Uterine Artery Doppler Waveforms Research Articles

First trimester maternal serum PAPP-A and uterine flow velocity waveforms in the prediction of adverse pregnancy outcome. – Preeclampsia, IUGR and preterm delivery represent main risk factors in today‘s obstetrics

This study investigates the early prediction of Preeclampsia (PIH), IUGR and prematurity using first trimester uterine artery doppler waveform analysis (UAD) and maternal serum PAPP-A analysis in a group of singleton pregnancies at 10–16 weeks‘gestation. A retrospective study was performed on two independent samples of singleton pregnancies using Brahms Kryptor analysis and color coded doppler flow waveform analysis (GE Voluson 730E). The pregnancies undergoing PAPP-A analysis (n=66) were grouped respectively according to normal and pathological birth results (IUGR<10th centile, prematurity<38 weeks, APGAR 5rsquor; <7, umbilical artery pH<7.2). PAPP-A levels from pregnancies with pathological birth results were compared to those with normal birth results using the Chi²- and Fisher‘s exact- test. The cutoff level was MoM PAPP-A (10th centile). For the doppler cohort (n=114) mean Pulsatility- and Resistance-Index of the uterine arteries were calculated using the system built-in algorithm. The correlation of PI and RI with PIH and pathological birth result was calculated using logistic regression. Lower PAPP-A values were associated with pathological birth result, but the PAPP-A levels within subgroups (normal/pathological birth result) differed without reaching statistical significance (p=0.068). This difference reached statistical significance in the subgroup of primaparae with a sensitivity of 67% (p=0,01). Results for first trimester UAD did not correlate with adverse pregnancy outcome. PAPP-A levels below 10th centile are associated with preterm delivery and IUGR and seemed to be a stronger first trimester predictor of adverse pregnancy outcome compared to first trimester UAD.

OP01.04: Total vascular resistance is already elevated at 24 weeks' gestation in patients with subsequent complications in persisting bilateral notching of uterine artery Doppler waveforms

OP01.04: Total vascular resistance is already elevated at 24 weeks' gestation in patients with subsequent complications in persisting bilateral notching of uterine artery Doppler waveforms

OC214: Prediction of pre‐eclampsia by uterine artery Doppler waveform analysis in pregnancies complicated by chronic arterial hypertension

OC214: Prediction of pre‐eclampsia by uterine artery Doppler waveform analysis in pregnancies complicated by chronic arterial hypertension

OC215: Elevated total vascular resistance more than persisting bilateral notches of uterine artery Doppler waveforms identifies patients at risk of pregnancy complications

OC215: Elevated total vascular resistance more than persisting bilateral notches of uterine artery Doppler waveforms identifies patients at risk of pregnancy complications

P41.05: Prediction of pre‐eclampsia using a combination of first trimester arterial pulse wave analysis and second trimester uterine artery Doppler waveform

Results: The resistance index in the pre-term pre-eclampsia group (mean = 0.7) was significantly higher (P < 0.0001) compared to the control group (mean = 0.54) as well as compared to the term pre-eclampsia group (P < 0.0001). In the term pre-eclampsia group, the resistance index (mean = 0.56) was just significantly higher compared to the controls (mean = 0.54, P = 0.02). ROC curves generated also showed that uterine artery Doppler had a very good sensitivity for predicting pre-term pre-eclampsia. The ROC data showed that uterine artery Doppler is not sensitive at all for predicting term pre-eclampsia (r2 = 0.99). Conclusion: These data showed that uterine artery Doppler had a good sensitivity for pre-term pre-eclampsia, but was not of value in predicting term pre-eclampsia. As uterine artery Doppler changes are known to reflect spiral artery transformation by the developing trophoblast, it is possible that defective transformation of spiral arteries is not a predisposing factor for term pre-eclampsia.

