In utero exposure to β-2-adrenergic receptor agonist and attention-deficit/hyperactivity disorder in children
Hong Liang1, Jianping Chen1, Maohua Miao1
1Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, 200032, China.
Insights
Maternal use of beta-2 adrenergic agonists (β2AA) during pregnancy was linked to a higher risk of attention-deficit/hyperactivity disorder (ADHD) in children. However, this association may be explained by confounding factors rather than a direct causal link.
Area of Science:
- Perinatal epidemiology
- Neurodevelopmental disorders
- Pharmacological research
Background:
- Maternal medication use during pregnancy is a significant concern for offspring neurodevelopment.
- Beta-2 adrenergic agonists (β2AA) are commonly prescribed for conditions like asthma.
- The potential impact of in utero β2AA exposure on the risk of attention-deficit/hyperactivity disorder (ADHD) requires thorough investigation.
Purpose of the Study:
- To investigate the association between prenatal exposure to beta-2 adrenergic agonists (β2AA) and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring.
- To explore the influence of different exposure windows (during pregnancy, before pregnancy, or both) on ADHD risk.
- To examine potential confounding factors, such as maternal asthma history, in the observed association.
Main Methods:
- A large cohort study was established using Danish national registers, including 672,265 children born between 1998 and 2008.
- Maternal prescription redemption of β2AA during pregnancy defined fetal exposure.
- Log-linear Poisson regression was employed to calculate adjusted incidence rate ratios (aIRRs) for ADHD, controlling for potential confounders.
Main Results:
- Children exposed in utero to β2AA exhibited a 1.31-fold increased risk of ADHD (aIRR=1.30, 95% CI: 1.20-1.42).
- Extended exposure windows, including exposure solely before pregnancy, solely during pregnancy, or both, were associated with elevated ADHD risks (aIRRs ranging from 1.30 to 1.38).
- No significant association between maternal β2AA use during pregnancy and ADHD risk was found in mothers with a history of asthma (aIRR=0.92, 95% CI: 0.74-1.15).
Conclusions:
- In utero exposure to beta-2 adrenergic agonists (β2AA) is associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in children.
- The observed association is likely influenced by confounding by indication, where underlying maternal conditions or related pathologies may contribute to both medication use and offspring ADHD risk.
- Further research is needed to disentangle the direct effects of β2AA from confounding factors in the development of ADHD.
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.
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