Normal Fetal Umbilical, Portal, and Hepatic Venous System: Four-dimensional STIC Rendering.

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Reliability and characteristics of ultrasound measurement of fetal umbilical venous blood flow volume according to the site of measurement.

PURPOSE: This study aimed at assessing the reliability and characteristics of fetal umbilical venous blood flow volume (UVFV) measurement using ultrasound. METHODS: We conducted a prospective study at our center from November 2017 to July 2019. We performed transabdominal ultrasound examinations at 18-34 weeks' gestation in uncomplicated singleton pregnancies. UVFV was calculated using vessel diameter (D) and maximum flow velocity (V) as follows: (D/2)2 × π × V × 0.5 × 60 (Q, mL/min). Two examiners measured each value three times in the free-loop (FL) and intra-abdominal (IA) portions of the umbilical vein. Intra-rater and inter-rater reliability was evaluated by intraclass correlation coefficient (ICC) and a Bland-Altman plot. RESULTS: Two hundred and eight cases were measured by two examiners. The rate of complete measurement at FL and IA was not significantly different (88.5% vs. 79.3%, respectively; p = 0.113). The intra-rater reliability of D and V was high at FL and IA. Regarding inter-rater reliability, the ICC of D, V, and Q was 0.973, 0.582, and 0.963 at FL, and 0.994, 0.912, and 0.989 at IA, respectively. A Bland-Altman plot showed that D and V had greater standard deviation at FL than IA. Regarding Q, the standard deviation at FL was also larger than at IA, and measurement variance at FL increased as the measured value increased, but that at IA did not. CONCLUSION: UVFV measurement showed high intra-rater and inter-rater reliability at FL and IA, but the variance of measurements at FL became large as the measured value increased. Properties of different measurement sites should be considered when evaluating UVFV.

Large fetal intra-abdominal umbilical vein varix: Antenatal sonographic diagnosis and follow-up.

Fetal intra-abdominal umbilical vein varix is an uncommon antenatal finding defined as focal dilatation of umbilical vein >9 mm or more than two standard deviations above the mean for the gestational age. We report the case of a 28-year-old gravida 2 diabetic lady, who presented at 35 weeks of gestation, whose antenatal ultrasonography showed a cystic lesion of size 4 × 3.8 cm showing turbulent venous flow in the fetal abdomen in continuity with the umbilical vein, diagnosed as umbilical vein varix without any other anomaly. Postnatal ultrasonography showed size reduction and thrombosis of varix. Isolated umbilical vein varix has a favorable outcome, whereas those associated with other structural anomalies have a variable prognosis. This case was reported because of the unusually large size of varix with a good outcome and also to stress the importance of detailed sonography and close fetal monitoring in the presence of umbilical vein varix.

The types of connections between the portal sinus and main portal vein in foetuses / Tipos de conexiones entre el seno portal y la vena porta principal en fetos

In the prenatal period, the three types of connections between the portal sinus and main portal vein have been published in the literature: T, X and H-shaped. The T type is the most frequent in the literature, and the aim of our study is to define the percentage of the connection types during the prenatal period in our population. In this prospective study, 237 women between 20 and 38 weeks of pregnancy without a foetal anomaly or pregnancy-related complications were included, and the precordial veins of the foetuses were examined using a wide-band color Doppler technique. The types of connections were determined by two specialists according to the shape of the colour coded vessels in Doppler examinations. The criteria of Czubalski & Aleksandrowicz (2000) were used. All of the connection types in patients were confirmed using video clips and were stored in the picture archiving and communication system. In 237 patients, the types of connection were determined by the first specialist as 189 foetuses (79.7 %) with the X-shaped or side-to-side connection, 16 foetuses (6.8 %) with the T-shaped or end-to-side type and 32 foetuses (13.5 %) with the H-shaped or parallel-coursed vessels connected with a short segment. The most common types of connections between the portal sinus and main portal vein in foetuses are X shaped or side-to-side, which is contrary to previous studies.

