Uteroplacental blood flow velocity-time waveforms in normal and complicated pregnancy

Summary. A simple continuous wave Doppler ultrasound system for recording arterial flow velocity waveforms in branches of the uterine artery in the placental bed is described. Twelve normal pregnancies were studied serially from 20 weeks to delivery. The diastolic flow velocity expressed as a percentage of the systolic provides an index of downstream vascular bed resistance and perfusion. This always exceeded 50% in normal pregnancy and there was a small increase with gestational age indicative of a decreasing flow resistance. Of the 91 complicated pregnancies, studied because of potential uteroplacental insufficiency and fetal risk, 25 resulted in the birth of an infant small-for-gestational-age. In 15 the uterine artery flow velocity waveform revealed a pattern of low diastolic flow velocity. It is postulated that these represent a subgroup of growth-retarded fetuses in whom there is reduced uterine artery perfusion. Reduced uterine artery diastolic flow velocity in these patients was associated with reduced umbilical artery diastolic flow velocity on the fetal side of the placenta. In contrast the 10 small-for-gestation infants associated with normal uterine artery waveforms suggest a primary fetal cause. Twelve patients with severe hypertensive disease of pregnancy were studied. Nine were associated with reduced uterine artery diastolic flow velocity (reduced uterine artery perfusion) consistent with vasospasm in the branches of the uterine artery in the placental bed.     

Flow velocity waveforms in the maternal uteroplacental and fetal umbilical placental circulations

A simple continuous-wave Doppler ultrasound system was used to record arterial flow velocity time waveforms from branches of the maternal uterine artery in the placental bed and the fetal umbilical arteries. The systolic-diastolic ratio of flow velocities was measured as an index of peripheral resistance. In normal pregnancy both circulations exhibit high diastolic flow velocities caused by low resistance. The study group consisted of 172 pregnancies with high fetal risk of which 53 resulted in delivery of a small-for-gestational age infant. The last study-to-delivery interval was less than 10 days. In the small-for-gestational age fetuses in whom both umbilical and uterine studies were normal there was good fetal outcome (19 cases). Neonatal morbidity occurred among those with abnormal umbilical studies with low diastolic flow velocities, indicating high resistance. Of these studies there were two subgroups. An abnormal uterine study (13 cases) indicated a primary maternal uteroplacental lesion and a normal study (21 cases) a primary fetal lesion. In cases of severe maternal hypertension, abnormal uterine artery waveforms were associated with abnormal umbilical artery waveforms.     

Umbilical and uterine flow velocity waveforms in pregnancies complicated by major fetal anomalies

A continuous wave Doppler unit was used to obtain umbilical and uterine artery flow velocity waveforms in pregnancies complicated by a major fetal abnormality. A total of 139 examinations were performed on 32 women between 26 to 41 weeks' gestation, and the records were reviewed to determine the changes associated with fetal malformation. The systolic/diastolic (A/B) ratio was used as an index of blood flow resistance in the umbilical artery and the systolic minus diastolic divided by systolic (A-B)/A for the branches of the uterine artery. Seventeen out of 32 patients showed high systolic/diastolic ratio in waveforms taken from the umbilical artery. In 30 out of 32 patients the uterine artery waveform was normal (in two patients the results were equivocal). It appears that a fetal mechanism may determine the changes in the umbilical placental circulation resulting in an umbilical artery pattern of high flow resistance in more than half of the patients with congenital anomalies.     

Umbilical and uterine artery flow velocity waveforms in pregnancy associated with major fetal abnormality

Flow velocity waveforms from the umbilical artery and branches of the uterine artery in the placental bed were recorded using continuous wave Doppler ultrasound. The records of 26 patients with pregnancy complicated by major fetal abnormality were reviewed to determine the changes of a primary fetal disturbance. The systolic/diastolic (A/B) ratio was used as an index of blood flow resistance. In 13 of the 26 patients the umbilical artery waveform systolic/diastolic ratio was high. It is postulated that in these patients there is a process of obliteration of small arteries in the placenta that is triggered by the abnormal fetus. In all patients the uterine artery waveform was normal. In seven of these 13 patients the infant had a birthweight greater than 10th centile. Placental weights were examined. A small placenta expressed as either low weight for gestational age or low placental/fetal weight ratio was associated with a normal umbilical artery waveform. It is suggested that fetuses in these groups have a low growth potential. In contrast a high placental/fetal weight ratio was associated with an abnormal umbilical artery waveform pattern.     

