Early Diastolic Notch Research Articles

Prediction of Pre-Eclampsia by Abnormal Uterine Doppler Ultrasound and Modification by Aspirin

Objective To assess the effect of low dose aspirin on severe pre-eclampsia when given to women identified as high risk by abnormal uterine artery Doppler ultrasound. Design Women with abnormal uterine artery flow velocity waveforms were recruited to the CLASP trial at 24 weeks. Abnormal uterine artery waveforms, with a high resistance index or an early diastolic notch, were identified at the 18–22 week anomaly scan and confirmed at 24 weeks. Of those women with persistently abnormal waveforms, 63 agreed to enter the CLASP trial. Three women were lost to follow up and five did not comply. Thus, 60 were randomised: 29 to placebo and 31 to low dose aspirin (60 mg daily) and analysis by intention to treat is reported. Results There were nine cases (29%) of pre-eclampsia in the aspirin group and twelve (41%) in the placebo group (odds ratio (OR) 0.58, confidence interval (CI) 0.2–1.69, P = 0.32). Severe pre-eclampsia developed in four women in the aspirin group and eleven women in the placebo group (OR 0.24, CI 0.07–0.88, P = 0.03) and intrauterine growth retardation occurred in eight cases in the aspirin group and twelve in the placebo group (OR 0.49, CI 0.17–1.47). The mean birthweight and gestation at delivery were 2.69 kg and 38.5 weeks in the aspirin group and 2.38 kg and 37.4 weeks in the placebo group, neither of which were statistically significant using the unpaired t test; P = 0.09 and P = 0.23, respectively. Conclusions In high risk pregnancy low dose aspirin commenced at 24 weeks may reduce the incidence of severe pre-eclampsia.

Effects of therapeutic amniocentesis on uterine and umbilical artery velocimetry in cases of severe symptomatic polyhydramnios

The objective of this study was to determine the effects of removal of amniotic fluid in cases of symptomatic severe polyhydramnios on Doppler waveform indices of the uterine and umbilical arteries and flow velocities of the uterine arteries. Nine women underwent therapeutic amniocentesis during ten pregnancies for symptomatic polyhydramnios due to Beckwith-Wiedemann Syndrome (n = 1), esophageal atresia (n = 2), chorioangioma (n = 1), twin-twin transfusion syndrome (n = 3), a presumed autosomal recessive syndrome (n = 2), and an unbalanced double translocation (n = 1; partial dup 3q and partial del 9p syndrome). An average of 2.78 ± 0.9 (range 1–4) 1 of fluid were removed at each procedure between the gestational ages of 18 and 34 weeks (mean of 28 weeks). The systolic/diastolic (S/D) ratio, pulsitility index (PI), and resistance index (RI) of the uterine and umbilical arteries were obtained before and after the procedure using color and pulsed Doppler. After angle correction, the peak systolic velocity (PSV) and mean velocity (MV) in centimeters/second (cm/s) of the uterine arteries were also determined. The presence or absence of a uterine artery waveform notch was determined. Dominant uterine arteries were defined as those with lower impedance indices or higher flow velocities. Statistical analysis was performed with the Wilcoxon signed-rank test. Significance was set at P < 0.05. There was a significant increase in the median value of the uterine artery MV (43.8 vs. 81.1 cm/s, P = 0.005) and PSV (74.2 vs. 125.5 cm/s, P = 0.007) after amniocentesis. The uterine S/D (3.0 vs. 1.84, P = 0.007), PI (1.12 vs. 0.68, P = 0.008), and RI (0.60 vs. 0.45, P = 0.005) impedance indices significantly decreased following amniocentesis. When uterine arteries were categorized as dominant vs. nondominant, there were greater improvements in impedance indices and flow velocities in the nondominant uterine arteries. There were three cases of unilateral and one case of bilateral early diastolic notches of the uterine artery waveforms which either resolved (n = 4) or improved (n = 1). There was no effect on the umbilical artery impedance indices. Therapeutic amniocentesis significantly improved uterine artery impedance indices and resulted in improved flow velocities, while there was no effect on umbilical artery waveform indices. The procedure resulted in the disappearance or improvement of the uterine waveform notch. Our findings suggest that in cases of severe polyhydramnios abnormal uterine artery velocimetry may not be due to lack of trophoblastic invasion of the spiral arteries but to increased intrauterine pressure secondary to polyhydramnios. © 1996 Wiley-Liss, Inc.