OP19.09: Qualitative characteristics of uterine Doppler waveforms during early gestation in patients after conservative myomectomy

Our purpose was to assess the features of uterine artery Doppler waveforms in patients during early pregnancy after conservative myomectomy. Retrospective study (2005–2007) of 58 pregnancies at 8 to 14 weeks after conservative myomectomy (32 with only postoperative scars and 26 with recurrence of myomas less then 4 cm). Doppler ultrasound examination (Acuson 128XP-10, Acuson, USA) of left and right uterine artery waveforms was performed at 8, 10, 12 and 14 weeks. The presence of early or end diastolic flow was evaluated, and waveforms with its absence were considered as normal. Among 32 pregnancies with postoperative scars 17 (53.1%) had normal waveforms, nine (28.1%) had absence of early diastolic flow, three (9.4%) absence of end diastolic flow and three (9.4%) absence of both diastolic flows. Among 26 pregnancies with recurrence of myomas the values were nine (34.6%), 10 (38.5%), three (11.5%) and four (15.4%) correspondingly. In the second group the hypertonic myometrial reaction (15 (57.7%) versus 13 (40.6%)) and vaginal bleeding (23.1% versus 12.5%) were observed more often. At 13–14 weeks after tocolytic treatment the clinical status was improved and Doppler waveform features became normal in 27 (84.4%) pregnancies in the first group, and in 21 (80.8%) in the second. The assessment of qualitative characteristics of uterine Doppler waveforms during early gestation in patients after conservative myomectomy may be useful in the evaluation of the effectiveness of treatment.

Maternal serum concentration of soluble fms-like tyrosine kinase 1 and vascular endothelial growth factor in women with abnormal uterine artery Doppler and in those with fetal growth restriction

This study was undertaken to determine whether maternal serum concentration of the angiogenic factor vascular endothelial growth factor (VEGF) and its circulating antagonist, soluble fms-like tyrosine kinase 1 (sFlt-1), which have been implicated in the pathogenesis of preeclampsia (PE), are altered in pregnancies that subsequently develop PE and in those with established fetal growth restriction (FGR). Three groups of healthy pregnant women at 23 to 25 weeks of gestation were examined: group A (n = 42) with normal uterine artery Doppler waveforms, group B (n = 49) with abnormal uterine artery Doppler waveforms, and group C (n = 15) with abnormal Doppler results and established FGR. Comparisons between multiple groups were performed by using 1-way analysis of variance or Kruskal-Wallis test. In group C, compared with group A, the median sFlt-1 was significantly higher (P < .0001) and VEGF was lower (P < .001). Group C included 3 women who had PE develop. In group B, 19 women had a normal outcome, 13 had PE develop, and 17 had FGR develop. There were no significant differences in sFlt-1 levels between any of the subgroups of group B and group A. Maternal serum concentration of sFlt-1 in pregnancies with FGR is increased but this increase is not evident in pregnancies with impaired placentation that subsequently had either FGR or PE develop.

Uterine Artery Doppler and Changes in Endothelial Function Before Clinical Disease in Preeclamptic Women

To the Editor: Khan et al1 screened women for increased risk of preeclampsia using uterine artery Doppler waveforms at 18 to 20 weeks gestation. However, at this gestational age a high proportion of the abnormal waveforms may still normalize. Bower et al showed that 16% of 2058 unselected women …

Influence of parity on second-trimester uterine artery Doppler waveforms in twin pregnancy

We performed uterine artery Doppler velocimetry in 16 nulliparous and 16 parous women with non-preeclamptic singleton gestations and 16 nulliparous and 16 parous women with dichorionic twin gestations at 17–18 and 26–27 weeks of gestation. In both singleton and twin pregnancies, the average pulsatility index (PI) in nulliparous women was significantly higher than that in parous women at 17–18 weeks of gestation. At 26–27 weeks of gestation, however, there were no significant differences in PI between nulliparous and parous women with either singleton or twin pregnancies. During the early second-trimester of non-preeclamptic singleton and twin pregnancies, parity has a significant effect on uterine artery blood flow.

