Genotype-informed docosahexaenoic acid dosing based on the FADS Indel to reduce preterm and prolonged gestation: A secondary analysis of the ADORE randomized trial.
Yan Ning Li, Kumar S D Kothapalli, Susan E Carlson et al.
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In 30 seconds
This post hoc secondary analysis of the multicentre ADORE randomised trial examined whether FADS Indel genotype modified the association between DHA dose and gestational outcomes. Among 761 participants with genetic data, those carrying an I allele assigned 1,000 mg/d DHA had lower early preterm birth (EPB) than I-allele carriers assigned 200 mg/d: 1.1% (2/205) versus 4.3% (9/214). High-dose DHA was associated with more births at ≥40 weeks among D/D participants. Genotype-by-dose interactions were supported for EPB and prolonged gestation, but not for preterm birth overall.
Key findings
- Among I-allele carriers, EPB was 1.1% (2/205) with 1,000 mg/d DHA versus 4.3% (9/214) with 200 mg/d.
- In I-allele carriers, preterm birth was 9.3% (19/205) with high-dose DHA versus 14.5% (31/214) with low-dose DHA.
- Genotype-by-dose interaction posterior probabilities were 0.99 for EPB and 0.98 for prolonged gestation; the interaction was not supported for preterm birth (PP = 0.56).
- Birth at ≥40 weeks was more frequent in the high-dose D/D group.
Why it matters
The findings suggest that genetic variation may help explain differing gestational responses to DHA dose, with potential relevance to both early delivery and prolonged gestation. This is clinically important because the analysis points toward a possible way to tailor supplementation rather than assuming a uniform response. However, the results are exploratory and do not establish a genotype-guided dosing strategy.
What to keep in mind
This was a post hoc secondary analysis, and genotype-by-dose comparisons were not a prespecified trial aim. Some subgroups had few preterm and early preterm events; the authors call for prospective confirmation.