Effects of therapeutic amniocentesis on uterine and umbilical artery velocimetry in cases of severe symptomatic polyhydramnios.

The objective of this study was to determine the effects of removal of amniotic fluid in cases of symptomatic severe polyhydramnios on Doppler waveform indices of the uterine and umbilical arteries and flow velocities of the uterine arteries. Nine women underwent therapeutic amniocentesis during ten pregnancies for symptomatic polyhydramnios due to Beckwith-Wiedemann Syndrome (n = 1), esophageal atresia (n = 2), chorioangioma (n = 1), twin-twin transfusion syndrome (n = 3), a presumed autosomal recessive syndrome (n = 2), and an unbalanced double translocation (n = 1; partial dup 3q and partial del 9p syndrome). An average of 2.78 +/- 0.9 (range 1-4) 1 of fluid were removed at each procedure between the gestational ages of 18 and 34 weeks (mean of 28 weeks). The systolic/diastolic (S/D) ratio, pulsitility index (PI), and resistance index (RI) of the uterine and umbilical arteries were obtained before and after the procedure using color and pulsed Doppler. After angle correction, the peak systolic velocity (PSV) and mean velocity (MV) in centimeters/second (cm/s) of the uterine arteries were also determined. The presence or absence of a uterine artery waveform notch was determined. Dominant uterine arteries were defined as those with lower impedance indices or higher flow velocities. Statistical analysis was performed with the Wilcoxon signed-rank test. Significance was set at P < 0.05. There was a significant increase in the median value of the uterine artery MV (43.8 vs. 81.1 cm/s, P = 0.005) and PSV (74.2 vs. 125.5 cm/s, P = 0.007) after amniocentesis. The uterine S/D (3.0 vs. 1.84, P = 0.007), PI (1.12 vs. 0.68, P = 0.008), and RI (0.60 vs. 0.45, P = 0.005) impedance indices significantly decreased following amniocentesis. When uterine arteries were categorized as dominant vs. nondominant, there were greater improvements in impedance indices and flow velocities in the nondominant uterine arteries. There were three cases of unilateral and one case of bilateral early diastolic notches of the uterine artery waveforms which either resolved (n = 4) or improved (n = 1). There was no effect on the umbilical artery impedance indices. Therapeutic amniocentesis significantly improved uterine artery impedance indices and resulted in improved flow velocities, while there was no effect on umbilical artery waveform indices. The procedure resulted in the disappearance or improvement of the uterine waveform notch. Our findings suggest that in cases of severe polyhydramnios abnormal uterine artery velocimetry may not be due to lack of trophoblastic invasion of the spiral arteries but to increased intrauterine pressure secondary to polyhydramnios.

The clinical implications of early diastolic notch in third trimester Doppler waveform analysis of the uterine artery.

To evaluate the clinical utility of third trimester Doppler waveform analysis of the uterine artery in predicting complicated pregnancies and fetal well-being, we compared adverse pregnancy outcomes in 2321 women with the presence of an elevated systolic-diastolic ratio (greater than 2.6) with the persistence of an early diastolic notch and with the combination of an elevated systolic-diastolic ratio and an early diastolic notch. The positive predictive values are 47.5%, 82.9%, and 92.6%, respectively. From these data we can conclude that determination of the presence or absence of an early diastolic notch is more valuable in predicting the perinatal outcome than is the presence of an elevated systolic-diastolic ratio alone. We also suggest that an assessment of the uterine artery systolic-diastolic ratio combined with the evaluation for persistent early diastolic notch would be a clinically useful test for fetal well-being.

