Qualitative venous Doppler waveform analysis improves prediction of critical perinatal outcomes in premature growth-restricted fetuses.

BACKGROUND: Our aim was to test the hypothesis that qualitative ductus venosus and umbilical venous Doppler analysis improves prediction of critical perinatal outcomes in preterm growth-restricted fetuses with abnormal placental function. METHODS: Patients with suspected intrauterine growth restriction (IUGR) underwent uniform fetal assessment including umbilical artery (UA), ductus venosus (DV) and umbilical vein (UV) Doppler. Absent or reversed UA end-diastolic velocity (UA-AREDV), absence or reversal of atrial systolic blood flow velocity in the DV (DV-RAV) and pulsatile flow in the umbilical vein (P-UV) were examined for their efficacy to predict critical outcomes (stillbirth, neonatal death, perinatal death, acidemia and birth asphyxia) before 37 weeks' gestation. RESULTS: Seventeen (7.6%) stillbirths and 16 (7.1%) neonatal deaths were observed among 224 IUGR fetuses. Forty-one neonates were acidemic (19.8%) and seven (3.1%) had birth asphyxia. Logistic regression showed that UA-AREDV had the strongest association with perinatal mortality (R(2) = 0.49, P < 0.001), stillbirth (R(2) = 0.48, P < 0.001) and acidemia (R(2) = 0.22, P = 0.002) while neonatal death was most strongly related to DV-RAV and P-UV (R(2) = 0.33, P = 0.007). UA waveform analysis offered the highest sensitivity and negative predictive value and DV-RAV and P-UV had the best specificity and positive predictive values for outcome prediction. Overall, DV-RAV or P-UV offered the best prediction of acidemia and neonatal and perinatal death irrespective of the UA waveform. In fetuses with UA-AREDV, prediction of asphyxia and stillbirth was significantly enhanced by venous Doppler. CONCLUSION: Prediction of critical perinatal outcomes is improved when venous and umbilical artery qualitative waveform analysis is combined. The incorporation of venous Doppler into fetal surveillance is therefore strongly suggested for all preterm IUGR fetuses.     

Doppler application in the delivery timing of the preterm growth-restricted fetus: another step in the right direction.

This article provides an opinion on a study of relationships between umbilical artery (UA) Doppler, ductus venosus (DV) Doppler, fetal heart rate variation, and perinatal outcome in preterm, intrauterine growth-restricted (IUGR) fetuses published in the same issue of this journal by Bilardo and coworkers. Recent evidence on venous Doppler surveillance in preterm IUGR fetuses was also reviewed and discussed in the context of the study with a special emphasis on delivery timing. A search was conducted through MEDLINE and eight articles with similar inclusion criteria and reporting format of outcomes were identified. Numbers for perinatal mortality, intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia and necrotizing enterocolitis (NEC) were extracted for cases where Doppler status was recorded in an identical format. Proportional distribution of outcomes was compared for fetuses with normal DV Doppler velocimetry, absent or reversed UA end-diastolic velocity (UA A/REDV), elevated DV Doppler index (abnormal DV) and absence or reversal of atrial velocity in the DV (DV-RAV). A total of 320 fetuses with normal and 202 with elevated DV Doppler indices were extracted. Of these fetuses, 101 with UA A/REDV only and 34 with DV-RAV were identified. Perinatal mortality was 5.6% (16/282) with normal DV, 11.9% (12/101) with UA A/REDV, 38.8% (64/165) with abnormal DV and 41.2% (7/17) with DV-RAV. With the exception of NEC, all complications were significantly more frequent with abnormal DV. With normal venous Doppler neonatal deaths account for most of the perinatal mortality, while with abnormal DV stillbirths and neonatal mortality are similar contributors to the significantly increased perinatal mortality. In conclusion, UA Doppler is a placental function test that provides important diagnostic and prognostic information in preterm IUGR. DV Doppler effectively identifies those preterm IUGR fetuses that are at high risk for adverse outcome (particularly stillbirth) at least 1 week before delivery, independent of the UA waveform. Relationships between perinatal outcome, arterial and venous Doppler status and gestational age require ongoing observational research effort. Randomized management trials are necessary to verify that delivery timing based on venous Doppler will impact on outcome in preterm IUGR.     

Doppler assessment of the aortic isthmus and perinatal outcome in preterm fetuses with severe intrauterine growth restriction.

