The 2004 asthma treatment guidelines for pregnant women, issued by the National Asthma Education and Prevention Program in January, meet a great need for guidance in this area. The guidelines, which also include a table on the stepwise approach to managing asthma in pregnancy, are the first to be issued on treating asthma in pregnant women in more than 10 years.
A better understanding of the inflammatory nature of the disease has promoted a major shift in therapy. Anti-inflammatory medications, most notably corticosteroids, and mast cell stabilizers (leukotriene inhibitors) are now the first-line treatments. Theophylline is rarely used today to treat asthma, but the guidelines say that at recommended doses it has proved safe in pregnancy.
The authors of the document, a multidisciplinary expert panel, systematically reviewed available evidence on asthma treatment in pregnancy. Some of the key findings are:
▸ Inhaled corticosteroids can reduce the risk of asthma exacerbations and improve lung function. There is no evidence linking them to increases in congenital malformations or other adverse outcomes. When taken through the inhaled route, systemic exposure is much less than with oral corticosteroids. Budesonide has the most data backing its safety in pregnancy, making it the “preferred inhaled corticosteroid,” the guidelines state. But the document notes that there are no data indicating the other agents are unsafe in pregnancy.
▸ Oral corticosteroids may be necessary for treating women with severe asthma. There are conflicting data on their safety in pregnancy, but they may be warranted in women with severe disease, according to the guidelines. In the general population, there is an association between use of oral corticosteroids in the first trimester and an increased risk for cleft lip and/or palate, compared with nonuse (0.3% vs. 0.1%), but not many asthmatic pregnant women have been included in these studies.
This risk for oral cleft has been shown in animals and in humans. Our Motherisk Program systematically reviewed studies and found a two- to threefold increase in oral cleft (with first-trimester exposure), which probably is not the case for inhaled steroids because the systemic dose is much smaller. Clearly, patients who are prescribed oral corticosteroids in the first trimester should be informed of this risk.
During the second and third trimester, oral steroids cannot cause malformations. But there are studies, which do not include patients with asthma, indicating that systemic exposure to corticosteroids may be associated with some CNS damage in babies. Most of these data were from studies of premature infants whose mothers received corticosteroids to enhance lung maturation.
There is evidence that repeating the dose of corticosteroids more than once may increase the risk of adverse brain outcome in premature babies. Although this evidence is not yet conclusive, it is fair to say that if a woman needs high-dose corticosteroids late in pregnancy, such a possibility should be discussed with her before prescribing these agents.
▸ The short-acting β2-agonist albuterol is the preferred drug in this class for treating acute symptoms, and the available data on the safety of β2-agonists are reassuring, the guidelines say. Albuterol has been studied in many millions of patients worldwide and in thousands of pregnant women, and there is no indication whatsoever that it has any teratogenic effects. Since it is inhaled, systemic exposure is not great.
▸ For women with persistent asthma who are not well controlled on low-dose inhaled corticosteroids, increasing the dose or adding a long-acting β-agonist is recommended, but there are not enough data indicating which approach is preferable, according to the guidelines. It is fair to say that β-agonists have not been shown to be teratogenic, and I agree with the panel that there is no reason to prefer one treatment option over the other.
▸ Cromolyn, used as a preventive treatment, appears to be safe, based on available evidence, the guidelines state.
▸ Leukotriene modifiers, the document notes, have “minimal” data on their use in pregnancy, but there are some reassuring animal data. We at Motherisk are prospectively collecting information on cases of pregnant women exposed to these drugs, and so far, they do not appear to be major teratogens.
I would also add that since asthma is often accompanied by allergy, effective management of allergic symptoms can prevent asthmatic attacks in many cases. H1 blockers are safe in pregnancy.
A copy of the guidelines can be found at www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm