Umbilical artery flow velocity waveform analysis in normal ovine pregnancy and after carunculectomy

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.     

高危孕妇胎儿缺氧与彩色多普勒超声结合四维超声检查的相关性研究

摘要 目的：探讨与研究高危孕妇胎儿缺氧与彩色多普勒超声结合四维超声检查的相关性。方法：2018年2月到2020年1月在本院进行建档分娩的高危孕妇108例作为研究对象,都给予彩色多普勒超声结合四维超声检查,记录影像学特征,判定胎儿缺氧发生情况并进行相关性分析。结果：在高危孕妇108例中,发生宫内缺氧28例（宫内缺氧组）,发生率为25.9 %;宫内缺氧组的大脑中动脉、脐动脉的阻力指数（RI）、搏动指数（PI）、收缩期峰值流速舒张期流速比值（S/D）均高于非宫内缺氧组（P<0.05）;宫内缺氧组的上腔静脉血流心室收缩期峰值流速（S波）、心房收缩期速度（A波）、心室舒张期峰值流速（D波）均高于非宫内缺氧组（P<0.05）;高危孕妇108例中,Spearsman分析显示大脑中动脉、脐动脉的RI、PI、S/D以及上腔静脉血流S、D、A均与宫内缺氧都存在相关性（P<0.05）;logistic多因素回归分析显示：大脑中动脉、脐动脉的S/D与上腔静脉血流S、A为导致胎儿缺氧的主要影响因素（P<0.05）。结论：高危孕妇胎儿缺氧与彩色多普勒超声结合四维超声检查特征具有相关性,彩色多普勒超声结合四维超声可作为检查胎儿缺氧的可行、简单无创、方便快捷的方式,具有极高的应用价值。     

Is intrauterine growth retardation with normal umbilical artery blood flow a benign condition?

OBJECTIVE--To determine whether intrauterine growth retardation associated with normal umbilical artery blood flow is a benign condition. DESIGN--A prospective comparative study of growth retarded fetuses with normal and abnormal umbilical artery blood flow. SETTING--The fetal assessment clinic of a large maternity hospital in Ireland. PATIENTS--179 Women with singleton pregnancies in which the fetal abdominal circumference, measured by ultrasonography, was below the fifth centile for gestation. MAIN OUTCOME MEASURES--Perinatal deaths, fetal distress requiring caesarean section, preterm delivery, cerebral irritation. RESULTS--Of 124 fetuses with normal flow, all physically normal fetuses survived but one baby had cerebral irritation; there were six preterm deliveries and four caesarean sections for fetal distress. Among 55 women with abnormal flow there were two midtrimester abortions, three perinatal deaths, and one case of cerebral irritation in physically normal fetuses. CONCLUSIONS--Intrauterine growth retardation associated with normal umbilical blood flow is a different entity from that associated with abnormal flow, normal flow being largely benign and abnormal flow carrying a serious risk of adverse outcome.     

Non-invasive measurement of human fetal circulation using ultrasound: a new method.

We combined two ultrasound techniques to develop a safe, non-invasive, transcutaneous method of observing the circulation in the umbilical arteries and vein in the fetus. The umbilical cord can be located by standard echo ultrasound procedures, and this information can be used to direct a Doppler ultrasound beam on to the vessels in the cord. The signals can be heard through audio headphones or recorded on a tape recorded and spectrum-analysed. The method was successful in each of 20 patients examined, whose pregnancies ranged from 12 to 40 weeks'' gestational age, and was suitable for outpatient use. It should be useful in assessing such conditions as pre-eclampsia and intrauterine growth retardation.     

Two cases with dichorionic diamniotic triplet pregnancy and early cord entanglement.

