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ABSTRACT: ABSTRACT BACKGROUND: Respiratory viral infections are common in pregnancy, but their health impact, especially in asthma is unknown. The objective of the study was to assess the frequency, severity and consequences of respiratory viral infection in pregnancy in women with and without asthma. METHODS: In this prospective cohort study, common cold symptoms were assessed during pregnancy in 168 women with asthma, and 117 women without asthma, using the common cold questionnaire and by self-report. Nasal and throat swabs were collected for suspected infections and tested by polymerase chain reaction for respiratory viruses. Pregnancy and asthma outcomes were recorded. RESULTS: Pregnant women with asthma had more prospective self-reported and questionnaire detected common colds than pregnant women without asthma ( incidence rate ratio 1.77, 95% confidence interval [1.30, 2.42], P<0.0001). Retrospectively reported common colds in early pregnancy and postpartum were increased in asthma compared to women without asthma. The severity of cold symptoms was also increased in asthma (total cold score median 8 interquartile range [5, 10] in asthma, vs 6 [5, 8] in controls, P=0.031). Among women with asthma, having a laboratory confirmed viral infection was associated with poorer maternal health, with 60% of infections associated with uncontrolled asthma and a higher likelihood of pre-eclampsia. CONCLUSIONS: Pregnant women with asthma have more common colds during pregnancy than pregnant women without asthma. Colds during pregnancy were associated with adverse maternal and pregnancy outcomes. Prevention of viral infection in pregnancy may improve the health of mothers with asthma.
Chest 03/2013; · 5.25 Impact Factor
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ABSTRACT: BACKGROUND & OBJECTIVE: Severe asthma exacerbations during pregnancy are a common complication leading to poor health outcomes for both mother and 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 (1) non-pregnant healthy controls, (2) pregnant non-asthmatics, (3) postpartum non-asthmatics, (4) non-pregnant asthmatics (5) pregnant asthmatics, and (6) postpartum asthmatics. Cells were cultured in vitro with the mitogen phytohaemagglutinin or with a strain of the 2009 pandemic swine influenza. Interferon-γ, interleukin-10, and interleukin-17 protein were measured from culture supernatant. Neutrophil counts were obtained in samples from pregnant and postpartum women. RESULTS: Following phytohaemagglutinin stimulation of peripheral blood mononuclear cells, pregnant asthmatics had significantly higher IL17 and significantly lower IFNγ responses compared to healthy non-pregnant women. Following infection with influenza, a significant reduction was also observed in interferon-γ and interleukin-10 production from PBMCs of pregnant asthmatics. The interleukin-17 response to phytohaemagglutinin correlated with the neutrophil percentage. Differences in interferon-γ interleukin-10 and interleukin-17 were found to persist for at least 6 months postpartum. CONCLUSIONS: A reduction in anti-viral and regulatory immunity with increased inflammation during pregnancy occurs in peripheral blood mononuclear cells from pregnant women with asthma. This novel information may relate to the increased susceptibility and disease severity to respiratory virus infections observed during pregnancy.
Respirology 02/2013; · 2.42 Impact Factor
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ABSTRACT: 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.
Journal of Asthma 01/2013; · 1.52 Impact Factor
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ABSTRACT: This systematic review and meta-analysis sought to investigate if asthma exacerbations, oral corticosteroid use, or asthma severity are associated with prematurity and intrauterine growth restrictionCohort studies published between 1975 and March 11, 2012 were considered for inclusion. 138 publications were identified for possible inclusion, and 9 papers met the inclusion criteria, by reporting perinatal outcomes of interest (low birth weight (<2500 gm), preterm 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 (RR3.02, 95%CI[1.87,4.89]) and RR 1.41,95%CI[1.04,1.93], respectively) and preterm 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 preterm delivery, low birth weight, and small for gestational age. Further studies on the effect of maternal asthma control on perinatal outcomes are warranted.
European Respiratory Journal 08/2012; · 5.89 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
The Journal of Infectious Diseases 06/2012; 206(5):646-53. · 6.41 Impact Factor
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ABSTRACT: 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.
To assess the perception of asthma control, quality of life (QoL), and perceived risks of therapy in pregnant women with asthma.
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.
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.
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.
Journal of Asthma 12/2011; 48(10):1032-40. · 1.52 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Clinical nutrition (Edinburgh, Scotland) 09/2011; 31(1):99-107. · 3.27 Impact Factor
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ABSTRACT: 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.
To determine whether pregnant women have reduced innate antiviral interferon (IFN) responses to HRV infection compared with non-pregnant women.
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.
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.
Reduced antiviral IFNs during pregnancy and asthma provide an important mechanism for increased susceptibility, morbidity and mortality in pregnant women with respiratory viral infection.
Thorax 09/2011; 67(3):209-14. · 6.84 Impact Factor
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ABSTRACT: 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.
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.
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).
Asthma exacerbations during pregnancy can be significantly reduced with a validated F(E)NO-based treatment algorithm.
National Health and Medical Research Council of Australia.
The Lancet 09/2011; 378(9795):983-90. · 38.28 Impact Factor
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ABSTRACT: 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.
Clinics in chest medicine 03/2011; 32(1):93-110, ix. · 2.51 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Thorax 08/2010; 65(8):739-44. · 6.84 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Thorax 08/2010; 65(8):677-83. · 6.84 Impact Factor
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ABSTRACT: Asthma and rhinitis are common medical conditions that complicate pregnancy. Asthma can have an adverse impact on pregnancy
outcomes, and pregnancy can modify the clinical status of pre-existing asthma and rhinitis. Coordinated medical and antenatal
care that combines optimal medication use with self-management skills and careful monitoring of the mother and her baby form
the basis of effective management of asthma and rhinitis in pregnancy.
