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Asthma during pregnancy is associated with a range of adverse perinatal outcomes. It is also linked to increased rates of neurodevelopmental conditions in the offspring. We aimed to assess whether fractional exhaled nitric oxide (F ENO )-based asthma management during pregnancy improves child developmental and behavioural outcomes compared to usual care. The Breathing for Life Trial was a randomised controlled trial that compared F ENO -based asthma management during pregnancy to usual care. Participants were invited to the developmental follow-up, the Breathing for Life Trial - Infant Development study, which followed up infants at 6 weeks, 6 months and 12 months. The primary outcomes were measured in infants at 12 months using the Bayley-III: Cognitive, Language and Motor composite scores. Secondary outcomes included Bayley-III social-emotional and adaptive behaviour scores, autism likelihood and sensory and temperament outcomes. The exposure of interest was the randomised intervention group. Two hundred and twenty-two infants and their 217 participating mothers were recruited to the follow-up; 107 mothers were in the intervention group and 113 were in the control group. There was no evidence of an intervention effect for the primary outcomes: Bayley-III cognitive (mean = 108.9 control, 108.5 intervention, p = 0.93), language (mean = 95.9 control, 95.6 intervention, p = 0.87) and motor composite scores (mean = 97.2 control, 97.9 intervention, p = 0.25). Mean scores for secondary outcomes were also similar among infants born to control and F ENO group mothers, with few results reaching p < 0.05., Conclusion:  In this sample, F ENO -guided asthma treatment during pregnancy did not improve infant developmental outcomes in the first year of life., Trial Registration: ClinicalTrials.gov Identifier: ACTRN12613000202763., What Is Known: • Maternal asthma during pregnancy has been associated with increased rates of neurodevelopmental conditions in offspring, including intellectual disability and autism., What Is New: • This is the first study to examine how managing asthma during pregnancy via a F ENO -guided algorithm or usual care affects infant developmental and behavioural outcomes. While the results of the study showed no impact of the intervention, and therefore do not support the integration of F ENO -based management of asthma in antenatal settings for optimal infant development, they do send a positive message about the implications of active asthma management during pregnancy on infant developmental outcomes., (© 2024. The Author(s).)

Background: A systematic review and meta-analysis from 2013 reported increased risks of congenital malformations, neonatal death and neonatal hospitalization amongst infants born to women with asthma compared to infants born to mothers without asthma., Objective: Our objective was to update the evidence on the associations between maternal asthma and adverse neonatal outcomes., Search Strategy: We performed an English-language MEDLINE, Embase, CINAHL, and COCHRANE search with the terms (asthma or wheeze) and (pregnan* or perinat* or obstet*)., Selection Criteria: Studies published from March 2012 until September 2023 reporting at least one outcome of interest (congenital malformations, stillbirth, neonatal death, perinatal mortality, neonatal hospitalization, transient tachypnea of the newborn, respiratory distress syndrome and neonatal sepsis) in a population of women with and without asthma., Data Collection and Analysis: The study was reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Quality of individual studies was assessed by two reviewers independently using the Newcastle-Ottawa Scale. Random effects models (≥3 studies) or fixed effect models (≤2 studies) were used with restricted maximum likelihood to calculate relative risk (RR) from prevalence data and the inverse generic variance method where adjusted odds ratios (aORs) from individual studies were combined., Main Results: A total of 18 new studies were included, along with the 22 studies from the 2013 review. Previously observed increased risks remained for perinatal mortality (relative risk [RR] 1.14, 95% confidence interval [CI]: 1.05, 1.23 n = 16 studies; aOR 1.07, 95% CI: 0.98-1.17 n = 6), congenital malformations (RR 1.36, 95% CI: 1.32-1.40 n = 17; aOR 1.42, 95% CI: 1.38-1.47 n = 6), and neonatal hospitalization (RR 1.27, 95% CI: 1.25-1.30 n = 12; aOR 1.1, 95% CI: 1.07-1.16 n = 3) amongst infants born to mothers with asthma, while the risk for neonatal death was no longer significant (RR 1.33, 95% CI: 0.95-1.84 n = 8). Previously reported non-significant risks for major congenital malformations (RR1.18, 95% CI: 1.15-1.21; aOR 1.20, 95% CI: 1.15-1.26 n = 3) and respiratory distress syndrome (RR 1.25, 95% CI: 1.17-1.34 n = 4; aOR 1.09, 95% CI: 1.01-1.18 n = 2) reached statistical significance., Conclusions: Healthcare professionals should remain aware of the increased risks to neonates being born to mothers with asthma., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Asthma is the most common chronic medical condition in pregnancy. Asthma exacerbations in pregnancy are unpredictable, and are associated with adverse maternal and fetal perinatal outcomes such as preterm birth and low birthweight. Goals of asthma management in pregnancy are to establish effective asthma control and prevent exacerbations. Optimising the management of asthma in pregnancy is an important goal of practice and future research.Treatable traits is a precision medicine paradigm proposed for the management of airways diseases, which holistically addresses the complexity and heterogeneity of airways disease. It is an individualised treatment approach that aims to improve outcomes. This makes treatable traits well suited for pregnant women with asthma, who have a high prevalence of obesity, mental health conditions, poor symptom perception and suboptimal asthma management skills including low treatment adherence. These traits are measurable and treatable. In this review, we explore current knowledge on the burden of asthma, maternal and perinatal consequences of asthma during pregnancy, the treatable traits paradigm, the prevalence of treatable traits in pregnant women with asthma, and consider how the treatable traits paradigm can be integrated into the management of asthma in pregnancy., Competing Interests: Conflicts of interests: E. Joshi's Doctor of Philosophy is supported by a scholarship from the University of Newcastle. P.G. Gibson has received fees from AstraZeneca, GlaxoSmithKline, Novartis and Sanofi. P.G. Gibson's institution has received grants from GlaxoSmithKline. V.M. McDonald has received fees from AstraZeneca, GlaxoSmithKline, Novartis and Boehringer Ingleheim. V.M. McDonald's institution has received fees from GlaxoSmithKline, AstraZeneca and Cyclopharm. V.E. Murphy would like to acknowledge her fellowship. V.E. Murphy is supported by an Investigator Grant funded by the Medical Research Future Fund (application ID 1196252)., (Copyright ©The authors 2023.)