OBJECTIVES: To evaluate the characteristics and association with perinatal outcome of the aortic isthmus (AoI) circulation as assessed by Doppler imaging in preterm growth-restricted fetuses with placental insufficiency. METHODS: This was a prospective cross-sectional study. Fifty-one fetuses with intrauterine growth restriction (IUGR) and either an umbilical artery (UA) pulsatility index (PI) > 95(th) centile or a cerebroplacental ratio < 5(th) centile were examined at 24-36 weeks' gestation. AoI impedance indices (PI and resistance index) and absolute velocities (peak systolic (PSV), end-diastolic and time-averaged maximum (TAMXV) velocities), were measured in all cases and compared with reference ranges by gestational age. Furthermore, fetuses were stratified into two groups according to the direction of the diastolic blood flow in the AoI: those with antegrade flow (n = 41) and those with retrograde flow (n = 10). Clinical surveillance was based on gestational age and Doppler assessment of the UA, middle cerebral artery and ductus venosus (DV). Adverse perinatal outcome was defined as stillbirth, neonatal death and severe morbidity (respiratory distress syndrome, bronchopulmonary dysplasia, Grade III/IV intraventricular hemorrhage, necrotizing enterocolitis and a neonatal intensive care unit stay > 14 days). RESULTS: Adverse perinatal outcome was significantly associated with an increased AoI-PI (area under the curve 0.77; 95% CI, 0.63-0.92; P < 0.005). A significant correlation (P < 0.001) was found between retrograde blood flow in the AoI and adverse perinatal outcome, the overall perinatal mortality being higher in the retrograde group (70% vs. 4.8%, P < 0.001). In 4/5 (80%) fetuses the reversal of flow in the AoI preceded that in the DV by 24-48 h. AoI-PSV and AoI-TAMXV were < 5(th) centile in 40/51 (78%) and 48/51 (94%) cases, respectively, whereas AoI-PI was > 95(th) centile in 21/51 (41%) cases. CONCLUSIONS: Retrograde flow in the AoI in growth-restricted fetuses correlates strongly with adverse perinatal outcome. Absolute velocities in the AoI are decreased in growth-restricted fetuses. The data suggest a potential role for Doppler imaging of the AoI in the clinical surveillance of fetuses with severe IUGR, which should be confirmed in larger prospective studies.     

Relationship between arterial and venous Doppler and perinatal outcome in fetal growth restriction.

OBJECTIVE: The aim of this investigation was to assess the relationship between abnormal arterial and venous Doppler findings and perinatal outcome in fetuses with intrauterine growth restriction (IUGR). METHODS: Doppler velocimetry of the umbilical artery (UA), middle cerebral artery (MCA), inferior vena cava (IVC), ductus venosus (DV) and free umbilical vein was performed in 121 IUGR fetuses with a UA pulsatility index (PI) > 2 SD above the gestational age mean and subsequent birth weight < 10th centile for gestational age. Groups based on the last Doppler exam were: 1 = abnormal UA-PI only (n = 42, 34.7%), 2 = MCA-PI > 2 SD below the gestational age mean (= 'brain sparing') in addition to abnormal UA-PI (n = 29, 24.0%), 3 = DV or IVC peak velocity index (PVIV) > 2 SD above the gestational age mean and/or pulsatile UV flow (n = 50, 41.3%). Z-scores (delta indices) were calculated for Doppler indices. Perinatal mortality, respiratory distress (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), circulatory failure and umbilical artery blood gases were recorded. RESULTS: Absence or reversal of umbilical artery end-diastolic flow was observed in 4 (9.5%) of fetuses in group 1, 10 (34.5%) fetuses in group 2 and 41 (82%) fetuses in group 3. A low middle cerebral artery pulsatility index was found in 39 (78%) fetuses in group 3. Multiple regression analysis with gestational age at delivery, delta indices and cord artery blood gas as independent parameters and individual perinatal outcomes as dependent variables was performed. In this analysis the association was strongest with gestational age for each complication. There were no significant differences in Apgar scores between groups. At delivery, 'brain sparing' was associated with hypoxemia and abnormal venous flows with acidemia. Perinatal mortality was highest in group 3 and stillbirth was only observed when venous flow was abnormal. All postpartum complications were more frequent in fetuses with abnormal venous flows. The only statistically significant relation between Doppler indices and outcome was the association between abnormal ductus venosus flow and fetal death (r2 = 0.24, P < 0.05). CONCLUSION: Growth restricted fetuses with abnormal venous flow have worse perinatal outcome compared to those where flow abnormality is confined to the umbilical or middle cerebral artery. In fetuses with low middle cerebral artery pulsatility, venous Doppler allows detection of further deterioration. While abnormal venous flows can be significantly associated with fetal demise, gestational age at delivery significantly impacts on all short-term outcomes.     

Doppler and biophysical assessment in growth restricted fetuses: distribution of test results.

