Is In-Utero Exposure to COVID-19 Tied With Infant Neurodevelopmental Status?

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Birth during the COVID-19 pandemic, but not in utero exposure to maternal SARS-CoV-2 infection, has been shown to be associated with differences in neurodevelopmental status at 6 months of age, according to study findings published in JAMA Pediatrics.

Previous research has found viral illnesses, like HIV during pregnancy, are associated with a higher risk for neurodevelopmental deficits, such as motor delays. Moreover, there is evidence that infants born during the 1918 H1N1 pandemic had lower educational level attainment in childhood and lower socioeconomic status in adulthood. However, research during the COVID-19 pandemic has found vertical transmission of SARS-CoV-2 from mother to fetus to be rare. The current researchers hypothesize in utero exposure to COVID-19 would be associated with social and motor development delays at age 6 months.

The objective of the current study was to determine whether maternal SARS-CoV-2 infection during pregnancy was associated with infant neurobehavioral developmental status at age 6 months.

 A cohort of infants who were exposed to maternal SARS-CoV-2 infection during pregnancy and unexposed controls were enrolled in the COVID-19 Mother Baby Outcomes (COMBO) Initiative at Columbia University Irving Medical Center (CUIMC), located in New York City. The analyses included infants who were enrolled in COMBO and were born between March 2020 (ie, the oldest enrolled infants) and December 2020. All of the mother-infant dyads who participated in COMBO received their prenatal care and underwent delivery at the CUIMC-affiliated New York-Presbyterian Morgan Stanley Children’s Hospital or New York-Presbyterian Allen Pavilion Hospital.

All dyads who experienced a documented SARS-CoV-2 infection during pregnancy (ie, the exposed cohort), according to electronic health records (EHRs), were invited to participate in the study. All of the dyads were enrolled during pregnancy or in the first few months postpartum. For each of the exposed dyads, between 1 and 3 unexposed dyads—that is, those with the absence of any EHR documentation of maternal SARS-CoV-2 infection during pregnancy and at delivery—were chosen as controls (based on infant sex, gestational age at birth, method of delivery, and date of birth within a 2-week window). A historical cohort of infants who were born prior to the pandemic and had completed the 6-month Ages & Stages Questionnaire, 3rd edition (ASQ-3) were included in secondary analyses.

Overall, a total of 596 of 1706 women who were invited to participate enrolled in the COMBO study. Among the enrollees, 385 women were invited to participate in the 6-month evaluation, with 70.6% (272 of 385) of them completing the ASQ-3. Data at age 6 months were available for 272 infants in the pandemic cohort and 71 infants in this historical cohort. Data from 17 infants in the pandemic cohort and 9 in the historical cohort were excluded from the analysis because the neurodevelopmental evaluation was completed outside of the window of eligibility. Thus, the final study sample included data from a total of 317 infants, 255 of who were in the pandemic cohort (114 exposed in utero and 141 unexposed) and 62 of whom were in the historical cohort. The median maternal age at delivery was 32.0 years (range, 19.0 to 45.0 years).

Results of the COMBO study showed that in utero exposure to SARS-CoV-2 infection was not associated with statistically significant differences on any ASQ-3 subdomain, regardless of timing or severity of the infection. Compared with the historical cohort, however, infants who were born during the COVID-19 pandemic had significantly lower scores on the gross motor (mean difference, –5.63; 95% CI, –8.75 to –2.51; P <.005), fine motor (mean difference, –6.61; 95% CI, –10.00 to –3.21; P <.005), and personal-social (mean difference, –3.71; 95% CI, –6.61 to –0.82; P <.05) ASQ-3 subdomains in fully adjusted models.

The researchers acknowledged the study had several limitations. The findings represent data from a first hard-hit COVID-19 epicenter, potentially limiting its generalizability. In addition, different developmental patterns may emerge after age 6 months. 

“In this study, birth during the pandemic, but not in utero exposure to maternal SARS-CoV-2 infection, was associated with differences in neurodevelopment at age 6 months. These early findings support the need for long-term monitoring of children born during the COVID-19 pandemic,” the researchers concluded.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Shuffrey LC, Firestein MR, Kyle MH, et al. Association of birth during the COVID-19 pandemic with neurodevelopmental status at 6 months in infants with and without in utero exposure to maternal SARS-CoV-2 infection. JAMA Pediatr. Published online January 4, 2022. doi:10.1001/jamapediatrics.2021.5563

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