Vanessa E. Murphy

Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes

Exacerbations of asthma during pregnancy represent a significant clinical problem and may be related to poor pregnancy outcomes. A systematic review of the literature was conducted for publications related to exacerbations during pregnancy. Four studies with a control group (no asthma) and two groups of women with asthma (exacerbation, no exacerbation) were included in meta-analyses using fixed effects models. During pregnancy, exacerbations of asthma which require medical intervention occur in about 20% of women, with approximately 6% of women being admitted to hospital. Exacerbations during pregnancy occur primarily in the late second trimester; the major triggers are viral infection and non-adherence to inhaled corticosteroid medication. Women who have a severe exacerbation during pregnancy are at a significantly increased risk of having a low birth weight baby compared with women without asthma. No significant associations between exacerbations during pregnancy and preterm delivery or pre-eclampsia were identified. Inhaled corticosteroid use may reduce the risk of exacerbations during pregnancy. Pregnant women may be less likely to receive oral steroids for the emergency management of asthma. The effective management and prevention of asthma exacerbations during pregnancy is important for the health of both the mother and fetus.

Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites

Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinctive gut microbiota, which increases the levels of the short-chain fatty acid, acetate. High-fibre or acetate-feeding led to marked suppression of allergic airways disease (AAD, a model for human asthma), by enhancing T-regulatory cell numbers and function. Acetate increases acetylation at the Foxp3 promoter, likely through HDAC9 inhibition. Epigenetic effects of fibre/acetate in adult mice led us to examine the influence of maternal intake of fibre/acetate. High-fibre/acetate feeding of pregnant mice imparts on their adult offspring an inability to develop robust AAD. High fibre/acetate suppresses expression of certain genes in the mouse fetal lung linked to both human asthma and mouse AAD. Thus, diet acting on the gut microbiota profoundly influences airway responses, and may represent an approach to prevent asthma, including during pregnancy.

A meta-analysis of adverse perinatal outcomes in women with asthma

Please cite this paper as: Murphy V, Namazy J, Powell H, Schatz M, Chambers C, Attia J, Gibson P. A meta‐analysis of adverse perinatal outcomes in women with asthma. BJOG 2011;118:1314–1323.

Severe asthma exacerbations during pregnancy

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 during pregnancy: mechanisms and treatment implications

Asthma is becoming increasingly prevalent worldwide. Numerous historical and prospective cohort studies have investigated the effects of maternal asthma on pregnancy outcome; however, the data has been conflicting and many studies have not used standard classifications for asthma severity. Overall, the literature suggests that asthmatic females are more at risk of low birth weight neonates, pre-term delivery and complications such as pre-eclampsia, especially in the absence of actively managed asthma treated with inhaled corticosteroids. Pregnancy with a female foetus may particularly increase the risk of these outcomes. In addition, pregnancy has an effect on the course of asthma. The risk of an exacerbation requiring medical intervention may be as high as 50% in females with severe asthma and this may further increase the risk of poor outcomes, particularly low birth weight and pre-term delivery. The mechanisms responsible for changes in asthma with pregnancy, or alterations in pregnancy outcomes due to asthma have not been thoroughly explored. Maternal inflammatory pathways may contribute to reduced foetal growth through alterations in placental function. Asthma treatment, by reducing maternal inflammation and preventing exacerbations, is safe for use in pregnant females and contributes to improved outcomes for both mother and foetus.

Alterations in Human Placental 11β-hydroxysteroid Dehydrogenase Type 1 and 2 with Gestational Age and Labour

11beta-hydroxysteroid dehydrogenase type 1 and type 2 may be important in the process of human parturition and the regulation of fetal growth, by the modulation of cortisol concentrations in the fetal compartment. Changes in the expression and activity of these enzymes in late gestation have not been well described. This study has examined the gene expression of placental 11beta-HSD1 and 2, activity of 11beta-HSD2 and fetal cortisol concentrations during the final few weeks of human pregnancy and with the onset of labour. Placental 11beta-HSD2 activity decreased significantly between 38 and 40 weeks. There were no significant changes in mRNA abundance or protein expression with gestational age or labour. Placental 11beta-HSD1 mRNA abundance significantly increased with spontaneous labour. Fetal cortisol concentrations increased significantly with spontaneous labour. This study is the first to describe a decrease in 11beta-HSD2 activity in the last few weeks of human gestation. This decrease in type 2 activity, along with an increase in 11beta-HSD1 gene expression may be a mechanism by which cortisol concentrations rise at term to regulate fetal maturation and activate pathways associated with labour.

