Liv Guro Engen Hanem1, Øyvind Salvesen2, Petur B Juliusson3, Sven M Carlsen4, Marit Cecilie Fonn Nossum5, Marte Øye Vaage5, Rønnaug Ødegård6, Eszter Vanky7. 1. Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: liv.g.e.hanem@ntnu.no. 2. Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. 3. Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Health Registries, Norwegian Institute of Public Health, Sentrum, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Pediatrics, Haukeland University Hospital, Bergen, Norway. 4. Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Torgarden, Trondheim, Norway. 5. Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. 6. Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Centre for Obesity Research, St. Olavs Hospital, Trondheim University Hospital, Torgarden, Trondheim, Norway. 7. Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, Torgarden, Trondheim, Norway.
Abstract
BACKGROUND:Metformin is increasingly used to treat gestational diabetes and type 2 diabetes in pregnancy, and in attempts to improve pregnancy outcomes in polycystic ovary syndrome and obesity. It passes across the placenta with possible long-term consequences for the offspring. We previously explored the effect of metformin, given to women with polycystic ovary syndrome during pregnancy, on children's growth up to 4 years of age. In this 5-10 year follow-up, we examined the cardiometabolic risk factors in these children. METHODS: This is a follow-up of children from the PregMet study, a double-blind, randomised controlled trial comparing metformin with placebo in polycystic ovary syndrome pregnancies. In the PregMet study, between Feb 4, 2005, and Jan 27, 2009, 257 pregnant women aged 18-45 years with polycystic ovary syndrome according to the Rotterdam criteria were included with 274 singleton pregnancies at 5-12 weeks of gestation at 11 study centres in Norway. 17 women participated twice. Pregnant women were randomised to metformin (2000 mg/day) or placebo from inclusion in the first trimester to birth. Randomisation was stratified according to metformin use at conception. In this follow-up, the primary endpoint was body-mass index (BMI) in the offspring at 5-10 years of age assessed by the standard deviation score (Z score). The primary endpoint was analysed with independent sample t tests. ClinicalTrials.gov number NCT00159536. FINDINGS: Of the 255 invited children from the PregMet study, 141 (55%) consented to participate and were included between April 29, 2014, and July 12, 2016. Maternal baseline characteristics in the first trimester were similar between groups. Children in the metformin group had a higher BMI Z score than those in the placebo group (difference in means=0·41, 95% CI 0·03-0·78, p=0·03). INTERPRETATION: The increased BMI in metformin-exposed children might indicate a potential risk of inferior cardiometabolic health. Implications for adult health cannot be excluded. FUNDING: The Research Council of Norway, Novo Nordisk Foundation, St Olavs University Hospital, and the Norwegian University of Science and Technology.
RCT Entities:
BACKGROUND:Metformin is increasingly used to treat gestational diabetes and type 2 diabetes in pregnancy, and in attempts to improve pregnancy outcomes in polycystic ovary syndrome and obesity. It passes across the placenta with possible long-term consequences for the offspring. We previously explored the effect of metformin, given to women with polycystic ovary syndrome during pregnancy, on children's growth up to 4 years of age. In this 5-10 year follow-up, we examined the cardiometabolic risk factors in these children. METHODS: This is a follow-up of children from the PregMet study, a double-blind, randomised controlled trial comparing metformin with placebo in polycystic ovary syndrome pregnancies. In the PregMet study, between Feb 4, 2005, and Jan 27, 2009, 257 pregnant women aged 18-45 years with polycystic ovary syndrome according to the Rotterdam criteria were included with 274 singleton pregnancies at 5-12 weeks of gestation at 11 study centres in Norway. 17 women participated twice. Pregnant women were randomised to metformin (2000 mg/day) or placebo from inclusion in the first trimester to birth. Randomisation was stratified according to metformin use at conception. In this follow-up, the primary endpoint was body-mass index (BMI) in the offspring at 5-10 years of age assessed by the standard deviation score (Z score). The primary endpoint was analysed with independent sample t tests. ClinicalTrials.gov number NCT00159536. FINDINGS: Of the 255 invited children from the PregMet study, 141 (55%) consented to participate and were included between April 29, 2014, and July 12, 2016. Maternal baseline characteristics in the first trimester were similar between groups. Children in the metformin group had a higher BMI Z score than those in the placebo group (difference in means=0·41, 95% CI 0·03-0·78, p=0·03). INTERPRETATION: The increased BMI in metformin-exposed children might indicate a potential risk of inferior cardiometabolic health. Implications for adult health cannot be excluded. FUNDING: The Research Council of Norway, Novo Nordisk Foundation, St Olavs University Hospital, and the Norwegian University of Science and Technology.
Authors: Elisabet Stener-Victorin; Vasantha Padmanabhan; Kirsty A Walters; Rebecca E Campbell; Anna Benrick; Paolo Giacobini; Daniel A Dumesic; David H Abbott Journal: Endocr Rev Date: 2020-07-01 Impact factor: 19.871
Authors: Daniel A Dumesic; Luis R Hoyos; Gregorio D Chazenbalk; Rajanigandha Naik; Vasantha Padmanabhan; David H Abbott Journal: Reproduction Date: 2020-01 Impact factor: 3.906