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The management of asthma during pregnancy
10.1
Introduction
Asthma is one of the most common potentially serious medical problems to complicate pregnancy, and may adversely affect both maternal quality of life and perinatal outcomes. Optimal management of asthma during pregnancy (MAP) is thus important for both mother and baby. While the management of asthma in pregnancy relies on guidelines that were based on studies of nonpregnant populations, special considerations regarding the safety of medications are required.
10.2
Effect of pregnancy on the course of asthma
The prevalence of asthma during pregnancy is estimated to be 5%–8% based on US Health surveys [ ]. The prevalence of asthma also appears to be increasing in child-bearing–aged women. An analysis of US Health plans between 2001 and 07 shows that the prevalence was 5.5% in 2001 and 7.8% in 2007 [ ].
Since the prevalence of asthma is increasing in child-bearing–aged women, it is important to understand how to provide adequate treatment of asthma during pregnancy.
Asthma course may worsen, improve, or remain unchanged during pregnancy, and the overall data suggest that these various courses occur with approximately equal frequency.
In a large prospective study of 1739 pregnant asthmatic women, severity classification (based on symptoms, pulmonary function, and medication use) worsened in 30% and improved in 23% of patients during pregnancy [ ]. Asthma also appears to be more likely to be more severe or to worsen during pregnancy in women with more severe asthma before becoming pregnant [ ].
In a recent report from US health care claims databases, between 2011 and 2015, about 19% had severe asthma [ ]. 28% of pregnant women with asthma who have public insurance have uncontrolled asthma during pregnancy. Supporting this finding are results of a cohort of inner-city pregnant women who experienced severe prenatal asthma exacerbation. The authors found that pregnant asthmatics in this cohort had a higher prevalence of long acting beta-agonist/inhaled corticosteroid and leukotriene modifier prescriptions. They also had a higher prevalence of cigarette smoking and upper respiratory infections [ ].
The course of asthma may vary by stage of pregnancy. The first trimester is generally well tolerated in asthmatics with infrequent acute episodes. Increased symptoms and more frequent exacerbations have been reported to occur between weeks 17 and 36 of gestation. In contrast, asthmatic women in general tend to experience fewer symptoms and less frequent asthma exacerbations during weeks 37–40 of pregnancy than during any earlier gestational period [ ].
In a prospective study of 50 enrolled women in the MAP program, 13 women had a total of 16 exacerbations in the year followed. Having more pronounced airway hyperresponsiveness and nonatopic state appeared to characterize these women as having a higher risk of exacerbations during pregnancy [ ].
The mechanisms responsible for the altered asthma course during pregnancy are unknown. The myriad of pregnancy-associated changes in levels of sex hormones, cortisol, and prostaglandins may contribute to changes in asthma course during pregnancy. In addition, exposure to fetal antigens, leading to alterations in immune function, may predispose some pregnant asthmatics to worsening asthma [ ]. Even fetal sex may play a role, with some data showing increased severity of symptoms in pregnancies with a female fetus [ ].
There are additional factors that may contribute to the clinical course of asthma during pregnancy. Pregnancy may be a source of stress for many women, and this stress can aggravate asthma. Adherence to therapy can change during pregnancy with a corresponding change in asthma control. Most commonly observed is decreased adherence as a result of a mother's concerns about the safety of medications for the fetus. One study found that women with asthma significantly decreased their asthma medication use from 5 to 13 weeks of pregnancy. During the first trimester, there was a 23% decline in inhaled corticosteroid prescriptions, a 13% decline in short-acting beta-agonist prescriptions, and a 54% decline in rescue corticosteroid prescriptions [ ].
Physician reluctance to treat may also affect the severity of asthma during pregnancy. A recent study found that less than 40% of women who classified themselves as “poorly controlled” reported use of a controller medication during pregnancy [ ]. Another study identified 51 pregnant women and 500 nonpregnant women presenting to the emergency department with acute asthma. Although asthma severity appeared to be similar in the two groups based on peak flow rates, pregnant women were significantly less likely to be discharged on oral steroids (38% vs. 64%). Presumably related to this undertreatment, pregnant women were three times more likely than nonpregnant women to report an ongoing exacerbation 2 weeks later [ , ].
