Rare Congenital TORCH Infections Tied to Greater Autism Risk in Kids

A collection of rare infections passed from mothers to fetuses raised the risk of autism or intellectual disability in offspring, according to a Swedish population-based cohort study.

Among nearly 3.7 million children born in Sweden, only 975 had congenital toxoplasmosis, syphilis, rubella, cytomegalovirus (CMV), or herpes simplex (TORCH) infections. Compared with uninfected children, however, those with TORCH infections were three times more likely to develop autism (adjusted HR 3.10) and seven times more likely to develop intellectual disabilities (adjusted HR 7.22).

Those numbers suggest TORCH infections would be responsible for just 0.034% of the overall population’s diagnosed autism cases — but roughly one in five infants exposed to a TORCH infection could be expected to develop autism, Renee Gardner, PhD, of Karolinska Institutet in Stockholm, and colleagues reported in JAMA Pediatrics.

“Our findings suggest that TORCH infections may represent a rare example of perinatal environmental risk factors, providing evidence toward a consistent association with autism and intellectual disability,” Gardner and colleagues wrote. “Associations were highly consistent between sibling and population-based models, indicating minimal confounding by shared familial factors.”

TORCH infections seem to be quite different from the more common infections that women experience during pregnancy, Gardner told MedPage Today. “These pathogens have the unusual ability to cross the placenta and directly infect the developing fetus, including the brain,” she explained.

While more common infections during pregnancy have been associated with autism and other neurodevelopmental conditions in simple comparisons of exposed and unexposed children, those associations largely disappear when studies compare siblings. “Those findings suggest that the infection itself is probably not causing the increased risk,” Gardner said. “Instead, characteristics shared within families — including genetic factors that may influence both susceptibility to infection and neurodevelopment — may explain the association.”

With TORCH infections, however, the association remained when the research team compared siblings. “That provides much stronger evidence that the infection itself can contribute to autism and intellectual disability,” she stated.

Strategies highlighting maternal TORCH infection risks may have a meaningful effect on the incidence of autism spectrum disorders (ASD), Mark Schleiss, MD, of the University of Minnesota in Minneapolis, said in an accompanying editorial.

In particular, awareness and knowledge of CMV’s risks “are disturbingly low,” Schleiss warned. Nearly half of the study’s TORCH infections were CMV (49.9%), with a rate of one to two cases per 10,000 births. Children with a congenital CMV infection were nearly five times more likely than children without a TORCH infection to develop autism (HR 4.57).

“CMV should receive higher public health emphasis as a preventable cause of intellectual disability and ASDs — and a major step forward would be realized by passage of the bipartisan Stop CMV Act of 2025,” Schleiss said. While a congenital CMV vaccine might prevent only a subset of ASD cases, he noted, it could be considered “as a vaccine to prevent autism.”

Expanding beyond TORCH infections to target other pathogens that endanger fetal brain development could lead to new vaccines “that may, by improving neurodevelopmental outcomes, help future generations of children achieve their full potential,” Schleiss added.

Gardner’s team analyzed health records for 3,666,002 children born between 1987 and 2021, 975 of whom were diagnosed with congenital TORCH infections in the first year of life, for a rate of 2.5 per 10,000 births. Among those with TORCH infections, 54.6% were male, compared with 51.4% of those without infections.

There were 5.39 autism diagnoses per 1,000 person-years among those with TORCH infections, compared with 1.71 per 1,000 person-years among those without TORCH infections. Intellectual disability diagnosis rates were 8.22 per 1,000 person-years with TORCH infection and 0.68 without infection.

After a congenital TORCH infection, autism with intellectual disability was more likely than autism without intellectual disability (HR 6.23). Even when a TORCH infection wasn’t linked with either autism or intellectual disability, the researchers found lasting cognitive performance deficits among adolescents. Among 420 such kids, a TORCH infection was linked to a drop of -1.50 points in their school grades.

The study showed a surprising lack of association between TORCH infections and neuropsychiatric outcomes, including non-affective psychosis such as schizophrenia, Gardner noted. A slightly increased risk of attention deficit-hyperactivity disorder disappeared in the study’s sibling comparison analysis, while obsessive compulsive disorder showed no links to TORCH infections.

“That specificity is important, because it suggests that TORCH infections do not simply increase the risk of neurodevelopmental conditions in general,” Gardner said. “Rather, their effects may be more closely tied to particular aspects of brain development and cognitive function.”

Study limitations include a lack of newborn screening for TORCH infections, which prevented outcomes assessment in those with asymptomatic infections. In addition, inability to establish timing of infections relative to factors such as birth complications may have weakened some associations.