In-utero exposure to metformin for type 2 diabetes or polycystic ovary syndrome: A prospective comparative observational study.

Objective: To evaluate the rate of major anomalies after first trimester (T1)-metformin exposure.

Methods: Comparative, observational cohort study done at the Israeli Teratology Information Service between 2000 and 2013.

Results: 170 T1-metformin-exposed pregnancies [119 for diabetes and 51 for polycystic ovary syndrome (PCOS)] were prospectively followed-up and compared with 93 pregnancies of T1-insulin treated women and 530 non-teratogenic exposed (NTE) pregnancies. The differences in the rate of major anomalies excluding genetic/cytogenetic, and spontaneously resolved cardiovascular anomalies were not significant [4.4% (2/45) - metformin-PCOS, 1.1% (1/90) - metformin-diabetes, 2.5% (2/80) - insulin, and 1.7% (9/519) - NTE; ORadj metformin/NTE 1.77; 95% CI 0.45-7.01; ORadj insulin/NTE 1.69; 95% CI 0.35-8.11]. The rate of Cesarean section was higher in both the metformin-diabetes 51/90 (56.7%) and insulin 45/79 (57.0%) groups compared with the NTE group [138/503 (27.4%)].

Conclusions: Metformin-T1-exposure per se is not associated with an increased risk of major anomalies.