Background Cerebral palsy (CP) is the most common physical developmental disability in childhood with a prevalence of 2 to 3 per 1000 live births. beta 2-adrenoreceptor agonist (beta 2AA) are widely used for the treatment of asthma. Maternal use of beta 2AAs may increase the risk of adverse neuro-psychiatric health outcomes in the offspring. No study, however, has evaluated the effect of prenatal exposure to beta 2AAs on the risk of CP. Objective To examine the association between prenatal exposure to beta 2AAs and the risk of childhood cerebral palsy. Methods This population-based cohort study included all live singleton births in Denmark from January 1, 1997 to December 31, 2003. The information on outpatient prescriptions of beta 2AAs was extracted from Danish National Prescription Registry. Children born to mothers who used beta 2AAs from 30 days before pregnancy until delivery were categorized as the exposed. To differentiate the effect of beta 2AAs from the underlying indications, the exposure window was further extended to 2 years before pregnancy and the exposed groups were re-defined to represent different periods of exposure to maternal use of beta 2AAs (use only before pregnancy, use only during pregnancy, and use both before and during pregnancy). Cases of CP were identified from the Danish Cerebral Palsy Register. Logistic regression was used to estimate incidence odds ratio (OR) of CP. Results Among all the 442,278 singletons, 19,616 (4.44%) were exposed to beta 2AAs in utero (from 30 days before pregnancy until delivery). The risk of childhood CP was 0.21% in exposed and 0.19% in unexposed group, yielding an adjusted OR (aOR) 1.12 (95% confidence interval (CI): 0.82, 1.53). When extending the exposure time window to 2 years prior to pregnancy, no overall significant association was observed regardless of the exposure period. However, an increased risk of CP (aOR = 1.41, 95% CI: 0.92, 2.18) for maternal beta 2AAs use during pregnancy was observed in female offspring, especially in those born at term (aOR = 1.65, 95% CI: 1.02, 2.67). This increase was mainly attributed to an increased risk in those born to mothers who used beta 2AAs both before and during pregnancy (aOR = 1.81, 95% CI: 0.99, 3.33). Conclusions We observed an association between maternal beta 2AAs use during pregnancy and an increased risk of CP in female offspring, but we could not rule out confounding by the underlying indications for beta 2AAs.
[1]Fudan Univ, Key Lab Reprod Regulat NPFPC, SIPPR, IRD, Shanghai, Peoples R China;
[2]Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark;
[3]Fudan Univ, Sch Publ Hlth, Shanghai, Peoples R China;
[4]Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
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