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Changes in intracardiac Doppler blood flow velocities in fetuses with absent umbilical artery diastolic flow
Changes in intracardiac Doppler blood flow velocities in fetuses with absent umbilical artery diastolic flow Kathryn L. Reed, M.D., Caroline F. Anderson, R.D.M.S., and Lewis Shenker, M.D.
Tucson, Arizona Umbilical artery Doppler blood flow velocity studies were used to identify 14 fetuses with absent flow during diastole to determine the significance of absent umbilical artery diastolic flow. Outcomes of these fetuses were recorded, and the associated intracardiac Doppler changes were identified in 12 of them. Maximal and mean intracardiac flow velocities were measured, and volume flows through the right (tricuspid valve, pulmonary valve) and left (mitral valve, aortic valve) sides of the heart were compared. Ratios of intracardiac peak flow velocity in late diastole to peak flow velocity in early diastole were calculated. Eleven fetuses had intrauterine growth retardation, and four had multiple congenital anomalies. Fetuses with no diastolic flow in the umbilical artery had increased volume flow across the tricuspid and pulmonary valves compared with normal fetuses of similar weights. The ratio of right-sided to left-sided volume flow in the heart (2.15: 1) was increased compared with values in normal fetuses (1.33: 1, p < 0.01 ). The ratio of late diastolic to early diastolic peak flow velocities across the mitral valve was decreased (p < 0.01). Absent umbilical artery diastolic flow is associated with increased tricuspid and pulmonary valve volume flow anq changes in mitral flow velocity patterns, which suggests that there are alterations in left ventricular h,mction. (AM J OBSTET GYNECOL 1987;157:774-9.)
Key words: Fetal heart, Doppler
Doppler investigations of the umbilical artery have been reported to identify fe~uses at increased risk for poor fetal outcome.'·• Normally, flow through the um bilical artery occurs in all phases of the cardiac cycle partly because of the low resistance of the placental circulation (Fig. 1).'·• Increased ratios of umbilical ar tery systolic to diastolic flow detected by Doppler in vestigation have been associated with increased peri natal morbidity and mortality and intrauterine growth retardation.'·• These studies attribute poor fetal out come to placental vascular changes; however, exami nations of the contribution of the fetal heart to the abnormal waveform and poor fetal outcome have not been performed. Placental vasculature in fetuses with iinrauterine growth retardation has been reported to have increased resistance!·' This increase in afterload for the fetal heart may result in changes that are de tectable in utero. Studies of intracardiac physiology in the human fetus witht Doppler are now possible.0·10 Studies in normal fetal hearts indicate that volume flow is increased ~hrough the fetal right heart compared with the left From the Department of Obstetrics and Gynecology, Arizona Health Sciences Center. Supported in part by a grant from the American Heart Assodation, Arizona affiliate. Presented at the Seventh Annual Meeting of The Society of Perinatal Obstetricians, Lake Buena Vista, Florida, February 5-7, 1987. Reprint requests: Kathryn L. Reed, M.D., Department of Obstetrics and Gynecology, 1501 N. Campbell Ave., Tucson, AZ 85724.
774
heart."· 8 • 9 Fetal intracardiac diastolic Doppler flow ve locity waveforms reveal a high peak during late diastole (after atrial contraction) compared with the peak dur ing early diastole. 7• 8 The purpose of this study was to examine fetuses with no umbilical artery Doppler blood flow velocity during diastole, an extreme example of umbilical artery Doppler abnormality. We also studied the intracardiac Doppler flow velocities in these fetuses to document the changes in cardiovascular disease associated with absent umbilical artery diastolic flow.
Material and methods Fetuses were examined with ultrasound for indica tions of a hypertensive disorder of pregnancy, sus pected growth retardation, or suspected fetal anomaly. Permission was obtained from each mother to perform Doppler studies. Approval for this project had been obtained from the Human Subjects Committee. Standard ultrasound measurements were obtained, including biparietal diameter, femljr length, abdominal diameters, and estimated amniotic fluid volume. Pla cental location was identified, and general fetal anat omy was assessed. The fetal heart was examined in detail, including four-chamber, short-axis/great vessel, long-axis/great vessel, and arch (aortic and pulmonary artery) views. Cardiac valve diameters were measured with two-dimensional images. Umbilical artery pulsed Doppler waveforms were re corded from at least four regions with 10 beats each.
