DHA dose and preterm birth may depend on a FADS genotype

Design

Post hoc secondary analysis of a randomised dose-comparison trial (ADORE)

Population

761 pregnant women at three US centres, genotyped for the FADS Indel

Primary outcome

Early preterm birth (<34 weeks) and preterm birth (<37 weeks)

Effect

Insertion-allele carriers: early preterm 4.3% on 200 mg vs 1.1% on 1,000 mg DHA; little dose effect in deletion homozygotes

This post hoc analysis of the ADORE trial genotyped 761 women for one variant, the FADS insertion/deletion, which affects how much arachidonic acid the body makes. Women had been randomised to 200 mg or 1,000 mg of docosahexaenoic acid (DHA) a day from mid-pregnancy.

Among carriers of the insertion allele on the low dose, early preterm birth before 34 weeks was 4.3% (9 of 214), against 0.8% in non-carriers on the same dose. On the high dose, carriers had 1.1% (2 of 205). Non-carriers gained little from the higher dose and had more births at 40 weeks or later. Preterm birth before 37 weeks fell similarly with the high dose in both genotypes.

The idea is mechanistically neat, and the insertion allele is commoner in women of African ancestry, who carry more preterm birth. But this was not a prespecified aim, event counts were small, and the analysis is Bayesian with credible intervals, not a confirmatory test.

Nothing here supports ordering a FADS test. It does support the existing view that a 1,000 mg DHA dose is reasonable for women at raised risk, and it gives a plausible reason some women benefit more than others.

• Do not order FADS genotyping to guide omega-3 dosing; it is research-stage
• High-dose DHA reduced preterm birth before 37 weeks in both genotypes in this analysis
• Ask about omega-3 intake at booking, especially in women with low fish consumption
• A possible downside of high-dose DHA in non-carriers was more pregnancies running to 40 weeks or beyond

Why it matters

It offers a reason why omega-3 trials for preterm birth have given mixed answers.

Don't overread it

A post hoc genotype subgroup with a handful of events cannot justify genotype-guided dosing.

The statistics, in plain English

A posterior probability of 0.99 means the model is very confident the difference is real given its assumptions, but the early preterm comparison rests on 9 events versus 2. With so few events, one or two births moving the other way would change the picture.

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