产前暴露于母体哮喘和哮喘药物与神经发育结局：179024名儿童的人群队列研究
2026/03/04
摘要
背景：妊娠期哮喘加重会对母婴健康产生不利影响。然而，产前接触哮喘药物本身可能会影响儿童的预后。本研究旨在确定产前暴露于哮喘药物是否与一系列神经发育结果相关。
方法：利用2009年至2016年威尔士活产儿童的相关健康和教育记录构建出生队列，随访长达12年。采用二项分布和logit关联函数的广义估计方程评估特殊教育需要（SEN）及其原因，包括自闭症谱系障碍（ASD）、沟通问题、行为、情感和社交困难、学习困难、身体和医疗困难以及感觉障碍。采用Cox比例风险模型研究注意缺陷多动障碍（ADHD）。
结果：在179024例后代中，11991例（6.7%）的母亲哮喘治疗过，4927例（2.8%）的母亲哮喘未治疗，5265例（2.9%）的母亲服用过哮喘药物而无哮喘记录。有50,955例（28.5%）儿童出现SEN。产前暴露于短效β激动剂（SABA）和吸入皮质类固醇（ICS）后，总体SEN和ADHD的风险更高，但未经治疗的哮喘母亲的后代也更高（SEN aOR 1.14, 95% CI 1.07-1.23; ADHD aHR 1.70, 95% CI 1.42-2.05）。ASD与接受治疗的哮喘相关，但与未接受治疗的哮喘无关，并且与产前药物的关联是SABA作为单一或多种治疗所特有的（aOR 1.20, 95% CI 1.05-1.37）。然而，治疗哮喘与未治疗哮喘的直接比较没有统计学意义。
结论：与总体SEN和ADHD的非特异性关联可能反映了它们与哮喘的关联，并因适应证/严重程度而混淆。与ASD的关联可能反映了SABA的治疗效果或严重程度的混淆。需要进一步的研究来证实或反驳前者，以支持基于证据的孕期哮喘管理。
Prenatal exposure to maternal asthma and asthma medication and neurodevelopmental outcomes: a population cohort study of 179,024 children
Lama A Shakhshir, Sarjit Singh, Jill P Pell, Scott M Nelson, Daniel F Mackay, Claire E Hastie, Logesh R Sivakumar, Michael Fleming
Abstract
Background: Asthma exacerbations during pregnancy can adversely affect maternal and foetal health. However, prenatal exposure to asthma medication may itself impact child outcomes. This study aims to determine whether prenatal exposure to asthma medication was associated with a range of neurodevelopmental outcomes.
Methods: A birth cohort was constructed using linked health and education records of children liveborn in Wales from 2009 to 2016, with up to 12 years follow-up. Generalized estimating equations with a binomial distribution and logit link function were employed to evaluate special educational need (SEN) and its causes, including autism spectrum disorder (ASD), communication problems, behavioural, emotional, and social difficulties, learning difficulties, physical and medical difficulties, and sensory impairment. Cox proportional hazard models were used to investigate attention deficit hyperactivity disorder (ADHD).
Results: Of the 179,024 offspring, 11,991 (6.7%) had mothers with treated asthma, 4927 (2.8%) had mothers with untreated asthma, and 5265 (2.9%) had mothers who took asthma medication without a record of asthma. SEN was recorded in 50,955 (28.5%) children. Risk of overall SEN and ADHD was higher following prenatal exposure to short-acting beta-agonists (SABA) and inhaled corticosteroids (ICS) but also higher in the offspring of mothers with untreated asthma (SEN aOR 1.14, 95% CI 1.07-1.23; ADHD aHR 1.70, 95% CI 1.42-2.05). ASD was associated with treated, but not untreated, asthma and the association with prenatal medication was specific to SABA as mono- or polytherapy (aOR 1.20, 95% CI 1.05-1.37). However, a direct comparison of treated with untreated asthma was not statistically significant.
Conclusions: The non-specific associations with overall SEN and ADHD are likely to reflect their associations with asthma and confounding by indication/severity. The associations with ASD may reflect a treatment effect of SABA or confounding by severity. Further studies are needed to confirm or refute the former, to support evidence-based asthma management during pregnancy.