Changes in fetal intracardiac Doppler blood flow
Volume 157 Numbe r 3
775
•
•
•
•
artery and vein in a normal fetus. Fig. 1. Dopple r flow velocity tracing of the umbilical
•
•
•
•
•
•
•
•• j
•
and vein in a fetus with absent diastolic Fig. 2. Dopple r flow velocity tracing of the umbilical artery after each peak. Fluctua tions in venous flow umbilical artery blood flow. Velocity decrea ses to zero ent. movem or velocity are not caused by fetal breath ing
Fetuses were includ ed in the study if no umbilical artery flow was presen t during diastole (Fig. 2). Pulsed Doppl er investigations of the intrac ardiac chamb ers and great vessels were perfor med as previ ously descri bed. 6 With two-di mensi onal guidan ce, the pulsed Doppl er gate was placed immed iately distal to the valve leaflets of the cardia c region being sampl ed. The direct ion of blood flow was estima ted to be per pendic ular to the valve anulus . Velocity measu remen ts
were accept ed if the angle of insona tion was <30 de grees from the estima ted direct ion of blood flow. Max imal and mean velocity measu remen ts were obtain ed from page print outpu ts from a strip chart record er. Maximal velocity was measu red from the zero line to the highes t point of the velocity peak. Temp oral mean velocity was calcul ated by planim eterin g the area be neath the gray scale spectr al velocity display and divid . ing by the time over which the velocity was traced
776
Reed, Anderson, and Shenker
September 1987 Am J Obstet Gynecol
Table I. Tricuspid and mitral valve values (mean ± SEM) Normal 6 · 7 (n = 47)
Tricuspid Maximal velocity (em/sec) Mean velocity (em/sec) Diameter (mm) Volume flow (mllkg/min) A-to-E ratio Mitral Maximal velocity (em/sec) Mean velocity (em/sec) Diameter (mm) Volume flow (ml/kg/min) A-to-E ratio A
=
Peak flow velocity during late diastole; E
51 12 8.0 307 1.29
± 4 ± l
± 0.5 ± 30 ± 0.04
47 ± ll ± 6.6 ± 232 ± 1.35 ±
=
4 l
0.4 25 0.01
No diastolic flow
p
(n = 12)
42 13 9.5 476 1.22 34 10 7.7 232 1.00
± 2
<0.001 <0.05 NS <0.05 NS
± l
± 0.6
± 15 ± 0.04
± 3 ±
<0.001 NS NS NS <0.01
2
± 0.4
± ll ± 0.04
peak flow velocity during early diastole; NS
=
not significant.
Table II. Pulmonary and aortic valve values (mean ± SEM) Normal 6 •9 (n = 32)
Pulmonary Maximal velocity (em/sec) Mean velocity (em/sec) Diameter (mm) Volume flow (mllkg/min) Aorta Maximal velocity (em/sec) Mean velocity (em/sec) Diameter (mm) Volume flow (ml/kg/min)
No diastolic flow (n
=
10)
60 16 7.6 312
± ± ± ±
4 2 0.3 11
56 18 8.0 450
± ± ± ±
2 2 0.3 ll
70 18 6.7 250
± ± ± ±
3 2 0.2 9
55± 13 ± 6.6 ± 222 ±
3 2 0.2 9
Volume flow was calculated by multiplying mean ve locity by the area ('IT r 2 ), through which blood was flow ing. Neonatal weights were used for calculating volume flow. Two-dimensional and Doppler measurements ob tained from patients in the study were compared with those of normal fetuses of similar weights, which have been reported elsewhere. 6 • 7 • 9 Values reported are mean ± SEM, except where otherwise noted. The instrument used was a 3.5 MHz scanner with pulsed Doppler capability. According to the manufac turer's specifications, fetuses were exposed to <46 mW/cm 2 ultrasound power density. Pregnancies were managed without relying on Doppler information. The outcomes of the fetuses were recorded, including method and reason for delivery, weight, Apgar scores, admission to the intensive care unit, and presence of congenital anomalies. The statistical method used was Student's t test for unpaired values, with significance at 0.05. Results
Fourteen fetuses were included in this series, with intracardiac studies in 12 fetuses. Maternal age was 24.6 ± 5.2 (mean ± SD) years, gravidity was 2.4 ± 1.7, and parity was 0.9 ± l.l. Hypertensive disorders
p NS
<0.01
NS
<0.01 <0.001 <0.001
NS NS
complicated 71% of the pregnancies, and fetal anom alies were suspected in 29%. Amniotic fluid volume was decreased or absent in 57%. Vaginal deliveries occurred in 43% of the patients; in only one case was this a vertex vaginal delivery of a live infant and consisted of midforceps for fetal distress. Cesarean sections were performed in eight of 14 (57%), in each case for fetal distress, defined by the presence of late decelerations detected with electronic fetal mon itoring. Four (29%) fetuses died in utero, three with known anomalies (trisomy 13, suspected trisomy 13, and trisomy 21); one mother of an otherwise normal fetus refused cesarean section with late decelerations with electronic fetal monitoring. Pericardia! or pleural effusions were present in four fetuses. In total, four (29%) of the fetuses had multiple congenital anomalies, including the trisomic fetuses, and one had hypoplastic lungs and polycystic kidneys. Two neonates died, one of multiple congenital anomalies and one of unknown causes. All live fetuses were admitted to the neonatal intensive care unit. Eleven (78%) were growth-retarded by institutional standards. Two of three fetuses without growth retardation were anomalous (one with cystic hygromas and trisomy 21 and one with polycystic kid neys). The total perinatal mortality was 42%. The mean fetal biparietal diameter was 6.9 ± 1.2 em
Changes in fetal intracardiac Doppler blood flow
Volume 157 Number 3
· .i.
