Simultaneous measurements of umbilical venous, fetal hepatic, and ductus venosus blood flow in growth-restricted human fetuses

OBJECTIVE: The purpose of this study was to evaluate the changes in the distribution of the umbilical venous blood flow to the liver and to the ductus venosus in intrauterine growth-restricted human fetuses in relationship with dilation of the ductal isthmic diameter. STUDY DESIGN: Umbilical venous flow, ductus venosus blood flow, and blood flow to the fetal liver were measured in 56 severely intrauterine growth-restricted fetuses with an abnormal pulsatility index of the umbilical artery and were compared with 137 normal control fetuses. Percentages of umbilical venous blood flow through the ductus venosus and to the fetal hepatic lobes were calculated. Z-scores for control fetuses and intrauterine growth-restricted fetuses were constructed by the evaluation of the inverted smoothed percentiles. The distributions of the Z-scores was compared with a 1-sample t-test. RESULTS: The ductus venosus blood flow that was corrected for fetal weight was increased significantly in intrauterine growth-restricted fetuses compared with control fetuses (P=0); the median values (interquartile range) for comparable ages of gestation was 41.3 mL/min/kg (range, 26.2-64.0 mL/min/kg) and 30.8 mL/min/kg (range, 19.9-42.8 mL/min/kg), respectively. As a consequence, ductus venosus shunting was increased in intrauterine growth-restricted fetuses compared with control fetuses (P =0). In 23 of 30 intrauterine growth-restricted fetuses, the percentage of umbilical blood flow that was shunted through the ductus was>90th percentile of control fetuses. Ductal diameters were significantly greater in growth-restricted fetuses than in control fetuses (P =.0001). The percentage of blood flow to the right lobe showed a significant reduction (P =.0223), with evidence of reversed blood flow from the right lobe and portal system into the ductus venosus that was provided both by volume blood flow calculations and by direct pulsed Doppler waveform direction. CONCLUSION: In severe intrauterine growth-restricted fetuses, Doppler examination of blood flow volume proved a significant increase in the shunting of umbilical vein blood flow through the ductus venosus that was associated with the dilation of the ductal isthmic diameter. These changes provide a relatively constant blood flow to the heart and brain at the expense of fetal hepatic perfusion.     

Agenesis of the ductus venosus that is associated with extrahepatic umbilical vein drainage: prenatal features and clinical outcome

OBJECTIVE: We sought to study the clinical and ultrasonographic findings and outcomes of fetuses with ductus venosus agenesis as the result of extrahepatic umbilical vein drainage. STUDY DESIGN: This was an observational study of 12 fetuses who were diagnosed with these anomalies between 1995 and 2001. RESULTS: The umbilical vein drained either directly into the right atrium (n = 7 fetuses), the inferior vena cava (n = 3 fetuses), or the iliac vein (n = 2 fetuses). Combined cardiac output (n = 8 fetuses) was nearly 2-fold increased to 891 +/- 210 mL/kg per minute. Other relevant findings were (1) considerable umbilical vein enlargement (12/12 cases; range, 8-13 mm) with an accelerated (peak, 0.53 +/- 0.1 m/s), (2) pulsatile Doppler flow pattern within its intra-abdominal course, (3) cardiomegaly (12/12 fetuses), (4) secundum atrial septal defects (5/12 fetuses), (5) extracardiac anomalies (5/12 fetuses), (6) polyhydramnios (4/12 fetuses), and (7) progressive heart failure (3/12 fetuses). Two fetuses died: 1 death was unexplained at 29 weeks of gestation; the other death from hydrops occurred after delivery at 32 weeks of gestation. So far, none of the survivors have had other long-term sequelae that were related to ductus venosus agenesis. CONCLUSION: Careful assessment of the umbilical venous return and the ductus venosus should be part of the routine evaluation of every fetus with heart failure and polyhydramnios.     

Doppler assessment of the fetal venous system

This article describes the achievements in Doppler measurements of the fetal venous circulation with emphasis on the clinical impact of these techniques. In rhesus isoimmunization, fetal venous flow assessment gives useful information on the fetal haematologic condition and on the impact of blood transfusion. In first trimester fetuses, Doppler evaluation of the ductus venosus and umbilical vein could attribute to the detection of cardiac defects and/or chromosomal abnormalities. The inferior vena cava flow velocity waveform could be studied in cases of fetal arrhythmias to be able to diagnose the type of fetal heart rhythm disturbances. One of the more important applications of venous Doppler assessment is its use in the evaluation of the intrauterine growth retarded fetus, who is suffering from placental insufficiency. Decrease of the late diastolic flow component in the ductus venosus waveform and the presence of umbilical venous pulsations are distinct alterations, which have been detected before cardiotocogram deterioration occurs. The clinical possibilities of venous Doppler measurements are limited, and the use of the techniques requires intensive training.     

