Práticas nutricionais e restrição de crescimento pós-natal em prematuros

Rev Assoc Med Bras ramb Revista da Associação Médica Brasileira Rev. Assoc. Med. Bras. 0104-4230 1806-9282 Associação Médica Brasileira RESUMO Objetivo: avaliar as práticas nutricionais em unidade de cuidados intensivos neonatais (UCIN) associadas a déficit de crescimento em recém-nascidos pré-termo (RNPT). Métodos: estudo retrospectivo de RNPT com peso entre 500 e 1.499 g internados em UCIN. Analisaram-se: evolução do crescimento e práticas de nutrição parenteral (NP) e enteral (NE). Resultados: dentre 184 RNPT divididos em G1 (500 a 990 g; n=63) e G2 (1.000 a 1.499 g; n=121), 169 receberam NP (G1=63; G2=106). Comparando-se com as recomendações, a NP foi iniciada tardiamente, sua progressão foi lenta e as ofertas máximas de glicose, aminoácidos, lipídios e energia foram baixas nos dois grupos. A oferta inicial de aminoácido e lipídio e a inicial e máxima de glicose e energia foram menores no G1. O início da NE foi precoce (1 a 2 dias), o tempo para atingir NE exclusiva foi adequado (11 a 15 dias), e o uso de leite humano foi possível por tempo razoável (7 a 13 dias). A análise multivariada mostrou que a síndrome do desconforto respiratório e o alcance tardio da oferta de 120 kcal/kg/dia aumentaram a chance de perda de peso superior a 10%. Sepse, oferta energética máxima por NP < 60 kcal/kg/dia e alcance tardio da oferta de 120 kcal/kg/dia aumentaram a chance de recuperar o peso de nascimento após 14 dias, enquanto a condição de pequeno para idade gestacional (PIG) ao nascimento reduziu essa chance. PIG ao nascimento, sepse e alcance de NE exclusiva após 14 dias aumentaram a chance de ser PIG na idade pós-conceptual de termo. Conclusão: aprimorar as práticas nutricionais em UCIN pode reduzir o déficit de crescimento em prematuros de muito baixo peso ao nascer. Introduction Postnatal growth is an important predictor of growth and development throughout childhood in preterm infants 1-3 but despite knowing the importance of optimizing growth rates in the neonatal period, reducing the rate of extra-uterine growth restriction is still one of the great challenges for neonatal intensive care units (NICU).4-6 The difficulties in providing adequate nutritional support in the hospitalization phase7-11 of newborns with very low weight is one of the main reasons for this postnatal growth deficit. A study to assess the nutritional practices adopted by four neonatal intensive care units, with different levels of complexity and dimensions, showed that after analysis and adaptation of the routines of each center to the recommendations established in the literature, there was a reduction in the number of days for starting parenteral and enteral nutrition, a shorter time for achieving exclusive enteral nutrition and an energy supply of 120 kcal/kg/day, reduced length of hospital stay, and reduced percentage of children with weight below the 10th percentile upon discharge.1 The objective of this study was to assess the nutritional practices in a NICU and their relationship to the growth of preterm newborns during hospitalization. Methods This was a retrospective analysis of the medical records of premature infants born between January 2000 and December 2005 in a public teaching hospital. Preterm infants with birth weight (BW) between 500 and 1,499 g admitted to the neonatal intensive care unit at Hospital São Paulo were considered eligible. The exclusion criteria were death ≤ 7 days, major congenital anomalies and genetic syndrome. The study was evaluated by the Ethics Committee of the Universidade Federal de São Paulo, which considered signing the informed consent form unnecessary. The data included about the newborns were gestational age, sex, birth weight, small for gestational age (SGA) characterized as birth weight below the 10th percentile (Alexander et al, 1996)12 and resuscitation in the delivery room. The morbidities analyzed were respiratory distress syndrome (RDS), sepsis, necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), peri-intraventricular hemorrhage (PIVH) grades III and IV, bronchopulmonary dysplasia (BPD) and frequency of SGA at post-conceptual age of term (weight below the 10th percentile). The drugs and procedures analyzed were use of surfactant, indomethacin, corticosteroids, mechanical ventilation and central venous catheter. Bodyweight was recorded daily in accordance