Metformin Treatment in PCOS Pregnancies Reduces Maternal Infections and Increases the Risk of Allergies and Eczema in the Offspring: Post Hoc Analyses of Two Randomised Controlled Trials and One Follow-Up Study.

Abstract

To evaluate the effect of metformin on immunological outcomes in pregnant women with polycystic ovary syndrome (PCOS) and their offspring. Post hoc analyses of two randomised controlled trials (PregMet and PregMet2) and one follow-up study (PedMet). Women followed at multiple hospitals in Norway, Sweden and Iceland, and offspring followed at multiple hospitals in Norway. Pregnant women with PCOS, randomised to metformin or placebo from the first trimester to delivery, and offspring exposed to metformin or placebo in utero. Maternal infections and allergic diseases in offspring were compared using logistic regression. Maternal body mass index (BMI), offspring BMI z-score and maternal infections were evaluated as effect modifiers or mediators. Incidence of maternal infections during pregnancy, delivery, and postpartum, and allergic diseases in offspring at 8-year follow-up. Altogether 634 women and 145 offspring were included. Women treated with metformin experienced fewer overall infections during pregnancy (OR = 0.68, 95% CI: 0.50-0.93), particularly viral infections (OR = 0.71, 95% CI: 0.51-0.99). Offspring exposed to metformin in utero had a higher incidence of allergies (OR = 4.83, 95% CI: 1.47-21.8) and eczema (OR = 2.42, 95% CI: 1.14-5.33). Maternal BMI did not modify the effect of metformin, and offspring BMI z-score or maternal infections did not mediate the relationship between metformin treatment and increased allergies and eczema in offspring. Metformin treatment in pregnant women with PCOS reduced maternal infections during pregnancy and increased the incidence of allergies and eczema in offspring at 8-year follow-up. ClinicalTrials.gov identifiers: NCT03259919, NCT00159536 and NCT01587378.