Marie-France Beauchesne

Use of inhaled corticosteroids during pregnancy and risk of pregnancy induced hypertension: nested case-control study

Abstract Objective To determine whether the use of inhaled corticosteroids during pregnancy increases the risk of pregnancy induced hypertension and pre-eclampsia among asthmatic women. Design Nested case-control study. Setting Three administrative health databases from Quebec: RAMQ, MED-ECHO, and Fichier des événements démographiques. Participants 3505 women with asthma, totalling 4593 pregnancies, between 1990 and 2000. Main outcome measuresPregnancy induced hypertension and pre-eclampsia. Results 302 cases of pregnancy induced hypertension and 165 cases of pre-eclampsia were identified. Use of inhaled corticosteroids from conception until date of outcome was not associated with an increased risk of pregnancy induced hypertension (adjusted odds ratio 1.02, 95% confidence interval 0.77 to 1.34) or pre-eclampsia (1.06, 0.74 to 1.53). No significant dose-response relation was observed between inhaled corticosteroids and pregnancy induced hypertension or pre-eclampsia. Oral corticosteroids were significantly associated with the risk of pregnancy induced hypertension (adjusted odds ratio 1.57, 1.02 to 2.41), and a trend was seen for pre-eclampsia (1.72, 0.98 to 3.02). Conclusion No significant increase of the risk of pregnancy induced hypertension or pre-eclampsia was detected among users of inhaled corticosteroids during pregnancy, while markers of uncontrolled and severe asthma were found to significantly increase the risks of pregnancy induced hypertension and pre—eclampsia.

Use of inhaled corticosteroids during the first trimester of pregnancy and the risk of congenital malformations among women with asthma

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.

Risk of perinatal mortality associated with asthma during pregnancy

Background: Thirteen studies investigating the association between asthma during pregnancy and perinatal mortality reported generally no increased risk. Most of these studies should be interpreted with caution because they were limited in terms of statistical power. A study was therefore undertaken to evaluate whether maternal asthma during pregnancy increases the risk of perinatal mortality. Methods: Through three administrative databases from Québec (Canada), a cohort of women with and without asthma who had at least one pregnancy between 1990 and 2002 was formed. Perinatal mortality was identified by diagnostic codes. The adjusted odds ratio (OR) of perinatal mortality in women with and without asthma was compared using Generalised Estimation Equation (GEE) models. The first model included all potential confounders (except small for gestational age, SGA), the second model excluded birth weight, gestational age at birth and SGA and the third model excluded birth weight, gestational age at birth but included only SGA. This analysis was also stratified for birth weight and gestational age at birth. Results: The cohort was formed of 13 100 and 28 042 single pregnancies in women with and without asthma. The crude OR of perinatal mortality was 1.35 (95% CI 1.08 to 1.67), which decreased to 0.93 (95% CI 0.75 to 1.17) after adjustment for birth weight and gestational age at birth. Women with asthma had a higher rate of low birthweight babies and preterm delivery than those without asthma. Conclusion: The increased risk of low birthweight babies and premature delivery in women with asthma may partly explain the association between maternal asthma and the increased risk of perinatal mortality.

Development and validation of database indexes of asthma severity and control.

Background: The use of administrative databases to perform epidemiological studies in asthma has increased in recent years. The absence of clinical parameters to measure the level of asthma severity and control is a major limitation of database studies. A study was undertaken to develop and validate two database indexes to measure the control and severity of asthma. Methods: Database indexes of asthma severity and control were derived from definitions in the Canadian Asthma Consensus Guidelines based on dispensed prescriptions and on medical services recorded in two large administrative databases from the Canadian province of Québec (Régie de l’Assurance Maladie du Québec (RAMQ) and MED-ECHO) over 12 months. The database indexes of asthma severity and control were validated against the pulmonary function test results of 71 patients with asthma randomly selected from two asthma clinics, and they were also applied to a cohort of patients with asthma followed up for 139 283 person-years selected from the RAMQ and MED-ECHO databases between 1 January 1997 and 31 December 2004. Results: According to the database indexes, 49.3%, 29.6% and 21.1% of patients recruited at the asthma clinics were found to have mild, moderate and severe asthma, respectively, while 53.5% were found to have controlled asthma. The mean predicted value of the forced expiratory volume in 1 s (FEV1) ranged from 89.8% for mild asthma to 61.5% for severe asthma (p<0.001), whereas the range from controlled to uncontrolled asthma was 89.5% to 67.3% (p<0.001). The ratio of the FEV1 to the forced vital capacity (FEV1/FVC ratio) measured in 56 patients ranged from 75.8% for mild asthma to 61.8% for severe asthma (p = 0.030), whereas the range from controlled to uncontrolled asthma was 75.3% to 65.7% (p<0.001). Conclusion: In the absence of clinical data, these database indexes could be used in epidemiological studies to assess the severity and control of asthma.