with the recommended standards. The maximum percentage of weight loss, time to regain birth weight, daily weight gain after recovery of birth weight and the number of days to reach 1800 grams were calculated. Nutritional data were recorded daily and included the period between birth and a weight of 1800 g. For parenteral nutrition (PN) the start date, duration, and maximum initial supply of glucose, protein, lipid and energy were collected. For enteral nutrition (EN), characterized by infusion of the diet via gastrostomy tube, the type of diet, start date and number of days of minimal enteral nutrition use (≤10 mL/kg/day, without increments), days to achieve exclusive enteral nutrition and energy supply of 120 kcal/kg/day were recorded. Nutritional therapy was prescribed by the attending physicians, according to routine of the neonatal intensive care unit during the study period. PN and EN should be initiated within the first 48 hours of life. The recommendations established for PN were 80 kcal/kg/day of energy, maximum initial supply of glucose 6 g/kg/day and 16 to 18 g/kg/day, respectively; amino acids and lipids starting within 48 hours of birth and initial doses, increments and maximum supply of 1.0, 1.0 and 3.5 g/kg/day of amino acids and 0.5 to 1.0 g/kg/day, 0.5 to 1.0 g/kg/day and 3.0 g/kg/day of lipids, respectively. Minimal enteral nutrition could be initiated within the first 48 hours of life and the progression to exclusively enteral nutrition was performed according to the clinical status of the child, with increments of 20 mL/kg/day in volume. Human milk was only to be used where possible, and formula for preterm infants when breast milk was not available. The use of additives to human milk started when human milk volume reached 100 mL/kg/day. The numerical variables were expressed as median and range, and compared using the Mann-Whitney U test, or the mean and standard deviation, compared using the Student's t test. The categorical variables were expressed as numbers and percentages, and compared using the chi-square or Fisher's exact test. To assess the factors associated with the percentage of weight loss, time to regain birth weight and frequency of small children for post-conceptual age, a logistic regression model was created using the variables with p value <0.15. The statistical analysis was performed using Stata 10.0 software. Statistical significance was set at 5% (p <0.05). Results During the study period, 305 preterm infants with birth weights between 500 and 1,499 g were admitted to the NICU at Hospital São Paulo. One hundred and one of these were excluded: 87 for death ≤7 days, 11 for major congenital malformations and 3 for not using PN and EN. Twenty medical records were not located, although some of the data was available. The study group and the group with incomplete information were similar according to the perinatal variables, but the use of central venous catheter was higher (p = 0.001) in the group with incomplete information (7 vs. 37.5%). The 184 newborns were divided into two subgroups according to birth weight: group (G1) - 500 to 999 g (n=63) and group (G2) - 1,000 to 1,499 g (n=121). Except for gender, all clinical variables were different between subgroups (Table 1). TABLE 1 Characteristics of the newborns in the hospitalization period. Group 1 (n=63) Group 2 (n=121) p Gestational age (weeks) 27.7±2.1 30.6±2.2 0.000 Male 25 (39.7%) 66 (54.5%) 0.055 Birth weight (g) 798.2±142.4 1258.3±137.1 0.000 SGA 13 (20.6%) 43 (35.5%) 0.037 Resuscitation in the delivery room 53 (84.0%) 60 (49.6%) 0.000 RDS 37 (58.1%) 35 (28.9%) 0.000 Sepsis 48 (76.1%) 44 (36.3%) 0.000 Necrotizing enterocolitis 12 (19.0%) 11 (9.0%) 0.053 Patent ductus arteriosus 28 (44.4%) 25 (20.6%) 0.001 PIVH 31 (49.2%) 20 (16.5%) 0.000 Bronchopulmonary dysplasia 35 (55.5%) 16 (13.2%) 0.000 Surfactant 34 (53.9%) 30 (24.8%) 0.000 Indomethacin 24 (38.1%) 22 (18.2%) 0.003 Corticoid 3 (4.8%) 3 (1.6%) 0.336 Central venous catheter 42 (66.7%) 34 (28.1%) 0.000 Mechanical ventilation (hours) 264 (24 – 1032) 120 (12 – 1296) 0.000 SGA: small for gestational age; RDS: respiratory distress syndrome; PIVH: peri–intraventricular hemorrhage. The infusion of glucose began within the first hours of life in all patients. PN was administered in 169 (92%) newborns (63 in G1 and 106 in G2) and their characteristics are shown in Table 2. TABLE 2 Characteristics of parenteral and enteral nutrition. Days to maximum supply Parenteral nutrition Group 1 (n=63) Group 2 (n=106) p Glucose 5 (1 – 26) 4 (1 – 35) 0.283 Amino acids 7 (2 – 33) 6 (2 – 31) 0.106 Lipids 6 (2 – 31) 7 (2 – 38) 0.085 Initial glucose (g/kg/day) 5.8 (1.5 – 10.0) 7.3 (0.3 – 11.5) 0.000 Maximum glucose (g/kg/day) 9.8 (5.7 – 18.2) 13.3 (5.3 – 18.6) 0.000 Initial amino acid (g/kg/day) 0.5 (0.5 – 1.5) 1.0 (0.5 – 2.0) 0.002 Maximum amino acid (g/kg/day) 2.0 (0.5 – 3.5) 2.0 (0.5 – 4.0) 0.967 Initial lipid (g/kg/day) 0.5 (0.5 – 1.0) 0.5 (0.5 – 1.5) 0.001 Maximum lipid (g/kg/day) 2.0 (0.5 – 3.0) 2.0 (0.5 – 3.5) 0.746 Initial energy (kcal/kg/day) 24.9 (10.1 – 42.3) 34.7 (1.0 – 49.1) 0.000 Maximum energy (kcal/kg/day) 51.1 (27.3 – 87.1) 60.1 (27.2 – 96.2) 0.000 Start of PN (days) 2 (1 – 6) 3 (1 – 11) 0.472 Duration of PN (days) 11 (2 – 104) 8.5 (1 – 68) 0.006 Enteral Nutrition Group 1 (n=63) Group 2 (n=121) p Human milk (days) 13 (1 – 60) 7 (1 – 44) 0.004 Human milk and Formula (days) 14 (1 – 97) 9 (1 – 46) 0.002 Preterm formula (days) 27 (2 – 88) 24 (1 – 64) 0.107 Start of EN (days) 4 (1 – 16) 3 (1 –11) 0.000 Duration of minimum EN (days) 2 (1 – 30) 1 (1 – 15) 0.000 Time for exclusive EN (days) 15 (3 – 42) 11 (5 – 69) 0.001 Duration of EN (days) 44 (1 – 95) 23.5 (7 – 76) 0.000 Time to 120 kcal/kg/day (days) 22 (10 – 52) 15 (7 – 63) 0.000 PN: parenteral nutrition; EN: enteral nutrition. The number of children receiving amino acids within the first 48 hours of life, between 48 and 72 hours and after 72 hours were, respectively, 36 (57.2%), 14 (22.2%) and 13 (20.6%) in G1, and 54 (50.9%), 31 (29.2%) and 21 (19.9%) in G2, while the ones receiving lipids in these periods were, respectively, 36 (57.2%), 14 (22.2%) and 13 (20.6%), in G1, and 49 (46.2%), 35 (33.0%) and 22 (20.8%), in G2, both without statistically significant differences. The duration of PN was longer (p=0.006) in G1 compared to G2. There was a significant difference between the groups for most of the EN variables (Table 2). Seven children (11.1%) in G1 and 3 children in G2 (2.5%) did not receive human milk (p=0.002). Most variables related to neonatal growth were different between the groups . The percentage of weight loss was greater (p=0.009) in G1 (13.4%; 0.4 to 44.7%) than in G2 (10.0%; 0.7 to 23.3% ), the time to regain birth weight was longer (p=0.005) in G1 (17.7, 9.5 days) compared to G2 (12.9, 6.0 days) and the average daily gain was lower (p=0.000) in G1 (20.5, 0.8 g) compared to G2 (25.7, 2.5 g). The time to reach 1800 g was longer (p=0.000) in the extremely low birth weight at birth group (46 days; 9 to 81 vs. 21 days; 9 to 25). The frequency of SGA infants at postconceptual age of term was higher in G1, 52 (82.5%) vs. 88 (72.7%), but without statistical significance (p=0.139). To assess the factors associated with maximum weight loss greater than 10% of birth weight, time to regain birth weight greater than 14 days and frequency of SGA at post-conceptual age of term, the logistic regression model included gender, birth weight, SGA at birth, respiratory distress syndrome, sepsis, necrotizing enterocolitis, mechanical ventilation > 7 days, use of PN > 8 days, maximum glucose supply < 16.0 g/kg/day, maximum amino acid supply < 2.0 g/kg/day, maximum lipid < 2.0 g/kg/day and energy supply < 60 kcal/kg/day and time to achieve exclusive EN and energy supply of 120 kcal/kg/day by EN for more than 14 days. The results are presented in Table 3. TABLE 3 Final logistic regression model to assess the relationship between clinical and nutritional variables and growth variables. OR 95CI p Weight loss >10% of birth weight Respiratory distress syndrome 3.024 [1.385; 6.605] 0.005 >14 days to 120 kcal/kg/day 3.442 [1.517; 7.719] 0.030 > 14 days to regain birth weight SGA 0.302 [0.127; 0.717] 0.007 Sepsis 2.636 [1.254; 5.540] 0.010 Maximum energy via PN <60 kcal/kg/day 3.029 [1.425; 6.442] 0.004 >14 days to 120 kcal/kg/day 4.551 [1.753; 11.814] 0.001 Small for post-conceptual age of term SGA at birth 9.995 [2.134; 46.826] 0.004 Sepsis 4.253 [1.496; 12.087] 0.006 >14 days for exclusive EN 6.994 [2.174; 22.501] 0.001 PN: parenteral nutrition; EN: enteral nutrition. Discussion With the increase in the survival of newborns with very low weight, reduction of morbidities and improved prognosis in the long term have become priorities. As such, neonatal nutrition is essential for adequate growth and development of preterm newborns. According to recent recommendations, PN can be initiated within the first hours of life, and is safe and effective even in very premature infants.13-15 In this study, PN was administered to 92% of newborns, but only 50% started it within the first 48 hours of life. Glucose administration was performed early, with an appropriate initial supply,16,17 and although the duration of PN was sufficient, the maximum supply achieved was lower than recommended. The incidence of hyperglycemia is high in extremely premature infants and may limit the administration of glucose in these newborns.18 The infusion of glucose with amino acids on the first day of life decreases protein catabolism, increases protein incorporation rates, can help lower plasma glucose concentrations and should be started within the first days of life.17,19 Studies comparing a high versus low supply of amino acids in the first days of life showed that high protein supplies resulted in increased protein incorporation without increasing toxicity,20-26 with initial supplies of 3.0 g/kg/day being recommended. In our study, only 53% received amino acids in the first 48 hours of life, and the initial and maximum supplies were low, taking 6 to 7 days to reach the maximum supply. This practice exposed newborns to a negative protein balance and may have contributed to the low supply of glucose and energy. Lipid emulsions are fundamental in PN for preterm newborns to meet the energy requirements for maintenance and growth and to prevent a deficiency of essential fatty acids. Lipid administration strategies include a minimum supply of 0.5 to 1.0 g/kg/day, starting on the first day of life, increasing 0.5 to 1.0 g/kg day to a maximum of 3.0 g/kg/day, attained in 4 to 5 days.15,16,27,28 In this study, approximately 50% of patients received lipid emulsion after 48 hours of life, the initial and maximum doses were low and it took 6 to 7 days to reach the maximum dose. This lipid supply was sufficient to meet the essential fatty acid requirements, but contributed to the low supply of energy. This conservative approach may have been the result of concerns with toxicity. However, a meta-analysis showed no differences between groups who received an early supply and those who did not receive an early supply of lipids in terms of growth, death and chronic lung disease outcomes.29 In the present study, EN was in line with the recommendations for best practices.30 Minimum EN was started early, its duration was short and the progression to exclusive EN was quick. EN in newborns of very low birth weight is often delayed for several days or weeks after birth, due to cardiorespiratory complications and concern about necrotizing enterocolitis.31 However, minimal enteral nutrition, especially human milk, provides numerous benefits and has been associated with a shorter time to reach exclusive EN, as well as reduced infection associated with central venous catheter, without increasing the incidence of necrotizing enterocolitis.32 The proposed increment of 20 mL/kg/day for EN is considered safe according to studies showing that increments of up to 30 mL/kg/day were not associated with increased incidence of necrotizing enterocolitis.33 With the increase in volume adopted, the time to achieve exclusive enteral nutrition was appropriate. The frequency of interruptions in EN was high (29.9%), but similar to those observed by Caple et al. of 26.8 and 29.6% for infants with low birth weight with increases in volume of 20 to 30 mL/kg/day, respectively.33 The diagnosis of necrotizing enterocolitis was frequent in this study (12.5%). The use of human milk was common, especially among newborns of extremely low birth weight, and may be a protective factor for enterocolitis;34,35 however, the mother's own milk or that from a donor was always pasteurized, which may have compromised its immunological capacity.36 In addition to stimulating the use of raw human milk from the actual mother, we should pay attention to some aspects of routine EN. As observed by Henderson et al., a shorter duration of minimal enteral nutrition and greater speed for attaining exclusive EN may be modifiable risk factors for the development of necrotizing enterocolitis.37 On the other hand, the time to reach 120 kcal/kg/day was long and may be related to the high frequency of feeding interruptions and diagnosis of necrotizing enterocolitis. The