Background: Asthma affects 12.7% of pregnant women in Australia. Key recommendations for asthma management during pregnancy include: 4-6 weekly review of lung function, medications, written asthma action plan, inhaler device technique, current asthma control and triggers; smoking cessation and vaccination advice. It is unknown if these key recommendations are provided to pregnant women with asthma in Australia., Aim: To explore usual antenatal asthma management (usual care) in Australia and the inclusion of key recommendations., Method: Pregnant women with asthma were invited to complete an online survey distributed in 2 antenatal clinics and via social media platforms from July 2017-Jan 2019., Results: The survey was completed by 142 pregnant women with asthma. 87(61%) were enrolled in an asthma management clinical trial and were therefore not receiving 'usual' care. Data presented is from 55(39%) women receiving usual care at survey completion. Of these women, 36% did not have their asthma reviewed during their pregnancy, 31% had a written asthma action plan, 11% had lung function assessed, 38% had an asthma medication review and 35% had their inhaler technique reviewed. 65% were not questioned about their asthma symptoms, 85% were not asked about asthma triggers, 96% were not given information about vaccinations and 95% did not receive smoking cessation information., Conclusions: Overall, the key recommendations for antenatal asthma management were not always provided for this sample of pregnant women receiving usual care. Improved knowledge and implementation of these key recommendations by health professionals may alter this situation and improve maternal and infant outcomes., (Copyright © 2023 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Asthma is the most prevalent chronic disease in pregnancy, and as symptoms can change with pregnancy, and exacerbations of asthma are common, regular review of asthma symptoms, the provision of self-management education, and appropriate medication use are the hallmarks of management. Co-morbidities are also prevalent among pregnant women with asthma, with obesity, gestational diabetes, hypertension, rhinitis, depression, and anxiety, more common among women with asthma than women without asthma. Less is known about reflux, obstructive sleep apnoea and vocal cord dysfunction, along with nutritional deficiencies to iron and vitamin D. Maternal asthma impacts the offspring's long-term health, particularly in increasing the risk of early life wheeze and asthma in childhood. While breastfeeding may modify the risk of infant wheeze, less is known about the mechanisms involved. More research is needed to further understand the relationship between asthma in pregnancy and the risk of poor neurodevelopmental outcomes, such as autism., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022. Published by Elsevier Ltd.)

Low 25-hydroxyvitamin D (25(OH)D) levels are common in pregnancy and associated with adverse maternal/neonatal outcomes. In pregnant women with asthma, this study examined the association of lifestyle- and asthma-related factors on 25(OH)D levels and maternal/neonatal outcomes by vitamin D status. Serum 25(OH)D was measured at 16 and 35 weeks gestation in women with asthma ( n = 103). Body mass index (BMI), gestational weight gain (GWG), smoking status, inhaled corticosteroid (ICS) use, asthma control, airway inflammation, and exacerbations, and maternal/neonatal outcomes were collected. Baseline and change (Δ) in 25(OH)D were modelled separately using backward stepwise regression, adjusted for season and ethnicity. Maternal/neonatal outcomes were compared between low (25(OH)D < 75 nmol/L at both time points) and high (≥75 nmol/L at one or both time points) vitamin D status. Fifty-six percent of women had low vitamin D status. Obesity was significantly associated with lower baseline 25(OH)D (Adj-R 2 = 0.126, p = 0.008); ICS and airway inflammation were not. Excess GWG and season of baseline sample collection were significantly associated with Δ25(OH)D (Adj-R 2 = 0.405, p < 0.0001); asthma-related variables were excluded ( p > 0.2). Preeclampsia was more common in the low (8.6%) vs. high (0%) vitamin D group ( p < 0.05). Obesity and excess GWG may be associated with gestational 25(OH)D levels, highlighting the importance of antenatal weight management.

Objective: We aimed to examine the prevalence and severity of psychological distress of women with asthma in both the prenatal and postnatal periods, and to determine whether asthmatic women with and without mental health problems differ in self-management, medications knowledge, and asthma symptoms. Methods : We assessed spirometry performance and asthma symptoms in 120 women (mean age 29.8 years) before 23 weeks gestation, as part of the Breathing for Life Trial (Trial ID: ACTRN12613000202763). Prenatal depression data was obtained from medical records. At 6 weeks postpartum, we assessed general health, self-reported asthma control, depression symptoms (with the Edinburgh Postnatal Depression Scale) and adaptive functioning (with the Achenbach System of Empirically Based Assessment scales). Results : Twenty percent of our sample reported having a current mental health diagnosis, 14% reported currently receiving mental health care, while 47% reported having received mental health care in the past (and may/may not have received a diagnosis). The sample scored high on the Aggressive Behavior, Avoidant Personality, and Attention Deficit/Hyperactivity scales. Poorer self-reported postnatal asthma control was strongly correlated with elevated somatic complaints, externalizing problems, antisocial personality problems, and greater withdrawal. Prenatal spirometry or asthma severity and control were largely not associated with measures of psychopathology. Conclusions : These findings indicate that pregnant women with asthma frequently report issues with psychopathology during the prenatal and postnatal periods, and that the subjective perception of asthma control may be more related to psychopathology than objective asthma measures. However, due to sample bias, these findings are likely to be understated.

Background and Objective: The aim of this secondary analysis of a randomized controlled trial (RCT) of asthma management in pregnancy was to determine the treatment decision differences between a symptom control algorithm and a fractional exhaled nitric oxide (FENO)-guided algorithm, and whether the approach was effective in non-eosinophilic asthma (NEA)., Methods: In this double-blind parallel group RCT, women with asthma were randomized prior to 22 weeks gestation to treatment adjustment according to a symptom control algorithm (control group), or a FENO-guided algorithm (inhaled corticosteroid (ICS) dose adjusted according to FENO with long-acting beta-agonist (LABA) added for uncontrolled symptoms). NEA was classified as baseline blood eosinophils <0.26 × 10 9 /L and FENO ≤29 ppb. Exacerbations requiring medical intervention were recorded., Results: Among 220 non-smokers (n = 109 control, n = 111 FENO), 1006 treatment decisions were made, with significant group differences after the first and second algorithm applications. 53% of women had NEA. Treatment was better targeted to phenotype in the FENO group: ICS use increased in eosinophilic asthma (EA, 48-86%), while ICS/LABA increased in NEA (11-30%). Fewer women in the FENO group had exacerbations during pregnancy in NEA only (18.9% FENO vs 44% control, P = 0.006)., Conclusion: The FENO algorithm was more effective in treating NEA, resulting in reduced exacerbations, compared to a symptom control algorithm. This was not the result of ICS overtreatment, since the benefits occurred at a lower median daily ICS dose. Two applications of the FENO-guided algorithm, one month apart, were sufficient to achieve beneficial effects in terms of asthma exacerbations, among pregnant women with asthma., (© 2019 Asian Pacific Society of Respirology.)

