Fetal Neuroprotection by choline supplementation in heavy drinking pregnant women

大量饮酒孕妇补充胆碱对胎儿神经的保护

基本信息

批准号：
10583742
负责人：
ROBERT COLIN CARTER
金额：
$ 48.9万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10583742
关键词：
Acetylcholine Adverse effects Affect Age Months Alcohols Anatomy Animals Anisotropy Area Award Birth Brain Brain region Cell membrane Cells Cellular Structures Choline Clinical Clinical Trials Cognitive Cognitive deficits Collaborations Communities Community Practice Counseling Coupled DNA Methylation Data Development Dietary Supplementation Diffusion Diffusion Magnetic Resonance Imaging Disadvantaged Dose Double-Blind Method Down Syndrome Energy Metabolism Enrollment Fetal Alcohol Exposure Fetal Alcohol Spectrum Disorder Fetal Development Fetal alcohol effects Fetus Funding General Hospitals Gestational Age Grant Growth Growth and Development function HIV Head circumference Heavy Drinking Hippocampus Infant Intake Intellectual functioning disability Intervention Investments Knowledge Learning Length Magnetic Resonance Imaging Massachusetts Measurable Measurement Measures Mediating Metabolic Metabolism Modeling N-acetylaspartate National Institute on Alcohol Abuse and Alcoholism Neonatal Nervous System Trauma Neural Tube Closure Neurocognitive Neurotransmitters Newborn Infant Nutrient Nutritional Nutritional status Outcome Perinatal Placebo Control Placebos Pregnancy Pregnant Women Prevalence Province Public Health Randomized Research Personnel Research Priority Rett Syndrome Role Short-Term Memory South Africa Structure Supplementation Test Result Treatment Efficacy United States National Institutes of Health Universities Weight Woman arm autism spectrum disorder brain volume choline supplementation cognitive development cognitive testing conditioned fear deep learning dietary drinking eyeblink conditioning fetal high risk human study improved infant outcome information processing magnetic resonance spectroscopic imaging medical schools memory recognition metabolic imaging methyl group multimodality neonatal brain neonatal magnetic resonance imaging neonate neurodevelopment neuroimaging neuromechanism neuroprotection postnatal prenatal prenatal intervention primary outcome processing speed psychosocial randomized placebo controlled trial randomized placebo-controlled clinical trial randomized, clinical trials recruit remediation rural area secondary outcome spectrograph standard of care white matter

Acetylcholine Adverse effects Affect Age Months Alcohols Anatomy Animals Anisotropy Area Award Birth Brain Brain region Cell membrane Cells Cellular Structures Choline Clinical Clinical Trials Cognitive Cognitive deficits Collaborations Communities Community Practice Counseling Coupled DNA Methylation Data Development Dietary Supplementation Diffusion Diffusion Magnetic Resonance Imaging Disadvantaged Dose Double-Blind Method Down Syndrome Energy Metabolism Enrollment Fetal Alcohol Exposure Fetal Alcohol Spectrum Disorder Fetal Development Fetal alcohol effects Fetus Funding General Hospitals Gestational Age Grant Growth Growth and Development function HIV Head circumference Heavy Drinking Hippocampus Infant Intake Intellectual functioning disability Intervention Investments Knowledge Learning Length Magnetic Resonance Imaging Massachusetts Measurable Measurement Measures Mediating Metabolic Metabolism Modeling N-acetylaspartate National Institute on Alcohol Abuse and Alcoholism Neonatal Nervous System Trauma Neural Tube Closure Neurocognitive Neurotransmitters Newborn Infant Nutrient Nutritional Nutritional status Outcome Perinatal Placebo Control Placebos Pregnancy Pregnant Women Prevalence Province Public Health Randomized Research Personnel Research Priority Rett Syndrome Role Short-Term Memory South Africa Structure Supplementation Test Result Treatment Efficacy United States National Institutes of Health Universities Weight Woman arm autism spectrum disorder brain volume choline supplementation cognitive development cognitive testing conditioned fear deep learning dietary drinking eyeblink conditioning fetal high risk human study improved infant outcome information processing magnetic resonance spectroscopic imaging medical schools memory recognition metabolic imaging methyl group multimodality neonatal brain neonatal magnetic resonance imaging neonate neurodevelopment neuroimaging neuromechanism neuroprotection postnatal prenatal prenatal intervention primary outcome processing speed psychosocial randomized placebo controlled trial randomized placebo-controlled clinical trial randomized, clinical trials recruit remediation rural area secondary outcome spectrograph standard of care white matter