A randomized controlled trial of aspirin in patients with abnormal uterine artery blood flow

To evaluate color Doppler imaging of the uterine arteries as a screening test in nulliparous women, and to examine the role of low-dose aspirin therapy in pregnancies with abnormal uteroplacental resistance. At the routine 18-week fetal morphology ultrasound scan, 955 nulliparous women underwent color Doppler imaging of the uterine arteries. Abnormal uteroplacental vascular resistance was defined with respect to both the systolic-diastolic ratio of the flow velocity waveform and the presence of an ipsilateral early diastolic notch. Those with abnormal uterine artery waveforms were asked to participate in a randomized controlled trial of aspirin therapy. Pregnancy outcomes were compared in women with normal or abnormal flow velocity waveforms, as well as in the two arms of the intervention study. Of 186 women with abnormal uteroplacental resistance according to criteria defined previously, 102 agreed to randomization to either low-dose aspirin (100 mg/day) or placebo for the remainder of the pregnancy. Abnormal uterine artery flow velocity waveforms were associated with statistically significant increases in preeclampsia (11 versus 4%), birth weight below the tenth percentile (28 versus 11%), and adverse pregnancy outcome (45 versus 28%). Prophylactic aspirin therapy did not result in a significant reduction in pregnancy complications. Abnormal uteroplacental resistance at 18 weeks' gestation was associated with a significant increase in adverse pregnancy outcome. Low-dose aspirin did not reduce pregnancy complications in women with uteroplacental insufficiency.

The clinical implications of early diastolic notch in third trimester Doppler waveform analysis of the uterine artery.

The clinical implications of early diastolic notch in third trimester Doppler waveform analysis of the uterine artery.

Computer analysis of the early diastolic notch in doppler sonograms of the uterine arteries

This article describes a set of processing and analysis techniques for automated identification and quantification of the early diastolic notch (EDN), a feature of Doppler sonograms from the uterine arteries which has been associated with adverse pregnancy outcomes such as preeclampsia and intrauterine growth retardation. Examples covering different sonogram types are provided to illustrate the effectiveness and reproducibility of the processing/analysis tools. Also, a receiver-operating characteristic-based evaluation of the EDN quantification and pulsatility indexes is presented, which examines the ability to predict hypertension and/or intrauterine growth retardation, using a set of uterine Doppler sonograms from 92 patients acquired at 18 weeks of gestation. In summary, the ROC results confirm the link between the EDN and abnormal pregnancy outcomes, and suggest that EDN quantification has a higher diagnostic accuracy than the pulsatility index, which characterises the flow waveform in a global manner and therefore does not take explicitly into account the localised nature of the EDN. Quantification of the EDN at 18 weeks of gestation appears to best predict the most severely abnormal pregnancy outcomes.

Doppler Ultrasound of the Uteroplacental Circulation in the Prediction of Pregnancy Outcome in Women With Raised Maternal Serum Alpha-Fetoprotein

Objective To determine whether Doppler waveforms from the uteroplacental circulation could improve the prediction of pregnancy outcome in women with raised maternal serum alpha-fetoprotein and a structurally normal fetus. The study further attempts to determine whether the presence of an early diastolic notch would constitute a better screening test than waveform patterns. Design An observational study. Setting A tertiary referral obstetric service. Subjects All women referred to St George's Hospital with a raised maternal serum alpha-fetoprotein had waveform measurements from the uteroplacental circulation after exclusion of fetal abnormalities. Pregnancy outcome was determined by questionnaire sent to the referring clinicians. Main outcome measures Adverse perinatal outcome in the form of preterm labour, low birthweight and perinatal mortality. Results Data from 332 cases were available for analysis. Women with a normal pattern of uteroplacental waveforms had a perinatal mortality of 9.6/1000. Women with a uniform high resistance pattern had a perinatal mortality of 846/1000, and those with a mixed resistance pattern had a perinatal mortality of 268/1000. Overall there were 27 cases of placental abruption which accounted for eight of the 50 perinatal deaths. The remainder were due to prematurity or low birthweight or both. The presence of the early diastolic notch did not improve on the waveform patterns in the prediction of perinatal death. Conclusion Women with raised maternal serum alpha-fetoprotein and normal Doppler waveform patterns from the uteroplacental circulation can be reassured, but mixed or uniform high resistance patterns should encourage increased surveillance and a search for intervention therapies.

