In utero exposure to β-2-adrenergic receptor agonist and attention-deficit/hyperactivity disorder in children

Hong Liang, Jianping Chen, Maohua Miao, Jakob Christensen, Søren Dalsgaard, Wei Yuan, Jiong Li

We aimed to examine the association between in utero exposure to β2AA and risk of attention-deficit/hyperactivity disorder (ADHD). We established a cohort of 672,265 children born from 1998 to 2008 in Denmark. Children were categorized as exposed if their mothers had redeemed a prescription of β2AA in pregnancy (from 30 days prior to conception until delivery). We identified children diagnosed with ADHD in the Danish National Hospital Register for the first time after his/her third birthday. Log-linear Poisson regression was used to estimate adjusted incidence rate ratio (aIRR) of ADHD. In total, 25,434 children were born to mothers who had redeemed a β2AA prescription in pregnancy. The exposed children had a 1.31-fold increased risk [aIRR = 1.30, 95% confidence interval (CI):1.20-1.42] of ADHD compared to unexposed children after adjusting for potential confounders. However, when extending the exposure window to 2 years prior to conception until delivery, exposure to maternal use of β2AA only before pregnancy, only during pregnancy, and both before and during pregnancy was associated with elevated risks of ADHD in children, with aIRRs of 1.31 (95% CI 1.22-1.40), 1.38 (95% CI 1.22-1.57), and 1.30 (95% CI 1.16-1.45), respectively. In mothers with a history of asthma, no association was observed between maternal use of β2AA during pregnancy and ADHD in offspring (aIRR = 0.92, 95% CI 0.74-1.15). In utero exposure to β2AA was associated with an increased risk of ADHD in children. However, it is more likely that confounding by indication, the underlying disorders or associated pathological conditions, may explain the association.