•
777
•
.
t
Fig. 3. Doppler flow velocity tracing across the mitral valve in a normal fetus. Two peaks are normally present during diastolic flow, one in early diastole (E) and one in later diastole (A). In the normal human fetus, the A is usually higher than the E, resulting in an A-to-E ratio of > l.
•
•
•
•
•
• • •
~=\~ 1
..\·
I
Fig. 4. Doppler flow velocity tracing across the mitral valve in a fetus with absent umbilical artery diastolic flow. A-to-E ratio is
(mean ± SD), mean fetal femur length was 5.2 ± 1.0 em, and mean estimated gestational age at diag nosis was 32 ± 5 weeks. Deliveries or fetal death oc curred an average of 6 days after diagnosis (range, 0 to 27 days). Mean neonatal weight was 1227 ± 255 gm, with a !-minute Apgar score of 5 ± 3 and a 5-minute Apgar score of 7 ± 3.
The two-dimensional ultrasound and Doppler results are shown in Tables I and II. Tricuspid and pulmonary volume flows were increased compared with normal values. The ratio of peak flow velocity during late diastole to peak flow velocity during early diastole was decreased (Table I, Figs. 3 and 4). Tricuspid valve measurements (maximal velocity, p < 0.05; mean
778
Reed, Anderson, and Shenker
September 1987 Am J Obstet Gynecol
Fig. 5. Volume flow in the normal fetal heart. Numbers rep resent milliliters per kilogram per minute. 307 = Tricuspid valve, 312 = pulmonary valve, 232 = mitral valve, and 250 = aortic valve.
Fig. 6. Volume flow in the heart of a fetus with absent diastolic flow in the umbilical artery. Numbers represent milliliters per kilogram per minute. 476 = Tricuspid valve, 450 = pul monary valve, 232 = mitral valve, and 222 = aortic valve.
velocity, p < 0.01; diameter, p < 0.05; and volume flow, p < 0.05) were greater than those of the mitral valve in the abnormal group. Pulmonary valve mea surements (mean velocity, p < 0.00 I; diameter, p < O.OI; and volume flow, p < O.OOI) were greater than those of the aortic valve in the abnormal group. The ratio of tricuspid valve to mitral valve volume flow was increased (2.32 ± 0.03: I) compared with normal (1.37 ± 0.05: I, p < O.OI). The ratio of pulmonary valve to aortic valve flow was also increased (2.I5 ± 0.03: I) compared with normal (1.33 ± 0.02: I, p < 0.001, Figs. 5 and 6). In individual fetuses no significant differences were found when tricuspid valve volume flows were compared with pulmonary valve volume flows (right-sided flows) and mitral valve volume flows were compared with aortic valve volume flows (left sided flows).
form without flow during diastole, which is therefore highly abnormal. In this report, umbilical artery Doppler flow velocity studies were used to identify fetuses with absent blood flow velocity during diastole. Perinatal morbidity (100%) and mortality (42%) were markedly abnormal in this group~ Intracardiac Doppler studies were per formed in these fetuses to examine the physiologic changes in the fetal heart that accompany these ab normal umbilical flow velocity patterns. Volume flows were increased on the right side of the fetal heart (tri cuspid and pulmonary artery valves) compared with the left side of the heart (mitral and aortic valves) and compared with normal fetuses of similar weights. Previous studies of intracardiac volume flow in nor mal fetuses have shown that the fetal right heart volume flows are greater than left heart volume flows by a ratio of 1.3: 1. 6 • 8 In this study we found an even greater increase in the right heart flow, with a tricuspid valve to-mitral valve volume flow ratio of 2.32: I and a pul monary valve-to-aortic valve volume flow ratio of 2.I5 : I. Left heart volume flow was unchanged com pared with normal. In addition, a decrease in the ratio oflate diastolic peak flow velocity to early diastolic peak flow velocity in the mitral valve suggested that there may also be a change in the diastolic function in the fetal left ventricle.