Background: Asthma affects approximately 12.7% of pregnant women in Australia. Increased maternal and infant morbidity is closely associated with poorly controlled asthma during pregnancy. Midwives are well placed to provide antenatal asthma management but data on current asthma management during pregnancy is not available, nor is the use of guidelines for clinical practice by this health professional group., Aim: To explore self-reported antenatal asthma management provided by midwives across Australia and how this reflects guideline recommendations., Method: An online survey was developed and distributed throughout Australia via the Australian College of Midwives, social media and healthcare facilities., Results: Responses from 371 midwives were obtained. Ten percent of midwives rated their knowledge as 'good' and 1% as 'very good', with 39% 'poor' or 'very poor'. Being 'somewhat' or 'not at all' confident to provide antenatal asthma management was noted by 87% of midwives. Clinical guidelines were referred to by 50% of midwives and 40% stated that their main role was to refer women to other healthcare professionals. Only 54% reported that a clear referral pathway existed. Most respondents (>90%) recognised key recommendations for asthma management such as smoking cessation, appropriate vaccinations, and the continuation of prescribed asthma medications., Conclusion: Although midwives appear aware of key clinical recommendations for optimal antenatal asthma management, low referral to clinical practice guidelines and lack of knowledge and confidence was evident. Further research is required to determine what care pregnant women with asthma are actually receiving and identify strategies to improve antenatal asthma management by midwives., (Copyright © 2019 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: Maternal asthma is associated with perinatal complications and respiratory illness in offspring. Obesity increases asthma exacerbation risk in pregnancy and risk of wheeze in offspring., Objectives: In this secondary analysis of a randomized controlled trial, we investigated the influence of maternal body mass index, gestational weight gain (GWG), and fractional exhaled nitric oxide (F E NO)-based management on asthma exacerbations in pregnancy and offspring wheeze., Methods: A total of 220 women were randomized to asthma treatment adjustment according to symptoms (control group), or F E NO and symptoms (F E NO group). Exacerbations were recorded prospectively. Height and weight were measured at baseline, and in late pregnancy. GWG was categorized according to Institute of Medicine guidelines. A validated parent-completed questionnaire assessed infant wheeze-related outcomes., Results: F E NO-based management was associated with a significantly lower incidence rate ratio for maternal exacerbations in nonobese mothers (0.52, 95% confidence interval [CI], 0.31-0.88, P = .015, n = 129), and women with GWG within recommendations (0.35, 95% CI, 0.12-0.96, P = .042, n = 43), but not for obese mothers (0.59, 95% CI, 0.32-1.08, P = .089, n = 88), or women with excess GWG (0.58, 95% CI, 0.32-1.04, P = .07, n = 104). Recurrent bronchiolitis occurred in 5.3% (n = 1) of infants born to non-overweight mothers, 16.7% (n = 3) of infants of overweight mothers, and 21.7% (n = 5) of infants of obese mothers in the control group. In the F E NO group, 2 infants of obese mothers had recurrent bronchiolitis (7.1%, P = .031)., Conclusions: The benefits of F E NO-based management are attenuated among obese mothers and those with excess GWG, indicating the importance of weight management in contributing to improved asthma management in pregnancy., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Studies demonstrate the prescription rate for inhaled corticosteroids (ICS) decreases in early pregnancy, possibly increasing exacerbation risk. This could be related to non-adherence to prescribed asthma medication or medication cessation by the patient or doctor. ICS use during pregnancy has not previously been summarized in a systematic review., Objective: The aim of this systematic review and meta-analysis was to evaluate the use of ICS during pregnancy among asthmatic women, specifically: (1) the prevalence of use, (2) changes of use during pregnancy compared with pre-pregnancy and (3) medication adherence among ICS users., Methods: We systematically searched literature in Embase, MEDLINE, CINAL and Cochrane, using terms related to asthma, pregnancy and medication use. All English articles reporting ICS among pregnant women with asthma were included. Prevalence, changes in ICS use during pregnancy and ICS adherence were pooled using STATA (version 15.0, StataCorp USA)., Results: A total of 4237 references were retrieved in the initial search. Screening and review led to the inclusion of 52 articles for one or more aims (Aim 1: N = 45; Aim 2, N = 13; and Aim 3, N = 5). The pooled prevalence of ICS use during pregnancy was 41% (95%CI 36%-45%); 49% (95%CI 44%-55%) in Europe, 39% (95%CI 32%-47%) in Australia and 34% (95%CI 27%-41%) in North America. In eight prescription databases, ICS prescription rates lowered in the first trimester of pregnancy, compared with pre-pregnancy, increased in the second trimester and decreased in the third trimester. Five studies reported ICS adherence among pregnant women, using four measures of self-reported non-adherence. In two comparable studies, pooled ICS non-adherence was 40% (95%CI 36%-44%)., Conclusions: The prevalence of ICS use among pregnant women with asthma is 41% and varies widely between countries and continents, and prescription rates for ICS change throughout pregnancy. More studies are needed to investigate ICS adherence during pregnancy in women with asthma., (© 2019 John Wiley & Sons Ltd.)

Objective: Asthma exacerbations and medication non-adherence are significant clinical problems during pregnancy. While asthma self-management education is effective, the number of education sessions required to maximise asthma management knowledge and inhaler technique and whether improvements persist postpartum, are unknown. This paper describes how asthma knowledge, skills, and inhaled corticosteroid (ICS) use have changed over time., Methods: Data were obtained from 3 cohorts of pregnant women with asthma recruited in Newcastle, Australia between 2004 and 2017 (N = 895). Medication use, adherence, knowledge, and inhaler technique were compared between cohorts. Changes in self-management knowledge/skills and women's perception of medication risk to the fetus were assessed in 685 women with 5 assessments during pregnancy, and 95 women who had a postpartum assessment., Results: At study entry, 41%, 29%, and 38% of participants used ICS in the 2004, 2007, and 2013 cohorts, respectively (p = 0.017), with 40% non-adherence in each cohort. Self-management skills of pregnant women with asthma did not improve between 2004 and 2017 and possession of a written action plan remained low. Maximum improvements were reached by 3 sessions for medications knowledge and one session for inhaler technique, and were maintained postpartum. ICS adherence was maximally improved after one session, but not maintained postpartum. Perceived risk of asthma medications on the fetus was highest for corticosteroid-containing medication; and was significantly reduced following education., Conclusions: There was a high prevalence of non-adherence and poor self-management skills in all cohorts. More awareness of the importance of optimal asthma management during pregnancy is warranted, since no improvements were observed over the past decade.

Objective: Maternal asthma during pregnancy is associated with a higher risk of negative perinatal outcomes. However, little is known about the direct effects of maternal asthma on infant cognitive development. We examined the evidence for an impact of maternal asthma during pregnancy on cognitive and behavioral development of the child., Data Sources: We conducted a MEDLINE, PsychINFO, and manual search of the databases for all available studies until January 9th, 2018., Study Selections: Studies were deemed relevant if they included child cognitive and behavioral development as the outcome, with maternal asthma as the determinant of interest., Results: Ten articles matched selection criteria. Some studies report that maternal asthma is associated with increased risk for autism and intellectual disability in children. However, these effects are small and are often eliminated when controlling for confounding variables. Other studies have found no association. The only prospective study found that well-managed asthma during pregnancy was not associated with negative developmental outcomes in children., Conclusions: The evidence suggests that the relationship between maternal asthma during pregnancy and poor developmental and behavioral outcomes of children is weak. Children of mothers with well-managed asthma during pregnancy have similar developmental trajectories to those born to healthy mothers. Prospective, longitudinal studies are needed to confirm these conclusions. Optimal asthma management is important in pregnancy as it may have longer term benefits for the health of the offspring. As the rate of asthma increases in the population, the implications of maternal asthma on child development will be of greater importance.

