Maternal Non-glycemic Contributors to Fetal Growth in Obesity and Gestational Diabetes: Spotlight on Lipids

Excess fetal growth is increasingly recognized as a risk factor for childhood obesity, and mounting evidence supports that maternal glucose is not the only driver. This review focuses on the role of clinically applicable maternal non-glycemic contributors to excess fetal growth, particularly lipids, in addition to amino acids (AA), insulin resistance, inflammation, maternal nutrition, and gestational weight gain (GWG) in obesity and gestational diabetes mellitus (GDM). Lipids, specifically triglycerides and free fatty acids, appear to be strong contributors to excess fetal fat accretion and adiposity at birth, particularly in obese pregnancies, which account for the largest number of large-for-gestational-age infants. Maternal pre-pregnancy body mass index (BMI), GWG, insulin resistance, inflammation, and glucose, lipid, and AA concentrations have both independent and interacting effects on fetal growth, operating both early and late in pregnancy. All are sensitive to maternal nutrition. Early vs. later gestational exposure to excess maternal fuels in fasting and postprandial conditions may differentially impact fetoplacental outcomes. Compelling evidence suggests that targeting interventions early in pregnancy beyond glucose may be critical to improve fetal growth patterns.