OBJECTIVE: Multi-vessel Doppler ultrasonography and biophysical profile scoring (BPS) are used in the surveillance of growth restricted fetuses (IUGR). The interpretation of both tests performed concurrently may be complex. This study examines the relationship between Doppler ultrasonography and biophysical test results in IUGR fetuses. METHODS: Three hundred and twenty-eight IUGR fetuses (abdominal circumference < 5th percentile, elevated umbilical artery (UA) pulsatility index (PI)) had concurrent surveillance with UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler ultrasonography and BPS (fetal tone, movement, breathing, maximal amniotic fluid pocket and fetal heart rate). Patients were stratified into three groups according to their Doppler examination: (1) abnormal UA alone; (2) brain sparing (MCA-PI > 2 SD below mean for gestational age); and (3) abnormal DV (PI > 2 SD above the mean for gestational age) and BPS groups: (1) normal (> 6/10); (2) equivocal (6/10); and (3) abnormal (< 6/10). Predictions of short-term perinatal outcomes by both modalities were compared for stratification. The distribution and concordance of Doppler and BPS test results were examined for the whole patient group and based on delivery prior to 32 weeks' gestation. RESULTS: Abnormal UA Doppler results alone were observed in 109 fetuses (33.2%), brain sparing in 87 (26.5%) and an abnormal DV in 132 (40.2%). The BPS was normal in 158 (48.2%), equivocal in 68 (20.7%) and abnormal in 102 (31.1%). Both testing modalities stratified patients into groups with comparable acid-base disturbance and perinatal outcome. Of the nine possible test combinations the largest subgroups were: abnormal UA alone/normal BPS (n = 69; 21%) and abnormal DV Doppler/abnormal BPS (n = 62; 18.9%). Assessment of compromise by both testing modalities was concordant in 146 (44.5%) cases. In 182 fetuses with discordant results the BPS grade was better in 115 (63.2%, P < 0.0001). Marked disagreement of test abnormality was present in 57 (17.4%) fetuses. Of these, abnormal venous Doppler in the presence of a normal BPS constituted the largest group (Chi-square P < 0.002). Stratification was not significantly different in patients delivered prior to 32 weeks' gestation. CONCLUSION: Doppler ultrasonography and BPS effectively stratify IUGR fetuses into risk categories, but Doppler and BPS results do not show a consistent relationship with each other. Since fetal deterioration appears to be independently reflected in these two testing modalities further research is warranted to investigate how they are best combined.     

Coronary artery blood flow visualization signifies hemodynamic deterioration in growth-restricted fetuses.

OBJECTIVE: To determine the relationship between fetal coronary blood flow (CBF) visualization in intrauterine growth restriction (IUGR), longitudinal changes in arterial and venous flow velocity waveforms and perinatal outcome. METHODS: A total of 48 IUGR fetuses (abdominal circumference below the 5th percentile for gestational age) with absent or reversed umbilical artery (UA) end-diastolic velocity (AREDV) were examined longitudinally by echocardiography attempting CBF visualization at each examination. Doppler evaluation of the middle cerebral artery, inferior vena cava (IVC), ductus venosus (DV) and umbilical vein (UV) was performed at each examination. Doppler measurements were correct for gestational age by conversion into Z-scores (delta-indices). Doppler results and outcome from fetuses in which CBF was visualized (group 1, n = 20) and those in which CBF was never visualized (group 2, n = 28) were compared. Outcome parameters analyzed included Apgar scores, cord arterial blood gases, perinatal mortality, respiratory distress, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis and postpartum circulatory failure requiring pressor support. RESULTS: There was no difference in Doppler indices between groups at study entry. CBF visualization coincides with a significant increase of UA-, IVC- and DV delta-indices. The greatest rate of change was observed for indices in the ductus venosus which occurred in the 24 h preceding CBF visualization. Group 1 fetuses required earlier delivery (median 27 + 4, vs. median 30 + 0), had lower birthweight (682 +/- 305 g vs. 936 +/- 416 g), lower cord pH (7.21 +/- 0.1 vs. 7.27 +/- 0.06) and cord pO2 (13 +/- 4.5 vs. 24.1 +/- 13.5 mmHg) compared to group 2 (all values P < 0.05). Mortality was similar (group 1 = 6/20, 30%; group 2 = 6/28, 21.4%). CONCLUSIONS: In IUGR, fetuses with AREDV and centralization are at high risk for hypoxemia, acidemia and adverse outcome. CBF visualization coincides with deteriorating venous flows. Operator dependence of CBF visualization and the strong association with abnormal venous flow stresses the importance of venous Doppler surveillance in these fetuses.     

Gestational age at delivery and Doppler waveforms in very preterm intrauterine growth-restricted fetuses as predictors of perinatal mortality.

OBJECTIVE: The aim of this study was to compare gestational age at delivery and the performance of middle cerebral artery (MCA), ductus venosus (DV), and umbilical artery Doppler parameters in the prediction of perinatal mortality and morbidity in intrauterine growth-restricted (IUGR) fetuses delivered at 32 weeks or earlier. METHODS: The study population consisted of 41 patients with IUGR fetuses. Delivery occurred for maternal or fetal indications. Two-tailed chi(2) and Fisher exact tests, an independent t test, and logistic regression were used for the analysis. P < .05 was considered statistically significant. RESULTS: Gestational age at delivery ranged between 23.1 and 32 weeks (median, 27.6 weeks). There were 17 perinatal deaths. Ninety-four percent of the perinatal deaths occurred when the fetuses were delivered before 29 weeks. No fetus survived when delivered before 25 weeks. Two parameters predicted the perinatal mortality: gestational age at delivery (odds ratio, 0.52; 95% confidence interval, 0.31-0.88) and the combination of abnormal MCA peak systolic velocity + DV reversed flow (odds ratio, 10.2; 95% confidence interval, 1.8-57). For each week of pregnancy, there was a reduction in perinatal mortality of 48%. No Doppler parameters were significantly associated with perinatal morbidity. CONCLUSIONS: Gestational age at delivery and the combination of abnormal MCA peak systolic velocity + DV reversed flow in very preterm IUGR fetuses were the best parameters in predicting perinatal mortality. The decreased perinatal mortality that is found for each week IUGR fetuses remain in utero should be taken into account when a decision to deliver an IUGR fetus before 30 weeks is made.     

