Long term adverse health outcomes for women and children following SARS-CoV-2 infection during pregnancy

Project Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the virus responsible for the global COVID-19 pandemic of unprecedented scale causes a multi-organ disease with widespread effects. Increasing evidence suggests long-term effects of SARS-CoV-2 infection in some individuals present up to a year after initial infection, referred to as Post-Acute Sequelae of SARS-CoV-2 (PASC). Pregnant women and their fetuses may be particularly vulnerable to the long-term effects of SARS-CoV-2 infection. The biological plausibility and emerging epidemiological evidence from SARS-CoV-2 infections in the population highlight the urgent need for research on the long-term effects of SARS-CoV-2 infection during pregnancy on women's cardiometabolic and neuropsychiatric health outcomes and children's growth and development. Limitations of current studies of both pregnant women with SARS-CoV-2 infection and their children exposed in utero, include a lack of long-term follow-up, lack of data on pre-existing conditions making it difficult to disentangle risk factors for the infection from its consequences, and limited ability to examine associations by predominant SARS-CoV-2 variant and vaccination status. The proposed study leverages Kaiser Permanente Northern California's (KPNC's) high-quality electronic health records (EHR) data on SARS-CoV-2 infection testing and results to assemble a longitudinal pregnancy cohort of >195,000 pregnant women (>22,000 women with SARS-CoV-2 infection during pregnancy and approximately>173,000 without) between March 2020 and December 2022. We will use our robust and comprehensive EHR to follow women and their children for up to 5 years and ascertain clinical diagnoses data. Additionally, we will recruit and survey a subsample of 2000 of the mother-child dyads when the child is 3 years old to ascertain women's and children's self/parent-reported subclinical health outcomes not available in the EHR, but that may suggest a need to monitor and/or provide early interventions. We will randomly identify 1000 dyads with SARS-CoV-2 infection during pregnancy (1/3 early variants, 1/3 Delta and 1/3 Omicron variants) and 1000 dyads without SARS-CoV-2 infection during pregnancy. Our study will assess the following: 1) Evaluate the long-term effects of a SARS-CoV-2 infection during pregnancy on women's cardiometabolic and neuropsychiatric outcomes (EHR and self-report), and 2) Evaluate the long-term effects of in utero exposure to SARS-CoV-2 infection on child growth trajectory and neurodevelopment (EHR and parent-report). We will examine variant, severity of infection and gestational age at infection in relation to all outcomes of interest and explore effect modification by vaccination status, race/ethnicity and pre-existing co-morbidities. Finally, our analyses will include infection status before, during and after pregnancy or birth allowing for estimation of joint effects. This project will fill a significant gap informing women and children exposed to SARS-CoV-2 infection during pregnancy, the public, clinicians, and health care systems of the full spectrum of health consequences of infection.