Fetal Growth and Birth Anthropometrics in Metformin-Exposed Offspring Born to Mothers With PCOS

Abstract Context Metformin is used in an attempt to reduce pregnancy complications associated with polycystic ovary syndrome (PCOS). Little is known about the effect of metformin on fetal development and growth. Objectives To compare the effect of metformin versus placebo on fetal growth and birth anthropometrics in PCOS offspring compared with a reference population in relation to maternal body mass index (BMI). Design Post hoc analysis of a randomized controlled trial. Setting Double-blind, placebo-controlled, multicenter study. Patients 258 offspring born to mothers with PCOS. Intervention 2000 mg metformin (n = 131) or placebo (n = 121) from first trimester to delivery. Main Outcome Measures Mean abdominal diameter and biparietal diameter (BPD) at gestational weeks 19 and 32. Head circumference (HC), birth length, and weight related to a reference population of healthy offspring, expressed as gestational age– and sex-adjusted z-scores. Results Metformin- versus placebo-exposed offspring had larger heads at gestational week 32 (BPD, 86.1 mm versus 85.2 mm; P = 0.03) and at birth (HC, 35.6 cm versus 35.1 cm; P < 0.01). Analyses stratified by maternal prepregnancy BMI, larger heads were observed only among offspring of overweight/obese mothers. Among normal-weight mothers, the effect of metformin compared with placebo was reduced length (z-score = −0.96 versus -0.42, P = 0.04) and weight (z-score = −0.44 versus 0.02; P = 0.03). Compared with the reference population, offspring born to PCOS mothers (placebo group) had reduced length (z-score = −0.40; 95% confidence interval, −0.60 to −0.40), but similar birth weight and HC. Conclusions Metformin exposure resulted in larger head size in offspring of overweight mothers, traceable already in utero. Maternal prepregnancy BMI modified the effect of metformin on offspring anthropometrics. Anthropometrics of offspring born to PCOS mothers differed from those of the reference population. Metformin versus placebo exposure in pregnancies of PCOS women resulted in increased offspring head size exposed to metformin, and maternal BMI interacted with offspring anthropometrics.