Outcome of 60 neonates who had ARED flow prenatally compared with a matched control group of appropriate-for-gestational age preterm neonates.

OBJECTIVE: To describe the course and outcome of fetuses with absent or reversed end-diastolic (ARED) flow in the umbilical artery (UA) and to examine the influence of prematurity according to gestational age at delivery. METHODS: Sixty pregnancies complicated by ARED flow in the UA were monitored by repeat Doppler measurements of arterial and venous vessels, non-stress tests (cardiotocogram (CTG)) and maternal investigations, and were delivered between 24 and 34 weeks. Fetal outcome was investigated and compared to a control group of appropriate-for-gestational age (AGA) preterm neonates, matched for gestational age. Mortality, birth weight, Apgar scores, postnatal cord arterial pH and need for ventilation were all recorded, as were cases of respiratory distress syndrome, bronchopulmonary dysplasia, persistent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, abnormal neurological findings and those requiring surgical intervention. Additionally, the group of fetuses with ARED flow was divided into three subgroups of different degrees of prematurity (delivery between 24 + 0 and 28 + 6 weeks, delivery between 29 + 0 and 31 + 6 weeks, and delivery after 32 weeks) and compared according to the above parameters. RESULTS: Pre- or postnatal death occurred in 16 cases. Comparing the 44 (61%) that were born alive with the AGA neonates, significant differences were found in birth weight (P < 0.001), arterial pH value (P < 0.001), bronchopulmonary dysplasia (P = 0.002) and intestinal complications (P < 0.01). Prematurity-related complications were: need for ventilation (P = 0.001), respiratory distress syndrome (P < 0.0001), periventricular leukomalacia (P = 0.002) and pathological neurological testing (P = 0.005). CONCLUSIONS: Neonates displaying ARED flow before birth are growth restricted, acidemic at delivery and are at high risk of developing bronchopulmonary dysplasia and intestinal complications. While perinatal mortality seems to be related to abnormal fetal Doppler velocimetry, age at delivery has a significant impact on short-term morbidity. After 32 weeks, morbidity is low and delivery should be considered. It could be speculated from our data that prolongation of pregnancy with Doppler velocimetry monitoring could help to reduce morbidity, although prolongation remains limited in most cases.     

Middle cerebral artery peak systolic velocity: a new Doppler parameter in the assessment of growth-restricted fetuses.

OBJECTIVE: The aims of this study were to determine if there is a relationship between middle cerebral artery (MCA) peak systolic velocity (PSV) and perinatal mortality in preterm intrauterine growth-restricted (IUGR) fetuses, to compare the performance of MCA pulsatility index (PI), MCA-PSV and umbilical artery (UA) absent/reversed end-diastolic velocity (ARED) in predicting perinatal mortality, to determine the longitudinal changes that occur in MCA-PI and MCA-PSV in these fetuses, and to test the hypothesis that MCA-PSV can provide additional information on the prognosis of hypoxemic IUGR fetuses. METHODS: This was a retrospective cross-sectional study of 30 IUGR fetuses (estimated fetal weight < 3(rd) percentile; UA-PI > 95% CI) in which the last MCA-PI, MCA-PSV and UA values were obtained within 8 days before delivery or fetal demise. Among the 30 fetuses, there were 10 in which at least three consecutive measurements were performed before delivery and these were used for a longitudinal study. MCA-PSV and MCA-PI values were plotted against normal reference ranges and were considered abnormal when they were above the MCA-PSV or below the MCA-PI reference ranges. RESULTS: Gestational age at delivery ranged between 23 + 1 and 32 + 5 (median, 27 + 6) gestational weeks. Birth weight ranged from 282 to 1440 (median, 540) g. There were 11 perinatal deaths. Forward stepwise logistic regression indicated that MCA-PSV was the best parameter in the prediction of perinatal mortality (odds ratio, 14; 95% CI, 1.4-130; P < 0.05) (Nagerlke R(2) = 31). In the 10 fetuses studied longitudinally, an abnormal MCA-PI preceded the appearance of an abnormal MCA-PSV. In these fetuses, the MCA-PSV consistently showed an initial increase in velocity; before demise or the appearance of a non-reassuring test in seven fetuses, there was a decrease in blood velocity. The MCA-PI presented an inconsistent pattern. CONCLUSIONS: In IUGR fetuses, the trends of the MCA-PI and MCA-PSV provide more clinical information than does one single measurement. A high MCA-PSV predicts perinatal mortality better than does a low MCA-PI. We propose that MCA-PSV might be valuable in the clinical assessment of IUGR fetuses that have abnormal UA Doppler.     

Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction.

OBJECTIVE: To investigate whether pathological changes in the umbilical artery (UA), ductus venosus (DV) and short-term fetal heart variation are related to perinatal outcome in severe, early intrauterine growth restriction (IUGR). METHODS: This multicenter, prospective, longitudinal, observational study was carried out in the Departments of Fetal Medicine and Obstetrics in Hamburg, Amsterdam, Utrecht and London. In 70 singleton pregnancies with IUGR fetuses, delivered at 26-33 weeks of gestation because of antepartum fetal distress, short-term variation (STV) of fetal heart rate, pulsatility index of the fetal UA (UA PI) and DV pulsatility index for veins (DV PIV) were assessed at least weekly. The final measurement was performed within 24 h of delivery. Standard cut-off levels (2 SD or 3 SD, absent flow or reversed flow) were used and new cut-off levels were calculated by means of receiver-operating characteristics analysis. Adverse outcome was defined as perinatal death, cerebral hemorrhage (> or = Grade II) or bronchopulmonary dysplasia before discharge. The predictive value for adverse outcome was calculated for different cut-off levels of the monitoring parameters, adjusted for gestational age (GA), by multivariate logistic regression analysis. Data were analyzed separately for three different time blocks, namely 8-14, 2-7 and 0-1 days before delivery. RESULTS: Adverse perinatal outcome occurred in 18/70 (26%) infants. During the last 24 h before delivery DV PIV and UA PI were significantly higher and STV lower in the adverse outcome group, while 2-7 days before delivery only DV PIV was significantly higher. Adverse perinatal outcome could be predicted at 0-1 days before delivery by DV PIV at a cut-off of three multiples of the SD (odds ratio (OR) 11.3; 95% CI 2.3-57) and GA (OR 0.4; 95% CI 0.3-0.8), at 2-7 days by DV PIV at 2 SD (OR 3.0; 95% CI 0.8-12) and GA (OR 0.5; 95% CI 0.3-0.8) and at 8-14 days by DV PIV at 2 SD (OR 3.9; 95% CI 0.8-20) and GA (OR 0.5; 95% CI 0.3-0.8). Other parameters did not contribute to the multivariate model. CONCLUSIONS: DV PIV measurement is the best predictor of perinatal outcome. This measurement may be useful in timing the delivery of early IUGR fetuses and in improving perinatal outcome, even when delivery may be indicated at an earlier GA. However, as GA was also an important factor influencing outcome, with poorer outcome at earlier gestation at delivery, this hypothesis needs to be tested in a multicenter, prospective, randomized trial.     

Abnormal fetal cerebral and umbilical Doppler measurements in fetuses with intrauterine growth restriction predicts the severity of perinatal morbidity

PURPOSE: This prospective study was performed to determine if the ratio of the middle cerebral artery (MCA) S/D ratio (ratio of peak systolic blood flow velocity to diastolic velocity) to the umbilical artery (UA) S/D ratio (MCA/UA S/D ratio) predicts the degree of neonatal morbidity in fetuses suspected of having intrauterine growth restriction (IUGR). METHODS: Sixty-one fetuses were identified prospectively by sonography as having an estimated fetal weight below the 10th percentile for gestational age. The 61 fetuses underwent Doppler sonography in the third trimester and then were stratified into 3 groups based on the MCA/UA S/D ratio: group A, MCA/UA S/D ratio > 1.0 (controls; n = 37); group B, MCA/UA S/D ratio < or = 1.0 (intracerebral blood flow redistribution; n = 16); and group C, reversed or absent UA diastolic flow (n = 8). Outcome variables assessed included gestational age at delivery, birth weight, UA pH, mode of delivery, respiratory distress syndrome requiring intubation, and intracranial hemorrhage. RESULTS: The mean MCA/UA S/D ratios in groups A and B were 1.69 + /- 0.61 and 0.59 + /- 0.24, respectively (p < 0.01). The mean gestational ages at delivery for groups A, B, and C were 34.7, 33.2, and 29.0 weeks, respectively. The mean birth weights were below the fifth percentile for age for groups B and C and significantly related to the severity of abnormal Doppler findings (p < 0.01) after correction for age. Mean UA pHs were 7.25 + /- 0.01, 7.19 + /- 0.01, and 7.14 + /- 0.13 for groups A, B, and C, respectively, with significant differences between groups A and B (p < 0.05) and groups A and C (p < 0.05). Respiratory distress syndrome and intracranial hemorrhage were not associated with abnormal Doppler findings after correction for gestational age. The interval between the abnormal Doppler examination and delivery (p < 0.001) and the occurrence of fetal distress requiring cesarean section (p < 0.001) were significantly related to the severity of Doppler findings. CONCLUSIONS: In fetuses with suspected IUGR, abnormal MCA/UA S/D ratios are strongly associated with low gestational age at delivery, low birth weight, and low UA pH. Abnormal MCA/UA S/D ratios are also significantly associated with shorter interval to delivery and the need for emergent delivery.     

