Infants exposed to the COVID-19 virus in utero did not show differences in early neurodevelopmental outcomes through 18 months of age compared with unexposed infants, with some uncertainty, according to a study published last week in The Journal of Pediatrics.
The study, led by researchers from the University of California San Francisco, drew on data from the Researching COVID to Enhance Recovery (RECOVER) pregnancy cohort, which enrolled pregnant women with and without COVID infection and followed their children through early childhood. The team analyzed neurodevelopmental outcomes among 1,179 infants born from January 2020 to December 2023 at 23 sites across the United States.
Of the infants in the cohort, 1,008 (85.5%) had confirmed exposure to SARS-CoV-2 in utero. Most exposures occurred when the Omicron variant was dominant and during the second or third trimester of pregnancy. Neurodevelopment was assessed at 12 months using the Ages and Stages Questionnaire, 3rd Edition (ASQ-3) and at 18 months using the ASQ Social-Emotional Questionnaire (ASQ-SE) and the Modified Checklist for Autism in Toddlers–Revised (M-CHAT-R).
The researchers found no association between COVID exposure in utero and lower overall ASQ-3 scores, which evaluate communication, gross motor, fine motor, problem solving, and personal-social skills, at age 12 months. The adjusted difference in total ASQ-3 score between exposed and unexposed infants was −0.61 points (95% confidence interval [CI], −10.03 to 8.81).
Similarly, at 18 months, no association was found between COVID exposure and social-emotional scores (0.19; 95% CI, −4.02 to 4.41) and autism screening results (−0.17; 95% CI, −0.53 to 0.18).
More assessments at older ages needed
Because in utero exposure to other viral infections, such as Zika and HIV, has been linked to impaired neurodevelopment in children, the researchers sought to determine whether exposure to COVID in utero could similarly affect neurocognitive outcomes.
While the current findings suggest that exposure to COVID in utero is not associated with neurocognitive outcomes at 12 months or social-emotional development or autism risk at 18 months, the authors caution that the findings should not be interpreted as definitive.
“It is important to note that our confidence intervals are wide, so we are unable to exclude a clinically meaningful association, and that the predictive validity of neurodevelopmental screening is low prior to 2 years of age,” they write. “Thus, our results should not be interpreted to suggest that there is no impact of intrauterine SARS-CoV-2 on neurodevelopment. Direct assessments at older ages are needed to assess the impact of intrauterine SARS-CoV-2 on neurodevelopment during later toddlerhood and the preschool-age period.”
The study had other limitations. Parents who enrolled in the study may have been concerned about their child’s development, which could have introduced selection bias, and some COVID infections were identified through antibody testing after pregnancy. In addition, the study mostly assessed children born during or after the emergence of the Omicron variant, so the findings may not reflect risks associated with earlier variants. The level of educational attainment among mothers in the study was higher than the US average (70% had a bachelor’s degree), which may make it harder to generalize the findings.
“Further research will be critical for understanding the relationship between intrauterine SARS-CoV-2 and child neurodevelopment and how it is affected by trimester of exposure and by SARS-CoV-2 variant,” conclude the authors.
