Prenatal maternal infection and risk for autism in offspring: A meta-analysis. 2021

Nina Tioleco, and Anna E Silberman, and Katharine Stratigos, and Sharmila Banerjee-Basu, and Marisa N Spann, and Agnes H Whitaker, and J Blake Turner
Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA.

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.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011248 Pregnancy Complications Conditions or pathological processes associated with pregnancy. They can occur during or after pregnancy, and range from minor discomforts to serious diseases that require medical interventions. They include diseases in pregnant females, and pregnancies in females with diseases. Adverse Birth Outcomes,Complications, Pregnancy,Adverse Birth Outcome,Birth Outcome, Adverse,Complication, Pregnancy,Outcome, Adverse Birth,Pregnancy Complication
D011297 Prenatal Exposure Delayed Effects The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH. Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000067877 Autism Spectrum Disorder Wide continuum of associated cognitive and neurobehavioral disorders, including, but not limited to, three core-defining features: impairments in socialization, impairments in verbal and nonverbal communication, and restricted and repetitive patterns of behaviors. (from DSM-V) Autistic Spectrum Disorder,Autism Spectrum Disorders,Autistic Spectrum Disorders,Disorder, Autistic Spectrum
D001321 Autistic Disorder A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-V) Autism, Infantile,Kanner's Syndrome,Autism,Autism, Early Infantile,Disorder, Autistic,Disorders, Autistic,Early Infantile Autism,Infantile Autism,Infantile Autism, Early,Kanner Syndrome,Kanners Syndrome
D012307 Risk Factors An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent. Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D015984 Causality The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. Causation,Enabling Factors,Multifactorial Causality,Multiple Causation,Predisposing Factors,Reinforcing Factors,Causalities,Causalities, Multifactorial,Causality, Multifactorial,Causation, Multiple,Causations,Causations, Multiple,Enabling Factor,Factor, Enabling,Factor, Predisposing,Factor, Reinforcing,Factors, Enabling,Factors, Predisposing,Factors, Reinforcing,Multifactorial Causalities,Multiple Causations,Predisposing Factor,Reinforcing Factor

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