Maternal Infection During Pregnancy and Risk of Autism Spectrum Disorders: A Systematic Review and Meta-analysis

Conflicting evidence exists with regard to the relationship between maternal infection during pregnancy and the risk of autism spectrum disorder (ASD) in offspring. The aim of this meta-analysis was to systematically assess this relationship. To identify relevant studies, we conducted systematic searches in PubMed and Embase of scientific articles published through March 2016. Random-effects models were adopted to estimate overall relative risk. A total of 15 studies (2 cohort and 13 case-control studies) involving more than 40,000 ASD cases were included in our meta-analysis. Our results showed that maternal infection during pregnancy was associated with an increased risk of ASD in offspring (OR=1.13, 95% confidence interval (CI): 1.03-1.23), particularly among those requiring hospitalization (OR=1.30, 95% CI: 1.14-1.50). Subgroup analyses suggested that risk may be modulated by the type of infectious agent, time of infectious exposure, and site of infection. These findings indicate that maternal infection during pregnancy increases the risk of ASD in offspring. Possible mechanisms may include direct effects of pathogens and, more indirectly, the effects of inflammatory responses on the developing brain.