The prenatal and early-life periods pose a crucial neurodevelopmental window whereby disruptions to the intestinal microbiota and the developing brain may have adverse impacts. As antibiotics affect the human intestinal microbiome, it follows that early-life antibiotic exposure may be associated with later-life psychiatric or neurocognitive outcomes.

To explore the association between early-life (in utero and early childhood (age 0–2 years)) antibiotic exposure and the subsequent risk of psychiatric and neurocognitive outcomes.

A search was conducted using Medline, PsychINFO and Excerpta Medica databases on 20 November 2023. Risk of bias was assessed using the Newcastle-Ottawa scale, and certainty was assessed using the grading of recommendations, assessment, development and evaluation (GRADE) certainty assessment.

Thirty studies were included (n = 7 047 853 participants). Associations were observed between in utero antibiotic exposure and later development of autism spectrum disorder (ASD) (odds ratio 1.09, 95% CI: 1.02–1.16) and attention-deficit hyperactivity disorder (ADHD) (odds ratio 1.19, 95% CI: 1.11–1.27) and early-childhood exposure and later development of ASD (odds ratio 1.19, 95% CI: 1.01–1.40), ADHD (odds ratio 1.33, 95% CI: 1.20–1.48) and major depressive disorder (MDD) (odds ratio 1.29, 95% CI: 1.04–1.60). However, studies that used sibling control groups showed no significant association between early-life exposure and ASD or ADHD. No studies in MDD used sibling controls. Using the GRADE certainty assessment, all meta-analyses but one were rated very low certainty, largely owing to methodological and statistical heterogeneity.

While there was weak evidence for associations between antibiotic use in early-life and later neurodevelopmental outcomes, these were attenuated in sibling-controlled subgroup analyses. Thus, associations may be explained by genetic and familial confounding, and studies failing to utilise sibling-control groups must be interpreted with caution. PROSPERO ID: CRD42022304128

产前和生命早期是一个重要的神经发育窗口，对肠道微生物群和发育中的大脑的破坏可能会产生不利影响。由于抗生素会影响人类肠道微生物组，因此早期接触抗生素可能与晚年的精神或神经认知结果有关。

探讨早期 （子宫内和幼儿期 （0-2 岁）） 抗生素暴露与随后的精神和神经认知结果风险之间的关联。

于 2023 年 11 月 20 日使用 Medline、PsychINFO 和 Excerpta Medica 数据库进行了检索。使用 Newcastle-Ottawa 量表评估偏倚风险，使用建议分级、评估、开发和评估 （GRADE） 质量评估评估质量。

纳入了 30 项研究 （n = 7 047 853 名参与者）。观察到宫内抗生素暴露与自闭症谱系障碍 （ASD） 的后期发展之间存在关联 （比值比 1.09,95% CI： 1.02-1.16） 和注意力缺陷多动障碍 （ADHD） （比值比 1.19,95% CI：1.11-1.27） 与儿童早期暴露和后期发展 ASD （比值比 1.19,95% CI： 1.01-1.40）、ADHD （比值比 1.33,95% CI： 1.20-1.48）和重度抑郁症 （MDD） （比值比 1.29,95% CI： 1.04-1.60）。然而，使用兄弟姐妹对照组的研究表明，早期暴露与 ASD 或 ADHD 之间没有显着关联。MDD 中没有研究使用同胞对照。使用 GRADE 质量评估，除一项分析外，所有荟萃分析都被评为极低质量，主要是由于方法学和统计学异质性。

虽然早期使用抗生素与以后神经发育结局之间的关联证据较弱，但在兄弟姐妹对照的亚组分析中，这些关联被减弱了。因此，关联可能用遗传和家族混杂来解释，未能利用兄弟姐妹对照组的研究必须谨慎解释。PROSPERO ID： CRD42022304128