Infant Immunologic and Neurologic Development following Maternal Infection in Pregnancy during Recent Epidemics

近期流行病期间妊娠期感染后婴儿的免疫和神经系统发育

• 批准号: 10784250
• 负责人: Jae U Jung
• 金额: $ 37万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-24 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10784250
• 关键词: 2019-nCoV; Address; Affect; Age; Americas; Antigens; Area; Awareness; Behavioral; Biological Markers; Birth; Brain; Brazil; COVID-19; COVID-19 pandemic; Cephalic; Child; Child Welfare; Childhood; Clinical; Cognition; Collaborations; Communicable Diseases; Data; Development; Diagnosis; Diagnostic; Discipline of obstetrics; Disease; Disease-Free Survival; Enrollment; Epidemic; Epidemiology; Evaluation; Exposure to; Fetus; Functional disorder; Future; Goals; Growth; Health; Image; Immune; Immune response; Immune system; Immunization; Immunoglobulin M; Immunologics; Immunology; Impairment; Infant; Infection; Inflammatory; Infrastructure; Knowledge; Language; Language Delays; Language Development; Learning; Learning Disabilities; Literature; Longitudinal cohort; Longitudinal cohort study; Maternal-Fetal Transmission; Maternally-Acquired Immunity; Methods; Molecular; Monitor; Mothers; Motor; Neurocognitive Deficit; Neurologic; Neuropathogenesis; Organ; Outcome; Pathogenesis; Patient Recruitments; Perinatal Infection; Personal Satisfaction; Population; Pregnancy; Pregnancy Trimesters; Pregnant Women; Productivity; Prospective cohort; Proteomics; Reporting; Research; Research Personnel; Risk; SARS-CoV-2 infection; School-Age Population; Scientist; Sensory; Severities; T-Lymphocyte; Technology; Time; United States; Vaccines; Vertical Transmission; Viral; Virus; Vulnerable Populations; ZIKA; ZIKV infection; Zika Virus; antenatal; autism spectrum disorder; calcification; chemokine; clinical research site; cohort; congenital infection; congenital zika syndrome; coronavirus disease; early childhood; experience; fetal; global health emergency; hearing impairment; immune activation; immune function; in utero; infant outcome; maternal outcome; multidisciplinary; neurodevelopment; neurological rehabilitation; neurosensory; neutralizing antibody; new outbreak; novel; novel coronavirus; pandemic disease; pathogen; prenatal; programs; response; sample collection; tool; vaccine response; virology

Abstract/Summary The massive outbreak of newly emerged coronavirus disease 2019 (COVID-19) saw rapid global spread, leading to a pandemic infection and an unprecedented global health emergency. Just years before, we witnessed the devastating impact of Zika virus (ZIKV) to unborn fetuses in the Americas. This proposal responds to the need to fill critical gaps in the understanding of the clinical repercussions of antenatal infections such as ZIKV and SARS-CoV-2 infection in pregnant women to the developing immune system of their infants, through the evaluation of cellular and humoral immune responses and clinical and neurodevelopmental outcomes following maternal immune activation (MIA) in this vulnerable population. Our team of researchers has been collaborating over the last 7 years to characterize the clinical and cellular effects of in utero transmission of Zika virus (ZIKV), with the collection of specimens from over hundreds of mother- infant pairs from Brazil. We reported on multiple obstetrical and clinical outcomes of infants with congenital ZIKV infection in the literature, including that ZIKV vertical transmission rate is at least 65%, that infected children do not develop ZIKV specific neutralizing antibodies despite an early IgM response, and that maternal humoral immune responses tend to be robust with highly neutralizing activity. During the COVID-19 pandemic we established a cohort of mother-infant pairs at UCLA and Fiocruz, Rio de Janeiro and controls with mother-infant dyads enrolled to date in both places. We are utilizing the existing infrastructure and scientific methods developed in the aftermath of the ZIKV epidemic to further evaluate clinical, cellular humoral and inflammatory parameters predicting immunologic outcomes in infants and children exposed to either maternal ZIKV and SARS Cov2 infection. The main goal of the proposed research is to comprehensively characterize repercussions of MIA on infant immune development and clinical outcomes, with a focus on immune pathogenesis. We include a longitudinal cohort of 200 mother- infant pairs with COVID-19 and 100 healthy control mother-infant pairs in the US and Brazil and 200 mother-infant pairs with ZIKV in Brazil and 100 healthy control pairs at the same clinical sites to address these goals. This RO1 proposes to evaluate the repercussions of MIA on infant well- being and immune development. State of the art technology is used to address the scientific aims, with the research led by experts in the field of immunology, infectious diseases & congenital infections who have ongoing successful, productive partnerships. The data rendered will be crucial for the knowledge of immune pathogenesis in pediatric populations with antenatal viral exposures.

摘要/摘要 2019年新出现的冠状病毒病（Covid-19）的大规模爆发迅速全球 传播，导致大流行感染和空前的全球健康紧急情况。只是 几年前，我们目睹了寨卡病毒（Zikv）对未出生的胎儿的破坏性影响 美洲。该提案回应在理解中填补关键空白的需求 怀孕的产前感染（例如ZIKV和SARS-COV-2感染）的临床影响 通过评估细胞和 母体后的体液免疫反应以及临床和神经发育结果 该脆弱人群中的免疫激活（MIA）。我们的研究人员团队已经 在过去的7年中，合作以表征子宫内的临床和细胞效应 寨卡病毒（ZIKV）的传播，收集了来自数百多个母亲的标本 来自巴西的婴儿。我们报告了婴儿的多个产科和临床结果 文献中先天性ZIKV感染，包括ZIKV垂直传输率至少为 65％，感染的儿童尽管早期不发展ZIKV特异性中和抗体 IgM反应，而母体的体液免疫反应往往很健壮 中和活性。在Covid-19大流行期间，我们建立了一群母亲 在加州大学洛杉矶分校和菲奥克鲁斯，里约热内卢和与母亲二元组的控制 在两个地方的日期。我们正在利用现有的基础设施和开发的科学方法 在ZIKV流行之后，以进一步评估临床，细胞体液和 预测婴儿和儿童的免疫结局的炎症参数 母体ZIKV和SARS COV2感染。拟议研究的主要目标是 全面表征了MIA对婴儿免疫发育和临床的影响 结果，重点是免疫发病机理。我们包括一个由200个母亲组成的纵向队列 在美国和巴西和100个健康对照组合的婴儿和100个健康对照的母亲成对和巴西和 在巴西有200个与ZIKV的母子对，在同一临床部位的100对健康对照对 解决这些目标。该RO1提议评估MIA对婴儿井的影响 存在和免疫发展。最先进的技术用于解决科学目标， 由免疫学领域，传染病和先天性领域的专家领导的研究 持续成功的生产伙伴关系的感染。渲染的数据将是 对产前病毒的小儿种群中免疫发病机理的了解至关重要 暴露。

项目成果

Infant movement classification through pressure distribution analysis.

• DOI: 10.1038/s43856-023-00342-5
• 发表时间: 2023-08-16
• 期刊: COMMUNICATIONS MEDICINE
• 作者: Kulvicius, Tomas;Zhang, Dajie;Nielsen-Saines, Karin;Bolte, Sven;Kraft, Marc;Einspieler, Christa;Poustka, Luise;Worgotter, Florentin;Marschik, Peter B
• 通讯作者: Marschik, Peter B