Maternal obesity and metabolic risk to the offspring: why lifestyle interventions may have not achieved the desired outcomes.

Obesity during pregnancy is associated with an increased risk of short- and long-term metabolic dysfunction in the mother and her offspring. Both higher maternal pregravid body mass index (kg m(-2)) and excessive gestational weight gain (GWG) have been associated with adverse pregnancy outcomes such as gestational diabetes, preeclampsia and fetal adiposity. Multiple lifestyle intervention trials consisting of weight management using various diets, increased physical activity and behavioral modification techniques have been employed to avoid excessive GWG and improve perinatal outcomes. These randomized controlled trials (RCTs) have achieved modest success in decreasing excessive GWG, although the decrease in GWG was often not within the current Institute of Medicine guidelines. RCTs have generally not had any success with decreasing the risk of maternal gestational diabetes (GDM), preeclampsia or excessive fetal growth often referred to as macrosomia. Although the lack of success for these trials has been attributed to lack of statistical power and poor compliance with study protocols, our own research suggests that maternal pregravid and early pregnancy metabolic condition programs early placenta function and gene expression. These alterations in maternal/placental function occur in the first trimester of pregnancy prior to when most intervention trials are initiated. For example, maternal accrural of adipose tissue relies on prior activation of genes controlling lipogenesis and low-grade inflammation in early pregnancy. These metabolic alterations occur prior to any changes in maternal phenotype. Therefore, trials of lifestyle interventions before pregnancy are needed to demonstrate the safety and efficacy for both the mother and her offspring.