FADS genotype may modify DHA effects on early preterm birth

A secondary analysis published in PLOS Medicine examined whether the FADS insertion-deletion variant rs66698963 modifies response to docosahexaenoic acid (DHA) supplementation during pregnancy. The analysis included 761 participants from the randomized ADORE trial at three US centers, enrolled at 12–20 weeks’ gestation and receiving 200 or 1,000 mg/day DHA. Outcomes included early preterm birth before 34 weeks and preterm birth before 37 weeks, assessed using Bayesian models.

Among insertion-allele carriers, estimated early preterm birth rates were 4.3% with 200 mg/day versus 1.1% with 1,000 mg/day, with nine events among 214 participants versus two among 205. Corresponding preterm birth rates were 14.5% versus 9.3%. The posterior probability for a genotype-by-dose interaction was 0.99 for early preterm birth. Birth at 40 weeks or later was more frequent among deletion-homozygous participants receiving higher-dose DHA; the interaction probability for prolonged gestation was 0.98. The overall preterm birth benefit did not clearly differ by genotype.

These findings identify a potential biomarker for DHA dose response, rather than establish a genotype-guided prescribing strategy. Although genotyping was blinded to outcomes, the genotype-by-dose comparison was post hoc and not a prespecified trial aim. Small event counts in some subgroups limit precision, and prospective confirmation is needed. The study was NIH-funded, with no sponsor role in its conduct or publication; authors declared no competing interests.