[Skip to Content]
[Skip to Content Landing]
Views 4,919
Citations 0
Original Investigation
July 14, 2020

Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia–Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Pediatrics, Faculty of Medicine, Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec, Canada
  • 2Department of Pediatrics, Cumming School of Medicine, University of Calgary, Foothills Medical Centre, Calgary, Alberta, Canada
  • 3Department of Obstetrics and Gynecology, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
  • 4School of Public Health, Université de Montréal, Montreal, Quebec, Canada
  • 5Department of Pediatrics, Université de Montréal, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
  • 6Division of Neonatology, Royal Alexandra Hospital, Edmonton, Alberta, Canada
  • 7Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
  • 8Division of Neonatology, Children’s Hospital of Eastern Ontario, Ottawa, Canada
  • 9Department of Neonatology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
  • 10Department of Endocrinology and Nephrology, Centre Hospitalier Universitaire de Québec-Université Laval, Quebec City, Quebec, Canada
  • 11Department of Pediatrics, Division of Neonatology, University of British Columbia, Vancouver, Canada
  • 12Department of Social and Preventive Medicine, Centre Hospitalier Universitaire de Québec-Université Laval, Hôpital du Saint-Sacrement, Quebec City, Quebec, Canada
  • 13Division of Neonatology, Montréal Children’s Hospital, McGill University, Montreal, Quebec, Canada
  • 14Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada
  • 15Department of Pediatrics, Royal Columbian Hospital, New Westminster, British Columbia, Canada
  • 16Department of Pediatrics, Section of Neonatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
  • 17Department of Maternity Care and Pediatrics, Victoria General Hospital, Island Health, Victoria, British Columbia, Canada
  • 18Department of Pediatrics, Université de Sherbrooke, Hôpital Fleurimont, Sherbrooke, Quebec, Canada
  • 19Faculty of Agricultural, Life, and Environmental Sciences, University of Alberta, Edmonton, Canada
  • 20Department of Pediatrics and Child Health, Max Rady School of Medicine, University of Manitoba, Winnipeg, Canada
  • 21Department of Pediatrics, Queen’s University, Kingston, Ontario, Canada
JAMA. 2020;324(2):157-167. doi:10.1001/jama.2020.8896
Visual Abstract. Maternal Docosahexaenoic Acid Supplementation and Bronchopulmonary Dysplasia–Free Survival in Breastfed Preterm Infants
Maternal Docosahexaenoic Acid Supplementation and Bronchopulmonary Dysplasia–Free Survival in Breastfed Preterm Infants
Key Points

Question  Does maternal docosahexaenoic acid (DHA) supplementation during the neonatal period improve bronchopulmonary dysplasia–free survival in breastfed infants born before 29 weeks of gestation?

Findings  In this randomized clinical trial that included 461 mothers and 528 preterm infants and was terminated early, maternal intake of DHA during the neonatal period did not significantly improve infants’ bronchopulmonary dysplasia–free survival at 36 weeks’ postmenstrual age (54.9% vs 61.6% with placebo).

Meaning  Supplementation with DHA in lactating mothers did not significantly improve bronchopulmonary dysplasia–free survival in preterm infants, although study interpretation is limited by early trial termination.

Abstract

Importance  Maternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive.

Objective  To determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia–free survival in breastfed infants born before 29 weeks of gestation.

Design, Setting, and Participants  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.

Interventions  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.

Main Outcomes and Measures  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.

Results  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], P = .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], P = .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], P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different.

Conclusions and Relevance  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.

Trial Registration  ClinicalTrials.gov Identifier: NCT02371460

×