Agenesis of the ductus venosus and its correlation to hydrops fetalis

Absence of the ductus venosus is a rare vascular anomaly. We report a late onset of a hydrops fetalis seen in a fetus at 34 completed weeks of gestation. A persistence of the cranial parts of the left and right umbilical veins and of the paired cranial vitelline veins with an absent ductus venosus led to a bilateral hydrothorax, ascites and skin-edema. Postnatally the hydrops resolved within 7 days most probably due to the change from the fetal to the adult circulation. The abnormal venous system was confirmed by angiography. Agenesis of the ductus venosus can manifest in two different morphologic patterns: The umbilical vein drains exclusively into the left branch of the intrahepatic portal vein or the umbilical vein drains into the inferior vena cava or directly into the right atrium by-passing the liver completely. In both patterns, the preferential direction of the flow towards the foramen ovale is not present. While the first pattern leads to hyperperfusion of the liver parenchyma, the latter would result in reduced perfusion and oxygenation. Our findings suggest that agenesis of ductus venosus might induce hydrops fetalis. We conclude, that in every case of hydrops fetalis the venous system should be evaluated by ultrasonography prenatally and/or immediately postnatally.     

Prenatal diagnosis of ductus venosus agenesis and its association with cytogenetic/congenital anomalies

OBJECTIVES: We present an observational study of 12 cases of anomalies of the umbilical and portal vein systems associated with absence of the ductus venosus (DV) diagnosed over the past 5 years. The hemodynamic implications of each pattern of umbilico-portal system anomalies associated with absence of the DV have been investigated, as well as the frequency and types of associated anomalies and their embryological origin. METHODS: In all cases ultrasound, color Doppler, and cytogenetic investigations were performed. RESULTS: Four main patterns of abnormal venous circulation were documented: (1). the umbilical vein (UV) bypasses the liver and drains into the right atrium directly or through a dilated coronary sinus (three cases); (2). the UV bypasses the liver, with an infrahepatic or suprahepatic connection directly to the inferior vena cava (IVC) (two cases); (3). the UV bypasses the liver and drains directly into the iliac or renal veins (four cases); and (4). the UV drains directly into the portal veins (three cases). Among seven cases with other associated anomalies (58%), there were three cases of Turner's and Noonan's syndromes. Two fetuses and two neonates died and there were two terminations of pregnancy (TOP). CONCLUSIONS: In utero diagnosis of ultrasound patterns associated with DV anomalies is feasible. Fetal karyotyping should be considered, serial ultrasound examinations recommended and, in the presence of heart failure, delivery can be anticipated.     

Predicting pH at birth in absent or reversed end-diastolic velocity in the umbilical arteries

OBJECTIVE: To investigate arterial and venous blood flow in fetuses with absent or reversed end-diastolic flow in the umbilical arteries and to correlate the Doppler results with umbilical artery blood pH at birth to predict the probability of acidosis at birth. METHODS: Ninety-one fetuses from singleton pregnancies without fetal malformations with a diagnosis of absent or reversed end-diastolic flow in the umbilical arteries were prospectively studied. On the day of delivery, Doppler velocimetry of the umbilical arteries, middle cerebral artery, and ductus venosus was performed and the results were correlated with umbilical artery pH at birth at the following cutoff levels: pH < 7.20, < 7.15, < 7.10, and < 7.05. The association between fetal arterial and venous Doppler velocimetry and acidosis was then individually analyzed by the chi(2) and Fisher exact tests. The ability of these tests to predict the probability of acidosis at birth was estimated using a logistic regression model. RESULTS: There was a negative correlation between pH at birth and umbilical artery pulsatility index (r = -0.39; P < .001) and pulsatility index for veins in the ductus venosus (r = -0.63; P < .001). Assessment of the fetal arterial circulation (middle cerebral artery) showed no statistical correlation with pH at birth. Using logistic regression analysis, probability curves were constructed for pH values less than 7.20 (odds ratio [OR] 8.03), less than 7.15 (OR 11.92), less than 7.10 (OR 12.16), and less than 7.05 (OR 8.20). CONCLUSION: The pulsatility index for veins of the ductus venosus was related to pH at birth, demonstrating that the higher the ductus venosus pulsatility index for veins, the lower the pH at birth. Once the pulsatility index for veins in the ductus venosus is known, the probability of acidosis at birth can be estimated.     

