.W. Effect of low versus high intravenous amino acid intake or very low birth weight infants in the early neonatal period.Pediatr Res. 2003; 53: 24-32Crossref PubMed Scopus (272) Google Scholar A preterm neonate without a supply of protein may have an endogenous protein loss of 0.5–1.0 g/kg/d.30Adamkin D.H. Issues in the nutritional support of the ventilated baby..Clin Perinatol. 1998; 25: 79-96PubMed Google Scholar Giving amino acids during the first hours of life with a goal of reaching fetal nutrient delivery rates as soon as possible is a cornerstone of this strategy. This strategy is the key to avoid the period of early neonatal malnutrition. Plasma amino acids fall within hours although hepatic enzyme activity is low.30Adamkin D.H. Issues in the nutritional support of the ventilated baby..Clin Perinatol. 1998; 25: 79-96PubMed Google Scholar Amino acids are important in the synthesis of insulin, insulin-like factors, and other growth-related hormones.31Brownlee K.G. Kelly E.J. Ng P.C. Kendall-Smith S.C. Dear P.R. Early or late parenteral nutrition for the sick preterm infant?.Arch Dis Child. 1993; 69: 281-283Crossref PubMed Scopus (27) Google Scholar, 32Pauls J. Bauer K. Versmold H. Postnatal body weight curves for infants below 1000 g birth weight receiving early enteral and parenteral nutrition.Eur J Pediatr. 1998; 157: 416-421Crossref PubMed Scopus (80) Google Scholar Earlier undernutrition can reduce the production of serum insulin-like growth factor-1. Low serum postnatal insulin-like growth factor-1 concentrations in preterm infants after birth were associated with slower rate of head circumference growth.33Löfqvist C. Engström E. Sigurdsson J. Hård A.L. Niklasson A. Ewald U. et al.Postnatal head growth deficit among premature infants parallels retinopathy of prematurity and insulin-like growth factor-1 deficit.Pediatrics. 2006; 117: 1930-1938Crossref PubMed Scopus (96) Google Scholar, 34Hansen-Pupp I. Hövel H. Hellström A. Hellström-Westas L. Löfqvist C. Larsson E.M. et al.Postnatal decrease in circulating insulin-like growth factor-1 and low brain volumes in very preterm infants.J Clin Endocrinol Metab. 2011; 96: 1129-1135Crossref PubMed Scopus (64) Google Scholar Early amino acids can stimulate endogenous insulin secretion, forestalling starvation response to improve glucose tolerance and to prevent hyperglycemia, hyperkalemia, and insulin requirement.30Adamkin D.H. Issues in the nutritional support of the ventilated baby..Clin Perinatol. 1998; 25: 79-96PubMed Google Scholar, 35Clark S.E. Karn C.A. Ahlrichs J.A. Wang J. Leitch C.A. Leichty E.A. et al.Acute changes in leucine and phenylalanine kinetics produced by parenteral nutrition in premature infants.Pediatr Res. 1997; 41: 568-574Crossref PubMed Scopus (36) Google Scholar Several controlled studies have shown the efficacy and safety of amino acids when initiated within the first 24 hours of life.36van Lingen R.A. van Goudoever J.B. Luijendijk I.H. Wattimena J.L. Sauer P.J. Effects of early amino acid administration during total parenteral nutrition on protein metabolism in preterm infants.Clin Sci (Lond). 1992; 82: 199-203Crossref PubMed Scopus (106) Google Scholar, 37Murdock N. Crighton A. Nelson L.M. Forsyth J.S. Low birthweight infants and total parenteral nutrition immediately after birth. II. Randomized study of biochemical tolerance of intravenous glucose, amino acids, and lipid.Arch Dis Child Fetal Neonatal Ed. 1995; 73: F8-F12Crossref PubMed Google Scholar, 38Ho M.Y. Yen Y.H. Hsieh M.C. Chen H.Y. Chien S.C. Hus-Lee S.M. Early versus late nutrition support in premature neonates with respiratory distress syndrome.Nutrition. 