Maternal bronchodilator use and the risk of orofacial clefts

BACKGROUND: Few epidemiological studies have explored the relationship between orofacial clefts and bronchodilators. We assessed whether mothers who used bronchodilators during early pregnancy were at an increased risk of delivering infants with orofacial clefts. METHODS: We used National Birth Defects Prevention Study case-control data from mothers of 2711 infants with orofacial clefts and 6482 mothers of live born infants without birth defects, delivered during 1997 through 2005. Information on medication use from 3 months before pregnancy through delivery was collected using a standardized interview. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for maternal bronchodilator use during the periconceptional period (1 month before pregnancy through the third month of pregnancy) while controlling for other covariates. RESULTS: We observed an association between maternal bronchodilator use during the periconceptional period and cleft lip only (CLO) (aOR 1.77, 95% CI: 1.08-2.88). The risk of cleft palate only (CPO) (aOR = 1.53, 95% CI: 0.99-2.37) was elevated but was not statistically significant. No association was observed for maternal bronchodilator use and the risk of cleft lip with cleft palate (aOR = 0.78, 95% CI: 0.46-1.31). The most commonly used bronchodilator was albuterol (88.7%). Maternal albuterol use was associated with CLO (aOR = 1.79, 95% CI: 1.07-2.99) and CPO (aOR = 1.65, 95% CI: 1.06-2.58). CONCLUSIONS: We observed a statistically significant association between maternal bronchodilator use during the periconceptional period and the risk of CLO after controlling for other risk factors. It is unclear whether the increased odds ratios observed in this study are due to the bronchodilators, the severity of asthma, or both, or to chance alone. Further studies to disentangle the role of asthma or asthma medications would help clarify these findings.