Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA.
Division of Child and Adolescent Psychiatry, The New York State Psychiatric Institute, New York, New York, USA.
Autism Res. 2021 Jun;14(6):1296-1316. doi: 10.1002/aur.2499. Epub 2021 Mar 15.
While prenatal maternal infection has received attention as a preventable and treatable risk factor for autism, findings have been inconsistent. This paper presents the results of a meta-analysis to determine whether the weight of the evidence supports such an association. Studies with a categorical diagnosis of autism as the outcome and an assessment of its association with prenatal maternal infection or fever (or the data necessary to compute this association) were included. A total of 36 studies met these criteria. Two independent reviewers extracted data on study design, methods of assessment, type of infectious agent, site of infection, trimester of exposure, definition of autism, and effect size. Analyses demonstrated a statistically significant association of maternal infection/fever with autism in offspring (OR = 1.32; 95% CI = 1.20-1.46). Adjustment for evident publication bias slightly weakened this association. There was little variation in effect sizes across agent or site of infection. Small differences across trimester of exposure were not statistically significant. There was some evidence that recall bias associated with status on the outcome variable leads to differential misclassification of exposure status. Nonetheless, the overall association is only modestly reduced when studies potentially contaminated by such bias are removed. Although causality has not been firmly established, these findings suggest maternal infection during pregnancy confers an increase in risk for autism in offspring. Given the prevalence of this risk factor, it is possible that the incidence of autism would be reduced by 12%-17% if maternal infections could be prevented or safely treated in a timely manner. LAY SUMMARY: This study is a meta-analysis of the association of maternal infection during pregnancy and subsequent autism in offspring. In combining the results from 36 studies of this association we find that a significant relationship is present. The association does not vary much across the types of infections or when they occur during pregnancy. We conclude that the incidence of autism could be substantially reduced if maternal infections could be prevented or safely treated in a timely manner.
虽然产前母体感染已被视为自闭症的可预防和可治疗的风险因素之一，但研究结果并不一致。本文报告了一项荟萃分析的结果，以确定证据的权重是否支持这种关联。研究采用自闭症的分类诊断作为结果，并评估其与产前母体感染或发热的关联（或计算这种关联所需的数据）。共有 36 项研究符合这些标准。两位独立的评审员提取了研究设计、评估方法、感染原类型、感染部位、暴露时间、自闭症定义和效应大小的数据。分析表明，母体感染/发热与后代自闭症之间存在统计学显著关联（OR=1.32；95%CI=1.20-1.46）。对明显的发表偏倚进行调整略微削弱了这种关联。感染原或感染部位对效应大小的影响差异不大。暴露时间的细微差异在统计学上没有显著意义。有一些证据表明，与结局变量状态相关的回忆偏倚导致暴露状态的分类错误存在差异。尽管如此，当去除可能受到此类偏倚影响的研究时，总体关联仅略有减少。虽然因果关系尚未得到确凿确立，但这些发现表明，妊娠期间母体感染会使后代患自闭症的风险增加。鉴于这种风险因素的普遍性，如果能及时预防或安全治疗母体感染，自闭症的发病率可能会降低 12%-17%。
简而言之：这项研究是对妊娠期间母体感染与后代自闭症之间关联的荟萃分析。通过合并 36 项关于这种关联的研究结果，我们发现存在显著的关系。这种关联在感染类型之间或在怀孕期间发生的时间上变化不大。我们得出结论，如果能及时预防或安全治疗母体感染，自闭症的发病率可能会大幅降低。
