Doppler assessment of the fetoplacental circulation in normal and growth-retarded fetuses

The Pulsatility Index (PI) of Doppler flow signals from umbilical arteries was used to study flow resistance of the placental villous circulation. A preliminary reference curve of PI values in normal pregnancy was composed from 23 healthy women examined every 2 wk from the 16th postmenstrual week until delivery. The gestational age-related decrease of PI values reflects a reduction of flow resistance in the placental villous circulation. In small-for-date fetuses significantly increased PI values were found, indicating that this simple technique may permit an early diagnosis of compromised fetoplacental circulation, even several weeks to months before fetal growth retardation is clinically presumed.     

Uterine and fetal Doppler flow changes after misoprostol and oxytocin therapy for induction of labor in post-term pregnancies.

OBJECTIVES: To compare the effect of misoprostol vs. oxytocin on blood flow in uteroplacental circulation during labor induction. METHODS: Ninety-one women with indications for induction of labor were assigned to receive either misoprostol 50 microg per vagina every 4 h as needed or intravenous oxytocin by means of a randomization table generated by computer. Doppler velocimetry of umbilical, uterine and arcuate arteries was performed immediately before and 2-3 h after administration of misoprostol or oxytocin. Pulsatility index (PI), resistance index (RI) and systolic/diastolic (S/D) ratios were measured for these arteries. The SAS system was used to perform statistical analysis. RESULTS: There were no significant changes of PI, RI and S/D ratios in umbilical arteries during misoprostol and oxytocin inductions. Vaginal application of misoprostol significantly increased PI, RI and S/D ratios in arcuate arteries and S/D ratio in uterine arteries. CONCLUSIONS: Our results indicate that intravaginal misoprostol administration increases uteroplacental resistance but probably does not substantially affect placental perfusion.     

New score indicating placental vascular resistance

BACKGROUND: Umbilical artery Doppler velocimetry is a routine method for fetal surveillance in high-risk pregnancy. Uterine artery Doppler seems to give comparable information, but it can be difficult to interpret as there are two arteries, which might show notching and/or increased pulsatility index (PI) as signs of increased vascular impedance. Combining the information on vascular resistance on both sides in a new score might simplify and improve evaluation of placental circulation. METHODS: Uterine and umbilical artery Doppler velocimetry was evaluated in 633 high-risk pregnancies. The managing clinician was informed only about the umbilical artery flow. The umbilical artery flow spectrum was semiquantitatively divided into four blood flow classes (BFC), expressing signs of increasing vascular resistance. The uterine artery Doppler flow spectrum was divided into five uterine artery scores (UAS), taking into account presence/absence of notching and/or increase in PI. By adding UAS to BFC, a new placental score (PLS) was constructed with values ranging from 0 to 7, indicating general placental vascular resistance. The scores were related to three outcome variables: small-for-gestational age (SGA), premature delivery (<37 weeks), and cesarean section. RESULTS: All three score systems showed a significant relationship between signs of increasing vascular resistance and outcome. The new PLS showed the best association to adverse outcomes, with optimal cut-off at values exceeding score 3. CONCLUSION: Doppler velocimetry on both sides of the placenta showed a strong relationship to an adverse outcome of pregnancy. The new PLS showed a better relationship to adverse perinatal outcome than the BFC and the UAS. The PLS can simplify evaluation of uteroplacental and fetoplacental Doppler velocimetry.     

Doppler analysis and placental nitric oxide synthase expression during fetal growth restriction

Objective. To assess placental nitric oxide (NO) metabolism related to changes in the uteroplacental circulation during fetal growth restriction (FGR).

Methods. The resistance index (RI) from the uterine arteries and pulsatility index (PI) from the umbilical artery were determined by Doppler analysis in 15 patients with FGR and 12 healthy controls, before elective cesarean section. Inducible (iNOS) and endothelial (eNOS) NO synthase expression were measured in placental samples. Immunohistochemistry was performed for iNOS location in the placenta.

