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.     

Qualitative venous Doppler flow waveform analysis in preterm intrauterine growth-restricted fetuses with ARED flow in the umbilical artery--correlation with short-term outcome.

OBJECTIVE: The aim of this retrospective study was to examine the significance of severe Doppler waveform abnormalities in the ductus venosus (DV) and the umbilical vein (UV) for the prediction of adverse outcomes in very preterm growth-restricted fetuses with absent or reversed end-diastolic flow in the umbilical artery (UA) at 24-34 weeks of gestation. METHODS: Seventy-four fetuses with intrauterine growth restriction (IUGR) and absent or reversed end-diastolic (ARED) flow in the UA at 24-34 weeks of gestation, which were delivered before 34 weeks' gestation, were examined. Absent or reversed flow during atrial contraction (a-wave) in the DV and pulsatile flow in the UV were examined to predict severe perinatal outcomes (stillbirth, neonatal death, perinatal death, acidemia, 5 min Apgar < 7, intraventricular hemorrhage and elevated nucleated red blood cell counts at delivery). RESULTS: Twelve (16.2%) perinatal deaths, of which eight were stillbirths (10.8%), and two (2.7%) neonatal deaths occurred among 74 fetuses. Logistic regression analysis confirmed that abnormal DV Doppler waveforms (R2 = 0.57, P < 0.001) together with gestational age at delivery (R2 = 0.57, P < 0.001) showed the strongest association with perinatal death, whereas only gestational age was significantly related to neonatal death (R2 = 0.67, P < 0.05). Abnormal DV Doppler waveforms (R2 = 0.86, P < 0.001) and gestational age (R2 = 0.49, P < 0.05) were strongly associated with adverse outcome (including stillbirth, perinatal death or neonatal death). Abnormal venous Doppler flow patterns performed better in the prediction of fetal or perinatal demise than did ARED flow or brain sparing. CONCLUSION: Abnormal venous Doppler waveforms in preterm IUGR fetuses with ARED flow are strongly related to adverse fetal and perinatal outcomes before 32 weeks of gestation. The possible benefit of prolonging these pregnancies can only be evaluated in a prospective randomized study.     

Increased risk of perinatal/neonatal death in infants who were smaller than expected at ultrasound fetometry in early pregnancy.

OBJECTIVES: To investigate if there is an association between perinatal/neonatal death and a discrepancy between gestational age by ultrasound fetometry in early pregnancy (GA(U)) and gestational age by last menstrual period (GA(LMP)), and to investigate possible causes for such an association. METHODS: The Swedish Medical Birth Registry was used to identify singleton pregnancies with information available on GA(LMP) and GA(U) that were delivered in Sweden between 1990 and 2000. A total of 718 011 pregnancies was included and information on the pregnancy and delivery was obtained from the National Board of Health. RESULTS: Infants with a GA(U) at least 7 days less than the GA(LMP) were at increased risk for stillbirth (odds ratio (OR), 1.45; 95% CI, 1.32-1.58), neonatal death within 1 month (OR, 1.87; 95% CI, 1.67-2.09), Apgar score < 7 at 5 min (OR, 1.18; 95% CI, 1.11-1.24), birth weight < 2500 g (OR, 1.48; 95% CI, 1.43-1.52), and preterm birth < 37 weeks (OR, 1.45; 95% CI, 1.42-1.49). The association between a postponed expected date of delivery and perinatal/neonatal death increased with gestational length and was especially pronounced among infants who were born after at least 40 completed weeks of pregnancy (GA(U)). CONCLUSIONS: A discrepancy between GA(U) and GA(LMP) may indicate early disturbances in fetal/placental development. Furthermore, it can be speculated that, as the risk significantly increased with gestational duration, at least a part of the increased risk for poor pregnancy outcome in adjusted pregnancies was due to consequences of true post-term pregnancies not being recognized as such.     

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.     

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.     

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.     

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.     

Ductus venosus shunting in growth-restricted fetuses and the effect of umbilical circulatory compromise.

