Maternal organophosphate pesticide exposure, low birth weight and placental injury

母亲接触有机磷农药、低出生体重和胎盘损伤

基本信息

批准号：
10166846
负责人：
Michele Renee Hacker
金额：
$ 25.41万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10166846
关键词：
Address Adult Africa Africa South of the Sahara Agriculture Air Pollution Anemia Animals Apoptosis Biological Biological Markers Birth Birth Weight Blood flow Childhood Chlorpyrifos Cholinesterases Chronic Chronic Disease Data Diet Discipline of obstetrics Disease Enrollment Environment Evaluation Exposure to Fetal Growth Fetal Growth Retardation Future Gestational Age Ghana Health Home Impairment Incidence Income Industrialization Infant Injury Intervention Investigation Life Link Literature Low Birth Weight Infant Malaria Malnutrition Measurement Measures Mediating Mediator of activation protein Medical History Methodology Methods Morbidity - disease rate Neonatal Mortality Newborn Infant Organ Organophosphates Outcome Oxidative Stress Parathion Pathology Pesticides Placenta Policies Population Positioning Attribute Predisposition Pregnancy Pregnant Women Premature Birth Prevalence Provider Public Health Randomized Research Risk Risk Factors Rural Sample Size Sampling Second Pregnancy Trimester Small for Gestational Age Infant Specimen System Tissues Ultrasonography Urine Weight Weights and Measures Woman Work World Health Organization Zika Virus base biobank cholinergic cohort cooking cost effective digital early pregnancy epidemiology study fight against high risk population human data innovation low and middle-income countries modifiable behavior mortality neonatal death neurotoxicity novel obstetric outcomes obstetrical complication pesticide exposure pesticide poisoning placental malaria pollutant prenatal prenatal environmental exposure response sociodemographics

项目摘要

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

项目概要/摘要背景/意义：低出生体重（LBW，<2500 克）的全球负担尚未针对传统风险因素的干预措施发生了显着变化；两千万婴儿继续每年出生低体重儿，增加了新生儿死亡率、儿童发育迟缓和成人慢性病的风险疾病。为了实现世界卫生组织到 2025 年将低体重儿减少 30% 的宏伟目标，必须确定新的风险因素，特别是在低收入/中等收入国家，其中 95% 以上的低体重儿婴儿出生。产前环境暴露是低出生体重的潜在可改变因素，但中低收入国家尚未得到充分探索。目的/目的：我们将评估怀孕期间接触有机磷农药 (OP) 的情况并确定其与撒哈拉以南非洲农村地区低出生体重的关系，那里六分之一的新生儿患有低出生体重。我们提出三个目标： 1) 描述有机磷农药暴露的特征并确定高暴露的预测因素成为未来减少暴露工作的目标； 3) 确定 OP 暴露与新生儿体重和出生时胎龄是低出生体重的两个因素；以及，3) 评估 OP 暴露与胎盘损伤之间的关联，胎盘损伤是 OP 毒性的潜在靶器官，可能介导 OP 暴露对出生结果的影响。方法：我们将利用来自加纳随机空气污染的现有出生队列健康研究 (GRAPHS)，其中 1,414 名妊娠 28 周前的孕妇参与其中并分配不同的产前烹饪策略。烹饪干预对出生没有影响体重、出生胎龄或其他产科结果；然而，广泛的母体生物库创建尿液样本和胎盘组织，并结合详细的协变量数据和严格收集的出生结果，提供了一个丰富的平台来解决我们有关 OP 暴露的问题和低体重。我们将测量重复母体尿液样本中特定 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-反应分析将得到增强评估胎盘组织以突出产前 OP 损伤的潜在机制。创新：这项研究是第一个评估非洲农村地区产前 OP 暴露和低出生体重的研究，其中农药接触率很高，六分之一的新生儿是低体重儿。我们将克服方法学的局限性来自工业化环境的先前文献，可以获取重复的产前尿液样本，以更好地描述暴露、大样本量和广泛的协变量数据，并将采用创新的解决农药暴露混合物和估计敏感性窗口的统计方法。我们的研究也将是第一个将胎盘评估纳入胎盘影响调查的研究产前 OP 暴露。 1