In utero Exposure to β-2-Adrenergic Receptor Agonist Drugs and Risk for Autism Spectrum Disorders

OBJECTIVES: The purpose of this study was to investigate associations between use of beta-2-adrenergic receptor (B2AR) agonist drugs during pregnancy and risk for autism spectrum disorders (ASD). METHODS: A case-control study was conducted by using Denmark's health and population registers. Among children born between 1997 and 2006, 5200 cases with ASD admission diagnoses and 52 000 controls without ASD were identified and individually matched on month and year of birth. Conditional logistic regression models were used to estimate odds ratios (OR) and confidence intervals (CI) for any B2AR agonist exposure during pregnancy, preconception, and by trimester. RESULTS: In total, 3.7% of cases and 2.9% of controls were exposed to B2ARs during pregnancy. Use of B2ARs during pregnancy was associated with increased risk of ASD, even after adjustment for maternal asthma and other covariates (OR: 1.3, 95% CI: 1.1-1.5). The elevated risk was observed with use of B2AR during preconception (OR: 1.3, 95% CI: 1.0-1.6), first trimester (OR: 1.3, 95% CI: 1.1-1.5), second trimester (OR: 1.5, 95% CI: 1.1-1.7), and the third trimester (OR: 1.4, 95% CI: 1.1-1.7). There was some evidence that longer B2AR within-pregnancy use was associated with the increased risk. CONCLUSIONS: B2AR agonist exposure during pregnancy may be associated with an increased risk for ASD. If the effect is real, any intervention must be balanced against benefits of indicated medication use by pregnant women.