More recent reassuring data have come from the Pregnancy Risk Assessment Monitoring System which collected data from 34 US states of over 40, 000 women. The prevalence of counseling on medications safe to take during pregnancy was about 89.2% (95%CI 88.7–89.7). Counseling was more common in women who used prescription medications before pregnancy and who reported having asthma before pregnancy [ ].
Infections during pregnancy can certainly affect the course of gestational asthma. Some degree of decrease in cell-mediated immunity may make the pregnant patient more susceptible to viral infection, and upper respiratory tract infections have been reported to be the most common precipitants of asthma exacerbations during pregnancy [ ]. Sinusitis, a known asthma trigger, has been shown to be six times more common in pregnant compared with nonpregnant women [ ]. In addition, pneumonia has been reported to be greater than five times more common in asthmatic than nonasthmatic women during pregnancy [ ]. A recent study tried to determine whether a diagnosis of upper respiratory infection or sinusitis was more common during pregnancy and whether pregnant women were more likely to receive a prescription for antibiotics. This study did not confirm the prior finding that sinusitis or antibiotic use for upper respiratory infections is increased in pregnancy. The report did find that respiratory comorbidities, such as asthma, increased the risk of antibiotic use during pregnancy [ ].
Obesity has been shown to be an inflammatory state that may play an important role in asthma initiation and control. Obesity during pregnancy has been associated with adverse perinatal outcomes including the following: gestational diabetes, preeclampsia, thromboembolic disorders, postpartum hemorrhage, large for gestational age, fetal death, and congenital anomalies. Higher body mass index (BMI) and gestational weight gain have been associated with an increased risk for asthma exacerbations in both nonpregnant and pregnant women [ ].The mechanisms leading to these outcomes are thought to be due to a heightened inflammatory response [ ]. In a follow-up study of the same group of pregnant asthmatics, asthma treatment was adjusted according to FeNO and symptoms. Authors report the benefits of a FeNO-based management are attenuated among obese mothers and those with excess gestational weight gain [ ].
Population-based studies have shown a relationship between smoking and airway hyperresponsiveness [ , ], implying that smoking is a risk factor for asthma. Asthma exacerbations during pregnancy are more common and more severe in current and former smokers than in never smokers [ ]. The potential for maternal smoking to both increase the risk of uncontrolled asthma and to directly adversely affect pregnancy suggests that discontinuation of smoking should be a high priority goal during pregnancy.
10.3
Effect of asthma on pregnancy
One of the largest controlled studies that have evaluated outcomes of pregnancy described 36,985 women identified as having asthma in the Swedish Medical Birth Registry. These outcomes were compared with the total of 1.32 million births that occurred during the years of the study (1984–95). Significantly increased rates of preeclampsia (OR 1.15), perinatal mortality (OR 1.21), preterm births (OR 1.15), and low birth weight infants (OR 1.21), but not congenital malformations (OR 1.05), were found in pregnancies of asthmatic versus control women [ ]. The risks appeared to be greater in patients with more severe asthma, which was confirmed in a more recent Swedish Medical Birth Registry report [ ]. A metaanalysis, derived from a substantial body of literature spanning several decades and including very large numbers of pregnant women (over 1,000,000 for low birth weight and over 250,000 for preterm labor), indicates that pregnant women with asthma are at a significantly increased risk of a range of adverse perinatal outcomes including low birth weight, small for gestational age, preterm labor and delivery, and preeclampsia [ ].
A recent study based on nationwide Finnish register–based cohort between 1996 and 2012 of over 25,000 pregnant asthmatics found that maternal asthma was associated with perinatal mortality 1.24(95%CI 1.05–1.46), preterm birth 1.18 (1.11–1.25), low birth weight 1.29 (1.21–1.37), fetal growth restriction (SGA) 1.32 (1.24–1.40), and asphyxia 1.09(1.02–1.17) [ ].
