The Impact of Maternal and Paternal Preconception Perfluoroalkyl Substance (PFAS) Exposure on Reproductive and Perinatal Outcomes

母亲和父亲受孕前接触全氟烷基物质 (PFAS) 对生殖和围产期结果的影响

• 批准号: 10162590
• 负责人: Carmen Messerlian
• 金额: $ 65.39万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-11 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10162590
• 关键词: Affect; Air; Amniotic Fluid; Animal Model; Biochemical; Biometry; Birth; Birth Rate; Blood; Chemicals; Clinic; Clinical; Clinical Data; Conceptions; Couples; Data; Eating; Environment; Environmental Epidemiology; Environmental Exposure; Environmental Pollution; Epidemiology; Epigenetic Process; Exposure to; Family; Female; Fertility; Fertilization; Food; Food Packaging; General Population; Germ Lines; Gestational Age; Government; Health; Home; Human; Human body; Impairment; Individual; Infertility; Investigation; Knowledge; Label; Life Style; Live Birth; Low Birth Weight Infant; Malignant Neoplasms; Manufacturer Name; Maternal Exposure; Measures; Methods; Neonatal; Nulliparity; Outcome; Outcome Study; Phase; Physiological; Plasma; Policies; Poly-fluoroalkyl substances; Population; Pregnancy; Pregnancy Outcome; Pregnancy loss; Premature Birth; Production; Public Health; Reproduction; Reproductive Health; Research; Research Design; Resistance; Risk; Sample Size; Schools; Seminal fluid; Serum; Stains; Textiles; Thyroid Diseases; Time; Toxic Environmental Substances; United States; Water; Woman; Workplace; adverse outcome; base; biological specimen archives; chemical property; cohort; consumer product; cost efficient; design; evidence base; exposed human population; failure Implantation; health goals; implantation; innovation; male; men; offspring; perfluorooctane sulfonate; perfluorooctanoic acid; perinatal health; perinatal outcomes; prospective; recruit; reproductive; reproductive epidemiology; reproductive outcome; reproductive success; sperm cell; substance use

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental toxicants that are associated with adverse health outcomes including cancer and thyroid disease. The potential for PFAS exposures to negatively influence human health has generated significant concerns in scientific, governmental and public realms. PFAS are used in numerous consumer products, including nonstick cookware, textiles, and food packaging. Importantly, these chemicals persist in the environment and have long elimination half-lives (~2 to 8 years) in the human body, leading to near-universal exposure (some PFAS have been detected in the serum of more than 99% of the U.S. population). While limited human studies and evidence from animal models implicate PFAS exposures in adverse reproductive and pregnancy outcomes including infertility, pregnancy loss, preterm birth, and low birthweight, knowledge remains scarce, particularly for newer PFAS and PFAS mixtures. Further, studies that examined perinatal outcomes such as preterm birth and low birthweight measured serum/plasma concentrations during pregnancy, which may result in confounding by pregnancy-related physiologic changes. Hence, there is a significant need for studies designed to measure PFAS exposure before conception. To better define the impact of PFAS exposure on reproductive and pregnancy outcomes, and because environmental exposures may also affect male reproductive success, we propose an innovative study to measure serum concentrations of relevant PFAS analytes in both men and women before conception. We will leverage the Environment and Reproductive Health (EARTH) Study (ES009718), a prospective preconception cohort of couples recruited from a fertility clinic and followed through delivery. The aims of this proposal are to determine the extent to which maternal and paternal preconception serum PFAS concentrations (individually and as PFAS mixtures) are associated with: AIM 1) reproductive outcomes of fertilization, implantation, and semen quality parameters; AIM 2) pregnancy outcomes of pregnancy loss and live birth; and AIM 3) birth outcomes of birthweight and gestational age. Innovations include the assessment preconception exposure to emerging and new PFAS and their mixtures in couples and the investigation of early reproductive and pregnancy outcomes that have not been previously studied. The proposed study is highly time- and cost-efficient, as we will have archived biospecimens and clinical data available for 834 nulliparous women and 435 men (435 couples). We will recruit an additional 225 nulliparous women and 180 male partners to increase statistical power to a total of 615 couples. Our team includes expertise in male and female reproductive and environmental epidemiology, PFAS exposure assessment, and advanced biostatistical and mixtures analysis methods. The proposed study will have important scientific and public health implications by examining both maternal and paternal PFAS exposure on reproductive, pregnancy, and birth outcomes, providing much needed data for evidence-based policy to reduce PFAS exposure and harm.

每种和多氟烷基物质（PFA）是无处不在的环境有毒物质，与 不良健康结果，包括癌症和甲状腺疾病。 PFA暴露于负面的潜力 影响人类健康对科学，政府和公共领域引起了重大关注。 PFA 用于众多消费产品，包括不粘炊具，纺织品和食品包装。 重要的是，这些化学物质在环境中持续存在，并且长期消除了半衰期（〜2至8年） 人体，导致几乎全世界的暴露（在血清中检测到一些PFA 99％的美国人口）。尽管有限的人类研究和来自动物模型的证据暗示了PFA 不良生殖和妊娠结局的暴露，包括不育，怀孕丧失，早产， 低出生体重，知识仍然很少，特别是对于新的PFA和PFA混合物而言。更远， 研究了围产期结局的研究，例如早产和低出生体重测量的血清/血浆 怀孕期间的浓度，这可能会导致与怀孕相关的生理变化混淆。 因此，旨在在受孕之前旨在测量PFAS暴露的研究非常需要。更好 定义PFA暴露对生殖和妊娠结局的影响，并且因为环境 暴露也可能影响男性的生殖成功，我们提出了一项创新的研究来测量血清 在受孕之前，男性和女性的相关PFA分析物的浓度。我们将利用 环境与生殖健康（EART）研究（ES009718） 夫妻从生育诊所招募，然后通过分娩。该提议的目的是确定 母体和父亲先入血清PFAS浓度的程度（单独和PFA 混合物）与：目标1）受精，植入和精液质量的生殖结果 参数;目标2）怀孕丧生和活产的妊娠结局；目标3） 出生体重和胎龄。创新包括对新兴和 夫妻中的新PFA及其混合物以及早期生殖和妊娠结局的研究 以前尚未研究。拟议的研究是高度时间和成本效益的，因为我们将拥有 可用于834名无效妇女和435名男性（435对夫妇）的存档生物测量和临床数据。我们 将招募另外225名无效妇女和180名男性伴侣，以将统计能力提高到总计 615对夫妇。我们的团队包括男性和女性生殖和环境流行病学的专业知识， PFAS暴露评估以及晚期生物统计和混合分析方法。拟议的研究 通过检查母亲和父亲PFA，将对科学和公共卫生产生重要的影响 在生殖，怀孕和出生结果上接触，为基于证据的数据提供了急需的数据 减少PFA暴露和危害的政策。