Asthma in pregnancy--immunological changes and clinical management

Asthma is one of the most common diseases complicating pregnancy and a risk factor for several maternal and fetal complications, posing a special challenge for physicians treating asthmatic pregnant women. Asthma influences the outcome of pregnancy and - vice versa - pregnancy affects asthma severity with bidirectional immunological interactions that are currently being examined. Supporting pregnancy-induced immunotolerance is the observation that attenuation of allergic responses can be detected in controlled asthmatic pregnant patients. However, uncontrolled asthmatic pregnant women show significant asthma-associated immune reactions, such as diminished pregnancy specific regulatory T cell proliferation, that may - besides other factors - influence fetal growth. Uncontrolled, symptomatic asthma may increase the risk of adverse perinatal outcomes; thus adequate regular anti-asthmatic treatment resulting in optimal asthma control represents a vital need during pregnancy. This review summarizes immunological changes characterizing pregnancy in asthmatic women together with the clinical implications of asthma management during pregnancy.     

Asthma in pregnancy

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.     

Management of the pregnant asthmatic patient

Asthma is not an uncommon medical problem during pregnancy. Various physiologic alterations of pregnancy may theoretically affect asthma. Fetal oxygenation is affected more by maternal alkalosis than by hypoxemia, both of which can occur during uncontrolled asthma. Clinical studies suggest a variable effect of pregnancy on asthma and increased maternal and fetal morbidity and mortality associated with severe asthma. Most antiasthmatic drugs are safe to use during pregnancy. Medications used during delivery by the obstetrician may affect asthma, and some antiasthmatic medications may alter labor. We review here a rational approach to the management of steroid preparation for delivery in steroid-dependent asthmatic patients. Asthmatic mothers may breast-feed with minimal risk of adverse drug effects on the infant.     

Pregnancy and asthma: recent developments

PURPOSE OF REVIEW: Asthma is the most common potentially serious medical problem to complicate pregnancy. Asthmatic women have been shown to be at an increased risk of complications during pregnancy. Managing asthma during pregnancy is unique because the effects of both the illness and the treatment on the developing fetus and the patient must be considered. RECENT FINDINGS: This review summarizes the recent studies addressing the interrelationships between asthma and pregnancy and general aspects of pharmacologic therapy of gestational asthma. SUMMARY: The prevalence of asthma in pregnant women appears to be increasing. Recent evidence supports that pregnant asthmatic women with moderate to severe asthma may have an increased risk of adverse perinatal outcomes. The goal of asthma management during pregnancy is to optimize maternal and fetal health.     

Pregnancy and birth outcomes in families with asthma.

Studies of maternal asthma in pregnancy have shown an increased risk of adverse neonatal and maternal outcomes such as preeclampsia, hypertension, cesarean delivery, prematurity, low birth weight, and perinatal/neonatal mortality. However, results are not consistent between studies. We studied the association between maternal asthma and various adverse neonatal and maternal outcomes and explored whether there is any evidence that pregnancy exacerbates maternal asthma. The data were collected as part of the Childhood Asthma Prevention Study. Pregnant women with asthma or women whose partners or other children had current symptoms of asthma were recruited at six Sydney hospitals. All women recruited were post 36 weeks gestation and were living within 30 km of the study recruitment center. Information about family history of asthma was collected using a questionnaire at 36 weeks gestation and subsequent information about antenatal and perinatal events was obtained from hospital records. Data from 611 pregnant women were available for analysis, 340 of whom had asthma. Hypertension was significantly more common in asthmatics than in nonasthmatics [OR = 2.16 (1.02-4.6), p < 0.043]. The prevalence of gestational diabetes, labor complications, delivery complications, and adverse neonatal outcomes did not differ significantly between the groups. We also found that the course of maternal asthma usually remains unchanged during pregnancy, but that more severe asthma is likely to get worse. We have confirmed previous observations that women with asthma are at increased risk of hypertension in pregnancy, which is consistent with studies that show that pregnant asthmatic women have a slightly increased risk of preeclampsia. However, we did not find evidence of an increased risk of adverse perinatal outcomes.     

