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Serial studies of umbilical artery flow velocity waveforms in one patient revealed two quite distinct waveforms at each study. The mean systolic/diastolic ratio difference between the studies was 2.2 units. After delivery, the placenta... more
Serial studies of umbilical artery flow velocity waveforms in one patient revealed two quite distinct waveforms at each study. The mean systolic/diastolic ratio difference between the studies was 2.2 units. After delivery, the placenta was seen to include a large infarcted lobule supplied by only one of the umbilical arteries. The finding of two very dissimilar umbilical artery flow velocity waveforms at the time of study should raise the suspicion of placental infarction, but management decisions should be based on the most normal study.
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Twenty fetal lambs were studied in utero using continuous wave Doppler ultrasound to analyse the fetal umbilical artery flow velocity waveforms. Satisfactory waveforms were obtained. Prepregnancy surgical removal of uterine caruncles was... more
Twenty fetal lambs were studied in utero using continuous wave Doppler ultrasound to analyse the fetal umbilical artery flow velocity waveforms. Satisfactory waveforms were obtained. Prepregnancy surgical removal of uterine caruncles was used to produce intrauterine fetal growth retardation in 14 of these ovine pregnancies of whom 8 delivered a small for gestational age fetus. In only one fetus was the umbilical artery flow velocity waveform abnormal with a high systolic diastolic ratio. We conclude that the growth restriction occurring in the ovine fetus following a reduction of placental implantation sites is not related to a restriction in the fetoplacental circulation and this is different from the most frequently observed human fetal growth retardation.
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Pregnancy, Placenta, Sheep, Ultrasonography, Female, and 5 moreAnimals, Fetus, Gestational Age, Uterus, and Blood Flow Velocity
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ABSTRACT
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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... more
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 uteropla...
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Various Doppler waveform indices have been used for assessment of the fetal circulation. Comparisons were made to show what relations exist between the indices, and to identify any differences or difficulties which might arise from using... more
Various Doppler waveform indices have been used for assessment of the fetal circulation. Comparisons were made to show what relations exist between the indices, and to identify any differences or difficulties which might arise from using one as opposed to another in clinical practice. Both normal pregnancy and cases of fetal growth failure were studied. Indices were obtained from the maximum velocity envelope of the umbilical artery waveform using a curve fitting technique. The values were very reproducible for all indices. The FHR, which varied over the entire normal range, did not significantly affect the values of any index. The downstream impedance indices calculated included the AB ratio, pulsatility index (PI) and Pourcelot ratio. These all gave very closely correlated results for normals but discrepancies occurred in the at risk group, where values were elevated. This could be attributed to differences in the underlying distributions. The indices suggested for cardiac contrac...
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Doppler ultrasound waveforms from the fetal umbilical artery were analyzed by a new quantitative technique. Normal pregnancy and cases of fetal growth failure were considered. Data from the spectrum analyzer were dumped to a... more
Doppler ultrasound waveforms from the fetal umbilical artery were analyzed by a new quantitative technique. Normal pregnancy and cases of fetal growth failure were considered. Data from the spectrum analyzer were dumped to a microcomputer, the velocity waveforms calculated and a representative waveform obtained by ensemble averaging. This curve was then fitted by a 4-parameter analytic function. We introduce R, the relative flow rate index, which measures the ratio of the average flow rate before the systolic peak to the average rate during the remainder of the cardiac cycle. In cases of fetal growth failure this ratio was significantly greater than in normal pregnancy. Other new quantities defined are the normalized systolic decay time index and the constant flow ratio. The AB ratio was also calculated. Fetal growth failure has been associated with raised placental resistance. We suggest that the fetus can initially compensate for this by increasing cardiac contractility. This can ...
