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， 神经管缺陷（NTDs）NTD被定义为一组出生缺陷， 脊柱的畸形是由胚胎神经管的不正确闭合引起的。最常见的NTD类型是 脊柱裂、脑膨出和无脑。5在全球范围内，约有30万至40万婴儿出生时患有NTD 每年导致88，000人死亡和860万残疾调整生命年（DADs），其中94%的严重 发生在中低收入国家的案件。在中低收入国家，每年出生的婴儿中有1.67/1000以上患有NTD，其中1.13/1000 无脑畸形为0.25/1000，脑膨出为0.15/1000。尽管重要的是 NTD方面，61.9%（120/194）的世界卫生组织（WHO）成员国缺乏NTD数据， 因此，呈报的NTD数字可能更高。在非洲，大多数撒哈拉以南国家 是低收入国家，据报告NTD的患病率为1.2/1000活产，其中0.49/1000有脊柱 无脑儿占0.23/1000，脑膨出占0.17/1000。在乌干达，NTD的负担 这仍然是一个严重的公共卫生挑战，尽管最新数据有限。有几个风险 这些因素已被假定为导致NTD患病率增加，尽管确切的原因仍然是 未知各种因素的组合已被报道，可能涉及环境-基因相互作用 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样本中叶酸代谢的基因。因此，本研究的主要目的是 确定相关危险因素与NTDs之间的关联及其对已报道基因的影响 和受体。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名新台币新生儿 和他们的母亲沿着与我们匹配的98个新生儿和他们的母亲没有NTD的交叉对照- 上面详细介绍的部分样品。我们将评估人口统计学，社会经济学，家族史，传染性 暴露、药物、草药使用、环境化学品暴露、营养缺乏和食物 使用结构化问卷调查消费模式。我们还将从新生儿和他们的 母亲，以确定血液中的黄曲霉毒素，伏马菌素，赭曲霉毒素水平;血液中的叶酸水平， 活性5-MTHF代谢物;以及hFR α、MTHFR和CELSR基因的遗传变异。我们的研究发现 将有助于为乌干达的NTD管理实践和政策提供信息，并为未来的NTD预防奠定基础 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.