Umbilical and uterine artery flow velocity waveforms in pregnancy associated with major fetal abnormality

Summary. Flow velocity waveforms from the umbilical artery and branches of the uterine artery in the placental bed were recorded using continuous wave Doppler ultrasound. The records of 26 patients with pregnancy complicated by major fetal abnormality were reviewed to determine the changes of a primary fetal disturbance. The systolic/diastolic (A/B) ratio was used as an index of blood flow resistance. In 13 of the 26 patients the umbilical artery waveform systolic/diastolic ratio was high. It is postulated that in these patients there is a process of obliteration of small arteries in the placenta that is triggered by the abnormal fetus. In all patients the uterine artery waveform was normal. In seven of these 13 patients the infant had a birthweight > 10th centile. Placental weights were examined. A small placenta expressed as either low weight for gestational age or low placental/feta1 weight ratio was associated with a normal umbilical artery waveform. It is suggested that fetuses in these groups have a low growth potential. In contrast a high placental/fetal weight ratio was associated with an abnormal umbilical artery waveform pattern.     

Doppler assessment of the cardiac and uteroplacental circulations in normal and complicated pregnancies

Summary. Blood flow velocity waveforms were recorded in four sites in the fetal circulation in a series of 271 normal and 71 complicated pregnancies. The sites were the umbilical artery, the uterine artery branches in the placental bed, and distal to the two arterial valves in the heart. The blood flow through the arterial valves was added to estimate combined cardiac output. Normal ranges for values in all sites were established in our own series, and were similar to other published results. Abnormality of the waveform in the umbilical artery proved the most useful predictor of perinatal morbidity. Reversal of the normal pattern of increasing diastolic flow in the umbilical artery with advancing gestation was an important prognostic finding in the pregnancies studied serially. The combined cardiac output did not fall until late in the course of fetal compromise, and low values were seen only with an abnormal umbilical artery tracing.     

Doppler assessment of the cardiac and uteroplacental circulations in normal and complicated pregnancies

Blood flow velocity waveforms were recorded in four sites in the fetal circulation in a series of 271 normal and 71 complicated pregnancies. The sites were the umbilical artery, the uterine artery branches in the placental bed, and distal to the two arterial valves in the heart. The blood flow through the arterial valves was added to estimate combined cardiac output. Normal ranges for values in all sites were established in our own series, and were similar to other published results. Abnormality of the waveform in the umbilical artery proved the most useful predictor of perinatal morbidity. Reversal of the normal pattern of increasing diastolic flow in the umbilical artery with advancing gestation was an important prognostic finding in the pregnancies studied serially. The combined cardiac output did not fall until late in the course of fetal compromise, and low values were seen only with an abnormal umbilical artery tracing.     

Predictive value of uterine artery velocity waveforms in pregnancies complicated by systemic lupus erythematosus and the antiphospholipid syndrome.

The objective of this study was to see if determination of uterine artery velocity waveforms between 20 and 30 weeks in lupus pregnancy and the antiphospholipid syndrome (APS) have a good predictive value for later fetal distress before labor, intrauterine growth retardation, and preeclampsia. Uterine and umbilical artery blood flow velocity waveforms were determined in 21 pregnancies complicated by systemic lupus erythematosus (SLE): 12 with antiphospholipid antibodies (aPL), 9 without aPL. We also studied 7 pregnancies with APS. This retrospective study was running from January 1st 1986 to July 31st 1991, at the Port-Royal Maternity, Paris, France. Abnormal uterine artery blood flow velocity waveforms were found in 10 out of 28 pregnancies at the first examination performed between 20 and 30 weeks gestational age. All the later adverse fetal and neonatal events were predicted by an abnormal uterine artery blood flow velocity waveform. From the 7 cases of fetal distress diagnosed during pregnancy, 6 were predicted by abnormal uterine waveforms and all of these pregnancies resulted in induced delivery before 32 weeks of gestational age. Twelve pregnancies with aPL and normal uterine artery waveforms were uncomplicated. Only 1 out of 7 pregnancies with abnormal uterine artery waveform and aPL ended without complication. Determination of uterine artery flow velocity waveform is a good adjunct to the management of pregnancies complicated by SLE or aPL. This determination has a better predictive value than the presence of aPL.     

