April 12, 2010 (Bethesda, Maryland) — The risk of obese women bearing children with congenital heart defects climbs with increasing maternal body-mass index (BMI); this applies to such defects in general but also for many in particular, suggests a population-based case-control study from New York.
The jump in risk was 15% for all obese women, those with a BMI >30, and double that for those with a BMI >40, compared with women of normal weight. Women who were simply "overweight" or "underweight" showed no significant change in overall risk. The analysis was published online April 7, 2010 in the American Journal of Clinical Nutrition.
Maternal obesity is a well-established risk factor for some congenital malformations, including, a lot of evidence suggests, heart defects, lead author Dr James L Mills (National Institute of Child Health and Human Development, Bethesda, MD) observed for heartwire . "Our study goes beyond that to show significantly increased risks for a number of individual [heart] defects."
But its most important finding, according to Mills, is that the greater the obesity, the higher the risk. It potentially means that obese women who lose weight also diminish their risk of bearing children with heart defects, something that should be explored further in trials, he said.
The analysis comprised 7392 children born with heart defects and their mothers along with 56 304 control cases without such defects, who were among a million and a half children born in upstate New York from 1993 to 2003.
The risk of any defect was significantly increased among women in both categories of obesity severity by BMI. The trend of risk worsening with obesity was significant at p<0.0001.
Odds Ratio (OR)* for Birth of Child With Heart Defect by Maternal BMI Weight Category, vs Reference BMI 19–24 Maternal weight group OR (95% CI) p
Underweight, BMI <19 1.00 (0.91–1.10) 0.97
Overweight, BMI 25–29 1.00 (0.94–1.06) 0.96
Obese, BMI 30–39 1.11 (1.04–1.20) 0.004
Morbidly obese, BMI >40 1.33 (1.15–1.54) 0.0001
All obese, BMI >30 1.15 (1.07–1.23) <0.0001
*Adjusted for maternal age, education, race, smoking status, and type of healthcare coverage
BMI=body mass index (kg/m2)
Women with a BMI of 30 to 39, those with a BMI >40, and both groups combined, compared with those with a BMI of 19 to 24, showed significantly increased individual risks of a wide range of congenital defects, including all septal and conotruncal defects, all left and right ventricular outflow-tract obstructions, and cases of hypoplastic left-heart syndrome, aortic-valve stenosis, pulmonic-valve stenosis, tetralogy of Fallot, and double-outlet right ventricle.
Underweight or simply overweight women weren't at increased overall risk of defects compared with those of normal weight. However, those with a BMI <19 had an increased risk of bearing children with aortic-valve stenosis (odds ratio 1.75; 95% CI 1.09–2.81; p=0.02).
Overweight women also had an exception, a significantly higher risk of offspring with tetralogy of Fallot (OR 1.28; 95% CI 1.01–1.62; p=0.045). But their risk of having children with total anomalous pulmonary venous return (p=0.02) or double-outlet right ventricle (p=0.046) was significantly reduced.
The databases used for the analysis didn't include data on any potentially teratogenic drugs the mothers were taking; the authors acknowledge that as a weakness of the study.
According to the authors, women with diabetes, a well-recognized teratogen, had been excluded from the study. The relationship between BMI and defects strengthened somewhat in a separate analysis that included diabetic women, but the study's overall findings were "not materially changed," they write.
Mills said the observed effect of increased BMI on congenital heart defects resembles the corresponding effects of maternal diabetes in at least one distinctive way: both conditions are associated with a range of metabolic abnormalities, and both appear to affect a variety of embryonically separate heart structures.
"I suspect that we're seeing the effects of not one, but probably more than one aberration in the metabolic milieu. It may be hyperglycemia, it may be lipid abnormalities, it may be insulin resistance, it may be inflammation, but I think it’s an intriguing area for further investigation."