OBJECTIVES: The purpose of this study was to investigate associations between use of β-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.
- ASD —
- autism spectrum disorders
- B2AR —
- β-2-adrenergic receptor
- CD —
- conception date
- CI —
- confidence interval
- ICD —
- International Classification of Diseases
- OR —
- odds ratio
However, lead author Nicole B. Gidaya, PhD, Drexel University School of Public Health, Philadelphia, Pennsylvania, warned that any concerns over ASD must be balanced against the risks posed by uncontrolled asthma.
"During an asthma exacerbation in pregnancy, the prenatal maternal stress response may be elevated, which would be harmful during a time when the fetal limbic system is considered to be the most vulnerable to such a stress response, especially before 32 weeks of gestation," Dr Gidaya told Medscape Medical News.
"Consequently, any ASD risk associated with maternal B2AR agonist drug use needs to be balanced against the benefits of indicated medication use by pregnant mothers."...
Regarding the potential risks posed by B2AR agonist use, Dr Gidaya noted: "Additional studies need to replicate this present study before the implications of prenatal B2AR agonist drug exposure through maternal use of these agents for asthma control on ASD risk can be considered when making individual decisions about asthma control in pregnancy."
She added: "Further consideration of the biological mechanisms underlying these exposure effects could also lead to an improved understanding of common etiologic pathways in ASD that, in turn, might then inform potential prevention or treatment strategies that would affect larger number of ASD cases."
Commenting on the findings for Medscape Medical News, Michael Rosanoff, MPH, director of public health at the advocacy organization Autism Speaks, said the current research represents "yet another study that hints at the complexity of autism and the sensitivity of child neurodevelopment during pregnancy.
Paul Wang, MD, a developmental/behavioral pediatrician and senior vice president and head of medical research at Autism Speaks, added that "all drugs have risks, and those risks have to be weighed against the risks of discontinuing the drugs.
"Asthma drugs are no exception. Leaving asthma untreated is dangerous for the mother and for her pregnancy."