Mycotoxin Exposure in Pregnancy and Birth Outcomes in Zimbabwe

描述（由申请人提供）：宫内损伤可增加不良出生结局的风险，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。真菌毒素的一个家族，黄曲霉毒素（AF），已被广泛研究，并已知会导致肝癌。另外两种真菌毒素伏马菌素（FUM）和脱氧雪腐镰刀菌烯醇（DON）通常与玉米中的AF共污染。所有这三种霉菌毒素都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，这些毒素或它们的组合都没有被严格研究过妊娠结局。本申请的目的是描述津巴布韦农村地区妊娠期暴露于多种真菌毒素及其与出生结局的关系。我们的过度假设是，AF暴露，单独或与FUM和DON结合，是全球不良出生结局（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和梅琳达·盖茨基金会（BMGF）资助的大型妊娠队列，具有出色的现场，实验室和数据管理：环境卫生婴儿营养功效（SHINE）试验。出生结局（流产、死产、早产、小于胎龄儿和小于胎龄儿）已经在测量中，我们有强有力的证据表明霉菌毒素暴露在本研究人群中普遍存在且意义重大。SHINE试验是一项正在进行的以社区为基础的试验，在津巴布韦的两个农村地区招募了4800对怀孕前半期的母婴。SHINE是一项析因聚类随机对照试验，研究改善水、环境卫生和个人卫生（WASH）和/或改善婴幼儿喂养（IYCF）对18个月龄时发育迟缓和贫血的独立和综合影响。 在这项提案中，我们利用现有的SHINE基础设施来评估怀孕期间的真菌毒素暴露。具体目标1是描述在津巴布韦农村地区的一个大型代表性孕妇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阴性母亲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）和小于胎龄]之间的关系。具体目标3将探索FUM、DON和AF的联合暴露与早产风险的关系。拟议的研究将产生关于怀孕期间多种真菌毒素（AF，FUM，DON）负担的新信息，以及黄曲霉毒素暴露对不良出生结果的相对贡献。这一证据将为未来的研究提供基础，探索霉菌毒素暴露与不良出生结局之间的潜在机制，并为开发和靶向干预措施以减少妊娠期间霉菌毒素暴露提供依据。

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.