Aim: To investigate whether the maternal use of different doses of inhaled corticosteroids (ICSs) during the first trimester of pregnancy for the treatment of asthma increases the risk of congenital malformations in the offspring.
Methods: From the linkage of three administrative Canadian databases, a cohort of 4561 pregnancies from women with asthma who delivered between 1990 and 2000 was reconstructed. A two-stage sampling cohort design was used to acquire additional data from the woman’s medical chart. Cases of congenital malformation were identified from the medical services database or the hospital database. Using refill patterns of medications, the average daily dose of ICSs used during the first trimester was calculated and categorised as follows: 0, 1–500, 500–1000 and >1000 μg/day in beclomethasone–chlorofluorocarbon equivalent. A Generalized Estimation Equation model was used to estimate the adjusted odds ratio of congenital malformation as a function of ICS daily dose. All analyses were performed for all malformations and major malformations separately.
Results: Within the cohort 418 babies were identified with a congenital malformation (9.2%), 278 of which had a major malformation. About 40% of women used ICSs during the first trimester, but only 5.3% of women used >500 μg/day. The adjusted odds ratio (95% CI) for all malformations associated with the use of ICSs during the first trimester was: 0.77 (0.53 to 1.13) for 1–500, 0.41 (0.19 to 0.92) for 501–1000 and 1.00 (0.42 to 2.36) for >1000 μg/day. The corresponding figures for major malformations were 0.90 (0.64 to 1.24), 0.56 (0.22 to 1.43) and 1.67 (0.56 to 5.03).
Conclusion: This study adds evidence to the safety of ICSs for the treatment of asthma during pregnancy, with regard to the likelihood of congenital malformation.
- CFC, chlorofluorocarbon
- GEE, Generalized Estimation Equation
- ICS, inhaled corticosteroid
- ISQ, Institut de la statistique du Québec
- RAMQ, Régie de l’assurance-maladie du Québec
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Funding: LB is the recipient of a new investigator salary support grant from the Canadian Institutes for Health Research (CIHR). This study was funded through grants received from the Fonds de la recherche en santé du Québec (FRSQ), the CIHR and the Canadian Foundation for Innovation. LB and M-FB co-chair the Endowment Pharmaceutical Chair AstraZeneca in Respiratory Health.
Competing interests: None.
The corresponding author (LB) had full access to all the data in the study and had final responsibility for the decision to submit for publication. The funding for this study comes from non-profit peer reviewed organisations that had no involvement in the study design, collection of data, analysis, interpretation of data, writing of the report and decision to submit the paper for publication.
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