Multivascular Doppler surveillance in high risk pregnancies

Objectives: Analysis of fetal arterial and venous Doppler predictability for adverse perinatal outcome. Methods: Blood flow in the uterine, umbilical and middle cerbral arteries, umbilical vein, ductus venosus and Galen vein were examined with in 72?h of delivery in 88 high-risk pregnancies. The managing clinicians were only informed about the results of the umbilical artery Doppler. The Doppler results were correlated to adverse perinatal outcome. Results: Doppler abnormalities were seen in both preterm and term pregnancies. Umbilical venous pulsations (n?=?13) were strongly correlated to Apgar score <7 at 5?min, abnormal blood gases, need for ventilation assistance and operative delivery for fetal distress. Twenty-four fetuses had brain sparing in the middle cerebral artery, and forty-five had abnormal umbilical artery Doppler. These were correlated to admission in the neonatal intensive care unit, operative delivery and prematurity. Brain sparing in middle cerebral artery was also correlated to ventilation disturbances in the newborns. Abnormal ductus venosus blood velocity was only seen in 9 cases and not related to adverse outcome. Galen vein pulsations (n?=?26) seem to appear earlier than pulsations in the umbilical vein and were not related to adverse outcome. conclusion: Umbilical vein pulsations were better correlated to adverse perinatal outcome than were other Doppler findings including ductus venosus.     

Doppler, cardiotocography, and biophysical profile changes in growth-restricted fetuses

OBJECTIVE: To assess from diagnosis to delivery the Doppler studies of the umbilical artery, middle cerebral artery, umbilical vein, ductus venosus, and amniotic fluid index of fetuses with idiopathic growth restriction. METHODS: A total of 145 singleton growth-restricted fetuses with abnormal umbilical artery pulsatility indexes were studied. Cesarean delivery was performed because of abnormal biophysical profile or nonreassuring fetal heart rate pattern. RESULTS: There were 4 fetal and 50 neonatal deaths. Two growth-restricted groups were identified: Group A (n = 44) included fetuses in whom all measures became abnormal preceding an abnormal biophysical profile or nonreassuring nonstress test. Group B (n = 101) included fetuses in whom 1 or more measures were normal at the time of cesarean delivery. There was no statistically significant difference in perinatal morbidity and mortality between the 2 groups. Neonatal death was increased in fetuses with umbilical artery reversed flow (odds ratio 2.34, 95% confidence interval 1.16-4.73; P < .05) and ductus venosus reversed flow (odds ratio 4.18, 95% confidence interval 2.01-8.69; P < .05). A significant correlation was also found between low birth weight and adverse perinatal outcome. CONCLUSION: In fetuses with idiopathic growth restriction, 1) low birth weight, 2) umbilical artery reversed flow, and 3) ductus venosus absent or reversed flow are associated with an increased perinatal morbidity and mortality.     

The assessment of fetal well-being by venous Doppler velocimetry

The assessment of fetal well-being by venous Doppler velocimetry, especially in cases of intrauterine growth restriction, has been growing in importance as a number of researchers have been improving their studies^1 - 5 as well as a consequence of better technologies in ultrasound equipment. Since different authors have studied the fetal blood circulation with color Doppler, initially focusing their attention on the arterial system^6 - 12, many questions and doubts have remained without a reasonable answer, especially concerning the optimal time at which to deliver these fetuses. Among these authors, some have expressed the opinion that all biophysical methods, including the cardiotocogram, should be used before the decision of fetus delivery should be made^13,14. It is possible, nowadays, to study several venous vessels, such as the ductus venosus, inferior vena cava, umbilical vein, portal vein, hepatic veins¹⁵, and, more recently^1,2, the cerebral transverse sinus. The purpose of this review is to describe the fetal circulation, the technique and rationale behind measuring venous Dopplers and to assess the clinical applications of venous Doppler velocimetry.     