Umbilical artery flow velocity waveforms and placental resistance: the effects of embolization of the umbilical circulation

Embolization of the umbilical placental circulation in fetal lambs was carried out to occlude the small vessels of the placental vascular bed and to observe the effect on the umbilical artery flow and flow velocity waveforms. Thirteen singleton fetuses were studied from day 120 of pregnancy. Embolization was achieved by injecting approximately 9 X 10(6) microspheres of 15 micron diameter into the fetal placental cotyledons along the umbilical arteries over 9 days. Umbilical and uterine flows were measured by radioactive microsphere counting. The umbilical placental resistance was increased (0.25 to 0.35 mm Hg.ml.min-1) by embolization, and there was an increase in the umbilical artery systolic/diastolic ratio. Embolization produced a significant fall in umbilical flow expressed either as total flow (312 to 237 ml.min-1) or when normalized by reference against splanchnic flow (3.36 to 1.53). We conclude that the umbilical artery flow velocity waveform systolic/diastolic ratio measures the reflection coefficient at the peripheral vascular bed (the "resistance vessels") of the placenta.     

Uterine and fetal umbilical artery flow velocity waveforms in normal first trimester pregnancies

In 85 normal singleton pregnancies between 8 and 13 weeks gestation, Doppler flow velocity waveform recordings were attempted from the left and right uterine artery and fetal umbilical artery. Acceptable waveforms were obtained from the uterine arteries in 83 and from the fetal umbilical artery in 61 of the 85 pregnancies. There was virtually no difference between the left and right uterine artery on average. The marked decrease in pulsatility (PI) and resistance (RI) indices from both uterine arteries reflects the ongoing process of secondary trophoblast invasion into the muscular part of the spiral arteries. Absent end-diastolic velocities were observed in 59 of 61 fetal umbilical artery flow velocity waveform recordings. PI values from the fetal umbilical artery suggest unaltered umbilical placental vascular resistance during the first trimester of pregnancy.     

Uterine and fetal umbilical artery flow velocity waveforms in normal first trimester pregnancies

Summary. In 85 normal singleton pregnancies between 8 and 13 weeks gestation, Doppler flow velocity waveform recordings were attempted from the left and right uterine artery and fetal umbilical artery. Acceptable waveforms were obtained from the uterine arteries in 83 and from the fetal umbilical artery in 61 of the 85 pregnancies. There was virtually no difference between the left and right uterine artery on average. The marked decrease in pulsatility (PI) and resistance (RI) indices from both uterine arteries reflects the ongoing process of secondary trophoblast invasion into the muscular part of the spiral arteries. Absent enddiastolic velocities were observed in 59 of 61 fetal umbilical artery flow velocity waveform recordings. PI values from the fetal umbilical artery suggest unaltered umbilical placental vascular resistance during the first trimester of pregnancy.     

Umbilical artery blood flow velocity waveforms during variable deceleration of the fetal heart rate

Blood flow velocities of the umbilical arteries were measured by Doppler ultrasonography during variable decelerations of the fetal heart rate. The flow velocity waveforms, being normal between uterine contractions, showed either an unchanged flow velocity waveform with an exclusive fetal heart rate effect on end-diastolic velocities or a rapid change to absent and reverse diastolic flow during the decelerations, indicating an abrupt increase in placental resistance with a halt in placental perfusion. Computer-aided reconstruction of the fetal heart rate curve revealed the exact temporal relationship between the reduction of umbilical artery perfusion and deceleration of fetal heart rate. We showed that variable decelerations of fetal heart rate can be observed during only slightly changed umbilical perfusion or can be caused by a halt in placental perfusion, which does not necessarily mean an absence of any movement of the fetal blood column, but is a result of a systolic forward and diastolic reverse flow to the same extent.     

Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance

Summary. Since the umbilical arteries carry fetal blood to the placenta we studied flow velocity waveforms in these vessels with a simple continuous wave Doppler system to assess placental blood flow. The ratio of peak systolic to least diastolic (A/B) flow velocity was measured as an index of placental flow resistance. In 15 normal pregnancies there was a small but significant decrease in this ratio through the last trimester. The A/B ratio was measured on 436 occasions in 168 high-risk pregnancies. In 32 of 43 fetuses subsequently shown to be small for gestational age there was an increase in placental flow resistance with reduced, absent or even reversed flow in diastole. This finding was also present in the one fetus which died in utero . Serial studies in patients with fetal compromise indicated increasing flow resistance, a reverse of the normal trend. These results were not available to the clinician yet of 24 fetuses born before 32 weeks 13 had a high A/B ratio, and all of them were born electively. Maternal hypertension was associated with an increase in fetal placental flow resistance. The umbilical artery A/B ratio provides a new and non-invasive measure of fetoplacental blood flow resistance.     

Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance

Since the umbilical arteries carry fetal blood to the placenta we studied flow velocity waveforms in these vessels with a simple continuous wave Doppler system to assess placental blood flow. The ratio of peak systolic to least diastolic (A/B) flow velocity was measured as an index of placental flow resistance. In 15 normal pregnancies there was a small but significant decrease in this ratio through the last trimester. The A/B ratio was measured on 436 occasions in 168 high-risk pregnancies. In 32 of 43 fetuses subsequently shown to be small for gestational age there was an increase in placental flow resistance with reduced, absent or even reversed flow in diastole. This finding was also present in the one fetus which died in utero. Serial studies in patients with fetal compromise indicated increasing flow resistance, a reverse of the normal trend. These results were not available to the clinician yet of 24 fetuses born before 32 weeks 13 had a high A/B ratio, and all of them were born electively. Maternal hypertension was associated with an increase in fetal placental flow resistance. The umbilical artery A/B ratio provides a new and non-invasive measure of feto-placental blood flow resistance.     

The Comparison of Uterine Artery Doppler Velocimetry with the Histopathology of the Placental Bed

We determined the relationship between the histopathological findings of the placental bed and Doppler flow measurements of the uterine artery in women with preeclampsia and fetal growth retardation. Doppler velocimetry in the uterine artery was evaluated in 17 pregnant women with preeclampsia, 15 of whom had fetal growth retardation, and 20 normal pregnant women, within 14 days of Caesarean delivery and placental bed biopsy. The placental bed biopsies were evaluated in terms of trophoblast migration into the myometrium and physiological changes of the spiral arteries. The results were compared with Doppler velocimetry values. Trophoblast migration and physiological changes were not detected in 10 (59%) cases with preeclampsia and in 4 (20%) with normal pregnancies (p<0.05). In the preeclamptic group, 9 of 15 cases that were complicated with intrauterine growth retardation had no trophoblastic migration into the myometrium. The mean systolic/diastolic ratio, resistance index and pulsatility index of the uterine artery in women with preeclampsia and fetal growth retardation was significantly higher than women with normal pregnancies (p<0.01). The mean resistance index of the uterine artery in the impaired migration group was significantly higher than the migration group (p=0.02). The incidence of impaired trophoblast migration was significantly higher in the group with a high systolic/diastolic ratio (above 2.5) and resistance index (above 0.58) than cases with low systolic/diastolic ratio and resistance index (72%, 23% respectively, p<0.05). The incidence of early diastolic notch in the impaired trophoblast migration group was significantly higher than the migration group (57% versus 13%, p<0.01). Our study supports the hypothesis that high uterine artery flow resistance is related to the reduced trophoblast migration into the myometrium and inadequate physiological changes in the spiral arteries in women with intrauterine growth retardation and preeclampsia.     

Antiphospholipid syndrome and pregnancy

The antiphospholipid antibody syndrome (APLS) is multisystem, autoimmune disease, which is characterized by: thrombosis, obstetrics complications and thrombocytopenia. The two most clinically significant antiphospholipid antibodies (APLa) that are associated with recurrent pregnancy loss and thrombosis are anticardiolipin antibodies (ACL) and lupus anticoagulant (LA). The laboratory diagnosis is based on the presence of moderate to high positive ACL and/or LA. The inhibitory effect of antiphospholipid antibodies /APLa/ on trophoblast intercellular fusion, hormone production and invasion may cause pregnancy loss. Once placentation is established their thrombogenic action leads to decreased placental perfusion and subsequent infarction. The APLa--mediated inhibition of trophoblastic invasion and APLa--mediated vasculopathy in the placental bed arteries result in abnormal uterine artery /UA/ Doppler waveforms. The association between APLa and high resistance index /RI/ and/or diastolic notch /DN/ in the Doppler waveforms is high predictive for adverse pregnancy outcome, including pre-eclampsia/eclampsia, intrauterine growth retardation, placental abruption, intrauterine fetal death. Maternal treatment and careful monitoring of fetal well-being are mandatory in the management of these high-risk pregnancies.     

Doppler umbilical and uterine flow waveforms in severe pregnancy hypertension

Summary. Doppler studies of the umbilical and uteroplacental bed arterial flow velocity waveforms were performed in a series of women suffering from severe proteinuric pregnancy hypertension. Ninety-five women were studied and the mean interval between the last study and delivery was 1–4 days. An abnormally elevated umbilical artery systolic:diastolic (AB) ratio was present in 61 (64%) of the women. All 10 perinatal deaths were associated with pregnancies with an abnormal umbilical artery AB ratio. An elevated umbilical artery AB ratio was significantly associated with small-for-gestation and neonatal morbidity. Infants associated with extremely high umbilical artery AB ratios (≥ 99th centile) spent twice as long in the neonatal nursery as those with a lower value. There was no relation between the duration of hypertension and the umbilical study result. The uteroplacental bed artery flow velocity waveform did not correlate with fetal or neonatal mortality or morbidity. Patients with abnormal uteroplacental AB ratios also had abnormal umbilical artery AB ratios. We conclude that an abnormal fetal umbilical artery Doppler flow velocity waveform correlates with adverse fetal outcome in severe proteinuric pregnancy hypertension and suggest that the associated placental lesion may precede the maternal hypertension.     

