Omega-3 supplementation from pregnancy to postpartum to prevent depressive symptoms: a randomized placebo-controlled trial

Randomized placebo-controlled trial in pregnant women at risk for postpartum depression and with low fish intake, recruited at a public health care center in Rio de Janeiro, Brazil. In the active fish oil arm, 32 participants were randomized and 32 were analyzed; 28 participants were randomized and analyzed in the placebo arm.

The active intervention was oral fish oil providing 1.8 g/day of n-3 polyunsaturated fatty acids, including 1.08 g EPA and 0.72 g DHA, delivered as six gelatin capsules daily. Participants took three capsules at lunch and three at dinner for 16 consecutive weeks, starting at gestational week 22 to 24, versus placebo.

Daily omega-3 supplementation did not prevent depressive symptoms during pregnancy or early postpartum overall. There were no significant differences between fish oil and placebo in the prevalence of EPDS score at least 11 at any time point, and EPDS trajectories over time were similar between groups. A subgroup signal suggested a greater reduction in EPDS scores from the second to the third trimester among women with a prior history of depression in ITT analyses (-1.0 (-3.0-0.0) vs -0.0 (-1.0-3.0), P = 0.038), with a longitudinal model estimate of β = -3.441; 95%CI: -6.532 to -0.350, P = 0.029. The fish oil arm showed higher serum total n-3, EPA, and DHA at T2, but these biomarker changes did not translate into an overall clinical benefit.

The trial was small and may have been underpowered for clinically important or subgroup effects. Follow-up was relatively short, extending only to 4 to 6 weeks postpartum, and the apparent benefit in women with prior depression was a subgroup finding that requires confirmation. Generalizability is limited by enrollment of pregnant women at risk for postpartum depression with low fish intake from a single public health center in Rio de Janeiro, Brazil.