June 10, 2022 — Infants exposed to SARS-CoV-2 in the womb are at increased risk for neurodevelopmental disorders in the first year of life, new research suggests.

But whether it is exposure to the pandemic or maternal exposure to the virus itself that may harm early childhood neurodevelopment is unclear, caution investigators, led by Roy Perlis, MD, with Massachusetts General Hospital in Boston.

“In this analysis of 222 offspring of mothers infected with SARS-CoV-2, compared with the offspring of 7,550 mothers in the control group (not infected) delivered during the same period, we observed neurodevelopmental diagnoses to be significantly more common among exposed offspring, particularly those exposed to third-trimester maternal infection,” they write.

The study was published online June 9 in JAMA Network Open.

Speech and Language Disorders

The study included 7,772 mostly singleton live births across six hospitals in Massachusetts between March and September 2020, including 222 (2.9%) births to mothers with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) testing during pregnancy.

In all, 14 of 222 children born to SARS-CoV-2-infected mothers (6.3%) were diagnosed with a neurodevelopmental disorder in the first year of life vs 227 of 7550 unexposed offspring (3%).

When factors such as preterm delivery, race, ethnicity, insurance status, child sex, and the mother’s age were taken into account, COVID-exposed babies were significantly more likely to receive a neurodevelopmental diagnosis in the first year of life.

The association with neurodevelopmental disorders was even greater with third-trimester SARS-CoV-2 infection.

The majority of these diagnoses reflected developmental disorders of movement or speech and language.

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The researchers note the finding of an association between prenatal SARS-CoV-2 exposure and neurodevelopmental diagnoses at 12 months are in line with a “large body of literature” linking maternal viral infection and the mother’s immune response with infants’ neurodevelopmental disorders later in life.

They caution, however, that whether a definitive connection exists between prenatal SARS-CoV-2 exposure and adverse neurodevelopment in babies is not yet known, in part because children born to women infected in the first wave of the pandemic haven’t reached their second birthday, a time when neurodevelopment disorders such as autism are typically diagnosed.

There is also the chance that the findings could be biased because infected mothers who were ill during pregnancy may be more inclined to seek medical evaluation, and clinicians may be more inclined to diagnose or refer them for evaluation, the researchers note.

Nonetheless, the study results support those of research released in a similar study at the European Psychiatric Association 2022 Congress. Those results also showed an association between maternal SARS-CoV-2 infection and impaired neurodevelopment in 6-week-old infants.

“Questions Remain”

In an accompanying commentary, Torri D. Metz, MD, with the University of Utah Health in Salt Lake City, says the preliminary findings of Perlis and colleagues are “critically important, yet many questions remain.”

“Essentially all of what we know now about the effects of in utero exposure to maternal SARS-CoV-2 infection is from children who were exposed to the early and Alpha variants of SARS-CoV-2, as those are the only children now old enough to undergo rigorous neurodevelopmental assessments,” Metz points out.

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Ultimately, Metz says it’s not surprising that the pandemic and in utero exposure to maternal SARS-CoV-2 infection may adversely affect neurodevelopmental outcomes in young children.

Yet, since this type of study only looks at data from the past, it can only show associations, not cause and effect.

“This type of work is intended to be hypothesis-generating, and that goal has been accomplished as these preliminary findings generate numerous additional research questions to explore,” Metz writes.

Among them: Are there genetic predispositions to adverse outcomes? Will we observe different effects depending upon which SARS-CoV-2 variant the mother was infected by, by the severity of her infection, and by trimester of infection? Is it the virus itself or all of the societal changes that occurred during this period, including differences in how those changes were experienced among those with and without SARS-CoV-2?

“Perhaps the most important question is how do we intervene to help mitigate the adverse effects of the pandemic on young children,” Metz notes.

Studies where the mothers are followed and observed over a period of time are needed “to validate these findings, tease out some of the nuance, and identify those at highest risk,” she adds.

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