title: In utero exposure to β-2-adrenergic receptor agonist and attention-deficit/hyperactivity disorder in children.
abstract: 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.
authors.affiliation: Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.affiliation: Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Miao
authors.affiliation: Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Christensen
authors.affiliation: National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.|Centre for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.|Hospital of Telemark, Kragerø, Norway.
authors.forename: Søren
authors.initials: S
authors.lastname: Dalsgaard
authors.affiliation: Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, China. yuanwei11@yahoo.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Alle 43-45, 8200, Aarhus N, Denmark.
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
mesh_terms: D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects*; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology; D012306:Risk; D012307:Risk Factors; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists
keywords: Asthma; Attention-deficit/hyperactivity disorder; Cohort study; Prenatal exposure; β-2-Adrenergic receptor agonist