Environmental phthalate exposure in the Human Placenta Project cohort

人类胎盘项目队列中的环境邻苯二甲酸盐暴露

• 批准号: 10924986
• 负责人: Kelly Ferguson
• 金额: $ 82.31万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10924986
• 关键词: Adult; Angiogenic Factor; Arteries; Assessment tool; Biological Markers; Biometry; Birth Weight; Blood flow; Breast Microcalcification; Chemical Exposure; Chemicals; Child; Collaborations; Data; Disease; Fetal Growth; Fetal Growth Retardation; Fetus; Functional disorder; Funding; Funding Mechanisms; Future; Goals; Growth; Health; Human; Image; Infarction; Lead; Measurement; Measures; Methodology; Motion; National Institute of Child Health and Human Development; Neonatal Mortality; Nutrient; Outcome; Oxygen; Participant; Pathologic; Perfusion; Placenta; Placentation; Pregnancy; Publishing; Research; Resolution; Risk Factors; Role; Sampling; Specimen; Spottings; Structure of umbilical artery; Technology; Three-Dimensional Imaging; Time; Tissues; Umbilical Blood; Urine; Uterus; Variant; Visit; Weight; Woman; Work; adverse outcome; adverse pregnancy outcome; circulating biomarkers; cohort; early pregnancy; environmental chemical exposure; fetal; health assessment; heart function; implantation; improved; in vivo; innovation; molecular marker; novel; phthalates; pregnant; recruit; stillbirth; ultrasound; urinary

Fetal growth restriction is a major risk factor for stillbirth, neonatal mortality, and for child and adult health complications. The most important contributing factor to growth restriction in the non-anomalous fetus is poor nutrient and oxygen transfer across the placenta. This can result from poor implantation early in pregnancy, infarction, or other complications that lead to poor perfusion. One potentially valuable tool for assessing placental dysfunction in vivo is ultrasound technology. Traditional ultrasound approaches for estimating placental function, such as uterine and umbilical artery Doppler, are limited because of the resolution of these images and the motion of tissues surrounding the arteries. However, ultrasound methodology is rapidly advancing and offers many opportunities for improved assessment of health of the placenta. Studies of environmental chemical exposures and fetal growth have been limited, and most focus on associations with birth weight alone. This measure inappropriately captures pathologic as well as normal variation in growth, and also fails to capture the mechanism (e.g., poor placental implantation) that precedes growth restriction. Studies of chemical exposures and placental function have also been limited to examining associations with its weight at delivery, uterine/umbilical blood flow assessed by doppler, circulating biomarkers such as angiogenic factors, or molecular markers in the placenta. Studies of non-persistent chemicals, such as phthalates, are also limited by poor exposure assessment. Because their half-lives are short, single spot urine samples likely do not accurately reflect exposure over the course of gestation. Additionally, because levels are variable, utilizing one measurement may miss information regarding which period of pregnancy is most relevant to adverse outcomes. The Human Placenta Project, funded by the NICHD, is a collaborative research effort to understand the role of the placenta in health and disease. Under this funding mechanism, Drs. Alfred Abuhamad and George Saade lead an innovative study aimed at identifying novel ultrasound measures that can be utilized to predict adverse pregnancy outcomes (R01 HD086313). Within their cohort, women are recruited early in pregnancy and complete ultrasound assessments at 8 time points during gestation that collect information on: 1) Standard ultrasound measures of fetal growth; 2) Comprehensive vasculature assessment of the placenta; 3) 3D imaging of fetal biometry as well as placental parameters; 4) Quantification of microcalcifications in the placenta; and 5) Fetal cardiac function. In collaboration with this project, the present study collected urine samples on pregnant participants at 8 visits during pregnancy. The combination of this ultrasound data and urine specimen availability offers a unique opportunity to examine the associations between phthalate exposure and pregnancy and placental development and function as well as fetal growth. This year we completed analysis of urinary phthalate metabolites in samples collected from the cohort and began publishing results on our primary aims. We examined variability and trajectories of phthalate and replacement biomarkers across the 8 study visits in Rosen et al. (PMID: 37607343). We also examined early pregnancy phthalates and replacements in relation to fetal growth (PMID: 37094650).

胎儿生长受限是死产、新生儿死亡以及儿童和成人健康并发症的主要危险因素。非异常胎儿生长受限的最重要因素是通过胎盘的营养和氧气输送不足。这可能是由于妊娠早期植入不良、梗死或其他导致灌注不良的并发症造成的。超声技术是评估体内胎盘功能障碍的一种潜在有价值的工具。用于估计胎盘功能的传统超声方法，例如子宫和脐动脉多普勒，由于这些图像的分辨率和动脉周围组织的运动而受到限制。然而，超声方法正在迅速发展，并为改善胎盘健康评估提供了许多机会。 环境化学品暴露和胎儿生长的研究有限，大多数集中在与出生体重的关联上。这种测量不适当地捕获了生长中的病理变化以及正常变化，并且也未能捕获机制（例如，胎盘植入不良），先于生长受限。化学暴露和胎盘功能的研究也仅限于检查分娩时的体重、多普勒评估的子宫/脐带血流量、循环生物标志物（如血管生成因子）或胎盘中的分子标志物之间的关系。邻苯二甲酸酯等非持久性化学品的研究也受到暴露评估不佳的限制。由于它们的半衰期很短，单点尿样可能无法准确反映妊娠过程中的接触情况。此外，由于水平是可变的，使用一种测量方法可能会错过关于哪个怀孕期与不良结局最相关的信息。 由NICHD资助的人类胎盘项目是一项合作研究，旨在了解胎盘在健康和疾病中的作用。在这一资助机制下，Alfred Abuhamad和乔治Saade博士领导了一项创新研究，旨在确定可用于预测不良妊娠结局的新型超声测量方法（R 01 HD 086313）。在其队列中，在妊娠早期招募女性，并在妊娠期间的8个时间点完成超声评估，其收集以下信息：1）胎儿生长的标准超声测量; 2）胎盘的全面脉管系统评估; 3）胎儿生物统计学以及胎盘参数的3D成像; 4）胎盘中微钙化的定量;和5）胎儿心脏功能。与该项目合作，本研究在妊娠期间的8次访视中收集了妊娠受试者的尿液样本。这种超声数据和尿液样本可用性的结合提供了一个独特的机会，以检查邻苯二甲酸酯暴露与妊娠和胎盘发育和功能以及胎儿生长之间的关联。 今年，我们完成了对从队列中收集的样本中的尿邻苯二甲酸酯代谢物的分析，并开始发表我们主要目标的结果。我们在罗森等人（PMID：37607343）的8次研究访视中检查了邻苯二甲酸酯和替代生物标志物的变异性和轨迹。我们还检查了妊娠早期邻苯二甲酸酯和替代品与胎儿生长的关系（PMID：37094650）。