Effect of maternal moderate to severe asthma on perinatal outcomes

BACKGROUND/OBJECTIVES It has been reported that adverse fetal outcomes are more prevalent in pregnant women with asthma than they are in women without asthma. In our study, we investigated the effect that the severity of asthma during pregnancy has on the risk of a small for gestational age (SGA) infant, low birth weight (LBW), and preterm birth. METHODS A population-based cohort of 13,007 pregnancies from asthmatic women was reconstructed through the linking of three of Quebecs (Canada) administrative databases covering the period between 1990 and 2002. A two-stage sampling cohort design was used to collect additional information on the selected womens life-style habits via a mailed questionnaire. Asthma severity during pregnancy was measured with a validated database index. A logistic regression model was used to obtain the adjusted odds ratios of SGA, LBW and preterm birth as a function of the level of asthma severity. RESULTS The proportions of women with mild, moderate and severe asthma were 82.5%, 12.5% and 5.0%, respectively. We sent 3,168 questionnaires to selected women, with a 40.2% (n=1274) response rate. Final estimates showed that the risk of SGA was significantly higher among severe (OR:1.48, 95%CI: 1.15-1.91) and moderate asthmatic women (OR: 1.30, 95%CI:1.10-1.55) than mild asthmatic women. No significant associations were found between asthma severity, preterm birth and LBW. CONCLUSIONS Mothers with severe and moderate asthma during pregnancy have a higher risk of SGA babies than those with mild asthma.

Asthma Worsenings: Approaches to Prevention and Management from the Asthma Worsenings Working Group

Most asthma patients prescribed maintenance asthma therapies still experience periods of asthma worsenings characterized by daytime or night-time symptoms, or an increased need for rescue medication. In fact, these episodes are highly prevalent even in patients with well-controlled disease. Published literature suggests that asthma worsenings likely represent a window of opportunity during which patients could intervene early to prevent exacerbations or further deterioration of asthma symptoms. However, current evidence suggests that most patients fail to respond or to self-manage appropriately during these periods.To address the issue of asthma worsenings, an interdisciplinary committee of respirologists, allergists, family physicians, pharmacists and certified asthma educators from across Canada developed a practical definition of asthma worsenings and provided approaches to the prevention and management of these episodes based on current literature. To date, combination inhaled corticosteroid/long-acting beta-agonist therapy, particularly single inhaler maintenance and reliever therapy, appears to be an effective strategy for preventing asthma worsenings and exacerbations. Addressing the potential barriers to appropriate patient self-management of asthma worsenings, such as failure to adequately identify and respond to worsenings, low expectations for controlling asthma, low health literacy and poor patient-health care professional communication, are also critical to the successful prevention and management of these episodes. Finally, an interdisciplinary team approach involving patients and their families, certified asthma educators, primary care physicians, pharmacists and specialists is likely to have the greatest impact on the identification, prevention and management of asthma worsenings.

Impact of maternal use of asthma-controller therapy on perinatal outcomes

Background Asthma during pregnancy usually requires treatment with controller medications about which more safety information is needed. The objectives are 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). Methods A cohort of women with asthma giving birth from 1998 to 2008 was constructed from Québec (Canada) administrative databases. LBW was defined as weight <2500 g, PB as delivery before 37 weeks’ gestation and SGA as a birth weight below the 10th percentile. The impact of the use of LABAs and the dose of ICSs during pregnancy on the outcomes was determined with generalised-estimating-equation models. Results The cohort included 7376 pregnancies: 8.8% exposed to LABAs and 56.9% exposed to ICSs. All LABA users also received ICSs. The prevalence of LBW, PB and SGA was 7.7%, 9.5% and 13.5%, respectively. LABA use was not found to be associated with increased prevalence of LBW (OR 0.81; 95% CI 0.58 to 1.12), PB (OR 0.84; 95% CI 0.61 to 1.15) or SGA (OR 0.92; 95% CI 0.70 to 1.20). Mean ICSs doses >125 μg/day (fluticasone-equivalent) were associated with a non-significant trend of increased LBW, PB and SGA. Conclusions Despite the possibility of residual confounding due to uncontrolled or more severe asthma or smoking status, the use of LABA and low to moderate doses of ICSs were not associated with increased prevalence of perinatal outcomes. Additional research on higher ICSs doses is required to better evaluate their safety during pregnancy.