2003; 19: 257-260Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar Recent studies have attempted to provide more nutrients to preterm infants and low-birth-weight infants, suggesting that when providing protein and amino acid nutrition directly, dosage may be increased from 0 g/kg/d to 4 g/kg/d. Earlier and higher rates of IV amino acid administration were given immediately after birth for preterm infants.29Thureen P.J. Melara D. Fennessey P.V. Hay Jr., W.W. Effect of low versus high intravenous amino acid intake or very low birth weight infants in the early neonatal period.Pediatr Res. 2003; 53: 24-32Crossref PubMed Scopus (272) Google Scholar, 39Senterre T. Rigo J. Reduction in postnatal cumulative nutritional deficit and improvement of growth in extremely preterm infants.Acta Paediatr. 2012; 101: e64-e70Crossref PubMed Scopus (128) Google Scholar Preterm infants of different gestational ages who were given appropriate protein requirements achieved standard anthropometric indices sooner (Table 2).40Ziegler E.E. Thureen P.J. Carlson S.J. Aggressive nutrition of the very low birthweight infant.Clin Perinatol. 2002; 29: 225-244Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar, 41Hay Jr., W.W. Aggressive nutrition of the preterm infant.Curr Pediatr Rep. 2013; 1https://doi.org/10.1007/s40124-013-0026-4Crossref PubMed Scopus (72) Google Scholar However, one study showed that high levels of some amino acids and blood urea nitrogen were found in infants who were fed aggressively compared with those whose feeding progressed at a more gradual pace. No difference in growth during hospitalization was found between these groups. Neurodevelopmental outcomes were found to be lower at 2 years, although the study that reported this finding was insufficiently statistically powered.42Blanco C.L. Gong A.K. Schoolfield J. Green B.K. Daniels W. Liechty E.A. et al.Impact of early and high amino acid supplementation on ELBW infants at 2 years.J Pediatr Gastroenterol Nutr. 2012; 54: 601-607Crossref PubMed Scopus (79) Google ScholarTable 2Recommended protein intake and protein/energy ratios for preterm infants, to meet normal human fetal lean body mass growth rates.Recommended protein intake & PERWithout need for catch-up growthWith need for catch-up growth26–30 wk PCA 16–18 g/kg/d LBM growth3.8–4.2 g/kg/d4.4 g/kg/d 14% protein retentionPER ± 3.0PER ± 3.030–36 wk PCA 14–15 g/kg/d LBM growth3.4–3.6 g/kg/d3.6–4.0 g/kg/d 15% protein retentionPER ± 2.8PER ± 3.036–40 wk PCA 13 g/kg/d LBM growth2.8–3.2 g/kg/d3.0–3.4 g/kg/d 17% protein retentionPER ± 2.4–2.6PER ± 2.6–2.8LBM = lean body mass; PCA = postconceptional age; PER = protein/energy ratios.Note. From "Aggressive nutrition of the very low birthweight infant," by E.E. Ziegler, P.J. Thureen, and S.J. Carlson, 2002, Clin Perinatol, 29, p. 225–44. Copyright 2002, Elsevier Inc. "Aggressive nutrition of the preterm infant," by W.W. Hay, 2013, Curr Pediatr Rep, 1, p. 229–39. Copyright 2013, Springer Inc. Reproduced with permission. Open table in a new tab LBM = lean body mass; PCA = postconceptional age; PER = protein/energy ratios. Note. From "Aggressive nutrition of the very low birthweight infant," by E.E. Ziegler, P.J. Thureen, and S.J. Carlson, 2002, Clin Perinatol, 29, p. 225–44. Copyright 2002, Elsevier Inc. "Aggressive nutrition of the preterm infant," by W.W. Hay, 2013, Curr Pediatr Rep, 1, p. 229–39. Copyright 2013, Springer Inc. Reproduced with permission. The optimum dose of amino acids for individual preterm infants needs to be determined. Low plasma concentrations of threonine, lysine, leucine, and arginine in preterm infants receiving total PN (TPN) have been associated with hyperammonemia, NEC, hyperglycemia, and increased respiratory morbidity.43Zamora S.A. Amin H.J. McMillan D.D. Kubes P. Fick G.H. Bützner J.D. et al.Plasma l-arginine concentrations in premature infants with necrotising enterocolitis.J Pediatr. 