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

IntroductionBenzodiazepine (BZD) prescribing rates during pregnancy have risen over the last two decades. There is little research into the potential relationship between in utero exposure to BZD and offspring risk of attention deficit/hyperactivity disorder (ADHD), although there is some evidence of negative neurodevelopmental outcomes. Objectives and ApproachWe used comprehensive linked administrative data to investigate the association between maternal use of prescription BZDs during pregnancy and ADHD in offspring. We included mother-newborn dyads in Manitoba born from 1996-2012, with follow-up through 2017. BZD exposure was defined as 2+ prescriptions between conception and delivery. We matched exposed children to unexposed children to account for differences in characteristics between women who used BZDs during pregnancy versus non-users. Several sensitivity analyses addressed the potential for residual confounding, including a negative control group and a group made entirely of recent users of BZDs. Cox Proportional Hazard Regression Models were used to estimate the risk of ADHD among offspring. ResultsAmong 495 children with at least two BZD exposures throughout pregnancy, 25.4% (n=452) had a diagnosis of ADHD compared with 18.0% (n=68) of children not exposed (adjusted HR 1.91, 95% CI 1.35-2.69). However, the association was unchanged in the negative control group analyses (aHR 1.76, 1.09-2.86), and not significant in the recent users of BZD (aHR 0.91, 0.63-1.30). Mother’s history of ADHD and teen births were also associated with ADHD in offspring. ConclusionsIn a large population-level analysis, in utero exposure to prescription BZDs during pregnancy appeared to increase risk of ADHD. However, sensitivity analyses suggest this relationship was likely due to residual confounding. The power to link data for the whole population and across generations enabled powerful sensitivity analyses that alter the initial inference.

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In Utero Exposure to Ischemic-Hypoxic Conditions and Attention-Deficit/Hyperactivity Disorder

PEDIATRICS ◽

10.1542/peds.2012-1298d ◽

2012 ◽

Vol 131 (1) ◽

pp. X17-X17

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

In Utero ◽

In Utero Exposure ◽

Hyperactivity Disorder ◽

Hypoxic Conditions

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Regional Brain Perfusion before and after Treatment with Methylphenidate According to the MspI Polymorphism of the Alpha-2A Adrenergic Receptor Gene in Children with Attention-Deficit Hyperactivity Disorder

Journal of korean Academy of Child and Adolescent Psychiatry ◽

10.5765/jkacap.2013.24.1.21 ◽

2013 ◽

Vol 24 (1) ◽

pp. 21-27 ◽

Cited By ~ 1

Author(s):

Subin Park ◽

Jeong-Hoon Bae ◽

Jae-Won Kim ◽

Young-Hui Yang ◽

Seungmin Oh ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Adrenergic Receptor ◽

Receptor Gene ◽

Brain Perfusion ◽

Mspi Polymorphism ◽

Hyperactivity Disorder ◽

Regional Brain ◽

Before And After ◽

Adrenergic Receptor Gene

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Long-term risk of epilepsy, cerebral palsy and attention-deficit/hyperactivity disorder in children affected by a threatened abortion in utero

International Journal of Epidemiology ◽

10.1093/ije/dyab069 ◽

2021 ◽

Author(s):

Elena Dudukina ◽

Erzsébet Horváth-Puhó ◽

Henrik Toft Sørensen ◽

Vera Ehrenstein

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Cerebral Palsy ◽

Attention Deficit ◽

Cox Regression ◽

In Utero ◽

Autism Spectrum ◽

Sibling Pairs ◽

Hyperactivity Disorder ◽

Hazard Ratios ◽

Threatened Abortion

Abstract Background The birth of a child affected by a threatened abortion (TAB) in utero is associated with autism spectrum disorder; association with other neurological disorders is unknown. Methods This nationwide registry-based cohort study included singletons live-born in Denmark (1979–2010), followed through 2016. The outcomes were epilepsy, cerebral palsy (CP) and attention-deficit/hyperactivity disorder (ADHD). We used Cox regression to compute hazard ratios (HRs), adjusted for birth year, birth order, parental age, morbidity, medication use and maternal socio-economic factors. To remove time-invariant family-shared confounding, we applied sibling analyses. Results The study population included 1 864 221 singletons live-born in 1979–2010. Among the TAB-affected children (N = 59 134) vs TAB-unaffected children, at the end of follow-up, the cumulative incidence was 2.2% vs 1.6% for epilepsy, 0.4% vs 0.2% for CP and 5.5% vs 4.2% for ADHD (for children born in 1995–2010). The adjusted HRs were 1.25 [95% confidence interval (CI) 1.16–1.34] for epilepsy, 1.42 (95% CI 1.20–1.68) for CP and 1.21 (95% CI 1.14–1.29) for ADHD. In the sibling design, the adjusted HRs were unity for epilepsy (full siblings: 0.96, 95% CI 0.82–1.12; maternal: 1.04, 95% CI 0.90–1.20; paternal: 1.08, 95% CI 0.93–1.25) and ADHD (full: 1.08, 95% CI 0.92–1.27; maternal: 1.04, 95% CI 0.90–1.20; paternal: 1.08, 95% CI 0.93–1.25). For CP, HRs shifted away from unity among sibling pairs (full: 2.92, 95% CI 1.33–6.39; maternal: 2.03, 95% CI 1.15–3.57; paternal: 3.28, 95% CI 1.36–7.91). Conclusions The birth of a child affected by TAB in utero was associated with a greater risk of CP, but not epilepsy or ADHD.

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