Link between maternal infection, offspring’s autism not causal, study shows

The association between maternal infection during pregnancy and children’s diagnoses of autism spectrum disorder and intellectual disability was not causal, according to a Swedish register-based cohort study.

The findings of the study, published in The Lancet Psychiatry, contradict “over 30 epidemiological studies [that] have reported consistent associations between maternal infections and autism” in recent years, Martin Brynge, MD, a psychiatrist and PhD student in the department of global public health at Karolinska Institutet in Stockholm, told Healio.

“We found no evidence to suggest that having an infection during pregnancy would increase the child’s risk of autism,” Brynge said. “Instead, it may be unmeasured genetic and/or environmental factors that cause both infections in these mothers and autism in their children separately. For intellectual disability, the results are less clear, and a causal role cannot be excluded; however, the relationship is not as strong as previously thought.”

According to a press release, the findings only apply to general diagnoses of infection, not “the well-established links between some specific viral infections during pregnancy, such as cytomegalovirus infection and rubella, and the risk of serious developmental conditions in the child.”

Brynge and colleagues studied 549,967 children born in Sweden between 1987 and 2010 who were included in the Medical Birth Register, lived in Stockholm County and were not adopted, and whose biological parents were both known. The researchers identified maternal infections during pregnancy, which were reported in the National Patient Register. They followed children’s diagnoses of autism and intellectual disability until they died, moved out of Stockholm or were aged 18 years, or until the date of the latest register update — Dec. 31, 2016 — was reached.

To account for confounding factors, Brynge and colleagues analyzed the impact of maternal infection during the year before pregnancy on offspring’s diagnoses, as well as compared children with their siblings.

In total, 445 (1.3%) and 1,123 (3.3%) of 34,013 children whose mothers had an infection during pregnancy had an intellectual disability and autism, respectively. Among 515,954 children who were unexposed to maternal infection, 5,087 (1%) and 13,035 (2.5%) had a diagnosis of intellectual disability or autism, respectively. Thus, compared with having no exposure to maternal infection, having been exposed to maternal infection was associated with both intellectual disability (HR = 1.37; 95% CI, 1.23-1.51) and autism (HR = 1.16; 95% CI, 1.09-1.23).

Prepregnancy maternal infections

The researchers found that maternal infection in the year before pregnancy — what they used as a negative control exposure — was also associated with an increased risk for autism in offspring (HR = 1.25; 95% CI, 1.14-1.36), but not intellectual disability (HR = 1.09; 95% CI, 0.94-1.27).

According to Brynge, the association between prepregnancy maternal infection and autism indicate “that mothers to children with autism may have an increased propensity for infections in general — not only during the pregnancy period specifically — and that the infections are not the cause of the neurodevelopmental conditions.”

Sibling comparisons

Additionally, the researchers included 394,093 children and their siblings in their sibling analyses. Compared with their siblings, children exposed to maternal infection while in utero had similar risk for intellectual disability (HR = 1.15; 95% CI, 0.95-1.4) and autism (HR = 0.94; 95% CI, 0.82-1.08).

“Prevention of maternal infections will likely not affect the prevalence of autism in the population and is not a meaningful strategy for prevention,” Brynge said. “For intellectual disability, the results are less clear, and this study does not contradict the established relationship between intellectual disability and certain congenital infections, such as rubella, Zika and cytomegalovirus.”

Moving forward, Brynge suggested further research is needed to “identify any potential causal and modifiable environmental factor acting during pregnancy and examine reasons for the increased incidence of infections among mothers to children with autism.”

References:

• Brynge M, et al. Lancet Psychiatry. 2022;doi:10.1016/S2215-0366(22)00264-4.
• New knowledge about the link between infection during pregnancy and autism. https://www.eurekalert.org/news-releases/963904. Published Sept. 7, 2022. Accessed Sept. 13, 2022.