Neurological Developmental Differences in Infants Born During the COVID-19 Pandemic

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

Globally, more than 200 million babies have been born since the start of the COVID-19 pandemic. 66 During the first 2 weeks of universal testing at the height of the pandemic in New York City (spring 2020), 14% of women in labor in the University of Irving Medical Center hospital system Columbia tested positive for SARS-CoV-2 by nasopharyngeal polymerase chain reaction.

To date, 2% of the world’s population has been infected at some point during the pandemic.

Although it is impossible to quantify precisely, even the most conservative estimates of the total number of babies worldwide with in utero exposures to maternal SARS-CoV-2 infection vary in the millions.

Fetal exposure to perturbations of the intrauterine environment is implicated in altered brain development and long-term vulnerability of offspring to psychiatric and neurodevelopmental sequelae. Although vertical transmission of SARS-CoV-2 from mother to fetus is rare, data from previous coronavirus outbreaks in humans (SARS and Middle East respiratory syndrome) suggest that severe infection during pregnancy may be associated with poor health. maternal and increased risk of several adverse childhood outcomes through mechanisms related to maternal immune activation.

Other viral diseases during pregnancy are associated with an increased risk of neurodevelopmental deficits, including motor delays, 23 as is the case in uninfected infants exposed to HIV in utero.

Additional epidemiological support for this association comes from naturalistic studies of viral epidemics that identified population-level associations. Cohort studies of the generation born during the 1918 influenza A H1N1 subtype pandemic found lower childhood educational attainment and lower adult socioeconomic status. The rubella pandemic of 1964 led to a 10- to 15-fold increase in autism spectrum disorder or schizophrenia in offspring.

Associations between fetal exposure to maternal SARS-CoV-2 infection and the neurodevelopmental status of the child need to be determined, especially given the well-established benefits of early identification of at-risk children.

The COVID-19 Mother and Baby Outcomes Initiative (COMBO) is a prospective cohort study established at Columbia University Irving Medical Center in spring 2020 to examine associations between in utero exposure to infection maternal mortality from SARS-CoV-2 and the health and well-being of both mothers and children living in New York City, the first epicenter of the pandemic in the US.

 Based on evidence from previous studies, we hypothesized that maternal SARS-CoV-2 infection during pregnancy would be associated with delays in social and motor development at 6 months of age. Additionally, we compared infants born during the COVID-19 pandemic to a historical cohort born at the same medical center using the same neurodevelopmental assessment.

Importance

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

Aim  

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

Design, environment and participants  

A cohort of infants exposed to maternal SARS-CoV-2 infection during pregnancy and unexposed controls were enrolled in the COVID-19 Infant and Mother Outcomes Initiative at Columbia University Irving Medical Center in the city. from New York. All women who delivered at Columbia University Irving Medical Center with a SARS-CoV-2 infection during pregnancy were contacted. 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 and Stages Questionnaire, 3rd edition (ASQ-3) at 6 months of age. A historical cohort of infants born before the pandemic who had completed the 6-month ASQ-3 was included in secondary analyses.

Exhibitions  

Maternal SARS-CoV-2 infection during pregnancy and childbirth during the COVID-19 pandemic.

Main results and measures  

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

Results  

Of 1,706 women contacted, 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 and Baby Outcomes Initiative (114 exposed in utero, 141 not exposed 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 babies born before the pandemic. In utero exposure to maternal SARS-CoV-2 infection was not associated with significant differences in any ASQ-3 subdomains, regardless of timing or severity of infection.

However, compared with the historical cohort, babies born during the pandemic had significantly lower gross motor scores (mean difference, −5.63; 95% CI, −8.75 to −2.51; F 1267 = 12.63; p < 0.005), fine motor skills (mean difference, −6.61; 95% CI, −10.00 to −3.21; F 1267 = 14.71; p < 0.005), and personal-social (mean difference, −3.71; 95% CI, −6.61 to −0.82; F 1,267 = 6.37; P <.05) subdomains in fully adjusted models.