A newly published study led by BBRF grantees sheds important new light on the question of whether infants born to mothers who were infected with the COVID-19 virus during pregnancy have been negatively affected in terms of neurodevelopment and early-life behaviors.

The question is important for public health globally “even if there is a slight increase” in the risk of adverse neurodevelopmental outcomes, say authors of the new study, who were led by Moriah E. Thomason, Ph.D., a 2012 and 2008 BBRF Young Investigator, and Clare McCormack, Ph.D., a 2023 BBRF Young Investigator, both of the Department of Child and Adolescent Psychiatry at NYU Langone Health. The reason is simple: an enormous number of people have been infected with the virus since the onset of the pandemic in 2020: 103 million in the U.S. and 778 million globally (1 in 10 people), as of May 2025. Inevitably, given these numbers, a large number of women have contracted COVID during their pregnancies over the last 5+ years.

Broadly speaking, those who contract COVID during pregnancy tend to have more severe symptoms, are less responsive to treatment, experience worse outcomes, and mount a less robust immune response to the virus, the authors note. Indeed, any time a pregnancy is marked by viral infection, there is some reason for concern. Activation of the maternal immune system is a well known and much studied risk factor for neurodevelopmental problems in offspring. A number of studies published during and after the pandemic have established, at the very least, that “vertical transmission” of the virus itself from mother to fetus is “extremely rare,” as the authors of the new study note.

Although the fetus very rarely contracts the COVID virus, this is not necessarily to say that it is unaffected. Fortunately, in addition to serving as an effective barrier against direct transmission of COVID, the placenta also “mounts a robust inflammatory response,” which is reflected in elevated expression of immune and other related placental genes. Cord blood and neonatal biological samples have indicated a similar pattern.

In view of this, it is perhaps not surprising that a number of initial studies have found no evidence of developmental problems associated with maternal COVID infection in pregnancy. But a number of important knowledge gaps remain, including whether brain structure and function are affected. The new study sought to address this, asking whether congenital COVID exposure correlates with variations in infant neural and behavioral outcomes.

The study, appearing in Pediatric Research, reports on results in 234 mother-infant dyads, on whom comprehensive data was collected pre- and postnatally. They are part of a cohort recruited at NYU Medical Center from the early days of the pandemic. Of the 234 mother-infant pairs in the current study, 77 infants (33%) were born to mothers infected with COVID during pregnancy. The researchers sought to provide a comprehensive body of evidence “across fundamental domains of infant development, including milestones, attention, sleep, temperament, and socioemotional development.” Sociodemographic factors, maternal mental health, illness severity, timing of infection, and birth outcomes were also considered. MRI scans focusing on whole-brain functional connectivity in a subset of the infants were also part of the dataset.

The mothers in the cohort were, on average, in their early 30s; 59% were White, 24% Hispanic, 7% Black; mean annual family income was over $100,000.

When all the data were analyzed, the team was able to conclude, broadly, that 1 year after birth, “few neurobehavioral differences exist in infants congenitally exposed” to the COVID virus, relative to unexposed infants. Where differences were noted, the team said, effect sizes (i.e., magnitude of the differences) were “modest” and didn’t remain statistically significant, in this cohort, following various adjustments made in the attempt to draw fair comparisons across mothers who were and were not infected during pregnancy.

“The approach taken here was to broadly evaluate fundamental domains of infant social, emotional, and cognitive function that develop rapidly across the first year of life,” they noted. During that first year, no differences were noted in observed behavior of the infants in both groups (mothers with/without infection during pregnancy) during a well-validated visual attention task, nor in measures of emotional reactivity and regulation during two standard tasks involving stress. No differences were observed in the achievement of developmental milestones based on a questionnaire focusing on communication, motor skills, problem-solving or personal/social interaction, or in aspects of infant temperament or socio-emotional development.

One area emerged as different among the two groups of infants in the data prior to statistical adjustments. This concerned observation at 12 months after birth of what developmental experts call “duration of orienting,” which concerns temperamental differences in infants’ ability to sustain attention over extended periods of time during play or engagement with objects. Infants in the COVID-exposure group were more likely to have reduced duration of orienting. Still, after statistical corrections, the team didn’t see differences in infant temperament or emotional reactivity or regulation, suggesting to them that the difference in orienting behavior “may not lead to sustained differences in behavior in these infants.” There was also some evidence, prior to adjustments, that the infants with COVID exposure had fewer awakenings during the night at the 6- and 12-month marks, but no difference in total sleep time, providing evidence reassuring to the team that prenatal exposure to COVID infection did not have negative impacts on infant sleep across the first year of life.

The MRI data, considered overall, revealed subtle differences in the COVID-exposed vs. unexposed infants. Specifically, functional connectivity, or communication between brain regions, showed a slightly more mature pattern of connection in the COVID-exposed group. This finding generally echoed an observation in one prior study of greater neural maturation in COVID-exposed infants. There was no evidence of behavioral impact of these differences, however, at 12 months, and further research will be needed to understand any potential developmental implications of these subtle differences, the researchers said.

Importantly, the researchers point out that their data, collected in the first year of life, cannot shed light on whether exposure to the COVID virus prenatally may impact domains such as executive function and language development that occur after the first year of life. It is also possible that differences in some aspects of infant attention or behavior may not emerge until later in development. “Thus, continued longitudinal follow-up [i.e., over time] is important for a more complete picture,” they said.

Among other caveats, the researchers pointed out that this cohort may represent “a lower end of the spectrum of illness severity” in COVID and thus may not reflect developmental effects among children born to a minority of mothers who experienced severe illness during pregnancy.

The cohort of mothers in the current study generally reported low levels of depression and anxiety symptoms. But it is possible that psychosocial stress experienced by mothers who were ill with COVID during pregnancy may, in more acute instances, prove to be an important factor in determining if the child has elevated risk for developmental problems. The varied and sometimes severe impacts of stress were widely noted across the population among those who contracted COVID, and especially in those who had severe cases and/or other sources of stress in their lives.

Overall, the team concluded, “replication and continued longitudinal research following these groups later into childhood will be necessary for drawing conclusions about behaviorally relevant and lasting neurodevelopmental effects of prenatal COVID exposure.”