OBJECTIVE: To determine the degree of ductus venosus (DV) shunting in fetuses with intrauterine growth restriction (IUGR) and the effect of various degrees of umbilical circulatory compromise. METHODS: This was a cross-sectional observational study. Sixty-four fetuses with IUGR (estimated weight < or = 2.5(th) percentile) underwent ultrasound examination. The diameter, velocity, and blood flow were determined in the DV and intra-abdominal umbilical vein (UV), and the fraction of shunting and DV : UV diameter ratios were calculated. Placental compromise was classified according to either normal umbilical artery (UA) pulsatility index (PI), UA-PI > 97.5(th) percentile, or absent or reversed end-diastolic flow velocity (A/REDV). Regression analysis was used to construct mean values, and SD scores were used to determine differences compared with a reference population (n = 212) after ln- or power-transformation. RESULTS: In the 64 growth-restricted fetuses, the average DV shunting was 39% compared with 25% in the reference group (overall P < 0.0001). The corresponding values in the subgroups with normal UA-PI, UA-PI > 97.5(th) percentile, and A/REDV were 31%, 35%, and 57%, respectively. Fetuses with IUGR and normal UA-PI (SD score: mean, 0.48; 95% CI, 0.04-0.92) did not shunt significantly more than did the reference fetuses (SD score: mean, 0.0; 95% CI, - 0.15 to 0.15), but those with UA-PI > 97.5(th) percentile (SD score: mean, 0.85; 95% CI, 0.41-1.29), and particularly those with A/REDV (SD score: mean, 1.56; 95% CI, 1.0-2.12) did shunt significantly more. With more DV shunting, these fetuses distributed correspondingly less umbilical blood to the liver, one of the mechanisms being a lower perfusion pressure as reflected in the lower DV blood velocity (P < 0.0001). CONCLUSIONS: DV shunting is higher and the umbilical blood flow to the liver is less in fetuses with IUGR, particularly in those with the most severe umbilical hemodynamic compromise.     

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.     

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.     

Computerized fetal heart rate analysis, Doppler ultrasound and biophysical profile score in the prediction of acid-base status of growth-restricted fetuses.

OBJECTIVE: To investigate the performance of non-stress test (NST), computerized fetal heart rate analysis (cCTG), biophysical profile scoring (BPS) and arterial and venous Doppler ultrasound investigation in the prediction of acid-base status in fetal growth restriction. METHODS: Growth-restricted fetuses, defined by abdominal circumference < 5(th) percentile and umbilical artery (UA) pulsatility index > 95(th) percentile, were tested by NST, cCTG, BPS, and UA, middle cerebral artery (MCA), ductus venosus (DV) and umbilical vein (UV) Doppler investigation. The short-term variation (STV) of the fetal heart rate was calculated using the Oxford Sonicaid 8002 cCTG system. Relationships between antenatal test results and cord artery pH < 7.20 were investigated, using correlation, parametric and non-parametric tests. RESULTS: Fifty-six of 58 patients (96.6%) received complete assessment of all variables. All were delivered by pre-labor Cesarean section at a median gestational age of 30 + 6 weeks. The UA pulsatility index (PI) was negatively correlated with the cCTG STV (Pearson correlation - 0.29, P < 0.05). The DV PI was negatively correlated with the pH (Pearson correlation - 0.30, P < 0.02). The cCTG mean minute variation and pH were not significantly correlated (Pearson correlation 0.13, P = 0.34). UV pulsations identified the highest proportion of neonates with a low birth pH (9/17, 53%), the highest number of false positives among patients with an abnormal BPS, abnormal DV Doppler and a STV < 3.5 ms, and also stratified false negatives among patients with an equivocal or normal BPS. Abnormal DV Doppler correctly identified false positives among patients with an abnormal BPS. cCTG reduced the rate of an equivocal BPS from 16% to 7.1% when substituted for the traditional NST. Elevated DV Doppler index and umbilical venous pulsations predicted a low pH with 73% sensitivity and 90% specificity (P = 0.008). CONCLUSION: In fetal growth restriction with placental insufficiency, venous Doppler investigation provides the best prediction of acid-base status. The cCTG performs best when combined with venous Doppler or as a substitute for the traditional NST in the BPS.     

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.     

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.     

Cardiovascular hemodynamics and umbilical artery N-terminal peptide of proB-type natriuretic peptide in human fetuses with growth restriction.

