Utilisation de médicaments pour le traitement de l’asthme durant la grossesse et impact sur les issues périnatales
Asthma is one of the most common chronic medical conditions encountered during pregnancy, affecting approximately 8% of pregnant women. Current asthma treatment guidelines emphasize the importance and safety of the use of asthma medications during pregnancy compared to the risk of poorly controlled asthma for the fetus. In the evaluation of the safety of asthma medications during pregnancy, the literature review shows that questions persist, amongst others, on the safety of high inhaled corticosteroids (ICSs) doses and that there is a paucity of data on the safety of long-acting beta2-agonists (LABAs). A two components research program was developed to answers some of these questions. In the first component, a cohort of asthmatic women giving birth from 1998 to 2008 was constructed from the Régie de l’assurance maladie du Québec (RAMQ) et de MED-ÉCHO databases to assess the impact of the use of long-acting β2-agonists (LABAs) and the dose of inhaled corticosteroids (ICSs) during pregnancy on the prevalence of low birth weight (LBW), preterm birth (PB), and small for gestational age (SGA). The cohort included 7,376 pregnancies: 8.8% exposed to LABAs and 56.9% exposed to ICSs. LABA use was not found to be associated with increased prevalence of LBW (OR=0.81; 95%CI: 0.58–1.12), PB (OR=0.84; 95%CI: 0.61–1.15), or SGA (OR=0.92; 95%CI: 0.70–1.20). In the LABAs comparison (salmeterol compared to formoterol as reference), the most important difference was observed for PAG (OR=1.16, 95%CI: 0.67–2.02). For the ICSs, increasing doses were associated with a trend of increased LBW, PB, and SGA. The maximal observed OR was for a dose > 500 ug/day (fluticasone-equivalent) for LBW: (OR=1.57, 95%CI: 0.86–2.87). The comparison of the most frequently used ICSs (fluticasone compared to budesonide as reference) revealed non-statistically significant differences with a maximal difference observed for SGA (OR=1.10, 95%CI: 0.85–1.44). In the second component, a sub-cohort of asthmatic women with medical visits for asthma exacerbations was constructed to compare the treatment of exacerbations during and outside of pregnancy. The results show a reduced and delayed use of systemic corticosteroids for the treatment of asthma exacerbations in women when pregnant than when non-pregnant. The preventive treatment of asthma (ICSs and/or BALAs) could also be optimized. The results presented in this thesis support the safety of the use during pregnancy of LABAs and low to moderate doses of ICSs for the outcomes of LBW, PB and SGA and point to the need for additional data on the safety of high ICS doses. A comparable safety between studied ICSs (budesonide and fluticasone) and BALAs (formoterol and salmeterol) was also demonstrated. We also observed a reduced and delayed use of systemic corticosteroids for the treatment of asthma exacerbations in women when pregnant than when non-pregnant.
exacerbation asthma pregnancy corticosteroids long-acting beta2-agonists low birth weight prematurity small for gestational age exacerbation