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The advent of sonography has changed the practice of obstetrics by providing a window to the womb through which the anatomic structure of the fetus can be evaluated. The addition of Doppler flow studies of maternal and fetal vessels has provided a tool where the physiology of the maternal-fetal unit can be assessed. This information can provide the physician and the patient with vital information for a subsequent approach to the pregnancy. The use of fetal Doppler blood flow studies has become common in the evaluation and management of pregnancies complicated by conditions such as suspected fetal growth restriction and red blood cell isoimmunization to guide intrauterine therapy and delivery. The most commonly assessed Doppler flow studies of the fetus are the umbilical artery and middle cerebral artery (MCA). Doppler flow studies of the MCA are used in the assessment of the fetus at risk for anemia and growth-restricted fetus. Doppler flow studies of the umbilical artery can reflect abnormalities in “down-stream” or the fetal side of placental resistance, and the assessment of the maternal vasculature evaluates “up-stream” blood flow or the maternal side of placental resistance. The purpose of this review is to describe the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in low and high risk populations.
In normal pregnancy, placental trophoblast cells invade the inner third of the myometrium and migrate the entire length of the maternal spiral arteries. Remodeling of these high resistance arteries results in a low resistance and high flow state in the intervillous space, which optimizes delivery of oxygen and nutrients to the fetus. This change in resistance is reflected in uterine artery Doppler studies by a high diastolic velocity with continuous flow during diastole (Figure 1, A-D). In women who develop preeclampsia there is failure of trophoblast invasion of the uterine vasculature with the result that the spiral arteries retain the muscle elastic coating and impedance to blood flow persists.
A similar mechanism of failed trophoblast invasion and high resistance has been described in women who subsequently deliver infants with growth restriction.
Theoretically, a pathological increase in placental vascular resistance should be detectable by abnormal Doppler flow studies of the maternal uterine vessels, and this could offer the potential to detect women at risk for diseases like preeclampsia and fetal growth restriction.
For Editors' Commentary, see Table of Contents
FIGURE 1Uterine artery Doppler ultrasound in the nonpregnant and pregnant patient
A, Nonpregnant patient. B, First trimester. C, Second trimester. D, Third trimester. E, Abnormal uterine artery Doppler wave form demonstrating high resistance.
Sciscione. Uterine artery Doppler flow studies in obstetric practice. Am J Obstet Gynecol 2009.
Uterine artery Doppler studies in normal pregnancy
Schulman and colleagues determined that in the nonpregnant state there is a rapid rise and fall in uterine artery flow velocity during systole and a “notch” in the descending waveform in early diastole (Figure 1, A).
During pregnancy, they noted a significant increase in uterine artery compliance between 8 and 16 weeks, which continued to a lesser extent until 26 weeks' gestation (Figure 1, A-D). This physiologic change in compliance resulted in the loss of the diastolic notch between 20 and 26 weeks' gestation.
This finding was corroborated by Jurkovic and Juaniaux, who found similar changes in the resistance index (RI) and pulsatility index (PI) of the uterine artery Doppler signal (Table 1). They determined that the RI decreased from 0.8 to 0.63 between 8 and 17 weeks, and that the PI decreased from 2.0 to 1.3 between 8 and 18 weeks' gestation.
The majority of research has centered on an elevation in the RI or PI, or the persistence of a uterine artery diastolic notch to detect the presence of increased uteroplacental vascular resistance. Criteria for an abnormal RI have varied from a single cutoff (eg, RI > 0.58) to a percentile cutoff value (eg, 75th, 90th, 95th). The FASTER study, a large prospective observation study, found a uterine artery Doppler RI value above the 75th percentile at 10-14 weeks' gestation to predict a 5.5-fold higher likelihood of subsequent growth restriction than those with a lower value.
Gomez et al evaluated the uterine artery PI in the first trimester, and was able to identify 30.8% of pregnancies that subsequently developed severe pregnancy complications by using the 95th percentile as a cutoff.
combined maternal history with uterine artery Doppler to determine a patient's specific risk. Accepting a false positive rate of 25%, they were able to identify 67.5% of women who would subsequently develop preeclampsia.
Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis.
It appears that as the impedance to flow increases in the placenta there is momentary closure of the uterine artery in late systole or early diastole, or an increase in downstream resistance as the relatively inflexible distal artery recoils from distention caused by the systolic pulse. This is manifested as an early diastolic notch in the Doppler wave form (Figure 2). Most studies use subjective criteria for the definition of a diastolic notch, but a drop of at least a 50 cm/s from the maximum diastolic velocity is a reasonable criterion after 20 weeks.
