Genotype-informed docosahexaenoic acid dosing based on the FADS Indel to reduce preterm and prolonged gestation: A secondary analysis of the ADORE randomized trial

A study analyzing data from the ADORE randomized trial has found that the FADS Indel genetic variant may influence the effectiveness of docosahexaenoic acid (DHA) supplementation in reducing preterm and prolonged gestation. The study, conducted by Yan Ning Li and colleagues, examined participants from three US medical centers who received either 200 or 1,000 mg/d of DHA.

Participants carrying at least one FADS Indel I allele (I/I or I/D) who received the low-dose DHA had a higher likelihood of preterm birth (9.3%) and spontaneous early preterm birth (4.3%) compared to those with the D/D genotype (8.7% and 0.8%, respectively). Conversely, high-dose DHA led to lower rates of preterm birth (9.3%) and spontaneous early preterm birth (1.1%) among individuals with the I-allele genotype, with little effect on those with the D/D genotype.

Interestingly, black women, who are more likely to carry the I allele, benefited the most from the high-dose DHA treatment. The study also noted that birth at 40 weeks or later was more frequent in the high-dose D/D group. While the genotype-by-dose interaction was statistically significant for EPB and prolonged gestation (PP = 0.99 and 0.98), the analysis was post hoc and not a prespecified trial aim, meaning the results should be interpreted with caution, particularly in subgroups with few preterm and early preterm birth events.

Overall, the findings suggest that the FADS Indel genotype could serve as a predictive biomarker for DHA dose response, and a genotype-informed precision-medicine strategy may help optimize gestational length, reducing preterm birth in the I-allele group and prolonged gestation in the D/D group.