Purpose of Review: Asthma affects up to 13% of pregnancies worldwide and has a varying and unpredictable clinical course during pregnancy. Pharmacological asthma treatment is recommended; however, studies show that some pregnant women with asthma cease their medication in early pregnancy. There is likely a large unmet disease burden arising from asthma in pregnancy., Recent Findings: Antenatal and asthma guidelines lack sufficient information on asthma management in pregnant women, and implementation of the current guidelines seems inadequate. Prescription databases provide evidence of cessation of asthma medication during pregnancy on a population level. Population-based databases also provide evidence of rare adverse perinatal outcomes. The risk of childhood asthma in the offspring of women with asthma is reduced by adequate control of maternal asthma during pregnancy. Vitamin D sufficiency during pregnancy could also reduce the risk of childhood asthma., Summary: The findings of this review demonstrate the need for improved asthma and antenatal guidelines regarding asthma management during pregnancy, and the need of adequate implementation of these guidelines. Furthermore, adequate asthma control during pregnancy is needed to reduce the risk of childhood asthma. To maintain asthma control, prepregnancy medication should be continued throughout pregnancy and adjusted according to the current treatment steps if required.

Background: Asthma affects 12.7% of pregnancies in Australia. Poorly controlled asthma is associated with increased maternal and infant morbidity and mortality. Optimal antenatal management of asthma during pregnancy has the potential to reduce complications relating to asthma. Evidence-based clinical practice guidelines help to translate health research findings into practice and when implemented can improve health outcomes. National and International guidelines currently provide recommendations for optimal asthma care in pregnancy., Aim: To appraise the existing asthma in pregnancy guidelines with respect to their evidence for recommendations, consistency of recommendations and appropriateness for clinical practice., Method: The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to appraise four English language asthma in pregnancy guidelines, published or updated between 2007 and 2016. The recommendations, range and level of evidence was analysed., Results: Two of the four guidelines scored highly in most domains of the appraisal. Many of the recommendations made in the appraised guidelines were consistent. Due to the lack of randomised controlled trials involving pregnant women with asthma, most recommendations were evidenced by consensus and expert opinion rather than high quality meta-analysis, systematic reviews of randomised controlled trials., Conclusion: The recommended antenatal asthma management was generally consistent among the guidelines but lacked clarity in some areas which then leave them open to interpretation. More randomised controlled trials involving pregnant women with asthma are required to fortify the recommendations made and asthma management guidelines should be included in Australian Antenatal Care Guidelines as they currently are not., (Copyright © 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

One in 10 pregnant women worldwide has asthma and of these, 10% will have a severe exacerbation requiring oral corticosteroids (OCSs) in pregnancy. This review of recent publications in the field will describe the effects of exacerbation on maternal and neonatal health, the use of asthma medications during pregnancy, and will suggest novel management approaches for asthma in pregnancy. Pregnancy results in unpredictable changes in the disease; therefore, regular monitoring of symptoms is recommended. Uncontrolled asthma is frequently described in cohorts of pregnant women with asthma, and some recent studies show associations with adverse perinatal outcomes, as previously demonstrated with exacerbations. Guidelines for the management of asthma recommend the continued use of inhaled corticosteroids (ICSs) in pregnancy, with budesonide having a particularly good safety profile. Recent data suggest small effects of asthma and/or asthma medication use on congenital malformations; however, there is less data available on the safety of ICS/long-acting β agonist combinations, which are increasingly used for maintenance treatment. Novel management strategies are needed to address the complex needs of pregnant women with asthma. These include medication nonadherence and the presence of numerous comorbidities which can affect asthma, such as rhinitis, cigarette smoking, obesity, and mental health issues. Inflammation-based management has been shown to be effective in reducing exacerbations in pregnancy and may also improve perinatal outcomes. The involvement of a multidisciplinary team and the assessment of comorbidities have potential to improve the health of mothers and their offspring., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: 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., Methods/design: 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., Discussion: 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., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12613000202763 .

Pregnancy is a unique state requiring alterations in maternal physiology to accommodate the growing fetus. Whilst the maternal immune system is normally well adept at performing this task, the presence of immune disorders, such as asthma, often lead to pregnancy-related complications affecting both mother and baby. Australia has a high prevalence of asthma; with approximately 12% of pregnant women reported to have current asthma. Poor control of asthma is of far greater risk than the use of asthma medications. Being able to identify complications associated with asthma during pregnancy is of great importance in providing appropriate asthma management and medical care to these pregnant women, which may have lifelong consequences for their offspring.

Objective: To investigate the relationship between asthma control and psychosocial outcomes in pregnant women with asthma., Methods: Secondary analysis (N = 221) of a randomized controlled trial of treatment adjustments, based on fractional exhaled nitric oxide versus clinical guideline-based algorithms. Psychosocial variables included generic and asthma-specific quality of life (SF12, AQLQ-M), illness perceptions (BIPQ), perceived control (PCAQ), perceived risk of side effects (PRSE) and anxiety (STAI-6). Asthma control was defined as controlled (Asthma Control Questionnaire (ACQ7) ≤1.5 at randomization and end of study), improved (ACQ7 > 1.5 at randomization and ≤1.5 at end of study) and unimproved (ACQ7 >1.5 at end of study). Regression models were fitted for each psychosocial measure at the end of the study, with adjustment for baseline values and smoking status, with predictor variable asthma control., Results: Women with unimproved asthma had poorer physical (SF12, p = 0.012) and asthma-specific quality of life across all domains (AQLQ-M, p ≤ 0.012) compared to women with controlled asthma. They believed that they had less control over their asthma (PCAQ total p = 0.014), had more symptoms and that their illness had a greater effect on their emotions and their lives in general (BIPQ identity, consequences, concern, emotional response p ≤ 0.015). Women with improved asthma control had significantly lower AQLQ-M breathlessness (p = 0.048) and lower total scores (p = 0.04) than women with controlled asthma., Conclusions: Pregnant women who are not able to get control of their asthma symptoms may experience worse quality of life and are likely to have more negative perceptions about their condition.