In a screening program of 2058 unselected women, Bower et al identified women with a uterine artery diastolic notch present or a high RI (> 95th percentiles) at 18-22 weeks, and repeated testing for these women at 24 weeks.
Uterine artery notching was defined subjectively but the authors demonstrated concordance in subjective criteria among sonographers before the study was performed. Three hundred twenty-nine (16%) women had abnormal RI values and/or uterine artery notching on the first evaluation, with 104 women having persistently abnormal testing. The presence of a diastolic notch was a better predictor of preeclampsia than an elevated RI. In an evaluation of women at increased risk for preeclampsia or growth restriction, Chan et al
compared the diagnostic accuracy of gestational-aged adjusted 90th and 95th percentile cutoffs for RI at 20, 28, 36 weeks' gestation with a cutoff of 0.58, and the presence or absence of a diastolic notch. They concluded that 20 weeks' gestation was the optimal time for testing, with an abnormal value being defined as above the 90th percentile. The presence of a diastolic notch carried a 57% positive predictive value for subsequent severe complications and 93% predictive value for any complication.
Although this combination had the strongest positive predictive value, the sensitivity remained low for any complications (21%) and for severe complications (27%).
In summary, there are no current standards for gestational age at testing or criteria for an abnormal uterine artery Doppler study. Once adequately trained in the technique, a reasonable approach would be to use an ultrasound machine with the capability to perform continuous wave and/or pulsed wave Doppler studies of the uterine, arcuate, and subplacental arteries. In 1 report, a proper waveform could be obtained within 20 minutes in all cases.
showed little difference between using an RI > 0.58 or an RI above the 95th percentile, and both were more effective at predicting an adverse outcome when combined with the presence of a diastolic notch.
A reasonable definition for a diastolic notch is a drop of at least 50 cm/s from the maximum diastolic velocity. PI has been less commonly reported, but using levels above the 95 percentile or a PI > 1.6 appears to be appropriate. Recent reports show some utility in assessment of uterine artery flow in the first trimester. However, the second trimester has yielded more consistent results. Performance at 18-20 weeks' gestation is a reasonable approach. There is some evidence that repeating the tests at 24-26 weeks may add further benefit.
Abnormal uterine artery Doppler studies in both the first and second trimesters have been shown to be associated with subsequent perinatal complications. For women with abnormal testing in the first trimester, the likelihood ratio (LR) for the development of preeclampsia is approximately 5, while those with normal Doppler flow studies have an LR of 0.5.
The effect of gestational age and placental location on the prediction of preeclampsia by uterine artery Doppler velocimetry in low-risk nulliparous woman.
The effect of gestational age and placental location on the prediction of preeclampsia by uterine artery Doppler velocimetry in low-risk nulliparous woman.
How useful is uterine artery Doppler flow velcimetry in the prediction of preeclampsia, intrauterine growth retardation and perinatal death? An overview.
Strict criteria regarding diagnostic interventions and outcome measures were used for inclusion. Twenty-eight studies met their criteria, encompassing a total of 12,994 patients. Analysis of studies involving low risk populations revealed that an abnormal velocity waveform with or without a diastolic notch carried an LR of 6.4 for subsequent development of preeclampsia (95% confidence interval [CI], 5.7-7.1), and a negative result carried an LR of 0.7 (95% CI, 0.6-0.8). Women with a positive test had an LR of 3.6 (95% CI, 3.2-4.0) for the development of fetal growth restriction and a negative result carried a 0.8 LR (95% CI, 0.8-0.9). Results for the prediction of perinatal death were less robust with an LR of 1.8 (95% CI, 1.2-2.9) for a positive test result, and 0.9 (95% CI, 0.8-1.1) for a negative result. A recent metaanalysis found a positive LR for preeclampsia of 7.5 (95% CI, 5.4-10.2) and a negative LR of 0.59 (95% CI, 0.47-0.71), and for severe preeclampsia a positive LR of 15.6 (95% CI, 13.3-17.3) and a negative LR of 0.4 (95% CI, 0.2-0.6). Furthermore, in women with abnormal uterine artery Doppler studies a positive LR of 9.1 (95% CI, 5.0-16.7) and a negative LR of 0.89 (95% CI, 0.85-0.93) were found for the occurrence of growth restriction.
How useful is uterine artery Doppler flow velcimetry in the prediction of preeclampsia, intrauterine growth retardation and perinatal death? An overview.
