Do fatty acids play a role in preterm birth?

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Meta-analyses have linked taking fish oil supplements in pregnancy with longer gestation. A new Danish study in EBioMedicine suggests there may be a connection between low levels of EPA and DHA in pregnancy and preterm birth (PTB).

In the first study of its kind, the researchers used the Danish National Birth Cohort (DNBC) to identify 376 early PTB cases (< 34 weeks’ gestation, excluding preeclampsia) and 348 controls. The DNBC includes approximately 100,000 stored plasma samples drawn at gestational weeks 9 and 25 and the diagnoses of early PTB reflected in the database are validated and confirmed against hospital records.

The investigators measured levels of EPA plus DHA at 9 and 25 weeks in plasma samples from the cohort. Using logistic regression, they estimated odds ratios and 95% confidence intervals (Cis) for associations between EPA plus DHA and risk of early PTB, with adjustment for the woman’s age, height, prepregnancy body mass index, parity, smoking, and socioeconomic factors. 

Analysis using restricted cubic splines of the mean of first and second sample measurements showed a strong and significant nonlinear association (P< 0.0001) in which risk of early PTB steeply increased when EPA plus DHA concentrations were lower than 2% and flattened out at higher levels. Women in the lowest quintile (EPA+DHA < 1.6%) had 10.27 times increased risk (95% CI 6.80-15.79; P< 0.0001) and women in the second lowest quintile had 2.86 times increased risk (95% CI 1.79-4.59; P< 0.0001) when compared to women in the three aggregated highest quintiles (EPA+DHA ≥ 1.8%).

The authors said their findings implicate body levels of fatty acids in the physiologic processes that lead up to PTB and that plasma measurements of EPA and DHA during pregnancy may help identify women at risk of early PTB. They cautioned, however, that population-based studies are needed elsewhere to replicate the results because rates of early PTB are low in Denmark. The authors also noted that variations in fatty acid desaturase genes may play a role in the observed association between EPA and DHA and early PTB, underscoring the need for research on dietary versus genetic factors. “The patterns we see might mechanistically be non-dietary in nature,” they said. “Plasma concentration of EPA+DHA at any point during pregnancy is influenced not only by a woman’s intake of fatty acids before and during pregnancy but also by placental transfer of essential fatty acids from the mother to the growing foetus, as well as by her own genetically determined capacity to metabolize polyunsaturated fatty acids.” 

Commenting on the strengths of the study, the researchers said that basing it on a large national birth cohort allowed adjustment for many potential confounders. Review of actual clinical records was done to verify all the early PTB cases. The observational design with potential for unmeasured confounding was a possible weakness but they believe that confounding or reverse causation are unlikely because of the strength of the observations and the prospective design.