Obstruction of ductus venosus stimulates cell proliferation in organs of fetal sheep

In growth restricted fetuses, hepatic blood flow is reduced. This suggests the hypothesis that liver blood flow controls fetal growth. In 11 near term sheep the ductus venosus was blocked with an embolization coil in one fetus (experimental) and left patent in the twin (control). Arterial catheters were placed in both fetuses. After termination [mean (s.d.) 5 days (2) after surgery] the fetal body and organs were weighed. The cell proliferation rate (pKi-67) was determined in tissue samples of the liver, heart, skeletal muscle, kidneys and placenta (n=6). Blood flow through the umbilical vein measured by Doppler ultrasound did not differ in control and experimental fetuses [experimental: 600 (101) ml/min; control: 626 (89) ml/min]. In experimental fetuses, blood flow through the ductus venosus was negligible (colour Doppler), and thus hepatic blood flow was increased. Absolute and relative (percentage of body weight) liver weights were increased in experimental fetuses [liver weight: 119 (34) g versus 84 (17) g; relative liver weight: 4.3 (0.8) per cent versus 3.4 (0.8) per cent;P=0.002, n=11]. The cell proliferation rate was increased significantly (twofold) in heart muscle, skeletal muscle and kidneys, and sixfold in liver. It is concluded that increases of hepatic blood flow stimulate cell proliferation in major organs of the ovine fetus.     

Structural evidence for mechanisms to redistribute hepatic and ductus venosus blood flows in nonhuman primate fetuses

OBJECTIVE: The ductus venosus (DV) and the intrahepatic branches of the portal vein (BPV) play an important role in umbilical blood distribution to the fetal liver and the rest of the fetal circulation. Increased DV shunting is a major fetal survival mechanism during stress situations. The availability of a nonpregnant primate animal model with similar structure and function would greatly improve our understanding of DV function. However, the anatomic and histologic structure of the DV and the BPV have not been thoroughly investigated in any nonhuman primate species. METHODS: Anatomic and immunohistochemical (Masson's and alpha-smooth actin stains) investigations were performed on 17 baboon fetuses at 173 +/- 5 days' gestation (mean +/- SEM, term = 180 days) (Papio sp. ) and 3 near term rhesus (Macaca mulatta) fetuses. RESULTS: In both species the branchless, funnel-shaped DV coursed cranially, posteriorly, and slightly oblique to the left side. The DV and the efferent hepatic veins drained into a dilated ampullary area (the collectus venosus) that joined directly with the inferior cava. The length of the DV in baboons increased with gestational age ( r = 0.86, n = 16). In 4 baboon fetuses, we observed an asymmetrical muscular lip at the isthmic portion of the DV. The media of intrahepatic BPV contained more smooth muscle cells than the media of the DV. CONCLUSION: In nonhuman primate fetuses, the DV drains into a dilated ampullary area. An asymmetrical muscular lip forms a contractile element of the isthmic portion of the DV. The increased thickness of smooth muscle tissue in the DV isthmus and intrahepatic BPV in nonhuman primate fetuses support the concept of a general organization of a contractile apparatus that performs a sphincter-like function in the central venous hepatic system and plays a key role in blood flow redistribution.     

Agenesis of the ductus venosus associated with direct umbilical venous return into the heart--case series and review of literature

OBJECTIVES: The purpose of our study was to review our own experience and the available literature on the prenatal diagnosis of absent ductus venosus associated with direct insertion of the umbilical vein into the heart. METHODS: A retrospective review of the database of a tertiary fetal cardiology centre. The literature was searched for cases with a prenatal diagnosis of such an umbilical venous anomaly. RESULTS: Between January 2000 and June 2003, nine fetuses were diagnosed as having absence of the ductus venosus with the umbilical vein directly draining into the heart. This represents the largest reported clinical experience of this anomaly. We also report, to our knowledge, the first prenatal diagnosis of insertion of the umbilical vein into the left atrium. Combining our series with those found in the literature, a total of 35 cases were identified. Cardiomegaly was reported in 25 of the 35 cases (71%). Structural cardiac abnormalities and other extra-cardiac anomalies were found in 13 of the 35 cases (37%). Hydrops was present or developed in 6 cases (17%). The outcome data were available for 33. The overall survival rate was 67% (22 of 33). CONCLUSIONS: Careful assessment of the ductus venosus and the umbilical vein should be a part of the evaluation of every fetus with unexplained cardiomegaly. All fetuses with abnormal connection of the umbilical vein should undergo a clinical and ultrasonographic assessment both in utero and after birth to exclude any cardiac and extra-cardiac abnormalities. During the prenatal period, serial ultrasound examinations are indicated and delivery is considered when there is evidence of progressive cardiovascular compromise.     