Results. During FGR, we observed a significant elevation of iNOS when compared with controls. Conversely, eNOS did not differ between the two groups. A negative correlation with eNOS (r = ?0.85) and a positive correlation with iNOS (r = 0.91) was found correlating to umbilical PI. The iNOS proteins were reduced in syncytiotrophoblast cells and increased in endothelium in the FGR group compared to the controls.

Conclusions. During FGR, placental iNOS expression is significantly increased; this increase possibly represents an adaptive physiological mechanism for overcoming a fetoplacental circulation deficiency.     

Placental ischemia and changes in umbilical and uteroplacental arterial and venous hemodynamics

Objective: To relate Doppler velocimetry findings in fetoplacental and uteroplacental circulation to placental histomorphology. Material and methods: In 14 uncomplicated and 31 high-risk pregnancies Doppler velocimetry was performed in umbilical artery and vein, and in maternal uterine veins and arteries during the second half of gestation. Histopathology of the placentas was examined, especially for signs of ischemia and inflammation. Results: All fetuses in uncomplicated pregnancies had normal flow velocity waveforms in umbilical artery; in the high-risk group, 18 fetuses had abnormal flow (increased PI or absent/reverse end-diastolic flow). The latter group had more often high ischemic score and infarctions in the placenta than found in pregnancies with normal umbilical artery flow (p?<?0.001 and p?=?0.02, respectively). Similarly, the abnormal uterine artery flow pattern (uterine artery score 3–4) occurred more often with high ischemic score and placenta infarctions (p?<?0.001 and p?<?0.001, respectively). No significant associations were found between the uterine venous flow type and placental ischemia. Conclusion: Placental ischemic morphological changes were associated with Doppler ultrasound signs of increased resistance to arterial blood flow, both on the fetal and maternal sides of the placenta. No significant relation to the uterine venous flow velocities was found.     

Oxygen and placental villous development: Origins of fetal hypoxia

The increasing practice of preterm delivery in the fetal interest for conditions such as pre-eclampsia or intrauterine growth restriction (IUGR) has provided an opportunity to study placental structure in pregnancies with prenatal evidence of fetal compromise. These data suggest that the origin of fetal hypoxia in IUGR with absent end-diastolic flow in the umbilical arteries is due to a failure of oxygen transport from intervillous space to umbilical vein. Failure of the fetoplacental circulation to extract oxygen from the intervillous space under such circumstances means intervillous Po_o is closer to maternal arterial values than under physiological conditions. Correspondingly the placental villi are chronically exposed to a higher oxygen tension than under normal circumstances — the term ‘hyperoxia’, relative to normal intraplacental oxygenation, is proposed to describe this situation. Both the trophoblast and villous core react to increased oxygen despite fetal hypoxia. These results challenge the generally accepted concept of ‘placental hypoxia’ in all circumstances where fetal hypoxia might arise. Therefore three categories are proposed for the origins of fetal hypoxia: (1) preplacental hypoxia; (2) uteroplacental hypoxia; and (3) postplacental hypoxia. Examples for these three disease states are listed in this review and the structural reaction patterns of placental villi to these differences in oxygenation are discussed.     

A comparative study of intraplacental villous arteries by latex cast model in vitro and color Doppler flow imaging in vivo.

OBJECTIVE: The purpose of this study was to determine whether color Doppler sonogram can accurately depict the placental vascular structures using a latex cast model of the placental vessels, and to make a nomogram of several blood flow parameters according to the vascular structures. METHODS: First, we made 9 latex cast models of placental arteries and performed morphologic observation and measurement. Second, the comparative anatomical observation of placental vessels by color flow mapping was performed for all 9 patients from whom the latex models were made. Third, a total of 102 uncomplicated pregnant women between 18 and 40 weeks gestation were examined by color Doppler imaging. The resistance indices (RI) and peak systolic velocity (PSV) were measured. RESULTS: In the latex cast model of placentas, cotyledons could be differentiated by the presence of independent vascular structure units. First, second, third and fourth branches were noted in one cotyledon. Cotyledons were easily identified and counted by color Doppler imaging. Each cotyledon contained only one first branch of the intraplacental villous artery (IPVA). The number of IPVA-1 on color Doppler imaging was equal to the number of the cotyledon calculated from the latex model. RI exhibited a negative, and PSV a positive correlation with gestational age (p < 0.05 in both cases). At any given gestational age, both RI and PSV in the peripheral arteries were significantly lower (p < 0.01) than those in the upstream arteries. CONCLUSIONS: Color Doppler flow sonography is a valuable tool for detecting the blood flow of intraplacental villous arteries in vivo and the images agree with the vascular anatomy of placenta in vitro. These results may also provide the basic parameters for future studies of some complicated pregnancies.     

