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Infants exposed to COVID-19 in utero appeared to be at greater risk of neurodevelopmental problems, particularly if the infection came in the last trimester, a cohort study showed.

Neurodevelopmental diagnoses were twice as common in the first year of life after gestational exposure (6.3% vs 3.0%), reported Roy Perlis, MD, MSc, of the Center for Quantitative Health at Massachusetts General Hospital in Boston, and colleagues in .

The association persisted with adjustment for race, ethnicity, insurance status, offspring sex, maternal age, and preterm birth (OR 1.86, 95% CI 1.03-3.36), and the relationship was most pronounced with coronavirus exposures during the third trimester (OR 2.34, 95% CI 1.23-4.44).

Previous studies have also demonstrated an association between viral infections, such as influenza, during pregnancy and developmental issues, such as autism, cognitive dysfunction, anxiety, and depression. Although many of these issues are not seen until adolescence or adulthood and "the magnitude of these effects and strength of association varies, the consistency of such associations is difficult to ignore," Perlis' group noted.

And COVID-19 in particular has been linked with neuropsychiatric symptoms that can sometimes last up to a year after infection in both children and adults.

Another recent study showed neurodevelopmental delays for 6-month-olds born during the pandemic, but no impact of maternal SARS-CoV-2 infection, suggesting a role more from the stress the mother felt while being pregnant during the pandemic.

But there were other potential explanations, such as the difference in age at ascertainment and universally symptomatic maternal infection in Perlis' study versus one-third being asymptomatic in the other, noted an accompanying by Torri Metz, MD, of the University of Utah in Salt Lake City.

"Given that we are only 2 years into the pandemic, much of the effect of in utero exposure to maternal SARS-CoV-2 infection remains poorly understood," she wrote, especially since existing data really only reflects the original strain (as in the current study) and Alpha variant, "as those are the only children now old enough to undergo rigorous neurodevelopmental assessments."

The Delta variant, however, "substantially damaged the placenta and was associated with a much higher risk of stillbirth compared with other variants," Metz pointed out. "Importantly, we also have no data on whether prior vaccination will have a protective effect against adverse neurodevelopmental outcomes for the offspring of mothers with SARS-CoV-2 beyond the direct benefit of persistent antibodies in the cord blood and through infancy."

She also emphasized the importance of helping affected children: "Perhaps the most important question is how do we intervene to help mitigate the adverse effects of the pandemic on young children? Prospective studies to validate these findings, tease out some of the nuance, and identify those at highest risk will help health care practitioners appropriately dedicate resources to improve outcomes as we follow the life course of this generation of children born during the COVID-19 pandemic."

Perlis' study was conducted using electronic health record (EHR) data from six community hospitals and two academic medical centers in order to identify live births occurring between March and September of 2020.

Of the 7,772 new mothers in the study, 222 (2.9%) tested positive by PCR for SARS-CoV-2 at any point during pregnancy. Of their exposed offspring, 14 received a neurodevelopment diagnosis in the first year of life, compared with 227 out of 7,550 unexposed offspring.

The types of neurodevelopmental disorders that occurred were similar across groups, most commonly affecting speech and motor function. However, exposed offspring tended to be diagnosed earlier (median 214 vs 275 days).

Preterm deliveries were also more common for children exposed to the virus in utero (14.4% vs 8.7%, P=0.003), though "adjustment for preterm birth did not account for all of the observed increased risk of incurring a neurodevelopmental diagnosis," the authors noted.

The researchers acknowledged that their study could not determine causality, and that more research will need to be done as the children born during the first wave of the pandemic grow up, as many common disorders do not appear until later childhood or later in life. A longer and larger study would also be required to determine an exact mechanism at work.

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