Colour Doppler Imaging of the Uteroplacental Circulation in the Mid‐Trimester: Features of the Uterine Artery Flow‐Velocity Waveform that Predict Abnormal Pregnancy Outcome

EDITORIAL COMMENT: We accepted this paper for publication because it presents data on the use of colour Doppler imaging in a screening test in healthy nulliparas to assess whether abnormal pregnancy outcome can be identified. Unexpectedly there were 4 perinatal deaths in this series and table 4 indicates that in the only case in which the perinatal death was potentially avoidable the 24‐week uterine Doppler studies were normal. There is mounting evidence that Doppler imaging of uteroplacental circulation is useful in the management of identified high‐risk pregnancies but the value of the method as a screening test remains unproven. If larger studies confirm the reliability of this investigation to detect patients who are destined to develop preeclampsia then a possible application of this is identification of women who warrant prophylactic aspirin therapy since recent results show that aspirin therapy is not indicated routinely in nulliparasSummary: The accuracy of raised Resistance Index (RI) and early diastolic notching (EDN) of mid‐trimester uterine artery flow velocity waveforms in predicting abnormal pregnancy outcome was assessed in a prospective longitudinal study using colour Doppler imaging at 14, 18, and 24 weeks. In 106 healthy nulliparas with a singleton pregnancy studied; 70 had a normal pregnancy outcome, 34 had an abnormal pregnancy outcome, and 2 were lost to follow‐up. EDN was more sensitive than raised RI at predicting subsequent abnormal pregnancy outcome but raised RI was more specific at 14 and 18 weeks. Sensitivities were highest for the pregnancies with the more severely abnormal outcomes. Uterine artery Doppler studies in the mid‐trimester can predict abnormal pregnancy outcome. The presence of an early diastolic notch is an important feature when defining an abnormal or high resisitance uteroplacental circulation.

Color Doppler imaging of the uteroplacental circulation in the middle trimester: observations on the development of a low-resistance circulation.

We aimed to study the changes in the flow dynamics of the uteroplacental and umbilical circulations in the middle trimester of normal pregnancy, and establish normal ranges for indices of the Doppler flow velocity waveforms (FVWs) from both circulations at 14, 18 and 24 weeks. A longitudinal study was conducted with the use of color Doppler imaging to localize both uterine arteries and umbilical arteries and obtain FVWs from 106 healthy nulliparous women with a singleton pregnancy. Of these, 70 did not have a complicated pregnancy outcome, defined as hypertension, growth retardation, preterm delivery or perinatal death. We measured the resistance index (RI), pulsatility index (PI), systolic/diastolic (S/D) ratio and presence of early diastolic notching in both uterine arteries, and RI, PI and S/D in one umbilical artery. The results showed a fall in all measured indices of blood flow impedance in the uteroplacental and umbilical circulations and a marked reduction in the incidence of the early diastolic notch in the uterine artery FVWs during the mid-trimester. Our conclusion was that color Doppler imaging allows for the accurate localization of both uterine and umbilical arteries. Doppler FVWs then obtained confirm the development of the low-resistance uteroplacental and umbilical circulations in the mid-trimester. Diastolic notching is common at 14 weeks in normal pregnancy but uncommon at 24 weeks.

The role of Doppler velocimetry in the structurally normal second-trimester fetus with elevated levels of maternal serum alpha-fetoprotein.

