Do long-acting beta agonists for asthma cause birth defects?
Or, How to Treat Asthma in Pregnancy
Do long-acting beta agonists cause birth defects when taken by pregnant women? A new study can’t settle the question, but might give women and their doctors more peace of mind when LABAs are necessary to control asthma during pregnancy. Current guidelines for treating asthma during pregnancy advise that for pregnant women whose asthma remains uncontrolled on low-dose inhaled corticosteroids (ICS), treatment should “step up” to either add a long-acting beta-agonist (LABA) or an increased inhaled steroid dose. An observational study in 2011 suggested women taking LABAs during pregnancy had a slightly increased risk for delivering babies with congenital malformations (odds ratio about 1.3-1.4). Short-acting beta agonists like albuterol were not associated with any birth defects. However, the association could easily have been due to increased asthma severity or other related factors, not the LABAs themselves. The same authors recently published a cohort study seeking to elucidate the teratogenic risks of LABAs while better controlling for asthma severity. Rather than measure risk for birth defects associated with any use of LABAs, they compared the incidence of congenital malformations among pregnant women using LABA-ICS with that of women using ICS alone. They matched women in cohorts that estimated asthma severity according to the dosages of inhaled steroids. The odds ratio for congenital malformations associated with LABA use was 1.1 to 1.2 when using this technique, with a wide confidence interval. Authors concluded "The risk of major malformations was similar with a LABA plus ICS combination and ICS monotherapy at higher doses, suggesting that both therapeutic options can be considered during pregnancy." However, there were only about 840 women in the cohorts, reducing the strength of any conclusions. The long-acting beta agonists formoterol and salmeterol are both category C in pregnancy (risk cannot be ruled out) — but so are all inhaled corticosteroids except budesonide (Pulmicort), which is category B (generally considered safe). But any theoretical risk for congenital malformations must be balanced against the very real risk of fetal injury during inadequately treated asthma exacerbations. National guidelines all recommend treating asthma as aggressively as is necessary to prevent significant asthma symptoms that might harm the mother, developing child, or both. The NIH has said, "For patients whose persistent asthma is not well controlled on low doses of inhaled corticosteroids alone, the guidelines recommend either increasing the dose of inhaled corticosteroid or adding another medication — a long-acting beta agonist. The expert panel concluded that data are insufficient to indicate a preference of one option over the other." The American College of Obstetricians and Gynecologists states "it is safer for pregnant women with asthma to be treated with asthma medications than it is for them to have asthma symptoms and exacerbations." ACOG recommended the use of combination products of inhaled steroids with the long-acting beta agonist salmeterol, for asthma uncontrolled by medium-dose corticosteroids alone. The ICS dose should be titrated up as needed to control the asthma. Oral corticosteroids like prednisone should be also be used when necessary. Theophylline and cromolyn are considered safe in the NIH guidelines, and leukotriene receptor antagonists (montelukast/Singulair) have since achieved category B. The leukotriene lipoxygenase inhibitor zileuton is category C and very little data exists on its use in pregnancy. Tiotropium (Spiriva) is also category C; inadequate data existed to assess the risk of anticholinergics at the time of the NIH guideline publication.
S Etonsy et al. Risk of congenital malformations for asthmatic pregnant women using a long-acting β2-agonist and inhaled corticosteroid combination versus higher-dose inhaled corticosteroid monotherapy. J Clin All Immunol Published Online: September 14, 2014
Clinical practice. Asthma in pregnancy. N Engl J Med. 2009 Apr 30;360(18):1862-9.
NIH guidelines for treatment of asthma in pregnancy