delay in attaining this energy supply was associated with greater weight loss and longer time to regain birth weight.38 The delay in regaining birth weight was also associated with low energy supply via PN, and the time to regain birth weight is a significant predictor of poor postnatal growth.39 The low energy supply via PN and the delay in achieving the maximum recommended supply in this population may be markers of an accumulated energy deficit and explain the higher percentage of weight loss and slower weight gain.40,41 Logistic regression analysis also showed that respiratory distress syndrome is associated with increased weight loss, which may be secondary to an inadequate supply of nutrients; this is especially difficult in children with respiratory failure.42 Sepsis increased the risk of delayed recovery of birth weight, and has been associated with slower weight gain during hospitalization;43 newborns with sepsis may develop intolerance to glucose and lipids, limiting the supply of these nutrients. As described by other researchers,43,44 SGA infants recovered their birth weight earlier. In this study, the SGA preterm infants had a greater gestational age than those of suitable weight for age (27.7 vs. 30.6 weeks) and may have presented a lower frequency of conditions that interfere with nutritional therapy. The restriction of intrauterine growth is extremely common in children with very low birth weight.6,14,44,45 In our population, the frequency of newborns with weight below the 10th percentile for age increased from 30.4% at birth to 76.1% at post-conceptual age of term, and the associated factors were SGA, sepsis and higher time for attaining exclusive enteral nutrition. The association between restriction of extra-uterine growth, SGA, bronchopulmonary dysplasia, number of days of parenteral nutrition and age to attain exclusive enteral nutrition has also been shown in other studies.6,40-42 Nutritional practices for preterm infants vary considerably between NICU and there is no definite strategy with proven capacity to safely optimize nutrition, growth and development.10 However, the implementation of a program with potentially better nutritional practices can promote a more adequate supply of nutrients and stimulate growth.9 1 Study conducted at Universidade Federal de São Paulo, São Paulo, SP, Brazil References 1 1 Relly B, Duenas M, Greecher C, Kimberlim L, Mujsce D, Miller D, et al. Evaluation, development, and implementation of potentially better practices in neonatal intensive care nutrition. Pediatrics. 2003; 111(4):461-70. Relly B Duenas M Greecher C Kimberlim L Mujsce D Miller D Evaluation, development, and implementation of potentially better practices in neonatal intensive care nutrition Pediatrics 2003 111 4 461 470 2 2 Olsen IE, Douglas KR, Schimid CH, Ausman LM, Dwyer JT. Intensive differences in weight growth velocity of extremely premature infants. Pediatrics. 2002; 110(6):1125-31. Olsen IE Douglas KR Schimid CH Ausman LM Dwyer JT Intensive differences in weight growth velocity of extremely premature infants Pediatrics 2002 110 6 1125 1131 3 3 Ehrenkranz RA. Growth outcomes of very low-birth weight infants in the newborn intensive care unit. Clin Perinatol. 2000; 27(2):325-45. Ehrenkranz RA Growth outcomes of very low-birth weight infants in the newborn intensive care unit Clin Perinatol 2000 27 2 325 345 4 4 Premer DM, Georgieff MK. Nutrition for ill neonates. Pediatr Rev. 1999; 20(9):56-62. Premer DM Georgieff MK Nutrition for ill neonates Pediatr Rev 1999 20 9 56 62 5 5 Stark AR, Carlo WA, Tyson JE, Papile LA, Wright LL, Shankaran S, et al. Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. 2001; 344(2):95-101. Stark AR Carlo WA Tyson JE Papile LA Wright LL Shankaran S Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network N Engl J Med 2001 344 2 95 101 6 6 Sakurai M, Itabashi K, Sato Y, Hibino S, Mizuno K. Extrauterine growth restriction in preterm infants of gestational age < 32 weeks. Pediatr Int. 2008; 50(1):70-5. Sakurai M Itabashi K Sato Y Hibino S Mizuno K Extrauterine growth restriction in preterm infants of gestational age < 32 weeks Pediatr Int 2008 50 1 70 75 7 7 Guzmán JM, Jaraba MJ, De La Torre MD, Ruiz-Conzález MD, Huertas RA, et al. Parenteral nutrition and immature neonates comparative study of neonates weighing under 1000 and 1000-1250 g at birth. Early Hum Dev. 2001; 65 suppl:s133-s144. Guzmán JM Jaraba MJ De La Torre MD Ruiz-Conzález MD Huertas RA Parenteral nutrition and immature neonates comparative study of neonates weighing under 1000 and 1000-1250 g at birth Early Hum Dev 2001 65 suppl s133 s144 8 8 Fanaroff AA, Stoll BJ, Wright LL, Carlo WA, Ehrenkranz RA, Stark AR, et al. Trends in neonatal morbidity and mortality for very low birthweight infants. Am J Obstet Gynecol. 