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

Abstract

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.

Fig. 1

Screening, randomization, and follow-up of study participants. Harper. Omega-3 for Repeat Preterm Birth Prevention. Obstet Gynecol 2010.

Fig. 2

Change in percent weight of total fatty acids from enrollment to 25–28 weeks of gestation. EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; AA, arachidonic acid. All P<.001. Harper. Omega-3 for Repeat Preterm Birth Prevention. Obstet Gynecol 2010.