Environmental phthalate exposure in the Human Placenta Project cohort

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胎盘营养和氧气转运不足。这可能是由于妊娠早期植入不良、脑梗塞或其他导致血流灌注不良的并发症所致。超声技术是评估体内胎盘功能障碍的一个潜在有价值的工具。传统的评估胎盘功能的超声方法，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，超声方法学正在迅速发展，并为改进胎盘健康评估提供了许多机会。关于环境化学物质暴露和胎儿生长的研究一直很有限，大多数研究都集中在与出生体重的关系上。这一措施不恰当地捕捉到了生长中的病理和正常变化，也未能捕捉到生长受限之前的机制(例如，胎盘植入不良)。对化学物质暴露和胎盘功能的研究也仅限于检查与分娩时体重、多普勒评估的子宫/脐血流、循环生物标记物(如血管生成因子)或胎盘中的分子标记物之间的关系。对邻苯二甲酸酯等非持久性化学物质的研究也受到暴露评估较差的限制。因为它们的半衰期很短，单一的尿样可能不能准确地反映怀孕期间的暴露情况。此外，由于水平是可变的，使用一种测量方法可能会遗漏关于怀孕期间与不良结果最相关的信息。 人类胎盘项目由NICHD资助，是一项合作研究努力，旨在了解胎盘在健康和疾病中的作用。根据这一资助机制，Alfred Abuhamad博士和George 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果的新超声波测量方法(R01 HD086313)。在她们的队列中，女性在怀孕早期被招募，并在怀孕期间的8个时间点完成超声评估，收集的信息包括：1)胎儿生长的标准超声测量；2)对胎盘的全面血管评估；3)胎儿生物测量以及胎盘参数的3D成像；4)胎盘中微钙化的量化；以及5)胎儿心功能。与该项目合作，本研究收集了怀孕期间8次就诊的孕妇的尿样。超声数据和尿样可获得性的结合为研究邻苯二甲酸盐暴露与怀孕、胎盘发育和功能以及胎儿生长之间的关系提供了一个独特的机会。 过去几年取得的进展 在2020财年，我们完成了这项研究参与者的招募和尿样采集，我们打算在超声测量胎盘和胎儿生长和功能的同时检测尿邻苯二甲酸盐代谢物。我们招募了大约300名参与者，他们在怀孕期间平均提供了7个尿样。

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. Last years progress In FY 2020 we completed recruitment and urine sample collection on participants for this study, in whom we intend to examine urinary phthalate metabolites in association with ultrasound measures of placental and fetal growth and function. We recruited approximately 300 participants who provided a mean of 7 urine samples during pregnancy.