Within a period of 6 years (1994-99) we registered 29 triplet deliveries out of a total of 13,969 hospital deliveries (0.02%). Since there is limited information about specific problems of chorionicity in triplet pregnancies, we analysed the 29 cases according to origin of pregnancy and chorionicity. We here report on two cases with a high risk according to chorionicity with dichorionic (DC) diamniotic (DA) triplet pregnancies. Out of the two cases, one pregnancy was spontaneous and one originated after in-vitro fertilization. In both pregnancies, cord entanglement was detected early in pregnancy (at 10 and 15 weeks) by color Doppler velocimetry demonstrating different heart rates within the segment of the entangled umbilical branches. The pregnancies were followed by documenting fetal behavior and color Doppler velocimetry of umbilical and fetal arteries at weekly intervals. In both cases, a primary Cesarean section was performed after detection of lung maturity. In the first case, one of the MA triplets had a transposition of the great arteries and abnormal lung vein drainage, which was the reason for neonatal death three weeks postnatally. Although early cord entanglement has been described in MA twins, this series demonstrates that it can as well be demonstrated in MA triplets. The early detection allows for extensive surveillance of the a priori high risk triplet pregnancy.     

Antenatal screening for intrauterine growth retardation with umbilical artery Doppler ultrasonography.

To assess the usefulness of continuous wave Doppler ultrasonography as an antenatal screening tool for the detection of intrauterine growth retardation and fetal compromise 2097 singleton pregnancies were studied. Umbilical artery velocity waveforms were obtained at 28, 34, and 38 weeks of gestation, from which the pulsatility index, A/B ratio, and resistance parameter were calculated. No abnormal features or indices of neonatal outcome were adequately predicted. The most sensitive index for being delivered of a growth retarded infant (less than 5th centile birth weight for gestation) was an A/B ratio at 34 weeks (sensitivity 40%, specificity 84%). Other measures that show poor neonatal nutritional state (ponderal index, skinfold thickness, and ratio of mid-arm circumference to head circumference) were even less well predicted. Acute and chronic hypoxia as determined by Apgar score, pH in blood from the cord artery, and packed cell volume correlated poorly with umbilical artery waveform indices, and there was no obvious difference between the indices of those who subsequently required operative or instrumental delivery for fetal distress and those requiring no intervention. There were three unexplained stillbirths in the series, in each of which the fetus had shown waveform patterns that suggested increased peripheral resistance, though the technique did not appear to be useful for predicting the time of subsequent death. Screening for small for dates babies in a three stage programme was of no value regardless of the threshold or index chosen. Obstetricians should resist the temptation to introduce screening with Doppler ultrasonography until its proper role has been determined.     

Nontrophoblastic placental tumors

The aim of the study was to investigate potential influence of placental tumors on fetal outcome. The study comprised 10 cases of placental tumors. The analysis included the sonographic assessment of the tumor, signs of fetal anemia, as well as signs of hemodynamic disturbances or heart failure, and intrauterine treatment. The fetal hemodynamic was examined on the basis of Doppler blood flow in the umbilical artery and vein, middle cerebral artery, and ductus venous. The evaluation of fetal heart included the measurement of heart size, blood flow through cardiac valves and the assessment of fetal heart function based on cardiovascular score. The fetal outcome was also assessed according to birthweight, gestational age at delivery, pH, Ap score at 5th minute, abnormal neurological development and the need of intrauterine therapy. Ten cases of placental tumors were prenatally detected from 1999 to 2011. Among them 7 cases of hypoechogenic, non-vascularized cysts were identified and these neither effected the hemodynamics nor complicated fetal outcome. The vascularized tumors (chorioangioma) were the cause of severe anemia and hemodynamic disturbances and these led to fetal cardiac heart failure. In all cases of vascularized tumors from 2-3 intrauterine transfusion were performed. Rich vascularized tumors (chorioangioma) may cause hemodynamic disturbances and fetal heart failure. This may require intrauterine treatment and may result in abnormal fetal outcome and neurological development.     