Background: Asthma is a complex disease that involves both genetic factors and environmental exposures. Aberrant epigenetic modifications, such as DNA methylation, may be important in asthma development. Fetal exposure to maternal asthma during critical periods of in utero development may lead to epigenetic alterations that predispose infants to a greater risk of developing asthma themselves. We investigated alterations in the DNA methylation profile of peripheral blood from infants exposed to maternal asthma during pregnancy., Methods: Peripheral blood was collected from 12-month-old infants born to women with (n = 25) and without (n = 15) doctor diagnosed asthma during pregnancy. Genomic DNA was extracted, bisulfite converted, and hybridized to Infinium Methylation 27 arrays (Illumina), containing over27,000 CpGs from 14,495 genes. CpG loci in only autosomal genes were classified as differentially methylated at the 99% level (P < 0.01, |DiffScore| > 22 and delta beta >0.06)., Results: There were 70 CpG loci, corresponding to 67 genes that were significantly differentially methylated. Twelve CpG loci (11 genes) showed greater than 10% comparative difference in DNA methylation, including hyper-methylated loci of FAM181A, MRI1, PIWIL1, CHFR, DEFA1, MRPL28, AURKA, and hypo-methylated loci of NALP1L5, MAP8KIP3, ACAT2, and PM20D1 in maternal asthma. Methylation of MAPK8IP3 was significantly negatively correlated with maternal blood eosinophils (r = -0.38; P = 0.022), maternal eNO (r = -0.44; P = 0.005), and maternal serum total IgE (r = -0.39, P = 0.015). Methylation of AURKA negatively correlated with maternal hemoglobin (r = -0.43; P = 0.008), infants height (r = -0.51; P < 0.001) and weight (r = -0.36; P = 0.021). Methylation of PM20D1 was lower in infants born to mothers with asthma on inhaled corticosteroid treatment. Methylation of PM20D1 was lower and MRI1 was higher in infants born to atopic mothers without asthma., Conclusions: In an Australian study population, exposure to maternal asthma during pregnancy is associated with differential methylation profiles of infants' peripheral blood DNA, which may act as risk factors for future asthma development., (© 2013 Wiley Periodicals, Inc.)

Objective: To investigate if maternal asthma is associated with an increased risk of maternal and placental complications in pregnancy., Methods: Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). Cohort studies published between January 1975 and March 2012 were considered for inclusion. Forty publications met the inclusion criteria, reporting at least one maternal or placental complication in pregnant women with and without asthma. Relative risk (RR) with 95% confidence intervals (CIs) was calculated., Results: Maternal asthma was associated with a significantly increased risk of cesarean section (RR = 1.31, 95%CI = [1.22-1.39]), gestational diabetes (RR = 1.39, 95%CI = [1.17-1.66]), hemorrhage (antepartum: RR = 1.25, 95%CI = [1.10-1.42]; postpartum: RR = 1.29, 95%CI = [1.18-1.41]), placenta previa (RR = 1.23, 95%CI = [1.07-1.40]), placental abruption (RR = 1.29, 95%CI = [1.14-1.47]) and premature rupture of membranes (RR = 1.21, 95%CI = 1.07-1.37). Moderate to severe asthma significantly increased the risk of cesarean section (RR = 1.19, 95%CI = [1.09-1.31]) and gestational diabetes (RR = 1.19, 95%CI = [1.06-1.33]) compared to mild asthma. Bronchodilator use was associated with a significantly lowered risk of gestational diabetes (RR = 0.64, 95%CI = [0.57-0.72])., Conclusions: Pregnant women with asthma are at increased risk of maternal and placental complications, and women with moderate/severe asthma may be at particular risk. Further studies are required to elucidate whether adequate control of asthma during pregnancy reduces these risks.

Objective: Maternal asthma is the most common chronic disease complicating pregnancy and is a risk factor for bronchiolitis in infancy. Recurrent episodes of bronchiolitis are strongly associated with the development of childhood asthma., Methods: We conducted a follow-up study of infants born to women with asthma who completed a double-blind randomised controlled trial during pregnancy. In this trial, pregnant women with asthma were assigned to treatment adjustment by an algorithm using clinical symptoms (clinical group) or the fraction of exhaled nitric oxide (FeNO group) and we showed that the FeNO group had significantly lower asthma exacerbation rates in pregnancy., Results: 146 infants attended the 12-month follow-up visit. Infants born to mothers from the FeNO group were significantly less likely to have recurrent episodes of bronchiolitis in the first year of life (OR 0.08, 95% CI 0.01 to 0.62; p=0.016) as compared with the clinical group., Conclusions: Optimised management of asthma during pregnancy may reduce recurrent episodes of bronchiolitis in infancy, which could potentially modulate the risk to develop or the severity of emerging childhood asthma.

Asthma commonly occurs in pregnant females, and recent data have outlined the risks of adverse perinatal outcomes among this population. There is an increased risk of low birth weight and small for gestational age, particularly among females with moderate-to-severe asthma and exacerbations during pregnancy. There is also an increased risk of preterm birth, especially with oral steroid use, a small but statistically significant increased risk of congenital malformations, particularly of cleft lip with or without cleft palate, and an increased risk of neonatal hospitalisation and death. Active management may reduce these risks, possibly through reductions in exacerbations. Additional reassuring data have been presented for asthma medication use, which support the benefits outweighing the risks of indicated asthma medication use in pregnancy. Viral infections are an important trigger of asthma exacerbations in pregnancy, and recent data provides possible immunological changes that may explain this. Poor medication adherence despite worsening asthma symptoms in pregnancy is a problem which continues to be demonstrated in the literature. Improving asthma control in pregnancy has the potential to improve not only the mother's health but also that of her child.

Background & Objective: Severe asthma exacerbations during pregnancy are a common complication leading to poor health outcomes for both the mother and the baby. Asthma exacerbations are caused most frequently by respiratory viruses. A balance between antiviral and inflammatory immune responses is critical during pregnancy; the balance may be altered by asthma and respiratory virus infection., Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from (i) non-pregnant healthy controls, (ii) pregnant non-asthmatics, (iii) post-partum non-asthmatics, (iv) non-pregnant asthmatics (v) pregnant asthmatics, and (vi) post-partum asthmatics. Cells were cultured in vitro with the mitogen phytohaemagglutinin or with a strain of the 2009 pandemic swine influenza. Interferon (IFN)-γ, interleukin (IL)-10 and IL-17 protein were measured from culture supernatant. Neutrophil counts were obtained in samples from pregnant and post-partum women., Results: Following the phytohaemagglutinin stimulation of PBMCs, pregnant asthmatics had significantly higher IL-17 and significantly lower IFN-γ responses compared with healthy non-pregnant women. Following infection with influenza, a significant reduction was also observed in IFN-γ and IL-10 production from PBMC of pregnant asthmatics. The IL-17 response to phytohaemagglutinin correlated with the neutrophil percentage. Differences in IFN-γ, IL-10 and IL-17 were found to persist for at least 6 months post-partum., Conclusions: A reduction in antiviral and regulatory immunity with increased inflammation during pregnancy occurs in PBMC from pregnant women with asthma. This novel information may relate to the increased susceptibility and disease severity to respiratory virus infections observed during pregnancy., (© 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.)