Pulmonary hypertension diagnosed by echocardiography during idiopathic myelofibrosis. A case report and a brief review of the literature

Asthma is one of the most common chronic medical conditions that may complicate pregnancy. Asthma influences the outcome of pregnancy and, vice versa, pregnancy affects asthma severity, but the underlying immunological mechanisms of this interaction are not fully understood. As a sign of pregnancy-induced immunotolerance, attenuation of allergic responses can be detected in controlled asthmatic pregnant patients; however non controlled asthmatic pregnant women show significant asthma-associated immune reactions that may, beside other factors, influence fetal growth. Generally, although uncontrolled asthma may increase the risk of adverse perinatal outcomes, women with well-controlled and adequately treated disease during pregnancy do not develop maternal or fetal complications.     

Maternal asthma is associated with reduced female fetal growth

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.     

Maternal influence in the transmission of asthma susceptibility

Asthma is one of the most common chronic diseases in children, with increasing morbidity and mortality. A genetic predisposition and exposure to allergens have been implicated as major risk factors for the development of asthma. However, increasing evidence indicates that the mother plays a crucial role in mediating the development of fetal-infant immune responses to inhaled allergens. The exact nature and mechanism of this maternal influence and how it might be associated with the development of allergic sensitization and asthma are not clear. Under normal conditions, the maternal environment during pregnancy promotes an initial Th2 skewed immune response in the offspring which transitions to a nonallergic Th1 type response after birth. However, the allergic mother's influence may delay the normal transition to a nonallergic immune response to inhaled allergens in her children, thus increasing the risk for the development of allergic sensitization and/or asthma. Understanding the underlying mechanisms by which the maternal immune environment can influence the development of the fetal-infant immune response to inhaled allergens may lead to identifying new targets for the prevention of allergic sensitization and asthma.     

Asthma during pregnancy: mechanisms and treatment implications.

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

Effect of Maternal Asthma and Gestational Asthma Therapy on Fetal Growth

Asthma is a common chronic condition that might seriously complicate pregnancy and fetal development. This article provides a comprehensive review of the existing literature regarding the effect on fetal growth of maternal asthma and common asthma medications used during pregnancy, including short-and long-acting β ₂-agonists, inhaled and oral corticosteroids, chromones, leukotriene receptor agonists, and theophylline. Evaluated outcomes of fetal growth include low birth weight, mean birth weight, small for gestational age, birth length and head circumference, and measures of asymmetrical growth retardation. Methodological and practical considerations related to safety of asthma medications in pregnancy and management of gestational asthma are discussed.     

Effect of Maternal Asthma and Gestational Asthma Therapy on Fetal Growth

Asthma is a common chronic condition that might seriously complicate pregnancy and fetal development. This article provides a comprehensive review of the existing literature regarding the effect on fetal growth of maternal asthma and common asthma medications used during pregnancy, including short-and long-acting β ₂-agonists, inhaled and oral corticosteroids, chromones, leukotriene receptor agonists, and theophylline. Evaluated outcomes of fetal growth include low birth weight, mean birth weight, small for gestational age, birth length and head circumference, and measures of asymmetrical growth retardation. Methodological and practical considerations related to safety of asthma medications in pregnancy and management of gestational asthma are discussed.     

Anticoagulation in pregnancy

Pregnancy-associated thrombosis is an important cause of morbidity and mortality during pregnancy. Anticoagulation therapy is an important component of the management of thrombotic complications in pregnancy but may result in fetal and maternal complications. Although evidence-based recommendations are available for the prevention and treatment of venous thromboembolism, the management of pregnant women with mechanical valves still presents a challenge, because there are no controlled clinical trials to provide guidelines for optimal antithrombotic therapy. This review presents information on anticoagulation therapy during pregnancy for thromboembolic prophylaxis in women with various cardiovascular disorders, focusing on patients with mechanical heart valves.     

The Asthma Risk Grid: clinical interpretation of symptom perception.

The ability to perceive accurately the onset and intensity of asthma symptoms is a cornerstone of effective asthma management. Research in pediatric and adult asthma patients has shown the important role of symptom perception in asthma management, morbidity, and mortality. Assessment of symptom perception ability has largely remained an empiric methodology rather than an applied clinical tool. The Asthma Risk Grid represents a clinical application of symptom perception measurement, and pediatric cases are described as clinical examples. Clinical and research applications of the Asthma Risk Grid are presented.     