Effect of antenatal glucocorticoid therapy on arterial and venous blood flow velocity waveforms in severely growth-restricted fetuses.

OBJECTIVE: To study the effects of antenatal glucocorticoid (betamethasone) therapy on blood flow velocity waveform patterns in the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) in severely intrauterine growth-restricted (IUGR) fetuses. METHODS: Fifty-five severely IUGR fetuses at 24-34 weeks of gestation were included in the study. The effect of antenatal glucocorticoid administration on Doppler findings in the UA, MCA and DV was studied using two statistical approaches, namely paired sample analysis and multilevel analysis. RESULTS: There were no effects of betamethasone on the pulsatility index (PI) of the vessels studied. The only changes noticed during the 14 days of observation were a gradual decrease of PI in the MCA, an increase in the UA-PI/MCA-PI ratio and an increase in the DV-PI. These changes with time may be explained by a progressive and gradual deterioration of the fetal condition. CONCLUSION: Antenatal glucocorticoids (betamethasone) do not affect fetal Doppler waveform patterns of the UA, MCA and DV in severely IUGR fetuses.     

Second-trimester ductus venosus measurement and adverse perinatal outcome in fetuses with congenital heart disease.

OBJECTIVE: The purpose of this study was to determine whether Doppler velocimetry of the ductus venosus (DV) predicts adverse perinatal outcome in congenital heart disease (CHD). METHODS: We conducted a retrospective cohort study of all pregnant women undergoing fetal echocardiography for CHD in a single perinatal center during a 2-year period. We compared outcomes for fetuses having a diagnosis of CHD in the second trimester and abnormal DV Doppler velocimetric findings with those having CHD and normal DV Doppler findings. Karyotype, gestational age at delivery, fetal loss rate, and rate of termination were assessed. The referral value for an abnormal DV pulsatility index was above the 95th percentile for gestational age. Statistical analysis included the t test, Fisher exact test, and chi(2) test. RESULTS: The incidence of CHD in our population was 7%. There were 98 patients with CHD; of those, 31 had DV measurement. A total of 9 patients had an abnormal DV. Three of this group (33%) had intrauterine fetal death or perinatal death. In patients with CHD and normal DV measurements, 83% had living children versus 33% in the group with an abnormal DV (P < .05). There was no statistically significant difference in the rate of aneuploidy between the normal DV (15%) and abnormal DV (20%) groups (P = .65). The mean gestational age at delivery was similar between the normal (37.63 weeks) and abnormal (38.33 weeks) DV groups (P = .71). There was no difference in the rate of pregnancy termination. CONCLUSIONS: Abnormal second-trimester DV measurements are predictive of adverse perinatal outcome in patients with CHD, independent of karyotype or gestational age at delivery. This information may have a role in the counseling of parents with CHD.     

Ductus Venosus S‐Wave/Isovolumetric A‐Wave (SIA) Index and A‐Wave Reversed Flow in Severely Premature Growth‐Restricted Fetuses

Objective. Ductus venosus (DV) Doppler waveforms show 2 periods of decreased velocity during iso‐volumetric relaxation (isovolumetric relaxation velocity [IRV]) and atrial contraction (A wave or end‐diastolic velocity [EDV]). In intrauterine growth‐restricted (IUGR) fetuses, both may become abnormal. The hypothesis for this study was that in severely premature IUGR fetuses, Doppler assessment of both the IRV and EDV allows a more accurate prediction of fetal outcome than absent/reversed end‐diastolic flow (A/REDF) alone. Methods. Ductus venosus Doppler waveforms were serially studied in 49 severely premature IUGR fetuses from diagnosis until death or delivery. The DV waveforms were assessed for peak systolic velocity (PSV), IRV, and EDV and qualitatively for forward end‐diastolic flow or A/REDF. The S‐wave/isovolumetric A‐wave (SIA) index [PSV/(IRV + EDV)] for each fetus was compared to fetal/neonatal outcomes. Results. There were 8 cases of fetal death (FD), 9 cases of neonatal death (ND), and 32 cases of neonatal survival (NS). A receiver operating characteristic (ROC) curve for the SIA index in all cases showed that values less than ?1.25 correlated with FD and those greater than ?1.25 correlated with live birth, with 100% sensitivity and 100% specificity. A second ROC curve of live births showed that values less than 2.07 correlated with NS and those greater than 2.07 correlated with ND with 67% sensitivity and 94% specificity. Ductus venosus A/REDF correlated with FD, ND, and NS with sensitivity values of 88%, 78%, and 32%, respectively. Of the 32 NSs, 11 (34%) had A/REDF with a median of 11 days before delivery. Conclusions. The SIA index is a novel Doppler parameter for assessment of severely premature IUGR fetuses that allows a much more accurate prediction of fetal outcome compared to A/REDF alone.     

