Abstract 16184: Elevated Maternal Glucose Levels During Gestation may Confer Specific Risk for Tetralogy of Fallot

Abstract

Introduction: Clinicians have long observed an association between maternal diabetes and risk of congenital heart disease (CHD) in offspring. Though the clinical diagnoses of Type 2 diabetes or gestational diabetes are strong maternal risk factors, this diagnostic classification captures only a subset of patients with overt hyperglycemia not more subtle abnormalities of glucose or insulin metabolism. We explored the potential risk for two different CHD phenotypes in offspring with with midpregnancy measures of glucose, insulin, and insulin resistance. Hypothesis: We hypothesize that continuous measures of blood analytes related to maternal diabetes will be associated with the risk for two CHD phenotypes tetralogy of Fallot (ToF) and d-Transposition of the Great Arteries (dTGA) which have been recently associated with overt diabetes. Methods: We assembled a prospective cohort of 277 women carrying infants with ToF (n=55), dTGA (n=42), or nonmalformed control infants without CHD (n=180), and measured serum insulin by a validated radioimmunoassay and glucose levels in second trimester blood samples. We performed univariable as well as multivariable analyses to investigate statistical associations. Results: Maternal glucose levels were associated with elevated risk for both CHD phenotypes in offspring with an adjusted odds ratio (OR) of 6.61 (95%CI 1.67-26.13), which in subgroup analysis was driven by a strong association with ToF (OR 18.45, 95%CI 3.34-102.08) compared to the much lower OR for dTGA (OR 1.24, 95%CI 0.16-9.59). Conclusions: We observed that maternal blood glucose levels are strongly associated with risk for ToF, which is consistent with recent epidemiological data. These results represent the first direct correlation of glucose as a continuous variable to risk for specific cardiac malformations. In conclusion the association between serum glucose and risk for ToF suggest the need for additional epidemiological and mechanistic investigations into the risk for conferred by insulin signaling and glucose metabolism during early pregnancy.