Anna Hjorth-Hansen1, Øyvind Salvesen2, Liv Guro Engen Hanem3, Torbjørn Eggebø2,4, Kjell Å Salvesen3,4, Eszter Vanky3,4, Rønnaug Ødegård2,5. 1. Department of Internal Medicine, Levanger Hospital, Levanger, Norway. 2. Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway. 3. Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. 4. Department of Obstetrics and Gynecology, St. Olav's University Hospital of Trondheim, Trondheim, Norway. 5. Centre of Obesity Research, St. Olav's University Hospital of Trondheim, Trondheim, Norway.
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.
RCT Entities:
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.
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