Balancing the Covariates in Studies on Enteral Feeding in Preterm Neonates

Correspondence

Indian Pediatr 2019;56: 693

	Balancing the Covariates in Studies on Enteral Feeding in Preterm Neonates
*Viraraghavan Vadakkencherry Ramaswamy and Sanghamitra Gummadapu** Department of Neonatology, Nori Multispeciality Hospital, Vijayawada, Andhra Pradesh, India. Email: * [email protected]
We congratulate Modi, et al. [1] for their work on early aggressive enteral feeding in neonates, published recently in Indian Pediatrics [1]. Successful establishment of enteral feeding and prevention of the dreaded complication of necrotizing Enterocolitis (NEC) in very and extreme preterm neonates is dependant on a multitude of factors. Some of the factors that can modify the risk of NEC as well as mortality include the use of maternal antibiotics, extended use of empirical antibiotics in the neonatal period, delayed cord clamping and probiotic use [2,3]. However, the above mentioned parameters fail to find a mention in the baseline characteristics in the present article, thus making it unclear if the covariates were equally balanced amongst the two groups. Though this trial is a randomized controlled trial (RCT), even RCTs are not immune from imbalance in baseline characteristics between the two treatment groups [4]. This imbalance is known to occur more frequently in trials with small sample sizes [4]. In spite of enrolling sick preterm neonates by the investigators, the NEC incidence rate of the subjects in either of the two groups was very low (1.5-3%). The Vermont Oxford Network and the National Institute of Child Health (NICHD) had reported the incidence of NEC to be 7.4% and 7% respectively in their cohort of very low birth weight (VLBW) neonates [5]. The ADEPT (Analysis of prospectively collected data from a randomised feeding trial, the Abnormal Doppler Enteral Prescription) trial, which had enrolled growth restricted preterm neonates <35 weeks gestation with antenatal doppler abnormalities had reported a NEC incidence rate of 18% in the early feeding group and 15% in the late feeding group [6]. Despite a higher percentage of growth retarded preterm neonates and the use of preterm formula milk as the second choice for enteral feeding in this study, the incidence rates of NEC are significantly lower than that reported from the Western literature. Could the authors dwell upon this unexpected finding of their study? References 1. Modi M, Ramji S, Jain A, Kumar P, Gupta N. Early aggressive enteral feeding in neonates weighing 750-1250 grams: A randomized controlled trial. Indian Pediatr. 2019;56:294-8. 2. Rose AT, Patel RM: A critical analysis of risk factors for necrotizing enterocolitis. Semin Fetal Neonatal Med. 2018;23:374-9. 3. Thompson-Branch AM, Havranek T. Influences of feeding on necrotizing enterocolitis. NeoReviews. 2018;19:e664-74. 4. Lewis SC, Warlow CP. How to spot bias and other potential problems in randomised controlled trials. J Neurol Neurosurg Psychiatry. 2004;75:181-7. 5. Sharma R, Hudak ML. A clinical perspective of necrotizing enterocolitis: Past, present, and future. Clin Perinatol. 2013;40:27-51. 6. Leaf 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:e1260-8.