Objective: To determine the relationship between psychosocial variables, future exacerbation risk during pregnancy, and perinatal outcomes., Methods: A secondary analysis of a randomized controlled trial of exhaled nitric oxide versus guideline-based treatment adjustment in pregnant women with asthma. Women were recruited between 12 and 20 weeks gestation and monitored for the remainder of the pregnancy. Psychosocial questionnaires including the Perceived Control of Asthma Questionnaire, the Brief Illness Perception Questionnaire, and the Six-Item Short-Form State Trait Anxiety Inventory were assessed at randomization. Exacerbations were defined as hospitalization, emergency visit, unscheduled doctor visit, or oral corticosteroid use for worsening asthma. Perinatal outcomes included preterm birth, small for gestational age, and cesarean section. Multiple logistic regressions were performed with predictor variables, including demographics and psychosocial and clinical variables., Results: The 175 participants had a mean (SD) age = 28.5(5.4) years, forced expiratory volume in 1 second (FEV(1)%) predicted = 95.9(13.4), and asthma control score = 0.88(0.70). Greater perceived control of asthma reduced the odds of subsequent exacerbation (odds ratio (OR) [95%CI] 0.92 [0.85, 0.98], p = .016), cesarean without labor (0.84 [0.75, 0.94], p = .003), and preterm birth (0.84 [0.72, 0.97], p = .019), while increased anxiety increased the odds of subsequent exacerbation (1.05 [1.01, 1.08], p = .008)., Conclusion: Women's perceptions of asthma control and their psychosocial state (anxiety) are related to future exacerbation risk, cesarean section, and preterm birth.

Background: Acute respiratory tract infections are common ailments to all individuals and the human rhinoviruses (HRVs) cause most of these infections. Pregnant women have increased susceptibility and disease severity to viral infections like influenza and HRVs, as do asthmatics. Successful pregnancy requires immunological modulation to permit fetal tolerance., Objectives: To determine whether pregnant women have reduced innate antiviral interferon (IFN) responses to HRV infection compared with non-pregnant women., Methods: An in vitro culture system was used, where peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of 54 women, including 10 stable asthmatics who were pregnant and 10 who were not pregnant, 10 non-asthmatic women who were pregnant, 10 who were ≥6 months post partum and 10 who were not pregnant. Samples were also collected from four exacerbating pregnant asthmatics. PBMCs were cultured with HRV43 and HRV1B. The antiviral proteins IFNα and IFNλ were measured from culture supernatants by ELISA., Results: Compared with healthy non-pregnant women, pregnant women had significantly reduced innate IFN responses to HRV infection (p<0.02), persisting ≥6 months post partum (p≤0.02). Pregnant asthmatics had significantly reduced IFNλ responses compared with healthy non-pregnant women (p≤0.034), while during current asthma exacerbations a decrease in IFNα (p≤0.023) and IFNλ (p=0.007) was observed. Induction by a TLR7 agonist induced a similar pattern of decreased innate IFNs during pregnancy as observed when HRV was the inducing agent., Conclusions: Reduced antiviral IFNs during pregnancy and asthma provide an important mechanism for increased susceptibility, morbidity and mortality in pregnant women with respiratory viral infection.

Background & Aims: One of the most prevalent complications of pregnancy is asthma which is associated with an increased incidence of intrauterine growth restriction. The mechanisms that affect fetal development in pregnancies complicated by asthma are not clearly defined. Antioxidants are particularly important during pregnancy due to their protective role against a state of high oxidative stress as gestation progresses. The current study was designed to characterise the circulating profile of tocopherols and carotenoids in pregnant women with asthma to determine whether asthma severity and dietary intake were associated with an altered antioxidant profile., Methods: Maternal dietary intake and plasma and erythrocyte concentrations of tocopherols and carotenoids were examined in women with (n = 84) and without asthma (n = 47) at 18, 30 and 36 weeks gestation. Tocopherol and carotenoid levels were related to fetal and birth outcomes., Results: Pregnant women with moderate/severe asthma were found to have increased plasma concentrations of total carotenoids (P < 0.05), lutein (P < 0.05 and α-tocopherol (P < 0.02) late in gestation compared to those women with mild asthma and healthy pregnant controls. Moderate/severe asthmatics had higher erythrocyte α-tocopherol quinone levels early in gestation relative to the controls (P < 0.02) but this marker of oxidative stress decreased as gestation progressed. Tocopherols and carotenoids were positively associated with birth weight centile (P < 0.05)., Conclusion: These findings suggest that the maternal system adjusts antioxidant pathways in response to the presence of a high oxidative load induced by asthma during pregnancy in an attempt to ensure continued fetal growth in an adverse environment., (Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Little is known about the psychosocial impact and perceived teratogenic (fetal harm due to medication) risks of asthma treatment (inhaled/oral corticosteroids and β-agonist) during pregnancy., Aims: To assess the perception of asthma control, quality of life (QoL), and perceived risks of therapy in pregnant women with asthma., Methods: Pregnant women with asthma (n = 125) were recruited between 12 and 20 weeks gestation. QoL (generic: Short Form-12 Health Survey v1, and asthma specific: Asthma Quality of Life Questionnaire-Marks (AQLQ-M)) and psychological variables were assessed using the Perceived Control of Asthma Questionnaire (PCAQ), the Brief Illness Perception Questionnaire, and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Women's perceptions of the teratogenic risks of asthma therapy were also assessed and analyzed for adherence to maintenance inhaled corticosteroids (ICSs), poor asthma control, and QoL., Results: Women reported good QoL (median AQLQ-M total score/maximum score = 0.88/10), moderate ability to deal with asthma symptoms (mean PCAQ score = 42.6/55), positive beliefs about their asthma and low anxiety (median STAI score = 26.7/80). Perceived teratogenic risks for asthma drugs were excessive and class dependent. Women perceived there was a 42% teratogenic risk for oral corticosteroid, a 12% risk for ICSs, and a 5% risk with short-acting β-agonist. Illness beliefs, emotional response to illness (p = .030), age ≥ 30 years (p = .046), and maintenance ICS use (p = .045) were significantly associated with uncontrolled asthma, while maintenance ICS use (p = .023), illness beliefs, consequences (p = .044), timeline (p = .016), and emotional response (p = .015) and anxiety (p ≤ .0001) were significantly associated with reduced QoL., Conclusions: In pregnancy, women with asthma experience good QoL but overestimate teratogenic risks of asthma medication. Maintenance ICS use, illness beliefs, and anxiety are associated with impaired QoL and asthma control.