Prognostic value of placental ultrasound in pregnancies complicated by absent end-diastolic flow velocity in the umbilical arteries

Our objective was to evaluate the utility of gray-scale placental ultrasound for the detection of pathological lesions in the placentas of preterm pregnancies with abnormal fetoplacental blood flow (defined by absent or reversed end-diastolic flow velocities [ARED] in the umbilical arteries) before 32 weeks of gestation. Sixty consecutive structurally and chromosomally normal singleton pregnancies were evaluated. Pre-defined criteria were used to describe placental appearances using gray-scale real-time ultrasound. Proximal uterine artery Doppler waveforms were recorded using pulsed and color Doppler ultrasound. Each patient had a thrombophilia profile. Following delivery, a single perinatal pathologist reviewed each placenta at a gross and microscopic level blinded to the placental ultrasound findings. Placental shape or texture was abnormal on gray-scale ultrasound in 43/59 (73%) and echogenic cystic lesions (ECL) were found in 16 (27%). Uterine artery Doppler was abnormal in 47/60 (78%) cases. Thirty-eight pregnancies were subsequently delivered by planned Caesarean section in the fetal and/or maternal interest (birthweights 540-2300 g, mean gestational age 30.6 weeks) and 21 pregnancies resulted in the vaginal delivery of a stillborn fetus where fetal weight and/or gestational age did not justify Caesarean section (birthweights 85-600 g, mean gestational age 24.9 weeks). ECL had a low positive predictive value for both villous infarcts (63%) and for focal/massive perivillous fibrin deposition (40%). Nevertheless, the combination of abnormal uterine artery Doppler and abnormal gray-scale findings (abnormal placental morphology or ECL) was strongly predictive of stillbirth (17/21; sensitivity 81%, PPV 52%, p = 0.006 Fisher's exact test). Pregnancies with ARED in the umbilical arteries have a high perinatal mortality associated with pathology of the placental villi. Ultrasound examination of the placenta and its maternal blood supply may contribute to the perinatal management of these pregnancies.     

Nitric oxide in the uteroplacental, fetoplacental, and peripheral circulations in preeclampsia.

OBJECTIVE: Altered production of nitric oxide by the vascular endothelium may influence the pathogenesis of preeclampsia. The aim of this study was to measure circulating levels of nitric oxide metabolites (nitrites) in the uteroplacental, fetoplacental, and peripheral circulation of preeclamptic pregnancies compared with normotensive controls. METHODS: Fifteen women with preeclampsia were compared with 16 women with normotensive pregnancies. At cesarean, blood samples were taken from the uterine vein draining the placental site, the umbilical vein, and the antecubital vein after delivery of the baby but before delivery of the placenta. Plasma nitrites were measured using the Greiss reaction after conversion of plasma nitrates to nitrites using nitrate reductase. RESULTS: Nitric oxide metabolites were higher in the uteroplacental (P < .01), fetoplacental (P < .001), and peripheral (P < .02) circulations in samples from preeclamptic pregnancies compared with control pregnancies. In samples from the fetoplacental circulation only, nitric oxide metabolite levels were negatively correlated with gestational age (r = -.489, P < .01) and birth weight (r = -.544, P < .004). Nitric oxide metabolite levels were not significantly correlated with blood pressure, placental weight, or maternal age. CONCLUSION: In established preeclampsia, production of nitric oxide was higher in the uteroplacental, fetoplacental, and peripheral circulation than in normotensive pregnancies. This increase may be part of a compensatory mechanism to offset the pathologic effects of preeclampsia.     