En el período prenatal, se han publicado en la literatura los tres tipos de conexiones entre el seno portal y la vena porta principal: en forma de T, X y H. El tipo T es el más frecuente, y el objetivo de nuestro estudio fue definir el porcentaje de tipos de conexión durante el período prenatal en nuestra población. En este estudio prospectivo, se incluyeron 237 mujeres entre 20 y 38 semanas de embarazo, sin anomalías fetales o complicaciones relacionadas con el embarazo, y se examinaron las venas precordiales de los fetos utilizando una técnica Doppler de banda ancha. Los tipos de conexiones fueron determinados por dos especialistas según la forma de los vasos codificados por color en los exámenes Doppler. Se utilizaron los criterios del estudio de Czubalski & Aleksandrowicz. Todos los tipos de conexión en los pacientes se confirmaron mediante videoclips y se almacenaron en el sistema de comunicación y en archivo de imágenes. En 237 pacientes, el primer especialista determinó en 189 fetos (79,7 %) la conexión en forma de X o de lado a lado; en 16 fetos (6,8 %) la forma de T o Tipo de extremo a lado; y en 32 fetos (13,5 %) los vasos en forma de H o paralelos, conectados con un segmento corto. Los tipos más comunes de conexiones entre el seno portal y la vena porta principal en los fetos son en forma de X o de lado a lado, lo que es contrario a estudios anteriores.

Extra-abdominal umbilical vein varix in a newborn.

Umbilical vein varices are rare fetal anomalies typically found intra-abdominally and identified on ultrasound prior to birth. Intra-abdominal umbilical vein varices account for approximately 4% of umbilical cord abnormalities and are thought to be a developmental abnormality rather than a congenital malformation. The umbilical vein varix anomaly been shown to be associated with a higher incidence of adverse perinatal outcomes and there is evidence of a relationship between this and chromosomal abnormalities. There have been few case reports of extra-abdominal varices. This case reviews a multiparous Hispanic female who delivered a baby with an extra-abdominal umbilical vein varix who was admitted to the neonatal intensive care unit but had an uncomplicated hospital course. The report reviews strategies for antenatal testing and surveillance of identified varices.

Altered development of fetal liver perfusion in pregnancies with pregestational diabetes.

BACKGROUND: Pregestational diabetes is associated with fetal macrosomia, and umbilical perfusion of the fetal liver has a role in regulating fetal growth. We therefore hypothesized that pregestational diabetes alters fetal liver blood flow depending on degree of glycemic control. METHODS: In a prospective study, 49 women with pregestational diabetes underwent monthly ultrasound examinations during 24-36 gestational weeks. Blood flow was determined in the umbilical vein, ductus venosus and portal vein, and blood velocity was measured in the left portal vein, the latter reflecting the watershed between splanchnic and umbilical flow. The measurements were compared with reference values by z-score statistics, and the effect of HbA1c assessed. RESULTS: The umbilical venous flow to the liver (z-score 0.36, p = 0.002), total venous liver flow (z-score 0.51, p<0.001) and left portal vein blood velocity (z-score 0.64, p<0.001), were higher in the study group. Normalized portal venous flow was lower (z-score -0.42, p = 0.002), and normalized total venous liver flow tended to be lower after 30 gestational weeks (z-score -0.54, p = 0.047) in the diabetic pregnancies compared with reference values from a low-risk population. The left portal vein blood velocity was positively, and the portal fraction of total venous liver flow negatively correlated with first trimester HbA1C. CONCLUSIONS: In spite of increased umbilical blood distribution to the fetal liver, graded according to glycemic control, the total venous liver flow did not match third trimester fetal growth in pregnancies with pregestational diabetes, thus contributing towards increased perinatal risks and possibly altered liver function with long-term metabolic consequences.

First-trimester ductus venosus velocity ratio as a marker of major cardiac defects.