Ultrasound detection of placental insufficiency in women with ‘unexplained’ abnormal maternal serum screening results

Serious placental insufficiency results in perinatal death or preterm birth from ischemic-thrombotic pathology, a process which has its origins in placental maldevelopment in the first trimester. A proportion of at-risk pregnancies may be identified from abnormalities in first or second trimester serum screening data, uterine artery Doppler waveforms or placental shape and texture at the time of the 18-20-week anatomical examination. In combination, these tests may be capable of recognizing a subset of at-risk pregnancies with 50% positive predictive values. Early recognition before fetal viability affords opportunities to direct women to regional perinatal care centres for enhanced maternal-fetal surveillance, corticosteroids to enhance fetal lung maturation, prophylactic measures to prevent pre-eclampsia and optimal decision making around the time of delivery. The creation of regional screening programs to use screening data with a placental focus is likely to be cost-effective, because existing patterns of care are utilized. More importantly, this strategy can direct women to participate in clinical research programs designed to reduce morbidity and mortality from this common group of conditions.

Changes in Endothelial Function Precede the Clinical Disease in Women in Whom Preeclampsia Develops

Endothelial dysfunction is important in the pathophysiology of preeclampsia. No study has examined endothelial function sequentially at different gestations before development of the clinical syndrome and after delivery (to compare maternal from placental influences). We sought to determine whether endothelial function changes before the clinical development of preeclampsia. We measured skin microvascular function using iontophoresis of acetylcholine and sodium nitroprusside, and laser Doppler imaging at 22, 26, 34 weeks' gestation and 6 weeks postpartum in women identified as being at increased risk of preeclampsia, based on uterine artery Doppler waveforms at 18 to 20 weeks, and controls with normal Doppler waveforms. Fifty-four women remained normotensive and preeclampsia developed in 15. In normotensive and preeclamptic women, acetylcholine responses were augmented during pregnancy compared with postpartum responses (P<0.001). Sodium nitroprusside responses were augmented during pregnancy compared with those postpartum (P<0.005) in preeclamptic women only. Microvascular responses were augmented in women in whom preeclampsia developed, compared with those in normotensive women, at 26 and 34 weeks for acetylcholine (P<0.05 and P<0.001, respectively) and at 22 and 26 weeks for sodium nitroprusside (P<0.05 and P<0.02, respectively). Postpartum acetylcholine and sodium nitroprusside responses were not significantly different between preeclamptic and normal women. Microvascular responses are enhanced during pregnancy in women in whom preeclampsia develops to a level above that seen in normotensive women. These changes precede the onset of clinical disease and might be related to a compensatory increased sensitivity of the microcirculation to nitric oxide.

OC32.03: Diastolic flow index of the uterine artery Doppler waveform: a novel marker for downstream placental resistance

Objective: Conventional Pulsatility Index (PI) analysis of the flow velocity waveform (FVW) of uterine artery Doppler involves velocities throughout the entire cardiac cycle. The range of velocities observed in systole are sensitive to local vessel characteristics of elasticity and recoil. Forward-flow velocities in diastole reflect the degree of ‘run-off’ during the relaxation phase of the cardiac cycle and hence, are a reflection of placental resistance downstream. We describe a new method of analysis of the forward-flow in diastole, which we have termed the diastolic flow index (DFI) and investigate its performance in the prediction of pre-eclampsia (PET). Methods: Pulsed-wave Doppler was prospectively used to obtain FVWs of uterine artery Doppler between 11–14 weeks and again between 21–23 weeks’ gestation in 1500 pregnancies. The velocitytime integral (VTI) of the waveform in diastole was measured. The index was controlled for variations in heart rate (HR) since the length of diastole is rate-dependent. The placental bed is viewed as an end-organ and flow to it must therefore be corrected for body surface area (BSA).

Primary Antiphospholipid Syndrome in Pregnancy: An Analysis of Outcome in a Cohort of 33 Women Treated With a Rigorous Protocol

