Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs

Metformin is used in pregnancy in women with gestational diabetes mellitus, polycystic ovary syndrome (PCOS), and obesity. Metformin passes the placenta. To explore the effects of metformin use in PCOS pregnancies on offspring growth to 4 years of age. Follow-up study of two randomized, double-blind, placebo-controlled trials. Secondary care centers. Eleven public hospitals in Norway. One hundred eighty-two children of mothers with PCOS who participated in two randomized controlled trials. Metformin 1700 or 2000 mg/d or placebo from first trimester to delivery in the original studies. No intervention in the current study. Height, weight, body mass index (BMI), and overweight/obesity at 4 years of age and head circumference at 1 year of age, converted to z scores. The difference in height z score means between the groups at 4 years of age was nonsignificant (0.07 [95% confidence interval (CI): –0.22 to 0.36]; P = 0.651). At 4 years of age, the metformin group had higher weight z score than the placebo group [difference in means: 0.38 (0.07 to 0.69); P = 0.017] and higher BMI z score [difference in means: 0.45 (0.11 to 0.78); P = 0.010]. There were more overweight/obese children in the metformin group [26 (32%)] than in the placebo group [14 (18%)] at 4 years of age [odds ratio: 2.17 (1.04 to 4.61); P = 0.038]. The difference in mean head circumference z score at 1 year of age was 0.27 (–0.04 to 0.58; P = 0.093). Metformin-exposed children had higher BMI and increased prevalence of overweight/obesity at 4 years of age.