12/2009: pages 485-497;
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ABSTRACT: Fetal growth varies in a sex-specific manner in response to maternal asthma during pregnancy, but the mechanisms are unclear.
We examined the influence of maternal asthma severity and associated exposures, inhaled glucocorticoid treatment, maternal cigarette use, and fetal sex on fetal growth and placental function during pregnancy and on the newborn insulin-like growth factor (IGF) axis. STUDY SUBJECTS AND DESIGN: Fetal growth was assessed in a prospective cohort of asthmatic and non-asthmatic women (n=145). At delivery, umbilical vein plasma was collected from male (n=61, controls n=16 and asthmatic n=45) or female (n=84, controls n=22 and asthmatic n=62) fetuses. Cord plasma insulin-like growth factor (IGF) binding protein (BP)-1, IGFBP-3, IGF-1 and IGF-2 were measured by radioimmunoassay and ELISA.
Cord plasma IGF-1 was the main component of the neonatal IGF axis altered by asthma and cigarette use. IGF-1 was increased in the presence of mild asthma and a male fetus and decreased in the presence of a female fetus and maternal asthma with cigarette use. IGFBP-3 was also decreased in the female fetuses of pregnancies complicated by asthma and cigarette use. Inhaled glucocorticoid use for the treatment of asthma did not affect the IGF axis. The strongest overall predictor of female birth weight after accounting for asthma severity, inhaled glucocorticoid treatment and cigarette use was IGF-1. For males, the strongest predictor of birth weight was IGFBP-3.
The data suggest male and female fetuses institute different strategies in response to adverse pregnancy conditions such as asthma and cigarette use.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 09/2009; 20(1):39-48. · 2.35 Impact Factor
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ABSTRACT: 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.
The Journal of Immunology 03/2009; 182(3):1411-20. · 5.79 Impact Factor
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ABSTRACT: The prevalence of asthma is higher in women than men of reproductive age and almost half of all hospitalisations for asthma in women occur during the perimenstrual phase of the cycle. The mechanisms of premenstrual asthma (PMA) are unknown and a definition of PMA has not been clearly presented in the literature. The objective of this study was to determine the prevalence of PMA using a variety of definitions, to investigate the cycle-to-cycle variation in PMA, the effects of oral contraceptive use and the relationship between PMA and premenstrual symptoms. Premenopausal women with asthma (n = 28) were prospectively followed for at least 12 weeks over 2-4 consecutive menstrual cycles. Asthma symptoms, beta(2)-agonist and inhaled corticosteroid use and morning and evening peak expiratory flow were recorded daily. The following types of PMA definitions were investigated: self-reported PMA, increased symptoms, increased medication use, decreased peak flow or a combination of changes in symptoms, medication and peak flow. Changes of more than 20%, for at least 2 consecutive days of the luteal phase (last 14 days of the cycle prior to menstruation) compared to the early follicular phase average (first 7 days after menstruation) were considered PMA. Using a composite definition where subjects experienced increased symptoms and medication use with or without a change in peak flow, 16 subjects were classified as having PMA (57%), while 12 did not have PMA. Only 4 subjects (25%) had PMA in every cycle examined. Fifty-five percent of subjects who used oral contraceptives had PMA, while 59% of subjects who did not use oral contraceptives had PMA. Women who were defined PMA using the composite definition were more likely than those without PMA to experience a 20% decrease in peak flow during the luteal phase. There was no relationship between asthma symptoms and premenstrual symptoms on day 1 of the menstrual cycle in women with PMA. PMA resulting in increased symptoms and medication use occurred in 57% of subjects studied for 2-4 menstrual cycles. The use of oral contraceptives is not protective and further work is required to elucidate the mechanisms of PMA.
Journal of Asthma 11/2008; 45(8):696-704. · 1.52 Impact Factor
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ABSTRACT: The environment in which the fetus develops is critical for its survival and long-term health. The regulation of normal human fetal growth involves many multidirectional interactions between the mother, placenta, and fetus. The mother supplies nutrients and oxygen to the fetus via the placenta. The fetus influences the provision of maternal nutrients via the placental production of hormones that regulate maternal metabolism. The placenta is the site of exchange between mother and fetus and regulates fetal growth via the production and metabolism of growth-regulating hormones such as IGFs and glucocorticoids. Adequate trophoblast invasion in early pregnancy and increased uteroplacental blood flow ensure sufficient growth of the uterus, placenta, and fetus. The placenta may respond to fetal endocrine signals to increase transport of maternal nutrients by growth of the placenta, by activation of transport systems, and by production of placental hormones to influence maternal physiology and even behavior. There are consequences of poor fetal growth both in the short term and long term, in the form of increased mortality and morbidity. Endocrine regulation of fetal growth involves interactions between the mother, placenta, and fetus, and these effects may program long-term physiology.
Endocrine Reviews 05/2006; 27(2):141-69. · 19.93 Impact Factor
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ABSTRACT: 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.
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).
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.
Inhaled glucocorticoids alone do not adversely affect fetal growth and placental function.
Australian and New Zealand Journal of Obstetrics and Gynaecology 05/2006; 46(2):136-40. · 1.24 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Respirology 02/2006; 11(1):41-8. · 2.42 Impact Factor
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ABSTRACT: To estimate the frequency of severe asthma exacerbations in pregnant women and to estimate whether there is an association with adverse perinatal outcomes.
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.
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.
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.
II-2.
Obstetrics and Gynecology 12/2005; 106(5 Pt 1):1046-54. · 4.73 Impact Factor
