Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia–Free Survival in Breastfed Preterm Infants
Authors: Isabelle Marc, Bruno Piedboeuf, Thierry Lacaze-Masmonteil, William Fraser, Benoît Mâsse, Ibrahim Mohamed, Mosarrat Qureshi, Jehier Afifi, Brigitte Lemyre, Georges Caouette, Julie Bartholomew, Anne Monique Nuyt, Pierre Julien, Anne Synnes, Michel Lucas, Thérèse Perreault, Lannae Strueby, Zenon Cieslak, Kamran Yusuf, Gustavo Pelligra, Edith Massé, Bodil Larsen, Cecilia de Cabo, Chelsea Ruth, Faiza Khurshid, Pascal M. Lavoie
Journal: JAMA (2020)

<h3>Importance</h3> Maternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive. <h3>Objective</h3> To determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia–free survival in breastfed infants born before 29 weeks of gestation. <h3>Design, Setting, and Participants</h3> Superiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier. <h3>Interventions</h3> There were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks' postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules. <h3>Main Outcomes and Measures</h3> The primary outcome was bronchopulmonary dysplasia–free survival in infants at 36 weeks' postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia. <h3>Results</h3> Enrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, –5.0% [95% CI, –11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04],<i>P</i> = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, –3.9% [95% CI, –6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13],<i>P</i> = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73],<i>P</i> = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different. <h3>Conclusions and Relevance</h3> Among breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia–free survival at 36 weeks' postmenstrual age compared with placebo. Study interpretation is limited by early trial termination. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02371460