2007; 196(2):1-8. Fanaroff AA Stoll BJ Wright LL Carlo WA Ehrenkranz RA Stark AR Trends in neonatal morbidity and mortality for very low birthweight infants Am J Obstet Gynecol 2007 196 2 1 8 9 9 Hans DM, Pylipow M, Long JD, Thurren PJ, Georgieff MK. Nutritional practices in the neonatal intensive care unit: analysis of a 2006 neonatal nutrition survey. Pediatrics. 2009; 123(1):51-7. Hans DM Pylipow M Long JD Thurren PJ Georgieff MK Nutritional practices in the neonatal intensive care unit: analysis of a 2006 neonatal nutrition survey Pediatrics 2009 123 1 51 57 10 10 Grover A, Khashu M, Mukherjee A, Kairamkonda V. Iatrogenic malnutrition in neonatal intensive care units: urgent need to modify practice. J Parenter Enteral Nutr. 2008; 32(2):140-4. Grover A Khashu M Mukherjee A Kairamkonda V Iatrogenic malnutrition in neonatal intensive care units: urgent need to modify practice J Parenter Enteral Nutr 2008 32 2 140 144 11 11 American Academy of Pediatrics Committee on Nutrition: nutricional needs of low birth weight infants. Pediatrics. 1985; 75:976-86. American Academy of Pediatrics Committee on Nutrition: nutricional needs of low birth weight infants Pediatrics 1985 75 976 986 12 12 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States National Reference for Fetal Growth. Obstet Gynecol. 1996; 87(2):163-8. Alexander GR Himes JH Kaufman RB Mor J Kogan M A United States National Reference for Fetal Growth Obstet Gynecol 1996 87 2 163 168 13 13 Koletzko B, Goulet O, Hunt J, Krohn k, Shamir R. Guidelines on paediatric parenteral nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and European Society for Clinical Nutrition and Metabolism (ESPEN), support by the European Society of Paediatric Research (ESPR). J Paediatr Gastroenterol Nutr. 2005; 41(Suppl 2):S19-S27. Koletzko B Goulet O Hunt J Krohn k Shamir R Guidelines on paediatric parenteral nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and European Society for Clinical Nutrition and Metabolism (ESPEN), support by the European Society of Paediatric Research (ESPR) J Paediatr Gastroenterol Nutr 2005 41 Suppl 2 S19 S27 14 14 De Curtis M, Rigo J. Extrauterine growth restriction in very-low-birthweight infants. Acta Paediatr. 2004; 93(12):1563-8. De Curtis M Rigo J Extrauterine growth restriction in very-low-birthweight infants Acta Paediatr 2004 93 12 1563 1568 15 15 Ibrahim HM, Jeroudi MA, Baier RJ, Dhanireddy R, Krouskop RW. Aggressive early total parenteral nutrition in low-birth-weight infants. J Perinatol. 2004; 24(8):482-6. Ibrahim HM Jeroudi MA Baier RJ Dhanireddy R Krouskop RW Aggressive early total parenteral nutrition in low-birth-weight infants J Perinatol 2004 24 8 482 486 16 16 Thureen PJ. Early aggressive nutrition in the neonate. Pediatr Rev. 1999; 20(9):45-55. Thureen PJ Early aggressive nutrition in the neonate Pediatr Rev 1999 20 9 45 55 17 17 Parimi P, S Kalhan. Carbohydrates including oligosaccharides and inositol. In: Tsang RC, Uauy R, Koletzko B, Zlotkin SH. Nutrition of the preterm infant. 2.ed. Digital Educational Publishing: Ohio, 2005. p.81-90. Parimi P Kalhan S Carbohydrates including oligosaccharides and inositol Tsang RC Uauy R Koletzko B Zlotkin SH Nutrition of the preterm infant 2.ed Digital Educational Publishing Ohio 2005 81 90 18 18 Hays SP, Smith EO, Sunehag AL. Hiperglycemia is a risk factor for early death and morbidity in extremely low birth-weight infants. Pediatrics. 2006; 118 (5):1811-8. Hays SP Smith EO Sunehag AL Hiperglycemia is a risk factor for early death and morbidity in extremely low birth-weight infants Pediatrics 2006 118 5 1811 1818 19 19 Thureen PJ, Anderson AH, Baron KA, Melara DJ, Hay WW, Fennessey PV. Protein balance in the first week of life in ventilated neonates receiving parenteral nutrition. Am J Clin Nutr. 1998; 68:1228-1136. Thureen PJ Anderson AH Baron KA Melara DJ Hay WW Fennessey PV Protein balance in the first week of life in ventilated neonates receiving parenteral nutrition Am J Clin Nutr 1998 68 1228 1136 20 20 Thurren PJ, Heird WC. Protein requirement of the preterm/low birthweight (LBW) infant. Pediatric Research. 