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: 10582726
• 负责人: Carmen Messerlian
• 金额: $ 62.22万
• 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/10582726
• 关键词: Affect; Air; Amniotic Fluid; Animal Model; Biochemical; Biometry; Birth; Birth Rate; Birth Weight; Blood; Breathing; 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; Health; Home; Human; Human body; Impairment; Individual; Infertility; Investigation; Knowledge; Label; Life Style; Live Birth; Low Birth Weight Infant; Malignant Neoplasms; Manufacturer; 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; Weights and Measures; Woman; Workplace; adverse outcome; 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.

全氟烷基和多氟烷基物质（PFAS）是普遍存在的环境毒物， 包括癌症和甲状腺疾病在内的不良健康后果。PFAS暴露于负 影响人类健康已经在科学、政府和公共领域引起了重大关注。PFAS 用于许多消费品，包括不粘炊具、纺织品和食品包装。 重要的是，这些化学品在环境中持久存在，并且在环境中具有较长的消除半衰期（约2至8年）。 人体，导致几乎普遍的接触（一些PFAS已被发现在血清中超过 美国人口的99%）。虽然有限的人类研究和动物模型的证据表明PFAS 不良生殖和妊娠结果的暴露，包括不孕症、流产、早产， 和低出生体重，知识仍然很少，特别是对新的全氟辛烷磺酸和全氟辛烷磺酸混合物。此外，本发明还 检查围产期结局（如早产和低出生体重）的研究测量了血清/血浆 妊娠期间的浓度，这可能会导致妊娠相关生理变化的混淆。 因此，有一个显着的需要进行研究，旨在衡量PFAS暴露在怀孕前。更好地 定义PFAS暴露对生殖和妊娠结局的影响， 暴露也可能影响男性生殖成功，我们提出了一项创新的研究，以测量血清 在受孕前，男性和女性中相关PFAS分析物的浓度。我们将利用 环境与生殖健康（EARTH）研究（ES 009718），一项前瞻性的 从生育诊所招募的夫妇，并跟踪分娩。本提案的目的是确定 母亲和父亲孕前血清PFAS浓度（单独和作为PFAS） 混合物）与：目的1）受精，植入和精液质量的生殖结果 参数; AIM 2）妊娠丢失和活产的妊娠结局;和AIM 3） 出生体重和胎龄。创新包括评估对新兴事物的先入为主的接触， 新型PFAS及其混合物在夫妇中的应用及早期生殖和妊娠结局的调查 这是以前没有研究过的。拟议的研究具有很高的时间和成本效益，因为我们将 834名未经产妇女和435名男子（435对夫妇）的存档生物标本和临床数据。我们 将再招募225名未经产的妇女和180名男性伴侣，以增加统计能力， 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方面的专业知识， PFAS暴露评估以及先进的生物统计和混合物分析方法。拟定研究 通过检查母亲和父亲的PFAS将具有重要的科学和公共卫生意义 生殖、妊娠和出生结果的暴露，为循证医学提供急需的数据。 减少PFAS暴露和危害的政策。