Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring

BACKGROUND: Maternal obesity increases the risk for pregnancy complications and adverse neonatal outcome and it has also been associated with long lasting adverse effects in the offspring, including increased body fat mass, insulin resistance and increased risk for premature cardiovascular disease. Lifestyle interventions in pregnancy have produced none or modest effects in reducing adverse pregnancy outcomes in obese mothers. Metformin use in Obese Pregnant women trial was associated with reduced adverse pregnancy outcomes and had no effect on birthweight. However, the long-term implications of metformin on the health of offspring remain unknown.

OBJECTIVE: The purpose of this study was to assess whether prenatal exposure to metformin can improve the cardiovascular profile and body composition in the offspring of obese mothers.

STUDY DESIGN: In 151 children from the Metformin use in Obese-Pregnant women trial we measured body composition, peripheral blood pressure and arterial pulse wave velocity. Central hemodynamics (central blood pressure and augmentation index) were estimated using the Vicorder device. Left ventricular cardiac function and structure were assessed by echocardiography.

RESULTS: 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 hemodynamics (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 lower 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.

CONCLUSION: Children of obese mothers who were prenatally exposed to metformin, compared to those exposed to placebo, have lower central hemodynamic and cardiac diastolic indices. These results suggest that administration of metformin in obese pregnant women may potentially have a beneficial cardiovascular effect for their offspring.