1412
Ultrasonographic velocimetry of the fetal ductus
In fetal lambs, the ductus
venosus
shunts well-
oxygenated blood directly to the heart, a pattern expected to be found also in the human fetus. We aimed to describe the human ductus venosus in a longitudinal sonographic study of two-dimensional imaging, colour flow mapping, and pulsed doppler velocimetry every 3-4 weeks during the second half of pregnancy. The fetuses of 29 healthy women were studied. The ductus venosus and its blood flow were identified and recorded for later analysis that included maximum velocity tracing. In the 184 examinations analysed, the ductus venosus appeared as a narrow vessel projecting a highvelocity jet posteriorly to reach the foramen ovale. The mean peak velocity in the ductus venosus increased from 65 cm/s in week 18 to 75 cm/s at term. Low values of the time-averaged maximum velocity were found in 2 fetuses with cardiovascular abnormalities (1 supraventricular tachycardia, 1 congestive heart failure), as a result of reversed flow in the ductus venosus during atrial systole. The high peak velocity in the ductus venosus, which is comparable with arterial velocities, probably gives the blood sufficient momentum to reach the foramen ovale without extensive mixing with deoxygenated blood. Velocimetry of the ductus venosus carries new diagnostic possibilities. Introduction The ductus venosus, the first of three physiological shunts through which fetal blood passes after leaving the umbilical vein, is a tiny vein only 2 cm long and 2 mm wide at term, and is occluded after birth.1-3 Studies in animals show that up to 60% of the umbilical blood bypasses the liver through the ductus venosus and is directly delivered to the thoracic inferior vena cava (IVC)." By crossing the foramen ovale to reach the left heart and finally the aorta, the ductus venosus flow supplies vital organs such as the brain with well-oxygenated blood/>-l1 The same arrangement may be found in the human fetus.6,7,11The ductus venosus has been visualised by means of ultrasonography,12-14 but little is known about its function in the human fetus in utero. The mean umbilical vein pressure in human beings is reported to be 4-5 mm Hg around 26 weeks of gestation. 15,16 The pressure in sheep is higher (15 mm Hg).7 This pressure probably constitutes the main driving force on the bloodstream through the ductus venosus. The velocity in the ductus venosus reflects the pressure gradient between the umbilical vein and the right atrium. Thus, it may be possible to diagnose disorders of atrial pressure or umbilical venous return in utero.
veriosus
Our
were to identify the ductus venosus in fetuses and to describe its blood flow velocity healthy We went on to investigate possible diagnostic patterns. measurements for clinical application in 2 fetuses with abnormal haemodynamics.
objectives
Subjects and methods 31 women were recruited from the routine ultrasound scanning programme during week 18 of gestation. All the women gave written informed consent according to a protocol approved by an ethics committee. The participants were all healthy non-smokers with a normal obstetric history and a normal singleton pregnancy, and they all gave birth to a healthy baby at term. We excluded the participant if her baby was small for gestational age (birthweight below the fifth centile) or if she had any disease during the pregnancy. A Vingmed CFM 750 ultrasound scanner (Vingmed Sound, Horten, Norway) was used to examine each patient every 3-4 weeks by combined two-dimensional imaging (5-00 and 3-75 MHz transducer), colour flow mapping, and pulsed doppler velocimetry (4-0 and 2-5 MHz with a spatial temporal average intensity set to 45 and 10 mW/cm2). The ductus venosus was identified, preferably near the midsagittal plane or in an oblique transection where it leaves the portal sinus (otherwise called the umbilical sinus) to join the IVC. Identification was accepted when a continuous luminal connection between the portal sinus and the IVC was seen. The smallest inner width was measured when the projection was adequate. Direction of flow was confirmed and flow delivery into the atrium traced by colour doppler imaging. Pulsed doppler signals were collected by a sample volume of 4-10 mm placed above the origin of the ductus venosus. Time relation to the heart cycle was sought by a widened sampling gate which allowed simultaneous recording of the IVC, since such a relation has been previously reported for the IVC.1’ The recordings were stored on a computer for later analysis. The maximum velocity tracings were used to calculate peak velocity (V eak)’ time-averaged maximum velocity (V,a), and the lowest in the cycle (V-). The criteria for a tracing to be included in the statistical analysis were: that it corresponded to at least four heart cycles; that the heart rate was 120-150 bpm; that the fetus was quiescent; and that the colour flow imaging was optimum and angle correction lowest. Two cases of fetal heart disease were examined by the ultrasonographic method.
