Cardiac blood flow studies in fetuses with homozygous alpha-thalassemia-1 at 12-13 weeks of gestation.

OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 develop anemia as early as the first trimester. Our objective was to study hemodynamic indices in affected fetuses at 12-13 weeks of gestation to determine whether these would be useful in the prediction of anemia. DESIGN: Prospective observational study. SUBJECTS: Women referred before 14 weeks of gestation for the prenatal diagnosis of homozygous alpha-thalassemia-1. METHODS: Transabdominal and/or transvaginal Doppler sonography was performed to measure the flow velocities in the fetal ascending aorta and pulmonary artery at 12-13 weeks. The Doppler indices were compared between those that were subsequently confirmed to be affected by homozygous alpha-thalassemia-1 and those that were unaffected. RESULTS: Between June 1997 and April 1998, 60 eligible women were recruited. Doppler examination was successful in 58 fetuses. Of these, 22 were subsequently confirmed to be affected by homozygous alpha-thalassemia-1. The diagnosis was made by chorionic villus sampling and DNA analysis in two affected fetuses and by cordocentesis and hemoglobin evaluation in 20 affected fetuses. Hemoglobin concentrations could be measured in ten fetuses and these ranged from 4 to 8 g/dl. The affected fetuses had significantly higher peak velocities at the pulmonary valve and ascending aorta and a larger inner diameter of the pulmonary valve than that in unaffected fetuses. The total cardiac output was increased by one-third in affected fetuses and was mainly due to an increase of the right-side cardiac output. CONCLUSION: In the early stage of anemia, the fetus responds mainly by increasing its right-side cardiac output. However, there is extensive overlap of the values of cardiac output between the affected and the unaffected fetuses, precluding its use in the prediction of anemia.     

Ductus venosus blood flow velocity characteristics of fetuses with single umbilical artery.

OBJECTIVES: Sonographic Doppler evaluation of the fetal ductus venosus has been proved to be useful in the evaluation of fetal cardiac function. The aim of this study was to investigate the ductus venosus blood flow profile in fetuses with single umbilical artery and to correlate it with the umbilical cord morphology. METHODS: Fetuses at >20 weeks' gestation with single umbilical artery who were otherwise healthy were consecutively enrolled into the study. The sonographic examination included evaluation of the following Doppler parameters: umbilical artery resistance index, maximum blood flow velocity of the ductus venosus during ventricular systole (S-peak) and atrial contraction (A-wave), ductus venosus time-averaged maximum velocity (TAMXV), and pulsatility index for veins (PIV). The cross-sectional area of the umbilical cord and its vessels were measured in all cases. The Doppler and morphometric values obtained were plotted on reference ranges. RESULTS: A total of 88 fetuses with single umbilical artery were scanned during the study period. Of these 52 met the inclusion criteria. The S-peak velocity, A-wave velocity, and TAMXV were below the 5th centile for gestational age in 57.7%, 59.6%, and 57.7% of cases, respectively. The PIV was within the normal range in 80.1% of cases. The umbilical vein cross-sectional area of fetuses with single umbilical artery was above the 95th centile for gestational age in 34.6% cases. CONCLUSIONS: The ductus venosus blood flow pattern is different in fetuses with single umbilical artery from that in those with a three-vessel cord. This difference may be caused in part by the particular morphology of umbilical cords with a single artery.     

正常孕10～19周胎儿静脉导管彩色血流频谱的初步探讨

目的探讨经腹彩色多普勒超声获取10～19周胎儿静脉导管血流频谱的正确采样及检测方法并建立其阻力指数（RI）、搏动指数（PI）、心室收缩期峰值流速与心房收缩期最低流速比值（S／A）的正常参考值范围；探讨生理性零或反向房收缩（RA）波在正常10～14周胎儿静脉导管中的发生率。方法随机选取111例孕10～19周的正常单胎孕妇，在不校正测量角度的情况下进行胎儿静脉导管血流频谱检测，对血流参数RI、PI和S／A值与孕周进行相关和回归分析。结果静脉导管的血流参数值随着胎龄的增加而减低，其95％的参考值范围分别为R10．34～0．90、P10．21～1．32和S／A1．23～6．65；10～14周胎龄段的50例胎儿静脉导管血流频谱中未见零或RA波。结论应用经腹彩色多普勒超声对10～19周胎儿静脉导管进行血流动力学评价方法简单，结果准确，容易掌握；静脉导管血流参数RI、PI和S／A值随着胎龄的增加而减低，其参考值范围可进一步应用于对胎儿染色体畸形和严重心脏畸形的研究；10～14周正常胎儿静脉导管内是否存在生理性零或RA波有待于进一步研究。     

