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

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.

Impact of Docosahexaenoic acid supplementation on proinflammatory cytokines release and the development of Necrotizing enterocolitis in preterm Neonates: A randomized controlled study

“…The study findings agree with data reported regarding the protective effect of n-3 LCPUFA against sepsis ( Al-Biltagi et al, 2017 ). The findings are also consistent with those of a recent study suggesting that daily enteral DHA supplementation can prevent NEC in preterm infants ( Bernabe-García et al, 2021 ). Unlike our study, results from that study only took into consideration neonates with confirmed NEC (evaluated with Bell’s scale from stage ≥ IIA).…”

Age of onset of necrotising enterocolitis (NEC) and focal intestinal perforation (FIP) in very preterm and low birthweight infants: a systematic review

“…Analysis was undertaken on 10 RCTs and 14 observational studies containing a total of 51 NEC cohorts, 23 randomised and 28 observational cohorts and 2 FIP cohorts 3 10–32. Details of these studies are in online supplemental table 5.…”

Necrotizing enterocolitis in premature infants—A defect in the brakes? Evidence from clinical and animal studies

“…In early clinical trials, lactoferrin used alone or when combined with probiotics decreased NEC in preterm infants 160 ; however, subsequent larger studies have not confirmed the prevention of NEC with lactoferrin 161 , 162 . Although docosahexaenoic acid has been shown in independent studies to decrease NEC incidence in preterm infants, a meta-analysis of clinical trials did not show protection 148 , 150 . Although several biologically active molecules have been tested to prevent NEC, current evidence suggest that only probiotics can reduce TLR-mediated NEC in premature infants 5 , 73 , 150 .…”

“…The elegant mechanistic studies by Good et al 147 and others 146 have shown that EGF in human milk protects against NEC by inhibiting LPS-mediated TLR4 activation and autophagy. Docosahexaenoic acid, an ω3 polyunsaturated fatty acid present in human milk, was also found to inhibit TLR4 expression and experimental NEC in neonatal rats 148 , 149 . Several other biologically active lipids, carbohydrates, or proteins with potential effects on TLR signaling have been shown to reduce experimental NEC 150 .…”