vefocity
Results Of 31 women, 2 were withdrawn (1 moved and 1 started smoking), and the 29 women remaining had 184 examinations for analysis. By a combination of twodimensional imaging and colour doppler imaging the ductus venosus was identified in all examinations. It pointed dorsally and turned obliquely upwards, projecting its fountain-like jet towards the foramen ovale (fig 1). The colour flow signals had a more constant forward direction and a higher intensity than the neighbouring venous signals ADDRESS: National Center for Fetal Diagnosis and Therapy, Department of Gynecology and Obstetrics, Trondheim University Hospital, N-7006 Trondheim, Norway (T Kiserud, MD, Prof S. H Eik-Nes, PhD, H-G K Blaas, MD, L R. Hellevik, MSc) Correspondence to Dr Torvid Kiserud.
1413
Fig 1-The ductus venosus. Upper: diagrammatic midsagittal section showing narrow, trumpetvenosus projecting its bloodstream towards foramen ovale (FO). RA = right atrium; RV = right ventricle; UV = umbilical vein. Lower: near midsagittal section of 24 wkfetus. Colourdopplerof blood stream inductusvenosus (2) passing IVC and entering foramen ova le (4) and left atrium (5) - 1 = umbilical vein; 3 = hepatic vein; 6 = right atrium; like ductus
A = aorta
of lower velocity and periodic zero or negative flow. The heart, naturally turning to the left, received this fountain at its atrial septum, which allowed the stream to enter the foramen ovale. In all cases, the ductus venosus was a narrow trumpet-like structure throughout the pregnancy. The inner width was measured in 60 examinations and the narrowest portion never exceeded 2 mm. Pulsed doppler signals from the ductus venosus were successfully obtained in all examinations. The maximum velocity tracing had a characteristic pattern similar to that in the IVC, reflecting ventricular systole, ventricular diastole, and atrial systole (fig 2A). Vmin corresponded to the atrial systole. By contrast to the IVC, reversed flow was never seen in the ductus venosus in normal fetuses. The time relation to the heart cycle was confirmed in 12 cases by a simultaneous recording of the ductus venosus and the IVC. Data from the maximum velocity tracings fitted a linear regression analysis. Vpeak had a mean of 65 cm/s in week 18 and increased only slightly to 75 cm/s by week 40. Although
Fig 2-Ductus venosus velocimetry by doppler sonography. A: Typical normal tracing, week 29 of gestation; VS=ventricular systole, VD=ventricu!ar diastole, AS= atriasystole. B: fetal supraventricular tachycardia, week 23. C: fetal congestive heart failure, week 29. atrial systole reduced velocity by about 25 cm/s during a short portion of the cycle, it had little effect on the V., which remained close to the V peak throughout the second half of pregnancy (fig 3). We observed reversed blood flow through the ductus venosus during atrial systole in a fetus with supraventricular tachycardia (220 bpm) during week 23 of gestation (fig 2B). Synchronous pulsatile changes were recorded in the
umbilical vein. When the heart rate returned to normal, reversed flow was no longer observed (fig 2B) and the Vta in
1414
diameter, velocity profile, and other haemodynamic properties, a simplified model may be applicable for clinical purposes. Reduction or inversion of the ductus venosus flow during atrial systole (V min) could indicate altered pressure during atrial systole or could be an early sign of reduced umbilical-atrial pressure gradient, as seen in our 2 cases (fig 2 B, C). Reversed ductus venosus flow may explain the previously reported pulsations in the umbilical vein.19 An overall reduction in velocity would be a more serious sign, implying reduced transport of oxygenated blood to the foramen ovale. V peak may indicate how far the fetus manages to build up the necessary ductus venosus velocity, and Vta may roughly estimate the proportion of ductus venosus flow that reaches this velocity. In our case of congestive heart
failure, high-velocity holosystolic tricuspid regurgitation may have been
important
the ductus
Fig 3-Ductusvenosustime-averaged maximum blood velocity
(Vta) in weeks 18-40. Linear regression with mean and 95% confidence Interval of 184 observations x-x= case of supraventricuar tachycardia before and after conversion to normal rhythm. *=case of congestive heart failure
the ductus
venosus
increased
by 50% from
26
cm/s to
38
cm/s (fig 3). In another case,
a
twin fetus had
section.
