Omega-3 fatty acid supplementation to prevent recurrent preterm birth: a randomized controlled trial.

Objective: To assess whether the addition of an omega-3 long-chain polyunsaturated fatty acid supplement would reduce preterm birth in women with at least one prior spontaneous preterm birth receiving 17alpha-hydroxyprogesterone caproate.

Methods: We conducted a randomized, double-masked, placebo-controlled trial in 13 centers. Women with a history of prior spontaneous singleton preterm birth and a current singleton gestation were assigned to either a daily omega-3 supplement (1,200 mg eicosapentaenoic acid and 800 mg docosahexaenoic acid) or matching placebo from 16-22 through 36 weeks of gestation. All participants received weekly intramuscular 17alpha-hydroxyprogesterone caproate (250 mg). The primary study outcome was delivery before 37 weeks of gestation. A sample size of 800 was necessary to have 80% power to detect a 30% reduction in the primary outcome from 30%, assuming a type I error two-sided of 5%.

Results: A total of 852 women were included, and none was lost to follow up. Delivery before 37 weeks of gestation occurred in 37.8% (164/434) of women in the omega-3 group and 41.6% (174/418) in the placebo group (relative risk 0.91, 95% confidence interval 0.77-1.07).

Conclusion: Omega-3 long-chain polyunsaturated fatty acid supplementation offered no benefit in reducing preterm birth among women receiving 17alpha-hydroxyprogesterone caproate who have a history of preterm delivery.

Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902.

Level Of Evidence: I.