Nuchal translucency in fetuses affected by homozygous alpha-thalassemia-1 at 12-13 weeks of gestation.

OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 are anemic in the first trimester. We studied their nuchal translucency (NT) measurements at 12-13 weeks of gestation. METHODS: Nuchal translucency was measured prospectively in fetuses at risk of homozygous alpha-thalassemia-1. Measurements of those fetuses subsequently confirmed to be affected by homozygous alpha-thalassemia-1 but with a normal karyotype were compared to those of 440 controls. The controls were from the general obstetric population who had NT measurements at 12 or 13 weeks with known normal outcome. All the NT measurements were expressed as multiples of the median (MoM) for the gestational day. RESULTS: Between 1996 and 1998, 94 at-risk pregnancies were studied. Of these, 32 were subsequently confirmed to be affected by homozygous alpha-thalassemia-1. Chromosome study was not carried out in three cases and these were excluded from the analysis. Nuchal translucency MoMs for cases and controls were found to fit a log Gaussian distribution. The log means (standard deviation) for case and control NT MoM were 0.075 (0.156) and -0.0019 (0.091), respectively. The median NT MoM (95% CI) for cases was 1.19 (1.08-1.62) and was significantly higher than that of the controls (p < 0.001). However, there was extensive overlap of NT between cases and controls. CONCLUSION: Overall, there was a 19% increase in NT MoM in fetuses affected by homozygous alpha-thalassemia-1. This represents a difference of only 0.3-0.4 mm, which is clinically insignificant. This finding indirectly suggests that the increased NT in trisomic fetuses cannot be explained by fetal anemia. Conversely, the presence of increased NT in a fetus at risk of homozygous alpha-thalassemia-1 should alert one to the possibility of chromosomal abnormality rather than being attributed to fetal anemia.     

Reference values for ductus venosus Doppler flow measurements at 10-14 weeks of gestation.

OBJECTIVES: To calculate reference ranges for ductus venosus Doppler measurements obtained transabdominally at 10-14 weeks of gestation. DESIGN: Two hundred and one normal fetuses with a crown-rump length (CRL) ranging from 38 to 88 mm were examined in a cross-sectional study. The pulsatility index for veins (PIV), peak velocity during ventricular systole (S-wave), lowest forward velocity during atrial contraction (A-wave) and time-averaged maximum velocity (TAMXV) were recorded from the ductus venosus. Flow velocity waveforms were also classified as normal or abnormal according to the presence (normal) or absence or reversal (abnormal) of frequencies during atrial contraction. RESULTS: Three of 201 fetuses showed an abnormal flow pattern (1.5%; 95% exact confidence interval, 0.3-4.3%). In the 198 fetuses with a normal flow pattern, the mean PIV ranged from 1.07 at a CRL of 38 mm to 1.00 at a CRL of 88 mm (r = -0.093; P = 0.19). A significant increase in mean blood flow velocity with increasing CRL was noted for the S-wave (27.0 cm/s to 33.6 cm/s; r = 0.17; P = 0.02), the A-wave (5.9 cm/s to 7.8 cm/s; r = 0.14; P = 0.04) and the TAMXV (19.4 cm/s to 25.3 cm/s; r = 0.19; P < 0.01). Crown-rump length-specific reference ranges for each parameter were calculated using the method of scaled absolute residuals. CONCLUSIONS: Abnormal ductus venosus flow patterns could be observed in normal fetuses, even if they ocurred with a low prevalence. Reference values for Doppler measurements were established in fetuses with normal patterns of flow.     

Ductus venosus index: a method for evaluating right ventricular preload in the second-trimester fetus.

