Maternal SARS-CoV-2 infection, placenta biology, and neurodevelopmental outcomes in the offspring

母体 SARS-CoV-2 感染、胎盘生物学和后代的神经发育结果

基本信息

批准号：
10819677
负责人：
Gianluca Ursini
金额：
$ 72.14万
依托单位：
LIEBER INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-05 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10819677
关键词：
2019-nCoV Address Affect Biological Markers Biology Brain Caring Child Data Development Disease Disease Outbreaks Ethnic Origin Event Fostering Future Genes Genomics Goals Guidelines Infant Infection Inflammatory Intervention Knowledge Mediating Mental Health Mission Molecular Biology Mothers Neurodevelopmental Disorder Newborn Infant Outcome Placenta Placental Biology Pregnancy Pregnancy Complications Prevention Process Psychometrics Public Health Readiness Recovery Research Risk Risk Factors SARS-CoV-2 exposure SARS-CoV-2 infection Sampling Stress Testing Time Tissues United States National Institutes of Health Vaccinated Vulnerable Populations Woman Work antenatal biomarker identification current pandemic fetal fetal blood genomic predictors immune activation improved innovation male neurodevelopment offspring pandemic disease perinatal outcomes placental morphology postnatal potential biomarker prenatal exposure protein expression sex social health determinants unvaccinated

项目摘要

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 (ND) 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 ND 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 ND 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 ND. We will compare unvaccinated and vaccinated 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, social determinants of health, 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.

项目概要妊娠期 SARS-CoV-2 感染对母体-胎盘-胎儿三联体生物学的影响程度早期研究表明 SARS-CoV-2 可以诱导后代的神经发育轨迹。胎盘的改变可能会增加不良围产期结局的风险，并且根据知识根据怀孕期间的其他传染性和炎症性疾病以及当前大流行的初步数据，增加后代神经发育障碍 (NDD) 的风险该提案的长期目标是及时确定持续的大流行对出生后出生的婴儿神经发育（ND）的影响母体 SARS-CoV-2 感染目的是分析母体 SARS-CoV-2 之间的关系。感染、胎盘生物学和 ND 结果，与 NDD 和性别的基因组风险 (GRS) 的相互作用。中心假设是母体 SARS-CoV-2 感染和感染相关的妊娠并发症会影响大脑发育的早期路径，特别是那些 NDD 的 GRS 较高的人和男性，并且这些影响是通过胎盘形态和分子生物学的改变介导的。建议完成后将确定识别和潜在预防 NDD 的关键目标受感染母亲的后代将通过追求以下具体目标来检验中心假设：1）确定产前 SARS-CoV-2 感染后的妊娠、胎盘和新生儿结局；2) 研究 SARS-CoV-2 母体感染、NDD 的 GRS 和胎盘分子之间的关系生物学；3) 评估妊娠期间母亲SARS-CoV-2感染与后代基因组之间的关系 NDD 的风险因素和 ND 结果我们将使用胎盘的创新组合来实现这一目标。我们将进行组织和母体及胎儿血液分析，以及早期儿童 ND 的综合心理测试。比较未接种疫苗和肺炎期间暴露于 SARS-CoV-2 感染的妇女-胎盘-婴儿三联征我们将研究如何在多个种族的大样本中，孕产妇感染和压力、健康的社会决定因素、NDD 的 GRS 以及性别都会产生不利影响通过胎盘基因/蛋白质改变介导的过程产生后代的神经发育结果拟议的研究具有重要意义，因为它将表征。母体 SARS-CoV-2 感染与后代神经发育结果之间的关系，以及还确定了调节、介导或作为生物标志物揭示这些的因素、分子和基因组预测因子这项工作的近期预期成果将是通过以下方式了解这些机制。孕产妇感染、基因组风险和性别、胎盘生物学和产后因素可能有助于定义 NDD 风险的结果将产生直接的积极影响，为有针对性的干预措施和指南提供信息。对于暴露于 SARS-CoV-2 的妇女及其婴儿，影响精英们如何评估和护理这些病例，并确定妊娠期间感染母亲的后代患 NDD 风险的潜在生物标志物。