本文由小咖机器人翻译整理

期刊来源：BMJ

原文链接：https://doi.org/10.1136/bmj-2023-076885

摘要内容如下：

客观

评估怀孕期间或婴儿早期使用抗生素与儿童神经发育障碍风险之间的关系。

设计

基于全国人口的队列研究和同胞分析。

设置

韩国国家健康保险服务母子链接数据库，2008-21。

参与者

2009年至2020年出生的所有儿童，随访至2021年，以比较在怀孕期间或婴儿早期（出生后前六个月）接触抗生素和未接触抗生素的儿童。

主要成果和措施

孤独症谱系障碍、智力障碍、语言障碍、儿童癫痫。在基于许多潜在混杂因素的1:1倾向评分匹配后，使用Cox比例风险模型估计具有95%置信区间的风险比。同胞分析还解释了未测量的家族因素。

结果

在倾向评分匹配后，1961744名儿童被确定用于妊娠分析，1609774名儿童被确定用于婴儿早期分析。尽管在整个队列中，妊娠期间抗生素暴露与所有四种神经发育障碍的风险增加相关，但在同胞分析中，这些估计值减弱为零（孤独症谱系障碍的风险比为1.06，95%置信区间为1.01至1.12；智力障碍1.00，0.93至1.07；语言障碍1.05，1.02至1.09；和癫痫（1.03，0.98至1.08）。同样，在同胞分析中，未观察到婴儿早期抗生素暴露与自闭症谱系障碍（风险比1.00，0.96至1.03）、智力障碍（1.07，0.98至1.15）和语言障碍（1.04，1.00至1.08）之间存在关联。然而，观察到癫痫风险略有增加（1.13，1.09至1.18）。除了在早期使用抗生素的儿童和使用抗生素超过15天的儿童中观察到的风险略有升高外，几个亚组和敏感性分析的结果总体上保持一致。

结论

在这项大型队列研究中，怀孕期间或婴儿早期接触抗生素与儿童自闭症谱系障碍、智力障碍或语言障碍的风险增加无关。然而，在几个亚组中观察到风险升高，如在生命早期使用抗生素的儿童和长期使用抗生素的儿童，这值得关注和进一步调查。此外，即使在控制了适应症和家族因素后，婴儿期使用抗生素也与癫痫有一定的相关性。在给孕妇和婴儿开抗生素处方时，临床医生应仔细权衡使用抗生素的益处和潜在风险。

英文原文如下：

Abstracts

OBJECTIVE  To evaluate the association between antibiotic use during pregnancy or early infancy and the risk of neurodevelopmental disorders in children.

DESIGN  Nationwide population based cohort study and sibling analysis.

SETTING  Korea's National Health Insurance Service mother-child linked database, 2008-21.

PARTICIPANTS  All children live born between 2009 and 2020, followed up until 2021 to compare those with and without antibiotic exposure during pregnancy or early infancy (first six months of life).

MAIN OUTCOMES MEASURES  Autism spectrum disorder, intellectual disorder, language disorder, and epilepsy in children. After 1:1 propensity score matching based on many potential confounders, hazard ratios with 95% confidence interval were estimated using Cox proportional hazard models. A sibling analysis additionally accounted for unmeasured familial factors.

RESULTS  After propensity score matching, 1 961 744 children were identified for the pregnancy analysis and 1 609 774 children were identified for the early infancy analysis. Although antibiotic exposure during pregnancy was associated with increased risks of all four neurodevelopmental disorders in the overall cohort, these estimates were attenuated towards the null in the sibling analyses (hazard ratio for autism spectrum disorder 1.06, 95% confidence interval 1.01 to 1.12; intellectual disorder 1.00, 0.93 to 1.07; language disorder 1.05, 1.02 to 1.09; and epilepsy 1.03, 0.98 to 1.08). Likewise, no association was observed between antibiotic exposure during early infancy and autism spectrum disorder (hazard ratio 1.00, 0.96 to 1.03), intellectual disorder (1.07, 0.98 to 1.15), and language disorder (1.04, 1.00 to 1.08) in the sibling analyses; however, a small increased risk of epilepsy was observed (1.13, 1.09 to 1.18). The results generally remained consistent across several subgroup and sensitivity analyses, except for slightly elevated risks observed among children who used antibiotics during very early life and those who used antibiotics for more than 15 days.

CONCLUSIONS  In this large cohort study, antibiotic exposure during pregnancy or early infancy was not associated with an increased risk of autism spectrum disorder, intellectual disorder, or language disorder in children. However, elevated risks were observed in several subgroups such as children using antibiotics during very early life and those with long term antibiotic use, which warrants attention and further investigation. Moreover, antibiotic use during infancy was modestly associated with epilepsy, even after control for indications and familial factors. When prescribing antibiotics to pregnant women and infants, clinicians should carefully balance the benefits of use against potential risks.

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