Background: Asthma exacerbations during pregnancy are common and can be associated with substantial maternal and fetal morbidity. Treatment decisions based on sputum eosinophil counts reduce exacerbations in non-pregnant women with asthma, but results with the fraction of exhaled nitric oxide (F(E)NO) to guide management are equivocal. We tested the hypothesis that a management algorithm for asthma in pregnancy based on F(E)NO and symptoms would reduce asthma exacerbations., Methods: We undertook a double-blind, parallel-group, controlled trial in two antenatal clinics in Australia. 220 pregnant, non-smoking women with asthma were randomly assigned, by a computer-generated random number list, before 22 weeks' gestation to treatment adjustment at monthly visits by an algorithm using clinical symptoms (control group) or F(E)NO concentrations (active intervention group) used to uptitrate (F(E)NO >29 ppb) or downtitrate (F(E)NO <16 ppb) inhaled corticosteroid dose. Participants, caregivers, and outcome assessors were masked to group assignment. Longacting β2 agonist and minimum dose inhaled corticosteroid were used to treat symptoms when F(E)NO was not increased. The primary outcome was total asthma exacerbations (moderate and severe). Analysis was by intention to treat. This study is registered with the Australian and New Zealand Clinical Trials Registry, number 12607000561482., Findings: 111 women were randomly assigned to the F(E)NO group (100 completed) and 109 to the control group (103 completed). The exacerbation rate was lower in the F(E)NO group than in the control group (0·288 vs 0·615 exacerbations per pregnancy; incidence rate ratio 0·496, 95% CI 0·325-0·755; p=0·001). The number needed to treat was 6. In the F(E)NO group, quality of life was improved (score on short form 12 mental summary was 56·9 [95% CI 50·2-59·3] in F(E)NO group vs 54·2 [46·1-57·6] in control group; p=0·037) and neonatal hospitalisations were reduced (eight [8%] vs 18 [17%]; p=0·046)., Interpretation: Asthma exacerbations during pregnancy can be significantly reduced with a validated F(E)NO-based treatment algorithm., Funding: National Health and Medical Research Council of Australia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Worldwide the prevalence of asthma among pregnant women is on the rise, and pregnancy leads to a worsening of asthma for many women. This article examines the changes in asthma that may occur during pregnancy, with particular reference to asthma exacerbations. Asthma affects not only the mother but the baby as well, with potential complications including low birth weight, preterm delivery, perinatal mortality, and preeclampsia. Barriers to effective asthma management and opportunities for optimized care and treatment are discussed, and a summary of the clinical guidelines for the management of asthma during pregnancy is presented., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Fetal growth inhibition is a known sequelae of in utero glucocorticoid exposure and has long-term consequences for adult health. Sex-specific fetal growth patterns are observed in pregnancies with maternal asthma and may be due to differential sensitivity of the placenta to glucocorticoids. It is currently unknown whether expression of the placental glucocorticoid receptor (GR) becomes altered with asthma or the use of inhaled corticosteroids., Methods: Pregnant women with mild asthma (n=52), moderate-severe asthma (n=71) and without asthma (n=51) were recruited at John Hunter Hospital, Newcastle, Australia. At delivery, placentae and cord blood were collected, and fetal sex and birth weight were recorded. Placental GR heterogeneous nuclear RNA (hnRNA), mRNA and protein were measured and cord blood cortisol concentrations were assessed., Results: Placental GR gene activity increased with cortisol exposure but decreased with inhaled corticosteroid treatment (p=0.05). With maternal asthma, female birth weight centiles were inversely associated with cortisol (r=-0.286, p=0.017) and, despite a decrease in placental GR mRNA (p=0.003), placental GRalpha protein levels were unchanged. In males, no change to cortisol, birth weight or placental GR were evident in pregnancies with asthma. Together, these results indicate that in pregnancies complicated by asthma, placental GR gene activity, but not mRNA expression or protein levels, is dependent on cortisol and inhaled corticosteroid treatment., Conclusions: The sex-specific associations between cortisol and birth weight observed in pregnancies with asthma are not due to altered GR expression; however, they may be due to differential glucocorticoid sensitivity via preferential transcription of GR isoforms or post-translational modifications.

Background: Smoking and severe asthma exacerbations in pregnancy are risk factors for low birth weight babies. No studies have assessed the clinical implications of smoking on asthma exacerbations in pregnancy., Methods: Pregnant women with current asthma (n=80) were prospectively assessed at clinic visits (18, 30, 36 weeks), during exacerbations and with fortnightly phone calls. The asthma control questionnaire was administered at each contact and exacerbations classified as severe (requiring medical intervention) or mild (self-managed). Medications, self-management skills, smoking history, fractional exhaled nitric oxide (FENO), exhaled carbon monoxide (ECO) and lung function were assessed. Pregnant women without asthma (controls, n=46) were assessed prospectively at clinic visits., Results: Women with asthma were more likely to smoke (34% current smokers) than women without asthma (15% current smokers). In women with asthma, the median (IQR) exacerbation rate during pregnancy was 2.0 (1.0-3.0) in current smokers, 2.0 (1.0-3.0) in ex-smokers and 1.5 (1.0-2.0) in never smokers. The asthma control score during exacerbations was higher in current smokers (median (IQR) 2.17 (1.17-2.7)) compared with never smokers (1.17 (0.8-2.17), p=0.056). An adjusted linear regression model found that smoking was significantly associated with higher asthma control score during exacerbation (P=0.04). birth weights were lower among children of smokers than non-smokers (p=0.023 control group, p=0.086 asthma group)., Conclusions: During pregnancy, asthma exacerbations are more common and more severe in current smokers than never smokers. The risk of effects of maternal asthma on the fetus may be greater among smokers.

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-alpha, IL-1beta, 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-alpha, IL-1beta, 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.

Background: Asthma is a common disease affecting 12% of Australian women with 55% of women experiencing at least one exacerbation during pregnancy. Exacerbations during pregnancy are associated with low birthweight neonates and stillbirth. One of the main reasons for maternal exacerbations during pregnancy is non-compliance with inhaled glucocorticoid treatment due to the misconception that inhaled glucocorticoids are harmful to the fetus., Aims and Methods: We have therefore assessed whether the commonly used inhaled glucocorticoids reduce placental glucocorticoid metabolising capacity, by measuring 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) activity. As these treatments potentially increase the exposure of the fetus to the growth-inhibiting effects of glucocorticoids, we also examined the question of whether inhaled glucocorticoid use was associated with reduced birthweight. Pregnant women using budesonide (n = 18), fluticasone propionate alone (n = 14) and fluticasone propionate in combination with the long-acting beta2 agonist salmeterol (n = 9) were compared to a non-asthmatic control group (n = 20)., Results: The use of inhaled budesonide was associated with significantly increased placental 11beta-HSD-2 activity relative to the control group. Inhaled glucocorticoid use for the treatment of asthma was associated with normal birthweight. In the small number of women using combination therapy (fluticasone and salmeterol), there was reduced birthweight compared to the control group., Conclusion: Inhaled glucocorticoids alone do not adversely affect fetal growth and placental function.