Treatment of women considered at low risk with abnormal uterine artery Doppler studies
Several studies (Table 2) have evaluated the potential benefits of therapeutic interventions for those with abnormal uterine artery Doppler studies. One of the largest, by Goffinet et al, was a multicenter trial of 3317 pregnant women.
Screening with a uterine Doppler in low risk pregnant women followed by low dose aspirin in women with abnormal results; a multicenter randomized controlled trial.
Low risk gravidas with an abnormal uterine artery Doppler between 20 and 24 weeks' gestation were treated with of 150 mg aspirin daily until 36 weeks' gestation. They found no significant reduction of intrauterine growth restriction and preeclampsia when these women were compared with women who did not receive aspirin therapy, and concluded that there was no justification for screening and treatment with uterine artery Doppler in low risk populations. These findings were supported by a subsequent study of 560 women with abnormal uterine artery Doppler studies at 22 to 24 weeks' gestation and who were randomly allocated to receive aspirin 150 mg daily or placebo until 36 weeks' gestation.
Fetal Medicine Foundation Second Trimester Screening Group Randomized control trial using low-dose asprin in the prevention of preeclampsia in women with abnormal uterine artery Doppler at 23 weeks' gestation.
Again, no differences in incidence of preeclampsia (18% vs 19%; P = .6), preeclampsia requiring delivery before 34 weeks (6% vs 8%, P = .36), birthweight below the 5th percentile (22% vs 24%; P = .4), perinatal death (3% vs 1%; P = .33), or placental abruption (4% vs 2%; P = .12) were seen. In a secondary analysis of a recently published prospective study of antioxidant therapy for the prevention of preeclampsia that found no significant benefit from 1000 mg of vitamin C and 400 IU of vitamin E given daily to at-risk woman, those with abnormal uterine Doppler studies at 18-22 weeks' gestation also failed to benefit from therapy (preeclampsia; 24% vs 25%; relative risk [RR], 0.95; 95% CI, 0.40-2.29; Table 1).
Screening with a uterine Doppler in low risk pregnant women followed by low dose aspirin in women with abnormal results; a multicenter randomized controlled trial.
Restriction of screening to populations at increased risk for adverse outcomes can improve the predictive value of the test. Based on this principle it is plausible that uterine artery Doppler studies could prove more useful when performed on at-risk women. The metaanalysis by Chien et al included 12 studies of high risk patients which met stringent inclusion criteria.
How useful is uterine artery Doppler flow velcimetry in the prediction of preeclampsia, intrauterine growth retardation and perinatal death? An overview.
The LR for preeclampsia after an abnormal test was 2.8 (95% CI, 2.3-3.4), resulting in an increase in the pretest probability from 9.8-23%. Similar results were obtained for the prediction of fetal growth restriction, with an LR of 2.7 (95% CI, 2.1-3.4), with the probability increasing from 17.8-36.7% with a positive test. The LR of perinatal death after an abnormal test was 4.0 (95% CI, 2.4-6.6), increasing the pretest probability from 8.9-27.8%. A recent metaanalysis on uterine artery Doppler and adverse pregnancy outcomes in high risk gravidas included 83 studies with approximately 18,000 women, and found that the presence of notching had a positive LR of 20.2 (95% CI, 7.5-29.5) and a negative LR of 0.17 (95% CI, 0.03-0.56) for preeclampsia. In the same analysis, women with an RI > 0.58 had a positive LR of 10.9 (95% CI, 10.4-11.4) and negative LR of 0.20 (95% CI, 10.4-11.4) for growth restriction.
Though an effective intervention to avoid complications has not been identified for high risk women with an abnormal uterine artery Doppler study, it is plausible that testing could be used to select those who are at lower risk based on a reassuring test. The patient with a negative study could then undergo fewer evaluations during the pregnancy, with a reduction in health care costs and time lost. Axt-Fliedner et al
considered this possibility in a prospective study of at-risk singleton pregnancies (history of essential hypertension or preeclampsia, prior infant with fetal growth restriction or intrauterine death, or prior placental abruption). Bilateral uterine artery notching was associated with a positive predictive value of 33% (RR, 12.7) for a composite morbidity defined as the occurrence of preeclampsia or fetal growth restriction requiring delivery before 34 weeks, or fetal demise or placental abruption at any gestational age. Alternatively, the negative predictive value was also high at 93-97%. The highest negative predictive value (97%) was seen for women with both a normal RI and the lack of bilateral uterine artery notching. The authors concluded that high-risk women who had normal uterine artery Doppler studies at 19-26 weeks' gestation could be considered to be a low-risk group suitable to less intensive antenatal care. Subsequent studies have also found high negative predictive values among high-risk populations. Harrington et al found reassuring testing to carry a negative predictive value of 99.2% for preeclampsia, 95.9% for SGA, 100% for abruption, and 97.7% for stillbirth and/or neonatal death.