Doppler changes in the main fetal brain arteries at different stages of hemodynamic adaptation in severe intrauterine growth restriction.

OBJECTIVE: To evaluate changes in the temporal evolution and regional distribution of arterial brain Doppler parameters in relation to different stages of hemodynamic adaptation in fetuses with severe intrauterine growth restriction (IUGR). METHODS: Thirty-six fetuses with severe IUGR ( 2 SD) were evaluated longitudinally with pulsed Doppler ultrasound at four different hemodynamic stages: Stage 1 (n = 36), mean UA-PI > 2 SD or absent UA end-diastolic flow; Stage 2 (n = 34), abnormal middle cerebral artery (MCA) PI (mean < 2 SD); Stage 3 (n = 30), reversed UA end-diastolic flow; Stage 4 (n = 12), absent or reversed atrial flow in the ductus venosus. In addition, 36 normally grown fetuses were studied for comparison. PI and time-averaged maximum velocity (TAMXV) in the MCA and the anterior cerebral (ACA), pericallosal (PER) and posterior cerebral (PCA) arteries were measured. RESULTS: In IUGR fetuses, PI values from all arteries were significantly reduced at Stage 2. At Stages 3 and 4, ACA-PI and PCA-PI did not change further, whereas MCA-PI and PER-PI showed a slight increase. In the ACA, MCA and PER, TAMXV in Stage 2 increased significantly. In Stages 3 and 4, ACA and PER-TAMXV remained unchanged, whereas MCA-TAMXV showed a slight decrease, mirroring the PI values. PCA-TAMXV values were similar to controls at all stages. CONCLUSION: In IUGR fetuses, the brain arteries differ in the magnitude and time sequence of Doppler parameters in relation to systemic hemodynamic adaptation, suggesting the existence of regional brain redistribution processes.     

Perinatal outcome in monochorionic twin pregnancies complicated by amniotic fluid discordance without severe twin-twin transfusion syndrome.

OBJECTIVES: To assess the natural history and perinatal outcome in monochorionic diamniotic twin pregnancies with discordant amniotic fluid volume without signs of severe twin-twin transfusion syndrome (TTTS). METHODS: This was an observational study of 84 consecutive monochorionic twin pregnancies which did not meet the criteria for severe TTTS and endoscopic laser coagulation of placental anastomoses at initial presentation. The population was subdivided into two groups. Group 1 consisted of 64 pregnancies (median gestational age, 20.1 (range, 15.6-24.7) weeks) with amniotic fluid discordance and no signs of congestive heart failure in the twin with the larger amniotic fluid volume (Twin 1) and positive end-diastolic flow in the umbilical artery of the twin with the smaller amniotic fluid volume (Twin 2). Group 2 (median gestational age, 19.1 (range, 16.0-24.4) weeks) consisted of 20 pregnancies with amniotic fluid discordance and intrauterine growth restriction (IUGR) (abdominal circumference < 5th percentile) in combination with absent or reversed end-diastolic (ARED) flow in the umbilical artery of Twin 2. After exclusion of one patient from Group 1, who opted for termination of pregnancy, nine patients in Group 1 and one in Group 2 developed severe TTTS, and laser coagulation was offered. The remaining 54 pregnancies of Group 1 were compared with the remaining 19 pregnancies of Group 2. RESULTS: Fetuses in Group 1 showed significantly higher survival rates (overall survival, 100/108 (92.6%) vs. 23/38 (60%), P < 0.0001; survival of both fetuses, 49/54 (90.7%) vs. 9/19 (47.4%), P = 0.0002) and median gestational age at delivery (33.6, (range, 27.6-37.8) weeks vs. 32.0 (range, 26.9-36.3) weeks, P = 0.0457). Overall, there was a significantly higher incidence of complications, defined as necessity for intrauterine intervention, fetal or neonatal death or delivery prior to 32 weeks, in Group 2 (Group 1: 30/63 (47.6%); Group 2: 16/20 (80%), P = 0.0188). CONCLUSIONS: Our data suggest that amniotic fluid discordance in monochorionic diamniotic twin pregnancies in combination with IUGR and umbilical artery ARED flow in one fetus represents an extremely high-risk constellation for adverse pregnancy outcome.     

Can the degree of retrograde diastolic flow in abnormal umbilical artery flow velocity waveforms predict pregnancy outcome?

