Prenatal origin of obesity and their complications: Gestational diabetes, maternal overweight and the paradoxical effects of fetal growth restriction and macrosomia

Abstract

Pregestational (PGDM) and gestational (GDM) diabetes may be associated with a variety of fetal effects including increased rate of spontaneous abortions, intrauterine fetal death, congenital anomalies, neurodevelopmental problems and increased risk of perinatal complications. Additional problems of concern are fetal growth disturbances causing increased or decreased birth weight. Optimal control of maternal blood glucose is known to reduce these changes. Among the long lasting effects of these phenomena are a high rate of overweight and obesity at childhood and a high tendency to develop the "metabolic syndrome" characterized by hypertension, cardio-vascular complications and type 2 diabetes. Similarly, maternal overweight and obesity during pregnancy or excessive weight gain are also associated with increased obesity and complications in the offspring. Although there are different causes for fetal growth restriction (FGR) or for fetal excessive growth (macrosomis), paradoxically both are associated with the "metabolic syndrome" and its long term consequences. The exact mechanism(s) underlying these long term effects on growth are not fully elucidated, but they involve insulin resistance, fetal hyperleptinemia, hypothalamic changes and most probably epigenetic changes. Preventive measures to avoid the metabolic syndrome and its complications seem to be a tight dietary control and physical activity in the children born to obese or diabetic mothers or who had antenatal growth disturbances for other known or unknown reasons.