OBJECTIVE: To test our hypothesis that human fetal N-terminal peptide of proB-type natriuretic peptide (NT-proBNP) secretion is increased in proportion to the severity of fetal cardiovascular compromise in intrauterine growth restriction. METHODS: This prospective cross-sectional study consisted of 42 growth-restricted fetuses who underwent Doppler ultrasonographic examination of cardiovascular hemodynamics within 7 days before delivery. Group 1 fetuses (n = 13) had normal umbilical artery (UA) velocimetry. Group 2 fetuses (n = 15) had abnormal UA and normal ductus venosus (DV) velocimetry. In Group 3 fetuses (n = 14), both UA and DV velocimetries were abnormal. At delivery, an UA blood sample was obtained for assessment of NT-proBNP. Normal values for UA NT-proBNP were determined in 49 neonates (control group) with uncomplicated pregnancy and delivery. RESULTS: Group 3 fetuses demonstrated greater (P < 0.05) UA and descending aorta pulsatility indices (PIs) and greater DV, left hepatic vein (LHV) and inferior vena cava PIs for veins (PIVs) than fetuses in Groups 1 and 2. Weight-indexed cardiac outputs and ventricular ejection forces were similar among the groups. Group 3 fetuses had higher (P < 0.05) UA NT-proBNP concentration than fetuses in Groups 1 and 2. In the control group, the 95(th) percentile value of UA NT-proBNP was 518 pmol/L. In Group 3, 13/14 neonates demonstrated abnormal UA NT-proBNP levels. The corresponding incidences were 4/13 and 7/15 in Groups 1 and 2. Significant positive correlations were found between UA, DV and LHV PIVs and UA NT-proBNP concentrations. CONCLUSION: In human fetal growth restriction, increased cardiac afterload and pulsatility in DV blood velocity waveform pattern are associated with elevated UA NT-proBNP concentrations.     

Sequential changes in uterine artery blood flow pattern between the first and second trimesters of gestation in relation to pregnancy outcome.

OBJECTIVE: To describe sequential changes in uterine artery waveform between the first and second trimesters of gestation and to analyze their association with the subsequent risk of hypertensive disorders and fetal growth restriction (IUGR). METHODS: Sequential uterine artery Doppler recordings were obtained in a final cohort of 870 singleton pregnancies over two gestational age intervals: 11-14 weeks and 19-22 weeks. The left and right uterine arteries were examined by color and pulsed Doppler and the mean pulsatility index (PI) as well as the presence of a bilateral protodiastolic notch were recorded during both intervals. Pregnancies were followed for occurrence of hypertensive disorders and IUGR. RESULTS: Mean uterine artery PI showed a significant linear decrease within each of the two intervals considered, while the prevalence of a bilateral notch showed decreasing values only throughout 11-14 weeks of gestation. Sixty-four (7.3%) pregnancies developed a hypertensive disorder and/or IUGR, including three (0.34%) cases of gestational hypertension, 24 cases of pre-eclampsia (2.75%) and 37 (4.25%) of IUGR. Compared with pregnancies with a normal outcome, complicated pregnancies showed a significantly higher prevalence of a bilateral notch and a higher mean PI in each of the two intervals studied. Compared with normal pregnancies, complicated pregnancies had a significantly higher persistence of a bilateral notch (30% vs. 8%), a higher proportion of women with an abnormal first-trimester uterine artery PI shifting to normal in the second trimester (14% vs. 4%) and a higher incidence of a normal first-trimester mean PI that shifted to abnormal in the second trimester (13% vs. 4%). Persistence of an abnormal mean PI from the first to the second trimester identified the group with the greatest risk for adverse perinatal outcome (OR, 10.7; 95% CI, 3.7-30.9). In addition, women in whom the uterine artery mean PI shifted from abnormal to normal between the two trimesters and women in whom the reverse shift occurred showed a similar intermediate risk (OR, 5; 95% CI, 2.1-10.6), comparable to that in women with persistence of a bilateral notch (OR, 5.6; 95% CI, 2.9-10.7). CONCLUSIONS: The sequence of changes in uterine flow between the first and second trimesters correlates with the subsequent development of hypertensive disorders and IUGR. Women with a persistent abnormal mean PI represent the group with the greatest risk for adverse perinatal outcome.     

