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: 10538706
• 负责人: Anthony Fuller
• 金额: $ 14.73万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10538706
• 关键词: Aflatoxins; Africa; African; Anencephaly; Basic Science; Birth; Blood; Blood specimen; Brain; Budgets; Case-Control Studies; 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; Goals; Guidelines; Health; Hospital Referrals; Hospitals; Intervention Studies; Lead; 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; Risk Factors; Role; Sampling; Science; Spinal Dysraphism; Structure; Sustainable Development; System; Technology; Toxic Environmental Substances; Training; Trust; Uganda; United Nations; Universities; Update; Vertebral column; Vision; World Health Organization; body system; case control; design; disability-adjusted life years; environmental chemical exposure; 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.

项目摘要 出生缺陷会影响每个器官系统，最常见的是先天性心脏缺陷。 通过神经管缺陷（NTD）。 NTD被定义为影响大脑或 脊柱是由胚胎神经管的不当闭合引起的。最常见的NTD类型是 脊柱裂，脑脊和Ancephaly.5在全球范围内，大约300,000至40万婴儿出生于NTD 每年导致88,000人死亡和860万残疾人的生命年（达利人），重度为94％ 案件发生在LMIC中。在LMIC中，每年出生的1.67/1000多名婴儿有NTD，其中1.13/1000 有脊柱裂，0.25/1000具有周年纪念日，0.15/1000具有脑静脉曲张。尽管很重要 NTD，世界卫生组织（WHO）成员国的61.9％（120/194）缺乏NTD和 因此，报告的NTD数字甚至可能更高。在大多数撒哈拉以南国家的非洲 是LMIC，据报道NTD的患病率为1.2/1000活产，其中0.49/1000具有脊柱 Bifida，0.23/1000的脑畸形，0.17/1000具有脑脑。在乌干达，NTD的燃烧有 尽管更新数据有限，但仍然是一个严重的公共卫生挑战。有几种风险 已发布的因素导致NTD的患病率增加，尽管确定的原因仍然是 未知。据报道，各种因素的组合可能涉及环境 - 基因的相互作用 在神经管发育过程中。迄今为止，关于报告风险的作用的信息很少 特定基因，受体和酶的形态学或功能的因素以及突变或变化 负责非洲NTD样品中的叶酸代谢。因此，当前研究的主要目标 是确定相关风险因素与NTD之间的关联及其对报告基因的影响 和接收器。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 NTD新生儿 以及他们的母亲以及我们对98名新生儿的匹配控制，他们的母亲没有交叉的NTD 上面详细介绍的部分样本。我们将评估人口统计学，社会经济，家族史，感染力 暴露，药物，草药使用，环境化学暴露，营养缺乏和食物 使用结构化问卷的消费模式。我们还将从新生儿及其 母亲确定黄曲霉毒素，富莫诺蛋白和尾毒素的血液水平；叶酸的血液水平和 活性5-MTHF代谢物； HFRα，MTHFR和CELSR基因的遗传变异。我们研究的发现 将有助于告知NTDS管理实践和乌干达的政策，并为未来的NTDS预防奠定舞台 和干预研究。