ESPE Abstracts (2018) 89 P-P1-114

Intrauterine Metformin Exposure and Offspring Metabolic Health at 8-Years Follow-up

Liv Guro Engen Hanema, Pétur Júlíussonb, Sven Carlsena,c, Marit Cecilie Fonnd, Marte Øye Vaaged, Øyvind Salvesend, Rønnaug Ødegårda,e & Eszter Vankya,f


aDepartment of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; bDepartment of Clinical Science, University of Bergen, Bergen, Norway; cDepartment of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; dFaculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; eChildren’s Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; fDepartment of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway


Background: Metformin is increasingly used in pregnancy and passes the placenta. Data on long-term effect on the offspring is essentially lacking. We explored possible effects of intrauterine metformin exposure on metabolic health, in 8-years-old children of women with PCOS.

Methods: Follow-up of children from the PregMet-study - an RCT comparing metformin (2000 mg) to placebo during PCOS pregnancies. The primary endpoint was Body Mass Index (BMI). Secondary endpoints included waist circumference, waist-to-height ratio, height, weight, head circumference, bioimpedance-determined muscle-mass and percentage body-fat (%BF), cholesterol, triglyceride, HDL-cholesterol, fasting glucose, HbA1c, blood pressure and heart rate. All anthropometric measurements were converted to, and presented as, standard deviation scores (SDS).

Findings: During April 2014–July 2016 we included 141 (55%) of the 255 invited children. Maternal baseline characteristics were comparable between groups. The BMI SDS was higher in the metformin group than in the placebo group [difference in means (d) =0.41, 95% CI 0.03 to 0.78, P=0.034]. Metformin exposed children had higher waist-to-height ratio SDS [d=0.36, 95% CI 0.06 to 0.67, P=0.021], higher waist circumference SDS [d=0.40, 95% CI 0.08 to 0.71, P=0.014], weighed more [weight SDS d=0.43, 95% CI 0.04 to 0.82, P=0.032], and had a tendency of higher %BF [d=3.04, 95% CI −0.58 to 6.67, P=0.099]. Height, head circumference, muscle-mass (kg), biochemical analyses, blood pressure and heart rate were comparable between groups. A larger proportion of the offspring in the metformin group, n=28 (39.4%) than in the placebo group, n=13 (18.8%), P=0.007 had eczema, while fewer children in the metformin group, 4 (5.6%), than in the placebo group 12 (17.4%), P=0.029 had constipation.

Interpretation: The increased BMI, waist circumference and waist-to-height ratio observed in metformin-exposed offspring indicates central adiposity and a possible risk of inferior metabolic health. However, as biochemical markers were comparable between the groups, the impact of metformin exposure on metabolic health of 8-years-old children might be limited. Implications for adult health are uncertain.

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