Asthma is the most common disorder of the respiratory system (the organs that help you breathe) in pregnancy, affecting up to one in eight women. During pregnancy asthma can improve, worsen or remain unchanged. Poorly controlled asthma may lead to complications for mothers including pre-eclampsia (high blood pressure and protein in the urine), gestational diabetes (high blood glucose) and caesarean birth; complications for babies may include death, preterm birth (before 37 weeks of pregnancy) and being born low birthweight. Maintaining adequate control of asthma during pregnancy, including effective management and prevention of exacerbations, is the goal of management. In pregnancy, women may be concerned about risks of taking medications, and their health professionals may be uncertain about best management strategies.
This review aimed to assess how effective and safe different interventions are for managing asthma during pregnancy. We were able to include eight randomised controlled trials involving 1181 women and their babies. The trials were of moderate quality overall. Five trials assessed medications. Inhaled magnesium sulphate helped to reduce further exacerbations for women with acute asthma, and helped to improve their lung function (one trial of unclear quality, 60 women). For ongoing therapy for pregnant women with stable asthma, the effect of inhaled corticosteroids on asthma exacerbations was not clear (two trials, 155 women; but data only analysed from one trial, 60 women); no difference was seen in the chance of exacerbations when inhaled corticosteroids were compared with oral theophylline, however more women receiving theophylline stopped treatment because of side effects (one trial, 385 women). Three trials assessed non-drug interventions. Adjusting women's asthma medications according to how much nitric oxide they exhaled (their fraction of exhaled nitric oxide (FENO)) was shown to reduce exacerbations and improve their quality of life (one trial, 220 women). Progressive muscle relaxation improved women's lung function and quality of life (one trial, 64 women), and asthma management led by a pharmacist helped to improve asthma control (one trial, 60 women).
Overall, we did not find enough evidence of benefits and harms from the randomised trials to be sure about the best way to manage asthma in pregnancy, although some interventions were promising. We need larger, high-quality trials, which should report on important health outcomes for mothers and babies, including longer-term outcomes for babies into childhood and adulthood. Five trials are currently being planned or are underway assessing interventions for asthma in pregnancy.
Based on eight included trials, of moderate quality overall, no firm conclusions about optimal interventions for managing asthma in pregnancy can be made. Five trials assessing pharmacological interventions did not provide clear evidence of benefits or harms to support or refute current practice. While inhaled magnesium sulphate for acute asthma was shown to reduce exacerbations, this was in one small trial of unclear quality, and thus this finding should be interpreted with caution. Three trials assessing non-pharmacological interventions provided some support for the use of such strategies, however were not powered to detect differences in important maternal and infant outcomes. While a FENO-based algorithm reduced exacerbations, the effects on perinatal outcomes were less certain, and thus widespread implementation is not yet appropriate. Similarly, though positive effects on asthma control were shown with PMR and pharmacist-led management, the evidence to date is insufficient to draw definitive conclusions.
In view of the limited evidence base, further randomised trials are required to determine the most effective and safe interventions for asthma in pregnancy. Future trials must be sufficiently powered, and well-designed, to allow differences in important outcomes for mothers and babies to be detected. The impact on health services requires evaluation. Any further trials assessing pharmacological interventions should assess novel agents or those used in current practice. Encouragingly, at least five trials have been identified as planned or underway.
Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong evidence however, that the adequate control of asthma can improve health outcomes for mothers and their babies. Despite known risks of poorly controlled asthma during pregnancy, a large proportion of women have sub-optimal asthma control, due to concerns surrounding risks of pharmacological agents, and uncertainties regarding the effectiveness and safety of different management strategies.
To assess the effects of interventions (pharmacologic and non-pharmacologic) for managing women's asthma in pregnancy on maternal and fetal/infant outcomes.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 June 2014) and the Cochrane Airways Group's Trials Register (4 June 2014).
