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

• 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
• 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

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

项目总结/摘要 背景/意义：全球低出生体重（LBW，<2500克）的负担并没有 针对传统风险因素的干预措施发生了重大变化; 2000万婴儿继续 每年出生低出生体重，增加新生儿死亡率，儿童发育迟缓和慢性成人 疾病为了实现世界卫生组织雄心勃勃的目标，即到2025年将低出生体重减少30%， 必须确定新的风险因素，特别是在低/中等收入国家， 婴儿出生了。产前环境暴露是导致出生体重不足的潜在可变因素， 在中低收入国家的研究不足。 目的/目标：我们将评估妊娠期间有机磷农药（OP）的暴露情况 并确定其与撒哈拉以南非洲农村地区LBW的关系，那里六分之一的新生儿是LBW。我们 提出三个目标：1）描述暴露于OP的特征，并确定高暴露的预测因素， 在未来减少暴露的努力中成为目标; 3）确定OP暴露与 新生儿体重和出生时胎龄是导致LBW的两个因素; 3）评估 OP暴露与胎盘损伤之间的联系，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， 在妊娠28周之前入组了1，414名孕妇 并被分配到不同的产前烹饪策略。烹饪干预对出生没有影响 体重、出生时胎龄或其他产科结局;然而， 创建尿液样本和胎盘组织，并结合详细的协变量数据， 严格收集出生结果，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。我们将测量重复母体尿液样本中特定OP生物标志物的浓度 （每胎4例）来评估我们的假设。我们的确认-响应分析将增加 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产前OP暴露和LBW的研究， 农药暴露率很高，六分之一的新生儿体重不足。我们将克服方法上的局限性， 先前来自工业化环境的文献可以获得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 采用统计方法处理农药接触的混合物并估计敏感性窗口。 我们的研究也将是第一个将胎盘的评估整合到调查的影响， 产前OP暴露。 1