Pregnant Asthmatic Women Research Articles

Pregnancy and asthma: recent developments

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. This review summarizes the recent studies addressing the interrelationships between asthma and pregnancy and general aspects of pharmacologic therapy of gestational asthma. 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.

Ventilator Strategy for Status Asthmaticus in Pregnancy: A Case-Based Review

Asthma is a common and potentially serious condition complicating pregnancy. However, the literature available on the management of severe asthma in pregnancy is limited. We describe two episodes of respiratory failure due to asthma in pregnant women and discuss their management in the context of a review of the literature. In both patients, adequate oxygenation was maintained by using controlled hypoventilation with a permissive hypercapnia strategy. Both patients received aggressive steroid therapy, aerosolized bronchodilators, sedation, and paralysis. Aggressive asthma treatment as in a nongravid female is recommended.

009. The effect of maternal asthma during pregnancy on placental function, fetal growth and childhood development

Fetal growth and neonatal birth weight are significant contributing factors to the development of adult disease states in later life. In human pregnancy, we have identified sexually dimorphic differences in fetal growth with the female fetus reducing growth in response to maternal asthma and the male fetus continuing to grow at a normal rate but being at an increased risk of in utero death. The physiological mechanisms that confer sex-specific differences in the fetal response to maternal asthma are unknown. However our research has identified differences in mechanisms associated with fetal glucocorticoid regulation, which are also associated with changes in childhood growth patterns. Asthmatic and control pregnant women were recruited at their first antenatal visit and followed through to delivery. Subjects were assessed for severity of asthma and their use of medication, including glucocorticoid therapy, was recorded. In addition to routine antenatal care, fetal growth was determined using Doppler ultrasound. Following delivery placentas and cord blood were collected. The children of the women followed during the study were examined by a paediatrician at 6 months of age and every 12 months after that initial visit. Our data shows that in response to maternal asthma, the female fetus has an increase in cortisol, which downregulates placental GR expression, immune and hypothalamic-pituitary-adrenal function and is associated with decreased growth. The male fetus responds to increased cortisol with an increase in GR expression and no change in HPA or immune function or growth. These data indicate that the male and female fetus have different strategies to control growth and in their response to a maternal stress, such as asthma.

Asthme et grossesse

Any asthmatic woman in the childbearing age may become pregnant. Generally, asthma is not a contraindication for pregnancy, and drug treatment of pregnant asthmatic women is indicated. Neither mother nor child are particularly at risk for complications, as demonstrated in recently published long-term studies. Pharmacologic data are reassuring, especially those concerning inhaled corticosteroids. Nevertheless, regular follow-up of asthmatic pregnant patients is necessary to assure good control of the patient's asthma.

The relationship of asthma medication use to perinatal outcomes

Maternal asthma has been reported to increase the risk of preeclampsia, preterm deliveries, and lower-birth-weight infants, but the mechanisms of this effect are not defined. We sought to evaluate the relationship between the use of contemporary asthma medications and adverse perinatal outcomes. Asthmatic patients were recruited from the 16 centers of the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network from December 1994 through February 2000. Gestational medication use was determined on the basis of patient history at enrollment and at monthly visits during pregnancy. Perinatal data were obtained at postpartum chart reviews. Perinatal outcome variables included gestational hypertension, preterm births, low-birth-weight infants, small-for-gestational-age infants, and major malformations. The final cohort included 2123 asthmatic participants. No significant relationships were found between the use of inhaled beta-agonists (n=1828), inhaled corticosteroids (n=722), or theophylline (n=273) and adverse perinatal outcomes. After adjusting for demographic and asthma severity covariates, oral corticosteroid use was significantly associated with both preterm birth at less than 37 weeks' gestation (odds ratio, 1.54; 95% CI, 1.02-2.33) and low birth weight of less than 2500 g (odds ratio, 1.80; 95% CI, 1.13-2.88). Use of inhaled beta-agonists, inhaled steroids, and theophylline do not appear to increase perinatal risks in pregnant asthmatic women. The mechanism of the association between maternal oral corticosteroid use and prematurity remains to be determined.

Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth

Background Inhaled steroids are recommended for the treatment of persistent asthma during pregnancy, but their potential effects on intrauterine growth have been inadequately evaluated. Objective The purpose of this study was to evaluate the association between maternal use of specific inhaled steroids and inhaled steroid dose during pregnancy and the incidence of infants who are small for gestational age (SGA) and mean birth weight. Methods Pregnant asthmatic women being treated with inhaled steroids were enrolled in the study before delivery by their managing allergists. Information regarding the specific inhaled steroid and daily dose used, requirement for oral steroids, occurrence of acute asthmatic episodes, maternal race, birth weight, gestational age, and congenital malformations was obtained for each patient. SGA was defined through use of a published normative sample of American births. Results A total of 474 women were enrolled in the study; of the 451 enrolled participants whose pregnancy ended in a singleton live birth, 396 (88%) completed the study. The incidence of infants with low birth weight, preterm births, and congenital malformations in this cohort was not greater than expected in the general population. The incidence of SGA was 7.1% (95% CI, 5.0% to 10.1%). No significant relationships between specific inhaled steroid or dose of inhaled steroid used and either SGA or mean birth weight were observed. Conclusion These data suggest that the use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth and supports the recommendation that inhaled steroids should be used in the management of persistent asthma during pregnancy.

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.

OUTCOMES OF PREGNANCY IN ASTHMATIC WOMEN

Gestational asthma may be associated with maternal, fetal, or neonatal mortality. Some studies suggest an increased risk of chronic hypertension, pre-eclampsia, antepartum bleeding, preterm labor, preterm birth, and cesarean delivery in pregnant asthmatic women compared with pregnant nonasthmatic women. Moreover, some studies suggest that infants of asthmatic mothers may be at increased risk compared with control infants for lower birth weight caused by intrauterine growth retardation or prematurity as well as TTN and neonatal hyperbilirubinemia. In addition, one study has reported an increased risk of congenital malformations in the offspring of asthmatic mothers. The mechanisms of these observations are not known for certain; however, the available data suggest that optimal control of asthma during pregnancy should at least reduce the risk of maternal mortality and fetal mortality associated with severe gestational asthma, as well as decrease the risk of intrauterine growth retardation. Although the data suggest that oral corticosteroids might increase the risks of pre-eclampsia, lower birth weight, and oral clefts, their benefits would still out-weigh their risks if definitely indicated for the treatment of severe gestational asthma. Finally, the association between some adverse pregnancy outcomes, such as pre-eclampsia and preterm labor or delivery, may be related to common pathogenetic factors that underlie both asthma and these perinatal complications. Further studies are necessary to clarify the magnitudes and exact mechanisms of these potential increased perinatal risks in the pregnancies of asthmatic women.

Influence of Asthma in Pregnancy on Labor and the Newborn

Asthma in pregnancy has been associated with maternal and fetal morbidity and mortality. This study examines the relations of asthma in pregnancy, its severity and its treatment to the labor process, maternal and fetal parameters. Hundred and one consecutive asthmatic women, who gave birth to single babies between November 1993 and November 1994 at the Soroka Medical Center were studied. A group of 77 nonasthmatic women, matched for age and ethnic origin, who gave birth to single babies during the same period served as controls. A larger percentage of asthmatic women suffered from respiratory and urinary tract infections than in the control group (p < 0.001). Severe asthma was associated with a higher rate of infections than milder asthma (p = 0.01). The incidence of smoking was higher among asthmatic women than among controls (p = 0.037). No association was found between socioeconomic status and smoking or infections. No association was found between maternal asthma or maternal use of corticosteroids and the following: maternal hypertension, maternal diabetes, low birth weight (<2,500 g), preterm delivery (<37 weeks), adequacy of weight to gestational age and Apgar scores. Three infants with congenital heart defects were born to asthmatic mothers. When the presentation of the fetus was not cephalic, all the asthmatic women were delivered by cesarean section, versus only 60% in the control group (p = 0.08). Labor was induced with oxytocin more often in the asthma group than in the control group (p = 0.07). We conclude that the labor and neonatal outcome in pregnant asthmatic women treated medically is good, even when asthma is severe and when the patient is treated with corticosteroids. There is, however, a relation between asthma in pregnancy, especially if severe, and predisposition to infections.

Asthma in pregnant women should be treated aggressively

Asthma in pregnant women should be treated aggressively

Perinatal Outcomes in the Pregnancies of Asthmatic Women: A Prospective Controlled Analysis

Prior studies have found an increased incidence of adverse perinatal outcomes of pregnancies in asthmatic mothers, but these studies have been poorly controlled for asthma therapy and other confounding factors. The purpose of this study was to assess perinatal outcomes in actively managed pregnant asthmatic women as compared with matched nonasthmatic controls. Using an inception cohort design, we studied a volunteer sample of 486 pregnant (< 28 wk) women with documented asthma and 486 pregnant nonasthmatic controls with normal pulmonary function. Cases and controls were matched for age, smoking status, parity, and year of delivery. Asthma was managed with step therapy to prevent acute asthmatic episodes and asthma symptoms that interfered with sleep or normal activity. Chronic hypertension was significantly more common (p = 0.007) in asthmatic subjects (3.7%) than in matched controls (1.0%). However, no significant differences in incidences of preeclampsia, perinatal mortality, preterm births, low-birth-weight infants, intrauterine growth retardation, or congenital malformations were observed in the pregnancies of the asthmatic women as compared with the matched controls. Trends were observed toward relationships between more severe asthma requiring emergency therapy or corticosteroids and increased incidences of preeclampsia and low-birth-weight infants, but these associations were not statistically significant. These data suggest that the overall perinatal prognosis for women with actively managed asthma during pregnancy is comparable to that for the nonasthmatic population.

