Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring.

Randomized, double-blind, placebo-controlled trial in pregnant women enrolled in the COPSAC 2010 cohort in Copenhagen, Denmark. The active n-3 LCPUFA arm randomized 736 participants total, with primary end-point data available for 346 in the treatment group; offspring were followed prospectively from birth through early childhood, with key respiratory outcomes assessed to age 5 years.

Pregnant participants received 2.4 g/day of n-3 long-chain polyunsaturated fatty acids (fish oil) in triacylglycerol form, containing 55% EPA and 37% DHA, as four identical 1 g oral capsules daily. Supplementation started at 22 to 26 weeks of gestation and continued until 1 week after delivery; the comparison group received placebo.

Prenatal n-3 LCPUFA supplementation reduced the risk of persistent wheeze or asthma in offspring. For the primary end point, persistent wheeze or asthma occurred in 16.9% of the treatment group versus 23.7% of controls, with a hazard ratio of 0.69 (95% CI 0.49 to 0.97; P = 0.035). Lower respiratory tract infections were also reduced, including 31.7% versus 39.1% at 3 to 5 years (HR 0.75; 95% CI 0.58 to 0.98; P = 0.033) and 38.8% versus 45.5% at 5 years (HR 0.77; 95% CI 0.61 to 0.99; P = 0.041). There was no statistically significant benefit for eczema, allergic sensitization, or lung function, and the strongest apparent benefit was seen in children of mothers with low preintervention EPA and DHA levels.

The trial was conducted in a single Danish birth cohort, which limits generalizability. Several outcomes were secondary or post hoc, and the subgroup signal was strongest among mothers with low baseline EPA and DHA, suggesting effect modification and indirectness for broader populations. Some analyses had modest numbers available for end-point assessment, and benefits were not seen for all prespecified respiratory or atopic outcomes.