Discussion
Despite its small size the ductus venosus could readily be identified, especially when colour doppler imaging was added. The maximum velocity tracing, which shows no reversed flow but does reflect atrial systole, is typical of the and should normally not be confused with of tracings neighbouring veins such as the IVC. With colour doppler we could confirm that in the human fetus the ductus venosus blood flow is directed towards the foramen ovale. A high momentum is probably necessary for the oxygenated blood in the ductus venosus to maintain its direction and travel all the way to the foramen ovale while avoiding extensive mixing. We found very high velocities in the ductus venosus, similar to those otherwise found on the arterial side. The umbilical vein blood already has a mean velocity of 15 cm/s before it enters the ductus venosus.18 To accelerate the blood, a pressure gradient is needed. For the ductus venosus, the pressure gradient is found between the umbilical vein and the atrium. Is the reported human umbilical venous pressure of 5 mm Hg15,16 sufficient to produce the high velocities recorded? A pressure of 15 mm Hg, as found in fetal lambs,’ is more likely to be sufficient. Nature seems to regulate this gradient by a "physiological stenosis", the ductus venosus. Whereas the fetus and its vessels grow steadily, the ductus venosus remains narrow, not exceeding 2 mm. Thus, it forms a high-velocity jet throughout the pregnancy. Does sonography of the ductus venosus provide any diagnostic possibilities? Aside from abnormalities in ductus
venosus
changing atrial pressure and velocity with a general offset
distorting (figs 2C, 3). Physiologists such as Barcroft6 and Dawes’ long ago pointed out that the ductus venosus is an important regulator of fetal circulation. Today the ductus venosus can regularly be identified by sonographic methods. Such studies have diagnostic potential in disorders of the fetal circulation and deserve closer attention from clinicians.
congestive heart failure
(hydrops, cardiomegaly, reduced ventricular excursions, a high velocity holosystolic tricuspid regurgitation, and umbilical venous pulsation) during week 29 owing to fetofetal transfusion. The ductus venosus flow was grossly distorted by reversed flow during atrial systole (fig 2C) and the Vta was low (fig 3). The fetus also had signs of a brain-sparing effect shown by a reduced pulsatility index of the middle cerebral artery. The baby was saved by caesarean
in
venosus
REFERENCES
Reynolds SR. Embryonic development in the human of the sphincter of the ductus venosus. Anat Rec 1953; 115: 151-73. 2. Barclay AE, Franklin KJ, Prichard MM. The mechanism of closure of the ductus venosus. Br J Radiol 1942; 15: 66-71. 3. Meyer WW, Lind J. The ductus venosus and the mechanism of its closure. Arch Dis Child 1966; 41: 597-605. 4. Edelstone DI, Rudolph AM, Heymann MA. Liver and ductus venosus blood in fetal lambs in utero. Circ Res 1978; 42: 426-33. 5. Edelstone DI. Regulation of blood flow through the ductus venosus. J Dev Physiol 1980; 2: 219-38. 6. Barcroft J. Researches on prenatal life. Oxford: Blackwell Scientific Publications, 1946. 7. Dawes GS. Foetal and neonatal physiology. Chicago: Year Book Medical Publishers, 1968. 8. Behrman RE, Lees MH, Peterson EN, DeLannoy CW, Seeds AE. Distribution of the circulation in the normal and asphyxiated fetal primate. Am J Obstet Gynecol 1970; 108: 956-69. 9. Edelstone DI, Rudolph AM. Preferential streaming of ductus venosus blood to the brain and heart in fetal lambs. Am J Physiol 1979; 237: 1. Chako AW,