Comment
Changes in the pattern of blood flow velocity in the umbilical artery are thought to reflect placental func tion and fetal well-being.'·• In the normal fetus, the ratio of systolic to diastolic flow decreases with advanc ing gestational age. If this trend is reversed and the ratio is increased, an abnormality of the fetoplacental vasculature may be present. An extreme example of this is the umbilical artery Doppler flow velocity wave-
Volume i57 Number 3
Our findings regarding fetal outcome are consistent with previous investigators who showed almost identical data (cesarean section for fetal distress, 75%; perinatal mortality, 40% 11 ) in fetuses with no flow in the umbilical artery during diastole. Our report is the first investi gation to our knowledge that attempts to examine the pathologic mechanism that may be responsible for these outcomes. One possible explanation for the intracardiac changes we report is that developing hypoxia results in dilation of the cerebral vasculature, as evidenced in directly by fetal cerebral artery studies. These studies indicate that a decrease in the ratio of systolic to dia stolic measurements in the cerebral arteries is associ ated with the development of fetal growth retarda tion.'2 In addition, in hypoxic neonates, the pulmonary vasculature constricts while the ductus enlarges. To in crease volume blood flow to the brain from the left ventricle, in the face of a dilated ductus supplied by the right ventricle, volume flow must increase across both ventricles. This interpretation is consistent with the findings of our study, with increased volume flow through the right side of the heart and increased com bined ventricular output. ' The alteration in flow across the mitral valve with a shift to more flow in early diastole is interesting. Pre vious investigators have shown that the normal fetal ventricle is noncompliant"; Doppler investigations have shown that the fetal diastolic function changes with advancing gestational age in a pattern consistent with gradually increasing compliance. 7 ihe changes in mitral flow velocity waveforms seen· in this study of abnormal fetuses may be based on a relative increase in left ventricular volume, which results in dilation and increased compliance. Increases in right and left ven tricular diameters have been reported in the presence of fetal growth failure. 14 We conclude from this study that the presence of umbilical artery blood flow velocity waveforms with no flow during diastole is associated with an increase in perinatal morpidity and mortality. Alterations in intra cardiac Doppler flow velocity waveforms are detectable in these fetuses. These changes may· explain the patho-
Changes in fetal intracardiac Doppler blood flow
779
physiology in the cardiovascular system that accom panies fetal growth failure and fetal distress. REFERENCES 1. Trudinger BJ, Giles WB, Cook CM. Flow velocity wave forms in the maternal uteroplacental and fetal umbilical placental circulation. AM j 0BSTET GYNECOL 1985;152: 155-63. 2. Trudinger BJ, Giles WB, Cook CM, Bombardierij, Col lins L. Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance. Br J Obstet Gy naecol 1985;92:23-30. 3. Giles WB, Trudinger BJ, Baird PJ. Fetal umbilical artery flow velocity waveforms and placental resistance: patho logical correlation. Br J Obstet Gynaecol 1985;92:31-8. 4. Fleischer A, Schulman H, Farmakides G, Bracero L, Blatt ner P, Randolph G. Umbilical velocity wave ratios in in trauterine growth retardation. AM J OBSTET GYNECOL 1985;151:502-6. 5. Kleinman CS, CopelJA, Weinstein EM, Santulli TV, Hob bins JC. In utero diagnosis and treatment of fetal supra ventricular tachycardia. Semin Perinatol 1985;9: 113-29. 6. Reed KL, Meijboom EJ, Sahn DJ, Scagnelli SA, Valdes Cruz LM, Shenker L. Cardiac Doppler flow velocities in human fetuses. Circulation 1986;73:41-6. 7. Reed KL, Sahn DJ, Scagnelli SA, Anderson CF, Shenker L. Doppler echocardiograp)lic studies of diastolic function in the human fetal heart: changes during ges tation.] Am Coli Cardiol1986;8:391-5. 8. Kenny JF, Plappert T, Doubilet P, et a!. Changes in intra cardiac blood flow velocities and right and left ventricular stroke volumes with gestational age in the normal human fe~us: a prospective Doppler echocardiographic study. Circulation 1986;74: 1208-16. 9. Reed KL, Anderson CF, Shenker L. Fetal pulmonary ar tery and aorta: two-dimensional and Doppler echocar diography. Obstet Gynecol 1987;69: 175-8. 10. Huhta JC, Moise KM, Fisher DJ, Sharif DS, Wasser strum N, Martin C. Detection and quantitation of con striction of the fetal ductus arteriosus by Doppler echo cardiography. Circulation 1987;75:406-12. 11. Rochelson B, Schulman H, Farmakides G, et a!. The sig nificance of absent end-diastolic velocity in umbilical ar tery velocity waveforms. AM J 0BSTET GYNECOL 1987; 156:1213-8. 12. Wladimiroff JW, Tonge HM, Stewart PA. Doppler ultra sound assessment of cerebral blood flow in the human fetus. Br J Obstet Gynaecol 1986;93:471-5. 13. Romero T, Covell J, Friedman WF. A comparison of pressure-volume relations of the fetal, newborn and adult heart. Am J Physiol 1972;222: 1285-90. J4. DeVore GR, Siassi B, Platt LD. Cardiac ventricular func tion in the human fetus: real-time-directed M-mode echo cardiographic assessment in health and disease. J Ultra sound Med (Suppl) 1983;2:102.
