Mycotoxin Exposure in Pregnancy and Birth Outcomes in Zimbabwe

津巴布韦妊娠和分娩结果中的霉菌毒素暴露

• 批准号: 8822411
• 负责人: REBECCA J STOLTZFUS
• 金额: $ 31.04万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-15 至 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8822411
• 关键词: Affect; Aflatoxin M1; Aflatoxins; Africa; Africa South of the Sahara; Age; Age-Months; Albumins; Anemia; Animal Model; Biological Markers; Birth; Carcinogens; Child; Child health care; Chinese People; Communities; Developed Countries; Developing Countries; Development; Environment; Environmental Pollution; Exposure to; Family; Fetal Growth; Fetal Growth Retardation; Fetus; Food; Food Safety; Foundations; Fumonisins; Funding; Gestational Age; Goals; Growth and Development function; HIV; Harvest; Health; Household; Human; Hygiene; Infant; Infant Health; Insulin-Like Growth Factor I; Intervention; Joints; Knowledge; Lead; Life; Link; Liver; Low Birth Weight Infant; Maize; Malignant neoplasm of liver; Maternal Exposure; Maternal and Child Health; Measures; Molds; Mothers; Mycotoxins; Outcome; Placenta; Placental Insufficiency; Policies; Population; Population Study; Populations at Risk; Pregnancy; Pregnancy Outcome; Pregnancy Trimesters; Pregnancy loss; Pregnant Women; Premature Birth; Premature Labor; Prevalence; Public Health; Rain; Randomized Controlled Trials; Recruitment Activity; Relative (related person); Reporting; Research; Research Infrastructure; Risk; Rural; Sampling; Sanitation; Severities; Small for Gestational Age Infant; Source; Spontaneous abortion; Surveys; System; Testing; Toxic effect; Toxin; Water; Woman; Zimbabwe; base; cohort; critical period; cytotoxic; data management; deoxynivalenol; efficacy trial; feeding; fetal; high risk; immune activation; improved; in utero; infancy; infant nutrition; maternal serum; novel; premature; public health relevance; reproductive; screening; stillbirth; urinary

DESCRIPTION (provided by applicant): Intrauterine insults can increase the risk of adverse birth outcomes, including miscarriage, prematurity, stillbirth and low birth weight. Mycotoxins are produced by molds that contaminate staple foods. One family of mycotoxins, aflatoxins (AF), has been widely studied and is known to cause liver cancer. Two other mycotoxins, fumonisin (FUM) and deoxynivalenol (DON) are often co-contaminants with AF in maize. All three mycotoxins have been shown to cross the placenta and may affect the fetus during critical periods of growth and development; however, none of these toxins or their combination has been rigorously studied with regard to pregnancy outcomes. The objective of this application is to characterize pregnancy exposure to multiple mycotoxins and its relation to birth outcomes in rural Zimbabwe. Our over-arching hypothesis is that AF exposure, alone or in combination with FUM and DON, is an important cause of adverse birth outcomes (poor fetal growth, miscarriage, stillbirth and preterm birth) globally. Our approach takes advantage of a large pregnancy cohort with outstanding field, lab and data management funded by the Bill & Melinda Gates Foundation (BMGF): the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial. Birth outcomes (miscarriage, stillbirth, prematurity, small-for-gestational age and stunted-for-gestational age) are already being measured, and we have strong evidence that mycotoxin exposures are prevalent and significant in this study population. The SHINE trial, an ongoing community-based trial of 4800 mother-infant pairs recruited during the first half of pregnancy in two rural districs of Zimbabwe. SHINE is a factorial cluster-randomized controlled trial investigating the independent and combined effects of improved water, sanitation and hygiene (WASH) and/or improved infant and young child feeding (IYCF) on stunting and anemia at 18 months of age. In this proposal, we leverage the existing SHINE infrastructure to assess mycotoxin exposure during pregnancy. Specific Aim 1 is to describe the prevalence and severity of multiple mycotoxin exposures in a large representative sample of pregnant women in rural Zimbabwe. Specific Aim 2 will characterize the relationship between maternal serum aflatoxin-albumin concentration during pregnancy and adverse birth outcomes [preterm birth, low birth weight (LBW), small-for-gestational age (SGA) and short-for-gestational age] in HIV-negative mothers Specific Aim 3 will explore the joint exposures of FUM, DON and AF in relation to risk of preterm birth. The proposed research will generate novel information about the burden of multiple mycotoxins (AF, FUM, DON) during pregnancy and the relative contribution of aflatoxin exposure to adverse birth outcomes. This evidence will provide foundations for future research exploring the potential mechanisms linking mycotoxin exposure to adverse birth outcomes and provide a rationale for the development and targeting of interventions to reduce mycotoxin exposure during pregnancy.

描述（由申请人提供）：宫内损伤会增加不良分娩结果的风险，包括流产、早产、死产和低出生体重。霉菌毒素是 由污染主食的霉菌产生。黄曲霉毒素 (AF) 是霉菌毒素的一个家族，已被广泛研究并已知会导致肝癌。另外两种霉菌毒素，伏马菌素 (FUM) 和脱氧雪腐镰刀菌烯醇 (DON)，通常是玉米中 AF 的共同污染物。所有三种霉菌毒素均已被证明可以穿过胎盘，并可能在生长和发育的关键时期影响胎儿；然而，尚未对这些毒素或其组合对妊娠结局的影响进行严格研究。该应用的目的是描述津巴布韦农村地区怀孕期间接触多种霉菌毒素的情况及其与出生结果的关系。我们的首要假设是，AF 暴露，无论是单独使用还是与 FUM 和 DON 结合使用，都是全球不良出生结果（胎儿生长不良、流产、死产和早产）的重要原因。 我们的方法利用了由比尔及梅琳达·盖茨基金会 (BMGF) 资助的大型妊娠队列以及出色的现场、实验室和数据管理：卫生婴儿营养功效 (SHINE) 试验。出生结果（流产、死产、早产、小于胎龄和胎龄发育迟缓）已经在测量中，我们有强有力的证据表明霉菌毒素暴露在该研究人群中普遍存在且显着。 SHINE 试验是一项正在进行的社区试验，招募了津巴布韦两个农村地区怀孕前半期的 4800 对母婴。 SHINE 是一项析因整群随机对照试验，调查改善水、环境卫生和个人卫生 (WASH) 和/或改善婴幼儿喂养 (IYCF) 对 18 个月龄发育迟缓和贫血的独立和综合影响。 在本提案中，我们利用现有的 SHINE 基础设施来评估怀孕期间的霉菌毒素暴露。具体目标 1 是描述津巴布韦农村地区孕妇的大量代表性样本中多种霉菌毒素暴露的患病率和严重程度。具体目标 2 将描述 HIV 感染者妊娠期间母体血清黄曲霉毒素白蛋白浓度与不良出生结局 [早产、低出生体重 (LBW)、小于胎龄 (SGA) 和短胎龄] 之间的关系-阴性母亲具体目标 3 将探讨 FUM、DON 和 AF 的联合暴露与早产风险的关系。拟议的研究将产生有关怀孕期间多种霉菌毒素（AF、FUM、DON）的负担以及黄曲霉毒素暴露对不良出生结果的相对影响的新信息。这一证据将为未来的研究奠定基础，探索霉菌毒素暴露与不良出生结局之间的潜在机制，并为制定和瞄准减少妊娠期间霉菌毒素暴露的干预措施提供依据。