H724-29. 10. Dawes GS. The umbilical circulation. Am J Obstet Gynecol 1984; 84: 1634-48. 11. Barclay AE, Franklin KJ, Prichard MM. The foetal circulation and cardiovascular system, and the changes that they undergo at birth. Oxford: Blackwell Scientific Publications Ltd, 1944. 12. Chinn DH, Filly RA, Callan PW. Ultrasonic evaluation of fetal umbilical and hepatic vascular anatomy. Radiology 1982; 144: 153-57. 13. Staudach A. Sectional fetal anatomy in ultrasound. Heidelberg: SpringerVerlag, 1987. 14. Champetier J, Yver R, Tomasella T. Functional anatomy of the liver of the human fetus: applications to ultrasonography. Surg Radiol Anat 1989; 11: 53-62. 15. Nicolini U, Talbert DG, Fisk NM, Rodeck CH. Pathophysiology of pressure changes during intrauterine transfusion. Am J Obstet Gynecol
1989; 160: 1139-45. 16. Weiner CP, Heilskov J, Plezer G, Grant S, Wenstrom K, Williamson RA. Normal values for human umbilical venous and amniotic fluid pressures and their alteration by fetal disease. Am J Obstet Gynecol 1989; 161: 714-17. 17. Reed KL, Appleton CP, Anderson CF, Shenker L, Sahn DJ. Doppler studies of vena cava flows in human fetuses. Circulation 1990; 81: 498-505. 18. Eik-Nes SH, Marsál K. Noninvasive measurement of blood flow in human fetal aorta and umbilical vein. In: Orlandi C, Polani P, Bovicelli L, eds. Recent advances in prenatal diagnosis. Chichester: John Wiley & Sons, 1981: 113-19. 19. Gudmundsson S, Huhta JC, Wood DC, Tulzer G, Cohen AW, Weiner S. Venous doppler ultrasonography in the fetus with nonimmune hydrops. Am J Obstet Gynecol 1991; 164: 33-37.
Ultrasonographic velocimetry of the fetal ductus
In fetal lambs, the ductus
venosus
shunts well-
oxygenated blood directly to the heart, a pattern expected to be found also in the human fetus. We aimed to describe the human ductus venosus in a longitudinal sonographic study of two-dimensional imaging, colour flow mapping, and pulsed doppler velocimetry every 3-4 weeks during the second half of pregnancy. The fetuses of 29 healthy women were studied. The ductus venosus and its blood flow were identified and recorded for later analysis that included maximum velocity tracing. In the 184 examinations analysed, the ductus venosus appeared as a narrow vessel projecting a highvelocity jet posteriorly to reach the foramen ovale. The mean peak velocity in the ductus venosus increased from 65 cm/s in week 18 to 75 cm/s at term. Low values of the time-averaged maximum velocity were found in 2 fetuses with cardiovascular abnormalities (1 supraventricular tachycardia, 1 congestive heart failure), as a result of reversed flow in the ductus venosus during atrial systole. The high peak velocity in the ductus venosus, which is comparable with arterial velocities, probably gives the blood sufficient momentum to reach the foramen ovale without extensive mixing with deoxygenated blood. Velocimetry of the ductus venosus carries new diagnostic possibilities. Introduction The ductus venosus, the first of three physiological shunts through which fetal blood passes after leaving the umbilical vein, is a tiny vein only 2 cm long and 2 mm wide at term, and is occluded after birth.1-3 Studies in animals show that up to 60% of the umbilical blood bypasses the liver through the ductus venosus and is directly delivered to the thoracic inferior vena cava (IVC)." By crossing the foramen ovale to reach the left heart and finally the aorta, the ductus venosus flow supplies vital organs such as the brain with well-oxygenated blood/>-l1 The same arrangement may be found in the human fetus.6,7,11The ductus venosus has been visualised by means of ultrasonography,12-14 but little is known about its function in the human fetus in utero. The mean umbilical vein pressure in human beings is reported to be 4-5 mm Hg around 26 weeks of gestation. 15,16 The pressure in sheep is higher (15 mm Hg).7 This pressure probably constitutes the main driving force on the bloodstream through the ductus venosus. The velocity in the ductus venosus reflects the pressure gradient between the umbilical vein and the right atrium. Thus, it may be possible to diagnose disorders of atrial pressure or umbilical venous return in utero.
