Many epidemiological studies have associated exposure to traffic-derived air pollution from motor vehicles, air toxics from industry and other environmental toxins by pregnant women with measures of poor birth outcomes including preeclampsia (PE), preterm birth (PTB) and intra-uterine growth restriction (IUGR). Preeclampsia, preterm birth and IUGR, collectively known as ischemic placental disease, are strongly correlated with infant morbidity and a host of adult diseases ranging from coronary artery disease to cancer. Although it is widely believed that the pathophysiological mechanisms leading to complications of ischemic placental disease and placental insufficiency have similar biological origins, starting as early as defective placental implantation, to date there are no predictive studies that prospectively examine placental structure and/or function. The objective of this proposal is to develop and evaluate a suit of cutting-edge multi-parametric magnetic resonance imaging (mp-MRI) technologies and translate these novel placental imaging modalities to assessing the impact of environmental pollution exposure on prediction of placental insufficiency. Our central hypothesis is that chronic exposure to high rates of environmental pollution, independent of socio-economic status (SES), increases the risk of placental insufficiency due to early gestational development of adverse placental structure/function as detected by mp- MRI technological advances. To test this hypothesis, our interdisciplinary research team at UCLA will first develop non- contrast free-breathing placental mp-MRI, consisting of multi-delay pseudo-continuous arterial spin labeling (pCASL) perfusion and high-resolution multi-contrast structural MRI, which will provide accurate measures of placental perfusion and tissue microstructure (AIM 1). The novel mp-MRI techniques will be compared to the uterine artery Doppler ultrasound through pregnancy, and validated ultimately by the gold standard histological pathology and vascularity of the post-parturient placenta (AIM 2). Lastly, we will perform in-depth analyses of recruited subjects for exposure to environmental pollution and correlate their rates of exposure to extensively collected pregnancy outcomes, towards building a predictive model (AIM 3). These studies will establish the impact of environmental pollution on placental structure and function, and related pregnancy outcomes, with obstetric and neonatal practices embracing surveillance tactics based on the residential location of pregnant women and their offspring. In addition, the proposed research will establish the potential for early recognition of placental insufficiency, thereby staging future strategies o preventive and interventional therapies targeting reversal before encountering detrimental consequences.
How environmental pollution contributes to poor pregnancy outcome is poorly understood. The first trimester of pregnancy is a particularly vulnerable time period for the developing fetus and a mother's exposure to air pollution may alter the way that the placenta is established and how it functions throughout the rest of pregnancy. This project aims to expand and develop new MRI technologies to assess real-time placental structure and function as pregnancy develops from the first to the third trimester so that early detection, prevention strategies, and early treatment of placental dysfunction as a result of pollution exposures may be developed.
