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)

项目总结 出生缺陷影响每个器官系统，其中最常见的是先天性心脏病，紧随其后的是 由神经管缺陷(NTDS)引起。NTDS被定义为一组影响大脑或 脊椎和胚胎神经管关闭不当所致。最常见的非专利药品类型有 脊柱裂、脑膨出和无脑畸形。5全球约有300,000到400,000名婴儿出生时患有NTDS 每年导致88,000人死亡和860万人伤残调整寿命年(DALY)，其中94%的严重 发生在低收入国家的病例。在LMIC，每年出生的婴儿中有超过1.67/1000患有NTDS，其中1.13/1000 有脊柱裂，0.25/1000有无脑，0.15/1000有脑膨出。尽管重要的是 非关税壁垒，61.9%(120/194)的世界卫生组织成员国缺乏关于非关税壁垒和非关税壁垒的数据 因此，报告的非关税壁垒数字甚至可能更高。在非洲，那里的大多数撒哈拉以南国家 都是LMIC，NTDS的患病率据报道为1.2/1000活产儿，其中0.49/1000有脊柱 先天性裂，0.23/1000为无脑畸形，0.17/1000为脑膨出。在乌干达，非关税壁垒的负担已经 仍然是一个严重的公共卫生挑战，尽管更新的数据有限。有几个风险 被认为导致NTDS患病率增加的因素，尽管确定的原因仍然是 未知。据报道，多种因素的组合可能涉及环境与基因的相互作用。 在神经管发育过程中。到目前为止，关于报告的风险的作用的信息很少。 因子与特定基因、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，目前研究的主要目标是 目的是确定相关危险因素与NTDS之间的联系及其对已报道基因的影响 和感受器。我们的主要研究设计是前瞻性病例对照研究。我们将招募98名新台币新生儿 和他们的母亲，以及我们对98名新生儿和他们没有NTDS的母亲的对照-- 上面详述的截面样本。我们将评估人口、社会经济、家族史、传染性 暴露、药物、草药使用、环境化学暴露、营养缺乏和食物 使用结构化问卷调查消费模式。我们还将采集新生儿和他们的血液样本 母亲测定血液中黄曲霉毒素、伏马菌素和赭曲霉毒素的水平；血液中的叶酸和 活性5-甲基四氢呋喃的代谢产物；以及氢化氢受体α、亚甲基四氢叶酸还原酶和CELSR基因的遗传变异。我们研究的发现 将帮助为乌干达的非关税壁垒管理做法和政策提供信息，并为今后预防非关税壁垒奠定基础 和干预研究。

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.