Umbilical artery Doppler waveform indices from normal pregnant women are related to vasodilatation of placental chorionic plate small arteries.

Blood flow control within the fetoplacental circulation is poorly understood despite the essential role of the placenta in pregnancy. Our study compared an in vitro assessment of placental chorionic plate small artery function with in vivo measures of umbilical artery blood flow. Umbilical artery Doppler waveform analysis was performed on women (N=8) with uncomplicated pregnancies within 24 hours of delivery. Small arteries (n=25) were dissected from the placental chorionic plate from biopsies at term and studied using parallel wire myography. Chorionic plate arteries developed maintained constrictions to the thromboxane-mimetic U46619. Nitric oxide (NO) donation with the endothelial-independent agent sodium nitroprusside elicited significant relaxation compared to paired control vessels. This vasodilatation correlated significantly with both pulsatility and resistance indices measured in the umbilical artery. We conclude that Doppler indices in the umbilical artery are inversely proportional to the maximal relaxation achieved by chorionic plate small arteries in response to a NO donor.     

异氟醚分娩镇痛对胎儿-母体循环影响的研究

目的　探讨异氟醚分娩镇痛对子宫胎盘和胎儿胎盘血流的影响。　方法　应用多普勒超声技术,对分娩活跃期异氟醚分娩镇痛组和对照组共５０例初产妇的子宫动脉和脐动脉血流速度指数及胎心率进行检测。　结果　实验前后,各组子宫动脉的平均Ｓ／Ｄ比值、搏动指数（ＰＩ）及脐动脉平均Ｓ／Ｄ比值、ＰＩ均无显著差异（Ｐ＞ ０．０５）;两组间无显著差异（Ｐ＞ ０．０５）,实验前后,各组平均胎心率均无显著差异（Ｐ＞ ０．０５）;两组间无显著差异（Ｐ＞ ０．０５）。　结论　异氟醚分娩镇痛对胎儿－母体循环未发现有不良影响     

Effects of Nifedipine on Isolated Arteries and Placental Perfusion in the Human Uteroplacental Unit

The effects of nifedipine were tested in isolated maternal intramyo-metrial and fetal placental chorionic and stem villous arteries mounted as ring preparations in organ baths. Furthermore, the effects of a single oral dose of nifedipine 20 mg on feto-placental haemodynamics were evaluated by Doppler technique in 14 women with pregnancy-induced hypertension. In maternal intramyometrial arteries, nifedipine inhibited the contractile effects of vasopressin and noradrenaline, and the compound also decreased responses to prostaglandin F_2α in fetal chorionic and stem villous arteries. In patients with pregnancy-induced hypertension, blood pressure was reduced without significant changes in heart rate or in arcuate artery pulsatility index (PI). Fetal heart rate remained unchanged and no significant changes were seen in fetal aortic rising slope, PI and blood flow, or in umbilical artery PI and venous blood flow. The results do not suggest significant negative effects on uteroplacental haemodynamics during treatment of pregnancy-induced hypertension with calcium antagonists like nifedipine.     

Ultrasound of the placenta: a systematic approach. Part II: functional assessment (Doppler)

Doppler velocimetry is the ideal clinical tool to assess placental performance in high-risk pregnancies. It also has value in predicting later complications and outcome in pregnancies which appear uncomplicated. All three circulations (fetal, placental and maternal) may be interrogated by Doppler technology. In the following review, we present basic physics aspects of Doppler and discuss mainly Doppler investigation of the fetal-placental circulation (umbilical artery, intraplacental circulation) as well as the uterine arteries. The assessment of umbilical blood flow provides information on blood perfusion of the fetal-placental unit. The diastolic blood flow velocity component in umbilical artery increases with advancing gestation. In pregnancies complicated by placental dysfunction, there may be a reduction in the number of functional villi and/or small blood vessels with, as a result, increased impedance, reflected, mainly, by a decrease in end-diastolic velocity. When the resistance increases even more, there is no diastolic forward velocity (absent end-diastolic velocity). Further increase in the resistance causes reversed end-diastolic velocity, which is considered a late step in the cascade of events leading to intrauterine fetal demise. Doppler assessment of the umbilical arteries was found to improve outcome of high-risk pregnancies, and reduce hospital admissions. On the contrary, routine Doppler ultrasound in low risk or unselected populations does not seem to confer benefit on mother or newborn. Uterine artery Doppler is a useful test in predicting pregnancies at high risk of developing complications related to uteroplacental insufficiency. It identifies women who may benefit from increased antenatal surveillance or prophylactic therapy. Three-dimensional power Doppler sonography can provide new insights into placental pathophysiology.     