Umbilical and uterine artery velocimetry was performed in 199 second-trimester pregnancies undergoing sonographic examination for unexplained elevated levels of maternal serum alpha-fetoprotein in order to evaluate the efficacy of Doppler waveforms for the prediction of adverse perinatal outcome. A total of 169 pregnancies resulted in term deliveries of infants with appropriate growth for age, and 30 pregnancies (15%) had adverse outcomes, including preterm delivery, growth retardation and death. The umbilical artery systolic/diastolic ratio was not statistically different in the two groups (3.9 vs. 4.2, p = 0.16). The uterine artery systolic/diastolic ratio was slightly greater in the group with abnormal outcome (5.7) than in the group with normal outcome (3.3), but the difference was not significant (p = 0.11). Forty-six patients had uterine artery waveforms that exhibited an early diastolic notch. Of these, 31 had a grade 1 notch in which the lowest part of the notch was not greater than one half of the diastolic frequency shift. Fifteen patients had a severe or grade II notch in which the deepest part of the diastolic notch was less than half of the diastolic flow. In patients with either no diastolic or grade I uterine artery notch, the incidence of adverse outcomes was 23/184 (12.5%). In patients with a grade II notch, 7/15 (47%) had a poor outcome. The rate of adverse outcome in patients with a grade II notch was more than three times that observed in women without severe uterine notch, yielding a relative risk of 3.4 (95% CI 1.9-6.0). Thus, the presence of a grade II uterine artery notch on second-trimester sonographic evaluation is associated with an increased risk for adverse perinatal outcome over unexplained elevated levels of maternal serum alpha-fetoprotein.

Doppler ultrasound of the uteroplacental circulation in the prediction of pregnancy outcome in women with raised maternal serum alpha-fetoprotein.

To determine whether Doppler waveforms from the uteroplacental circulation could improve the prediction of pregnancy outcome in women with raised maternal serum alpha-fetoprotein and a structurally normal fetus. The study further attempts to determine whether the presence of an early diastolic notch would constitute a better screening test than waveform patterns. An observational study. A tertiary referral obstetric service. All women referred to St George's Hospital with a raised maternal serum alpha-fetoprotein had waveform measurements from the uteroplacental circulation after exclusion of fetal abnormalities. Pregnancy outcome was determined by questionnaire sent to the referring clinicians. Adverse perinatal outcome in the form of preterm labour, low birthweight and perinatal mortality. Data from 332 cases were available for analysis. Women with a normal pattern of uteroplacental waveforms had a perinatal mortality of 9.6/1000. Women with a uniform high resistance pattern had a perinatal mortality of 846/1000, and those with a mixed resistance pattern had a perinatal mortality of 268/1000. Overall there were 27 cases of placental abruption which accounted for eight of the 50 perinatal deaths. The remainder were due to prematurity or low birthweight or both. The presence of the early diastolic notch did not improve on the waveform patterns in the prediction of perinatal death. Women with raised maternal serum alpha-fetoprotein and normal Doppler waveform patterns from the uteroplacental circulation can be reassured, but mixed or uniform high resistance patterns should encourage increased surveillance and a search for intervention therapies.

Improved prediction of preeclampsia by two-stage screening of uterine arteries using the early diastolic notch and color Doppler imaging

To assess the value of the early diastolic notch and color Doppler imaging of the uterine arteries at 24 weeks' gestation in a two-stage Doppler screening test for preeclampsia.Two thousand fifty-eight unselected women had an initial screening study with continuous-wave Doppler at 18-22 weeks' gestation. Color Doppler imaging was used at 24 weeks' gestation to examine both uterine arteries in 273 women with initial abnormal results (high resistance index or diastolic notch).Three hundred twenty-nine women (16%) had abnormal flow velocity waveforms at the first stage and 104 (5.1%) at the second stage of Doppler screening. The presence of an early diastolic notch in the flow velocity waveform was significantly better than a high resistance index at predicting preeclampsia at both 20 and 24 weeks; the relative risk of developing significant preeclampsia for a woman with a persistent notch at 24 weeks was increased 68-fold. All women delivered before 34 weeks because of severe preeclampsia had abnormal waveforms at both stages of screening.An early diastolic notch in the flow velocity waveform is a better predictor of preeclampsia than are conventional impedance indices. Preeclampsia can be predicted effectively by two-stage Doppler screening.

