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Maternal asthma: Management strategies

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ROLES OF CONTROLLER THERAPY AND RESCUE THERAPY

Inhaled corticosteroids

Inhaled corticosteroids are the mainstay of asthma controller therapy during pregnancy. A meta-analysis of 16 studies showed no increased risk of congenital malformations, cesarean delivery, or stillbirth among mothers who used these agents during pregnancy.20 Because there are more safety data for budesonide, it is currently the preferred inhaled corticosteroid during pregnancy.9 However, if a patient’s asthma is controlled with a different corticosteroid before pregnancy, that agent may be continued during pregnancy, especially if it is thought that switching formulations could adversely affect asthma control.12 This is mainly because current data do not prove that other inhaled corticosteroids are unsafe.

Inhaled beta-agonists

Inhaled beta-agonists, both short-acting and long-acting, are used for rescue therapy. Al­buterol is the preferred short-acting agent for rescue therapy in pregnant women with asthma.12 Meta-analysis has shown no increased risk of major or minor congenital malformations in pregnant patients who use bronchodilators.20 Long-acting beta-agonists typically are used as add-on therapy when asthma cannot be controlled by an inhaled corticosteroid. They should not be used without a controller medication (ie, an inhaled corticosteroid).

Guidelines for rescue therapy are similar to those for nonpregnant asthmatic patients. Although data are limited as to the gestational effects of long-acting beta-agonists (ie, formoterol, salmeterol), it can be assumed that the toxicologic and pharmacologic profiles are similar to those of the short-acting bronchodilators. Thus, the safety of albuterol can be extended potentially to the long-acting beta-agonists.12

Combining controller and rescue therapy

When asthma is not adequately controlled on inhaled corticosteroids, a long-acting beta-agonist can be added or the dose of corticosteroid can be increased. The 2004 NAEPP guidelines stated that based on available literature, there was no clear advantage of one option over the other.12 A study that compared the 2 approaches found no difference in rates of congenital malformations.21

Leukotriene receptor antagonists

There is little in the literature regarding the use of leukotriene receptor antagonists during pregnancy. However, animal safety data are reassuring,12 and human studies have not found a higher risk of major congenital malformations.22,23 Thus, they are an alternative for patients whose asthma has been well controlled on these agents before pregnancy. Montelukast and zafirlukast are in former FDA pregnancy risk factor category B (probably safe) (Table 3). However, 5-lipoxygenase inhibitors such as zileuton are contraindicated based on animal studies showing teratogenicity.24

Omalizumab

Omalizumab, a recombinant anti-immunoglobulin E antibody, can be used for allergic asthma not controlled with inhaled corticosteroids (Table 3). An analysis of the omalizumab pregnancy registry25 found no significant increase in the rate of major congenital malformations, prematurity, or babies small for gestational age in asthmatic women taking omalizumab 8 weeks before conception or during pregnancy vs pregnant asthmatic women not taking omalizumab. However, this drug carries a risk of anaphylaxis and so should not be started during pregnancy.25

Theophylline

Because of potential toxicity, use of theophylline during pregnancy requires careful monitoring to ensure the serum concentration remains between 5 and 12 µg/mL.12 Drug interactions are also common: for example, alcohol may increase the serum concentration of theophylline, and theophylline may increase the toxic effect of formoterol.

Systemic corticosteroids

Pregnant women with asthma that is not well controlled despite the therapies described above may require a daily oral corticosteroid such as prednisone to achieve adequate control. Oral steroids are also a mainstay of treatment of asthma exacerbation.

Although use of corticosteroids in the first trimester was associated with orofacial cleft in infants,12 these studies did not include many women with asthma. In 2011, a nationwide cohort study from Denmark showed no increase in the risk of orofacial cleft with the use of corticosteroids during pregnancy.26

Preeclampsia, low birth weight, and preterm delivery have been described with corticosteroid use in pregnancy. It is not known whether these problems were a result of corticosteroid use or were due to the uncontrolled nature of the underlying condition that led to the steroid use. Since the risk of uncontrolled asthma to mother and fetus outweighs the risk of systemic corticosteroids, these drugs are recommended when indicated for management of maternal asthma.12

ACUTE EXACERBATIONS REQUIRE AGGRESSIVE MANAGEMENT

Based on a systematic review, 20% of pregnant women with asthma require some intervention for an asthma exacerbation during pregnancy, and 5.8% are admitted to the hospital for an exacerbation.11 Exacerbations were associated with a higher risk of low birth weight compared with rates in women without asthma.

Exacerbations are more common late in the second trimester and are unlikely to occur during labor and delivery.2 The incidence of exacerbations increases with the severity of asthma, from 8% in mild asthma, to 47% in moderate asthma, to 65% in severe asthma.27 Risk factors for exacerbations include poor prenatal care, obesity, and lack of appropriate treatment with inhaled corticosteroids.2 The main triggers are viral respiratory infections and noncompliance with inhaled corticosteroid therapy.11

Management of asthma exacerbations in pregnancy

Asthma exacerbations during pregnancy should be managed aggressively (Table 4),12 as the risk to the fetus of hypoxia far outweighs any risk from asthma medications. Close collaboration between the primary care physician and the obstetrician allows closer monitoring of mother and fetus.

The goal oxygen saturation must be above 95%.12 Signs of acute respiratory failure in a pregnant patient include a partial pressure of arterial oxygen less than 70 mm Hg or a partial pressure of carbon dioxide greater than 35 mm Hg.

In a multicenter study comparing nonpregnant and pregnant women visiting the emergency room for asthma exacerbations,28 pregnant women were less likely to be prescribed systemic corticosteroids either in the emergency room or at the time of hospital discharge, and they were also more likely to describe an ongoing exacerbation at 2-week follow-up. However, a recent study showed a significant increase in systemic corticosteroid treatment in the emergency room (51% to 78% across the time periods, odds ratio 3.11, 95% confidence interval 1.27–7.60, P = .01). There was also an increase in steroid treatment at discharge (42% to 63%, odds ratio 2.49, 95% confidence interval 0.97–6.37, P = .054), though the increase was not statistically significant.29 Although emergency room care for pregnant asthmatic women has improved, this group concluded that further improvement is still warranted, as 1 in 3 women is discharged without corticosteroid treatment.

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