OBJECTIVES: To examine ductus venosus (DV) flow in fetuses with and those without a cardiac defect and to evaluate different phases of DV flow in addition to the standard assessment of DV pulsatility index for veins (PIV) and the a-wave. METHODS: This was a retrospective study of singleton pregnancies that underwent first-trimester ultrasound screening, which included DV flow assessment, at the University of Tübingen (between 2010 and 2017) or the University of Cologne (between 2013 and 2016). The study population comprised normal fetuses and fetuses with major cardiac defects at a ratio of 10:1. For each fetus, the following parameters of the DV waveform were evaluated: qualitative assessment of the a-wave, PIV measurement and ratios of flow velocities during the S-wave (S) or D-wave (D) and the a-wave (a) or v-wave (v). Reproducibility of DV-PIV and DV flow ratios was evaluated in 30 fetuses in which the DV flow was assessed twice. RESULTS: Our study population included 480 anatomically normal fetuses and 48 with a cardiac defect. Median fetal nuchal translucency (NT) in the normal and in the affected group was 1.9 mm and 2.6 mm, respectively. In five (1.0%) of the normal and 18 (37.5%) of the affected cases, fetal NT thickness was above the 99th centile. In the normal group, the DV a-wave was reversed in 15 (3.1%) cases and the DV-PIV was above the 95th centile in 25 (5.2%). In the cases with cardiac defects, the a-wave was reversed and the DV-PIV measurement was above the 95th centile in 26 (54.2%). The reproducibility of measurement of the ratios of DV flow velocities was similar to that of the DV-PIV. Most cardiac defects were associated with an abnormal a/S or a/D ratio. If the cut-off for these two ratios was set at the 5th centile of the normal distribution, the detection rate of fetal cardiac anomalies would be 62.5%. This compares favorably with the DV-PIV, which detects 26 (54.2%) of the affected fetuses for the same threshold. CONCLUSION: In the first trimester, the a/S ratio has the potential to detect approximately 60% of congenital cardiac defects for a false-positive rate of 5%. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Independent validation of metric optimized gating for fetal cardiovascular phase-contrast flow imaging.

PURPOSE: To validate metric optimized gating phase-contrast MR (MOG PC-MR) flow measurements for a range of fetal flow velocities in phantom experiments. 2) To investigate intra- and interobserver variability for fetal flow measurements at an imaging center other than the original site. METHODS: MOG PC-MR was compared to timer/beaker measurements in a pulsatile flow phantom using a heart rate (∼145 bpm), nozzle diameter (∼6 mm), and flow range (∼130-700 mL/min) similar to fetal imaging. Fifteen healthy fetuses were included for intra- and interobserver variability in the fetal descending aorta and umbilical vein. RESULTS: Phantom MOG PC-MR flow bias and variability was 2% ± 23%. Accuracy of MOG PC-MR was degraded for flow profiles with low velocity-to-noise ratio. Intra- and interobserver coefficients of variation were 6% and 19%, respectively, for fetal descending aorta; and 10% and 17%, respectively, for the umbilical vein. CONCLUSION: Phantom validation showed good agreement between MOG and conventionally gated PC-MR, except for cases with low velocity-to-noise ratio, which resulted in MOG misgating and underestimated peak velocities and warranted optimization of sequence parameters to individual fetal vessels. Inter- and intraobserver variability for fetal MOG PC-MR imaging were comparable to previously reported values.

The fate of the vitelline and umbilical veins during the development of the human liver.

Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, and used Amira 3D reconstruction and Cinema 4D remodeling software for visualization. The vitelline and umbilical veins enter the systemic venous sinus on each side via a common entrance, the hepatocardiac channel. During expansion into the transverse septum at Carnegie Stage (CS)12 the liver bud develops as two dorsolateral lobes or 'wings' and a single ventromedial lobe, with the liver hilum at the intersection of these lobes. The dorsolateral lobes each engulf a vitelline vein during CS13 and the ventromedial lobe both umbilical veins during CS14, but both venous systems remain temporarily identifiable inside the liver. The dominance of the left-sided umbilical vein and the rightward repositioning of the sinuatrial junction cause de novo development of left-to-right shunts between the left umbilical vein in the liver hilum and the right hepatocardiac channel (venous duct) and the right vitelline vein (portal sinus), respectively. Once these shunts have formed, portal branches develop from the intrahepatic portions of the portal vein on the right side and the umbilical vein on the left side. The gall bladder is a reliable marker for this hepatic vascular midline. We found no evidence for large-scale fragmentation of embryonic veins as claimed by the 'vestigial' theory. Instead and in agreement with the 'lineage' theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the 'hemodynamic' theory, the left-right shunts develop de novo.

Sexual Dimorphism in Umbilical Vein Blood Flow During the Second Half of Pregnancy: A Longitudinal Study.