Continuous-Wave Doppler Investigation of Uteroplacental Vessels in High-Risk Pregnancies as Predictor of Fetal Growth Retardation and Pregnancy-Induced Hypertension

Continuous-wave Doppler sonography of uteroplacental vessels and the umbilical artery was used as an additive method in the management of risk pregnancies. Its major advantage lies in permitting noninvasive access to placental perfusion. In a sample of 650 singleton pregnancies considered at risk, flow patterns of the right and left uterine and arcuate arteries and of the umbilical artery were obtained. Increased resistance in uteroplacental circulation alone (90th percentile of resistance index and/or notching) was seen in 62 of 100 patients with confirmed growth retardation, proving the key role played by uteroplacental perfusion disorders. Early diastolic notching as well as incomplete vascular flow patterns were also found significantly more often in the growth-retarded group compared to the controls, especially in pregnancies additionally beset by hypertensive disorders. Doppler study of both utero- and fetoplacental circulation increased the sensitivity to 76% in pregnancies with intrauterine growth retardation, and to 90% in those cases with an additional risk of pregnancy-induced hypertension, while the false-positive rate (100-specificity) remained acceptable (17%).

Doppler ultrasound screening as part of routine antenatal scanning: prediction of pre-eclampsia and intrauterine growth retardation.

To assess the value of incorporating continuous wave Doppler ultrasound of the uterine arteries into the routine scan as a screening test in an unselected population. A cross sectional study by multiple operators using continuous wave Doppler ultrasound to obtain flow velocity waveforms (FVW) from both uterine arteries of all women attending for routine anomaly scan at 18 to 22 weeks over a period of 12 months. An abnormal FVW in either uterine artery was used to predict intrauterine death, antepartum haemorrhage and three different degrees of severity of pre-eclampsia and growth retardation, singly and in combination. King's College Hospital, London. Two thousand, four hundred and thirty women attending for routine anomaly ultrasound scan. A total of 2430 women were scanned with a 90% follow up rate. The results demonstrate higher sensitivities than previous studies, but with a high proportion of false positive tests. By including an early diastolic notch in the definition of an abnormal FVW the prediction of pre-eclampsia is markedly improved; the relative risk to a woman with an abnormal waveform of developing moderate or severe pre-eclampsia is increased 24-fold. Although the positive predictive value for babies less than the 5th centile for gestation is only 15%, those at risk of neonatal complications may be identified. This simple test can be performed at a routine visit and a group of women can be identified for further assessment and possible therapeutic intervention.

Braxton-Hicks contractions can alter uteroplacental perfusion.

Color flow imaging was used to study the effect of spontaneous low-amplitude uterine contractions (Braxton-Hicks) on flow velocity waveforms obtained from the main uterine artery in 13 women between 26 and 34 weeks' gestation. Eight women had abnormal waveforms, as defined by the presence of an early diastolic notch, and five women had normal waveforms. In the former group, three women with chronic hypertension were started on the calcium antagonist nifedipine during this study. Contractions, which were monitored by external tocography, occurred more frequently in the group with abnormal waveforms and were temporally associated with an increase in impedance to blood flow. This effect occurred to the same degree in both normal and abnormal groups, but in the abnormal group the already impaired blood flow to the intervillous space was further diminished, resulting in absence of forward flow in diastole. Such acute reductions of flow in response to frequent, impalpable uterine contractions may cause a prolonged and silent insult to uteroplacental perfusion, which could hasten fetal compromise. This effect appeared to be abolished in patients on nifedipine, suggesting a possible therapeutic role for this drug in uteroplacental insufficiency.

Development of uterine artery compliance in pregnancy as detected by Doppler ultrasound

Uterine artery velocimetry was performed by means of a continuous-wave Doppler ultrasound. Serial studies were done on 12 nonpregnant and 79 normal pregnant women. Measurements were made on both uterine arteries and averaged. From the proliferative phase of the menstrual cycle through 40 weeks of pregnancy, four developmental phases are described. These changes are based on the calculation of the systolic-diastolic ratio and the disappearance of the early diastolic notch in the velocity wave. The ratio after 26 weeks averaged 2 ± 0.3. These data provide a foundation for the study of pregnancies in which these normal evolutionary changes do not occur.