Beta₂‐agonists use during pregnancy and the risk of congenital malformations

Abstract

BACKGROUND 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. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.

Asthma exacerbations during the first trimester of pregnancy and congenital malformations: revisiting the association in a large representative cohort

“…Interestingly, this study, along with a second study from our group,16 were the only studies that measured asthma exacerbations during the first trimester of pregnancy, that is, the most critical period for congenital malformations. Regarding the study populations, the type of health insurance plan was not specified in six of the nine studies,7 8 10 12 14 21 one study was conducted among women with private healthcare insurance,13 and our two studies were conducted among women with public drug insurance only 15 16. The meta-analysis, which included four of the nine studies, reported that asthma exacerbations during pregnancy were not associated with an increased prevalence of congenital malformation 23…”

Safety of Drugs during Pregnancy and Breastfeeding in Cystic Fibrosis Patients

“…However, results from a recent meta-analysis suggest that these associations may be chance findings or related to the underlying asthma severity [41] . In contrast, no increase in malformation rate was reported by large database studies [44,50,56,57] . Several studies support the absence of obstetrical or perinatal complications associated with SABA use [44,[58][59][60] .…”

“…Several studies support the absence of obstetrical or perinatal complications associated with SABA use [44,[58][59][60] . There are limited observational data on the safety of LABA during pregnancy, although an increase in cardiac malformations has been reported in one study [56] . No difference in perinatal risks has been reported between salmeterol and formoterol [61] .…”

Associations of maternal asthma severity and control with pregnancy complications

“…The asthma diagnostic codes recorded in the RAMQ medical database were shown to be a valid method of identifying patients with asthma [25], and data on medications recorded in the RAMQ prescription database were found to be comprehensive and valid [26]. This cohort has already been used to study the impact of asthma and asthma medications on the health of the mother and the newborn [27][28][29][30].…”