Placental transfer of theophylline in an in vitro closed perfusion system of human placenta isolated lobule.

Theophylline (TH) is a methylated xanthine widely used in the treatment of asthmatic pregnant women. Because of the scant available information on the transplacental profile, the time course of TH transfer was studied by an in vitro human placental perfusion. 6 placentas were perfused with Earle's enriched bicarbonate buffer for 180 min using recirculating maternal and fetal circuits. The physiological and biochemical properties of the tissue were well maintained. TH data were compared to those of antipyrine (AP), an usual marker in placental perfusions. The disappearance of TH from the maternal circuit was studied after administration of 15 mg/l in maternal perfusate. TH appeared in the fetal circuit within 5 min. Equilibrium was achieved in both circuits. TH fetomaternal mass ratio became constant (FMM = 0.45 +/- 0.01) after 80 min of perfusion and maternal to fetal clearance was 2.59 +/- 0.24 ml/min. About 16% of TH maternal dose was recovered in the tissue, while 18% appeared in fetal circulation. TH recovery was 89 +/- 9%. On the basis of our results, similar concentrations could be predicted in mother and fetus after maternal TH intake. The TH transfer profile is consistent with in vivo values reported in humans and animals at delivery.

Severity of asthma and perinatal outcome

OBJECTIVE: Our objective was to determine the impact of asthma and its severity, as determined by medication requirements, on perinatal outcome. STUDY DESIGN: A case-controlled study was conducted. Among 30,940 live births at Long Beach Memorial Medical Center Women's Hospital, 183 deliveries occurred between Jan. 1, 1985, and Dec. 31, 1990, that were coded for the diagnosis of asthma. Eighty-one that required the chronic use of medications to control their disease were identified. Thirty-one patients were steroid dependent and 50 were non-steroid-medication dependent. A control group was randomly selected (excluding maternal transports), and selected perinatal variables were compared between groups. RESULTS: When compared with controls, steroid-dependent asthmatics were at significantly increased risk for gestational (1.5% vs 12.9%) and insulin-requiring diabetes (0% vs 9.7%). Preterm delivery and preterm premature ruptured membranes occurred significantly more often in both asthmatic groups. Overall cesarean section rate was significantly increased in the non-steroid-medication-dependent asthmatic group when compared with controls (56.0% vs 30.0%). Delivery by primary cesarean section was significantly more common in the steroid-dependent group (38.7% vs 19.2%), and a strong trend was noted among the non-steroid-medication-dependent patients (34.0% vs 19.2%). Cesarean delivery for fetal distress was also more common in these two asthmatic groups. Neonates born to both groups of asthmatic pregnant women were significantly more likely to be of birth weight <2500 gm but did not have an increased frequency of intrauterine growth restriction. No significant differences in low 5-minute Apgar scores were found; however, neonates born to both steroid-dependent and non-steroid-medication-dependent asthmatics were significantly more likely to be admitted to the neonatal intensive care unit (39.0% and 22.0% vs 7.7%). Preterm delivery and low birth weight were complications observed significantly more often in the steroid-dependent asthma group when compared with the non-steroid-medication -dependent group (54.8% vs 14.0% and 45.2% vs 14.0%). CONCLUSIONS: Perinatal outcome is compromised in the pregnancy complicated by chronic medication-dependent asthma. The extent is variable and is associated with disease severity, as measured by medication requirements. ( Am J Obstet Gynecol 1992;167:963–7.)

