The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected hundreds of million individuals globally. Pregnant women are particularly susceptible to respiratory infections because they are in a state of immune suppression. Early case studies reported a relationship between severe COVID-19 and risk of adverse child outcomes, including preterm birth and low birth weight.

To carefully investigate the impact of maternal SARS-CoV-2 infection, Anna-Sophie Rommel and her colleagues set up a large-scale prospective pregnancy cohort, Generation C, at the Mount Sinai Health System in New York City in the early weeks of the pandemic (with the goal of recruiting 3,000 pregnant women)¹. Specifically, their aims were to establish maternal SARS-CoV-2 IgG status and the level of maternal inflammatory response early and late in pregnancy to assess the effect of SARS-CoV-2 infection and inflammation on short- and long-term child outcomes and to examine the extent to which SARS-CoV-2 infections disproportionately impact mother-child pairs from underserved communities.

As part of the current study protocol, the Generation C team obtains: (1) blood samples early and late in pregnancy, (2) IgG antibodies to SARS-CoV-2, (3) peripheral inflammatory markers (IL-1ß, IL-6, IL-8, IL-10, IL-17, Treg and Th17 cells), (4) clinical data from electronic medical records, (5) self-reports on COVID-19 symptoms and vaccination status, (6) placental tissues and (7) self-reports of maternal mental health pre- and postnatally. To date, Rommel and her colleagues have recruited 2,717 women into the study, of which 18 percent have been exposed to SARS-CoV-2. The cohort is representative of New York City’s racial/ethnic and socioeconomic diversity.

Epidemiological evidence implicates maternal infection during pregnancy as a risk factor for neurodevelopmental conditions such as autism spectrum disorder (ASD). Animal models corroborate this association, showing that maternal immune activation during pregnancy alone is sufficient to impart lifelong neuropathology and behavioral phenotypes relevant to ASD in offspring.

The large, well-defined sample and extensive biospecimen collection of the Generation C cohort affords the unique opportunity to better understand the impact of maternal infection and inflammation on risk for neurodevelopmental conditions such as ASD. Consequently, it is important to follow up on the children of Generation C to investigate the relationship between SARS-CoV-2 exposure, inflammation and neurodevelopment.

The supplemental funding from SFARI will build on the successful ongoing Generation C cohort by setting up the infrastructure to retain participants for longitudinal follow-up to investigate longer-term effects of SARS-CoV-2 infection and inflammation on child neurodevelopment. Rommel and her colleagues hypothesize that maternal infection and inflammation will have clinically relevant adverse effects on neurodevelopment, increasing the risk for ASD.

Specifically, they plan to develop a comprehensive database to track participants, including address history, phone numbers, email addresses, social media accounts and the contact information of locators (e.g., a spouse or relative). They will also employ community building and other engagement activities to build and maintain a strong relationship with the participants.

Long-term investigations will study the impact of prenatal exposure to SARS-CoV-2 infection on cognitive, social and motor development at one and two years of age using the Ages and Stages Questionnaire, the Preschool version of the Child Behavior Checklist and the Social Responsiveness Scale. Potential impacts on child brain function will be assessed using electroencephalogram (EEG).