Tucson, Arizona Umbilical artery Doppler blood flow velocity studies were used to identify 14 fetuses with absent flow during diastole to determine the significance of absent umbilical artery diastolic flow. Outcomes of these fetuses were recorded, and the associated intracardiac Doppler changes were identified in 12 of them. Maximal and mean intracardiac flow velocities were measured, and volume flows through the right (tricuspid valve, pulmonary valve) and left (mitral valve, aortic valve) sides of the heart were compared. Ratios of intracardiac peak flow velocity in late diastole to peak flow velocity in early diastole were calculated. Eleven fetuses had intrauterine growth retardation, and four had multiple congenital anomalies. Fetuses with no diastolic flow in the umbilical artery had increased volume flow across the tricuspid and pulmonary valves compared with normal fetuses of similar weights. The ratio of right-sided to left-sided volume flow in the heart (2.15: 1) was increased compared with values in normal fetuses (1.33: 1, p < 0.01 ). The ratio of late diastolic to early diastolic peak flow velocities across the mitral valve was decreased (p < 0.01). Absent umbilical artery diastolic flow is associated with increased tricuspid and pulmonary valve volume flow anq changes in mitral flow velocity patterns, which suggests that there are alterations in left ventricular h,mction. (AM J OBSTET GYNECOL 1987;157:774-9.)
Key words: Fetal heart, Doppler
Doppler investigations of the umbilical artery have been reported to identify fe~uses at increased risk for poor fetal outcome.'·• Normally, flow through the um bilical artery occurs in all phases of the cardiac cycle partly because of the low resistance of the placental circulation (Fig. 1).'·• Increased ratios of umbilical ar tery systolic to diastolic flow detected by Doppler in vestigation have been associated with increased peri natal morbidity and mortality and intrauterine growth retardation.'·• These studies attribute poor fetal out come to placental vascular changes; however, exami nations of the contribution of the fetal heart to the abnormal waveform and poor fetal outcome have not been performed. Placental vasculature in fetuses with iinrauterine growth retardation has been reported to have increased resistance!·' This increase in afterload for the fetal heart may result in changes that are de tectable in utero. Studies of intracardiac physiology in the human fetus witht Doppler are now possible.0·10 Studies in normal fetal hearts indicate that volume flow is increased ~hrough the fetal right heart compared with the left From the Department of Obstetrics and Gynecology, Arizona Health Sciences Center. Supported in part by a grant from the American Heart Assodation, Arizona affiliate. Presented at the Seventh Annual Meeting of The Society of Perinatal Obstetricians, Lake Buena Vista, Florida, February 5-7, 1987. Reprint requests: Kathryn L. Reed, M.D., Department of Obstetrics and Gynecology, 1501 N. Campbell Ave., Tucson, AZ 85724.
774
heart."· 8 • 9 Fetal intracardiac diastolic Doppler flow ve locity waveforms reveal a high peak during late diastole (after atrial contraction) compared with the peak dur ing early diastole. 7• 8 The purpose of this study was to examine fetuses with no umbilical artery Doppler blood flow velocity during diastole, an extreme example of umbilical artery Doppler abnormality. We also studied the intracardiac Doppler flow velocities in these fetuses to document the changes in cardiovascular disease associated with absent umbilical artery diastolic flow.
Material and methods Fetuses were examined with ultrasound for indica tions of a hypertensive disorder of pregnancy, sus pected growth retardation, or suspected fetal anomaly. Permission was obtained from each mother to perform Doppler studies. Approval for this project had been obtained from the Human Subjects Committee. Standard ultrasound measurements were obtained, including biparietal diameter, femljr length, abdominal diameters, and estimated amniotic fluid volume. Pla cental location was identified, and general fetal anat omy was assessed. The fetal heart was examined in detail, including four-chamber, short-axis/great vessel, long-axis/great vessel, and arch (aortic and pulmonary artery) views. Cardiac valve diameters were measured with two-dimensional images. Umbilical artery pulsed Doppler waveforms were re corded from at least four regions with 10 beats each.
