Risk of congenital malformations for asthmatic pregnant women using a long-acting ß2-agonist and inhaled corticosteroid combination versus higher-dose inhaled corticosteroid monotherapy.

BACKGROUND: Current recommendations for managing persistent asthma during pregnancy when low-dose inhaled corticosteroids (ICSs) are insufficient include adding a long-acting ß2-agonist (LABA) or increasing the ICS dose. However, there are no data to help clinicians evaluate the safest regimen during pregnancy. OBJECTIVE: We sought to compare the risk of major congenital malformations in asthmatic women exposed to a LABA plus ICS combination and those exposed to ICS monotherapy at higher doses during the first trimester. METHODS: A cohort of asthmatic pregnant women exposed to ICSs during the first trimester who delivered between January 1990 and March 2009 was established. The primary outcome was major malformation recorded at birth or during the first year of life. Two subcohorts were established as follows: (1) users of a LABA plus low-dose ICS combination or users of a medium-dose ICS and (2) users of a LABA plus medium-dose ICS combination or users of a high-dose ICS. Generalized estimating equations were used to compare the risk of major malformations between the groups. RESULTS: In one subcohort there were 643 women who used a LABA plus low-dose ICS and 305 who used a medium-dose ICS; the other subcohort included 198 users of a LABA plus medium-dose ICS and 156 users of a high-dose ICS. The prevalence of major malformations was 6.9% and 7.2%, respectively. The adjusted odds ratio for major malformations was 1.1 (95% CI, 0.6-1.9) when a LABA plus low-dose ICS was used compared with a medium-dose ICS and 1.2 (95% CI, 0.5-2.7) when a LABA plus medium-dose ICS was used compared with a high-dose ICS. CONCLUSION: The risk of major malformations was similar with a LABA plus ICS combination and ICS monotherapy at higher doses, suggesting that both therapeutic options can be considered during pregnancy.