Doppler ultrasonographic assessment of maternal and fetal blood flow in abnormal canine pregnancy

The aim of this study was to describe the changes of uterine artery, umbilical artery and fetal abdominal aorta, renal and internal carotid arteries blood flow in abnormal canine pregnancy. Twenty-two, Brucella-negative pregnant bitches were retrospectively classified into abnormal (which had either interrupted their pregnancy between days 52 and 60 or had perinatal death >60% of the litter; n=11) and normal (which had delivered healthy puppies at term; n=11). In all the animals, color and pulsed-wave Doppler examinations of uterine artery were conducted every 10 days from Day 20 to 50 from estimated luteinizing hormone peak. Doppler ultrasonography was also conducted in the fetuses to assess umbilical artery, abdominal aorta, renal and internal carotid arteries from Day 40 to 60 of gestation. Throughout the study, resistance index (RI) of uterine, umbilical and fetal renal arteries decreased up to -15% compared to -36% (P<0.01), -11% compared to -23% (P<0.05) and 2% compared to -13% (P<0.05), respectively in the abnormal and normal bitches. Fetal abdominal aorta and internal carotid did not differ between groups (P>0.05). It is concluded that in dogs, uterine artery, umbilical artery and fetal renal artery RI differ between normal and abnormal gestation being useful for the prediction of adverse obstetric outcome.     

Nitric oxide synthesis in placenta is increased in intrauterine growth restriction and fetal hypoxia

In order to study the possible role of nitric oxide (NO) in the human placenta, we measured the concentration of its stable metabolite nitrite (NO2-) in the placentas of women with normal pregnancies and those from pregnancies complicated by intrauterine growth restriction (IUGR) with or without fetal hypoxia. We have measured nitrites by the Griess reaction in 15 placentas from IUGR pregnancies and 12 controls. Cerebroumbilical ratio (C:U) was recorded by color Doppler ultrasound and values below 1 were considered to be a predictor for fetal hypoxia. NO2- levels measured in pathological placentas were increased for at least 93% as compared to control. Subjects from pregnancies complicated by IUGR and fetal hypoxia had increased NO2- as compared to the placentas from pregnancies with IUGR and normal fetal oxygenation. NO production in placenta is increased in pregnancies with IUGR. This effect is more pronounced in those with compromised fetal oxygenation.     

Fetal tissue sampling. The San Francisco experience with 190 pregnancies.

Prenatal diagnosis of genetic defects was done using fetal blood sampling in 167 at-risk pregnancies, by fetal skin biopsy in 15 pregnancies, and by fetal liver biopsy in 8 pregnancies. Fetal blood sampling was done by fetoscopy through January 1985 and by sonographically directed percutaneous umbilical blood sampling since then. In our series, cytogenetics has become the major indication for fetal blood sampling, increasing from 6% of the cases with fetoscopy to 48% with umbilical blood sampling. Fetoscopy provided pure fetal blood in 61% of cases while umbilical blood sampling provided pure fetal blood 97% of the time. The corrected risk of fetal demise after percutaneous umbilical fetal blood sampling was 2% and after fetoscopy was 4%.     

Study of the development of uteroplacental and fetal feline circulation by triplex Doppler

The objective was to evaluate blood flow in fetal and maternal vessels by Triplex Doppler and its association with development of blood vessels during gestation in the domestic cat. Ten queens were examined weekly from 14 to 63 d after mating. Peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI) and pulsatility index (PI) of uteroplacental, aorta and umbilical fetal arteries and caudal vena cava of the fetus were evaluated. Throughout pregnancy, there was an increase in PSV and EDV in the aorta and umbilical arteries. In the caudal vena cava, there was an increase in PSV, whereas the EDV was constant, with a significant increase on Day 63. Peak systolic velocity and EDV of the uteroplacental artery reduced significantly on Day 63. Resistance index of the umbilical artery progressively decreased. In the aorta, this reduction was detected only on Day 42, with no defined pattern in the caudal vena cava and uteroplacental artery. Pulsatility index of the aorta varied. Although pulsatility increased in the caudal vena cava on Day 35 and remained elevated, pulsatility was significantly reduced in the umbilical artery by Day 63. The pulsatility index of the uteroplacental artery was constant (increased only on Day 63). Triplex Doppler evaluation could be a useful adjunct for prenatal care of pregnant queens, including assessment of vascular gestational development and prediction of gestational age.     

