OBJECTIVE: To estimate the frequency of severe asthma exacerbations in pregnant women and to estimate whether there is an association with adverse perinatal outcomes. METHODS: Asthma exacerbations were evaluated in 146 women who were enrolled in a prospective cohort study of asthma and pregnancy. A severe exacerbation was defined as a hospital admission, emergency department presentation, or unscheduled doctor visit for asthma or a course of oral corticosteroids. Women were classified as having mild (n = 63), moderate (n = 34), or severe (n = 49) asthma. RESULTS: Severe exacerbations occurred in 8% (95% confidence interval [CI] 1.3–14.6%) of women with mild asthma, 47% (95% CI 30.3–63.8%) of women with moderate asthma, and 65% (95% CI 52–78.6%) of women with severe asthma at a mean gestational age of 25.1 ± 0.9 (range 9–39) weeks of gestation. Among women who had severe exacerbations, there were 2 male stillbirths (P = .102) and a significantly increased rate of male low birth weight (P = .03). Maternal age, lung function, body mass index, gravidity, and parity were not different between women who did or those who did not have a severe exacerbation. Maternal pregnancy weight gain was significantly lower in women who had a severe exacerbation (P = .039). Forty-three percent of severe exacerbations occurred in winter, 34% were associated with self-reported viral infection, and 29% with nonadherence to inhaled corticosteroid medication. CONCLUSION: The exacerbation rate among pregnant women with asthma is high and associated with poor outcomes for the male fetus. Improvements in asthma management to prevent severe exacerbations may lead to a better outcome for both mother and baby. LEVEL OF EVIDENCE: II-2

Asthma is a common comorbidity during pregnancy and its prevalence is increasing in the community. Exacerbations are a major clinical problem during pregnancy with up to 45% of women needing to seek medical help, resulting in poor outcomes for mothers and their babies, including low birth weight and preterm delivery. The goals of effective asthma management in pregnancy are to maintain the best possible asthma control and prevent exacerbations. This is achieved by aiming to prevent day- and night-time symptoms, and maintain lung function and normal activity. In addition, maintaining fetal oxygenation is an important consideration in pregnancy. Guidelines recommend providing asthma advice and review prior to conception, and managing asthma actively during pregnancy, with regular 4-weekly review, provision of a written action plan, use of preventer medications as indicated for other adults with asthma, and management of comorbid conditions such as rhinitis.Improvements have been made in recent years in emergency department management of asthma in pregnancy, and multidisciplinary approaches are being proposed to optimise both asthma outcomes and perinatal outcomes. One strategy that has demonstrated success in reducing exacerbations in pregnancy is treatment adjustment using a marker of eosinophilic lung inflammation, the exhaled nitric oxide fraction (F_eNO). The use of an algorithm that adjusted inhaled corticosteroids (ICS) according toF_eNOand added long-acting β-agonists when symptoms remained uncontrolled resulted in fewer exacerbations, more women on ICS but at lower mean doses, and improved infant respiratory health at 12 months of age. Further evidence is needed to determine whether this strategy can also improve perinatal outcomes and be successfully translated into clinical practice.Key points: Asthma is the most common chronic disease to affect pregnant women. Exacerbations occur in up to 45% of pregnant women with asthma. Asthma should be managed during pregnancy as for other adults. Treatment adjustment using a marker of airway inflammation reduces the exacerbation rate in pregnancy. Educational aims: To identify the goals of and steps associated with effective asthma management in pregnancy. To understand the maternal and perinatal risks associated with asthma during pregnancy. To describe a management strategy that has been shown to reduce exacerbations in pregnant women with asthma.

Background.Pregnant women are considered to have a high risk for influenza virus infection, although little is known about the biological reasons for this risk. Antiviral immunity is critical during influenza virus infection, and understanding the changes that occur during pregnancy and the effect of vaccination is essential for improving health outcomes for mother and baby. Methods.Peripheral blood mononuclear cells (PBMCs) were isolated from 26 healthy, nonpregnant women and 28 healthy pregnant women and cultured with 2009 pandemic influenza A virus subtype H1N1 (H1N1/09). Protein concentrations of interferon α (IFN-α), IFN-λ, and IFN-γ were measured from culture supernatant. Messenger RNA expression of protein kinase R (PKR) and Toll-like receptors 3, 7, and 9 was also measured from cell lysates. Results.PBMCs from pregnant women produced significantly less IFN-α (median level, 114.06 pg/mL [range, 51.48–394.9]) and IFN-λ (median level, 30.65 pg/mL [range, 0–260]), compared with PBMCs from nonpregnant women (median level, 800.38 pg/mL [range, 259–1458] and 479.87 pg/mL [257.1–1113], respectively; P < .01). PKR expression was also significantly reduced in PBMCs from pregnant women (P < .05). Vaccination significantly improved innate and adaptive immunity in pregnancy (P < .01). Conclusion.PBMCs from nonvaccinated pregnant women have attenuated antiviral immunity following H1N1/09 stimulation, but vaccination improves this response. These novel findings help improve understanding of the increased susceptibility and disease severity to influenza virus infection during pregnancy and the importance of influenza vaccination.

Asthma exacerbations are common during pregnancy and associated with an increased risk of adverse perinatal outcomes. Adjusting asthma treatment based on airway inflammation rather than symptoms reduces the exacerbation rate by 50 %. The Breathing for Life Trial (BLT) will test whether this approach also improves perinatal outcomes. BLT is a multicentre, parallel group, randomised controlled trial of asthma management guided by fractional exhaled nitric oxide (FENO, a marker of eosinophilic airway inflammation) compared to usual care, with prospective infant follow-up. Women with physician-diagnosed asthma, asthma symptoms and/or medication use in the previous 12 months, who are 12–22 weeks gestation, will be eligible for inclusion. Women randomised to the control group will have one clinical assessment of their asthma, including self-management education. Any treatment changes will be made by their general practitioner. Women randomised to the intervention group will have clinical assessments every 3–6 weeks during pregnancy, and asthma treatments will be adjusted every second visit based on an algorithm which uses FENO to adjust inhaled corticosteroid (ICS) dose (increase in dose when FENO >29 parts per billion (ppb), decrease in dose when FENO <19 ppb, and no change when FENO is between 19 and 29 ppb). A long acting beta agonist (LABA) will be added when symptoms remain uncontrolled. Both the control and intervention groups will report on exacerbations at a postpartum phone interview. The primary outcome is adverse perinatal outcome (a composite measure including preterm birth, intrauterine growth restriction, neonatal hospitalisation at birth or perinatal mortality), assessed from hospital records. Secondary outcomes will be each component of the primary outcome, maternal exacerbations requiring medical intervention during pregnancy (both smokers and non-smokers), and hospitalisation and emergency department presentation for wheeze, bronchiolitis or croup in the first 12 months of infancy. Outcome assessment and statistical analysis of the primary outcome will be blinded. To detect a reduction in adverse perinatal outcomes from 35 % to 26 %, 600 pregnant women with asthma per group are required. This trial will provide evidence for the effectiveness of a FENO-based management strategy in improving perinatal outcomes in pregnant women with asthma. If successful, this would improve the management of pregnant women with asthma worldwide. Australian New Zealand Clinical Trials Registry ACTRN12613000202763 .