Elsevier

Placenta

Volume 33, Issue 11, November 2012, Pages 893-901
Placenta

Beyond the placental bed: Placental and systemic determinants of the uterine artery Doppler waveform

https://doi.org/10.1016/j.placenta.2012.07.011Get rights and content

Abstract

The uterine artery Doppler waveform has been extensively investigated, though its widespread clinical use as a predictor of adverse pregnancy outcome remains under debate. The determinants of the waveform have classically been ascribed to transformation of the spiral arteries and the development of a low resistance uteroplacental circulation, failure of which predisposes to pre-eclampsia, fetal growth restriction and other adverse outcomes. It has become increasingly evident that although spiral artery transformation determines in some part the characteristics of the Doppler waveform, factors pertaining to maternal vascular and endothelial function are also important.

Introduction

Since the early 1980s, uterine artery blood flow in pregnancy and its determinants have been of great interest to scientists studying the placental bed, to clinicians screening for conditions associated with abnormal placentation and to those involved in caring for women and with pre-eclampsia and their often growth restricted babies. Doppler ultrasound is widely used to assess the uterine artery Doppler waveform as high impedance or abnormal waveforms in the first, and particularly, second trimesters are related to adverse pregnancy outcome [1]. The adaptation of the uterine spiral arteries is classically believed to be related to the success of placentation [2]. However, it is increasingly evident that factors external to placenta and the placental bed are also important determinants of the uterine artery waveform Table 1.

In this review, we discuss the development and refining of ultrasound techniques to assess the uterine artery blood flow. We explore how uterine artery impedance is related to adverse pregnancy outcome and its association with placentation. Finally we consider the extra-placental factors that are emerging as additional determinants of the uterine artery waveform.

Section snippets

Development of techniques for ultrasound assessment

The use of Doppler ultrasound for assessment of the uteroplacental circulation was first reported in 1983 [3]. Prior to this, uterine artery blood flow could only be measured through invasive techniques or those using radio-dilution. However, it was the arcuate vessels in the uterine wall, rather than the uterine arteries, and blood flow, rather than impedance, was measured. Through the use of a linear array ultrasound and a combination of continuous wave and pulsed Doppler, a normogram of

Use of uterine artery Doppler in screening

That abnormal uteroplacental waveforms may be an early predictor of preeclampsia became apparent with the first studies relating Doppler findings to outcome [8]. It was postulated that women with abnormal waveforms in the second trimester could benefit from increased surveillance. With the recognition that both deficient placentation and abnormal uterine or spiral artery Doppler waveforms were associated with adverse obstetric outcomes, and that these were possibly linked, the role of uterine

Models of resistance and flow

With an increased understanding that pathological processes within the uteroplacental bed affected the uterine artery waveform, computer and bio-engineering models were developed to examine the effects of various factors. Electrical analogue modelling indicated that the early diastolic notch was most likely due to wave reflection and the persistence of this into the late second trimester is indicative of abnormally high placental bed resistance [17]. Further, computer modelling has demonstrated

Associations of uterine artery Doppler with histopathology of the placenta

The mechanisms of trophoblast invasion of the spiral arteries and the defects in spiral artery remodelling in relation to pregnancy complications has been comprehensively reviewed [21], [22]. However, though the uterine artery Doppler waveform has proved predictive for adverse outcomes related to utero-placental insufficiency, is the underlying pathological processes associated with these Doppler abnormalities understood?

Brosens' seminal work in 1967 [23] reported that the spiral arteries

Arterial stiffness and endothelial function

In 1985, Trudinger et al. [5] stated that “flow velocity is influenced by the ejection systolic pulse, arterial wall compliance, blood stream inertia and downstream peripheral resistance.” Whilst clinico-pathological findings of the placenta and placental bed correlate with the uterine artery Doppler waveform due to their major contributions to downstream peripheral resistance, other influences have been largely overlooked. The uterine artery waveform in pregnancy is also a reflection of

Maternal heart rate

Heart rate of the women affects uterine artery PI, showing a significant negative correlation [54]. This may appear intuitive, as the slower the heart rate, the longer an individual uterine systolic/diastolic cycle will be, allowing the end diastolic component to tend towards the baseline - in other words a higher PI. Although this effect is recognised, it is not adjusted for in clinical practice nor has it been in screening studies. Adjustment for heart rate can however improve both positive

Hormonal

Variations in impedance of the uterine arteries through the menstrual cycle [7], [56], [57], [58] and even diurnally [59] are described. Uterine artery impedance falls during the luteal phase of the menstrual cycle, particularly in the vessel ipsilateral to the corpus luteum. These reductions in impedance to the secretory endometrium at a time when implantation may occur is strongly correlated with increased plasma levels of progesterone and oestrodiol [7].

In women with polycystic ovary

Nitric oxide

Nitric oxide (NO), generated in the endothelium by the endothelial nitric oxide synthase (eNOS), is essential for proper endothelial function and regulation of vascular tone [63] (Fig. 4). eNOS activity is increased in the uterine arteries in normal pregnancy [64] and nitric oxide plays a key role in systemic vasodilation in normal pregnancy [65]. These effects are mediated predominantly through activation of soluble guanylate cyclase (sGC) by NO and the subsequent conversion of guanosine

Antihypertensive agents and uterine artery Doppler

Antihypertensive agents commonly used to treat hypertensive disorders of pregnancy have largely shown no effect on the uterine artery PI. These include the calcium-channel blockers nifedipine [79], [80], [81] and verapamil [82], hydralazine [79] and labetalol (a mixed alpha/beta antagonist) [83], [84], [85]. Alpha-methyldopa showed a significant decrease in uterine artery impedance in a single study in preeclampsia [86]. Nifedipine is occasionally used for tocolysis at much higher doses than is

Extra-uterine pregnancy

Normal (i.e. low impedance) uterine artery Doppler waveforms have been recorded in extra-uterine pregnancies [88], [89]. This might at first sight appear to be bizarre as there is no intrauterine placental bed to cause downstream resistance. Whilst these case reports do not provide a mechanism for this phenomenon, they do provide one of the clearest indications that factors external to placental resistance may also be responsible for the pregnant uterine artery waveform.

Malaria

One study has investigated the effect of the malaria causing parasite, Plasmodium falciparum, on the uterine artery Doppler waveform [90]. The uterine artery Doppler waveforms were twice as likely to be abnormal in women with malaria parasites detected on blood film and women with abnormal waveforms were likely to delivery prematurely with lower birth weight babies. Acute P. falciparum infection appears to be the cause of increased resistance in the uteroplacental vasculature, although this may

Postpartum

Following delivery, uterine artery impedance and waveforms have been studied for up to 3 months [91]. There is considerable inter-individual variation in the post-partum changes with some studies showing a steady increase in impedance from the first day post-partum to normal values at 4–6 weeks post-partum [92], [93] and others showing uterine artery impedance remaining low until 4 weeks post-partum [94], [95]. Similarly, where an early diastolic notch was present in pregnancy it may reappear

Conclusion

It is evident that the uterine artery waveform in normal pregnancy is a composite of downstream resistance (the placental circulation) and maternal arterial function. That a normal uterine waveform in pregnancy reflects successful trophoblastic invasion and conversion of the spiral arteries is true, but this does not reflect the whole truth. Conversely, that abnormal uterine artery waveforms represent raised placental bed resistance is true – but this also does not represent the complete

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