The response of the umbilical and femoral artery pulsatility indices in fetal sheep to progressively reduced uteroplacental blood flow

Fetal artery Doppler velocimetry may provide noninvasive information on the state of fetal oxygenation. It was hypothesized that during decreasing fetal oxygenation, the pulsatility index in the femoral artery will increase, whereas the pulsatility index in the umbilical artery will not change. Decreasing fetal oxygenation was induced in ten chronically-instrumented fetal sheep by progressive occlusion of the maternal common internal iliac artery. The pulsatility index in the umbilical artery was serially measured in six fetuses (group I, n = 6) and the pulsatility index in the femoral artery was serially measured in four fetuses (group II, n = 4). Fetal arterial oxygen content decreased by 72% in group I (P less than 0.0001) and by 79% in group II (P less than 0.0001). Fetal heart rate did not change. Fetal blood pressure increased by 11% in group I (P less than 0.02) and by 15% in group II (P less than 0.005). The umbilical artery pulsatility index (group I) did not significantly change during decreasing fetal oxygenation, whereas the femoral artery pulsatility index (group II) increased by 150% (P less than 0.005). It is concluded that progressively reduced uteroplacental blood flow results in fetal hypoxaemia, which is associated with increased pulsatility index in the femoral artery, while the pulsatility index in the umbilical artery does not change.     

Measurement of human fetal blood flow.

Real-time B-mode ultrasonography was combined with a pulsed Doppler ultrasound technique for transcutaneous measurement of human fetal blood flow in the aorta and intra-abdominal part of the umbilical vein. The target vessel was located and its diameter measured in the two-dimensional real-time image. The pulsed Doppler transducer was attached to the real-time transducer at a fixed angle. By processing the Doppler shift signals the instrument estimated the mean and maximum blood velocities and the integral under the velocity curves. This permitted calculation of the blood flow. The method was applied to 26 fetuses in normal late pregnancies. Mean blood flow in the descending part of the fetal aorta based on maximum velocity was 191 ml/kg/min. Mean flow in the intra-abdominal part of the umbilical vein was 110 ml/kg/min. This method of measurement is non-invasive and opens new perspectives in studying fetal haemodynamics.     

Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study

ABSTRACT: BACKGROUND: During early pregnancy, the placenta develops to meet the metabolic demands of the foetus. The objective of this analysis was to examine the effect of malaria parasitaemia prior to 20 weeks' gestation on subsequent changes in uterine and umbilical artery blood flow and intrauterine growth restriction. METHODS: Data were analysed from 548 antenatal visits after 20 weeks' gestation of 128 women, which included foetal biometric measures and interrogation of uterine and umbilical artery blood flow. Linear mixed effect models estimated the effect of early pregnancy malaria parasitaemia on uterine and umbilical artery resistance indices. Log-binomial models with generalized estimating equations estimated the effect of early pregnancy malaria parasitaemia on the risk of intrauterine growth restriction. RESULTS: There were differential effects of early pregnancy malaria parasitaemia on uterine artery resistance by nutritional status, with decreased uterine artery resistance among nourished women with early pregnancy malaria and increased uterine artery resistance among undernourished women with early pregnancy malaria. Among primigravidae, early pregnancy malaria parasitaemia decreased umbilical artery resistance in the late third trimester, likely reflecting adaptive villous angiogenesis. In fully adjusted models, primigravidae with early pregnancy malaria parasitaemia had 3.6 times the risk of subsequent intrauterine growth restriction (95% CI: 2.1, 6.2) compared to the referent group of multigravidae with no early pregnancy malaria parasitaemia. CONCLUSIONS: Early pregnancy malaria parasitaemia affects uterine and umbilical artery blood flow, possibly due to alterations in placentation and angiogenesis, respectively. Among primigravidae, early pregnancy malaria parasitaemia increases the risk of intrauterine growth restriction. The findings support the initiation of malaria parasitaemia prevention and control efforts earlier in pregnancy.     

