Environmental phthalate exposure in the Human Placenta Project cohort

National Institute Of Environmental Health Sciences

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Abstract

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 published findings on the relationship between phthalates and replacement exposures in pregnancy and gestational blood pressure and hypertensive disorders of pregnancy (PMID: 40311894). We also made substantial progress on a new project to examine 3D ultrasound measures of fetal organ volume in utero.