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1. Lancet. 1989 Jul 15;2(8655):171. Plasma exchange and the anticardiolipin syndrome in pregnancy. Fulcher D, Stewart G, Exner T, Trudinger B, Jeremy R. PMID: 2567950 [PubMed - indexed for MEDLINE] Publication Types: Case Reports; Letter.... more
1. Lancet. 1989 Jul 15;2(8655):171. Plasma exchange and the anticardiolipin syndrome in pregnancy. Fulcher D, Stewart G, Exner T, Trudinger B, Jeremy R. PMID: 2567950 [PubMed - indexed for MEDLINE] Publication Types: Case Reports; Letter. MeSH Terms: ...
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Antibodies, Pregnancy, Humans, Female, Lancet, and 3 moreAdult, Syndrome, and Combined Modality Therapy
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TIME, Pregnancy, Humans, Female, Technique, and 9 moreHeart, Mitral Valve Repair, Foetus, Time, Contraction, Fetus, Gestation, Aortic Valve, and Fetal Heart
A mathematical model of the umbilical placental circulation was used to examine the effect of different physiological variables on the pulsatility index (PI) of the umbilical artery Doppler waveform. The variables include the umbilical... more
A mathematical model of the umbilical placental circulation was used to examine the effect of different physiological variables on the pulsatility index (PI) of the umbilical artery Doppler waveform. The variables include the umbilical and placental resistances, the volume flow rate and the pressure. In the model the branching structure of the placental villous tree is considered in detail, while each arterial branch is itself represented simply using a resistor and a capacitor. Placental vascular disease is modelled as obliteration of a fraction of the terminal branches of the tree. The model umbilical artery PI depends on the ratio of the placental resistance to the umbilical artery resistance. The PI increases with vascular disease, but the rate of increase is not uniform. Initially, the placental resistance and the PI increase very slowly with vessel obliteration. Once the level of vessel obliteration has reached a large enough value--typically between 60% and 90% obliteration--the PI begins to rise sharply. A larger placental vascular bed can accommodate a greater level of vessel obliteration before this rapid PI rise begins. The umbilical artery PI also depends on the pulsatility of the input (aortic bifurcation) pressure waveform, but blood pressure variations in the physically attainable range cannot account for the very high PI values associated with fetal compromise. Physically attainable pressure waveform changes would, however, enable the fetus with substantial placental vascular disease to maintain umbilical volume flow rate, and at the same time exhibit a raised umbilical artery PI value.
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The isovolumetric contraction time (ICT) is known to be an index of cardiac contractility. In this study, we examined the relationship between the fetal ICT and fetal heart rate (FHR) and evaluated the usefulness of ICT in the assessment... more
The isovolumetric contraction time (ICT) is known to be an index of cardiac contractility. In this study, we examined the relationship between the fetal ICT and fetal heart rate (FHR) and evaluated the usefulness of ICT in the assessment of fetal cardiac contractility in cases with fetal tachyarrhythmia. Seven cases with fetal tachyarrhythmia between 32 and 40 weeks' gestation were included in this study. The fetal ICT was measured using a continuous Doppler device and digital filters. The relationship between the fetal ICT and FHR was analyzed using the Spearman's rank correlation test in each fetus. Based on the FHR and ultrasound findings of hydrops at the measurement of ICT, the obtained data were divided into three groups: normal, tachyarrhythmia only and hydrops. The clinical usefulness of ICT was assessed using the random effect model. In 7 fetuses, a total of 60 data points were obtained. A significant correlation between fetal ICT and FHR was not noted in each fetus. The ICT of the hydrops group was significantly prolonged compared with those of the normal and tachyarrhythmia-only groups (p < 0.01). An association between the fetal ICT and FHR is not noted and the fetal ICT might have some utility to detect impaired fetal cardiac contractility even in fetuses with tachyarrhythmia.