Prenatal maternal alcohol consumption and hospitalization with asthma in childhood: a population-based follow-up study

BACKGROUND: Asthma may have a prenatal origin. We examined whether maternal alcohol consumption during pregnancy increases the risk of hospitalization with asthma in children. METHODS: We conducted a follow-up study on 10,440 singletons born at approximately 36 weeks of gestation or later to mothers attending midwife centers between April 1984 and April 1987 in Denmark. The mothers completed a questionnaire regarding lifestyle and socioeconomic factors, including alcohol consumption. The children were followed up through the Danish Hospital Discharge Registry. We determined the first hospitalization with a discharge diagnosis of asthma as recorded in the Danish Hospital Discharge Registry. RESULTS: Most pregnant women (81.5%) drank at least some alcohol during pregnancy, but only a few (2.1%) consumed 120 g or more per week. In total, 307 children were hospitalized at least once with a discharge diagnosis of asthma during follow-up (the cumulative incidence risk was 3.5% from birth to 12 years of age or the end of follow-up). After adjusting for maternal socioeconomic factors, dietary components, and other lifestyle factors, children whose mothers drank alcohol during pregnancy did not have an increased risk of hospitalization with asthma compared with the children of mothers who reported no alcohol consumption during pregnancy (adjusted incidence rate ratio, 0.95; 95% confidence interval, 0.70-1.29). Further analyses showed no association with the dose and type of alcohol or with binge drinking. CONCLUSIONS: The study provides no support for a causal link between maternal alcohol intake during pregnancy and asthma in childhood.     

Immediate and long-term follow-up of percutaneous balloon mitral valvuloplasty in pregnant patients with rheumatic mitral stenosis

Percutaneous mitral balloon valvuloplasty (PMV) can be performed during pregnancy without significant maternal risk or fetal morbidity or mortality. However, little is known about long-term follow-up results after PMV in populations of pregnant women. Thus, the present study was undertaken to determine the immediate and long-term outcomes after PMV in a large cohort of pregnant patients with severe mitral stenosis. The patient population consisted of 71 consecutive pregnant women with severe rheumatic mitral stenosis admitted to the hospital with severe congestive heart failure (New York Heart Association class III and IV) for PMV. All patients underwent clinical and obstetric evaluations, electrocardiography, and 2-dimensional and Doppler echocardiography. PMV was successful in all patients, resulting in a significant increase in mitral valve area from 0.9 +/- 0.2 to 2.0 +/- 0.3 cm2 (p <0.001). At the end of pregnancy, 98% of the patients were in New York Heart Association functional class I or II. At a mean follow-up of 44 +/- 31 months, the total event-free survival rate was 54%. The mean gestational age at delivery time was 38 +/- 1 weeks. Preterm deliveries occurred in 9 patients (13%), including 2 twin pregnancies. The remaining 66 of 75 newborns (88%) had normal weight (mean 2.8 +/- 0.6 kg) at delivery. At long-term follow-up of 44 +/- 31 months after birth, the 66 children exhibited normal growth and development and did not show any clinical abnormalities. In conclusion, PMV is safe and effective, has a low morbidity and mortality rate for the mother and the fetus, and has favorable long-term results in pregnant women with rheumatic mitral stenosis in New York Heart Association functional class III or IV.     

Managing Asthma in Expectant Mothers

Pregnancy does not appear to have a consistent effect on the frequency or severity of asthma. The most common cause of worsening asthma in pregnancy is likely to be noncompliance with medication. Emphasizing to the patient in advance that fetal well-being is dependent on maternal well-being may help prevent this.In general, well controlled asthma is not associated with a higher risk of adverse pregnancy outcomes. Essential to successful asthma management is patient education that helps to ensure effective medication use, avoidance of triggers, and prompt treatment. This education should include measurement of peak expiratory flow rate and a written asthma action plan. Most of the medications that are used to control asthma in the general population can be safely used in pregnant women. Inhaled beta-adrenoceptor agonists (beta-agonists), cromolyn sodium (sodium cromoglycate), and inhaled and systemic corticosteroids all appear to be very well tolerated by the fetus. Budesonide and beclomethasone should be considered as the preferred inhaled corticosteroids for the treatment of asthma in pregnancy. Use of the leukotriene receptor antagonists zafirlukast and montelukast in pregnancy is probably safe but should be limited to special circumstances, where they are viewed essential for asthma control. Zileuton should not be used in pregnancy.Acute asthma exacerbations in pregnant women should be treated in a similar manner to that in non-pregnant patients. Maternal blood glucose levels should be monitored periodically in pregnant women receiving systemic corticosteroids because of the deleterious effects of hyperglycemia upon embryos and fetuses. During pregnancy, maternal arterial oxygen saturations should be kept above 95% if possible for fetal well-being. Ambulatory oxygenation should be checked prior to discharge to ensure that women do not desaturate with their daily activities.Acute exacerbations of asthma during labor and delivery are rare. Dinoprost, ergometrine, and other ergot derivatives can cause severe bronchospasm, especially when used in combination with general anesthesia, and should be avoided in asthmatic patients. Pregnant women who have been treated with corticosteroids in the past year may require stress-dose corticosteroids during labor and delivery. Most asthma medications, including oral prednisone, are considered compatible with breast-feeding.     

