Safety of aggressive nutrition bundle-aggressive parenteral nutrition, standardized feeding policy, human milk fortification and probiotics in babies born less than 34 weeks of gestation: a prospective analytical cohort study

Mubashir H. Shah, Nitin P. Rachwani, Reashma Roshan, Gaurav Patwardhan, Tushar Parikh, Sandeep S. Kadam


Background: Despite changes in nutritional interventions in neonatal intensive care units worldwide, significant proportion of preterm babies are growth restricted at discharge. Authors intended to look at the feasibility of aggressive nutrition bundle (aggressive parenteral nutrition, standardized feeding policy, fortification and probiotics) in preterm neonates.

Methods: This single centre prospective analytical cohort study, involving babies born before 34 weeks of gestation, was conducted in a tertiary hospital. Aggressive parenteral nutrition and enteral nutrition bundle intervention was started within 24 hours of birth. Clinical, laboratory and anthropometrical parameters were monitored longitudinally to ensure safety of this intervention.

Results: Mean gestational age and birth weight of the cohort (n=107) was 30.6 weeks (SD±2.6) and 1147 grams (SD±287) respectively. Out of 107 babies, 67.3% (n=72) have extra uterine growth retardation (EUGR) at discharge and was more in small for gestational age neonates (p=0.001). With this aggressive parenteral and enteral nutrition bundle intervention, medical necrotizing enterocolitis (NEC) developed in 7.4 % (n=8) babies while surgical NEC was seen in 1.9%. (n=2). Early onset and late-onset sepsis occurred in 1.8% and 5.4% of babies respectively while mild hyperammonemia, mild hypertriglyceridemia, raised creatinine and urea developed in 12.4%, 4.6%, 7.4% and 11.7% respectively. Hyperglycemia and hypoglycemia were present in 8.8% and 5.6% babies respectively.

Conclusions: Aggressive nutrition bundle (aggressive parenteral nutrition, standardized feeding policy, fortification and probiotics) can be safely employed in preterm babies. There is an urgent need to design a study to see the impact of this approach on incidence of EUGR in preterm babies.


Aggressive nutrition bundle, Parenteral nutrition, Preterm babies, Safety

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Velaphi S. Nutritional requirements and parenteral nutrition in preterm infants. South African J Clin Nutr. 2011;24(3):27-31.

Lapillonne A, Ian J. Griffin M. Feeding preterm infants today for later metabolic and cardiovascular outcomes. J Paediatr. 2013;162(3):s7-16.

Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA PW. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Paediatr. 2006;117:1253-61.

Stephens BE, Walden RV, Gargus RA, Tucker R, McKinley L, Mance M, et al. First-week protein and energy intakes are associated with 18-month developmental outcomes in extremely low birth weight infants. Pediatr. 2009;123(5):1337-43.

Ehrenkranz RA. Extrauterine growth restriction: is it preventable?. J Pediatr. 2014;90(1):01-3.

Ehrenkranz RA. Early nutritional support and outcomes in ELBW infants. Early Hum Dev. 2010;86(1):s21-5.

Martin CR, Brown YF, Ehrenkranz RA, O’Shea TM, Allred EN, Belfort MB, et al. Nutritional Practices and Growth Velocity in the First Month of Life in Extremely Premature Infants. Paediatr. 2009;124(2).

Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59.

Hay WW. Aggressive Nutrition of the Preterm Infant. Curr Pediatr Rep. 2013;1(4):229-39.

Thureen PJ, Melara D, Fennessey PV, Hay WW. Effect of low versus high intravenous amino acid intake on very low birth weight infants in the early neonatal period. Pediatr Res. 2003;53(1):24-32.

Ibrahim HM, Jeroudi MA, Baier RJ, Dhanireddy R, Krouskop RW. Aggressive early total parental nutrition in low-birth-weight infants. J Perinatol. 2004;24:482-6.

Poindexter BB, Langer JC, Dusick AM, Ehrenkranz RA. 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.

Wang DH. Multicenter study of the nutritional status of premature infants in neonatal intensive care unit in China: report of 974 cases. Chinese J Pediatr. 2009;47(1):12-7.

Shukla A, Jung B, Chandra S. Maximizing nutrition to minimize extrauterine growth retardation in Low Birth weight neonates and assessing retinopathy of prematurity in this population. Accessed at: Accessed on: 20 December 2018.

Mukhopadhyay K, Louis D, Mahajan R, Kumar P. Predictors of Mortality and Major Morbidities in Extremely Low Birth Weight Neonates. Indian Pediatr. 2013;50:119-23.

Obasa TO, Mohammed SS, Ernest SK, Mokuolu OA. Extrauterine growth restriction occurring in babies with gestational ages equal to and less than 32 weeks managed at the University of Ilorin Teaching Hospital. J Med Sci. 2012;3(9):562-8.