Histomorphology of the placenta and the placental bed of growth restricted foetuses and correlation with the Doppler velocimetries of the uterine and umbilical arteries

The aim of the present study was to evaluate the histomorphology of the placenta and the placental bed and to correlate this with the Doppler study of the uterine and umbilical arteries of intrauterine growth restricted pregnancies. The study group consisted of 47 women with intrauterine growth restricted foetuses. Twenty-five uneventful pregnancies with appropriate for gestational age foetuses were selected as controls. Doppler studies of umbilical and uterine arteries were performed within the last week before delivery. Placental bed biopsies were obtained at Caesarean section with direct visualization of the placental site. The incidence of pathologic bed biopsies in control, IUGR with normal uterine artery Doppler velocimetry and IUGR with abnormal uterine artery Doppler velocimetry was 0 per cent, 16.6 per cent and 79.3 per cent respectively (P< 0.001). Placentae from IUGR cases with abnormal umbilical artery Doppler velocimetries had a significantly increased number of villous infarcts, cytotrophoblast proliferation and thickening of the villous trophoblastic basal membrane (P=0.001, P=0.038 and P=0.02 respectively). Abnormal placental bed biopsy pathology was significantly associated with abnormal uterine artery velocimetry (OR 33.7, 6.5-173.6; P< 0.001). Abnormal placental pathology was significantly associated with abnormal umbilical artery Doppler velocimetry (OR 21.04, 3.8-115.9;P< 0.001). Women with both abnormal uterine and umbilical artery Doppler velocimetries were delivered earlier and their babies had lower mean birth and placental weight (P< 0.001). In conclusion, placental bed biopsy and placental pathologies are best reflected by abnormal uterine and umbilical artery velocity waveforms, respectively. The most severe clinical outcomes and perinatal mortality are present when both uterine and umbilical districts are altered.     

Misoprostol and dinoprostone therapy for labor induction: a Doppler comparison of uterine and fetal hemodynamic effects

OBJECTIVE: To compare the effect of misoprostol (PGE(1)) versus dinoprostone (PGE(2)) on blood flow in uteroplacental circulation during labor induction. STUDY DESIGN: Eighty-four women with indications for induction of labor were assigned to receive either misoprostol 50 microg per vagina every 4 h as needed or 0.5 mg doses of dinoprostone given intra-cervically every 6 h by means of a randomization table generated by computer. Doppler velocimetry of umbilical, uterine and arcuate arteries was performed immediately before and 2-3 h after the administration of misoprostol or dinoprostone. The SAS system was used to perform statistical analysis. RESULTS: There were no significant changes of pulsatility index (PI), resistance index (RI) and systolic/diastolic (S/D) ratio in umbilical arteries after both prostaglandin compounds. Vaginal application of misoprostol significantly increased all ratios in arcuate artery and S/D ratio in uterine artery. Intra-cervically dinoprostone significantly increased PI, RI and S/D ratio in arcuate and uterine arteries. CONCLUSIONS: Our results indicate that vaginal misoprostol and cervical dinoprostone administration increases uteroplacental resistance but does not affect umbilical blood flow. Misoprostol would be as safe and effective agent as dinoprostone for cervical ripening and labor induction.     

