Metformin exposure in utero may increase infant head size

Among babies born to women with polycystic ovary syndrome, those who were exposed to metformin in utero had larger head circumferences compared with those exposed to placebo, researchers in Norway found.

“Women with PCOS have poorer metabolic health and increased risk of developing complications in pregnancy, such as gestational diabetes mellitus, preeclampsia and preterm delivery,” Anna Hjorth-Hansen, MD, of the department of internal medicine at Levanger Hospital, Norway, and colleagues wrote. “Birth characteristics are associated to metabolic health later in life, but the effect of maternal PCOS status on newborn anthropometric data, as well as metabolic health is scarce and diverging.”

The researchers performed a post-hoc analysis of a double-blind, randomized controlled trial in which pregnant women with PCOS were randomly assigned to 2,000 mg of metformin (n = 131) or placebo (n = 121) daily from the first trimester to time of delivery. The main outcome was fetal mean abdominal diameter and bi-parietal diameter at weeks 19 and 32 during gestation. The newborns’ birth length, weight and head circumference were compared to a reference population of healthy infants.

Two hundred fifty-eight babies were born during the study. Those in the metformin group had larger heads compared with those in the placebo group at 32 weeks’ gestation, Hjorth-Hansen and colleagues wrote (bi-parietal diameter, 86.1 mm vs. 85.2 mm; P = .03). This difference also held true at birth (head circumference, 35.6 cm vs. 35.1 cm; P < .01).

When the researchers stratified the analysis by maternal pre-pregnancy BMI, they reported that larger heads were observed only in the children of mothers with overweight or obesity. Among women with normal weight, metformin appeared to reduce birth length (z score, -0.96 vs. -0.42; P = .04), as well as weight (z score, -0.44 vs. 0.02; P = .03).

Infants born to mothers in the placebo group had a reduced length compared with reference population (z score, -0.40 [-0.60 to -.40]), but demonstrated similar head circumference and birth weight.

“Head-size alteration was traceable already in utero,” the researchers wrote. “Placebo-exposed offspring born to mothers with PCOS were shorter, but not lighter than the reference population. Metformin administration to normal-weight mothers with PCOS might restrict fetal growth.” – by Andy Polhamus

Disclosures: The authors report no relevant financial disclosures.