Early recurrent miscarriage, placental insufficiency, intrauterine growth restriction (IUGR), and late fetal death all are possible consequences of primary antiphospholipid syndrome (APS). The authors undertook a prospective study of how best to manage APS pregnancies in 33 affected women who were pregnant. Nearly 80% of patients had a history of pregnancy-related morbidity and 36% had had thrombotic events. Four very premature live-born infants had died. One third of women had had three or more consecutive first-trimester miscarriages. A first-trimester ultrasound study was done to confirm viability and for accurate dating. Uterine artery Doppler waveform studies were done at 20 and 24 weeks gestation, and growth scans at monthly intervals starting at 24 to 26 weeks. The timing of delivery was individualized. Induction was recommended at 38 to 40 weeks gestation, although pregnancies were allowed to go beyond this if there were no complications. Operative delivery was done on obstetric indications. Aspirin and low-molecular-weight (LMW) heparin were given until labor began or until the day before planned delivery. Women taking warfarin were admitted 10 to 14 days before planned delivery and converted to either full-dose LMW heparin or intravenous unfractionated heparin up to the time of delivery. LMW heparin was continued after delivery when there was a history of venous thrombosis. The live birth weight in this series was 91%; there were only three failed pregnancies. Mean birth weight was 2853 g, and mean gestational age was 36.7 weeks. Complications included four cases of IUGR (two with concurrent preeclampsia), transient ischemic attacks in five women receiving LMW heparin, and one case of placental abruption. Renal function declined in one patient who had glomerular thrombotic microangiopathy. Lupus anticoagulant was the strongest predictive factor for a thrombotic event in pregnancy. Levels of anticardiolipin antibody were less predictive, but a past thrombotic event was a strong risk factor. A history of IUGR or fetal death predicted IUGR in the current pregnancy. The operative delivery rate in this series was 59%. This study shows that a very high live birth rate is achievable in women with primary APS who have a history of significant pregnancy-related morbidity and/or thrombosis.

A Prospective Analysis of the Role of Uterine Artery Doppler Waveform Notching in the Assessment of At-Risk Pregnancies

Objective. To determine the value of second trimester uterine artery Doppler waveform notching in the prediction of adverse pregnancy outcome in a high-risk group. Design. Analysis of data from a consecutively collected cohort. Setting. St. James University Hospital, Leeds, UK. Population. Three hundred thirty women known to be at risk of preeclampsia (PET) or intrauterine growth restriction (IUGR) were assessed for notching of the uterine artery Doppler waveform between 24–30 weeks of pregnancy. Main Outcome Measures. Preeclampsia (PET), small-for-gestational-age at birth (SGA), preterm delivery (PTD), perinatal death. Results. Two hundred thirty-two women (70.3%) had a normal uterine artery Doppler waveforms, and 98 (29.7%) demonstrated either unilateral or bilateral notching. In women where notching was present, 20 (20%) developed PET compared with 8 (3.5%) in the normal group [Odds ratio (OR) 7.2, CI 3–17]; SGA birthweight was present in 24 (24.5%) of the notched group and in 21 (9%) of normal group (OR 3.3; CI 1.7–6.2); 40 (41%) of the notched group delivered preterm ( < 37 weeks) as compared with 37 (16%) of the normal group (OR 7.9; CI 4.6–13). This difference was even more marked when delivery before 32 weeks was considered, occurring in 8 (8%) of the notched group and 4 (1.7%) of the normal group (OR 11.5; CI 4.5–29.4). Of the six perinatal deaths, five (5.1%) occurred in the notched group (OR 12.4; CI 1.4–108). Conclusion. This study demonstrates that the addition of uterine Doppler waveform analysis to the monitoring profile of women at risk of PET, SGA, IUD and preterm delivery can further define those in a higher risk group and the majority that have a risk no higher than the background.

Second-trimester sex hormone-binding globulin and subsequent development of pre-eclampsia

To investigate whether maternal plasma sex hormone-binding globulin (SHBG) concentrations are reduced in women who subsequently develop pre-eclampsia. This was a cross-sectional study, carried out at antenatal clinics in seven hospitals in and around London. Healthy women underwent uterine artery Doppler velocimetry as a screening method for pre-eclampsia at 22-24 weeks of gestation. The first group (408 women) had normal uterine artery Doppler waveforms (mean uterine artery pulsatility index (PI) below 1.6). The second group (274 women) had increased impedance to flow in the uterine arteries (mean PI above the 95th centile, 1.6). Maternal plasma SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. Pre-eclampsia was as defined by the International Society for the Study of Hypertension in Pregnancy. Plasma SHBG concentrations in the 80 (11.7%) women who subsequently developed pre-eclampsia were significantly lower than in the 585 (85.8%) women with normal pregnancy outcomes (median 336, range 142-674 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.001). There was a strong correlation between SHBG concentrations and body mass index (r =-0.232246, p < 0.0001). There were no significant differences in maternal plasma SHBG concentrations in women with abnormal uterine artery Doppler (n = 274) compared with controls (n = 408) (median 324, range 101-635 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.09). Maternal plasma SHBG concentrations are reduced in women who subsequently develop pre-eclampsia.

