Maternal Obesity and Congenital Heart Defects

Study Questions:

How does severity of maternal overweight and obesity impact rates of complex and specific heart defects in offspring?

Methods:

A Swedish cohort including 2,050,491 live singleton infants born between 1992 and 2012 was analyzed. Maternal and infant diagnoses were obtained from national registries. Prenatal maternal body mass index (BMI) categories were: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5 to <25 kg/m2), overweight (BMI 25 to <30 kg/m2), obesity class I (BMI 30 to <35 kg/m2), class II (BMI 35 to <40 kg/m2), and class III (BMI ≥40 kg/m2). Outcomes were complex congenital heart defects (tetralogy of Fallot, transposition of the great arteries, atrial septal defects, aortic arch defects, and single-ventricle heart), and other heart defects diagnosed before age 5 and adjusted prevalence rate ratios (PRRs) were calculated.

Results:

There were 28,628 (1.4%) children with ≥1 congenital heart defect and overall rates were increased with maternal BMI. PRRs of aortic arch defects and transposition of the great arteries were doubled in offspring of mothers with severe obesity. Rates of atrial septal defects and patent ductus arteriosus in term infants were higher among offspring of mothers with increased BMI. There was no clear association between BMI and rates of several other complex and specific heart defects.

Conclusions:

PRRs of certain congenital heart defects (aortic branch defects, atrial septal defects, and persistent ductus arteriosus) increased with higher maternal BMI.

Perspective:

Maternal obesity is recognized as a risk factor for congenital heart defects among offspring. This study shows that certain defects (aortic arch defects, atrial septal defects, and persistent ductus arteriosus) were associated with increasing BMI, but others were not. The mechanism by which obesity increases the risk of fetal malformations may be related to diabetes, insulin resistance, inflammation, endothelial dysfunction, and oxidative stress causing adverse gene expression and organ development. Prior animal studies have shown that hyperglycemia is associated with increased risks of congenital malformations, and that supplementation with antioxidants (vitamins C and E) could potentially inhibit damage by free oxygen radicals. Maternal malnutrition may also contribute to congenital defects, as obese women have been observed to have lower levels of folic acid and are less responsive to supplementation in standard doses. Further studies could examine specific associations between fat distribution such as visceral fat. Given the high rates of obesity in the United States, primary prevention efforts aimed at reducing obesity among women of childbearing age should be a priority.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Prevention, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement

Keywords: Aorta, Thoracic, Body Mass Index, Diabetes Mellitus, Ductus Arteriosus, Ductus Arteriosus, Patent, Heart Defects, Congenital, Infant, Newborn, Mothers, Obesity, Overweight, Pregnancy, Primary Prevention, Risk Factors, Tetralogy of Fallot, Transposition of Great Vessels, Women


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