Perinatal diagnosis of passive ITP: use of percutaneous umbilical blood sampling (PUBS)

Fetal blood samples can be obtained in utero by direct sampling of the umbilical cord vessels, using an ultrasound guided technique termed percutaneous umbilical sampling (PUBS). This procedure is being used more frequently in high risk pregnancies to obtain direct fetal laboratory data. In specialized centers, with trained personnel, the technique can be used with a high degree of safety and efficiency. Direct access to the fetal circulation can also allow an accurate determination of the fetal platelet count in cases of suspected fetal thrombocytopenia. The technique may be used to plan appropriate clinical management of maternal ITP as well as to diagnose the presence of fetal alloimmune thrombocytopenia. A logical strategy for obstetric management and evaluation of fetal risk can be planned. The procedure also has the potential to allow direct fetal treatment as has been the case in the management of severe fetal anemia.     

Prenatal asphyxia,hyperlacticaemia, hypoglycaemia,and erythroblastosis in growth retarded fetuses.

The umbilical venous oxygen and carbon dioxide tensions, pH, lactate and glucose concentrations, nucleated red cell (erythroblast) count, and haemoglobin concentration were measured in 38 cases of intrauterine growth retardation in which fetal blood sampling was performed by cordocentesis. The oxygen tension was below the normal mean for gestational age in 33 cases; in 14 it was below the lower limit of the 95% confidence interval for normal pregnancies. The severity of fetal hypoxia correlated significantly with fetal hypercapnia, acidosis, hyperlacticaemia, hypoglycaemia, and erythroblastosis. These findings indicate that "birth asphyxia" is not necessarily due to the process of birth.     

Reactivity of human placental chorionic plate vessels from pregnancies complicated by intrauterine growth restriction (IUGR)

A successful pregnancy is dependent on liberal placental perfusion via the maternal and fetal circulations. Doppler waveform analyses of umbilical arteries suggest increased resistance to flow in the fetoplacental circulation of pregnancies complicated by intrauterine growth restriction (IUGR). Neither the site nor the mediators responsible for this altered vascular reactivity are known, to date. In placentas in normal pregnancy, reduced oxygenation promotes contraction of the in vitro-perfused placental cotyledon and modulates agonist-induced contraction of chorionic plate arteries and veins. Placental oxygenation has also been suggested to be reduced in IUGR. We tested the hypothesis that oxygen tension could directly modify placental chorionic plate vessel vasoreactivity in IUGR. Small arteries and veins from the chorionic plate were dissected from biopsies from placentas of pregnancies complicated by IUGR and were studied using parallel wire myography. Vasoconstriction at 20%, 7%, and 2% oxygen was assessed utilizing the thromboxane mimetic U46619. Experiments were also performed in the presence of 4-aminopyridine (4AP), a blocker of voltage-gated potassium channels. Increased oxygenation reduced venous vasoconstriction but did not modify arterial vasoconstriction. 4AP increased basal tone in arteries and veins. We suggest that venoconstriction in response to hypoxia may provide a mechanism for increased fetoplacental vascular resistance associated with IUGR.     

Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction

Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction (IUGR) were the focus of our study. Our objective was to test the hypothesis that the fetal ovine myocardium adapts during an IUGR gestation by increasing glucose transporter protein expression, plasma membrane-bound glucose transporter protein concentrations, and insulin signal transduction protein concentrations. Growth measurements and whole heart tissue were obtained at 55 days gestational age (dGA), 90 dGA, and 135 dGA (term = 145 dGA) in fetuses from control (C) and hyperthermic (HT) pregnant sheep. Additionally, in 135 dGA animals, arterial blood was obtained and Doppler ultrasound was used to determine umbilical artery systolic (S) and diastolic (D) flow velocity waveform profiles to calculate pulsatility (S - D/mean) and resistance (S - D/S) indices. Myocardial Glut-1, Glut-4, insulin signal transduction proteins involved in Glut-4 translocation, and glycogen content were measured. Compared to age-matched controls, HT 90-dGA fetal body weights and HT 135-dGA fetal weights and gross heart weights were lower. Heart weights as a percent of body weights were similar between C and HT sheep at 135 dGA. HT 135-dGA animals had (i) lower fetal arterial plasma glucose and insulin concentrations, (ii) lower arterial blood oxygen content and higher plasma lactate concentrations, (iii) higher myocardial Glut-4 plasma membrane (PM) protein and insulin receptor beta protein (IRbeta ) concentrations, (iv) higher myocardial glycogen content, and (v) higher umbilical artery Doppler pulsatility and resistance indices. The HT ovine fetal myocardium adapts to reduced circulating glucose and insulin concentrations by increasing plasma membrane Glut-4 and IRbeta protein concentrations. The increased myocardial Glut-4 PM and IRbeta protein concentrations likely contribute to or increase the intracellular delivery of glucose and, together with the increased lactate concentrations, enhance glycogen synthesis, which allows for maintained myocardial growth commensurate with fetal body growth.     

The urinary excretion of pregnanediol during pregnancy determined by gas-liquid chromatography. II. Its relation with other parameters controling pregnancy (author's transl)]

The relation between the urinary pregnanediol determined by gas-liquid chromatography during pregnancy, with ultrasonic findings (biparietal diameter, thickness and echorrefringency of the placenta and the appreciated quantity of amniotic fluid), with biochemical parameters of control of pregnancy (beta-glucoronidase, total and thermostable alkaline phosphatase), with amnioscopic findings, and with several studied parameters of the amniotic fluid by amniocentesis, were studied. A good relation exists with the parameters which denote placentary insufficiency and fetal risk (irregularity in the homogeneity of the placenta, elevation of the total and thermostable alkaline phosphatase, positive amnioscopy) and also with those that are related with fetal maturity (biparietal diameter, shake test, organge cells, creatinine in amniotic fluid, etc.). These results indicate that the determination of urinary pregnanediol can be one of the tests controlling the normal and pathological pregnancies, being useful in the detection of fetal risk and the diagnosis of the intrauterine fetal maturity.     

Multiple exposures to environmental pollutants and oxidative stress: Is there a sex specific risk of developmental complications for fetuses?

Medically assisted procreation significantly contributes to an increase in twin pregnancies. One of the major factors contributing to more twin births is the use of fertility treatments. Twin pregnancy is not without a risk for fetal organ development and the health outcome of new‐borns, children, and adults. Multiple pregnancies are associated with an increased risk of developmental complications, such as perinatal mortality, premature births, and low birth weight. Oxidative stress is involved in pregnancy disorders such as abortion, intrauterine growth retardation, and prenatal mortality. The link between oxidative stress and prenatal development, poorly perceived in the medical community, is a major problem in human reproductive medicine and health outcomes. The sex‐based considerations and analyses are also, often neglected in biomedical research. In addition, fetal sexual dimorphism in antioxidant pathways following intrauterine exposure to environmental pollutants has not been explored. This is an important area of research because sexually dimorphic antioxidant adaptive responses to early life exposure‐induced oxidative stress may have long‐term effects on offspring health outcome and increase the risk of non‐communicable diseases in men and women. This concept is useful, since it may open the avenue to develop antenatal antioxidant therapeutic strategies to developmental disorders and complications related to multiple pregnancies, and in association with acute or chronic environmental exposure. This article reviews the status of research, supporting data, possible pathogenic mechanisms, and future perspectives in the proposed area. Birth Defects Research (Part C) 108:351–364, 2016. © 2016 Wiley Periodicals, Inc.