Assessment of neural tube defects among newborns in Uganda: A study of prevalence, risk factors, and the role of gene-environmental interactions (NTDs in Uganda)

乌干达新生儿神经管缺陷的评估：关于患病率、危险因素和基因-环境相互作用（乌干达 NTD）的作用的研究

• 批准号: 10706626
• 负责人: MICHAEL M. HAGLUND
• 金额: $ 14.12万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706626
• 关键词: Aflatoxins; Africa; African; Anencephaly; Basic Science; Birth; Blood; Blood specimen; Brain; Budgets; Case/Control Studies; Categories; Cessation of life; Clinical; Collaborations; Congenital Abnormality; Congenital Heart Defects; Congenital cerebral hernia; Country; Data; Defect; Development; Economic Development; Embryo; Environmental Risk Factor; Enzymes; Family; Folic Acid; Foundations; Fumonisins; Future; Genes; Genetic; Genetic Variation; Guidelines; Health; Hospital Referrals; Hospitals; Intervention Studies; Life; Live Birth; Longevity; MTHFR gene; Malnutrition; Maternal Health; Mental Health; Morphology; Mothers; Mutation; Neural Tube Defects; Neural Tube Development; Neural tube; Neurology; Newborn Infant; Operative Surgical Procedures; Paper; Pattern; Personal Satisfaction; Pharmaceutical Preparations; Policies; Practice Management; Premature Mortality; Prevalence; Prevalence Study; Prevention; Prevention program; Public Health; Questionnaires; Recording of previous events; Rehabilitation therapy; Reporting; Research; Research Design; Research Project Grants; Resource-limited setting; Resources; Risk Factors; Role; Sampling; Science; Spinal Dysraphism; Structure; Sustainable Development; System; Technology; Toxic Environmental Substances; Training; Trust; Uganda; United Nations; Universities; Update; Vertebral column; World Health Organization; body system; case control; design; disability-adjusted life years; environmental chemical exposure; epidemiologic data; folic acid metabolism; food consumption; gene interaction; improved; insight; low and middle-income countries; member; mortality; neonatal health; nervous system disorder; neurosurgery; prospective; receptor; recruit; socioeconomics; success; years of life lost

PROJECT SUMMARY Birth defects impact every organ system with the most common being congenital heart defects closely followed by neural tube defects (NTDs). NTDs are defined as the group of birth defects that impact either the brain or spine and are caused by the improper closure of the embryonic neural tube. The commonest types of NTDs are spina bifida, encephalocele, and anencephaly.5 Globally, about 300,000 to 400,000 babies are born with NTDs resulting in 88,000 deaths and 8.6 million disability adjusted life years (DALYs) annually with 94% of severe cases occurring in LMICs. In LMICs, over 1.67/1000 babies born annually have NTDs, and of these 1.13/1000 have spina bifida, 0.25/1000 have anencephaly, and 0.15/1000 have encephalocele. Despite the importance of NTDs, 61.9% (120/194) of the World Health Organization (WHO) member countries lack data on NTDs and therefore the reported figures of NTDs may even be higher. In Africa, where most of the Sub-Saharan countries are LMICs, the prevalence of NTDs is reported to be 1.2/1000 live births and of these 0.49/1000 have spina bifida, 0.23/1000 have anencephaly, and 0.17/1000 have encephalocele. In Uganda, the burden of NTDs has continued to be a serious public health challenge, though there is limited updated data. There are several risk factors that have been postulated to lead to the increased prevalence of NTDs though the definitive cause is still unknown. A combination of various factors has been reported that may involve environmental-gene interactions during neural tube development. To date, there is a paucity of information about the role of the reported risk factors and the mutations or alterations in morphology or functions of specific genes, receptors, and enzymes responsible for folic acid metabolism in African NTD samples. Therefore, the main objective of the current study is to determine the association between relevant risk factors and NTDs and their influence on the reported genes and receptors. Our primary study design is a prospective case-control study. We will recruit 98 NTD newborns and their mothers along with our matched control of 98 newborns and their mothers without NTDs from the cross- sectional sample detailed above. We will assess demographic, socioeconomic, family history, infectious exposures, medications, herbal use, environmental chemical exposure, nutritional deficiencies, and food consumption patterns using a structured questionnaire. We will also take blood samples from newborns and their mothers to determine the blood levels of aflatoxins, fumonisins, and ochratoxins; blood levels of folic acid and active 5-MTHF metabolite; and genetic variation in hFRα, MTHFR, and CELSR genes. Findings from our study will help inform NTDs management practices and policies in Uganda and set the stage for future NTDs prevention and intervention studies.

项目概要 出生缺陷会影响每个器官系统，其中最常见的是先天性心脏病，其次是先天性心脏病 神经管缺陷 (NTD) 被定义为影响大脑或大脑的出生缺陷。 神经管缺陷 (NTD) 是由胚胎神经管闭合不当引起的。 脊柱裂、脑膨出和无脑畸形。5 全球范围内，大约 300,000 至 400,000 名婴儿出生时患有 NTD 每年导致 88,000 人死亡和 860 万伤残调整生命年 (DALY)，其中 94% 为重度伤残 中低收入国家每年有超过 1.67/1000 名婴儿患有 NTD，其中 1.13/1000 名婴儿患有 NTD。 患有脊柱裂，0.25/1000 患有无脑畸形，0.15/1000 患有脑膨出。 被忽视的热带病，61.9% (120/194) 的世界卫生组织 (WHO) 成员国缺乏有关被忽视热带病的数据， 因此，在非洲，大多数撒哈拉以南国家，报告的被忽视热带病的数字可能更高。 据报道，中低收入国家的 NTD 患病率为 1.2/1000 活产婴儿，其中 0.49/1000 患有脊柱疾病 在乌干达，NTD 的负担已增加，其中 0.23/1000 人患有无脑畸形，0.17/1000 人患有脑膨出。 尽管更新数据有限，但仍然是一个严重的公共卫生挑战，存在多种风险。 尽管最终的原因仍然是被假定导致 NTD 患病率增加的因素 据报道，可能涉及环境基因相互作用的各种因素的组合。 迄今为止，关于所报告的风险的作用的信息很少。 因素以及特定基因、受体和酶的形态或功能的突变或改变 负责非洲 NTD 样本中的叶酸代谢，因此是当前研究的主要目标。 目的是确定相关危险因素与 NTD 之间的关联及其对报告基因的影响 我们的主要研究设计是一项前瞻性病例对照研究，我们将招募 98 名 NTD 新生儿。 和他们的母亲，以及我们对 98 名没有 NTD 的新生儿和他们的母亲进行的对照对照。 我们将评估人口、社会经济、家族史、传染性。 暴露、药物、草药的使用、环境化学物质暴露、营养缺乏和食物 我们还将使用结构化问卷调查消费模式。 母亲测定血液中黄曲霉毒素、伏马菌素、赭曲霉毒素和叶酸的水平； 活性 5-MTHF 代谢物；以及 hFRα、MTHFR 和 CELSR 基因的遗传变异。 将帮助乌干达了解被忽视热带病的管理实践和政策，并为未来的被忽视热带病预防奠定基础 和干预研究。