Asthma self-management skills and the use of asthma education during pregnancy

During pregnancy, patients with asthma are at risk of poor outcomes, particularly when asthma is poorly controlled. The aim of this study was to determine the level of asthma self-management skills and knowledge among pregnant subjects and describe the implementation of an asthma education programme delivered in an antenatal clinic setting. Pregnant subjects with asthma were assessed by an asthma educator at 20 (n = 211) and 33 weeks gestation (n = 149). Lung function, symptoms, medication use, adherence, knowledge and inhaler technique were assessed. They were asked whether they had a written asthma action plan, or performed peak flow monitoring. Asthma was classified as mild, moderate or severe. At the first visit with the asthma educator, 40% of females reported nonadherence to inhaled corticosteroids, inhaler technique was assessed as inadequate in 16% and 42% had inadequate medication knowledge. Peak flow monitoring was performed by 3% and 15% had a written action plan. There were significant improvements in all aspects of asthma self-management following education. In females with severe asthma, night symptoms and reliever medication use significantly decreased after education. In conclusion, during pregnancy, patients with asthma have poor asthma knowledge and skills, and may benefit from self-management education as part of their obstetric care.

Placental Cytokine Expression Covaries with Maternal Asthma Severity and Fetal Sex

In the presence of maternal asthma, we have previously reported reduced placental blood flow, decreased cortisol metabolism, and reductions in fetal growth in response to maternal asthma and asthma exacerbations. We have proposed that these changes in placental function and fetal development may be related to activation of proinflammatory pathways in the placenta in response to maternal asthma. In the present study, we examined the influence of maternal asthma severity, inhaled glucocorticoid treatment, maternal cigarette use, placental macrophage numbers, and fetal sex on placental cytokine mRNA expression from a prospective cohort study of pregnant women with and without asthma. Placental expression of TNF-α, IL-1β, IL-6, IL-8, and IL-5 mRNA were all increased significantly in placentae of female fetuses whose mothers had mild asthma, but no changes were observed in placentae of male fetuses. The proinflammatory cytokines TNF-α, IL-1β, and IL-6 were negatively correlated with female cord blood cortisol, but there were no such correlations in placentae from males. Multivariate analysis indicated the strongest predictor of both cytokine mRNA expression in the placenta and birth weight was fetal cortisol but only in females. Placental cytokine mRNA levels were not significantly altered by inhaled glucocorticoid use, placental macrophage numbers, cigarette use, moderate-severe asthma, or male sex. These data suggest that placental basal cytokine mRNA expression is sex specifically regulated in pregnancies complicated by asthma, and interestingly these changes are more prevalent in mild rather than severe asthma.

Effects of asthma severity, exacerbations and oral corticosteroids on perinatal outcomes

This systematic review and meta-analysis sought to investigate whether asthma exacerbations, oral corticosteroid use or asthma severity are associated with prematurity and intrauterine growth restriction. Cohort studies published between 1975 and March 11, 2012 were considered for inclusion. 138 publications were identified for possible inclusion, and nine papers met the inclusion criteria, by reporting perinatal outcomes of interest (low birth weight, <2500 g), pre-term birth (<37 weeks gestation unless otherwise stated) and small for gestational age (<10th percentile for gestational age and sex) in groups of asthmatic patients stratified by history of exacerbations, oral corticosteroid use or asthma severity. Maternal asthma exacerbations and oral corticosteroid use had a significant effect on outcomes, including low birth weight (RR 3.02, 95% CI 1.87–4.89 and RR 1.41, 95% CI 1.04–1.93, respectively) and pre-term delivery (RR 1.54, 95% CI 0.89–2.69 and RR 1.51, 95% CI 1.15–1.98, respectively). Moderate-to-severe asthma during pregnancy was associated with an increased risk of small for gestational age (RR 1.24, 95% CI 1.15–1.35) and low birth weight (RR 1.15, 95% CI 1.05–1.26) infants. These data suggest that asthma exacerbations, oral corticosteroid use or asthma severity defined as moderate-to-severe may be associated with pre-term delivery, low birth weight, and small for gestational age infants. Further studies on the effect of maternal asthma control on perinatal outcomes are warranted.

The risk of congenital malformations, perinatal mortality and neonatal hospitalisation among pregnant women with asthma: a systematic review and meta-analysis.

There is conflicting literature on the effect of maternal asthma on congenital malformations and neonatal outcomes.