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. No additional data available.

中文翻译：

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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、语言障碍和癫痫风险之间的关联：基于人群的队列研究


目的 评估妊娠期或婴儿早期抗生素使用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兄弟姐妹分析。设置韩国国民健康保险服务母子链接数据库，2008-21。参与者 所有在 2009 年至 2020 年期间出生的儿童，均进行随访直至 2021 年，以比较在怀孕或婴儿早期（生命的前六个月）期间接触或未接触抗生素的儿童。主要结果衡量儿童自闭症谱系障碍、智力障碍、语言障碍和癫痫。基于许多潜在混杂因素进行 1:1 倾向评分匹配后，使用 Cox 比例风险模型估计置信区间为 95% 的风险比。兄弟姐妹分析还考虑了未测量的家庭因素。结果倾向评分匹配后，共筛选出1 961 744名儿童进行妊娠分析，1 609 774名儿童进行婴儿早期分析。尽管怀孕期间接触抗生素与整个队列中所有四种神经发育障碍的风险增加相关，但这些估计值在兄弟姐妹分析中被减弱为零（自闭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；癫痫 1.03，0.98 至 1.08）。同样，在兄弟姐妹分析中，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）之间的关联。 ;然而，观察到癫痫风险略有增加（1.13，1.09 至 1.18）。除了在生命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之外，几个亚组和敏感性分析的结果总体保持一致。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，例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研究。此外，即使在控制了适应症和家族因素之后，婴儿期抗生素的使用与癫痫也有一定的相关性。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的益处和潜在风险。没有其他可用数据。