veriosus
Our
were to identify the ductus venosus in fetuses and to describe its blood flow velocity healthy We went on to investigate possible diagnostic patterns. measurements for clinical application in 2 fetuses with abnormal haemodynamics.
objectives
Subjects and methods 31 women were recruited from the routine ultrasound scanning programme during week 18 of gestation. All the women gave written informed consent according to a protocol approved by an ethics committee. The participants were all healthy non-smokers with a normal obstetric history and a normal singleton pregnancy, and they all gave birth to a healthy baby at term. We excluded the participant if her baby was small for gestational age (birthweight below the fifth centile) or if she had any disease during the pregnancy. A Vingmed CFM 750 ultrasound scanner (Vingmed Sound, Horten, Norway) was used to examine each patient every 3-4 weeks by combined two-dimensional imaging (5-00 and 3-75 MHz transducer), colour flow mapping, and pulsed doppler velocimetry (4-0 and 2-5 MHz with a spatial temporal average intensity set to 45 and 10 mW/cm2). The ductus venosus was identified, preferably near the midsagittal plane or in an oblique transection where it leaves the portal sinus (otherwise called the umbilical sinus) to join the IVC. Identification was accepted when a continuous luminal connection between the portal sinus and the IVC was seen. The smallest inner width was measured when the projection was adequate. Direction of flow was confirmed and flow delivery into the atrium traced by colour doppler imaging. Pulsed doppler signals were collected by a sample volume of 4-10 mm placed above the origin of the ductus venosus. Time relation to the heart cycle was sought by a widened sampling gate which allowed simultaneous recording of the IVC, since such a relation has been previously reported for the IVC.1’ The recordings were stored on a computer for later analysis. The maximum velocity tracings were used to calculate peak velocity (V eak)’ time-averaged maximum velocity (V,a), and the lowest in the cycle (V-). The criteria for a tracing to be included in the statistical analysis were: that it corresponded to at least four heart cycles; that the heart rate was 120-150 bpm; that the fetus was quiescent; and that the colour flow imaging was optimum and angle correction lowest. Two cases of fetal heart disease were examined by the ultrasonographic method.
vefocity
Results Of 31 women, 2 were withdrawn (1 moved and 1 started smoking), and the 29 women remaining had 184 examinations for analysis. By a combination of twodimensional imaging and colour doppler imaging the ductus venosus was identified in all examinations. It pointed dorsally and turned obliquely upwards, projecting its fountain-like jet towards the foramen ovale (fig 1). The colour flow signals had a more constant forward direction and a higher intensity than the neighbouring venous signals ADDRESS: National Center for Fetal Diagnosis and Therapy, Department of Gynecology and Obstetrics, Trondheim University Hospital, N-7006 Trondheim, Norway (T Kiserud, MD, Prof S. H Eik-Nes, PhD, H-G K Blaas, MD, L R. Hellevik, MSc) Correspondence to Dr Torvid Kiserud.