Characteristics of flow velocities in the umbilical arteries,assessed by Doppler ultrasound

Measuring blood velocities by Doppler ultrasound has introduced a new noninvasive technique into obstetrical diagnostics. This study evaluates the information about fetoplacental hemodynamics that can be extracted from Doppler signals obtained from umbilical arteries.The most significant blood flow characteristic is blood flow pulsatility expressed as pulsatility index (PI). The PI is the difference between systolic and diastolic velocity, divided by the mean velocity. The PI strongly correlates with downstream impedance to flow.It is demonstrated that sophisticated spectral analysis of the Doppler signals has no practical advantages over the simple zero-crossing technique for establishing PI values, since blood flow in umbilical arteries has a blunt-to-flat profile.This study shows that the PI is a gestational-age-related, intra- and inter-observer-reproducible variable. The significant decrease of PI values with advancing gestational age reflects a progressive reduction of placental vascular resistance to umbilical blood flow. The PI holds promise as a simple method for early diagnosis of impaired umbilical circulation.     

Adrenomedullin is increased in the fetoplacental circulation in intrauterine growth restriction with abnormal umbilical artery waveforms

OBJECTIVE: To examine whether adrenomedullin, a novel vasoactive peptide produced by the placenta, participates in the uteroplacental hemodynamic alterations in intrauterine growth restriction, we studied the correlation between adrenomedullin levels and fetoplacental blood flow. STUDY DESIGN: Maternal and umbilical blood samples were collected in pregnancies complicated by intrauterine growth restriction with abnormal umbilical artery Doppler findings and in control pregnancies. Adrenomedullin levels were measured by means of a specific radioimmunoassay, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. RESULTS: Mean adrenomedullin values in umbilical plasma were higher (P <.05) in patients with intrauterine growth restriction (63.7 +/- 34.2 pg/mL; n = 16) than in control subjects (38.1 +/- 14.8 pg/mL; n = 16). A significant correlation was found between maternal adrenomedullin levels and umbilical artery pulsatility index. Moreover, fetal adrenomedullin concentrations correlated negatively with middle cerebral artery pulsatility index and positively with umbilical artery pulsatility index/middle cerebral artery pulsatility index ratio. CONCLUSION: This study provides evidence that adrenomedullin is increased in fetuses with intrauterine growth restriction in response to reduced uteroplacental blood flow and suggests that it may participate in the fetal hemodynamic modifications.     

Prostacyclin deficiency and reduced fetoplacental blood flow in pregnancy-induced hypertension and preeclampsia

BACKGROUND: Low endothelial generation of prostacyclin (PGI(2)) is a typical feature of pregnancy-induced hypertensive disorders. The aim of the current study was to establish whether changes in PGI(2) are accompanied by alterations in fetoplacental blood flow and to test the hypothesis that PGI(2) deficiency contributes to reduced fetoplacental perfusion in pregnancy-induced hypertension (PIH) and preeclampsia. METHODS: The study included 11 women with normal pregnancies, 12 with PIH/preeclampsia, and 7 with otherwise complicated pregnancies. Fetoplacental blood flow was assessed both by umbilical artery Doppler sonography measuring the resistance index (RI) and by means of neonatal birth weight. PGI(2) formation was measured in umbilical arteries prepared immediately after birth. PGI(2), RI and birth weight were correlated with and without correction for gestational age. Furthermore, data from patients with PIH/preeclampsia were compared with normal pregnancies as controls. RESULTS: A significant inverse correlation was found between umbilical PGI(2) formation and umbilical RI and between birth weight and RI, whereas PGI(2) and birth weight were directly related. Patients with PIH/preeclampsia showed reduced PGI(2) formation, markedly increased gestational age-corrected RI and significantly reduced percentile birth weight. CONCLUSIONS: These results provide evidence showing that PGI(2) is a relevant mediator of fetoplacental blood flow and suggest an important role of PGI(2) deficiency in PIH/preeclampsia.     

Doppler ultrasonographic features of the developing placental circulation: Correlation with anatomic findings.

Color Doppler was used to study the placental circulations of 28 pregnancies between 10 and 17 weeks' gestation. A histomorphometric investigation was performed on placental tissue samples from those pregnancies, and the results were compared with Doppler features. Important changes were found around 14 weeks' gestation in both uterine and umbilical circulations. The appearance of end-diastolic frequencies in the umbilical arteries was related to an abrupt and significant (p less than 0.005) increase in uterine velocity and to the establishment of a continuous intervillous circulation.