Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial

Multicenter, randomized, double-blind, adaptive-design superiority trial conducted at three US centers. Participants: pregnant women aged 18 years or older with singleton pregnancies between 12 and 20 weeks gestation, able to read English or Spanish. Exclusions: multifetal gestations; age <18; gestation <12 or >20 weeks; unwilling to discontinue a daily prenatal vitamin containing DHA. Analyses followed intention-to-treat; Bayesian adaptive design; trial registered NCT02626299.

Docosahexaenoic acid (DHA) supplementation: baseline 200 mg DHA capsule daily, plus two additional capsules daily that either contain 0 mg DHA (corn oil/soybean oil placebo) or 400 mg DHA per capsule (algal DHA), for total daily DHA exposure of 200 mg (low-dose) or 1000 mg (high-dose). Taken daily from enrollment (12–20 weeks gestation) until delivery.

High-dose DHA (1000 mg/day) reduced early preterm birth (<34 weeks) compared with low-dose DHA (200 mg/day): EPB 1.7% vs 2.4% (posterior probability that high-dose is better = 0.81). Among women with low DHA status at enrollment, EPB 2.0% vs 4.1% (pp = 0.93); among those with high DHA status at enrollment, EPB 1.4% vs 1.1% (pp = 0.57). The higher dose was associated with fewer maternal and neonatal serious adverse events. Authors conclude that 1000 mg DHA daily during pregnancy could reduce EPB in women with low DHA status if DHA status can be screened, supporting targeted DHA supplementation to reduce EPB risk.

Relatively few EPB events; results may be imprecise. No placebo group (two active-dose regimens only). Generalizability may be limited to US settings; DHA-status screening was used, which may limit applicability where screening is not available. Long-term maternal/child outcomes not assessed; some subgroup findings are exploratory and need replication.