Randomised and quasi-randomised controlled trials comparing any intervention used to manage asthma in pregnancy, with placebo, no intervention, or an alternative intervention. We included pharmacological and non-pharmacological interventions (including combined interventions). Cluster-randomised trials were eligible for inclusion (but none were identified). Cross-over trials were not eligible for inclusion.
We included multi-armed trials along with two-armed trials. We also included studies published as abstracts only.
At least two review authors independently assessed trial eligibility and quality and extracted data. Data were checked for accuracy.
We included eight trials in this review, involving 1181 women and their babies. Overall we judged two trials to be at low risk of bias, two to be of unclear risk of bias, and four to be at moderate risk of bias.
Five trials assessed pharmacological agents, including inhaled corticosteroids (beclomethasone or budesonide), inhaled magnesium sulphate, intravenous theophylline, and inhaled beclomethasone verus oral theophylline. Three trials assessed non-pharmacological interventions, including a fractional exhaled nitric oxide (FENO)-based algorithm versus a clinical guideline-based algorithm to adjust inhaled corticosteroid therapy, a pharmacist-led multi-disciplinary approach to management versus standard care, and progressive muscle relaxation (PMR) versus sham training.
The eight included trials were assessed under seven separate comparisons.
Pharmacological interventions
Primary outcomes: one trial suggested that inhaled magnesium sulphate in addition to usual treatment could reduce exacerbation frequency in acute asthma (mean difference (MD) -2.80; 95% confidence interval (CI) -3.21 to -2.39; 60 women). One trial assessing the addition of intravenous theophylline to standard care in acute asthma did not report on exacerbations (65 women). No clear difference was shown in the risk of exacerbations with the use of inhaled beclomethasone in addition to usual treatment for maintenance therapy in one trial (risk ratio (RR) 0.36; 95% CI 0.13 to 1.05; 60 women); a second trial also showed no difference, however data were not clearly reported to allow inclusion in a meta-analysis. No difference was shown when inhaled beclomethasone was compared with oral theophylline for maintenance therapy (RR 0.88; 95% CI 0.59 to 1.33; one trial, 385 women). None of these trials reported on neonatal intensive care admissions.
Secondary outcomes: inhaled magnesium sulphate in acute asthma was shown to improve lung function measures (one trial, 60 women); intravenous theophylline in acute asthma was not associated with benefits (one trial, 65 women). No clear differences were seen with the addition of inhaled corticosteroids to routine treatment in three trials (374 women). While inhaled beclomethasone, compared with oral theophylline, significantly reduced treatment discontinuation due to adverse effects in one trial (384 women), no other differences were observed, except for higher treatment adherence with theophylline. Four of the five trials did not report on adverse effects.
Non-pharmacological interventions
Primary outcomes: in one trial, the use of a FENO-based algorithm was shown to significantly reduce asthma exacerbations (RR 0.61; 95% CI 0.41 to 0.90; 220 women); and a trend towards fewer neonatal hospitalisations was observed (RR 0.46; 95% CI 0.21 to 1.02; 214 infants). No exacerbations occurred in one trial assessing pharmacist-led management; this approach did not reduce neonatal intensive care admissions (RR 1.50; 95% CI 0.27 to 8.32; 58 infants). One trial (64 women) assessing PMR did not report on exacerbations or neonatal intensive care admissions.
Secondary outcomes: the use of a FENO-based algorithm to adjust therapy led to some improvements in quality of life scores, as well as more frequent use of inhaled corticosteroids and long-acting β-agonists, and less frequent use of short-acting β-agonists (one trial, 220 women). The FENO-based algorithm was associated with fewer infants with recurrent episodes of bronchiolitis in their first year of life, and a trend towards fewer episodes of croup for infants. Pharmacist-led management improved asthma control scores at six months (one trial, 60 women); PMR improved lung function and quality of life measures (one trial, 64 women). No other differences between comparisons were observed.