This study was designed to examine ventricular preload by measuring the ductus venosus index during the second trimester of pregnancy. A total of 137 women were entered into the study. Each fetus was examined with real-time, color and pulsed Doppler ultrasound. The color Doppler maximal velocity setting was adjusted so that the umbilical vein was homogeneous in color, did not demonstrate aliasing, and filled the venous lumen. The pulsed Doppler gate was placed within the ductus venosus in all subjects. Color Doppler identified a turbulent flow velocity within the ductus venosus which was not present in the umbilical vein, hepatic vein or inferior vena cava. The ductus venosus pulsed Doppler waveform demonstrated flow velocity from the umbilical vein to the heart during ventricular systole, the rapid filling phase of ventricular diastole, and atrial systole. However, flow velocity was decreased during atrial systole compared to ventricular systole and the rapid filling phase of diastole. The ductus venosus index was computed from the Doppler waveform of the ductus venosus at points consistent with ventricular and atrial systole ((ventricular systole - atrial systole)/ventricular systole). Regression analysis demonstrated a significant (p = 0.001) relationship between the ductus venosus index and gestational age (ductus venosus index = 75.5757 - 7.25484 x weeks gestation), standard error of the estimate = 7.21959; R = -0.451. One fetus with a hypoplastic left atrium and ventricle demonstrated a normal ductus venosus index. Two fetuses, one with pulmonary atresia and the second with severe cardiovascular dysfunction, demonstrated an abnormal ductus venosus index associated with absent flow velocity during atrial systole. This was associated with notching in the umbilical vein. The ductus venosus index is an angle-independent measurement from which right ventricular preload may be evaluated.     

彩色多普勒超声监测生长迟缓胎儿脐动脉血液循环的变化

目的 应用彩色多普勒超声监测生长迟缓（IUGR）胎儿的脐动脉血液循环。方法 测定130例妊娠20－42周妇女（其中正常49例,IUGR81例）脐动脉时间平均血流速度（TAMX）,收缩期最大血流速度与舒张末期血流速度的比值（S／D）,搏动指数（PI）,阻力指数（RI）,收缩期最大血流速度（Vmax)与舒张末期血流速度（Vmin)。结果 正常孕妇随孕龄增长,胎盘功能增强,胎儿血液循环日渐丰富,IUGR者则明显障碍,在20周时脐动脉TAMX显著下降,在30周后S／D,PI及RI显著升高,Vmin显著下降,在35周时Vmax显著下降,出现舒张期血流停止或倒流。结论 彩色多普勒超声可直接测定脐动脉血流循环,能在早期诊断UGR,判断病情及估计预后。     

The role of fetal nuchal translucency and ductus venosus Doppler at 11-14 weeks of gestation in the detection of major congenital heart defects.

OBJECTIVE: To determine whether, in a selected high-risk population, Doppler velocimetry of the ductus venosus can improve the predictive capacity of increased nuchal translucency in the detection of major congenital heart defects in chromosomally normal fetuses at 11-14 weeks of gestation. METHODS: Ductus venosus Doppler ultrasound blood velocity waveforms were obtained prospectively at 11-14 weeks of gestation in 1040 consecutive singleton pregnancies. Waveforms were classified either as normal in the presence of a positive A-wave, or as abnormal if the A-wave was absent or negative. All cases were screened for chromosomal defects by a combination of maternal age and fetal nuchal translucency thickness. In 484 cases karyotyping was performed. Those fetuses found to be chromosomally normal by prenatal cytogenetic analysis, and which had abnormally increased nuchal translucency and/or abnormal ductus venosus Doppler velocimetry, underwent fetal echocardiography at 14-16 weeks of gestation. Ultrasound examination was repeated at 22-24 weeks of gestation in all women. The sensitivity, specificity and positive and negative predictive values for the detection of major cardiac defects of increased nuchal translucency thickness alone, ductus venosus Doppler alone and increased nuchal translucency thickness in association with abnormal ductus venosus Doppler were determined. RESULTS: In 29 of 998 fetuses presumed to be chromosomally normal, reversed or absent flow during atrial contraction was associated with increased (> 95(th) centile for crown-rump length) nuchal translucency. Major cardiac defects were observed in 9 of these 29 fetuses. No other major cardiac abnormalities were found in chromosomally normal fetuses in spite of the presence of either increased nuchal translucency alone or abnormal ductus venosus velocimetry. A total of 25 cardiac malformations were observed in the population. Fifteen were associated with aneuploidy and 10 fetuses had a normal karyotype. Nine of the 10 had major cardiac anomalies and one had a ventricular septal defect. The nine cases with normal karyotype and major cardiac anomalies had both increased nuchal translucency and abnormal ductus venosus flow velocity waveforms. CONCLUSION: In chromosomally normal fetuses with increased nuchal translucency, assessment of ductus venosus blood flow velocimetry could improve the predictive capacity for an underlying major cardiac defect.     