Changes in fetal intracardiac Doppler blood flow
Volume 157 Numbe r 3
775
•
•
•
•
artery and vein in a normal fetus. Fig. 1. Dopple r flow velocity tracing of the umbilical
•
•
•
•
•
•
•
•• j
•
and vein in a fetus with absent diastolic Fig. 2. Dopple r flow velocity tracing of the umbilical artery after each peak. Fluctua tions in venous flow umbilical artery blood flow. Velocity decrea ses to zero ent. movem or velocity are not caused by fetal breath ing
Fetuses were includ ed in the study if no umbilical artery flow was presen t during diastole (Fig. 2). Pulsed Doppl er investigations of the intrac ardiac chamb ers and great vessels were perfor med as previ ously descri bed. 6 With two-di mensi onal guidan ce, the pulsed Doppl er gate was placed immed iately distal to the valve leaflets of the cardia c region being sampl ed. The direct ion of blood flow was estima ted to be per pendic ular to the valve anulus . Velocity measu remen ts
were accept ed if the angle of insona tion was <30 de grees from the estima ted direct ion of blood flow. Max imal and mean velocity measu remen ts were obtain ed from page print outpu ts from a strip chart record er. Maximal velocity was measu red from the zero line to the highes t point of the velocity peak. Temp oral mean velocity was calcul ated by planim eterin g the area be neath the gray scale spectr al velocity display and divid . ing by the time over which the velocity was traced
776
Reed, Anderson, and Shenker
September 1987 Am J Obstet Gynecol
Table I. Tricuspid and mitral valve values (mean ± SEM) Normal 6 · 7 (n = 47)
Tricuspid Maximal velocity (em/sec) Mean velocity (em/sec) Diameter (mm) Volume flow (mllkg/min) A-to-E ratio Mitral Maximal velocity (em/sec) Mean velocity (em/sec) Diameter (mm) Volume flow (ml/kg/min) A-to-E ratio A
=
Peak flow velocity during late diastole; E
51 12 8.0 307 1.29
± 4 ± l
± 0.5 ± 30 ± 0.04
47 ± ll ± 6.6 ± 232 ± 1.35 ±
=
4 l
0.4 25 0.01
No diastolic flow
p
(n = 12)
42 13 9.5 476 1.22 34 10 7.7 232 1.00
± 2
<0.001 <0.05 NS <0.05 NS
± l
± 0.6
± 15 ± 0.04
± 3 ±
<0.001 NS NS NS <0.01
2
± 0.4
± ll ± 0.04
peak flow velocity during early diastole; NS
=
not significant.
Table II. Pulmonary and aortic valve values (mean ± SEM) Normal 6 •9 (n = 32)
Pulmonary Maximal velocity (em/sec) Mean velocity (em/sec) Diameter (mm) Volume flow (mllkg/min) Aorta Maximal velocity (em/sec) Mean velocity (em/sec) Diameter (mm) Volume flow (ml/kg/min)
No diastolic flow (n
=
10)
60 16 7.6 312
± ± ± ±
4 2 0.3 11
56 18 8.0 450
± ± ± ±
2 2 0.3 ll
70 18 6.7 250
± ± ± ±
3 2 0.2 9
55± 13 ± 6.6 ± 222 ±
3 2 0.2 9
Volume flow was calculated by multiplying mean ve locity by the area ('IT r 2 ), through which blood was flow ing. Neonatal weights were used for calculating volume flow. Two-dimensional and Doppler measurements ob tained from patients in the study were compared with those of normal fetuses of similar weights, which have been reported elsewhere. 6 • 7 • 9 Values reported are mean ± SEM, except where otherwise noted. The instrument used was a 3.5 MHz scanner with pulsed Doppler capability. According to the manufac turer's specifications, fetuses were exposed to <46 mW/cm 2 ultrasound power density. Pregnancies were managed without relying on Doppler information. The outcomes of the fetuses were recorded, including method and reason for delivery, weight, Apgar scores, admission to the intensive care unit, and presence of congenital anomalies. The statistical method used was Student's t test for unpaired values, with significance at 0.05. Results
Fourteen fetuses were included in this series, with intracardiac studies in 12 fetuses. Maternal age was 24.6 ± 5.2 (mean ± SD) years, gravidity was 2.4 ± 1.7, and parity was 0.9 ± l.l. Hypertensive disorders
p NS
<0.01
NS
<0.01 <0.001 <0.001
NS NS
complicated 71% of the pregnancies, and fetal anom alies were suspected in 29%. Amniotic fluid volume was decreased or absent in 57%. Vaginal deliveries occurred in 43% of the patients; in only one case was this a vertex vaginal delivery of a live infant and consisted of midforceps for fetal distress. Cesarean sections were performed in eight of 14 (57%), in each case for fetal distress, defined by the presence of late decelerations detected with electronic fetal mon itoring. Four (29%) fetuses died in utero, three with known anomalies (trisomy 13, suspected trisomy 13, and trisomy 21); one mother of an otherwise normal fetus refused cesarean section with late decelerations with electronic fetal monitoring. Pericardia! or pleural effusions were present in four fetuses. In total, four (29%) of the fetuses had multiple congenital anomalies, including the trisomic fetuses, and one had hypoplastic lungs and polycystic kidneys. Two neonates died, one of multiple congenital anomalies and one of unknown causes. All live fetuses were admitted to the neonatal intensive care unit. Eleven (78%) were growth-retarded by institutional standards. Two of three fetuses without growth retardation were anomalous (one with cystic hygromas and trisomy 21 and one with polycystic kid neys). The total perinatal mortality was 42%. The mean fetal biparietal diameter was 6.9 ± 1.2 em
Changes in fetal intracardiac Doppler blood flow
Volume 157 Number 3
· .i.
