ORLANDO – Subclinical elevated maternal blood glucose levels during the second trimester are strongly associated with increased risk of tetralogy of Fallot, Dr. James R. Priest reported at the American Heart Association scientific sessions.
It’s well established that maternal type 2 diabetes and gestational diabetes are strong maternal risk factors for structural congenital heart disease in their offspring. But the women in this study didn’t meet criteria for those diagnoses. They were asymptomatic, and their elevations in blood glucose in random nonfasting measurements obtained in the second trimester were below the 200 mg/dL threshold.
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Thus, this study provides the first evidence that maternal blood glucose as a continuous variable is associated with increased risk of specific congenital heart defects in offspring, according to Dr. Priest, a pediatric cardiologist at Stanford (Calif.) University.
Of note, in this study of nondiabetic women, an elevated blood glucose was not associated with increased risk of d-transposition of the great arteries (dTGA), which, like tetralogy of Fallot, has been associated with maternal diabetes.
Dr. Priest presented an observational study of 277 pregnant, nondiabetic women, of whom 55 gave birth to a baby with tetralogy of Fallot, 42 had a baby with dTGA, and 180 gave birth to a baby without congenital heart disease or other malformations. Random nonfasting blood glucose and serum insulin levels were obtained from all subjects during weeks 15-18 of pregnancy.
The median maternal blood glucose level was 91.5 mg/dL in controls, similar at 90 mg/dL in the mothers of infants with dTGA, and significantly increased at 97 mg/dL in the mothers of offspring with tetralogy of Fallot. In a multivariate analysis adjusted for maternal age and ethnicity, elevated nonfasting second-trimester maternal glucose was associated with a 7.54-fold increased risk of having an infant with tetralogy of Fallot.
Maternal serum insulin level wasn’t associated with the risk of congenital heart disease.
Dr. Priest emphasized that while this study breaks new ground, the findings must be considered preliminary.
“Maternal blood glucose levels are influenced by diet, exercise, beta-cell function, and insulin resistance. Thus, blood glucose levels may simply be a marker of risk conferred by another physiologic process. The question remains whether elevated blood glucose or a variety of correlated but independent traits is behind the observed association,” he noted.
He plans to answer this key question by studying the relationship between these physiologic traits and blood glucose levels earlier in pregnancy.
This study was funded by the Stanford Cardiovascular Institute and the National Institutes of Health. Dr. Priest reported having no financial conflicts of interest.