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项目摘要

PROJECT SUMMARY Fetal alcohol spectrum disorders represent the most prevalent cause of preventable intellectual disability. Prevalence in high-risk communities in the Western Cape region of South Africa may be as high as 20.9%. Prenatal alcohol exposure (PAE) impacts the developing brain, resulting in cognitive deficits, growth restriction and structural brain changes. Despite psychosocial interventions, heavy drinking during pregnancy continues to be a major public health challenge in the Western Cape, U.S. and worldwide. In a recent preliminary study, we showed that high dose maternal choline supplementation during pregnancy mitigates adverse effects of PAE on infant growth and cognitive development, as well as neonatal brain structure. This proposal will add on to a recently NIH-funded fully-powered, double-blind, randomized placebo-controlled trial in which 288 heavy drinking Western Cape women will be given choline or placebo during pregnancy and infants will be assessed through 12 months of age. We propose the addition of neonatal neuroimaging, including brain anatomical, diffusion and metabolic spectral imaging, to examine neural mechanisms mediating the beneficial effects of maternal choline supplementation on infant developmental outcomes. We hypothesize that choline supplementation in heavy drinking pregnant women will reduce the adverse impact of PAE on the developing fetal brain by normalizing anatomical development, connectivity, and brain energy metabolism. Brain development is energy demanding and highly sensitive to nutritional reserves. Alcohol measurably disrupts brain metabolites. Choline is a precursor to acetylcholine, a metabolite critical in healthy cell development. Depletion of choline reserves coupled with alcohol-induced disruption adversely affects fetal brain development. Our preliminary infant brain anatomical data show clear developmental effects of PAE and the mitigating effects of maternal choline supplementation. We will combine the clinical and nutritional information and infant cognitive test results from the clinical trial with the brain anatomical, connectivity and metabolic measurements from the current study to augment our understanding of the mechanistic underpinnings of the neuroprotective benefits of prenatal maternal choline supplementation on the developing fetus in the setting of PAE. We will develop capacity for acquiring region-specific neurometabolic information using magnetic resonance spectroscopic imaging (MRSI) and deep learning to identify neonatal brain regions. This project builds on the decades-long collaborations between Drs. Meintjes (University of Cape Town), S. and J. Jacobson (Wayne State University School of Medicine), van der Kouwe (Massachusetts General Hospital) and Carter (Columbia University). Drs. Choi and Lee, experts on measuring energy metabolism in prescribed brain regions using MRSI, will serve as consultants on this study.

项目摘要胎儿酒精谱系障碍是可预防的智力残疾的最普遍原因。南非西开普地区高风险社区的患病率可能高达20.9％。产前酒精暴露（PAE）会影响发展的大脑，导致认知缺陷，生长限制和结构大脑的变化。尽管进行了社会心理干预措施，但怀孕期间的饮酒仍在继续成为西开普省，美国和全球的主要公共卫生挑战。在最近的初步研究中我们表明，怀孕期间的高剂量母体胆碱补充剂减轻了对婴儿的生长和认知发育以及新生儿大脑结构。该建议将增加最近由NIH资助的完全供电的双盲，随机安慰剂对照试验，其中288个重型在怀孕期间，饮用西开普省妇女将被给予胆碱或安慰剂，并评估婴儿到12个月大。我们建议增加新生儿神经影像学，包括大脑解剖学，扩散和代谢光谱成像，以检查介导的神经机制对婴儿发育效果的补充。我们假设胆碱补充大量饮用的孕妇将减少PAE对发展中的不利影响胎儿大脑通过标准化解剖学发展，连通性和大脑能量代谢。大脑发育是需要能量的，并且对营养储量高度敏感。酒精可衡量破坏脑代谢产物。胆碱是乙酰胆碱的前体，乙酰胆碱是健康细胞中至关重要的代谢物发展。胆碱储量的消耗以及酒精诱导的破坏对胎儿的影响大脑发育。我们的初步婴儿大脑解剖数据显示了PAE和孕产妇胆碱补充剂的缓解作用。我们将结合临床和营养信息和婴儿的认知测试来自临床试验，其脑解剖学，连通性和从当前研究中的代谢测量来增强我们对机械的理解在发育中补充产前母胆碱的神经保护益处的基础胎儿在PAE的环境中。我们将使用磁性开发能够获取区域特异性神经代谢信息的能力共振光谱成像（MRSI）和深度学习以鉴定新生儿大脑区域。这个项目建立在DRS之间长达数十年的合作之上。 Meintjes（开普敦大学），S。和J。雅各布森（韦恩州立大学医学院），范德科韦（马萨诸塞州综合医院）和卡特（哥伦比亚大学）。博士。 Choi和Lee，测量处方大脑能量代谢的专家使用MRSI的地区将担任这项研究的顾问。