•
777
•
.
t
Fig. 3. Doppler flow velocity tracing across the mitral valve in a normal fetus. Two peaks are normally present during diastolic flow, one in early diastole (E) and one in later diastole (A). In the normal human fetus, the A is usually higher than the E, resulting in an A-to-E ratio of > l.
•
•
•
•
•
• • •
~=\~ 1
..\·
I
Fig. 4. Doppler flow velocity tracing across the mitral valve in a fetus with absent umbilical artery diastolic flow. A-to-E ratio is
(mean ± SD), mean fetal femur length was 5.2 ± 1.0 em, and mean estimated gestational age at diag nosis was 32 ± 5 weeks. Deliveries or fetal death oc curred an average of 6 days after diagnosis (range, 0 to 27 days). Mean neonatal weight was 1227 ± 255 gm, with a !-minute Apgar score of 5 ± 3 and a 5-minute Apgar score of 7 ± 3.
The two-dimensional ultrasound and Doppler results are shown in Tables I and II. Tricuspid and pulmonary volume flows were increased compared with normal values. The ratio of peak flow velocity during late diastole to peak flow velocity during early diastole was decreased (Table I, Figs. 3 and 4). Tricuspid valve measurements (maximal velocity, p < 0.05; mean
778
Reed, Anderson, and Shenker
September 1987 Am J Obstet Gynecol
Fig. 5. Volume flow in the normal fetal heart. Numbers rep resent milliliters per kilogram per minute. 307 = Tricuspid valve, 312 = pulmonary valve, 232 = mitral valve, and 250 = aortic valve.
Fig. 6. Volume flow in the heart of a fetus with absent diastolic flow in the umbilical artery. Numbers represent milliliters per kilogram per minute. 476 = Tricuspid valve, 450 = pul monary valve, 232 = mitral valve, and 222 = aortic valve.
velocity, p < 0.01; diameter, p < 0.05; and volume flow, p < 0.05) were greater than those of the mitral valve in the abnormal group. Pulmonary valve mea surements (mean velocity, p < 0.00 I; diameter, p < O.OI; and volume flow, p < O.OOI) were greater than those of the aortic valve in the abnormal group. The ratio of tricuspid valve to mitral valve volume flow was increased (2.32 ± 0.03: I) compared with normal (1.37 ± 0.05: I, p < O.OI). The ratio of pulmonary valve to aortic valve flow was also increased (2.I5 ± 0.03: I) compared with normal (1.33 ± 0.02: I, p < 0.001, Figs. 5 and 6). In individual fetuses no significant differences were found when tricuspid valve volume flows were compared with pulmonary valve volume flows (right-sided flows) and mitral valve volume flows were compared with aortic valve volume flows (left sided flows).
form without flow during diastole, which is therefore highly abnormal. In this report, umbilical artery Doppler flow velocity studies were used to identify fetuses with absent blood flow velocity during diastole. Perinatal morbidity (100%) and mortality (42%) were markedly abnormal in this group~ Intracardiac Doppler studies were per formed in these fetuses to examine the physiologic changes in the fetal heart that accompany these ab normal umbilical flow velocity patterns. Volume flows were increased on the right side of the fetal heart (tri cuspid and pulmonary artery valves) compared with the left side of the heart (mitral and aortic valves) and compared with normal fetuses of similar weights. Previous studies of intracardiac volume flow in nor mal fetuses have shown that the fetal right heart volume flows are greater than left heart volume flows by a ratio of 1.3: 1. 6 • 8 In this study we found an even greater increase in the right heart flow, with a tricuspid valve to-mitral valve volume flow ratio of 2.32: I and a pul monary valve-to-aortic valve volume flow ratio of 2.I5 : I. Left heart volume flow was unchanged com pared with normal. In addition, a decrease in the ratio oflate diastolic peak flow velocity to early diastolic peak flow velocity in the mitral valve suggested that there may also be a change in the diastolic function in the fetal left ventricle.
