Background/Purpose: Cardiac septal defects, which include atrial septal defects (ASD) and ventricular septal defects (VSD), are the most frequent congenital heart anomalies in the general population. Uncontrolled small studies of children born to women with SLE suggest a potentially increased prevalence of structural heart defects, such as ASD and VSD. In a large population-based study, we aimed to determine if offspring born to mothers with SLE have an increased risk of ASD and VSD compared to offspring born to mothers without SLE.

Methods: The “Offspring of SLE mothers Registry (OSLER)” includes all women who had ≥1 hospitalization for delivery after SLE diagnosis, identified through Quebec’s universal healthcare databases (1989-2009). OSLER also includes a randomly selected control group of women, matched at least 4:1 for age and year of delivery, who did not have a diagnosis of SLE prior to or at the time of delivery. We identified children born live to SLE mothers and their matched controls, and ascertained ASD and VSD based on ≥1 hospitalization or physician visit with a relevant diagnostic code, within the first 12 months of life.

We performed multivariate analyses to adjust for maternal demographics, sex and birth order of child, and maternal co-morbidities. In a subsample analysis of children with maternal public drug coverage throughout pregnancy, we further adjusted for relevant maternal medications.

Results: 509 women with SLE had 719 children, while 5824 matched controls had 8493 children. Compared to controls, children born to women with SLE experienced more ASD [2.9% (95%CI 1.9, 4.4) vs 0.8% (95%CI 0.6, 1.0) and VSD [1.7% (95%CI 1.0, 2.9) vs 0.7% (95%CI 0.5, 0.9)]. Among children with cardiac septal defects, those born to SLE mothers had more repair procedures compared to controls [9.7% (95%CI 3.4, 24.9) vs 4.4% (95%CI 1.9, 9.9)].

In multivariate analyses (n=9212), children born to women with SLE had a substantially increased risk of both ASD (OR 3.36, 95%CI 1.99, 5.70) and VSD (OR 2.48, 95%CI 1.20, 4.76) compared to controls. In addition, offspring of SLE mothers had a substantially increased risk of having a cardiac septal defect repair compared to controls (OR 4.90, 95%CI 1.11, 21.73).

When accounting for the possibility of detection bias by excluding children with ≥ 1 fetal echocardiography (n=331), adjusted effect estimates were similar to the primary multivariate analysis results for both ASD (OR 2.48, 95%CI 1.26, 4.87) and VSD (OR 2.09, 95%CI 0.96, 4.53). In the subsample analysis further controlling for relevant maternal medications (n=1925), though a trend remained for increased risk of ASD and VSD (combined) for offspring of SLE mothers versus controls, due to reduced sample size the 95% CI was wide and included the null value (both ASD and VSD combined; OR 1.83, 95%CI 0.59, 5.69).

Conclusion: Compared to children from the general population, children born to women with SLE have an increased risk of ASD and VSD, as well as an increased risk of having a cardiac septal defect repair. The effect of SLE on cardiac septal defects does not seem to be explained by detection bias and might be independent of medication exposures.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-cardiac-septal-defects-in-children-born-to-women-with-systemic-lupus-erythematosus-results-from-the-o-s-l-e-r-study/