Maternal asthma may raise congenital heart defect risk in offspring

Asthma and allergic tendency in mothers appear to elevate the risk of congenital heart defect (CHD) in their children, suggests a study, noting that nonallergic asthma also contributes to such risk.

“Our study confirms that maternal asthma is associated with an increased risk of CHDs in offspring. We also demonstrate that maternal allergic tendency, even in the absence of asthma, carries a similar risk for CHD as allergic asthma,” said lead study author Dr Mari Kemppainen, Vantaa and Kerava Wellbeing County, Martinlaakso Health Station, Vantaa, Finland.

Kemppainen and colleagues conducted this retrospective, population-based study using a comprehensive birth cohort of all singleton births in Finland between 1996 and 2018. They obtained data by linking four high-coverage national health registers.

A total of 1,274,540 mother‒child pairs met the eligibility criteria. Of the mothers, 106,544 (8.4 percent) were diagnosed with asthma or prescribed an asthma medication during pregnancy. Of the offspring, 18,772 (1.5 percent) had a CHD diagnosis, and 8,855 were diagnosed with ventricular septal defect (VSD). [Acta Obstet Gynecol Scand 2025;104:1849-1858]

Maternal asthma showed a modest association with overall CHD (odds ratio [OR], 1.18, 95 percent confidence interval [CI], 1.12‒1.24) and with VSD (OR, 1.19, 95 percent CI, 1.10‒1.27). This association was present in both allergic (OR, 1.33, 95 percent CI, 1.18‒1.50) and nonallergic asthma (OR, 1.27, 95 percent CI, 1.04‒1.56).

“VSD is the largest CHD subgroup and has the greatest associations with maternal asthma in this study,” Kemppainen said. “In most cases, VSD occurs in the muscular part of the heart ventricular septum with only a small portion affecting the perimembranous part.” [Orphanet J Rare Dis 2014;9:144]

Likewise, maternal allergic conditions, such as atopic dermatitis and allergic rhinitis, correlated with overall CHD (OR, 1.13, 95 percent CI, 1.02‒1.25) and VSD (OR, 1.20, 95 percent CI, 1.04‒1.38).

“These findings suggest that maternal allergic inflammation may have teratogenic effects during foetal cardiac development,” Kemppainen said. “This knowledge may enhance our understanding of CHD pathogenesis and contribute to the development of future prevention strategies.”

Mechanism

The mechanism by which allergic inflammation interferes with heart development or septation of the ventricles during pregnancy remains unclear, based on a review of existing literature.

One study, however, showed the association of maternal antinuclear SSA and SSB antibodies with foetal heart development. These antibodies have been shown to cause damage to cardiac conduction pathways. [Best Pract Res Clin Obstet Gynaecol 2020;64:41‐51]

Apart from CHD, maternal asthma has been found to be associated with pregnancy complications, such as pre-eclampsia, placenta previa, placental abruption, gestational diabetes, breech presentation, and intensive care admission during pregnancy. [Am J Obstet Gynecol 2013;208:127.e1-8]

CHDs, on the other hand, have also been shown to correlate with placental abnormalities. [Placenta 2021;112:189‐196]

“Disruption in the maternal side of the placenta may be associated with abnormal development of the uteroplacental unit also on the foetal side, leading to changes in vascular resistance and haemodynamic changes in the developing foetal heart, ultimately leading to CHD,” Kemppainen said. [J Matern Fetal Med 2000;9:282‐286]

Kemppainen and colleagues explored this possibility by assessing known risk factors for placental abruption, including smoking, maternal thrombotic tendency, and chronic hypertension. They used placental abruption risk factors as surrogate for placental diseases, since abruption correlates with maternal vascular malperfusion, a common placental disease. [Placenta 2020;94:39‐43]

“Interestingly, thrombotic tendency, hypertension, and smoking were associated with the risk for particularly right‐sided CHD,” said Kemppainen, noting that these findings are consistent with those of previous studies. [J Am Coll Cardiol 2017;69:859‐870; JAMA 2015;314:1588‐1598]