Clinical significance of the doppler evaluation in ductus venosus, hepatic veins and pulmonary veins

Doppler evaluation of the fetal venous system at present improves assessment of fetal well-being in many conditions. Actually, analysis of ductus venosus waveforms seems to be the most important. It place role in detection of genetic abnormalities (in low pregnancies), prediction of outcomes growth-restricted fetuses, assessment of severity of heart failure due to congestive heart anomalies, fetal infections, hydrops fetalis. Hepatic veins are known rather as an additional parameter (for ductus venosus) in the severely compromised fetus. Doppler evaluation of pulmonary veins may be useful in prediction of fetal lung maturity and in detection some difficult circulatory anomalies.     

Normalisation of a severely abnormal ductus venosus Doppler flow velocity waveform in a growth-retarded fetus with absent end-diastolic flow in the umbilical artery and congenital anomalies

Doppler recordings of fetal venous blood flow seem to be superior to arterial velocimetry and CTG concerning the prediction of fetal outcome and optimal time of delivery in pregnancies with fetal growth retardation and AREDV. An improvement of arterial Doppler flow velocities has been described. We report the reappearance of a normal end-diastolic flow velocity in a ductus venosus temporarily showing reversed end-diastolic flow in a growth-retarded fetus with congenital anomalies. This normalization was accompanied by an improvement of the CTG, a loss of umbilical vein pulsations, a reappearance of umbilical diastolic flow and a progressive return of cerebral and venous blood flow into the 'normal' range. Improvement of fetal condition may be the explanation for our observation.     

The importance of Doppler ultrasonography in the management of fetal growth restriction

AIM: To evaluate the importance of Doppler ultrasonography in fetuses in the management of fetal growth restriction (FGR). METHODS: Sixty-five pregnant women, aged between 23 to 39 years and from 27 to 37 weeks of pregnancy were selected; they all carried a single fetus showing a diminished growth curve in respect to the previous echographic examinations. Women affected with diabetes types I and II, renal pathologies and/or past endocrinopathies were excluded. All the patients with fetal growth restriction underwent accurate flussimetric mapping of some fetal districts such as umbilical artery and ductus venosus. Modalities of birth and the neonatal outcome were also considered. RESULTS: The patients selected were divided into 4 groups according to the velocimetrical data. The neonatal outcome was positive when the end diastolic flow was present in the umbilical artery associated with a normal flow in the ductus venosus. In cases where the end diastolic flow was absent in the umbilical artery, the management and neonatal outcome varied in relation to the morphology of the flow in the ductus venosus: the absence or reverse A phase of the mentioned flow is often indicative of acute fetal distress and unfavourable prognosis. Reverse end diastolic flow in the umbilical artery was always associated with the intrauterine death of the fetus. CONCLUSIONS: Our results confirm the validity of Doppler ultrasonography in the management and in the choice of timing for birth in cases of fetal growth restriction.     

Absent ductus venosus in the fetus: review of the literature and first report of direct umbilical venous drainage to the coronary sinus

The ductus venosus connects the portal and umbilical veins with the inferior vena cava and acts as a sphincter to protect the fetus from placental overcirculation. Its absence usually causes hydrops fetalis and is associated with high mortality rate, chromosomal anomalies and congenital malformations. In this condition, the umbilical vein almost always drains directly into right-sided structures such as inferior vena cava or right atrium. We reviewed the literature and describe the first case of a fetus with absent ductus venosus and direct connection of the umbilical vein to the coronary sinus.     

Doppler sonography of the fetal venous circulation

Venous Doppler sonography has been used for assessment of the fetal hemodynamics in the last 15 years. The velocimetries of the central fetal veins — umbilical vein (UV), ductus venosus (DV), hepatic veins (HV) and inferior vena cava (IVC) — reflect the cardiac function and its impairment due to changes in cardiac preload or afterload, and due to changes in the cardiac rhythm. It is possible to see the severity of the disturbance in cardiac function and venous Doppler is broadly used in the surveillance of pregnancies, which are disturbed by severe placental insufficiency, cardiac defects, arrhythmias, anemia, hydrops fetalis and hyper- or hypovolemia as in twin-to-twin transfusion syndrome. Herein we summarize the past, present and eventual future developments of venous Doppler sonography, reflecting the physiology and pathophysiology of the fetal venous circulation and describing the state of the art of its clinical application.     

