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J Clin Endocrinol Metab. 2018 Apr 1;103(4):1612-1621. doi: 10.1210/jc.2017-02419.

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

Author information

1
Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
2
Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
3
Department of Clinical Science, University of Bergen, Bergen, Norway.
4
Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
5
Department of Public Health and Primary Care, KU Leuven-University of Leuven, Leuven, Belgium.
6
Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
7
Children's Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Abstract

Context:

Metformin is used in pregnancy in women with gestational diabetes mellitus, polycystic ovary syndrome (PCOS), and obesity. Metformin passes the placenta.

Objective:

To explore the effects of metformin use in PCOS pregnancies on offspring growth to 4 years of age.

Design:

Follow-up study of two randomized, double-blind, placebo-controlled trials.

Setting:

Secondary care centers. Eleven public hospitals in Norway.

Participants:

One hundred eighty-two children of mothers with PCOS who participated in two randomized controlled trials.

Intervention:

Metformin 1700 or 2000 mg/d or placebo from first trimester to delivery in the original studies. No intervention in the current study.

Main Outcome Measures:

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.

Results:

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).

Conclusion:

Metformin-exposed children had higher BMI and increased prevalence of overweight/obesity at 4 years of age.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00159536 NCT03259919.

PMID:
29490031
DOI:
10.1210/jc.2017-02419
[Indexed for MEDLINE]

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