**1. Introduction**

Maternal uterine artery blood flow is one of the critical factors that contribute to the preservation of the intrauterine environment, which permits normal placental function to support fetal growth and development. This is so, not only because maternal blood carries nutrition and removes waste, but also because oxygen delivered to the developing fetoplacental unit is directly limited by uterine blood flow. Spiral arterioles that perfuse the intervillous space undergo significant morphologic changes during this process, with uterine vascular adaptations resulting in five to 10-fold dilatation to meet the requirements of the fetoplacental unit [1]. It has long been believed that inadequate development of the uterine vasculature may be a consequence of primary defective placentation, which may lead to the development of both preeclampsia and fetal growth restriction. Understanding the relationship between uterine artery blood flow and placental development is fundamental to understanding normal placentation and its disruption in both preeclampsia and fetal growth restriction. This review focuses on the relationship between uterine artery blood flow and the trophoblast function, and discusses the insights provided into the pathophysiology of preeclampsia.

### **2. Uterine Artery Blood Flow Assessment**

Maternal uterine arteries can be readily and reliably identified via ultrasound by the use of a color Doppler and the pulsatility index (resistance to blood flow), assessed concurrently with a pulsed wave Doppler. Resistance to blood flow in the uterine arteries falls with advancing gestation, a finding attributed to progressive trophoblastic invasion and transformation of the uterine spiral

arteries into large vessels of low resistance [2]. Failure to transform has been described in preeclampsia and fetal growth restriction, resulting in the use of a uterine artery blood flow Doppler assessment to screen for these pregnancy problems [3]. A recent review of reviews for preeclampsia screening methods demonstrated that uterine artery Doppler assessment as a stand-alone test had the best predictive value for the prediction of early-onset preeclampsia when compared to other tests with a moderate predictive value, such as increased body mass index (BMI), placental growth factor (PLGF), and placental protein 13 (PP13). The analysis also showed that no single biomarker met the standards required for a clinical screening test, but that models, that combined markers, were more promising for the prediction of preeclampsia [4]. In a recent randomized controlled trial, the use of such multimodal screening to determine the risk of preterm preeclampsia, followed by the prescription of low-dose Aspirin prophylaxis before 16 weeks' gestation to the high-risk group, has been shown to halve the risk of preterm preeclampsia [5,6].

#### **3. Uterine Artery Doppler Indices and Trophoblast Biology**

The process of implantation, trophoblast development, and spiral artery transformation must involve many cellular and tissue processes to their e ffect. In view of the strong association between high uterine artery Doppler indices and the subsequent development of preeclampsia and fetal growth restriction, numerous authors have investigated trophoblast biology in samples obtained from pregnancies demonstrating high or low uterine artery Doppler resistance. Persistence of high resistance in the uterine artery Doppler indices in early pregnancy suggests that impaired trophoblast invasion and inadequate spiral artery remodeling has occurred [7].
