A Randomized Trial of Prenatal n-3 Fatty Acid Supplementation and Preterm Delivery.

Obstetrical & Gynecological Survey

Sep 2019

DOI: 10.1097/OGX.0000000000000772

Citations:73

Influential Citations:1

Interventional (Human) Studies

Enhanced Details

Methods

Multicenter, double-blind, randomized trial of pregnant women with singleton or multiple fetuses; conducted at six centers across four Australian states; recruited at first antenatal visit from Nov 1, 2013, to Apr 26, 2017; 5544 pregnancies in 5517 women were randomized; primary outcome: early preterm delivery (<34 weeks); design: randomized, double-blind, controlled trial.

Intervention

n-3 group: three 500-mg fish-oil capsules per day (≈900 mg total n-3 long-chain polyunsaturated fatty acids per day; ≈800 mg DHA and ≈100 mg EPA), started before 20 weeks gestation and continued to 34 weeks gestation or delivery, taken orally. Control group: three 500-mg vegetable-oil capsules per day (≈15 mg DHA and ≈4 mg EPA per day), started before 20 weeks gestation and continued to 34 weeks gestation or delivery, taken orally; control capsules contained 5% tuna oil to aid masking.

Results

No reduction in early preterm delivery with n-3 LCPUFA supplementation from <20 weeks to 34 weeks gestation (2.2% vs 2.0%; adjusted relative risk 1.13, 95% CI 0.79–1.63; P=0.50). No significant differences in post-term interventions or other major pregnancy/neonatal outcomes. Infants born very large for gestational age were more frequent in the n-3 group (adjusted RR 1.30, 95% CI 1.02–1.65). Minor gastrointestinal disturbances were more common with n-3; serious adverse events did not differ. Conclusion: Prenatal n-3 LCPUFA supplementation from early pregnancy to 34 weeks did not reduce early preterm delivery; routine use for this purpose is not supported; potential effect on fetal growth requires further study.

Limitations

Adherence to the regimen declined in mid-to-late pregnancy; participants had relatively high baseline DHA status, which may have attenuated potential benefits; many prespecified secondary outcomes were not adjusted for multiplicity, increasing the chance of chance findings; the trial included both singleton and multiple gestations, which may limit generalizability; masking with tuna oil was imperfect, and results may not generalize to populations with lower baseline omega-3 intake.

Abstract

BACKGROUND Previous studies have suggested that maternal supplementation with n-3 long-chain polyunsaturated fatty acids may reduce the incidence of preterm delivery but may also prolong gestation beyond term; however, more data are needed regarding the role of n-3 long-chain polyunsaturated fatty acids in pregnancy. METHODS We performed a multicenter, double-blind, randomized trial in which women who were pregnant with single or multiple fetuses were assigned to receive either fish-oil capsules that contained 900 mg of n-3 long-chain polyunsaturated fatty acids (n-3 group) or vegetable-oil capsules that contained trace n-3 long-chain polyunsaturated fatty acids (control group) daily, beginning before 20 weeks of gestation and continuing to 34 weeks of gestation or delivery, whichever occurred first. The primary outcome was early preterm delivery, defined as delivery before 34 completed weeks of gestation. Other pregnancy and neonatal outcomes were also assessed. RESULTS A total of 5544 pregnancies in 5517 women were randomly assigned at six centers in Australia; 5486 pregnancies were included in the primary analysis. Early preterm delivery occurred in the case of 61 of 2734 pregnancies (2.2%) in the n-3 group and 55 of 2752 pregnancies (2.0%) in the control group; the between-group difference was not significant (adjusted relative risk, 1.13; 95% confidence interval [CI], 0.79 to 1.63; P = 0.50). There were no significant differences between the groups in the incidence of interventions in post-term (>41 weeks of gestation) deliveries, in adverse events, or in other pregnancy or neonatal outcomes, except that a higher percentage of infants born to women in the n-3 group than in the control group were very large for gestational age at birth (adjusted relative risk, 1.30; 95% CI, 1.02 to 1.65). Percentages of serious adverse events did not differ between the groups. Minor gastrointestinal disturbances were more commonly reported in the n-3 group than in the control group. CONCLUSIONS Supplementation with n-3 long-chain polyunsaturated fatty acids from early pregnancy (<20 weeks of gestation) until 34 weeks of gestation did not result in a lower incidence of early preterm delivery or a higher incidence of interventions in post-term deliveries than control. (Funded by the Australian National Health and Medical Research Council and the Thyne Reid Foundation; ORIP Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729.). show less