TORCH Infections During Pregnancy: Study Shows Link to Autism

Certain infections transmitted from the mother to the unborn child during pregnancy are rare. However, when such a congenital infection does occur, the potential effects on the child’s development can be significant. A large-scale Swedish study has now investigated whether so-called TORCH infections are associated with later developmental disorders. The researchers found a clear statistical association with autism and intellectual disability.

The study was conducted by scientists at the Karolinska Institutet and published in the journal “JAMA Pediatrics.” The researchers analyzed health and educational data from more than 3.6 million people born in Sweden between 1987 and 2021. The results show an increased risk of various developmental problems among individuals who were diagnosed with a congenital TORCH infection before or shortly after birth.

At the same time, an important limitation must be noted: These infections are very rare. Therefore, despite the sometimes high relative risks, they account for only a small proportion of all cases of autism and disability in the population.

What are TORCH Infections?

The term TORCH describes a group of infections that can be transmitted to the unborn child during pregnancy. These include, among others, cytomegalovirus, rubella virus, Toxoplasma gondii, and herpes simplex viruses. Syphilis was also included in the study.

Many infections that a pregnant woman contracts do not reach the fetus directly. However, some pathogens can cross the placenta and thereby cause an infection in the unborn child. This can be particularly problematic during certain phases of pregnancy. As the brain and other organs develop, numerous highly complex biological processes take place. An infection or an inflammatory response triggered by it could potentially influence this development.

Congenital infections have therefore been recognized for many years as a possible cause of various health problems. These include, among other things, developmental disorders of the nervous system. Until now, it has been less clear whether such infections could also be linked to autism. It was precisely this connection that the Swedish researchers wanted to investigate more closely.

More Than 3.6 Million People Studied

For the study, data from a total of 3,666,002 people born in Sweden between 1987 and 2021 were analyzed. Of these individuals, 975 had a documented congenital TORCH infection.

As a result, the group of affected individuals represented only a very small portion of the entire study population. However, it was precisely the enormous size of the control group that enabled the researchers to statistically examine even rare associations.

The participants were followed over many years. In some cases, the follow-up period extended into adulthood. This allowed the researchers to determine whether those affected were later diagnosed with conditions such as autism or intellectual disability. Additionally, other neuropsychiatric disorders as well as academic performance were examined.

The long follow-up period is particularly important for this type of research. Many developmental diagnoses are not made immediately after birth. Some abnormalities are not recognized until kindergarten, school, or even later.

Risk of Autism Was About Three Times Higher

One of the most important findings concerns autism. In the study, people with a congenital TORCH infection were significantly more likely to receive a diagnosis of autism later in life. The statistically determined risk—or rate—of a later diagnosis was approximately three times higher than in people without a documented congenital TORCH infection.

At first glance, this figure seems very high. However, it must be put into proper perspective. A threefold increase in relative risk does not mean that three out of four children with such an infection will later develop autism. Rather, it describes the difference between two groups.

Since congenital TORCH infections are very rare overall, the number of autism cases that may be associated with such infections remains very small relative to the total number of autism cases.

The study thus shows, above all, that children with an actually diagnosed congenital TORCH infection represent a group whose long-term developmental trajectories are of particular interest to researchers.

The Association With Intellectual Disability Was Even More Pronounced

The association was even stronger in the case of intellectual disability. Here, the rate of subsequent diagnoses among people with a congenital TORCH infection was more than seven times higher than among those without such an infection. The difference was particularly striking in cases of severe to profound intellectual disability. In this group, the statistical measure was significantly higher, reaching a value of 23.51 in the main analysis.

This figure should not be confused with a probability of 23.51 percent or a 23-fold higher absolute risk of developing the condition. This is what is known as a hazard ratio. It describes the difference in the rate at which an event occurs in two groups during the observation period. The stronger the association, the higher this statistical measure is. However, it does not directly indicate how many individual children will actually be affected.

The researchers also investigated whether the results differed when autism occurred in conjunction with an intellectual disability. Here, too, a clear pattern emerged. In individuals with a congenital TORCH infection, the association with autism and concurrent intellectual disability was stronger than with autism without intellectual disability.

A hazard ratio of 6.23 was found for autism in combination with intellectual disability. For autism without a concurrent diagnosis of intellectual disability, the corresponding value was 1.97. This suggests that congenital TORCH infections may be particularly strongly associated with forms of neurodevelopmental disorders in which multiple areas of development are affected.

However, the study cannot explain why this difference exists. The registry data show which diagnoses were made later on. They do not, however, provide a complete explanation of the biological processes that occurred during pregnancy in individual children.

High Relative Risks do not mean many cases

The relative risks were very high in some cases. Nevertheless, congenital TORCH infections are so rare that they can account for only a small proportion of cases in the general population. For example, the researchers estimate that congenital TORCH infections could be associated with about 0.034 percent of autism cases in Sweden. For severe intellectual disabilities, the corresponding estimate was approximately 1.2 percent.

This highlights the difference between individual risk and population risk. For a child who is actually born with a congenital TORCH infection, the infection can be a relevant risk factor. However, when considered in relation to the general population, such infections account for only a very small proportion of all cases. The results should therefore not be interpreted to mean that TORCH infections are a common cause of autism.