背景：妊娠期哮喘加重会对母婴健康产生不利影响。然而，产前接触哮喘药物本身可能会影响儿童的预后。本研究旨在确定产前暴露于哮喘药物是否与一系列神经发育结果相关。
方法：利用2009年至2016年威尔士活产儿童的相关健康和教育记录构建出生队列，随访长达12年。采用二项分布和logit关联函数的广义估计方程评估特殊教育需要（SEN）及其原因，包括自闭症谱系障碍（ASD）、沟通问题、行为、情感和社交困难、学习困难、身体和医疗困难以及感觉障碍。采用Cox比例风险模型研究注意缺陷多动障碍（ADHD）。
结果：在179024例后代中，11991例（6.7%）的母亲哮喘治疗过，4927例（2.8%）的母亲哮喘未治疗，5265例（2.9%）的母亲服用过哮喘药物而无哮喘记录。有50,955例（28.5%）儿童出现SEN。产前暴露于短效β激动剂（SABA）和吸入皮质类固醇（ICS）后，总体SEN和ADHD的风险更高，但未经治疗的哮喘母亲的后代也更高（SEN aOR 1.14, 95% CI 1.07-1.23; ADHD aHR 1.70, 95% CI 1.42-2.05）。ASD与接受治疗的哮喘相关，但与未接受治疗的哮喘无关，并且与产前药物的关联是SABA作为单一或多种治疗所特有的（aOR 1.20, 95% CI 1.05-1.37）。然而，治疗哮喘与未治疗哮喘的直接比较没有统计学意义。
结论：与总体SEN和ADHD的非特异性关联可能反映了它们与哮喘的关联，并因适应证/严重程度而混淆。与ASD的关联可能反映了SABA的治疗效果或严重程度的混淆。需要进一步的研究来证实或反驳前者，以支持基于证据的孕期哮喘管理。
（北京朝阳医院呼吸与危重症医学科 顾宪民 摘译 中日友好医院呼吸与危重症医学科 林江涛 审校）
（BMC Med. 2026 Feb 20. doi: 10.1186/s12916-026-04699-x. Online ahead of print.）
（BMC Med. 2026 Feb 20. doi: 10.1186/s12916-026-04699-x. Online ahead of print.）
Prenatal exposure to maternal asthma and asthma medication and neurodevelopmental outcomes: a population cohort study of 179,024 children
Lama A Shakhshir, Sarjit Singh, Jill P Pell, Scott M Nelson, Daniel F Mackay, Claire E Hastie, Logesh R Sivakumar, Michael Fleming
Abstract
Background: Asthma exacerbations during pregnancy can adversely affect maternal and foetal health. However, prenatal exposure to asthma medication may itself impact child outcomes. This study aims to determine whether prenatal exposure to asthma medication was associated with a range of neurodevelopmental outcomes.
Methods: A birth cohort was constructed using linked health and education records of children liveborn in Wales from 2009 to 2016, with up to 12 years follow-up. Generalized estimating equations with a binomial distribution and logit link function were employed to evaluate special educational need (SEN) and its causes, including autism spectrum disorder (ASD), communication problems, behavioural, emotional, and social difficulties, learning difficulties, physical and medical difficulties, and sensory impairment. Cox proportional hazard models were used to investigate attention deficit hyperactivity disorder (ADHD).
Results: Of the 179,024 offspring, 11,991 (6.7%) had mothers with treated asthma, 4927 (2.8%) had mothers with untreated asthma, and 5265 (2.9%) had mothers who took asthma medication without a record of asthma. SEN was recorded in 50,955 (28.5%) children. Risk of overall SEN and ADHD was higher following prenatal exposure to short-acting beta-agonists (SABA) and inhaled corticosteroids (ICS) but also higher in the offspring of mothers with untreated asthma (SEN aOR 1.14, 95% CI 1.07-1.23; ADHD aHR 1.70, 95% CI 1.42-2.05). ASD was associated with treated, but not untreated, asthma and the association with prenatal medication was specific to SABA as mono- or polytherapy (aOR 1.20, 95% CI 1.05-1.37). However, a direct comparison of treated with untreated asthma was not statistically significant.
Conclusions: The non-specific associations with overall SEN and ADHD are likely to reflect their associations with asthma and confounding by indication/severity. The associations with ASD may reflect a treatment effect of SABA or confounding by severity. Further studies are needed to confirm or refute the former, to support evidence-based asthma management during pregnancy.
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肥胖与哮喘：肥胖在整个2型炎症谱中引发并加重哮喘
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度普利尤单抗对中重度哮喘患者黏液负荷的影响：VESTIGE研究
