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Principal Investigator: Gianluca Ursini
Organization: LIEBER INSTITUTE, INC.
Fiscal Year: 2024
Award: $1,431,755
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
PROJECT SUMMARY
The extent to which SARS-CoV-2 infection in pregnancy affects the biology of the maternal-placental-fetal triad
and neurodevelopmental trajectory in offspring is not known. Early studies indicate that SARS-CoV-2 can induce
alterations in the placenta which can increase risk for adverse perinatal outcomes and, based on knowledge
from other infectious and inflammatory disorders in pregnancy and preliminary data on the current pandemic,
increase risk for neurodevelopmental disorders (NDDs) in offspring. The long-term goal of this proposal is to
timely identify the impact of the ongoing pandemic on the neurodevelopment of infants born following maternal
SARS-CoV-2 infection. The objective is to analyze the relationships between maternal SARS-CoV-2 infection,
placenta biology, and neurodevelopmental outcomes, in interaction with genomic risk (GRSs) for NDDs and sex.
The central hypothesis is that maternal SARS-CoV-2 infection and infection-related pregnancy complications
affect early paths of brain development, particularly in those with high GRSs for NDDs and in males, and that
these effects are mediated by alterations in placenta morphology and molecular biology. The rationale underlying
the proposal is that completion will define critical targets for identification and potentially prevention of NDDs in
the offspring of infected mothers. The central hypothesis will be tested by pursuing the following specific aims:
1) Determine pregnancy, placental, and newborn outcomes following antenatal SARS-CoV-2 infection; 2)
Investigate the relationship between SARS-CoV-2 maternal infection, GRSs for NDDs, and placenta molecular
biology; 3) Evaluate the relationship between maternal SARS-CoV-2 infection in pregnancy, offspring genomic
risk factors for NDDs, and neurodevelopmental outcomes. We will pursue the aims using an innovative
combination of placenta tissue and maternal and fetal blood analysis, and comprehensive psychometric testing
of early child neurodevelopment. We will compare woman-placenta-infant triads exposed to SARS-CoV-2
infection during pregnancy to unvaccinated and vaccinated controls. We will study how, in a large sample of
multiple ethnicities, maternal infection and stress, GRSs for NDDs, and sex, adversely affect
neurodevelopmental outcomes of the offspring though processes mediated by alteration in placenta gene/protein
expression and maternal immune activation. The proposed research is significant, because it will characterize
the relationship between maternal SARS-CoV-2 infection and neurodevelopmental outcome of the offspring, and
also identify factors, molecules and genomic predictors that modulate, mediate or – as biomarkers – reveal such
relationship. The proximate expected outcome of this work will be an understanding of the mechanisms through
which maternal infection, genomic risk and sex, placenta biology, and postnatal factors may contribute to define
risk for NDDs. The results will have an immediate positive impact to inform targeted interventions and guidelines
for SARS-CoV-2 exposed women and their infants, impacting how clinicians evaluate and care for these cases,
and to identify potential biomarkers of risk for NDDs in offspring of mothers with infection during pregnancy.
Terms: <0-11 years old><0-4 weeks old><1st trimester><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2nd trimester><AD/HD><ADHD><ASD><Active Follow-up><Affect><Age><Age Months><Attention deficit hyperactivity disorder><Autism><Autistic Disorder><Biological Markers><Biology><Birth><Blood Vessels><Body Tissues><Brain><Brain Nervous System><COVID crisis><COVID epidemic><COVID pandemic><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 exposure><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 pandemic><COVID-19 period><COVID-19 positive><COVID-19 positivity><COVID-19 public health crisis><COVID-19 virus><COVID-19 virus infection><COVID-19 years><COVID19 infection><COVID19 virus><Caring><Cells Placenta-Tissue><Cerebral Palsy><Child><Child Support><Child Youth><Childhood><Children (0-21)><Chronologic Fetal Maturity><Clinical><CoV-2><CoV2><Control Groups><DNA Molecular Biology><Data><Decidua Basalis><Developing fetus><Development><Discipline of obstetrics><Disease><Disease Outbreaks><Disorder><EPH Gestosis><Early Infantile Autism><Early Placental Phase><Education for Intervention><Educational Intervention><Encephalon><Environment><Ethnic Origin><Ethnicity><Evaluation><Event><Exhibits><Fetal Age><Fetal Development><Fetal Growth><Fetal Growth Restriction><Fetal Growth Retardation><Fever><First Pregnancy Trimester><First Trimester><Fostering><Future><Gene Expression><Genes><Genomics><Gestation><Gestational