Risk of perinatal mortality associated with inhaled corticosteroid use for the treatment of asthma during pregnancy

BACKGROUND Four studies investigating the association between inhaled corticosteroid (ICS) use during pregnancy and perinatal mortality reported no significantly increased risk. These studies must be interpreted with caution because they have insufficient statistical power and a lack of adjustment for potential confounders. OBJECTIVES We sought to evaluate whether asthmatic women exposed to ICSs during pregnancy are more at risk of perinatal mortality than asthmatic women not exposed. We also sought to estimate the risk of perinatal mortality as a function of the daily ICS dose taken during pregnancy. METHODS From the linkage of 3 administrative databases from Quebec, a cohort including 13,004 single pregnancies from asthmatic women was constructed. We used a 2-stage sampling cohort design to obtain information on cigarette smoking from the medical charts of 487 mothers. The final estimates of the odds ratios (ORs) of perinatal mortality were estimated with a logistic regression model. RESULTS The cohort was formed of 4,140 women who used greater than 0 to 250 μg/d ICS, 1,140 women who used greater than 250 μg/d ICS, and 7,724 nonusers of ICSs during pregnancy. Women exposed to ICSs (any dose) had a nonsignificant increased risk of perinatal mortality (OR, 1.07; 95% CI, 0.70-1.61). The use of greater than 250 μg/d ICS was associated with a nonsignificant 52% increased risk of perinatal mortality (OR, 1.52; 95% CI, 0.62-3.76). CONCLUSION The risk of perinatal mortality was not found to be significantly associated with ICS use during pregnancy. The result associated with higher doses of ICSs is limited due to a lack of statistical power and a possibility of residual confounding by asthma severity and control.

Community Pharmacists’ Interventions in Asthma Care: A Descriptive Study

BACKGROUND Factors influencing community pharmacists’ interventions have been identified, but little information is available regarding these factors in asthma care. OBJECTIVE To describe the type and frequency of pharmacists’ asthma care interventions and to identify factors influencing those interventions. METHODS A pretested, self-administered questionnaire was mailed to all community pharmacists registered with the Ordre des pharmaciens du Québec in 2006. The form included questions about the pharmacists’ interventions in asthma care in the community setting (21 questions), factors influencing the provision of those interventions (13 questions), and the responders’ characteristics (17 questions). RESULTS A total of 4587 questionnaires were sent; 917 pharmacists returned the questionnaires (response rate 20%), and 877 were eligible for analysis. Overall, community pharmacists who completed the questionnaire appeared to intervene frequently when the initial prescription for asthma medication was filled. About 98% of responders reported providing verbal information always or often on new asthma medication prescriptions. Furthermore, checking for overuse of rescue medication and underuse of maintenance therapy always or often was reported by 91% and 85.8% of responders, respectively. Other interventions at follow-up were not as frequently reported. For example, only 8.4% of pharmacists reported reassessing inhalation technique always or often. Lack of time was reported to be an important barrier to the type and frequency of intervention, while interest on the part of the patient appeared to be a significant facilitator. About 99% of pharmacists agreed with the statement that they have an important role in asthma care. CONCLUSIONS Community pharmacists appear to intervene with patients with asthma mostly at the initiation of treatment, but some interventions at follow-up are not frequently done, which could be attributed to organizational factors.

Effect of fetal gender on maternal asthma exacerbations in pregnant asthmatic women

Recent studies have found that asthmatic women pregnant with a female fetus reported more symptoms and had slightly lower lung function than women pregnant with a male fetus. In order to further investigate this association, we studied the effect of fetal sex on maternal asthma exacerbations and the use of asthma medications during pregnancy. A large cohort of pregnant asthmatic women and their babies was reconstructed between 1990 and 2002 from the linkage of three administrative databases of the Canadian province of Quebec. Asthma exacerbations were defined as a filled prescription of oral corticosteroids, an emergency department visit, or a hospitalization for asthma. Women pregnant with a female fetus were compared to women with a male fetus with respect to their rate of asthma exacerbation, their weekly doses of inhaled short-acting beta(2)-agonists (SABA), and their daily dose of inhaled corticosteroids (ICS) during pregnancy. Logistic and linear regression models were used to obtain effect measures adjusted for several potential confounders such as asthma severity and control prior to pregnancy. The cohort included 5529 pregnancies with a single female fetus and 5728 pregnancies with a single male fetus. No significant differences were found between mothers of a female and male fetus as to the occurrence of asthma exacerbations (adjusted rate ratio=1.02; 95% CI: 0.92-1.14), the daily dose of ICS (adjusted mean difference (AMD): 2.46 microg; 95% CI: -4.01 to 8.93), and the weekly dose of SABA (AMD: 0.004 dose; 95% CI: -0.23 to 0.24). Based on the results, we conclude that fetal gender is unlikely to affect maternal asthma during pregnancy to the point where acute care and medications are more often required among women pregnant with a female fetus.