Increased Transient Tachypnea of the Newborn in Infants of Asthmatic Mothers

To compare the incidence of transient tachypnea of the newborn (TTN) in infants of asthmatic vs nonasthmatic mothers. Case-control analysis. Group model health maintenance organization. A volunteer sample of 294 pregnant asthmatic women and 294 pregnant nonasthmatic women with normal pulmonary function test results, matched on the basis of age and smoking status. All subjects entered the study before their third trimester of pregnancy. Subjects with multiple gestations and abortions (less than 20 weeks' gestation) were excluded. Asthma was treated in the allergy department. Routine obstetric, neonatal, and pediatric care was provided to all patients by staff physicians. Transient tachypnea occurred in 11 infants (3.7%) of asthmatic women and in one control infant (0.3%). There were no significant differences between asthmatic and matched control subjects in previously defined TTN risk factors, such as the occurrence of longer labors, failure to progress, cesarean sections, premature births, male sex, Apgar scores of less than 7 at 1 minute, or birth weight greater than 4 kg. Although infants of asthmatic mothers were more likely to exhibit wheezing by age 15 months compared with control infants (12.0% vs 3.2%), none of the infants with TTN manifested wheezing by age 15 months. No relationships could be identified in the asthmatic cohort between the occurrence of TTN and asthma severity or medication use (during the pregnancy in general or during labor and delivery in particular). Although the mechanism is uncertain, maternal asthma appears to increase the risk of infant TTN.

Intrauterine Growth Is Related to Gestational Pulmonary Function in Pregnant Asthmatic Women

Asthmatic mothers have been reported to deliver infants of lower mean birth weight than nonasthmatic mothers. This study examined the relationship between intrauterine growth and serial gestational spirometry in 352 pregnant asthmatic women who were prospectively treated and observed during pregnancy. A small (r = 0.11) but significant (p less than 0.04) direct correlation was demonstrated between infant birth weight and individual mean percent predicted FEV1 during pregnancy. In addition, lower maternal mean FEV1 during pregnancy was associated with increased incidences of birth weight in the lower quartile of the infant population (p = 0.002) and ponderal indices less than 2.2 (suggestive of asymmetric intrauterine growth retardation) (p less than 0.05), but not with increased incidences of preterm (less than 38 weeks) or low birth weight (less than 2,500 g) infants. Although lower mean birth weight occurred in infants of smoking compared with nonsmoking asthmatic mothers (p less than 0.02), the relationships of lower FEV1 to birth weight in the lower quartile of the population (odds ratio 3.0, p = 0.002) and ponderal indices less than 2.2 (odds ratio 2.8, p less than 0.05) were shown by multivariate analysis to be above and beyond the influence of smoking and also independent of the effects of age, parity, acute asthmatic episodes, and asthma medications. These data support the hypothesis that lower maternal gestational FEV1 during pregnancy is related to intrauterine growth retardation and suggest that the goals of gestational asthma therapy should include optimization of pulmonary function in addition to achievement of symptomatic control.

Metabolism and distribution of labeled theophylline in the pregnant rat. Impairment of theophylline metabolism by pregnancy and absence of a blood-brain barrier in the fetus.

Summary: Theophylline was shown to cross the placenta and to be distributed after 1 h among the organs of the fetus and the pregnant rat except for the brain. Lower radioactivity was found in the central nervous system of the pregnant rat compared to the other organs and particularly the brain of the fetus. The blood-brain barrier was observed for theophylline in the adult rat. The degree of exposure of the fetal brain is shown to be twice that of the adult brain. The total absence of a blood-brain barrier for the fetus is thus demonstrated. A ratio of brain to blood theophylline concentration of 0.40 and 0.87 was found respectively for the pregnant rat and the fetus. The presence of a blood-brain barrier observed in the rat cannot be extrapolated to the human. Either the absence or a less efficient blood-brain barrier in the human fetus and neonate has to be taken into consideration. After theophylline administration to pregnant asthmatic women, some of the neonates displayed clinical symptoms that may have been related to placental transfer of theophylline (7, 37).The ability of rat fetus to methylate theophylline into caffeine is demonstrated. Traces of caffeine are produced in utero that may be explained by the absence of theophylline accumulation in the fetus.Urinalysis of the metabolites showed that unchanged theophylline amounted to 73 ± 6% of total urine radioactivity in the pregnant rat as compared to 35 ± 3% in the non-pregnant animal. This impairment of theophylline metabolism in late pregnancy is explained by the decreased formation of 1,3-dimethyluric acid (−68%). The production of 1-methyluric acid was less affected (−30%). Modification of theophylline metabolism during human pregnancy has never been studied. Although 1,3-dimethyluric is the most important theophylline metabolite both in the rat and man, there are such important species differences in the quantitative metabolic pathways that it is important to show whether or not the results obtained from rat studies can be extrapolated to the human.Speculation: In the human, the exposure of the fetus to impaired theophylline metabolism during pregnancy or the absence of a blood-brain barrier could explain clinical symptoms of neurotoxia observed in the neonate when theophylline was administered to pregnant women.