Mechanisms postulated to explain the possible increase in perinatal risks in pregnant asthmatic women demonstrated in previous studies have included [ ] hypoxia and other physiologic consequences of poorly controlled asthma [ ], medications used to treat asthma, and [ ] pathogenic or demographic factors associated with asthma but not actually caused by the disease or its treatment, such as abnormal placental function.
Several prospective studies [ ] have shown that the pregnant asthmatic with mild to moderate severity can have excellent maternal and fetal outcomes. In contrast, suboptimal control of asthma or more severe asthma during pregnancy may be associated with increased maternal or fetal risk [ , , ]. A recent prospective cohort study highlighted recurrent uncontrolled asthma as a greater contributor to poor perinatal outcomes than asthma exacerbations [ ].
10.4
Asthma management
The ultimate goal of asthma therapy in pregnancy is maintaining adequate oxygenation of the fetus preventing hypoxic episodes in the mother. The management of asthma can be summarized in four categories: assessment and monitoring, education of patients, control of factors contributing to severity, and pharmacologic therapy.
The first step is assessment of severity (in patients not already on controller medications) or assessment of control (in patients already on controller medications). Severity is assessed in untreated patients based on the frequency of daytime and nighttime symptoms, rescue therapy use, activity limitation, and pulmonary function (ideally spirometry, minimally peak flow rate) ( Table 10.1 ). Based on this, severity assessment controller therapy is initiated. Patients should be monitored monthly for asthma control ( Table 10.2 ), and if not responding adequately to treatment should have their level of treatment adjusted ( Table 10.3 ).
Table 10.1
Classification of asthma severity in pregnant patients a .
| Asthma severity | Symptom frequency | Night time awakening | Interference with normal activity | FEV 1 or peak flow (predicted percentage of personal best) |
|---|---|---|---|---|
| Intermittent | 2 days per week or less | Twice per month or less | None | More than 80% |
| Mild persistent | More than 2 days per week, but not daily | More than twice per month | Minor limitation | More than 80% |
| Moderate persistent | Daily symptoms | More than once per week | Some limitation | 60%–80% |
| Severe persistent | Throughout the day | Four times per week or more | Extremely limited | Less than 60% |
FEV 1 , forced expiratory volume in the first second of expiration.
a Data from Dumbrowski MP, Schatz M. ACOG Committee on Practice Bulletins - Obstetrics. ACOG practice bulletin: clinical management guidelines for obstetrician -gynecologists number 90, February 2008: asthma in pregnancy. Obstet Gynecol 2008; 111:457–464.
Table 10.2
Assessment of asthma control in pregnant women a .
| Variable | Well-controlled asthma | Asthma not well controlled | Very poorly controlled asthma |
|---|---|---|---|
| Frequency of symptoms | ≤2 days/week | >2 days/week | Throughout the day |
| Frequency of night time awakening | ≤2 times/month | 1–3 times/week | ≥4 times/week |
| Interference with normal activity | None | Some | Extreme |
| Use of short-acting β-agonist for symptoms control | ≤2 days/week | >2 days/week | Several times/day |
| FEV 1 or peak flow (% of the predicted or personal best value) | >80 | 60–80 | <60 |
| Exacerbation requiring use of systemic corticosteroid (no.) | 0–1 in the past 12 months | ≥2 in the past 12 months | ≥2 in the past 12 months |
a Data from Schatz M, Dombrowski M. Asthma in pregnancy. N Engl J Med 2009;360:1862–69.
Table 10.3
Steps of asthma therapy during pregnancy a .
| Step | Preferred controller medication | Alternative controller medication |
|---|---|---|
| 1 | None | – |
| 2 | Low dose ICS | LTRA, theophylline |
| 3 | Medium dose ICS | Low dose ICS + either LABA, LTRA or theophylline |
| 4 | Medium dose ICS + LABA | Medium dose ICS + LTRA or theophylline |
| 5 | High dose ICS + LABA | – |
| 6 | High dose ICS + LABA + oral prednisone | – |
ICS , inhaled corticosteroids; LABA , long-acting beta-agonists; LTRA , leukotriene receptor antagonists.
a Data from Schatz M, Dombrowski M. Asthma in pregnancy. N Engl J Med 2009;360:1862–69.
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