found superimposed preeclampsia to develop in 12% of women with abnormal flow studies and in none of those with reassuring studies among 78 gravidas with chronic hypertension. The rate of fetal growth restriction was also low among women with reassuring Doppler studies (2% vs 52%).
There are limited studies of uterine artery Doppler in women with multiple gestations. The uterine arteries in twin gestations have been shown to have lower RIs
Doppler assessment of the uterine circulation I. The second trimester in twin pregnancies: prediction of pre-eclampsia, fetal growth restriction and birth weight discordance.
it has been suggested that the sensitivity of the PI and RI for prediction of untoward outcomes is lower in twins than singletons given a similar 5% screen-positive rate.
Until further information is available, the role of uterine artery Doppler screening in women with multiple gestations is unclear, and a negative test should not be used to reassure the patient regarding potential adverse pregnancy outcomes.
recently evaluated the potential role of uterine artery Doppler flow studies in the detection of chromosomally abnormal fetuses and found that the majority of chromosomally abnormal fetuses to have a PI in the normal range for euploid fetuses (below the 95th percentile). They concluded that the high risk of fetal demise and growth restriction in aneuploid fetuses does not appear to be the consequence of impaired placentation in the first trimester of pregnancy.
Regardless of the pathophysiology, it appears that uterine artery Doppler studies are not helpful in differentiating aneuploid from euploid fetuses.
Conclusion
Abnormal uterine artery Doppler studies in the first and second trimester have been associated with subsequent adverse pregnancy outcomes including preeclampsia, fetal growth restriction, and perinatal mortality. However, the predictive value of Doppler testing in a low-risk population of women appears to be low, and currently there are no available interventions to prevent adverse outcomes based on an abnormal result. Effective interventions to prevent late pregnancy complications (eg, preeclampsia, growth restrictions, and perinatal mortality) in women considered at low risk with abnormal early pregnancy uterine artery Doppler studies are needed. Until such time as these are available, routine uterine artery Doppler screening of women considered at low risk is not recommended. Uterine artery Doppler screening of high-risk women (eg, history of chronic hypertension or preeclampsia, prior fetal growth restriction, or stillbirth) with singleton gestations appears to identify those at substantially increased risk for adverse pregnancy outcomes. Abnormal testing in these women could potentially lead to increased surveillance (eg, earlier and more frequent assessment of fetal growth and maternal clinical condition) and interventions that might improve clinical outcomes. Normal Doppler studies could potentially lead to a reduction in such testing and interventions. However, further study is needed to determine which high-risk conditions are amenable to such screening, what testing regimen is optimal for a normal or abnormal test in these women, and what interventions based on these findings will improve pregnancy outcomes.
At this time, the evidence does not support routine screening with uterine artery Doppler in any particular group of patients. Use of umbilical artery Doppler should be individualized, and a plan of management based on the results should be put in place. Because standards for the study technique, gestational age, and criteria for an abnormal test are lacking, uterine artery Doppler studies should not be considered to be a required medical practice in low or high risk populations.
References
Lin S.
Shimizu I.
Suehara N.
Nakayama M.
Aono T.
Uterine artery Doppler velocimetry in relation to trophoblast migration into the myometrium of the placental bed.
Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis.
The effect of gestational age and placental location on the prediction of preeclampsia by uterine artery Doppler velocimetry in low-risk nulliparous woman.
Screening with a uterine Doppler in low risk pregnant women followed by low dose aspirin in women with abnormal results; a multicenter randomized controlled trial.
Editor's Commentary: The Society for Maternal Fetal Medicine has approved this paper as representing a valid summary of the current use of uterine artery Doppler studies in obstetric practice.
An Editors' Commentary for the Review article “Uterine artery Doppler flow studies in obstetric practice” by Anthony C. Sciscione, DO, and Edward J. Hayes, MD, published in the August 2009 issue (Am J Obstet Gynecol 2009;201:121-6), states: “The Society for Maternal-Fetal Medicine has approved this article as representing a valid summary of the current use of uterine artery Doppler studies in obstetric practice.”
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