In utero exposure to maternal SARS-CoV-2 infection not associated with neurodevelopmental deficits at 6 months

1. In a prospective cohort study of about 250 infants, infants born to mothers with COVID-19 during pregnancy had no significant neurodevelopmental differences compared to unexposed infants at 6 months old.

2. Compared to a cohort born before the COVID-19 pandemic, infants born during the pandemic had lower survey scores in several neurodevelopmental domains.

Evidence Rating Level: 2 (Good)

Study Rundown: The impact, if any, of in utero exposure to SARS-CoV-2 on pediatric outcomes such as early neurological development remains unclear. This study at a single academic center in New York City aimed to identify developmental delays in a cohort of infants whose mothers had a SARS-CoV-2 infection at any point during pregnancy via comparison to unexposed infants born both during and before the COVID-19 pandemic. 255 mothers, 114 of whom had had COVID-19 during pregnancy, completed an Ages & Stages Questionnaire (ASQ-3) about their 6 month-old infants. The pre-pandemic control group included 62 infants. Exposed and unexposed infants within the pandemic cohort did not significantly differ in overall ASQ-3 scores nor in any developmental subdomains. Disease severity and timing within pregnancy also did not significantly affect scores. However, the combined group of exposed and unexposed infants born during the pandemic scored significantly lower in the gross motor, fine motor, and personal-social subdomains than the pre-pandemic group. Overall, this study suggests no direct association between in utero COVID-19 exposure and neurodevelopmental delay, but instead points to an overall epidemiologic difference associated with the COVID-19 pandemic era. This study’s relatively small size and dependence on a survey subject to recall bias are both limitations. However, a population-wide neurodevelopmental effect related to the stresses of the pandemic is plausible and warrants further study, including examination of any relationship with factors such as birth weight and prematurity.

Click to read the study in JAMA Pediatrics

Click to read an accompanying editorial in JAMA Pediatrics

Relevant Reading: Pregnancy and COVID-19

In-Depth [prospective cohort]: Controls were matched by infant sex, gestational age at birth, mode of delivery, and date of birth within 2 weeks. Infants born before 37 weeks gestational age were excluded. Infants in the pandemic cohort were born between March and December 2020 and the pre-pandemic cohort between November 2017 and January 2020. Maternal COVID-19 infections were identified based on polymerase chain reaction or serology test; 39 of the 114 women were asymptomatic. 5 infants in the pandemic cohort had a COVID-19 infection themselves between birth and the 6 month assessment. Analyses of covariance were used to compare infants between groups as well as within the exposed group based on factors including infection timing and severity. Mothers with SARS-CoV-2 infection differed significantly from noninfected mothers in race, ethnicity, and educational level, reflecting the disparate demographics of the pandemic. Models adjusted for maternal demographics. Exclusion of infants with asymptomatically infected mothers, preterm birth, or neonatal intensive care unit (NICU) admission in sensitivity analyses did not lead to significant differences between exposed and unexposed groups. Out of total scores of 60 on each subdomain, gross motor scores were 5.63 points lower, fine motor 6.61 points lower, and personal-social 3.71 points lower in the pandemic compared to pre-pandemic group, all with p<0.001.

Image: PD

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