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In placental vascular disease identified by umbilical artery Doppler study we have shown the existence of a factor in fetal plasma that causes activation of endothelial cells in culture with expression of cell adhesion molecules and... more
In placental vascular disease identified by umbilical artery Doppler study we have shown the existence of a factor in fetal plasma that causes activation of endothelial cells in culture with expression of cell adhesion molecules and nitric oxide synthase, apoptosis, and proinflammatory cytokine production. The present work was carried out to investigate a maternal origin for this factor active in the fetal circulation. We collected maternal plasma from pregnant women with Doppler-defined umbilical placental vascular disease and examined its effect on endothelial cells in culture. Aliquots from a common culture of human umbilical vein endothelial cells (HUVEC) were incubated with maternal plasma from women with normal pregnancy (n = 23), umbilical placental vascular disease defined by abnormal umbilical artery Doppler (n = 30, with or without preeclampsia), and preeclampsia with normal umbilical artery Doppler (n = 14). The expression of mRNA for inducible and endothelial constitutive nitric oxide synthase (iNOS and ecNOS, respectively) was assessed by reverse transcriptase polymerase chain reaction. There was no significant increase in either the iNOS or the ecNOS mRNA expression by HUVEC cultured with maternal plasma from pregnancies with umbilical placental vascular disease compared with normal pregnancy (iNOS 1.49 +/- 0.35 versus 1.38 +/- 0.25; ecNOS 1.51 +/- 0.35 versus 1.25 +/- 0.27; P >.05). In the placental vascular disease group the results were similar for the presence or absence of maternal preeclampsia. In the samples from women with preeclampsia with normal umbilical Doppler, both iNOS and ecNOS mRNA expression (iNOS 1.42 +/- 0.53; ecNOS 1.46 +/- 0.39; P >.05) did not differ from normal. Maternal plasma from pregnancies with umbilical placental vascular disease did not affect endothelial cell expression of nitric oxide synthase. This finding does not support a maternal origin for the factor demonstrated in fetal plasma. These results suggest separate pathogenic pathways for the endothelial cell activation seen in preeclampsia and fetal growth restriction associated with abnormal umbilical artery Doppler flow velocity waveforms. These findings are also consistent with the concept that the vascular pathology in the fetal placenta may be primary and that the uteroplacental circulation is reduced in response rather than acts as a constraint.
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We developed a noninvasive Doppler technique for measuring fetal cardiac isovolumetric contraction time (ICT). The purpose of this study was to determine how well our method reflects real cardiac performance using fetal lamb as an... more
We developed a noninvasive Doppler technique for measuring fetal cardiac isovolumetric contraction time (ICT). The purpose of this study was to determine how well our method reflects real cardiac performance using fetal lamb as an instrumented model. The true ICT was measured by simultaneous recording of the pressure waves of the left ventricle and ascending aorta. The maximum first derivative of the left ventricular pressure wave (Max dp/dt) was calculated. The Doppler ICT was measured in the appropriately filtered Doppler cardiac signals. Positive and negative inotropic agents were administered to change the cardiac contractility. There was an inverse relationship between the Doppler ICT and the Max dp/dt. Excellent linear correlation was found an absolute value and changes from control value between the true ICT and the Doppler ICT (r = 0.959, r = 0.962). The Doppler ICT measurement provides useful information about changes in ventricular performance.
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We examined the hypothesis that fetal proinflammatory cytokine release is a feature of placental vascular disease causing fetal compromise. We measured the concentrations of fetal proinflammatory cytokines interleukin 6 (IL-6), tumor... more
We examined the hypothesis that fetal proinflammatory cytokine release is a feature of placental vascular disease causing fetal compromise. We measured the concentrations of fetal proinflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interleukin-8 (IL-8) in the presence of vascular disease in the umbilical placental villous circulation. Vascular disease was identified by high-resistance umbilical artery Doppler flow velocity waveform studies. We measured levels of the inflammatory cytokines IL-6 and TNF-alpha and the chemokine IL-8 in fetal blood. Blood was collected from the umbilical vein at delivery, and serum was stored at -70C until assayed using chemiluminescent and enzyme-linked immunosorbent assay methods. We studied 36 normal pregnancies delivered by elective cesarean at term and 50 pregnancies with a high-resistance umbilical artery Doppler flow velocity waveform pattern indicative of fetal placental vascular disease delivered by elective cesarean because of potential fetal compromise. In the presence of umbilical placental vascular disease there were significantly higher levels of IL-6 (median 5.3 pg/mL, P <.05) and IL-8 (median 26.5 pg/mL, P <.01) compared with normal pregnancies (median value of IL-6 and IL-8 were below assay threshold). There was no difference for TNF-alpha, with the median results undetectable in both groups. We found higher concentrations of IL-6 and IL-8 in the fetal circulation in the presence of umbilical placental vascular disease.