2005; 57(5):95-8. Thurren PJ Heird WC Protein requirement of the preterm/low birthweight (LBW) infant Pediatric Research 2005 57 5 95 98 21 21 Braake FWJ, van den Akker CHP, Wattimena DJL, Huijmans JGM, van Goudoever JB. Amino acid administration to premature infants directly after birth. J Pediatr. 2005; 147:457-61. Braake FWJ van den Akker CHP Wattimena DJL Huijmans JGM van Goudoever JB Amino acid administration to premature infants directly after birth J Pediatr 2005 147 457 461 22 22 Van Den Akker CHP, Te Braake FWJ, Wattimena DJL, Voortman G, Schierbeek H, Vermes A, et al. Effects of early amino acid administration on leucine and glucose kinetics in premature infants. Pediatr Res. 2006; 59(5):732-5. Van Den Akker CHP Te Braake FWJ Wattimena DJL Voortman G Schierbeek H Vermes A Effects of early amino acid administration on leucine and glucose kinetics in premature infants Pediatr Res 2006 59 5 732 735 23 23 Poindexter BB, Langer JC, Disick AM, Ehrenkranz RE. Early provision of parenteral amino acids in extremely low birth-weight infants: relation to growth and neurodevelopmental outcome. J Pediatr. 2006; 148(3):300-5. Poindexter BB Langer JC Disick AM Ehrenkranz RE Early provision of parenteral amino acids in extremely low birth-weight infants: relation to growth and neurodevelopmental outcome J Pediatr 2006 148 3 300 305 24 24 Embleton ND. Optimal protein and energy intakes in preterm infants. Early Hum Dev. 2007; 83(12):831-7. Embleton ND Optimal protein and energy intakes in preterm infants Early Hum Dev 2007 83 12 831 837 25 25 Jadhav P, Parimi PS, Kalhan SC. Parenteral amino acid and metabolic acidosis in premature infants. J Parenter Enter Nutr. 2007; 31(4):278-83. Jadhav P Parimi PS Kalhan SC Parenteral amino acid and metabolic acidosis in premature infants J Parenter Enter Nutr 2007 31 4 278 283 26 26 Valentine CJ, Rogers SF, Gulati P, Hayes J, Lore P, Puthoff T, et al. Early amino-acid administration improves preterm infant weight. J Perinatol. 2009; 29(6):428-32. Valentine CJ Rogers SF Gulati P Hayes J Lore P Puthoff T Early amino-acid administration improves preterm infant weight J Perinatol 2009 29 6 428 432 27 27 Koletzko B, Innis SM. Lipids. In: Tsang RC, Uauy R, Koletzko B, Zlotkin SH. Nutrition of the preterm infant. 2.ed. Digital Educational Publishing: Ohio, 2005. p.97-127. Koletzko B Innis SM. Lipids Tsang RC Uauy R Koletzko B Zlotkin SH Nutrition of the preterm infant 2.ed Digital Educational Publishing Ohio 2005 97 127 28 28 Ziegler EE, Thureen PJ, Carlson SJ. Aggressive nutrition of the very low birthweight infant. Clin Perinatol. 2002; 29(2):225-44. Ziegler EE Thureen PJ Carlson SJ Aggressive nutrition of the very low birthweight infant Clin Perinatol 2002 29 2 225 244 29 29 Simmer K, Rao SC. Early introduction of lipids to parenterally-fed preterm infants. Cochrane Database Syst Rev. 2005:CD005256. Simmer K Rao SC Early introduction of lipids to parenterally-fed preterm infants Cochrane Database Syst Rev 2005 CD005256 30 30 Ehrenkranz RA. Early, aggressive nutritional management for very low birth weight infants: what's is the evidence? Semin Perinatol 2007; 31(2):48-55. Ehrenkranz RA Early, aggressive nutritional management for very low birth weight infants: what's is the evidence? Semin Perinatol 2007 31 2 48 55 31 31 Tyson JE, Kennedy KA, Lucke JF, Pedroza C. Dilemmas initiating enteral feedings in high risk infants: how can they be resolved? Semin Perintal. 2007; 31(2):61-73. Tyson JE Kennedy KA Lucke JF Pedroza C Dilemmas initiating enteral feedings in high risk infants: how can they be resolved? Semin Perintal 2007 31 2 61 73 32 32 Kennedy KA, Tyson JE, Chamnanvanakij S. Rapid versus slow rate of advancement of feeding for promoting growth and preventing necrotizing enterocolitis in parenterally fed low birth weight infants. Cochrane Database Syst Rev. 2000:CD001241. Kennedy KA Tyson JE Chamnanvanakij S Rapid versus slow rate of advancement of feeding for promoting growth and preventing necrotizing enterocolitis in parenterally fed low birth weight infants Cochrane Database Syst Rev 2000 CD001241 33 33 Caple J, Armentrout D, Huseby V, Halbardier B, Garcia J, Sparks JW, et al. Randomized, controlled trial of slow versus feeding volume advancement in preterm infants. Pediatrics 2004; 114(6):1597-600. Caple J Armentrout D Huseby V