评价孕期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。
基于全国人群的队列研究和兄弟姐妹分析。
韩国国民健康保险服务母子关联数据库,2008-21.
所有出生在2009年至2020年之间的儿童,随访至2021年,以比较在怀孕或婴儿早期(生命的前六个月)期间有和没有抗生素暴露的儿童。
自闭症谱系障碍,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.兄弟姐妹分析还考虑了未测量的家族因素。
倾向得分匹配后,1961744名儿童被确定用于妊娠分析,1609774名儿童被确定用于早期婴儿期分析。尽管在整个队列中,怀孕期间的抗生素暴露与所有四种神经发育障碍的风险增加有关,在同胞分析中,这些估计值朝向零值衰减(自闭症谱系障碍的风险比1.06,95%置信区间1.01~1.12;智力障碍1.00,0.93~1.07;语言障碍1.05,1.02~1.09;癫痫1.03,0.98~1.08).同样,未观察到婴儿早期抗生素暴露与自闭症谱系障碍之间的关联(风险比1.00,0.96至1.03),智力障碍(1.07,0.98至1.15),兄弟姐妹分析中的语言障碍(1.04、1.00至1.08);然而,观察到癫痫的风险略有增加(1.13,1.09~1.18).在几个亚组和敏感性分析中,结果总体上保持一致,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。
在这项大型队列研究中,怀孕或婴儿早期接触抗生素与自闭症谱系障碍的风险增加无关,智力障碍,或儿童语言障碍。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,值得关注和进一步调查。此外,婴儿期使用抗生素与癫痫有一定的相关性,即使在控制适应症和家族因素之后。给孕妇和婴儿开抗生素时,临床医生应仔细平衡使用的益处和潜在的风险.
To evaluate the association between antibiotic use during pregnancy or early infancy and the risk of neurodevelopmental disorders in children.
Nationwide population based cohort study and sibling analysis.
Korea\'s National Health Insurance Service mother-child linked database, 2008-21.
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).
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.
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.
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.