Comparison of Siblings Provides Additional Insights

A key component of the study was the comparison within families. The researchers compared children with a congenital TORCH infection not only with other children from the general population but also with their own siblings, in whom no such infection had been detected.

Why is this important? Siblings often share many genetic and familial factors. They frequently grow up in the same household and have similar social and economic circumstances. If an association were to arise solely because certain family characteristics are linked to both infections and subsequent developmental disorders, the difference between siblings might be smaller.

However, the association persisted even in the sibling comparison. For autism, the hazard ratio was 3.19. For intellectual disability, a hazard ratio of 11.28 was determined. This suggests that shared family factors likely do not fully explain the observed association. However, even a comparison of siblings cannot rule out all influencing factors. The study remains an observational study and therefore cannot provide definitive proof of a direct causal relationship.

Academic Performance also Differed

The researchers also examined the academic performance of the children and adolescents. They found that individuals with a congenital TORCH infection, on average, achieved lower grades than those without such an infection. Interestingly, this difference was also evident among children who had not been diagnosed with either autism or an intellectual disability.

This could suggest that the potential effects of a congenital infection do not occur exclusively in children who are later given a clearly defined neurodevelopmental diagnosis. However, this finding must also be interpreted with caution.

In the analysis of sibling pairs, the difference in school grades was no longer statistically significant. This shows that the findings regarding academic performance are less robust than some of the associations observed with autism and intellectual disability.

The researchers also examined other neuropsychiatric disorders. They found no convincing or consistent association with obsessive-compulsive disorder. The results were also less clear-cut for attention-deficit/hyperactivity disorder, or ADHD for short. A correlation that was apparent in the initial analysis weakened when siblings were compared.

The results do not suggest that a congenital TORCH infection automatically increases the risk for all mental or neuropsychiatric disorders. Rather, the clearest statistical correlations were concentrated on autism and intellectual disability.

Why Can Infections Influence Brain Development?

The study itself does not examine in detail the biological mechanisms underlying the results. Scientifically, however, several possible pathways are conceivable. Some viruses and other pathogens can directly infect the tissues of the unborn child. Other possible effects could arise from inflammatory responses that the body develops in reaction to the infection.

The brain of a fetus undergoes an intensive phase of development throughout the entire pregnancy. Nerve cells form, migrate to specific locations, establish connections with one another, and organize complex networks. If such processes are affected by an infection or a severe inflammatory response, this could have long-term consequences.

However, whether and to what extent such mechanisms actually play a role in the children studied must be clarified through further research. The current study primarily demonstrates a statistical association and not a direct biological cause.

Rubella Highlights the Importance of Prevention

Rubella is among the infections that can be particularly problematic during pregnancy. An infection can cause serious harm to the unborn child. Thanks to vaccination programs, the number of rubella infections has been drastically reduced in many countries. In Sweden, too, rubella has become extremely rare as a result of the long-standing vaccination strategy.

This example illustrates the importance of preventive measures for infections that can be transmitted to the unborn child during pregnancy. The fewer such infections that occur, the fewer children are exposed to the potential consequences of a congenital infection.

In addition to vaccinations, other measures may play a role depending on the pathogen and the individual situation. These include, for example, medical examinations during pregnancy, hygiene precautions, and medical care in cases of specific infection risks. However, which measures are appropriate in each individual case depends on the specific pregnancy and the particular pathogen.

What the Study Means for Affected Families

The results should not lead parents to automatically assume that their child will have a developmental disorder following an infection during pregnancy. A TORCH infection does not necessarily mean that a child will later develop autism or an intellectual disability. Rather, the study shows that, within a very small group of people with a confirmed congenital infection, certain diagnoses occurred more frequently statistically.

For families in which a congenital infection has been diagnosed, long-term medical and developmental monitoring may therefore be advisable. Depending on the pathogen and individual findings, pediatricians and other specialists can provide targeted support for the child’s development.

It is important not to focus solely on potential problems. Many children develop differently despite health challenges and do not automatically require the same tests or support services.

A Large Study with Significant Limitations

The strength of the Swedish study lies primarily in its scale. More than 3.6 million people were included and observed over many years. This allowed the researchers to examine even rare congenital infections and analyze their potential long-term associations with later diagnoses. In addition, the sibling comparison made it possible to account for some shared familial risk factors.

Nevertheless, even such a large study has its limitations. The researchers analyzed existing registry data; therefore, they were unable to capture every medical or social influencing factor. Furthermore, congenital TORCH infections were very rare, so the number of people actually affected remained relatively small.

Above all, however, this is not a controlled study capable of clearly establishing cause and effect. The results show an association. They do not prove that a TORCH infection was the cause of a subsequent autism diagnosis or intellectual disability in every single case.

What Still Needs to Be Researched

The new study therefore raises as many questions as it answers. Future studies must examine more closely which individual pathogens are particularly relevant. The timing of the infection during pregnancy could also play an important role. Furthermore, it remains unclear why some children develop severe developmental problems following a congenital infection, while others do not receive such diagnoses. Genetic factors, the strength of the immune response, and the specific nature of the infection could also influence how a child develops in the long term.

The study provides no evidence that TORCH infections are a common cause of autism. Rather, it shows that certain infections can have long-term effects on development even before birth.

For the medical community, the study thus underscores the importance of prevention, early detection, and long-term monitoring of affected children. At the same time, further research is needed to better understand how infections during pregnancy can influence the development of a child’s brain.