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

Abstract

Importance: Associations between in utero exposure to maternal SARS-CoV-2 infection and neurodevelopment are speculated, but currently unknown.

Objective: To examine the associations between maternal SARS-CoV-2 infection during pregnancy, being born during the COVID-19 pandemic regardless of maternal SARS-CoV-2 status, and neurodevelopment at age 6 months.

Design, setting, and participants: A cohort of infants exposed to maternal SARS-CoV-2 infection during pregnancy and unexposed controls was enrolled in the COVID-19 Mother Baby Outcomes Initiative at Columbia University Irving Medical Center in New York City. All women who delivered at Columbia University Irving Medical Center with a SARS-CoV-2 infection during pregnancy were approached. Women with unexposed infants were approached based on similar gestational age at birth, date of birth, sex, and mode of delivery. Neurodevelopment was assessed using the Ages & Stages Questionnaire, 3rd Edition (ASQ-3) at age 6 months. A historical cohort of infants born before the pandemic who had completed the 6-month ASQ-3 were included in secondary analyses.

Exposures: Maternal SARS-CoV-2 infection during pregnancy and birth during the COVID-19 pandemic.

Main outcomes and measures: Outcomes were scores on the 5 ASQ-3 subdomains, with the hypothesis that maternal SARS-CoV-2 infection during pregnancy would be associated with decrements in social and motor development at age 6 months.

Results: Of 1706 women approached, 596 enrolled; 385 women were invited to a 6-month assessment, of whom 272 (70.6%) completed the ASQ-3. Data were available for 255 infants enrolled in the COVID-19 Mother Baby Outcomes Initiative (114 in utero exposed, 141 unexposed to SARS-CoV-2; median maternal age at delivery, 32.0 [IQR, 19.0-45.0] years). Data were also available from a historical cohort of 62 infants born before the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with significant differences on any ASQ-3 subdomain, regardless of infection timing or severity. However, compared with the historical cohort, infants born during the pandemic had significantly lower scores on gross motor (mean difference, -5.63; 95% CI, -8.75 to -2.51; F1,267 = 12.63; P<.005), fine motor (mean difference, -6.61; 95% CI, -10.00 to -3.21; F1,267 = 14.71; P < .005), and personal-social (mean difference, -3.71; 95% CI, -6.61 to -0.82; F1,267 = 6.37; P<.05) subdomains in fully adjusted models.

Conclusions and relevance: 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.

Figure 1.. Ages & Stages Questionnaire, 3rd Edition (ASQ-3) Scores at Age 6 Months

A, Total raw scores on each ASQ-3 domain for infants with in utero exposure to maternal SARS-CoV-2 infection vs unexposed infants. No significant group differences were identified on any of the ASQ-3 domains in either minimally or fully adjusted models. B, Total raw scores on each ASQ-3 domain for infants born during the pandemic vs a historical cohort born at the same hospital. Blue dashed horizontal lines represent the cutoff indicating possible delay on each subscale (communication, 29.65; gross motor, 22.25; fine motor, 25.14; problem solving, 27.72; personal-social, 25.34). Analyses performed on fully adjusted models. ^aP < .001. ^bP = .01.

Figure 2.. Association Between Gestational Trimester at Pandemic Peak and Ages & Stages Questionnaire, 3rd Edition (ASQ-3) Scores at Age 6 Months

A, Representation of the COVID-19 pandemic in New York City during the time infants in the cohort were born and the gestational timing assignment for the trimester of pregnancy during which the mother experienced the peak of the pandemic. The histogram in black represents the number of recorded daily SARS-CoV-2–positive cases in New York City between March and December 2020. The histogram in purple represents the dates of birth in 2-day bins of infants enrolled in the pandemic cohort. For meaningful comparison with the historical cohort (n = 62), only full-term infants admitted to the Well Baby Nursery were included in the pandemic cohort (n = 227). Gestational timing at the peak of the COVID-19 pandemic in New York City, defined as April 6, 2020 (the date with the highest number of SARS-CoV-2–positive cases), was computed using date of birth and gestational age at birth. The diagram below depicts the trimester of pregnancy corresponding to the dates of birth of infants in the pandemic cohort. Infants with third trimester pandemic exposure were born between March and June 2020, infants with second trimester pandemic exposure were born between June and October 2020, and infants with first trimester pandemic exposure were born between October and December 2020. B, ASQ-3 gross motor, fine motor, and personal-social scores for infants in the historical cohort vs infants in the pandemic cohort by maternal trimester of pregnancy at the peak of the pandemic in New York City. Gray horizontal lines represent the cutoff indicating possible delay on each subscale (gross motor, 22.25; fine motor, 25.14; and personal-social, 25.34). Analyses performed on fully adjusted models. ^aP = .02. ^bP = .002. ^cP = .03.