Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial.

Mariela Bernabe-García,Luis Chávez-Sánchez,Leovigildo Mateos-Sánchez,Gabriel Lara-Flores,Augusto Aguilera-Joaquín,Philip Calder,Leonardo Cruz-Reynoso,Raúl Villegas-Silva,Luisa Sánchez-García,Maricela Rodríguez-Cruz

doi:10.3390/nu13020648

Abstract

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell’s scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: n = 105; control-group: n = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; p = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = −7%, (95% CI −12.00 to −1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); p = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.

Highlights

Necrotizing enterocolitis (NEC) is a multifactorial inflammatory bowel disease
A randomized double-blind parallel-group clinical trial was conducted in preterm newborn infants with birthweight ≤ 1500 g, but ≥ 1000 g, with an expected functional gastrointestinal tract; infants were recruited between October 2012 and October 2017 from two hospitals affiliated with the Instituto Mexicano del Seguro Social (IMSS) in México
225 preterm infants were recruited and randomized; 214 infants received at least one dose of docosahexaenoic acid (DHA) or sham and from them, 100 infants per group were analysed per protocol (Figure 1)

Summary

Introduction

Necrotizing enterocolitis (NEC) is a multifactorial inflammatory bowel disease. This condition starts with an unbalanced pro-inflammatory response that rapidly evolves without warning into a necrotic bowel and/or death. Most cases occur in preterm infants (birth weight < 1500 g or < 32 weeks of gestational age) [1,2], and NEC remains a leading cause of morbidity and mortality in neonatal intensive care units (NICUs) worldwide [3]. The pathophysiology of NEC involves bowel and immune immaturity, including scarce mucus, low secretory immunoglobulin A, poor closure between enterocytes along with an altered intestinal bacterial diversity (dysbiosis) related to antibiotic administration, and the type of feeding, among other factors, especially in formula-fed infants [5,6].

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