Echogenic bowel in fetuses with homozygous alpha-thalassemia-1 in the first and second trimesters.

OBJECTIVE: Fetal echogenic bowel has been observed in fetuses with meconium peritonitis, cystic fibrosis, aneuploidy, congenital viral infection and intrauterine growth restriction. The pathogenesis of echogenic bowel is unknown, but it may be attributed to bowel ischemia. Fetuses affected by homozygous alpha-thalassemia-1 are severely anemic and hypoxic. We investigated the incidence of echogenic bowel in these hypoxic fetuses in the first and second trimesters. DESIGN: Prospective observational study. SUBJECTS: Women referred for the prenatal diagnosis of homozygous alpha-thalassemia-1 before 24 weeks' gestation. METHODS: All subjects had one or more abdominal and/or vaginal ultrasound examination between 12 and 24 weeks' gestation. Echogenic bowel was diagnosed if the bowel appeared either isoechogenic or more echogenic than the bone. RESULTS: Between March 1997 and July 1998, 126 pregnancies were studied. Thirty-six fetuses were confirmed to be affected by homozygous alpha-thalassemia-1, and 11 of them (31%, 95% CI 16-48%) had echogenic bowel. These observations were made before the invasive test results were available. None of the fetuses unaffected by homozygous alpha-thalassemia-1 had echogenic bowel. CONCLUSION: There is a strong association between homozygous alpha-thalassemia-1 and echogenic bowel. The pathogenesis is unknown. Speculations include bowel hypoperistalsis or bowel wall edema due to severe anemia and hypoxia.     

Fetal Doppler velocimetry at high altitude.

OBJECTIVES: To determine impedance and velocity characteristics of the fetal circulation using Doppler ultrasound, at extremely high altitude (4300 m) in the Peruvian Andes compared to an ethnically similar population at sea level. METHODS: This was a cross-sectional study of 196 women resident at high altitude (Cerro de Pasco, 4300 m above sea level) and 196 women resident at sea level (Lima) with normal singleton pregnancies. Pulsatility index (PI), maximum velocity (Vmax) and minimum velocity (Vmin) in the umbilical artery, the descending aorta, the middle cerebral artery and the ductus venosus were compared between the two populations using fractional polynomial regression analysis. RESULTS: The PI was higher at high altitude than at sea level in the umbilical artery (regression coefficient = 0.112, P < 0.001), and not significantly different in the descending aorta, middle cerebral artery and ductus venosus. Vmax was lower at high altitude than at sea level in all three arterial vessels assessed; Vmin was lower in two: the umbilical artery and the descending aorta. The high-altitude/sea-level ratios for umbilical artery Vmax and Vmin were 0.93 and 0.82, respectively (P < 0.001 for each), the ratios for descending aorta Vmax and Vmin were 0.93 and 0.89, respectively (P = 0.003 and P < 0.001, respectively), and the regression coefficient for the middle cerebral artery Vmax was -2.844 (P = 0.003). There was no significant difference in the middle cerebral artery Vmin or in the ductus venosus Vmax and Vmin. CONCLUSIONS: Despite the lower ambient oxygen at high altitude and an increase in umbilical artery PI, the fetal circulation does not exhibit a 'brain sparing effect'. This and the overall decrease in blood flow velocities in the fetal circulation at high altitude may be due to the increased fetal hematocrit, which will result in increased blood viscosity.     