Freitas BA, Priore SE, Lima LM, Franceschini SD. Extrauterine growth restriction: Universal problem among premature infants. Nutrition Magazine. 2016;29(1):53-64.

Rover MD, Viera CS, de Oliveira Toso BR, Grassiolli S, Bugs BM. Growth of very low birth weight preterm until 12 months of corrected age. J Human Growth Development. 2015;25(3):351-6.

Corvaglia L, Fantini MP, Aceti A, Gibertoni D, Rucci P, Baronciani D, Faldella G. Predictors of full enteral feeding achievement in very low birth weight infants. PLoS One. 2014;9(3):e92235.

Graziano PD, Tauber KA, Cummings J, Graffunder E, Horgan MJ. Prevention of postnatal growth restriction by the implementation of an evidence-based premature infant feeding bundle. J Perinatol. 2015;35(8):642.

McCallie KR, Lee HC, Mayer O, Cohen RS, Hintz SR, Rhine WD. Improved outcomes with a standardized feeding protocol for very low birth weight infants. J Perinatol. 2011;31(S1):S61-7.

Valentine CJ, Fernandez S, Rogers LK, Gulati P, Hayes J, Lore P, et al. Early amino-acid administration improves preterm infant weight. J Perinatol. 2009;29:428-32.

Ridout E, Melara D, Rottinghaus S, Thureen PJ. Blood urea nitrogen concentration as a marker of amino-acid intolerance in neonates with birthweight less than 1250 g. J Perinatol. 2005;25(2):130-3.

Burgess L, Morgan C, Mayes K, Tan M. Plasma arginine levels and blood glucose control in very preterm infants receiving 2 different parenteral nutrition regimens. JPEN J Parenter Enter Nutr. 2014;38(2):243-53.

Mavaheer A, Grime C, Morgan C. Increasing early protein intake is associated with a reduction in insulin-treated hyperglycemia in very preterm infants. Nutr Clin Pract. 2012;27(3):399-405.

Burattini I, Bellagamba MP, Spagnoli C, D’Ascenzo R, Mazzoni N, Peretti A, et al. Targeting 2.5 versus 4 g/kg/day of amino acids for extremely low birth weight infants: a randomized clinical trial. J Pediatr. 2013;163(5):1278-2.

Vlaardingerbroek H, Vermeulen MJ, Rook D, van den Akker CH, Dorst K, Wattimena JL, et al. Safety and efficacy of early parenteral lipid and high-dose amino acid administration to very low birth weight infants. J Pediatr. 2013;138(3):638-44.

Wu G, Jaeger LA, Bazer FW, Rhoads JM. Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications. J Nutr Biochem. 2004;15(8):442-51.

Kashyap S, Ohira-Kist K, Abildskov K, Towers HM, Sahni R, Ramakrishnan R, et al. Effects of quality of energy intake on growth and metabolic response of enterally fed low-birth-weight infants. Pediatr Res. 2001;50(3):390-7.

Jadhav P, Parimi PS, Kalhan SC. Parenteral amino acid and metabolic acidosis in premature infants. JPEN J Parenter Enter Nutr. 2007;31(4):278-83.

Eichenwald EC, Stark AR. Management and Outcomes of Very Low Birth Weight. N Engl J Med. 2008;358(16):1700-11.

Neu J. In: Fanaroff AA, Benitz WE, Donn SM, Neu J, Papile L, editors. Commentary in 2012 year book of neonatal and perinatal medicine. Philadelphia: Elsevier. 2012:216-9.

Alaedeen DI, Walsh MC, Chwals WJ. Total parenteral nutrition associated hyperglycemia correlates with prolonged mechanical ventilation and hospital stay in septic infants. J Pediatr Surg. 2006;41(1):239-44.

Kumar M, Tripathi S, Agrawal N, Singh SN. Growth of premature neonates admitted in a level III neonatal unit. Clin Epidemiol Glob Heal. 2014;2(2):56-0.

Dusick AM, Poindexter BB, Ehrenkranz RA, Lemons JA. Growth failure in the preterm infant: can we catch up? Semin Perinat. 2003;27(4):302-10.

Kim ES, Sohn JA, Lee EH, Choi EJ, Lee HJ, Lee JA, et al. Extrauterine Growth Restriction in Very Low Birth Weight Infants. J Korean Soc Neonato. 2010;17:53-63.

Shan HM, Cai W, Sun JH, Cao Y, Shi YY, Fang BH. Extrauterine growth retardation and correlated factors in premature neonates. Chinese J Pediatr. 2007;45(3):183-8.

Barone G, Maggio L, Saracino A, Perri A, Romagnoli C, Zecca E. How to feed small for gestational age newborns. Italian J Pediatr. 2013;39(1):28.

Radmacher PG, Looney SW, Rafail ST, Adamkin DH. Prediction of extrauterine growth retardation (EUGR) in VVLBW infants. J Perinat. 2003;23(5):392.