1413
Fig 1-The ductus venosus. Upper: diagrammatic midsagittal section showing narrow, trumpetvenosus projecting its bloodstream towards foramen ovale (FO). RA = right atrium; RV = right ventricle; UV = umbilical vein. Lower: near midsagittal section of 24 wkfetus. Colourdopplerof blood stream inductusvenosus (2) passing IVC and entering foramen ova le (4) and left atrium (5) - 1 = umbilical vein; 3 = hepatic vein; 6 = right atrium; like ductus
A = aorta
of lower velocity and periodic zero or negative flow. The heart, naturally turning to the left, received this fountain at its atrial septum, which allowed the stream to enter the foramen ovale. In all cases, the ductus venosus was a narrow trumpet-like structure throughout the pregnancy. The inner width was measured in 60 examinations and the narrowest portion never exceeded 2 mm. Pulsed doppler signals from the ductus venosus were successfully obtained in all examinations. The maximum velocity tracing had a characteristic pattern similar to that in the IVC, reflecting ventricular systole, ventricular diastole, and atrial systole (fig 2A). Vmin corresponded to the atrial systole. By contrast to the IVC, reversed flow was never seen in the ductus venosus in normal fetuses. The time relation to the heart cycle was confirmed in 12 cases by a simultaneous recording of the ductus venosus and the IVC. Data from the maximum velocity tracings fitted a linear regression analysis. Vpeak had a mean of 65 cm/s in week 18 and increased only slightly to 75 cm/s by week 40. Although
Fig 2-Ductus venosus velocimetry by doppler sonography. A: Typical normal tracing, week 29 of gestation; VS=ventricular systole, VD=ventricu!ar diastole, AS= atriasystole. B: fetal supraventricular tachycardia, week 23. C: fetal congestive heart failure, week 29. atrial systole reduced velocity by about 25 cm/s during a short portion of the cycle, it had little effect on the V., which remained close to the V peak throughout the second half of pregnancy (fig 3). We observed reversed blood flow through the ductus venosus during atrial systole in a fetus with supraventricular tachycardia (220 bpm) during week 23 of gestation (fig 2B). Synchronous pulsatile changes were recorded in the
umbilical vein. When the heart rate returned to normal, reversed flow was no longer observed (fig 2B) and the Vta in
1414
diameter, velocity profile, and other haemodynamic properties, a simplified model may be applicable for clinical purposes. Reduction or inversion of the ductus venosus flow during atrial systole (V min) could indicate altered pressure during atrial systole or could be an early sign of reduced umbilical-atrial pressure gradient, as seen in our 2 cases (fig 2 B, C). Reversed ductus venosus flow may explain the previously reported pulsations in the umbilical vein.19 An overall reduction in velocity would be a more serious sign, implying reduced transport of oxygenated blood to the foramen ovale. V peak may indicate how far the fetus manages to build up the necessary ductus venosus velocity, and Vta may roughly estimate the proportion of ductus venosus flow that reaches this velocity. In our case of congestive heart
failure, high-velocity holosystolic tricuspid regurgitation may have been
important
the ductus
Fig 3-Ductusvenosustime-averaged maximum blood velocity
(Vta) in weeks 18-40. Linear regression with mean and 95% confidence Interval of 184 observations x-x= case of supraventricuar tachycardia before and after conversion to normal rhythm. *=case of congestive heart failure
the ductus
venosus
increased
by 50% from
26
cm/s to
38
cm/s (fig 3). In another case,
a
twin fetus had
section.
Discussion
Despite its small size the ductus venosus could readily be identified, especially when colour doppler imaging was added. The maximum velocity tracing, which shows no reversed flow but does reflect atrial systole, is typical of the and should normally not be confused with of tracings neighbouring veins such as the IVC. With colour doppler we could confirm that in the human fetus the ductus venosus blood flow is directed towards the foramen ovale. A high momentum is probably necessary for the oxygenated blood in the ductus venosus to maintain its direction and travel all the way to the foramen ovale while avoiding extensive mixing. We found very high velocities in the ductus venosus, similar to those otherwise found on the arterial side. The umbilical vein blood already has a mean velocity of 15 cm/s before it enters the ductus venosus.18 To accelerate the blood, a pressure gradient is needed. For the ductus venosus, the pressure gradient is found between the umbilical vein and the atrium. Is the reported human umbilical venous pressure of 5 mm Hg15,16 sufficient to produce the high velocities recorded? A pressure of 15 mm Hg, as found in fetal lambs,’ is more likely to be sufficient. Nature seems to regulate this gradient by a "physiological stenosis", the ductus venosus. Whereas the fetus and its vessels grow steadily, the ductus venosus remains narrow, not exceeding 2 mm. Thus, it forms a high-velocity jet throughout the pregnancy. Does sonography of the ductus venosus provide any diagnostic possibilities? Aside from abnormalities in ductus
venosus
changing atrial pressure and velocity with a general offset
distorting (figs 2C, 3). Physiologists such as Barcroft6 and Dawes’ long ago pointed out that the ductus venosus is an important regulator of fetal circulation. Today the ductus venosus can regularly be identified by sonographic methods. Such studies have diagnostic potential in disorders of the fetal circulation and deserve closer attention from clinicians.