Reproducibility of ductus venosus Doppler flow measurements at 11-14 weeks of gestation.

OBJECTIVES: To assess the intra- and interobserver repeatabilities of fetal ductus venosus Doppler measurements at 11-14 weeks of gestation. DESIGN: Flow velocity waveforms were recorded transabdominally. Intraobserver repeatability was studied in 22 fetuses in whom four repeated measurements were performed by the same observer. Interobserver repeatability was assessed in 54 fetuses in each of whom two observers performed two repeated measurements. The pulsatility index for veins (PIV), peak velocity during ventricular systole (S wave), peak velocity during atrial contraction (A wave) and time-averaged maximum velocity (TAMV) were recorded. Reproducibility of the Doppler measurements was analyzed by calculating repeatability coefficient, coefficient of variation (CV), intraclass correlation coefficient (ICC), mean differences and their limits of agreement. Cohen's k-coefficient was used for categorical data. RESULTS: Intraobserver repeatability was good with a CV of 10%, 13%, 22% and 13% and an ICC of 0.85, 0.94, 0.94 and 0.95, respectively, for PIV, S wave, A wave and TAMV. Interobserver repeatability was also good, and no bias between the observers was detected. A CV of 8.8%, 14%, 27% and 15% and an ICC of 0.86, 0.84, 0.87 and 0.84, respectively, for PIV, S wave, A wave and TAMV were obtained. There was 100% agreement for the detection of normal/abnormal blood flow. CONCLUSIONS: Intra- and interobserver repeatability of all parameters was acceptable, allowing for the detection of moderate to large changes in Doppler measurements.     

Longitudinal changes in the ductus venosus, cerebral transverse sinus and cardiotocogram in fetal growth restriction.

OBJECTIVE: To evaluate the changes in flow velocity waveforms in the transverse cerebral sinus in growth-restricted fetuses and to correlate these changes with (1) flow velocity waveforms in the ductus venosus and (2) changes in computerized analysis of the fetal cardiotocogram. DESIGN: Fetuses between 22 and 37 weeks' gestation with an estimated fetal weight below the fifth centile were included in this prospective longitudinal study. Doppler measurements of the umbilical artery, descending aorta, middle cerebral artery, transverse cerebral sinus and ductus venosus were recorded. Fetal heart rate was analyzed by a computer system according to the Dawes-Redman criteria. RESULTS: We measured a significant correlation between pulsatility index in the cerebral transverse sinus and in the ductus venosus over the study period and at delivery. There was a negative correlation between these indices and short- and long-term variability of the fetal heart rate. There was a parallel increase in pulsatility in the ductus venosus and the transverse cerebral sinus. These changes were inversely correlated with fetal heart rate variability and preceded fetal distress. CONCLUSION: Cerebral venous blood flow in IUGR fetuses may be a useful additional investigation to discriminate between fetal adaptation and fetal decompensation in chronic hypoxemia.     

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.     

Effect of fetal gender on first-trimester ductus venosus blood flow.

OBJECTIVES: Recent reports have suggested that nuchal translucency (NT) measurements in the first trimester may be influenced by fetal gender. Since both NT and central venous blood flow are considered to be related to fetal cardiac function, we investigated gender-related differences in first-trimester ductus venosus Doppler indices. METHODS: A total of 73 male and 79 female normal fetuses at 10-14 weeks of gestation were included in the study. The pulsatility index for veins (PIV), peak velocity during ventricular systole (S-wave), time-averaged maximum velocity (TAMV) and A-wave velocity (A-wave) were recorded in each case and converted to the corresponding Z-scores. RESULTS: The mean Z-score values of PIV, S-wave and TAMV were significantly lower in male fetuses compared to female fetuses (P < 0.01 for all three indices). By contrast, A-wave velocities were not different in the two groups. The correlation between S-wave velocity and TAMV was significant in both male (P < 0.001) and female (P < 0.001) fetuses, while PIV did not appear to be related to TAMV either in males (P = 0.90) or in females (P = 0.49). A-wave velocity had a significant negative correlation with PIV in both groups. Finally, PIV was significantly correlated with S-wave velocity in female fetuses (P < 0.01) but not in males (P = 0.14). CONCLUSION: These findings suggest that early cardiovascular development may be different in male and female fetuses.     

