Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: A United Kingdom population-based study

Abstract

Background: Clinical advice to pregnant women with asthma is to maintain optimal therapeutic management, however, potential adverse effects of asthma treatments on fetal development remain uncertain. We assessed the association of maternal asthma and gestational exposure to asthma medications with risk of major congenital malformation in offspring.

Methods: Matched case-control study using The Health Improvement Network primary care database. Children with malformations were matched to control children on birth year, general practice and singleton or twin delivery.

Results: We included 5,124 cases of liveborn children with congenital malformations and 30,053 controls. Risk of any major malformation in children born to women with asthma was marginally higher than that in children born to women without asthma (adjusted Odds Ratio(OR)=1.10, 95% confidence interval(CI) 1.01-1.20). However, no association was present in children born to mothers receiving asthma treatment in the year before or during pregnancy (OR=1.06, 95%CI 0.94-1.20). In assessing teratogenicity of medications, we found no increased risk of malformation with gestational exposures to short or long acting β-agonists, inhaled corticosteroids, oral corticosteroids, other bronchodilators or cromones. These findings were similar for each of 11 system-specific malformation groups, except for an increase in musculoskeletal system malformation associated with cromone exposure.

Conclusions: Overall, gestational exposure to commonly used asthma medications was found to be safe, although moderate teratogenic risk of cromones cannot be excluded. We found some evidence of a small increased risk of congenital malformation in children born to women with asthma, but this was not explained by gestational exposure to asthma drugs.