Second-trimester sex hormone-binding globulin and subsequent development of pre-eclampsia

Objective: To investigate whether maternal plasma sex hormone-binding globulin (SHBG) concentrations are reduced in women who subsequently develop pre-eclampsia. Methods: This was a cross-sectional study, carried out at antenatal clinics in seven hospitals in and around London. Healthy women underwent uterine artery Doppler velocimetry as a screening method for pre-eclampsia at 22-24 weeks of gestation. The first group (408 women) had normal uterine artery Doppler waveforms (mean uterine artery pulsatility index (PI) below 1.6). The second group (274 women) had increased impedance to flow in the uterine arteries (mean PI above the 95th centile, 1.6). Maternal plasma SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. Pre-eclampsia was as defined by the International Society for the Study of Hypertension in Pregnancy. Results: Plasma SHBG concentrations in the 80 (11.7%) women who subsequently developed pre-eclampsia were significantly lower than in the 585 (85.8%) women with normal pregnancy outcomes (median 336, range 142-674 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.001). There was a strong correlation between SHBG concentrations and body mass index (r =-0.232246, p < 0.0001). There were no significant differences in maternal plasma SHBG concentrations in women with abnormal uterine artery Doppler (n = 274) compared with controls (n = 408) (median 324, range 101-635 nmol/l vs. median 336, range 142-674 nmol/l, p = 0.09). Conclusion: Maternal plasma SHBG concentrations are reduced in women who subsequently develop pre-eclampsia.

P08.03: The effect of palm vitamin E supplementation on first and second trimesters uterine artery Doppler waveform—a preliminary report

notch and clinical risk factors were present in 41.9% and 11% of women respectively. There were statistically significant differences between Doppler indices from pregnancies with or without subsequent PE or associated complications: mean PI 1.75 vs 2.04 (P = 0.002, t-Student test) and mean RI 0.75 vs 0.79 (P = 0.000, t-Student test). A multivariate logistic regression produced a two parameter model (including the mean PI and the presence of clinical risk factors) with the best sensitivity (46.27%) and specificity (80.99%) for the prediction of PE and its associated complications. Conclusion: There are differences in uterine Doppler blood flow indices at 11–14 weeks in pregnancies with or without subsequent PE and /or associated complications. The combination of mean PI with the presence of clinical risk factors at this gestational age show the best sensitivity and specificity for the prediction of PE and its associated complications in our population.

Prognostic value of placental ultrasound in pregnancies complicated by absent end-diastolic flow velocity in the umbilical arteries

Our objective was to evaluate the utility of gray-scale placental ultrasound for the detection of pathological lesions in the placentas of preterm pregnancies with abnormal fetoplacental blood flow (defined by absent or reversed end-diastolic flow velocities [ARED] in the umbilical arteries) before 32 weeks of gestation. Sixty consecutive structurally and chromosomally normal singleton pregnancies were evaluated. Pre-defined criteria were used to describe placental appearances using gray-scale real-time ultrasound. Proximal uterine artery Doppler waveforms were recorded using pulsed and color Doppler ultrasound. Each patient had a thrombophilia profile. Following delivery, a single perinatal pathologist reviewed each placenta at a gross and microscopic level blinded to the placental ultrasound findings. Placental shape or texture was abnormal on gray-scale ultrasound in 43/59 (73%) and echogenic cystic lesions (ECL) were found in 16 (27%). Uterine artery Doppler was abnormal in 47/60 (78%) cases. Thirty-eight pregnancies were subsequently delivered by planned Caesarean section in the fetal and/or maternal interest (birthweights 540–2300 g, mean gestational age 30.6 weeks) and 21 pregnancies resulted in the vaginal delivery of a stillborn fetus where fetal weight and/or gestational age did not justify Caesarean section (birthweights 85–600 g, mean gestational age 24.9 weeks). ECL had a low positive predictive value for both villous infarcts (63%) and for focal/massive perivillous fibrin deposition (40%). Nevertheless, the combination of abnormal uterine artery Doppler and abnormal gray-scale findings (abnormal placental morphology or ECL) was strongly predictive of stillbirth (17/21; sensitivity 81%, PPV 52%, p=0.006 Fisher's exact test). Pregnancies with ARED in the umbilical arteries have a high perinatal mortality associated with pathology of the placental villi. Ultrasound examination of the placenta and its maternal blood supply may contribute to the perinatal management of these pregnancies.