Age><Goals><Guidelines><Hospitals><Hyperthermia><IUGR><Immune Cell Activation><Individual><Infant><Infantile Autism><Infection><Inflammatory><Instruction Intervention><Intervention><Intervention Strategies><Intrauterine Growth Retardation><Kanner's Syndrome><Knowledge><Link><Maternal Health><Maternal placenta><Mediating><Midtrimester><Mission><Molecular Biology><Mothers><NIH><National Institutes of Health><Neonatal><Neural Development><Neurodevelopmental Disorder><Neurological Development Disorder><Neurology><Newborn Infant><Newborns><Non-Polyadenylated RNA><Normal Placentoma><Obstetrics><Outbreaks><Outcome><Parturition><Pathology><Peptides><Placenta><Placenta Biology><Placenta Embryonic Tissue><Placental Biology><Placentome><Pre-Eclampsia><Predominantly Hyperactive-Impulsive Type Attention-Deficit Disorder><Predominantly Hyperactive-Impulsive Type Hyperactivity Disorder><Preeclampsia><Pregnancy><Pregnancy Complications><Pregnancy Histories><Pregnancy Toxemias><Pregnant Women><Premature Birth><Prematurely delivering><Preparedness><Preterm Birth><Preventative intervention><Prevention><Process><Proteins><Proteinuria-Edema-Hypertension Gestosis><Proteomics><Psychometrics><Public Health><Pyrexia><RNA><RNA Gene Products><Readiness><Recovery><Research><Ribonucleic Acid><Risk><Risk Factors><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 epidemic><SARS-CoV-2 exposure><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 infection><SARS-CoV-2 pandemic><SARS-CoV-2 positive><SARS-CoV-2 positivity><SARS-CoV2><SARS-CoV2 exposure><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Schizophrenia><Schizophrenic Disorders><Second Pregnancy Trimester><Second Trimester><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 CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><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 epidemic><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 positive><Severe acute respiratory syndrome coronavirus 2 positivity><Severe acute respiratory syndrome related corona virus 2><Severities><Stress><Testing><Therapeutic Intervention><Tissues><Training Intervention><United States National Institutes of Health><Vaccinated><Vertical Transmission><Viral Diseases><Virus Diseases><Woman><Work><Wuhan coronavirus><active followup><adverse pregnancy outcome><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><ages><antenatal><antepartum><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><bio-markers><biologic marker><biomarker><biomarker identification><cohort><complications during pregnancy><congenital infection><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 exposure><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 positive><coronavirus disease 2019 positivity><coronavirus disease 2019 public health crisis><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 virus><current pandemic><dementia praecox><developmental><expectant mother><expecting mother><experience><exposed in utero><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><febrile><febris><fetal><fetal blood><fetal exposure><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><genomic predictors><hCoV19><identification of biomarkers><identification of new biomarkers><immune activation><impaired fetal growth><improved><in utero><in utero exposure><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><innovate><innovation><innovative><instructional intervention><intervention for prevention><intervention therapy><interventional strategy><intra-uterine environmental exposure><intra-uterine growth><intra-uterine growth restriction><intra-uterine growth retardation><intrauterine environmental exposure><intrauterine growth><intrauterine growth restriction><kids><male><marker identification><maternal stress><nCoV2><neurodevelopment><neurodevelopmental disease><newborn child><newborn children><non vaccinated><not vaccinated><offspring><pandemic><pandemic containment><pandemic control><pandemic disease><pandemic mitigation><pandemic response><pediatric><perinatal outcomes><placenta morphology><placental morphology><post SARS-CoV-2 infection><postnatal><potential biological marker><potential biomarker><pre-eclamptic><pre-pandemic><pregnancy toxemia/hypertension><pregnancy-related complications><pregnant mothers><premature childbirth><premature delivery><prenatal><prenatal exposure><prenatal growth disorder><prenatally exposed><present pandemic><preterm delivery><prevention intervention><preventional intervention strategy><preventive intervention><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><programs><protein expression><recruit><scRNA-seq><schizophrenic><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><stressed mothers><symptomatic COVID-19><symptomatic COVID19><symptomatic SARS-CoV-2 infection><symptomatic coronavirus disease 2019><unborn><unvaccinated><vascular><viral infection><virus infection><virus-induced disease><youngster>