Environmental Determinants of Neural Tube Defects

神经管缺陷(NTD)是一种常见的严重畸形，与过高的发病率和死亡率有关。虽然有几种已知的NTDS的病因，但在大多数病例中无法确定特定的病原体(S)。母亲接近危险废物场地和接触杀虫剂都被认为是后代NTDS的危险因素，但不被认为是确定的危险因素。关于这些与其他环境暴露和NTD风险之间的联系的明确结论一直受到这种结果的罕见(1/1000出生)、不同研究之间暴露评估的差异以及过于简单化的病因模型的阻碍。本申请中提出的研究旨在最大限度地减少这些限制，同时解决主要研究假设：母亲暴露在多环芳烃和无机砷中会增加子代患NTDS的风险，这些环境暴露的影响会受到营养和遗传因素的影响。在我们对这一假设的评估中，我们将考虑这样一种可能性，即环境和遗传风险因素的相互作用可能与NTDS的风险更相关，而不是任何单一因素的独立主效应。此外，我们将考虑母体和胚胎的基因型别作为母体暴露与子代患NTDS风险之间关系的潜在修饰性因素。

Neural tube defects (NTDs) are common, serious malformations that are associated with both excess morbidity and mortality. Although there are several known causes of NTDs, a specific etiologic agent(s) cannot be identified in the majority of cases. Maternal proximity to hazardous waste sites and exposure to pesticides have both been implicated as, but are not considered to be established risk factors for NTDs in offspring. Definitive conclusions regarding the association between these, and other environmental exposures and NTD risk have been hampered by the rarity of this outcome (<1/1000 births), differences in exposure assessment between studies, and overly simplistic etiological models. The studies proposed in this application are designed to minimize these limitations while addressing the primary study hypothesis: maternal exposure to polycyclic aromatic hydrocarbons and inorganic arsenic contributes to the risk of NTDs in offspring, and the effects of these environmental exposures are modified by nutritional and genetic factors. In our evaluation of this hypothesis we will consider the possibility that the interplay of environmental and genetic risk factors may be more relevant to the risk of NTDs than is the independent main effect of any single factor. In addition, we will consider both the maternal and the embryonic genotypes as potential modifiers of the association between maternal exposures and risk of NTDs in offspring.