1997; 131: 226-232Abstract Full Text Full Text PDF PubMed Scopus (136) Google Scholar, 44Amin H.J. Zamora S.A. McMillan D.D. Fick G.H. Butzner J.D. Parsons H.G. et al.Arginine supplementation prevents necrotising enterocolitis in the premature infant.J Pediatr. 2002; 140: 425-431Abstract Full Text Full Text PDF PubMed Scopus (218) Google Scholar Most TPN solutions were also deficient in glutamine, which is important for reducing inflammation and promoting growth and neurological development; however, this study did not show any extra benefit of adding glutamine.45Poindexter B.B. Ehrenkranz R.A. Stoll B.J. Wright L.L. Poole W.K. Oh W. et al.Parenteral glutamine supplementation does not reduce the risk of mortality or late-onset sepsis in extremely low birth weight infants.Pediatrics. 2004; 113: 1209-1215Crossref PubMed Scopus (151) Google Scholar Another study showed that positive protein balance in more aggressively fed preterm infants was safe and effective and that it was not associated with hyperammonemia and metabolic acidosis.46Ridout E. Melara D. Rottinghaus S. Thureen P.J. Blood urea nitrogen concentration as a marker of amino-acid intolerance in neonates with birthweight less than 1250 g.J Perinatol. 2005; 25: 130-133Crossref PubMed Scopus (89) Google Scholar Our concern is that increased blood urea nitrogen level is a sign of amino acid oxidation, which releases ammonia despite the fact that the liver is intact and healthy. Providing aggressive PN is very important in the 1st day of life for preterm infants. Although an intake of 50 kcal/kg/d may be sufficient to match ongoing expenditure, it does not meet additional requirements of growth. The ideal energy intake was 120 kcal/kg/d, or higher in the case of infants with chronic lung disease.47Koletzko B. Goulet O. Hunt J. Krohn K. Shamir R. Parenteral Nutrition Guidelines Working Group et al.1. Guidelines on paediatric parenteral nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), Supported by the European Society of Paediatric Research (ESPR).J Pediatr Gastroenterol Nutr. 2005; 41: S1-S87Crossref PubMed Google Scholar, 48Ziegler E.E. Protein requirements of very low birth weight infants.J Pediatr Gastroenterol Nutr. 2007; 45: S170-S174Crossref PubMed Scopus (42) Google Scholar As shown in Table 3, after the 1st day, calories should be increased gradually until the optimal caloric requirement is reached.Table 3Protein and energy requirements of preterm infants.Body weight (g)Enteral feedingParenteral nutritionProtein (g/kg/d)Energy (kcal/kg/d)Protein (g/kg/d)Energy (kcal/kg/d)500–7004.01053.589700–9004.01183.592900–12004.01193.51011200–15003.91273.41081500–18003.61283.21091800–22003.41313.0111Note. From "Protein requirements of very low birth weight infants," by E.E. Ziegler, 2007, J Pediatr Gastroenterol Nutr, 45, p. s170–4. Copyright 2007, Lippincott Williams & Wikins Inc. Reproduced with permission. Open table in a new tab Note. From "Protein requirements of very low birth weight infants," by E.E. Ziegler, 2007, J Pediatr Gastroenterol Nutr, 45, p. s170–4. Copyright 2007, Lippincott Williams & Wikins Inc. Reproduced with permission.