Prenatal maternal infection and risk for autism in offspring: A meta‐analysis

Abstract

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.

Genetic variants associated with cross-disorder and disorder-specific risk for psychiatric disorders are enriched at epigenetically active sites in peripheral lymphoid cells

“…Many aspects of our data are compatible with this concept. For example, our finding that trans-and cis-diagnostic risk variants are enriched at sites epigenetically activated by delayed T cell responses to a wide range of pro-inflammatory cytokine stimuli seems consistent with the epidemiological finding that increased risk of multiple psychiatric disorders is found following a wide range of different infections 12,28,29,64,65 . Atypical T cell phenotypes could conceivably have effects on the brain by at least two broad routes: via stimulus-driven T cell activation and via developmental pathways (Figure 5).…”

Influence of Prenatal Drug Exposure, Maternal Inflammation, and Parental Aging on the Development of Autism Spectrum Disorder

“…Associations between ASD and prenatal infection with specific pathogens, such as rubella and cytomegalovirus, have been repeatedly reported ( 153 ). Meta-analyses revealed a mild but significant increase in the risk of ASD in children of mothers who experienced infection during pregnancy, regardless of the pathogen ( 154 , 155 ). One study estimated that maternal infection accounts for 12–17% of ASD cases ( 155 ).…”

“…Meta-analyses revealed a mild but significant increase in the risk of ASD in children of mothers who experienced infection during pregnancy, regardless of the pathogen ( 154 , 155 ). One study estimated that maternal infection accounts for 12–17% of ASD cases ( 155 ). The risk of ASD appears to correlate with the severity of maternal infection, in which the risk was further elevated when mothers required hospitalization because of the infection ( 154 ).…”

Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder—A Nested Case-Control Study

“…The use of antimicrobial therapy during pregnancy has been associated with various unwanted outcomes in the offspring, including cerebral palsy, epilepsy, immune system alterations, childhood asthma, changes in gut microbiota, obesity, and functional impairments (24). The effect of antimicrobial use during pregnancy on ASD risk is not yet clear: while some studies have reported that the use of antimicrobials during pregnancy is associated with an increased risk of ASD (17,21,(30)(31)(32)(33)(34), other studies did not find such association (35). Therefore, the objective of this study was to investigate the association between the use of antimicrobials during pregnancy and the risk of ASD in the offspring.…”