In utero SARS-CoV-2 exposure may predispose children to altered brain volumes, impaired cognition, and internalizing emotional problems such as anxiety and depression, researchers from Children’s National Hospital and George Washington University write in Brain, Behavior, and Immunity.
The team enrolled 39 mother-baby pairs in Washington, DC, who had been exposed to COVID-19 during pregnancy from 2020 to 2022 and compared them with 103 normative pairs from before the pandemic (2016 to 2019). None of the infected women had been vaccinated against SARS-CoV-2.
When infants were 2 weeks old, they underwent quantitative 3D volumetric magnetic resonance imaging (MRI). Two years later, they were assessed with the Third Edition of the Bayley Scales of Infant and Toddler Development (BSID-III) and the Infant-Toddler Social and Emotional Assessment (ITSEA). Mothers were also evaluated with the Perceived Stress Scale to account for psychological distress that may have exacerbated the effects of SARS-CoV-2 exposure on the fetus.
From the beginning of the COVID-19 pandemic to December 2023, when the Centers for Disease Control and Prevention stopped collecting data on SARS-CoV-2, 163,140 infants were born to mothers infected with the virus, the study authors noted.
“In historical viral epidemics, such as the H1N1 influenza and Zika viruses, prenatal exposures were correlated with risk for neuropsychiatric conditions in offspring,” they wrote. “However, the long-term effects of prenatal COVID-19 viral exposure on offspring neurodevelopment are still being discovered.”
52% of exposed kids at high risk for delayed development
In utero SARS-CoV-2 exposure was tied to significantly larger cortical gray matter and left hippocampal volumes and significantly smaller subcortical gray matter and white matter volumes. In unadjusted analyses at 2 years, 14% of toddlers in the prepandemic group were at high risk for developmental delays on the BSID-III, in contrast to 51.6% in the COVID-19 group.
While there was no significant association between SARS-CoV-2 exposure and overall BSID-III composite language score, receptive language (ability to understand written and spoken language) scores dropped significantly with in utero viral exposure.
On the ITSEA, 11% of children in the prepandemic group were at high risk for internalizing behavioral difficulties, compared with 24.7% in the SARS-CoV-2 group.
There was no significant link between viral exposure and the ITSEA externalizing, dysregulation, or competence domains. Likewise, no statistically significant difference was noted in reported maternal psychological distress between the prepandemic group (21.7%) and those who had COVID-19 (29.4%).
Possible effects on a whole generation
The researchers said the findings highlight the potential effects of in utero SARS-CoV-2 exposure on this generation of children, including the internalizing behaviors in toddlers, an independent risk factor for the development of mood disorders over time. While many mechanisms behind the elevated risks in this group have been proposed, none have been fully elucidated.
These findings highlight the need for continued surveillance to best identify and provide early interventions for at-risk children and provide new insights regarding prenatal exposures on early fetal programming.
“These findings highlight the need for continued surveillance to best identify and provide early interventions for at-risk children and provide new insights regarding prenatal exposures on early fetal programming,” they wrote.
“Further studies into the longitudinal effects of this exposure are currently ongoing. Further work is required to see how children exposed to the virus potentially differ from their peers who grew up with similar societal and lifestyle constraints, and if these early differences persist or diminish over time,” they added.