Reference ranges for fetal venous and atrioventricular blood flow parameters.

This cross-sectional study establishes reference ranges with gestation for Doppler parameters of fetal venous and atrioventricular blood flow. Color flow Doppler was used to examine 143 normal singleton pregnancies at 20-40 weeks' gestation. Flow velocity waveforms were recorded from the ductus venosus, right hepatic vein and inferior vena cava. The waveforms are triphasic, reflecting ventricular systole, early diastole and atrial contraction. Peak velocities for these parameters were measured with pulsed Doppler and a new index, the peak velocity index for veins (PVIV), was calculated. Similarly, time-averaged maximum velocities for the whole cardiac cycle were measured and the pulsatility index for veins (PIV) was calculated. Flow velocity waveforms were also recorded at the level of the atrioventricular valves and the ratios of peak velocities at early diastolic filling (E) and atrial contraction (A) were calculated. Regression analysis was used to define the association of each measured and calculated Doppler parameter with gestational age. Blood flow velocities in the fetal veins and velocities and E/A ratios across the atrioventricular valves increased significantly with gestation, whereas PVIV and PIV decreased. Blood flow velocities were highest in the ductus venosus and lowest in the right hepatic vein, and PVIV and PIV were highest in the hepatic vein and lowest in the ductus venosus. In the ductus venosus, there was always forward flow throughout the heart cycle, whereas in the inferior vena cava and hepatic vein during atrial contraction, flow was away from or towards the heart or there was no flow. Pulsatility of flow velocity waveforms in the venous system is the consequence of changes in pressure difference between the venous system and the heart during the heart cycle. The finding that PVIV and PIV decrease with gestation is consistent with decreasing cardiac afterload and maturation of diastolic ventricular function.     

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。     

Longitudinal reference ranges for ductus venosus flow velocities and waveform indices.

OBJECTIVES: Serial Doppler measurements of the ductus venosus are used increasingly for monitoring fetuses at risk of hemodynamic compromise, but existing reference ranges are based on cross-sectional studies and thus are less suitable for comparison with serial measurements. We aimed to establish longitudinal reference ranges for ductus venosus flow velocities and waveform indices and to provide the necessary terms for calculating conditional reference ranges for serial measurements. METHODS: This was a longitudinal study of 160 low-risk pregnancies. Pulsed Doppler ultrasound was used to record ductus venosus blood flow velocities at 4-week intervals from 20-22 weeks of gestation onwards. RESULTS: With a success rate of 93%, 547 measurements (four or five in each fetus) were used to establish reference ranges. The time-averaged maximum velocity was 50 cm/s at 21 weeks of gestation, increased to 60 cm/s at 32 weeks, and remained so until term. Similarly, the peak systolic velocity increased from 59 cm/s at 21 weeks to 71 cm/s at 31 weeks and remained so until term. The end-diastolic velocity showed a continuous increase from 31 cm/s at 21 weeks to 43 cm/s at 40 weeks. The pulsatility index for veins decreased from 0.57 at 21 weeks to 0.44 at 40 weeks. When conditioned by a previous measurement, the reference ranges for the next observation became narrower and commonly shifted compared with those of the entire population. CONCLUSION: The new longitudinal reference ranges presented here reflect the development of the ductus venosus flow velocities and velocity indices and are thus appropriate for serial measurements, particularly if conditional terms are included.     

Reversed end-diastolic flow in the umbilical artery at 10-14 weeks of gestation is associated with absent pulmonary valve syndrome.

