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Principal Investigator: Leena Bhattacharya Mithal
Organization: LURIE CHILDREN'S HOSPITAL OF CHICAGO
Fiscal Year: 2024
Award: $83,196
Funding agency: National Institute of Allergy and Infectious Diseases
Project Abstract
Pregnant people are uniquely susceptible to SARS-CoV-2 infection, with risks of severe maternal COVID-19
illness and obstetric complications. However, far less is known about the long-term impact of pregnancy-
associated SARS-CoV-2 infection on developing infants. Given the global burden, it is estimated that millions of
pregnant people have had SARS-CoV-2 infection. Prior work by our Studying Novel Infectious Pathogens in
Pregnancy (SNIPP) research team has identified distinct types of SARS-CoV-2-associated injury to the placenta,
such as maternal vascular malperfusion and COVID placentitis. Further, we have identified unique inflammatory
cytokine alterations in patients with specific types of placental lesions following SARS-CoV-2 during pregnancy.
Maternal infection and inflammation can have a complex impact on early brain development and
neurodevelopmental health outcomes. However, there have been very limited studies with differing conclusions
addressing neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 in pregnancy. The
existing literature to date utilizes methods limited by assessment of infants too early (≤12 months) and with
diagnosis codes rather than direct evaluation of the child. With continued viral evolution and a generation of
infants affected by the COVID-19 pandemic, it remains critical to learn if and how SARS-CoV-2 infection in
pregnancy impacts childhood neurodevelopment health and risk of future dysfunction. Our central hypothesis is
that pregnancy-associated SARS-CoV-2 infection and associated placental injury increases risk of adverse early
childhood neurodevelopmental outcomes. We will investigate this hypothesis by utilizing our longitudinal SNIPP
cohort of mother-infant pairs affected by SARS-CoV-2 infection during pregnancy (n~4000) with archived
placental histopathology. We aim to characterize early childhood neurodevelopmental outcomes of infants
following maternal SARS-CoV-2 during pregnancy by Aim 1(a): performing developmental assessments on
infants born to the SARS-CoV-2-infected cohort along with pandemic timeframe uninfected controls; and Aim
1(b): exploring associations between neurodevelopmental abnormalities and placental injury with or without
SARS-CoV-2 infection. In collaboration with Institute for Innovations in Developmental Sciences faculty,
assessments will be performed using validated online parent surveys and remote video visits, focusing on both
broad neurodevelopment and key domains for adaptive functioning: self-regulation and communication. A major
impact of this work would be the identification of high-risk children who need close developmental monitoring.
Strengths of our proposal include our large SNIPP cohort with paired biospecimens, sampling across the
pandemic timeframe, and our transdisciplinary approach harnessing expertise in perinatal infection, placental
pathology, and cutting-edge, pragmatic neurodevelopmental paradigms. This project uniquely poises us to
address an important gap in knowledge that can impact near-term neurodevelopmental care and, through future
research, lead to innovative risk stratification, mechanistic insight, and novel therapeutics to reduce harm.
Terms: <0-11 years old><0-4 weeks old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><Active Follow-up><Address><Adverse effects><Affect><Archives><Area><B.1.617.2><Biometrics><Biometry><Biostatistics><Birth><Blood Vessels><Brain><Brain Nervous System><COVID complications><COVID related complications><COVID-19><COVID-19 complications><COVID-19 infection><COVID-19 pandemic affected><COVID-19 pandemic consequence><COVID-19 pandemic effects><COVID-19 pandemic impact><COVID-19 pandemic impacted><COVID-19 predisposition><COVID-19 related complications><COVID-19 susceptibility><COVID-19 virus><COVID-19 virus infection><COVID-19 vulnerability><COVID19 infection><COVID19 virus><CV-19><Caring><Cells Placenta-Tissue><Child><Child Development><Child Health><Child Youth><Childhood><Children (0-21)><Clinical><CoV-2><CoV2><Code><Coding System><Collaborations><Communication><Complex><Coronavirus Infectious Disease 2019><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 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to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Preeclampsia><Pregnancy><Pregnancy Toxemias><Pregnant Women><Premature Birth><Prematurely delivering><Preterm Birth><Proteinuria-Edema-Hypertension Gestosis><Psychological Health><Public Health><Reporting><Research><Research Specimen><Risk><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 B.1.617.2><SARS-CoV-2 delta><SARS-CoV-2 infection><SARS-CoV-2 predisposition><SARS-CoV-2 susceptibility><SARS-CoV-2 vulnerability><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Science><Self Regulation><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 predisposition><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vulnerability><Severe acute respiratory syndrome related corona virus 2><Specimen><Subgroup><Survey Instrument><Surveys><Therapeutic Research><Variant><Variation><Viral><Work><Wuhan coronavirus><access to vaccination><access to vaccines><active followup><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><biobank><biorepository><cohort><compare to control><comparison control><complications due to COVID-19><congenital infection><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic consequence><coronavirus disease 2019 pandemic impact><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><cytokine><developmental><early childhood><effects following the COVID-19 pandemic><expectant mother><expecting mother><follow up><follow-up><followed up><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><followup><hCoV19><heavy metal Pb><heavy metal lead><high risk><impact of the SARS-CoV-2 pandemic><improved><in utero><infancy><infant outcome><infantile><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><injuries><innovate><innovation><innovative><insight><kids><long-term study><longitudinal outcome studies><longterm study><male><nCoV2><neurodevelopment><new drug target><new drug treatments><new druggable target><new drugs><new pharmacological therapeutic><new pharmacotherapy target><new therapeutic target><new therapeutics><new therapy><new therapy target><newborn child><newborn children><next generation therapeutics><novel><novel drug target><novel drug treatments><novel druggable target><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel pharmacotherapy target><novel therapeutic target><novel therapeutics><novel therapy><novel therapy target><obstetrical complication><pandemic><pandemic disease><parent><pathogen><pathophysiology><pathway><pediatric><post SARS-CoV-2 infection><pre-eclamptic><predisposed to Coronavirus disease 2019><pregnancy toxemia/hypertension><pregnant><pregnant mothers><premature childbirth><premature delivery><prenatal><preterm delivery><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><psychologic><psychological><risk stratification><severe acute respiratory syndrome coronavirus 2 B.1.617.2><sex><stillbirth><stillborn><stratify risk><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><unborn><vaccination access><vaccination availability><vaccine access><vaccine availability><vascular><video visit><vulnerable to COVID-19><vulnerable to Coronavirus disease 2019><vulnerable to SARS-CoV-2><vulnerable to Severe acute respiratory syndrome coronavirus 2><youngster>