Doppler umbilical and uterine flow waveforms in severe pregnancy hypertension

Doppler studies of the umbilical and uteroplacental bed arterial flow velocity waveforms were performed in a series of women suffering from severe proteinuric pregnancy hypertension. Ninety-five women were studied and the mean interval between the last study and delivery was 1.4 days. An abnormally elevated umbilical artery systolic:diastolic (AB) ratio was present in 61 (64%) of the women. All 10 perinatal deaths were associated with pregnancies with an abnormal umbilical artery AB ratio. An elevated umbilical artery AB ratio was significantly associated with small-for-gestation and neonatal morbidity. Infants associated with extremely high umbilical artery AB ratios (greater than or equal to 99th centile) spent twice as long in the neonatal nursery as those with a lower value. There was no relation between the duration of hypertension and the umbilical study result. The uteroplacental bed artery flow velocity waveform did not correlate with fetal or neonatal mortality or morbidity. Patients with abnormal uteroplacental AB ratios also had abnormal umbilical artery AB ratios. We conclude that an abnormal fetal umbilical artery Doppler flow velocity waveform correlates with adverse fetal outcome in severe proteinuric pregnancy hypertension and suggest that the associated placental lesion may precede the maternal hypertension.     

Placental morphometry and Doppler flow velocimetry in cases of chronic human fetal hypoxia

OBJECTIVE: To investigate the structural basis of abnormal Doppler waveforms in the utero-placental circulations in cases of chronic fetal hypoxia. STUDY DESIGN: Morphometric analysis was performed on placental samples from 58 pregnancies with abnormal Doppler waveforms in the uterine, placental and umbilical circulations at 32-34 weeks, and 10 pregnancies with normal waveforms. RESULTS: The volume of placental villi reduced from 350.5 cm3 in controls to 286.4 cm3 (P<0.05) in the severest cases. The volume of the fetal capillaries reduced from 59.7 cm3 to 20.5 cm3 (P<0.05). These reductions were associated with increased placental infarction. The myometrial segments of the spiral arteries were severely constricted, demonstrating failure of physiological conversion secondary to deficient trophoblast invasion. CONCLUSION: The placental vascular bed is greatly reduced in cases of chronic fetal hypoxia. We propose impaired placental perfusion causes oxidative stress and regression of the fetal vasculature, leading to fetal growth retardation and distress.     

Amniotic fluid nitric oxide and uteroplacental blood flow in pregnancy complicated by intrauterine growth retardation

Objective To examine the correlation between placental nitric oxide production and uteroplacental blood flow.
Participants Thirty-one pregnant women with fetuses with intrauterine growth retardation and 27 normal pregnancies as controls.
Design Correlation between amniotic fluid measurements of nitrite metabolite in the third trimester and flow velocimetry waveforms recorded from uterine, umbilical and fetal middle cerebral arteries. Intrauterine growth retarded pregnancies were compared with controls.
Main outcome measures Concentrations of nitric oxide metabolites (NO₂^- and NO₃^-) in amniotic fluid were correlated with flow velocimetry waveforms findings by the determination of correlation coefficient.
Results Overall median nitrite values in amniotic fluid were higher (   P < 0.01  ) in intrauterine growth retarded patients (median 8.6 μmol/mg creatinine) than in controls (5.6 μmol/mg creatinine). Pathologic uterine flow velocimetry waveforms in uterine artery (-2SD) were observed in 12 women of the intrauterine growth retarded group, and the concentration of amniotic fluid nitrite was significantly lower (   P < 0.01  ) in these patients (median 4.45 μmol/mg creatinine) than in those with normal flow velocity waveforms (median 11.43 μmol/mg creatinine). A significant negative correlation was observed between nitrite concentrations and uterine artery resistance index, umbilical artery pulsatility index and umbilical artery pulsatility index:middle cerebral artery pulsatility index ratio.
Conclusions We conclude that placental nitric oxide is significantly associated with uteroplacental blood flow and may be important in maintaining adequate uteroplacental perfusion in intrauterine growth retarded pregnancies.