Rare pregnancy infections may triple the risk of autism

"It is important to emphasize that it is unusual for these infections to be transmitted from mother to child. They account for a very small proportion of all cases of autism in the population, but for those children who are actually affected, we see a clearly elevated risk of both autism and intellectual disability," says Reneé Gardner, a researcher at the Department of Global Public Health at Karolinska Institutet, who contributed to the study.

The research focused on a group known as TORCH infections. This category includes, among others, cytomegalovirus, rubella, toxoplasma and herpesvirus. While most common infections do not directly reach a developing fetus, these pathogens can sometimes cross the placenta and cause a congenital infection.

Study Followed 3.7 Million People

The researchers examined health and education records for 3.7 million people born in Sweden between 1987 and 2021. Among this population, 975 people had been diagnosed with a congenital TORCH infection.

Participants were followed for as long as three decades, allowing the team to investigate whether these infections were associated with later neurodevelopmental diagnoses and educational outcomes.

Children with a congenital TORCH infection were about three times more likely to later be diagnosed with autism than those without an infection. Their likelihood of receiving an intellectual disability diagnosis was more than seven times higher.

For severe to profound intellectual disability, the difference was even larger, with the risk rising as much as 30 fold.

Large Risk Increase, but Few Cases Overall

Those figures represent substantial increases in relative risk, but congenital TORCH infections are rare. As a result, they account for only a small proportion of autism and intellectual disability cases across the population.

The researchers estimate that congenital TORCH infections may be associated with about 1.2 percent of severe intellectual disability cases in Sweden. They estimate that about 0.034 percent of autism cases in the country can be attributed to these infections.

At the individual level, however, the researchers estimate that roughly one in five children born with a TORCH infection may later develop autism.

"It has long been known that these infections can cause intellectual disability. However, the link to autism has been less clear in previous research, which has often been based on small patient groups. This study is the largest to date in this field and is based on national register data covering almost the entire population of Sweden," says Hugo Sjöqvist, a PhD student and lead author of the study.

Sibling Comparison Tests the Association

The researchers also used sibling comparisons to investigate whether the findings might instead be explained by characteristics shared within families.

They compared children who had experienced a TORCH infection with their own siblings who had not. The pattern remained similar in these comparisons, suggesting that shared family factors alone are unlikely to explain the associations.

The researchers did not identify clear links between congenital TORCH infections and other neuropsychiatric conditions, including ADHD or obsessive-compulsive disorder.

They did, however, find differences in school performance. Even among children who were not diagnosed with autism or an intellectual disability, those with a congenital TORCH infection received lower grades on average than children without an infection.

Potential Long-Term Effects on the Brain

"Our results suggest that certain infections transmitted to the fetus during pregnancy may have long-term effects on brain development. Although these congenital infections are rare, some of them can be prevented, which makes them important from a public health perspective," says Reneé Gardner.

The researchers say the findings highlight the importance of preventing infections that can be transmitted to a fetus during pregnancy.

Rubella is one example of how prevention can make a major difference. The infection has virtually disappeared in Sweden since national vaccination programs were introduced. According to the researchers, maintaining vaccination programs and other preventive measures remains important for reducing infections that can pass from a pregnant woman to a developing fetus.

The research was funded by the Swedish Research Council. Co-author David Mataix-Cols states that he has received author's fees from UpToDate Inc and that he is a partner in Scandinavian E-Health AB, which is unrelated to the publication.