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.

BACKGROUND Previous studies have suggested that maternal supplementation with n−3 long-chain polyunsaturated fatty acids may reduce the incidence of preterm delivery but may also prolong gestation beyond term; however, more data are needed regarding the role of n−3 long-chain polyunsaturated fatty acids in pregnancy. METHODS We performed a multicenter, double-blind, randomized trial in which women who were pregnant with single or multiple fetuses were assigned to receive either fish-oil capsules that contained 900 mg of n−3 long-chain polyunsaturated fatty acids (n−3 group) or vegetable-oil capsules that contained trace n−3 long-chain polyunsaturated fatty acids (control group) daily, beginning before 20 weeks of gestation and continuing to 34 weeks of gestation or delivery, whichever occurred first. The primary outcome was early preterm delivery, defined as delivery before 34 completed weeks of gestation. Other pregnancy and neonatal outcomes were also assessed. RESULTS A total of 5544 pregnancies in 5517 women were randomly assigned at six centers in Australia; 5486 pregnancies were included in the primary analysis. Early preterm delivery occurred in the case of 61 of 2734 pregnancies (2.2%) in the n−3 group and 55 of 2752 pregnancies (2.0%) in the control group; the between-group difference was not significant (adjusted relative risk, 1.13; 95% confidence interval [CI], 0.79 to 1.63; P = 0.50). There were no significant differences between the groups in the incidence of interventions in post-term (>41 weeks of gestation) deliveries, in adverse events, or in other pregnancy or neonatal outcomes, except that a higher percentage of infants born to women in the n−3 group than in the control group were very large for gestational age at birth (adjusted relative risk, 1.30; 95% CI, 1.02 to 1.65). Percentages of serious adverse events did not differ between the groups. Minor gastrointestinal disturbances were more commonly reported in the n−3 group than in the control group. CONCLUSIONS Supplementation with n−3 long-chain polyunsaturated fatty acids from early pregnancy (<20 weeks of gestation) until 34 weeks of gestation did not result in a lower incidence of early preterm delivery or a higher incidence of interventions in post-term deliveries than control.

In current protocols for the medical management of ectopic pregnancies, the first indication of treatment response is obtained no sooner than day 7. We examined whether human chorionic gonadotrophin (bhCG) trends between days 0 and 4 after methotrexate provide an earlier indication of the likely outcome. Of 33 patients where serum bhCG dropped between days 0 and 4 after methotrexate, the ectopic pregnancy was resolved in 88% of cases without further treatment. Of 12 women where serum bhCG rose between days 0 and 4, only 42% had treatment success. A fall in bhCG between days 0 and 4 after treatment with methotrexate for ectopic pregnancy predicts a high likelihood of treatment success.Keywords Biomarker, ectopic pregnancy, human chorionic gonadotrophin, medical management, methotrexate.Please cite this paper as: Skubisz M, Lee J, Wallace E, Tong S. Decline in bhCG levels between days 0 and 4 after a single dose of methotrexate for ectopic pregnancy predicts treatment success: a retrospective cohort study.