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

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

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.

Keywords: DHA; hospital stay; infant; inflammation; n-3 fatty acids; necrotizing enterocolitis; neonatal intensive care unit; omega-3; prematurity; very low birth weight.

Conflict of interest statement

P.C.C. acts as a consultant to BASF AS, Smartfish, DSM, Cargill, Danone/Nutricia, and Fresenius-Kabi. All other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
CONSORT diagram depicting the flow of the infants through the study. DHA, docosahexaenoic acid; NEC, necrotizing enterocolitis; and ITT, intent-to-treat.
Figure 2
Figure 2
Decision tree obtained from Chi-square automatic interaction detection multiple regression analysis for the prediction of confirmed necrotizing enterocolitis (NEC). The order of the variables, from top to bottom, shows their ranking for the prediction of confirmed NEC; the first was the intervention, the second was gestational age, and the last was presenting apnea.
Figure 3
Figure 3
The decision tree obtained from the Chi-square automatic interaction detection multiple regression analysis showed that no infants in the control group who received any volume of human milk developed necrotizing enterocolitis (NEC).

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