Ultrasound diagnosis of severe thrombotic placental damage in the second trimester: an observational study.

To screen women with uteroplacental insufficiency between 18 and 26 weeks' gestation for sonographic evidence of destructive placental lesions, to observe the effect of low molecular-weight heparin (LMWH) in these cases, and to compare the outcome with similar but untreated controls. We screened 180 women at high risk for placental damage using 16-week maternal serum screening (alpha-fetoprotein and human chorionic gonadotropin), placental shape and texture, and uterine artery Doppler waveforms at the 18-20-week level II examination. Serial gray-scale examinations of placental texture were performed at 22, 24 and 26 weeks. LMWH was offered to women with ultrasound evidence of destructive placental lesions in the absence of intrauterine growth restriction and/or pre-eclampsia. We prospectively identified six women (3.3%) with abnormal maternal serum screening and uterine artery Doppler in whom abnormal placental texture (echogenic cystic lesions) suggestive of destructive lesions in the placental parenchyma was found either at the 18-20-week ultrasound examination (n = 4), or by 26 weeks of gestation (n = 2). All six received LMWH and had live births (gestational age at delivery, 33-37 weeks; birth weight, 1000-3200 g). A further 14 women were referred with similar multiparameter evidence of placental damage at or after 26 weeks, outside the screening study. All had significant fetal growth restriction and were therefore not offered heparin. In 9/14 cases there was a perinatal death. Ischemic and/or thrombotic placental pathology was confirmed in each case, but no maternal thrombophilia disorders were identified in the 20 women. Integrated biochemical and ultrasound testing of placental function at 16-20 weeks of gestation, followed by serial placental gray-scale ultrasound, may be an effective method of identifying a subset of pregnancies at high risk of adverse pregnancy outcome due to destructive lesions in the placental parenchyma. This strategy of identifying thrombo-occlusive placental lesions before the development of pregnancy complications may prove useful in the design of trials to study the effectiveness of LMWH in the prevention of clinical complications resulting from thrombo-occlusive placental disease.

Delayed normalisation of uterine artery doppler waveforms is not a benign phenomenon

Objective: To evaluate the pregnancy outcome in patients with abnormal uterine artery Doppler flow velocity waveforms (FVW’s) at 19–21 weeks, which were subsequently normal by 24–26 weeks, and to study the effect of low-dose aspirin on these waveforms. Design: The study group consisted of 49 patients who had abnormal uterine artery flow velocity waveforms (FVW’s) at 19–21 weeks. These women were initially commenced on 100 mg slow-release aspirin at 20 weeks, which was discontinued at the follow-up visit, after confirming normal uterine artery Doppler FVW. The control group consisted of 730 patients with normal uterine artery Doppler waveforms at 19–21 weeks. The main outcome measures were: small for gestational age (SGA) <10th centile, pre-eclampsia, placental abruption, and perinatal mortality rate (PMR). Results: When compared with the control group, the study group had an increased risk of placental abruption (2% versus 0.27%, P=0.05) 95% Confidence Intervals CI=0.01–0.13), low birth weight (3087 versus 3383 gm, P=0.0003), SGA <10th centile (32.7% versus 11.9%, P≤0.0001, CI=0.14–0.5), and PMR (2/49 versus 1/730, P<0.0001, CI=0.003–0.37). Conclusions: These findings suggest that delayed normalisation of the uterine artery Doppler waveform is not a benign phenomenon. This subgroup of patients is at increased risk of pregnancy complications, in particular SGA and placental abruption. These patients could benefit from serial ultrasound scans in the third trimester to evaluate fetal growth and well-being. Aspirin does not appear to play a major part in modifying uterine artery blood flow.