Women with polycystic ovarian syndrome (PCOS) who took metformin had newborns with larger heads than the offspring of women with PCOS who took a placebo, though PCOS offspring were, on average, shorter than newborns in a reference population, according to a recent study.
Metformin is commonly prescribed to women with PCOS, and though metformin passes the placental barrier and can reach therapeutic concentrations in the umbilical cord blood, it hasn’t been proven teratogenic, said Anna Hjorth-Hansen, MD, of the internal medicine department at Levanger Hospital, Norway.
Dr. Anna Hjorth-Hansen
The study was a post hoc analysis of data from the PregMet study, which was run from 2005 to 2009, and compared metformin to placebo, in combination with diet and lifestyle changes, for women with PCOS, said Dr. Hjorth-Hansen. The PregMet study tested the hypothesis that women with PCOS who received metformin from the first trimester until delivery had fewer pregnancy complications overall than women who did not.
Though women receiving placebo in the PregMet study had no more eclampsia, preterm delivery, or gestational diabetes than those who received metformin, the newborns who had in utero metformin exposure had significantly larger head circumference.
Dr. Hjorth-Hansen said that the study looked at in utero growth and anthropometric measurements at birth of infants born to women taking metformin, to determine whether metformin could affect fetal growth and newborn anthropometrics.
Ultrasound examination was used to measure crown-rump length, biparietal diameter (BPD), and mean abdominal diameter (MAD). At birth, head circumference (HC), length, and weight were measured.
Maternal characteristics were comparable between the metformin (131 patients) and placebo (127 patients) groups, said Dr. Hjorth-Hansen. Specifically, there were no significant differences between groups in terms of PCOS phenotype, blood glucose levels, and parity.
Infants born to women who took metformin had, on average, a larger BPD at 32 weeks gestation, compared with the infants whose mothers took placebo (86.1 mm versus 85.2 mm, P = .027). This larger head size was also seen at birth (mean HC, metformin, 35.6 cm; placebo, 35.0 cm; P = .007).
There were no significant differences between the groups in MAD or weight, either as assessed by ultrasound at 32 weeks gestation or as measured at birth.
Although the two groups did not differ in length at birth, the aggregate study population of infants born to women with PCOS was shorter than a large Swedish reference population.
When Dr. Hjorth-Hansen and her colleagues stratified the results by maternal body mass index (BMI), looking at babies born to women with BMIs below 25 kg/m2, compared with those with BMI of 25 kg/m2 and greater, they saw no differences in infant anthropometric measurements for women who had taken placebo.
However, when the investigators dichotomized maternal BMI for the metformin group, they found that infants born to the higher BMI group had a larger head size (P = .022), and were heavier (P = .002) and longer (P = .003) than infants born to women with BMIs less than 25.
“Metformin resulted in a larger head size, traceable already in utero,” said Dr. Hjorth-Hansen. However, she said, there’s a “PCOS effect” that results in the offspring of women with the condition to have a shorter body, compared with offspring of women without PCOS.
Dr. Hjorth-Hansen reported no relevant disclosures.
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