Arterial and ductus venosus Doppler in fetuses with absent or reverse end-diastolic flow in the umbilical artery: correlation with short-term perinatal outcome

BACKGROUND: High perinatal morbidity and mortality rates have been reported in association with absent or reverse end-diastolic flow velocities in the umbilical artery. Doppler of fetal venous blood flow might be a helpful instrument for predicting fetal outcome. However, clinical data addressing this issue are rare. Thus, the aim of this study was to evaluate arterial and ductus venosus blood flow velocities as a predictor of short-term outcome in fetuses with umbilical absent or reverse end-diastolic flow velocities. METHODS: Thirty-five high-risk single pregnancies complicated by umbilical absent or reverse end-diastolic flow velocities were monitored by serial measurement of the pulsatility index of the umbilical artery, middle cerebral artery, and ductus venosus waveforms over a period of 1-75 days. RESULTS: The mean observation period between first detection of an umbilical absent or reverse end-diastolic flow velocity and delivery was 8.9 days. A significant correlation was found between parameters of short-term perinatal outcome (art. pH, art. base excess, development of intraventricular hemorrhage, mortality) and end-diastolic flow velocity waveform or pulsatility index of the ductus venosus waveform, but not with arterial Doppler parameters. Gestational age proved to be the best predictor for duration of assisted ventilation and development of respiratory distress syndrome. CONCLUSIONS: Our results indicate that in high-risk pregnancies with umbilical absent or reverse end-diastolic flow velocities, determination of blood flow velocities in the ductus venosus is a useful additional parameter for prediction of fetal outcome and for timing delivery.     

Fetal Doppler: umbilical artery, middle cerebral artery, and venous system

One of the most important applications of Doppler ultrasonography in obstetrics is the detection of fetal anemia in pregnancies complicated by either red-cell alloimmunization or by other causes of fetal anemia. Doppler of the umbilical artery also has prognostic value in pregnancies affected by twin-twin transfusion syndrome undergoing in-utero intervention. Another potential major application is the use of Doppler ultrasound in the management of intrauterine-growth-restricted fetuses. At the present time, there is no single test that appears superior to the other available tests for timing the delivery of the growth-restricted fetus. Therefore, the decision to deliver a fetus, especially at <32 weeks, remains mostly based on empirical management. Doppler may provide a more reliable and systematic basis for timing these deliveries. This review emphasizes the three following concepts: (a) normal and abnormal Doppler of the umbilical artery, middle cerebral artery, mitral and tricuspid valves, umbilical vein, and ductus venosus; (b) some clinical applications of Doppler sonography in obstetrics; and (c) potential future research of Doppler in obstetrics.     

Reversal of compensatory flow in severe intrauterine growth restriction: middle cerebral artery and intracardiac volume flow modifications

AIM: The aim of the study was to investigate cerebral and cardiac volume flow modifications in a group of preterm severely growth restricted (GR) fetuses with absent end diastolic flow (AEDF) in the umbilical artery. METHODS: Doppler indices of GR fetuses born at less than 32 weeks of gestation with AEDF in umbilical artery were longitudinally analyzed. Ductus venosus S/A, umbilical artery PI, middle cerebral artery (MCA) pulsatility index (PI), MCA volume flow and intracardiac flows were checked daily. The value of volume flow was determined by multiplying the vessel area obtained by means of a power angiography by the integral of the velocimetric curve. In Group 1 the time of delivery was decided when abnormal Doppler index in ductus venosus (S/A>3) was detected. In Group 2, decisions about delivery were based on maternal indications or on various cardiotocographic (CTG) abnormalities. The division in the two groups was made with a retrospective method. RESULTS: Fifteen GR fetuses were studied: seven cases entered Group 1 and eight cases Group 2. In Group 2 velocimetric (PI) and quantitative (volume flow) values remained stable until delivery. In all cases in Group 1 ductus venosus anomalies (S/A>3) were preceded by 24 hours by cerebral volume flow indices indicating the loss of MCA vasodilatation and by changes in intracardiac volume flow indices, while the PI increase in MCA was present only 24 hours after the changes detected by the volume flow study and were simultaneous to ductus venosus modifications. CONCLUSION: The decrease in volume flow through the middle cerebral artery occurs at least 24 hours before the increase of middle cerebral artery PI and before the ductus venosus anomalies. Flow through the four cardiac valves show modification in agreement to the changes of the middle cerebral artery flow.