Cardiometabolic Follow Up of the Offspring From the Metformin in Obese Non-Diabetic Pregnant (MOP) Women Trial

Abstract

Background: Maternal obesity is associated with adverse cardiometabolic outcome in the offspring. We aimed to assess whether prenatal exposure to metformin can improve the cardiovascular profile and body composition in the offspring of obese mothers. Methods: In 151 children from the MOP trial we measured body composition, peripheral blood pressure and arterial pulse wave velocity. Central haemodynamics (central blood pressure and augmentation index) were estimated using the Vicorder device. Left ventricular cardiac function and structure were assessed by echocardiography. In 39 children from each group the metabolic profile was assessed. Findings: Children were 3.9±1.0 years of age and 77 were exposed to metformin prenatally. There was no significant difference in peripheral blood pressure, arterial stiffness and body composition apart from gluteal and tricep circumferences which were lower in the metformin group (p<0.05). The metformin, compared to the placebo group, had lower central haemodynamics (mean adjusted decrease -0.707mmHg for aortic systolic blood pressure, -1.65mmHg for aortic pulse pressure and -2.68% for augmentation index, p<0.05 for all) and improved left ventricular diastolic function (adjusted difference in left atrial area -0.525cm2, in isovolumic relaxation time -0.324msec and in pulmonary venous systolic wave 2.97cm/s, p<0.05 for all). There were no significant differences in metabolic profile between the groups. Interpretation: Children of obese mothers who were prenatally exposed to metformin, compared to those exposed to placebo, have improved central haemodynamic and cardiac diastolic indices. These results suggest that administration of metformin in obese pregnant women may reduce the cardiovascular risk for their offspring. Funding Statement: The study was supported by a grant from the Fetal Medicine Foundation (Charity No: 1037116). MC acknowledges financial support from the Department of Health through the National Institute for Health Research (NIHR) Healthcare Technology Co-operative for Cardiovascular Diseases at Guy’s and St Thomas’ NHS Foundation Trust. Declaration of Interests: The authors state: None. Ethics Approval Statement: Ethical approval for the study was obtained from the London-Surrey Borders Research Ethics Committee (REC no 08/H0806/80). Signed informed consent was obtained from the parents and assent from the child when possible.