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Preterm premature rupture of the membranes (PROM) has been attributed to ascending infection and a choriodecidual inflammatory response (ie, on the maternal side). However, on the fetal side those most at risk of morbidity have a systemic... more
Preterm premature rupture of the membranes (PROM) has been attributed to ascending infection and a choriodecidual inflammatory response (ie, on the maternal side). However, on the fetal side those most at risk of morbidity have a systemic proinflammatory cytokine response. We have recently defined a similar proinflammatory response in pregnancies complicated by vascular disease on the fetal side of the placenta. A factor(s) present in fetal plasma from these pregnancies can stimulate human umbilical vein endothelial cells (HUVECs) to express mRNA for the proinflammatory cytokines, interleukin (IL)-6 and IL-8. The hypothesis of this study was that a similar factor(s) was present in preterm PROM. A standard culture of HUVECs was incubated with fetal plasma, obtained immediately following delivery, from normal pregnancies delivering vaginally at term (n=16) and pregnancies delivering following preterm PROM (n=19). Expression of mRNA for IL-6 and IL-8 was assessed by reverse transcription polymerase chain reaction (RT-PCR) and standardized to GAPDH mRNA expression. Endothelial cell expression of IL-6 mRNA (median [25-75th centile] 0.295 [0.252-0.507] vs term vaginal delivery 0.208 [0.151-0.307]; P=.009) was enhanced in response to the fetal plasma from PROM cases compared to pregnancies delivering vaginally at term. In contrast, mRNA expression of IL-8 (median [25-75th centile] preterm PROM 0.41 [0.21-0.78] vs term vaginal delivery 0.49 [0.16-0.68]; P=.46) was not different in the two groups. We have demonstrated that in fetuses delivered following preterm PROM there is a factor(s) capable of stimulating a local endothelial cell proinflammatory cytokine (IL-6) response. This factor(s) that we have demonstrated may be responsible for the increased cytokine production seen in fetuses with the fetal inflammatory response syndrome.
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Measurement of the plasma concentration of glycocalicin, the extracellular portion of platelet glycoprotein Ib, should prove to be clinically useful in the investigation of causes of thrombocytopaenia and as an indirect method of... more
Measurement of the plasma concentration of glycocalicin, the extracellular portion of platelet glycoprotein Ib, should prove to be clinically useful in the investigation of causes of thrombocytopaenia and as an indirect method of determining platelet lifespan. We describe an immunoradiometric method for the measurement of glycocalicin in plasma using two murine monoclonal antibodies. The assay has good reproducibility with coefficients of intra- and inter-assay variation of 5.4% and 7.0% respectively, requires standard laboratory skills only and, after overnight coating of the wells, enables analysis of multiple samples in approximately 4 h. With citrated plasma the result of the assay does not appear to be affected by one cycle of freeze-thaw, nor was there any observed difference in result between platelet-poor plasma (PPP) prepared by centrifugation at 1100 g for 15 min and plasma that was confirmed to be platelet-free. The plasma concentrations of citrate and ethylenediaminetetraacetate were found to affect the result of the assay thus making it important that only samples with the same type and similar concentration of anticoagulant be compared and that standards should be diluted in glycocalicin-depleted plasma with the same concentration of these anticoagulants as the unknowns.