Asthma continues to be one of the most common chronic conditions complicating pregnancy; approximately 8% of pregnant women in the United States report a current diagnosis. Asthmatic women are at increased risk of adverse birth outcomes and perinatal complications, including spontaneous abortion, preterm delivery, reduced birth weight, preeclampsia, and in selected studies, congenital anomalies. In some cases, these increased risks have been linked to specific medications (for example, oral corticosteroid use is linked with orofacial clefts). But much of the current evidence is also consistent with the interpretation that at least some of the excess risk can be attributed to the underlying severity/inadequate control of maternal asthma.

However, two recently published studies suggest that beta₂-agonists – mainstays of treatment and control of asthma symptoms – may be associated with increased risks of congenital anomalies.

The first, an analysis conducted with data from the National Birth Defects Prevention Study, focused specifically on orofacial clefts as the outcome and bronchodilators as the exposure. Using a case control design, researchers interviewd 2,711 mothers of infants with oral clefts and 6,482 mothers of infants with no malformations in 10 states between 1997 and 2005 about bronchodilator use for asthma during and just before pregnancy. The authors separately evaluated risks for cleft lip alone, cleft lip with cleft palate, and cleft palate alone, as each of these defect categories may have distinct etiologies. Almost 3% (247 women) reported exposure to any bronchodilator in the periconceptional period, with nearly 90% of those exposures limited to the widely used short-acting beta₂-agonist, albuterol.

Significantly increased risks were noted for any bronchodilator use (without an additional anti-inflammatory drug) and cleft lip alone (adjusted odds ratio, 1.77; 95% confidence interval, 1.08-2.88); however, with the addition of an anti-inflammatory drug (four cases), the odds were attenuated and no longer statistically significant. Limiting the analysis to only those reporting use of albuterol, the estimated risks for cleft lip alone (adjusted OR, 1.79; 95% CI, 1.07-2.99) and cleft palate alone (adjusted OR, 1.65; 95% CI, 1.06-2.58) were both significantly elevated. No increased risks were noted for use of any bronchodilator and cleft lip with cleft palate. If these findings represent a causal association, the estimated odds ratios would translate to less than one excess case each of cleft lip alone and cleft palate alone for every 1,000 women using albuterol in the first trimester (Hum. Reprod. 2011;26:3147-54).

Reports of even small increased risks for asthma medications during pregnancy can further deter women from appropriate treatment, with possible unintended risks for both mother and baby.

As the authors pointed out, there was no mechanism in the study to adjust for the contribution of underlying disease severity/asthma symptom control in these mothers. However, the lack of an association between orofacial clefts and bronchodilators among those women who also used an anti-inflammatory drug suggests that perhaps women on polytherapy had more optimum treatment and therefore better control.