Objective and Background: The course of asthma may be altered during pregnancy with at least one-third of women experiencing a worsening of asthma and 20% having an exacerbation during pregnancy. This study used the novel proteomic technique, surface-enhanced laser desorption ionization-time of flight mass spectrometry to determine if the presence of asthma during pregnancy was associated with alterations in plasma proteins., Methods: Plasma collected from healthy (n = 23) and asthmatic (n = 27) pregnant women at 18 and 30 weeks gestation was applied to strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using Ciphergen Protein Biology System IIc and significant differences in individual peak intensities between groups determined., Results: At 18 weeks gestation, 91 peaks were significantly different between pregnant women with and without asthma, representing 28% of the total peaks identified. At 30 weeks gestation, 51 peaks were significantly different. There were two peaks that were significantly different between groups at both 18 and 30 weeks gestation and expressed at a similar level at both time points. One was increased in asthmatics (MW = 6444 Da) whereas the other decreased in asthmatics compared with non-asthmatic women (MW = 1846 Da)., Conclusions: This study demonstrated that there are differences in protein patterns between pregnant women with and without asthma. Other techniques are needed to define the molecular species and classify pathophysiological significance. Surface-enhanced laser desorption ionization-time of flight mass spectrometry has potential as a tool to monitor disease progression in situations such as 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.

Objective: We conducted a comparative proteomic analysis of placental and umbilical cord blood proteins using surface-enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF MS) to examine the associations among asthma, fetal gender, and protein profiles., Methods: Placental tissue and umbilical vein plasma were collected from 10 healthy and 20 asthmatic women. Placental proteins were extracted using phosphate-buffered saline containing protease inhibitors. Samples were applied to the surfaces of strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using a Ciphergen Protein Biology System IIc (Freemont, CA), and differences in individual peak intensities between groups were determined., Results: Fourteen placental peaks were significantly different between asthmatic and non-asthmatic women (seven more highly expressed and seven less highly expressed). Ten umbilical cord blood peak differences were identified, with four peaks more highly expressed and six peaks less highly expressed in asthmatics. Four placental and three umbilical cord blood proteins differed significantly between male and female fetuses. Two placental and five umbilical cord blood peaks were specifically increased in a subgroup of samples collected from asthmatic women who did not use inhaled glucocorticoids and were pregnant with a female fetus, a group previously found to have altered placental function., Conclusions: This study demonstrates the abilities of the SELDI technique as a tool for protein profiling in tissue or plasma. Further work to positively identify the candidate peptides found in this study may provide a greater understanding of the placental mechanisms leading to alterations in fetal growth in patients with bronchial asthma.

Asthma during pregnancy is associated with a low birth weight, although the mechanisms contributing to this outcome remain unknown. The relationship between maternal asthma and its treatment, placental function, fetal sex, and low birth weight was examined to establish the effect of asthma on fetal growth. Glucocorticoid intake by women with asthma was assessed throughout pregnancy. The placenta was collected after delivery, and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity was measured. Fetal cortisol and estriol were measured in the umbilical vein plasma at delivery. Those with asthma were compared with a nonasthmatic control group. In women with asthma who did not use inhaled steroids and were pregnant with a female fetus, we observed significantly reduced birth weights, whereas male birth weights were unaffected. The presence of a female fetus was associated with significantly increased maternal circulating monocytes, significantly reduced placental 11beta-HSD2 activity and fetal estriol, and a trend toward elevated fetal plasma cortisol. This study provides evidence that in pregnancies complicated by asthma there is a fetal sex-specific effect on the maternal immune system with adverse effects on placental function and female fetal growth.

Pregnancies complicated by asthma are associated with an increased risk of low birth weight. Currently, the mechanisms causing this outcome are unknown. To investigate whether impaired placental function may be a determinant, we measured placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity, protein and mRNA, placental CRH mRNA, fetal cortisol, and fetal estriol concentrations at delivery. Asthmatic subjects were classified according to inhaled glucocorticoid intake during pregnancy and compared with a control nonasthmatic group. There was a 25% reduction in neonatal birth weight centile in asthmatic women who did not use inhaled glucocorticoid treatment. This was accompanied by significantly reduced placental 11beta-HSD2 activity, significantly increased fetal cortisol, and a trend toward increased placental CRH mRNA and reduced fetal estriol concentrations. The use of inhaled glucocorticoids for treatment was associated with birth weight centile, 11beta-HSD2 activity, CRH mRNA, fetal cortisol, and estriol concentrations similar to control levels. There was a significant inverse correlation between fetal cortisol and fetal estriol concentrations across all groups. These studies demonstrate that inhaled glucocorticoid intake for the treatment of asthma is associated with improved placental function and fetal outcome, suggesting that inflammatory factors associated with asthma may be detrimental to fetal growth and development in these pregnancies.

The article discusses a study that assessed the frequency, severity and consequences of respiratory viral infection during pregnancy in women with and without asthma. Findings show that pregnant women with asthma experience more common colds during pregnancy than those without asthma. The association between colds during pregnancy and adverse maternal and pregnancy outcomes is explored.

Respiratory virus-induced asthma exacerbations occur frequently during pregnancy and are associated with adverse outcomes for mother and child. Primary nasal epithelial cells (pNECs) provide a useful method to study immune responses in pregnancy. pNECs were obtained by nasal brushings from pregnant and non-pregnant women with and without asthma. pNECS were infected in vitro with major group Rhinovirus 43 (RV43) and seasonal influenza (H3N2). Following infection, pNECs showed measurable quantities of interferon (IFN)-λ, IL-1β, IL-8, IP-10 and MIP1-α. pNECs provide a safe and effective method for studying respiratory epithelial cell responses during pregnancy. [ABSTRACT FROM AUTHOR]

Summary: Background & aims: One of the most prevalent complications of pregnancy is asthma which is associated with an increased incidence of intrauterine growth restriction. The mechanisms that affect fetal development in pregnancies complicated by asthma are not clearly defined. Dietary fatty acids (FA) especially polyunsaturated fatty acids (PUFA) are particularly important during pregnancy due to their role in fetal growth and development. Dietary PUFAs also have a role in clinical outcomes for non-pregnant asthmatics. The current study was designed to characterize the fatty acid profile in pregnant women with asthma to determine whether asthma severity or reduced fetal growth were associated with an altered FA profile. Methods: Maternal dietary intake and plasma fatty acid profile were examined in women with and without asthma at 18, 30 and 36 weeks gestation. Maternal fatty acids levels were related to measures of fetal growth using Doppler ultrasound and birth outcomes. Results: The data found that pregnant women with moderate/severe asthma had increased circulating plasma fatty acid levels at 36 weeks gestation but reduced dietary intake of fats compared to those women with mild asthma and healthy pregnant controls. In addition, women with moderate/severe asthma had increased circulating n-3PUFA levels at 36 weeks gestation which was associated with reduced fetal and neonatal head circumference. Conclusion: These observations suggest moderate/severe asthma may disrupt lipid metabolism, transport or cellular uptake during pregnancy which subsequently contributes to reduced fetal growth. [Copyright &y& Elsevier]