Abstract

Treatment of asthma symptoms during pregnancy is crucial for maternal and fetal health. Short-acting beta2-agonists (SABA) are frequently used as rescue medications and long-acting beta2-agonists (LABA) are used as add-on controller therapy for asthma during pregnancy. The objective of this study was to investigate the association between exposure to SABA and LABA in the first trimester of pregnancy and the risk of congenital malformations among women with asthma. A cohort of pregnancies from women with asthma was formed through linkage of three administrative databases from Québec, Canada. The primary outcomes were major and any congenital malformations. The primary exposures were exposure to SABA and LABA during the first trimester, while secondary exposure was weekly SABA doses. The associations between congenital malformations (any, major, and specific) and SABA and LABA exposure were assessed with generalized estimating equations models. From a group of 13,117 pregnancies, we identified 1242 and 762 infants with any (9.5%) and major (5.8%) congenital malformations, respectively. The adjusted odds ratios (95% confidence interval [CI]) for any malformations associated with the use of SABA and LABA were 1.04 (95% CI, 0.92-1.17) and 1.37 (95% CI, 0.92-2.17), respectively. The corresponding figures were 0.93 (95% CI, 0.80-1.08) and 1.31 (95% CI, 0.74-2.31) for major malformations. Significant increased risks of major "cardiac" and major "other and unspecified" congenital malformations were observed with LABA use. Our study supports the evidence of SABA safety during pregnancy, but more research is required to assess whether the increased risk of malformations among LABA users is due to the medication, bias by asthma severity, or chance alone.

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