Undernutrition-helminth-alcohol interactions, placental mechanisms, and FASD risk

营养不良-蠕虫-酒精相互作用、胎盘机制和 FASD 风险

基本信息

批准号：
9104456
负责人：
JENNIFER F FRIEDMAN
金额：
$ 27.24万
依托单位：
RHODE ISLAND HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-06 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9104456
关键词：
1 year old Accounting Address Affect Age-Months Alcohol consumption Alcoholic Beverages Alcohols Apoptosis Area Asians Biological Assay Birth Blood Blood Circulation Comorbidity Consumption Country DNA DNA Damage Endotoxins Enrollment Equation Etiology Fetal Alcohol Exposure Fetal Alcohol Spectrum Disorder Fetal Growth Fetal Growth Retardation Filipino Funding Gene Targeting Gestational Age Goals Growth Health Helminthiasis Helminths Histologic Hybrids Immunohistochemistry Impairment Infant Development Infant Health Infection Inflammation Inflammatory Insulin Intake Intervention Joints Low Birth Weight Infant Malnutrition Maternal-Fetal Exchange Measures Modeling Modification Molecular Morbidity - disease rate Neurocognitive Deficit Newborn Infant Nutritional status Outcome Pathogenesis Pathology Pathway interactions Perinatal Philippines Placenta Placentation Praziquantel Pregnancy Pregnant Women Randomized Controlled Trials Recruitment Activity Reference Standards Reporting Research Infrastructure Research Personnel Risk Risk Factors Schistosomiasis Serum Signal Transduction Spottings Structure Techniques Training Umbilical Cord Blood United States National Institutes of Health Weight Weight Gain Wine Woman adverse pregnancy outcome alcohol exposure attributable mortality base burden of illness design disability-adjusted life years disorder risk experience infancy infant outcome inflammatory marker innovation intestinal fatty acid binding protein low and middle-income countries maternal serum microbial mortality placental morphology premature prenatal intervention promoter public health relevance

项目摘要

DESCRIPTION (provided by applicant): Low birth weight, particularly as a result of fetal growth restriction (FGR), disproportionately affects women residing in low and middle income countries (LMICs) and places newborns at increased risk of morbidity and mortality. In LMICs, FGR contributes more significantly to the burden of LBW than does prematurity. Despite this, significant lacunae remain with respect to our understanding of the etiology of FGR, hampering the design of rationale interventions to address this enormous burden. The overarching goals of this application are to 1) build an infrastructure for studies of alcohol and pregnancy in LMICs and 2) further our understanding of the mechanisms through which alcohol exposure interacts with other exposures unique to the LMIC setting to increase risk for adverse pregnancy outcomes seen in the context of fetal alcohol spectrum disorders, in particular FGR. FASDs are responsible for approximately 12.5% of alcohol-attributable deaths globally, with a significant portion of the global burden of disease is related to morbidity. In our recently completed NIH funded RCT of Praziquantel treatment during pregnancy, over 75% of subjects reported continued alcohol consumption at 12-16 weeks gestation. For the current application we will recruit N=400 women at 10-16 weeks gestation to examine the independent contribution of prevalent exposures in LMICs (alcohol, helminthiasis, undernutrition) and formally address whether these exposures interact to increase risk for adverse newborn and infant outcomes, in particular FGR (SA1). We hypothesize that each of these exposures will disrupt gut integrity, as we have demonstrated in the context of schistosomiasis, culminating in microbial translocation whereby endotoxin and other microbial products are detectable in the maternal systemic circulation and at the maternal fetal interface. In SA2, we will assess the placental mechanisms through which these exposures culminate in adverse birth outcomes, including a shift to a more pro-inflammatory placental micro-environment, disruptions in placentation captured with histologic and molecular techniques, and downmodulation of IGF pathways. In SA3, we will construct sophisticated Structural Equation Models to investigate how prevalent exposures impact placental health to ultimately contribute to the enormous global burden of disease due to FGR, growth stunting in infancy, and neurocognitive deficits at 12 months of age. Given the interdisciplinary expertise of co-investigators and the extensive experience of our field staff in Leyte, we are poised to rapidly initiate these innovative studies, which will inform pre-natal interventions to reduce these risks.

描述（由适用提供）：低出生体重，特别是由于胎儿生长限制（FGR）的结果，对居住在低收入国家（LMIC）（LMIC）（LMIC）的妇女（LMIC）的妇女不成比例，并使新生儿的发病率和死亡风险增加。在LMIC中，FGR对LBW的燃烧贡献比早产性更大。尽管如此，在我们对FGR病因的理解方面仍然存在着重要的空白，从而阻碍了解决这一巨大伯宁的理由干预措施的设计。本应用的总体目标是1）建立一个基础设施，用于研究LMIC的酒精和妊娠研究，以及2）进一步了解我们对酒精暴露与LMIC环境所特有的其他暴露相互作用的机制，以增加在胎儿酒精疾病的背景下看到的不良妊娠结局的风险，尤其是FGR。 FASD在全球范围内约有约12.5％的酒精杀伤力死亡，其中大部分全球疾病燃烧与发病率有关。在我们最近完成的NIH资助的妊娠praziquantel治疗RCT中，超过75％的受试者报告妊娠12-16周持续饮酒。对于当前的应用，我们将在10-16周的妊娠中招募N = 400名女性，以检查LMICS（酒精，Helminthiasis，Helminthiasis，Bentrition）中普遍暴露的独立贡献，并正式解决这些暴露以增加对不良新生儿和婴儿的风险是否相互作用，尤其是FGR（SA1）。我们假设这些暴露中的每一种都会破坏肠道完整性，正如我们在血吸虫病的背景下所证明的那样，最终在微生物易位中达到内毒素和其他微生物产物，可在母体系统的圆圈中检测到内毒素和其他微生物产物。在SA2中，我们将评估这些曝光以提前出生结果达到最终结束的位置机制，包括转移到更促炎性的局部性位置微环境，用组织学和分子技术捕获的位置中的破坏以及IGF途径的下调。在SA3中，我们将构建复杂的结构方程模型，以调查普遍的暴露如何影响plapenal健康，以最终导致由于FGR，婴儿期生长stought缩并且神经认知能力定义在12个月大时的巨大疾病负担。鉴于共同投资者的跨学科专业知识以及我们在莱特（Leyte）的现场工作人员的丰富经验，我们被毒死以迅速启动这些创新研究，这将为您降低这些风险的产前干预措施提供信息。