Circadian rhythm of maternal blood pressure and fetal growth

This study aimed at examining any relation between the circadian variation in blood pressure (BP) in human pregnancy and fetal growth. A prospective study included 52 pregnant women monitored during the third trimester of pregnancy. There were 33 uncomplicated pregnancies with normal fetal growth (Group 1) and 19 pregnancies complicated by intrauterine growth retardation (IUGR), confirmed at birth (Group 2). Ten women (five in each group) had pregnancy-induced hypertension. All women were hospitalized and followed a similar daily routine. BP was recorded with an automatic wearable device. Measurements were obtained every 20 min for 24 ± 1 h. BP profiles were analyzed by conventional statistical methods and by cosinor, involving the least squares fit of cosine curves with an anticipated period (24 h) to the data. BP parameters, fetal outcome, demographic and obstetric characteristics were compared between the two groups. Logistic regression and multivariate analyses were used to assess factors putatively associated with fetal outcome. The circadian amplitude of diastolic BP was found to be larger in normotensive women with IUGR. As gauged by odds ratios (OR), the circadian amplitude of diastolic BP (OR = 1.7, 95% CI: 1.1–2.8; P = 0.03) and hematocrit (OR = 1.4, 95% CI: 1.0–1.9; P = 0.04) were the only variables positively and independently associated with IUGR. In the presence of maternal hypertension, the circadian amplitude of systolic BP was negatively associated with IUGR (OR = 0.7, 95% CI: 0.5–1.0; P = 0.03). A larger circadian variation in diastolic BP, rather than a difference in the mean value of systolic or diastolic BP, was found to be statistically significantly associated with IUGR. This study adds another condition in which the circadian BP amplitude constitutes a harbinger of elevated risk, apart from an association with a shortened lifespan in the absence or presence of malignant hypertension and with an increased risk of stroke and nephropathy reported earlier.     

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.     

Sonographic measurement of cervical length in preterm prelabor amniorrhexis.

OBJECTIVE: To determine whether sonographic measurement of cervical length in pregnancies complicated by preterm prelabor amniorrhexis helps distinguish between those women who deliver within 7 days and those who do not. METHODS: In 101 women with singleton pregnancies presenting with preterm prelabor amniorrhexis at 24-36 (median, 32) weeks of gestation cervical length was measured by transvaginal ultrasound. Exclusion criteria were active labor defined by the presence of cervical dilatation of > or = 3 cm and iatrogenic delivery for fetal or maternal indication when not in active labor. The clinical management was determined by the attending obstetrician. The primary outcome of the study was delivery within 7 days of presentation. RESULTS: Delivery within 7 days of presentation occurred in 58/101 (57%) pregnancies. Logistic regression analysis demonstrated that significant independent contribution in the prediction of delivery within 7 days was provided by cervical length (odds ratio (OR) = 0.91, 95% CI 0.86-0.96, P = 0.001), gestation at presentation (OR = 1.35, 95% CI 1.14-1.59, P = 0.001) and presence of contractions at presentation (OR = 3.07, 95% CI 1.05-8.92, P = 0.039) with no significant independent contribution from ethnic origin, maternal age, body mass index, parity, previous history of preterm delivery, cigarette smoking, vaginal bleeding or the administration of tocolytics, antibiotics or steroids. CONCLUSION: In women with preterm prelabor amniorrhexis prediction of delivery within 7 days is provided by cervical length, gestation and presence of contractions at presentation.     

Management and outcomes of acute coronary syndrome with minimal myocardial necrosis: analysis of a large prospective registry from a non-interventional centre

The aim of this study was to assess the clinical risk of minimal myonecrosis below the cut-off for acute myocardial infarction (MI) in comparison with other grades of acute coronary syndrome (ACS). One-thousand four hundred and sixty seven consecutive patients with ACS admitted between May 2001 and April 2002 were studied in a non-interventional centre. Patients were divided into unstable angina (UA) (cTnT < 0.01 microg/l), non-ST elevation ACS with minimal myonecrosis (0.01 or= 0.1 microg/L) and ST elevation myocardial infarction (STEMI). UA (n = 638) was associated with the fewest events at 6 months (2% cardiac death or MI). Patients with any myonecrosis (n = 829) had worse outcomes (6-month cardiac death or MI 18.3-23.3%). Compared with ACS patients with minimal myonecrosis, UA patients were at significantly lower risk (OR 0.21, 95% CI 0.12-0.45, p < 0.001), NSTEMI patients were at similar risk (OR 1.45, 95% CI 0.89-2.35, p = 0.13), and STEMI patients were at higher risk (OR 2.12 95% CI 1.26-3.85, p = 0.008) in adjusted analyses. Nearly 85% of cardiac deaths occurred within 6 months. The risk of adverse events was higher among patients managed by non-cardiologists (OR 1.66, 95% CI 1-2.75, p = 0.049). Patients with non-ST elevation ACS and minimal myonecrosis are a high-risk group more comparable with NSTEMI and clearly distinguishable from patients with UA.