The Association of Maternal Obesity and Gestational Diabetes during Pregnancy with Offspring Adiposity and Dysmetabolism: The Intergenerational Transmission of Obesity (ITO) Study
Abstract Objective To assess the mechanisms by which intrauterine exposure to maternal obesity and/or gestational diabetes mellitus (GDM) contribute to offspring adiposity and dysmetabolism. Study Design Prospective cohort study at two U.S. centers that enrolled pregnant individuals carrying non-anomalous, singletons at 36 to 40 weeks who met criteria for three groups: (1) normal BMI without GDM, (2) obesity without GDM, and (3) GDM. We collected fasting maternal blood at enrollment; neonatal anthropometrics, air displacement plethysmography, and umbilical cord blood at delivery; and infant body composition at 3 months. Biomarkers and outcomes were compared between maternal exposure groups. Multivariable regression with backward selection identified predictors of offspring outcomes. Results Of 283 participants enrolled, 278 were included in the final analysis: 95 (34.2%) had normal BMI, 104 (37.4%) had obesity without GDM, and 79 (28.4%) had GDM. Maternal biomarkers differed between groups with highest HbA1c, insulin, glucose, triglycerides, and free fatty acids in GDM. Leptin, IL-6, and CRP were highest with obesity, and adiponectin was highest with normal BMI. Neonates born to participants with GDM had higher birthweight, head and abdominal circumferences, and higher C-peptide and leptin levels. No differences were observed between fat free mass, fat mass, percent fat or body mass. By 3 months, only head circumference remained different between groups. Maternal triglycerides was a predictor of multiple neonatal outcomes including birthweight, head and abdominal circumference and leptin. Marital status and delivery gestational age were also associated with multiple outcomes whereas maternal age, gestational weight gain, HbA1c, and cholesterol were only associated with one outcome. Chronic hypertension, income, and IL-6 were not associated with any outcomes. Conclusion Maternal obesity and GDM are associated with neonatal overgrowth, and hypertriglyceridemia may be an important contributor. These findings underscore the importance of metabolic optimization (weight loss, glycemic control, lipid management) before conception to mitigate intergenerational transmission of obesity and metabolic disease. Key Points Metabolic biomarkers vary by obesity and GDM. Neonatal size and biomarkers differ by obesity and GDM. Maternal triglyceridemia may contribute to adverse outcomes.