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。导致正常胎儿生长受限的最重要因素是胎盘中营养和氧气的输送不足。这可能是由于妊娠早期植入不良、梗塞或其他并发症导致灌注不良所致。在体内评估胎盘功能障碍的一个潜在的有价值的工具是超声技术。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，并提供了许多机会，以改善评估健康的胎盘。环境化学物质暴露和胎儿生长的研究有限，而且大多数只关注与出生体重的关系。这种测量方法不恰当地捕捉到生长的病理和正常变化，也未能捕捉到生长限制之前的机制（例如，胎盘植入不良）。化学物质暴露与胎盘功能的研究也仅限于检查其与分娩时体重、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）或胎盘分子标志物的关系。对邻苯二甲酸盐等非持久性化学品的研究也受到不良接触评估的限制。由于它们的半衰期很短，单点尿样可能不能准确反映妊娠期间的暴露情况。此外，由于水平是可变的，使用一种测量方法可能会遗漏有关怀孕期间与不良后果最相关的信息。

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).