Halbardier B Garcia J Sparks JW Randomized, controlled trial of slow versus feeding volume advancement in preterm infants Pediatrics 2004 114 6 1597 1600 34 34 Yu VYH, Simmer K. Enteral nutrition: aspects, strategy and management. In: Tsang RC, Uauy R, Koletzko B, Zlotkin SH. Nutrition of the preterm infant 2.ed. Digital Educational Publishing: Ohio, 2005. p.311-22. Yu VYH Simmer K Enteral nutrition: aspects, strategy and management Tsang RC Uauy R Koletzko B Zlotkin SH Nutrition of the preterm infant 2.ed Digital Educational Publishing Ohio 2005 311 322 35 35 Sullivan S, Schanler RJ, Kim JH, Patel AL, Trawoger R, Kiechl-Kohlendorfer U, et al. An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milkbased products. J Pediatr. 2010; 156:562-7. Sullivan S Schanler RJ Kim JH Patel AL Trawoger R Kiechl-Kohlendorfer U An exclusively human milk-based diet is associated with a lower rate of necrotizing enterocolitis than a diet of human milk and bovine milkbased products J Pediatr 2010 156 562 567 36 36 Schanler RJ, Lau C, Hust NM, Smith EO. Radomized trial of donor human milk versus preterm formula as substitutes for mother's own milk in the feeding of extremely premature infants. Pediatrics. 2005; 116(2):400-6. Schanler RJ Lau C Hust NM Smith EO Radomized trial of donor human milk versus preterm formula as substitutes for mother's own milk in the feeding of extremely premature infants Pediatrics 2005 116 2 400 406 37 37 Henderson G. Craig S, Brocklehurst P, McGuire W. Enteral feeding regimens and necrotizing enterocolitis in preterm infants: a multicentre case-control study. Arch Dis Child Fetal Neonatal. 2009; 94(2):120-3. Henderson G Craig S Brocklehurst P McGuire W Enteral feeding regimens and necrotizing enterocolitis in preterm infants: a multicentre case-control study Arch Dis Child Fetal Neonatal 2009 94 2 120 123 38 38 Diekmann M, Genzel-Boroviczény O, Zoppelli L, von Poblotzki M. Postnatal growth curves for extremely low birth weight infants with early enteral nutrition. Eur J Pediatr. 2005; 164(12):714-23. Diekmann M Genzel-Boroviczény O Zoppelli L von Poblotzki M Postnatal growth curves for extremely low birth weight infants with early enteral nutrition Eur J Pediatr 2005 164 12 714 723 39 39 Yu VYH, Simmer K. Enteral nutrition: aspects, strategy and management. In: Tsang RC, Uauy R, Koletzko B, Zlotkin SH. Nutrition of the preterm infant 2.ed. Digital Educational Publishing: Ohio, 2005. p.311-22. Yu VYH Simmer K Enteral nutrition: aspects, strategy and management Tsang RC Uauy R Koletzko B Zlotkin SH Nutrition of the preterm infant 2.ed Digital Educational Publishing Ohio 2005 311 322 40 40 Tyson JE, Kennedy KA, Lucke JF, Pedroza C. Dilemmas initiating enteral feedings in high risk infants: How can they be resolved? Semin Perintal. 2007; 31(2):61-73. Tyson JE Kennedy KA Lucke JF Pedroza C Dilemmas initiating enteral feedings in high risk infants: How can they be resolved? Semin Perintal 2007 31 2 61 73 41 41 Radmacher PG, Looney SW, Rafail ST, Adamkin DH. Prediction of extrauterine growth retardation (EUGR) in VVLBW infants. J Perinatol. 2003; 23(5):392-5. Radmacher PG Looney SW Rafail ST Adamkin DH Prediction of extrauterine growth retardation (EUGR) in VVLBW infants J Perinatol 2003 23 5 392 395 42 42 Clark RH, Thomas P, Peabody J. Extrauterine growth restriction remains a serious problem in prematurely born neonates. Pediatrics. 2003; 111(5):98690. Clark RH Thomas P Peabody J Extrauterine growth restriction remains a serious problem in prematurely born neonates Pediatrics 2003 111 5 98690 43 43 Ehrenkranz RA, Younes N, Lemons JA, Fanaroff AA, Donovan EF, Wright LL, et al. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics. 1999; 104(2):280-9. Ehrenkranz RA Younes N Lemons JA Fanaroff AA Donovan EF Wright LL Longitudinal growth of hospitalized very low birth weight infants Pediatrics 1999 104 2 280 289 44 44 Embleton NE, Pang N, Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics. 2001; 107(2):270-3. Embleton NE Pang N Cooke RJ Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics 2001 107 2 270 273 45 45 Shan HM, Cai W, Cao Y, Fang BH. Extrauterine growth retardation in premature infants in Shanghai: a multicenter retrospective review. Eur J Pediatr. 2009; 168(9):1055-9. Shan HM Cai W Cao Y Fang BH Extrauterine growth retardation in premature infants in Shanghai: a multicenter retrospective review Eur J Pediatr 2009 168 9 1055 1059