Harvard, Mass General Researchers Find Link Between Covid-19 in Mothers and Neurodevelopmental Disorders in Children

Harvard Medical School and Massachusetts General Hospital researchers found a correlation between Covid-19 infection contracted during pregnancy and risk of neurodevelopmental disorders in offspring in a paper published last month.

The paper, published on March 23 in JAMA Network Open, examined more than 18,000 health records of infants born in Massachusetts during the pandemic. Roughly 880 of their mothers had tested positive for Covid-19 during pregnancy. The researchers followed up with the cohort post-delivery and found that in utero exposure to Covid-19 was linked to an increased risk of neurodevelopmental disorders, such as speech and motor delays.

Specifically, the study found that male infants are 90 percent more likely to experience speech and motor delays than their female counterparts, according to study co-author Andrea G. Edlow.

Edlow, an associate professor at HMS and a maternal-fetal medicine specialist at MGH, said the discrepancy between male and female infants is “multifactorial” and can depend both on genetics and environment.

“The male fetus in general has increased fragility in utero compared to the female fetus,” she said. “For example, a male and a female neonate born prematurely at the same age — the male will have an increased risk of mortality.”

Previous studies have established that exposure to other viruses such as influenza during pregnancy is correlated with neurodevelopmental disorders in children. The onset of the pandemic in 2020 prompted researchers at HMS and MGH to investigate whether Covid-19 infection would pose a similar risk.

The researchers believe the neurodevelopmental disorders may be attributable to the activation of the mother’s immune system during infection.

“It’s that factor, more than any specific virus or bacterial infection, that can result in these later neurodevelopmental outcomes in children or offspring,” Edlow said.

Still, the relationship between the severity of illness and its impact on neurodevelopmental risk has yet to be studied. According to co-author Roy H. Perlis, Psychiatry professor at HMS and director of the Center for Quantitative Health at MGH, dividing the births into groups based on the intensity of infection would require a substantially larger amount of data for accurate statistical analysis.

“Though 18,000 is the largest cohort that we’re aware of to date, even that size of cohort doesn’t allow us to tease apart those finer points,” Edlow added.

Edlow and Perlis said the long-term implications of the study remain unclear, and further observation is necessary to determine whether these disorders have lasting effects on children. The researchers plan to follow the cohort of children over time by tracking their electronic health records.

“A really important aspect of the study is going to be understanding not just how these children look at 12 months or 18 months, but coming to see how they look at two years and three years and five years and so forth,” Perlis said. “Now that we’ve established this cohort, we can continue to follow them over time.”

Edlow said pregnant women and children have historically been understudied in medical research, and this research is often underfunded.

“One of the best ways that we can help vulnerable, understudied populations is by performing research on them and including them in research,” she said.

Correction: April 5, 2023

A previous version of this article incorrectly referred to study co-author Andrea G. Edlow as an assistant professor at Harvard Medical School. In fact, Edlow is an associate professor.