OBJECTIVE: Reverse end-diastolic flow is the most pathological type of the umbilical artery flow velocity waveform. We aimed to investigate whether additional prognostic information can be obtained from umbilical artery waveforms in cases with reverse end-diastolic flow. SUBJECTS AND METHODS: Umbilical artery Doppler velocity waveforms from 44 fetuses with reverse end-diastolic flow were analyzed and the following parameters measured: the highest amplitude and the area below the maximum velocity curve of forward and reverse flow (A, B and C, D, respectively) and the duration of forward and reverse flow (Tc and Td, respectively). Ratios A/B, C/D and Tc/Td were calculated. The cut-off values for A/B, C/D and Tc/Td with the best predictive values for perinatal death were established with the help of receiver operating characteristics curves. The three curves were compared with each other. RESULTS: Of the three ratios, A/B and C/D had the best capacity to predict perinatal death. Both ratios had acceptable sensitivities, specificities and positive predictive values. In this regard, A/B and C/D were comparable. The cut-off values for A/B and C/D were 4.3 and 4.52, respectively. Survivors had I significantly higher A/B and C/D ratios than non-survivors (P = 0.0001 and 0.0003, respectively). Significantly more fetuses with A/B or C/D below the established cut-off values had pulsations in the venous system (P < 0.05). In fetuses with a gestational age < =210 gestational days the survival rate was significantly higher in those with A/B or C/D above the cut-off values (P = 0.03 and 0.003, respectively). CONCLUSIONS: The A/B or C/D ratio can be used for quantification of the reverse end-diastolic flow waveforms in the umbilical artery and may offer additional information to the evaluation of fetal condition.     

Fetal adrenal artery velocimetry measurements in appropriate-for-gestational age and intrauterine growth-restricted fetuses.

OBJECTIVE: To investigate adrenal artery blood flow in the fetus. DESIGN AND METHOD: Sixty-two appropriate-for-gestational-age (AGA) and 20 intrauterine growth-restricted (IUGR) fetuses were recruited to this cross-sectional study between 22 and 42 weeks of pregnancy in a tertiary referral fetal medicine unit of a university hospital. ENDPOINTS: Doppler velocimetry of the fetal adrenal, umbilical (UA), renal and middle cerebral arteries (MCA). Pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV), time-averaged maximum velocity (TAMXV) and cerebroplacental ratio (MCA RI/UA RI; CPR). Obstetric outcome. RESULTS: The adrenal artery was detected in 82% of the fetuses. All flow velocity waveforms obtained from the adrenal artery indicated low impedance blood flow. No significant changes in PI, RI, PSV and TAMXV occurred with advancing gestation. The blood flow parameters of the adrenal artery did not differ between AGA and IUGR fetuses. In five IUGR fetuses with signs of redistribution of cardiac output in favor of the brain, the adrenal artery velocimetry results were unremarkable. The adrenal artery PI, RI, PSV and TAMXV values were higher in female fetuses than in male fetuses (P < 0.05). A relationship was observed between the velocity measurements and the estimated fetal weight (P < 0.01). CONCLUSIONS: The fetal adrenal artery could be readily detected. We observed no redistribution of blood flow in favor of the fetal adrenals in IUGR fetuses which were not severely compromised.     

中晚孕期正常胎儿静脉导管血流动力学研究

目的 建立中晚孕期正常胎儿静脉导管多普勒血流参数参考范围。方法 应用彩色多普勒超声检查138例16-41孕周正常单胎胎儿。在静脉导管入口处记录静脉导管血流波形，测定血流参数包括：心室收缩期峰值流速（S）、心室舒张期峰值流速（D）、心房收缩期最大流速（A）、平均流速（Vmean）、S／A值、S／D值、（S-A）／S值、（S-A）／D值和（S-A）／Vmean值。结果 正常胎儿静脉导管的血流参数S、D、A、Vmean随着孕龄的增加而增加（均P〈0．01或P〈0．05）；而S／A、（S-A）／S、（S-A）／Vmean和（S-A）／D值随着孕龄增加而减低（均P〈0．01或P〈0．05），S／D与孕龄相关性差（r=0．1，P〉0．05）。结论 正常胎儿静脉导管血流波形呈特殊的三相波形，血流速度随着孕龄增加而增加，而阻力指数随着孕龄增加而减低，S／D值在妊娠中持续不变。     

Relationship between placental blood flow resistance and precordial venous Doppler indices.

OBJECTIVE: To characterize the relationship between placental blood flow resistance and precordial venous Doppler indices in normal fetuses. METHODS: This was a prospective cross-sectional Doppler study of uncomplicated pregnancies. Umbilical artery (UA), inferior vena cava (IVC) and ductus venosus (DV) were examined. Multiple indices were calculated for each vein and correlated with the UA pulsatility index (PI) and gestational age (GA). In addition, an arteriovenous ratio (AV ratio) between the UA PI and multiple venous indices was calculated and related to GA. RESULTS: In the 237 patients studied all venous indices showed a linear relationship with the UA PI. All venous indices except the IVC preload index (PLI) had a significant positive correlation with the UA PI. Seven AV ratios were calculated and each had a linear negative relationship with GA. The relationship between UA PI and IVC pulsatility index for veins (PIV) and DV PIV remained constant throughout gestation. The AV ratio that utilized the IVC PLI and DV systolic/a-wave ratio showed a significant decline with GA. CONCLUSION: Placental blood flow resistance least influences the IVC PLI while the converse is true for the PIV in both veins. A differential effect of placental afterload on various venous indices needs to be accounted for in situations of elevated placental blood flow resistance. AV Doppler ratios may be useful for this purpose.