OBJECTIVE: To determine the incidence of reversed end-diastolic flow (REDF) in the umbilical artery in high-risk first-trimester pregnancies and evaluate associated conditions. METHODS: This was a prospective evaluation of the umbilical artery Doppler waveforms of 614 consecutive high-risk pregnancies between 10 and 14 weeks of gestation, to determine those with REDF. The associated anomalies and characteristics of these fetuses were then investigated. RESULTS: In 278/614 (45.3%) fetuses, there was positive end-diastolic flow in the umbilical artery; in 331/614 (53.9%) end-diastolic flow was absent and in 5/614 (0.8%) there was REDF. Three of the five fetuses with REDF had tetralogy of Fallot (TOF) with absent pulmonary valve syndrome (APVS) and a patent ductus arteriosus, and all three showed signs of cardiac failure, with reversed blood flow in the ductus venosus during atrial systole and generalized skin edema. Another fetus had a large ventricular septal defect and the remaining fetus had agenesis of the ductus venosus. Three fetuses had trisomy 18 and one had trisomy 13. CONCLUSIONS: REDF in the umbilical artery is very rare in early pregnancy and mostly occurs in association with major fetal vascular anomalies and cardiac defects, particularly TOF with APVS and patent arterial duct. We propose that the patency of the arterial duct in TOF with APVS leads to heart failure with subsequent demise early in pregnancy. Therefore, the frequent absence of the arterial duct observed in APVS in later pregnancy is more likely to be a result of early selection than a prerequisite for the development of this lesion as has been proposed previously.     

Venous Doppler ultrasound in 146 fetuses with congenital heart disease.

OBJECTIVE: To assess the influence of isolated congenital heart disease (CHD) on fetal venous Doppler blood flow velocity waveforms. METHODS: Doppler flow velocimetry was performed in the inferior vena cava and ductus venosus in 146 consecutive fetuses with antenatally diagnosed CHD. Gestational age ranged between 19 and 39 weeks. Fetuses with isolated CHD without non-immune hydrops fetalis (NIHF) (Group A, n = 89) were separated from seven fetuses showing isolated CHD with NIHF (Group B) and 50 cases complicated by chromosomal or other extracardiac malformations, intrauterine growth restriction or non-cardiogenic NIHF (Group C). The control group comprised 109 healthy fetuses of uncomplicated pregnancies. Individual peak velocity index for veins (PVIV) measurements were converted into their Z-scores (delta values) for statistical analysis. RESULTS: There was no statistical difference between fetuses with isolated CHD (Group A) and controls, for the delta PVIV of neither the ductus venosus nor the inferior vena cava. Statistical analysis revealed significant differences between non-isolated CHD fetuses (Group C) and controls for both vessels. However, in a separate analysis of isolated right heart malformations compared with the remaining isolated heart malformations (Groups A and B), a significant difference was observed for the ductus venosus, but not the inferior vena cava. There was an overall survival of 62%. In Group A, 58% of fetuses survived despite increased PVIV and 22% of fetuses with normal venous Doppler had an adverse outcome. All fetuses with cardiogenic NIHF (Group B) died. CONCLUSION: Doppler studies of the ductus venosus and inferior vena cava in fetuses with isolated CHD do not present sufficient alterations to be a reliable marker for screening purposes for CHD in mid-second- and third-trimester fetuses. Furthermore, venous Doppler did not predict fetal outcome in cases of isolated CHD. Abnormal venous Doppler results were mainly attributable to myocardial dysfunction and also to severe right heart obstruction even in the absence of congestive heart failure. Therefore, venous Doppler studies are clinically helpful in indirectly monitoring cardiac function in fetuses with cardiac malformations.     

Cardiac defects in chromosomally normal fetuses with abnormal ductus venosus blood flow at 10-14 weeks.

OBJECTIVE: To assess a possible relationship between ductus venosus blood flow abnormalities and cardiac defects in chromosomally normal fetuses with increased nuchal translucency thickness at 10-14 weeks of gestation. METHODS: Ductus venosus Doppler ultrasound blood flow velocity waveforms were obtained at 10-14 weeks' gestation immediately before fetal karyotyping in 200 consecutive singleton pregnancies with increased nuchal translucency. Fetal echocardiography was subsequently carried out in those with normal fetal karyotype. RESULTS: Reverse or absent flow during atrial contraction was observed in 11 of the 142 chromosomally normal fetuses with increased nuchal translucency. Major defects of the heart and/or great arteries were present in seven of the 11 with abnormal ductal flow and increased nuchal translucency, but in none of the 131 with normal flow. CONCLUSION: These preliminary results suggest that abnormal ductus venosus blood flow in chromosomally normal fetuses with increased nuchal translucency identifies those with an underlying major cardiac defect.