本文由小咖机器人翻译整理

期刊来源：JAMA

原文链接：https://doi.org/10.1001/jama.2024.3172

摘要内容如下：

重要性

多项研究表明，怀孕期间使用对乙酰氨基酚（扑热息痛）可能会增加儿童神经发育障碍的风险。如果这是真的，这将对怀孕期间疼痛和发烧的管理产生实质性的影响。

目的

研究怀孕期间使用对乙酰氨基酚与儿童患自闭症、注意力缺陷/多动障碍（ADHD）和智力残疾的风险之间的关系。

设计、设置和参与者

这项采用同胞对照分析的全国性队列研究纳入了瑞典1995年至2019年出生的2480797名儿童的人群样本，随访至2021年12月31日。

曝光

从产前和处方记录中前瞻性记录妊娠期间对乙酰氨基酚的使用。

主要成果和措施

根据《国际疾病分类》第九次修订版和《国际疾病分类》第十次修订版健康登记代码，自闭症、多动症和智力残疾。

结果

总共有185909名儿童（7.49%）在怀孕期间接触了对乙酰氨基酚。在10岁时，未暴露于对乙酰氨基酚的儿童与暴露于对乙酰氨基酚的儿童相比，患自闭症的绝对风险分别为1.33%和1.53%，患多动症的绝对风险分别为2.46%和2.87%，患智力残疾的绝对风险分别为0.70%和0.82%。在没有同胞对照的模型中，妊娠期间使用对乙酰氨基酚与未使用对乙酰氨基酚相比，自闭症风险略微增加（风险比[HR]，1.05[95%CI，1.02-1.08]；10岁时的风险差异[RD]，0.09%[95%CI，-0.01%至0.20%]），ADHD（HR，1.07[95%CI，1.05-1.10]；RD，0.21%[95%CI，0.08%-0.34%]）和智力残疾（HR，1.05[95%CI，1.00-1.10]；RD，0.04%[95%CI，-0.04%至0.12%]）。为了解决未观察到的混杂因素，还分析了匹配的全同胞对。同胞对照分析发现，没有证据表明怀孕期间使用对乙酰氨基酚与自闭症相关（HR，0.98[95%CI，0.93-1.04]；RD，0.02%[95%CI，-0.14%to 0.18%]），ADHD（HR，0.98[95%CI，0.94-1.02]；RD，-0.02%[95%CI，-0.21%至0.15%]），或智力残疾（HR，1.01[95%CI，0.92-1.10]；RD，0%[95%CI，-0.10%至0.13%]）。同样，在同胞对照分析中也没有剂量反应模式的证据。例如，与未使用对乙酰氨基酚的孤独症患者相比，低（<第25个百分位数）、中（第25-75个百分位数）和高（>第75个百分位数）平均每日使用对乙酰氨基酚的患者的HR分别为0.85、0.96和0.88。

结论和相关性

在同胞对照分析中，怀孕期间使用对乙酰氨基酚与儿童患自闭症、多动症或智力残疾的风险无关。这表明在其他模型中观察到的关联可能归因于家族混杂。

英文原文如下：

Abstracts

Importance  Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy.

Objective  To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability.

Design, Setting, and Participants  This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021.

Exposure  Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records.

Main Outcomes and Measures  Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers.

Results  In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, -0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, -0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, -0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, -0.02% [95% CI, -0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, -0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively.

Conclusions and Relevance  Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.

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