Pregnancy outcomes in asthmatic women

Asthma is considered to be the most common respiratory disorder complicating pregnancy. Seventy-six asthmatic and 152 non-asthmatic pregnant women were studied. Maternal asthma was significantly associated with adverse infant outcomes, including prematurity, low birth weight and the need for Cesarean delivery. The results of this study could indicate that pregnant women with asthma were at substantially increased risk for adverse infant outcomes and suggest the need for extra attention to mothers with asthma before and during pregnancy.     

Management of asthma during pregnancy.

Asthma is estimated to affect up to 4% of pregnancies. Management of asthma during pregnancy follows the same approach as in the general population. Aggressive treatment should be entertained because asthma under poor control during pregnancy can lead to poor outcomes for the mother and child. The foundations of management are environmental avoidance procedures, proper pharmacologic agents, and specific allergen immunotherapy. For pregnant women with persistent asthma, the use of inhaled cromolyn or inhaled budesonide should be considered as first-line agents. Short-acting beta-agonists can be used as needed in all asthma categories. Other agents such as salmeterol, leukotriene modifiers, newer inhaled corticosteroids, and omalizumab may be considered in women who showed a good response to these agents before pregnancy.     

Asthma among senior adults

Elderly patients with asthma are a specific group with particular needs. These must be addressed in order to provide appropriate asthma care. Asthma causes higher morbidity and mortality rates among the elderly patients. Older patients often fail or have problems with compliance and self-management due to age-specific factors. Older patients with asthma are often misdiagnosed, due to an impaired patient perception of symptom severity, different opinions of what kind of asthma-control is possible, or not sufficient communication skills. Often the quality of life is impaired by asthma. Improvement in self management skills in a special way may enhance the health status of elderly patients with asthma.     

Lack of Relationship between Birth Conditions and Allergic Disorders in Japanese Children Aged 3 Years

Background. The current cross-sectional study examined the associations between low birth weight (LBW), preterm birth, and small-for-gestational-age (SGA) and the prevalence of wheeze, asthma, and eczema in Japanese children aged 3 years. Methods. Study subjects were 2004 children. All data were obtained using a questionnaire. Outcomes were defined according to the criteria of the International Study of Asthma and Allergies in Childhood. Adjustment was made for sex, number of siblings, breastfeeding duration, paternal and maternal educational level, paternal and maternal history of allergic disorders, maternal smoking during pregnancy, secondhand smoke exposure at home, and gestational age at birth. Results. The prevalence of wheeze, asthma, and eczema in the previous 12 months were 22.1%, 9.0%, and 17.5%, respectively, and 8.4% were classified as LBW (<2500 g), 4.7% as preterm birth (<37 weeks), and 7.1% as SGA (<10th percentile). There were no significant associations between LBW, preterm birth, or SGA and the prevalence of wheeze, asthma, or eczema. A positive relationship between preterm birth and asthma was of borderline significance in children whose mothers had smoked during pregnancy (adjusted OR: 4.71 [95% CI: 0.97?21.39]), but not in those whose mothers had never smoked during pregnancy; the multiplicative interaction between preterm birth and maternal smoking during pregnancy with respect to asthma was significant (p = .04). Conclusions. The current study failed to detect significant associations between birth conditions and allergic disorders. Nevertheless, we did find evidence for an interaction between preterm birth and maternal smoking during pregnancy affecting asthma.