congestive heart failure
(hydrops, cardiomegaly, reduced ventricular excursions, a high velocity holosystolic tricuspid regurgitation, and umbilical venous pulsation) during week 29 owing to fetofetal transfusion. The ductus venosus flow was grossly distorted by reversed flow during atrial systole (fig 2C) and the Vta was low (fig 3). The fetus also had signs of a brain-sparing effect shown by a reduced pulsatility index of the middle cerebral artery. The baby was saved by caesarean
in
venosus
REFERENCES
Reynolds SR. Embryonic development in the human of the sphincter of the ductus venosus. Anat Rec 1953; 115: 151-73. 2. Barclay AE, Franklin KJ, Prichard MM. The mechanism of closure of the ductus venosus. Br J Radiol 1942; 15: 66-71. 3. Meyer WW, Lind J. The ductus venosus and the mechanism of its closure. Arch Dis Child 1966; 41: 597-605. 4. Edelstone DI, Rudolph AM, Heymann MA. Liver and ductus venosus blood in fetal lambs in utero. Circ Res 1978; 42: 426-33. 5. Edelstone DI. Regulation of blood flow through the ductus venosus. J Dev Physiol 1980; 2: 219-38. 6. Barcroft J. Researches on prenatal life. Oxford: Blackwell Scientific Publications, 1946. 7. Dawes GS. Foetal and neonatal physiology. Chicago: Year Book Medical Publishers, 1968. 8. Behrman RE, Lees MH, Peterson EN, DeLannoy CW, Seeds AE. Distribution of the circulation in the normal and asphyxiated fetal primate. Am J Obstet Gynecol 1970; 108: 956-69. 9. Edelstone DI, Rudolph AM. Preferential streaming of ductus venosus blood to the brain and heart in fetal lambs. Am J Physiol 1979; 237: 1. Chako AW,
H724-29. 10. Dawes GS. The umbilical circulation. Am J Obstet Gynecol 1984; 84: 1634-48. 11. Barclay AE, Franklin KJ, Prichard MM. The foetal circulation and cardiovascular system, and the changes that they undergo at birth. Oxford: Blackwell Scientific Publications Ltd, 1944. 12. Chinn DH, Filly RA, Callan PW. Ultrasonic evaluation of fetal umbilical and hepatic vascular anatomy. Radiology 1982; 144: 153-57. 13. Staudach A. Sectional fetal anatomy in ultrasound. Heidelberg: SpringerVerlag, 1987. 14. Champetier J, Yver R, Tomasella T. Functional anatomy of the liver of the human fetus: applications to ultrasonography. Surg Radiol Anat 1989; 11: 53-62. 15. Nicolini U, Talbert DG, Fisk NM, Rodeck CH. Pathophysiology of pressure changes during intrauterine transfusion. Am J Obstet Gynecol
1989; 160: 1139-45. 16. Weiner CP, Heilskov J, Plezer G, Grant S, Wenstrom K, Williamson RA. Normal values for human umbilical venous and amniotic fluid pressures and their alteration by fetal disease. Am J Obstet Gynecol 1989; 161: 714-17. 17. Reed KL, Appleton CP, Anderson CF, Shenker L, Sahn DJ. Doppler studies of vena cava flows in human fetuses. Circulation 1990; 81: 498-505. 18. Eik-Nes SH, Marsál K. Noninvasive measurement of blood flow in human fetal aorta and umbilical vein. In: Orlandi C, Polani P, Bovicelli L, eds. Recent advances in prenatal diagnosis. Chichester: John Wiley & Sons, 1981: 113-19. 19. Gudmundsson S, Huhta JC, Wood DC, Tulzer G, Cohen AW, Weiner S. Venous doppler ultrasonography in the fetus with nonimmune hydrops. Am J Obstet Gynecol 1991; 164: 33-37.