Comment
Changes in the pattern of blood flow velocity in the umbilical artery are thought to reflect placental func tion and fetal well-being.'·• In the normal fetus, the ratio of systolic to diastolic flow decreases with advanc ing gestational age. If this trend is reversed and the ratio is increased, an abnormality of the fetoplacental vasculature may be present. An extreme example of this is the umbilical artery Doppler flow velocity wave-
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Our findings regarding fetal outcome are consistent with previous investigators who showed almost identical data (cesarean section for fetal distress, 75%; perinatal mortality, 40% 11 ) in fetuses with no flow in the umbilical artery during diastole. Our report is the first investi gation to our knowledge that attempts to examine the pathologic mechanism that may be responsible for these outcomes. One possible explanation for the intracardiac changes we report is that developing hypoxia results in dilation of the cerebral vasculature, as evidenced in directly by fetal cerebral artery studies. These studies indicate that a decrease in the ratio of systolic to dia stolic measurements in the cerebral arteries is associ ated with the development of fetal growth retarda tion.'2 In addition, in hypoxic neonates, the pulmonary vasculature constricts while the ductus enlarges. To in crease volume blood flow to the brain from the left ventricle, in the face of a dilated ductus supplied by the right ventricle, volume flow must increase across both ventricles. This interpretation is consistent with the findings of our study, with increased volume flow through the right side of the heart and increased com bined ventricular output. ' The alteration in flow across the mitral valve with a shift to more flow in early diastole is interesting. Pre vious investigators have shown that the normal fetal ventricle is noncompliant"; Doppler investigations have shown that the fetal diastolic function changes with advancing gestational age in a pattern consistent with gradually increasing compliance. 7 ihe changes in mitral flow velocity waveforms seen· in this study of abnormal fetuses may be based on a relative increase in left ventricular volume, which results in dilation and increased compliance. Increases in right and left ven tricular diameters have been reported in the presence of fetal growth failure. 14 We conclude from this study that the presence of umbilical artery blood flow velocity waveforms with no flow during diastole is associated with an increase in perinatal morpidity and mortality. Alterations in intra cardiac Doppler flow velocity waveforms are detectable in these fetuses. These changes may· explain the patho-
Changes in fetal intracardiac Doppler blood flow
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physiology in the cardiovascular system that accom panies fetal growth failure and fetal distress. REFERENCES 1. Trudinger BJ, Giles WB, Cook CM. Flow velocity wave forms in the maternal uteroplacental and fetal umbilical placental circulation. AM j 0BSTET GYNECOL 1985;152: 155-63. 2. Trudinger BJ, Giles WB, Cook CM, Bombardierij, Col lins L. Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance. Br J Obstet Gy naecol 1985;92:23-30. 3. Giles WB, Trudinger BJ, Baird PJ. Fetal umbilical artery flow velocity waveforms and placental resistance: patho logical correlation. Br J Obstet Gynaecol 1985;92:31-8. 4. Fleischer A, Schulman H, Farmakides G, Bracero L, Blatt ner P, Randolph G. Umbilical velocity wave ratios in in trauterine growth retardation. AM J OBSTET GYNECOL 1985;151:502-6. 5. Kleinman CS, CopelJA, Weinstein EM, Santulli TV, Hob bins JC. In utero diagnosis and treatment of fetal supra ventricular tachycardia. Semin Perinatol 1985;9: 113-29. 6. Reed KL, Meijboom EJ, Sahn DJ, Scagnelli SA, Valdes Cruz LM, Shenker L. Cardiac Doppler flow velocities in human fetuses. Circulation 1986;73:41-6. 7. Reed KL, Sahn DJ, Scagnelli SA, Anderson CF, Shenker L. Doppler echocardiograp)lic studies of diastolic function in the human fetal heart: changes during ges tation.] Am Coli Cardiol1986;8:391-5. 8. Kenny JF, Plappert T, Doubilet P, et a!. Changes in intra cardiac blood flow velocities and right and left ventricular stroke volumes with gestational age in the normal human fe~us: a prospective Doppler echocardiographic study. Circulation 1986;74: 1208-16. 9. Reed KL, Anderson CF, Shenker L. Fetal pulmonary ar tery and aorta: two-dimensional and Doppler echocar diography. Obstet Gynecol 1987;69: 175-8. 10. Huhta JC, Moise KM, Fisher DJ, Sharif DS, Wasser strum N, Martin C. Detection and quantitation of con striction of the fetal ductus arteriosus by Doppler echo cardiography. Circulation 1987;75:406-12. 11. Rochelson B, Schulman H, Farmakides G, et a!. The sig nificance of absent end-diastolic velocity in umbilical ar tery velocity waveforms. AM J 0BSTET GYNECOL 1987; 156:1213-8. 12. Wladimiroff JW, Tonge HM, Stewart PA. Doppler ultra sound assessment of cerebral blood flow in the human fetus. Br J Obstet Gynaecol 1986;93:471-5. 13. Romero T, Covell J, Friedman WF. A comparison of pressure-volume relations of the fetal, newborn and adult heart. Am J Physiol 1972;222: 1285-90. J4. DeVore GR, Siassi B, Platt LD. Cardiac ventricular func tion in the human fetus: real-time-directed M-mode echo cardiographic assessment in health and disease. J Ultra sound Med (Suppl) 1983;2:102.