近日，英国利物浦大学Shakila Thangaratinam团队研究了妊娠期母体使用乙酰氨基酚（扑热息痛）与后代患自闭症谱系障碍和注意力缺陷/多动障碍的风险的关联。相关论文于2025年11月10日发表在《英国医学杂志》上。

为了评估孕妇在怀孕期间使用扑热息痛（对乙酰氨基酚）和后代患自闭症谱系障碍（简称自闭症）和注意缺陷/多动障碍（ADHD）风险的证据的质量、偏差和有效性，研究组进行了一项系统评价的总括性评价。数据来源为Medline、Embase、PsycINFO、Cochrane系统评价数据库，以及灰色文献、Epistemonikos和纳入研究的参考文献列表（起始至2025年9月30日）。

纳入系统评价随机试验和队列、病例对照或横断面研究，这些研究均报告了母亲在怀孕期间使用扑热息痛和后代诊断为自闭症或ADHD。研究组分析了综述中纳入的主要研究细节，包括对关键混杂因素（母体特征、使用扑热息痛的适应症和家族因素）和未测量混杂因素的调整以及结果的确定。

9篇综述（40项研究）报道了后代的自闭症（6项研究）和多动症（17项研究）。4篇综述进行了荟萃分析。综述中包括的主要研究的重叠非常高（校正覆盖面积23%）。回顾报告了母亲对乙酰氨基酚摄入量与后代的自闭症或ADHD或两者之间可能存在很强的联系。9篇综述中有7篇建议在解释研究结果时要谨慎，因为纳入的研究存在潜在的偏倚和混淆风险。根据AMSTAR 2（评估系统评价的测量工具）标准，对评价结果的置信度较低（2个评价）至极低（7个评价）。

只有一篇综述（n=2）纳入了报告后代自闭症和多动症的研究，这些研究通过兄弟姐妹对照分析适当地调整了家族因素和未测量的混杂因素。在这两项研究中，在全队列分析中观察到的后代患自闭症（1项研究，风险比1.05,95%可信区间1.02 ~ 1.08）和ADHD（2项研究，风险比1.07、1.05 ~ 1.10和2.02、1.17 ~ 3.25）的风险增加，在兄弟姐妹对照分析中没有出现自闭症（0.98、0.93 ~ 1.04）和ADHD（0.98、0.94 ~ 1.02和1.06、0.51 ~ 2.05）的风险增加。

研究结果表明，目前尚无证据表明孕妇妊娠期间使用扑热息痛与后代自闭症或ADHD之间存在明显联系。

附：英文原文

Title: Maternal paracetamol (acetaminophen) use during pregnancy and risk of autism spectrum disorder and attention deficit/hyperactivity disorder in offspring: umbrella review of systematic reviews

Author: Jameela Sheikh, John Allotey, Soha Sobhy, Maria Nieves Plana, Hilario Martinez-Barros, Harshitha Naidu, Fatima Junaid, Reecha Sofat, Ben W Mol, Louise C Kenny, Melissa Gladstone, Helena Teede, Javier Zamora, Shakila Thangaratinam

Issue&Volume: 2025/11/10

Abstract:

Objective To assess the quality, biases, and validity of evidence on maternal paracetamol (acetaminophen) use during pregnancy and the risk of autism spectrum disorder (referred to as autism) and attention deficit/hyperactivity disorder (ADHD) in offspring.

Design Umbrella review of systematic reviews.

Data sources Medline, Embase, PsycINFO, and the Cochrane Database of Systematic Reviews, along with grey literature, Epistemonikos, and the reference lists of included studies (inception to 30 September 2025).

Inclusion criteria Systematic reviews of randomised trials and cohort, case-control, or cross sectional studies that reported maternal paracetamol use during pregnancy and the diagnosis of autism or ADHD in offspring. Details of the primary studies included in the reviews are reported, including adjustments for key confounders (maternal characteristics, indication for paracetamol use, and familial factors) and unmeasured confounders and ascertainment of outcomes.

Results Nine reviews (40 studies) reporting on autism (six studies) and ADHD (17 studies) in offspring were included. Four reviews undertook meta-analysis. The overlap of primary studies included in the reviews was very high (corrected covered area 23%). The reviews reported a possible to strong association between maternal paracetamol intake and autism or ADHD or both in offspring. Seven of the nine reviews advised caution when interpreting the findings owing to the potential risk of bias and confounding in the included studies. Confidence in the findings of the reviews was low (two reviews) to critically low (seven reviews) based on the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews) criteria. Only one review included studies (n=2) reporting autism and ADHD in offspring that appropriately adjusted for familial factors and unmeasured confounding through sibling controlled analyses. In both studies, the increased risk of autism in offspring (one study, hazard ratio 1.05, 95% confidence interval 1.02 to 1.08) and ADHD (two studies, 1.07, 1.05 to 1.10 and 2.02, 1.17 to 3.25 ) observed in the whole cohort analyses did not persist in sibling controlled analyses for autism (0.98, 0.93 to 1.04) and ADHD (0.98, 0.94 to 1.02 and 1.06, 0.51 to 2.05).

Conclusion Existing evidence does not clearly link maternal paracetamol use during pregnancy with autism or ADHD in offspring.

DOI: 10.1136/bmj-2025-088141

Source: https://www.bmj.com/content/391/bmj-2025-088141