Rare Pregnancy Infections Linked to Higher Risk of Autism

Rare infections transmitted from a pregnant woman to her fetus may be associated with substantially higher risks of autism and intellectual disability later in childhood, according to a large Swedish study from Karolinska Institutet published in JAMA Pediatrics.

The researchers examined a group of infections known as TORCH, which includes cytomegalovirus, rubella, toxoplasmosis and herpesvirus infections. Although most infections do not reach the fetus, some pathogens can cross the placenta and cause congenital infections.

The researchers analyzed health and education records of 3.7 million people born in Sweden between 1987 and 2021. Among them, 975 had been diagnosed with a congenital TORCH infection. Participants were followed for up to 30 years, allowing researchers to examine potential links between these infections and later neurodevelopmental and educational outcomes.

Children with a congenital TORCH infection were approximately three times more likely to be diagnosed with autism than children without such an infection. Their risk of intellectual disability was more than seven times higher. For severe to profound intellectual disability, the risk was up to 30 times higher.

Despite these large relative increases, congenital TORCH infections are rare and therefore account for only a small proportion of autism and intellectual disability cases in the overall population.

The researchers estimated that congenital TORCH infections may be associated with about 1.2% of severe intellectual disability cases in Sweden and approximately 0.034% of autism cases. At the individual level, they estimated that around one in five children born with a TORCH infection may later develop autism.

Previous research has established a link between some congenital infections and intellectual disability, but their relationship with autism has been less clear. According to the researchers, the new study is the largest investigation of its kind and uses national registry data covering nearly the entire Swedish population.

To assess whether family-related factors could explain the findings, the researchers also compared children with congenital TORCH infections with their siblings who did not have the infections. The association remained similar in these analyses, suggesting that shared family characteristics alone are unlikely to account for the results.

The study did not find clear associations between congenital TORCH infections and several other neuropsychiatric conditions, including ADHD and obsessive-compulsive disorder.

However, the researchers found differences in educational performance. Even children who did not develop autism or intellectual disability tended to receive lower school grades if they had experienced a congenital TORCH infection.

The findings suggest that some infections transmitted to the fetus during pregnancy may have long-term effects on brain development. The researchers note that some congenital infections can be prevented, making them relevant from a public health perspective.

Rubella provides an example of the potential impact of prevention. The infection has become virtually eliminated in Sweden following the introduction of national vaccination programs. The researchers emphasize that maintaining vaccination and other preventive measures remains important for reducing infections that can be transmitted from mother to fetus.

The study was funded by the Swedish Research Council. Co-author David Mataix-Cols reported receiving author fees from UpToDate Inc. and being a partner in Scandinavian E-Health AB, which is unrelated to the publication.

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