New Details Link Maternal Weight and Congenital Heart Defects

January 14, 2019

A nationwide study from Sweden provides insights into the role of excess maternal weight and increased rates of some, but not all, congenital heart defects (CHDs) in children.

"It is well established that maternal obesity increases risks of severe pregnancy complications, including congenital heart defects. However, it has so far been unclear if maternal obesity associates with risks of specific and complex heart malformations," study author Martina Persson, MD, PhD, Karolinska Institute, Stockholm, said when reached by email.

The researchers found CHD rates increased across rising maternal body mass index (BMI) categories, with risks for atrial septal defect (ASD) and patent ductus arteriosus (PDA) increasing significantly with maternal overweight and obesity severity in a dose–response pattern.

"The most important period of fetal organ development occurs in the first 8 weeks of pregnancy," Persson said. "Thus, women in reproductive age should ideally be informed about risks with obesity in pregnancy and offered support to reach normal weight before conception."

Their results were published January 7 in the Journal of the American College of Cardiology.

For this analysis, researchers used national health registries to calculate prevalence rate ratios (PRRs) of five complex and seven specific CHDs diagnosed in the first 5 years of life in 2,050,491 singletons born in Sweden between 1992 and 2012. In multivariable models, PRRs were adjusted for maternal factors, offspring sex, and birth year.

A total of 28,628 (1.4%) children had at least one CHD. As expected, CHD rates increased across rising maternal BMI categories.

CHD Cases by BMI
Weight Category BMI, kg/m² CHD Rate, %
Normal weight 18.5 - <25 13.4
Overweight 25 - <30 14.3
Obese class I 30 - <35 16.2
Obese class II 35 - <40 18.4
Obese class III ≥40 21.6

Adjusted risks for ASD and PDA increased with maternal overweight and obesity severity in a dose–response pattern (P < .0001).

Specifically, the adjusted PRR of ASD in the offspring of overweight mothers was 1.08 (95% CI, 1.02 - 1.14); this climbed to 1.65 (95% CI, 1.34 - 2.03) in the offspring of mothers with class III obesity. For PDA, the corresponding PRRs were 1.16 (95% CI, 1.06 - 1.27) and 2.32 (95% CI, 1.73 - 3.12), respectively.

PRRs of mitral–tricuspid valve and pulmonary valve defects increased with obesity severity, but this pattern did not persist in adjusted analyses.

There were generally no associations between BMI and risks for ventricular septal defect (VSD), aortic valve defects, or right ventricle defects, the authors report.

"One of the new and interesting findings in the Persson et al. study is the association of maternal obesity severity with increased prevalence of PDA among term infants," Adolfo Correa, MD, PhD, University of Mississippi Medical Center, Jackson, writes in an accompanying editorial.

Although it is not possible on the basis of a single report to assess the nature of this association, he noted that an early case–control study showed a strong association between PDA and maternal gestational diabetes mellitus in infants born to mothers at least 30 years of age, but not in mothers with pregestational diabetes.

The current study was not designed to explore potential pathophysiologic mechanisms; however, maternal obesity is associated with metabolic disturbances, a state of subclinical inflammation, vascular dysfunction, and oxidative stress, Persson said.

"These metabolic, inflammatory, and vascular alterations may adversely impact the development, gene expression, and function of the placenta of potential harm to the embryo," she said.

Complex CHD

Although the team found no evidence of a dose–effect relation for transposition of the great arteries (TGA), there was an association with class III obesity, compared with normal weight (PRR, 1.85 vs 1.00; P = .0013).

There was a stepwise increase in adjusted PRRs of aortic arch defects with rising maternal obesity severity, climbing 30% from normal weight BMI to class I obesity, and nearly doubling for class III obesity (1.00 vs 1.32 vs 1.87; P < .0001).

No clear associations were found between maternal BMI and PRRs of tetralogy of Fallot, atrioventricular septal defects (AVSD), or single-ventricle heart, although the PRR of single-ventricle heart was increased in offspring of mothers with class I obesity, the authors report.

Previous Findings

The patterns of dose–effect relations for maternal obesity severity and prevalence of ASD and aortic arch defects in the study "are generally consistent with those observed in previous studies," Correa noted.

Even though associations for single-ventricle/hypoplastic left heart syndrome, pulmonary valve stenosis, and AVSD did not reach statistical significance — possibly because of a small sample sizes for class I and II obesity — the observed patterns suggest a dose–effect relation consistent with previous studies, he added.

The TGA findings, however, are in contrast with those of a recent meta-analysis, whereas the findings for VSD are inconsistent with previous reports, Correa said.

"In future studies, it will be valuable to include more details regarding ascertainment and classification systems used, as well as inclusion and exclusion criteria, for VSDs to facilitate comparisons of findings across studies," he said.

Comparisons of studies are hampered by differences in study design and populations, as well as different definitions of both exposure and outcome, Persson said. Also, very large datasets are required for accurate estimation of risks. Further, a recent meta-analysis also reported no clear association between maternal BMI and risk for VSD.

Limitations of the study include lack of information on fat distribution, malformations in stillbirths, miscarriage, induced abortions, and maternal alcohol and drug use during pregnancy, the authors said.

The researchers and Correa agree on the need for further research, in particular, the importance of endogenous fat distribution on CHD risks.

"A better understand of underlying mechanisms may open up new possibilities for prevention," Persson said.

The researchers point out that worldwide, 21% of women are projected to be severely obese by 2025. In Sweden, the proportion of pregnant women with obesity climbed to 38% in 2014, even with its widely touted lifestyle of lagom, or "just enough."

On this point, Correa reiterated the words of Sir Michael Marmot, who said, "if you want to tackle obesity, then tackle the social determinants of obesity. Tackle inequality."

The study authors and Correa reported no relevant conflicts of interest.

J Am Coll Cardiol. 2019;73;44-53 and 54-57. Abstract, Editorial

Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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