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

Objective: To evaluate the effect of metformin on immunological outcomes in pregnant women with polycystic ovary syndrome (PCOS) and their offspring.

Design: Post hoc analyses of two randomised controlled trials (PregMet and PregMet2) and one follow-up study (PedMet).

Setting: Women followed at multiple hospitals in Norway, Sweden and Iceland, and offspring followed at multiple hospitals in Norway.

Population or sample: Pregnant women with PCOS, randomised to metformin or placebo from the first trimester to delivery, and offspring exposed to metformin or placebo in utero.

Methods: 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.

Main outcome measures: Incidence of maternal infections during pregnancy, delivery, and postpartum, and allergic diseases in offspring at 8-year follow-up.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov identifiers: NCT03259919, NCT00159536 and NCT01587378.

Keywords: allergy; asthma; eczema; infections; metformin; polycystic ovary syndrome; pregnancy.