Maternal organophosphate pesticide exposure, low birth weight and placental injury

项目摘要/摘要 背景/意义：全球低出生体重负担(2500克)还没有 针对传统风险因素的干预措施显著改变；2000万婴儿继续 每年出生的LBW，增加了新生儿死亡、儿童发育迟缓和慢性成人的风险 疾病。为了实现世界卫生组织到2025年将LBW减少30%的雄心勃勃的目标， 必须确定新的风险因素，特别是在低收入/中等收入国家，这些国家95%的LBW 婴儿出生了。产前环境暴露是LBW的潜在可改变因素，但 在LMIC中未得到充分开发。 目的/目的：我们将评估孕期接触有机磷农药(OPs)的情况。 并在撒哈拉以南非洲农村地区确定其与LBW的关联，那里每六个新生儿中就有一个是LBW。我们 提出三个目标：1)确定接触有机磷农药的特征，并确定可能 在未来的减少暴露工作中成为目标；3)确定OP暴露与 新生儿体重和出生时胎龄，这两个因素对LBW有贡献；以及，3)评估 OP暴露与胎盘损伤之间的关系，OP毒性的潜在靶器官可能 调节有机磷暴露对出生结局的影响。 方法：我们将利用来自加纳随机空气污染的现有出生队列 和健康研究(GRAPS)，其中1,414名孕妇在怀孕28周前登记 并被分配到不同的产前烹饪策略。烹饪干预对分娩没有影响 体重、出生时胎龄或其他产科结果；然而，母体的广泛生物库 尿样和胎盘组织被创建，并结合详细的协变量数据和 严格收集的出生结局，提供了一个丰富的平台来解决我们关于OP暴露的问题 和LBW。我们将在重复的母体尿样中检测特定OP生物标志物的浓度。 (每次怀孕4次)来评估我们的假设。我们的暴露-反应分析将得到加强 评估胎盘组织以突出产前OP损伤的潜在机制。 创新：这项研究是第一次在非洲农村地区评估产前OP暴露和LBW，那里 接触杀虫剂的比例很高，每六个新生儿中就有一个是LBW。我们将克服方法学上的局限性 以前的文献从工业化环境中获得重复的产前尿样到更好 表征风险暴露、大样本量和广泛的协变量数据，并将采用创新 处理混合农药暴露和估计敏感窗口的统计方法。 我们的研究还将首次将对胎盘的评估纳入对胎盘影响的调查 产前手术暴露。 1

PROJECT SUMMARY/ABSTRACT Background/Significance: The global burden of low birth weight (LBW, <2500 grams) has not changed significantly with interventions targeted at traditional risk factors; twenty million infants continue to be born LBW each year, increasing their risks of newborn mortality, childhood stunting, and chronic adult disease. To achieve the World Health Organization's ambitious target of reducing LBW by 30% by 2025, novel risk factors must be identified, particularly in low/middle income countries where >95% of LBW infants are born. Prenatal environmental exposures are potential modifiable contributors to LBW but have been underexplored in LMICs. Objectives/Aims: We will evaluate exposure to organophosphate pesticides (OPs) during pregnancy and determine its association with LBW in rural sub-Saharan Africa where one in six newborns is LBW. We propose three aims: 1) To characterize exposure to OPs and identify predictors of high exposure that may be targeted in future exposure reduction efforts; 3) To determine the association of OP exposure with newborn weight and gestational age at birth, the two contributors to LBW; and, 3) To evaluate the association between OP exposure and placental injury, a potential target organ for OP toxicity that may mediate the effect of OP exposure on birth outcomes. Methods: We will leverage an existing birth cohort derived from the Ghana Randomized Air Pollution and Health Study (GRAPHS) in which 1,414 pregnant women were enrolled prior to 28 weeks gestation and assigned to distinct prenatal cooking strategies. The cooking interventions had no impact on birth weight, gestational age at birth, or other obstetric outcomes; however, an extensive biobank of maternal urine specimens and placental tissue was created and, in combination with detailed covariate data and rigorously collected birth outcomes, provides a rich platform to address our questions about OP exposure and LBW. We will measure concentrations of specific OP biomarkers in repeated maternal urine samples (4 per pregnancy) to evaluate our hypotheses. Our exposure-response analysis will be augmented with evaluation of placental tissue to highlight potential mechanisms of prenatal OP injury. Innovation: This study is the first to evaluate prenatal OP exposure and LBW in rural Africa, where pesticide exposure is high and one in six newborns is LBW. We will overcome methodologic limitations of prior literature from industrialized settings with access to repeated prenatal urine samples to better characterize exposure, a large sample size and extensive covariate data and will employ innovative statistical approaches to address mixtures of pesticide exposures and estimate windows of susceptibility. Our study will also be the first to integrate evaluation of the placenta into investigation of the impacts of prenatal OP exposure. 1