Objective To identify a polyunsaturated fatty acid (PUFA) biomarker able to detect which women with singleton pregnancies are most likely to benefit from omega‐3 supplementation to reduce their risk of early preterm birth. Design Exploratory analysis of a randomised controlled trial. Setting Six Australian hospitals. Population Women with a singleton pregnancy enrolled in the ORIP trial. Methods Using maternal capillary whole blood collected ~14 weeks’ gestation, the fatty acids in total blood lipids were quantified using gas chromatography. Interaction tests examined whether baseline PUFA status modified the effect of omega‐3 supplementation on birth outcomes. Main outcome measure Early preterm birth (<34 weeks’ gestation). Results A low total omega‐3 PUFA status in early pregnancy was associated with a higher risk of early preterm birth. Among women with a total omega‐3 status ≤4.1% of total fatty acids, omega‐3 supplementation substantially reduced the risk of early preterm birth compared with control (0.73 versus 3.16%; relative risk = 0.23, 95% confidence interval [CI] 0.07–0.79). Conversely, women with higher total omega‐3 status in early pregnancy were at lower risk of early preterm birth. Supplementing women with a baseline status above 4.9% increased early preterm birth (2.20 versus 0.97%; relative risk = 2.27, 95% CI 1.13–4.58). Conclusions Women with singleton pregnancies and low total omega‐3 PUFA status early in pregnancy have an increased risk of early preterm birth and are most likely to benefit from omega‐3 supplementation to reduce this risk. Women with higher total omega‐3 status are at lower risk and additional omega‐3 supplementation may increase their risk. Tweetable abstract Low total omega‐3 fat status helps identify which women benefit from extra omega‐3 to reduce early prematurity.

Feeding preterm infants milk containing 3 times the standard amount of DHA did not result in any clinically meaningful change to language development or behavior when assessed in early childhood. Whether longer-term effects of dietary DHA supplementation can be detected remains to be assessed. This trial was registered with the Australia and New Zealand Clinical Trial Registry at www.anzctr.org.au as 12606000327583.