- Design
- Post hoc secondary analysis of a randomised dose trial (ADORE), Bayesian models
- 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
- I-allele carriers: early preterm 1.1% on 1,000 mg vs 4.3% on 200 mg; genotype × dose interaction posterior probability 0.99
ADORE randomised pregnant women at 12–20 weeks to 200 or 1,000 mg/day docosahexaenoic acid (DHA). This post hoc analysis genotyped 761 participants for the FADS Indel, a variant that increases arachidonic acid synthesis and, in theory, prostaglandin-driven labour.
On low-dose DHA, carriers of at least one insertion (I) allele had early preterm birth (before 34 weeks) of 4.3% against 0.8% in D/D women. High-dose DHA brought I-allele carriers down to 1.1%. In D/D women the high dose did little for early preterm birth but was linked to more births at or after 40 weeks. Black women carried the I allele more often and appeared to gain most.
The genotype-by-dose comparison was not a prespecified aim, and early preterm births numbered in single figures per group. The authors themselves ask for prospective confirmation.
For now this is hypothesis-generating. It does not support routine genotyping, but it does fit the wider picture that higher-dose omega-3 helps some women more than others.
- Do not order FADS genotyping in pregnancy — this is research only.
- Ask about omega-3 intake at booking, particularly in women with low fish consumption.
- Follow your current guideline on DHA supplementation; this analysis has not changed one.
- Note that the high dose was linked to more prolonged pregnancies in D/D women.
Why it matters
It offers one explanation for why omega-3 trials for preterm birth have given mixed results.
Don't overread it
A post hoc subgroup with very few events cannot establish that genotype should guide dosing.
The statistics, in plain English
Results are Bayesian: a posterior probability of 0.99 means the model is very confident the difference is real given the data, but with 9 versus 1 early preterm births the estimate is fragile. A subgroup found after the fact is weaker evidence than the trial's main result.
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