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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

Ryssdal M, Skage JE, Jarmund AH, Hanem LGE, Løvvik TS, Giskeødegård GF, Iversen AC, Vanky E

BJOG : an international journal of obstetrics and gynaecology, 2025

634 participants · 1 citation

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…

How strong is the evidence?

Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 634 participants or records.

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