OBJECTIVES: To investigate gestational age-specific serial changes in umbilical vein (UV) volume blood flow during the second half of normal pregnancy and establish sex-specific reference ranges. METHODS: This work was a prospective longitudinal study of singleton low-risk pregnancies. The UV diameter and maximum blood flow velocity were serially measured by sonography at the intra-abdominal portion of the UV over 19 to 41 weeks. Umbilical vein volume blood flow was calculated and normalized for estimated fetal weight. RESULTS: One hundred seventy-nine women and their fetuses (87 male and 92 female) were included in the final analysis, and a total of 746 observations were used to construct sex-specific reference intervals. We found no statistically significant sex-specific differences in the UV parameters examined. However, the temporal development patterns of normalized UV volume blood flow appeared to differ between male and female fetuses during the second half of pregnancy, with crossovers at 24 and 32 weeks' gestation. CONCLUSIONS: Umbilical vein volume blood flow is similar among male and female fetuses in quantitative terms, but the pattern of gestational age-dependent temporal changes may be different, which may have important physiologic implications with regard to in utero development and maturation of the fetoplacental unit.

Length to width ratio of the ductus venosus in simple screening for fetal congenital heart diseases in the second trimester.

Antenatal diagnosis of congenital heart disease (CHD) is still low even though screening was first introduced over 25 years ago. The purpose of our study was to determine the efficacy of a second-trimester prenatal ultrasonographic method of screening for CHD.From September 2012 to September 2013, the length and width of the fetal ductus venosus were measured sonographically in 1006 singleton fetuses, and the ratio of length to width was calculated. The accuracy of each fetal measurement and Doppler ultrasonography were determined. The standard fetal echocardiographic evaluations including 2-dimensional gray-scale imaging, color, and Doppler color flow mapping were performed. The transducer was aligned to the long axis of the fetal trunk to view the ductus venosus in its full length, including the inlet (isthmus) and outlet portions of the vessel. The diameters of the vessel inner wall and mid-point of the ductus venosus were measured using calipers. All scans and fetal measurements were conducted by a registered sonographer with more than 20 years of perinatal ultrasound screening experience.Of the 1006 singleton fetuses between 19 and 28 weeks' gestation, 36 had CHD. The ductus venosus length/width ratio (DVR) for the first CHD screening was extremely sensitive at 88.90%, with a specificity of 99.10% for the cardiac abnormalities included in this study. Chromosomal anomalies accompanied CHD in 0.4% (4/1006) of all cases and 11.11% (4/36) of the CHD cases.The DVR differed significantly between fetuses with CHD and normal fetuses during the second trimester. Careful assessment of the ratio should be a part of the sonographic examination of every fetus. In the case of a small DVR, advanced echocardiography and karyotype analysis should be performed. The ratio is a helpful tool for screening CHD abnormalities prenatally in the Chinese population.

A retrospective single centre review of the incidence and prognostic significance of persistent foetal right umbilical vein.

The objective of our study was to appraise the incidence and significance of persistent right umbilical vein (PRUV), the most common foetal venous aberration. Based on a south Indian antenatal cohort, we identified 23 cases of PRUV amongst 20,452 foetuses of consecutive pregnancies, from 2009 to 2014, yielding an incidence of 1 in 889 total births (0.11%). The median maternal age was 24 (IQR, 22-26) years, and median gestational age at diagnosis was 23 (IQR, 22-24) weeks. Intrahepatic drainage of PRUV was seen in 91.3% cases. In three cases (13%), ductus venosus was absent. In 52.2% of the cases, additional major abnormalities were observed - predominantly cardiovascular (39.1%). The common minor marker was single umbilical artery (13%). The karyotype was found to be normal in six cases (26%) which underwent invasive testing. When associated anomalies were inconsequential or absent, the postnatal outcome was good, which reflected in 60.9% of our cases.

Type 1 and 3 inositol trisphosphate receptors are required for extra-embryonic vascular development.

The embryonic-maternal interface of the placental labyrinth, allantois, and yolk sac are vital during embryogenesis; however, the precise mechanism underlying the vascularization of these structures remains unknown. Herein we focus on the role of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R), which are intracellular Ca(2+) release channels, in placentation. Double knockout (DKO) of type 1 and 3 IP3Rs (IP3R1 and IP3R3, respectively) in mice resulted in embryonic lethality around embryonic day (E) 11.5. Because IP3R1 and IP3R3 were co-expressed in endothelial cells in the labyrinth, allantois, and yolk sac, we investigated extra-embryonic vascular development in IP3R1- and IP3R3-DKO mice. The formation of chorionic plates and yolk sac vessels seemed dysregulated around the timing of the chorio-allantoic attachment, immediately followed by the disorganization of allantoic vessels, the decreased expression of the spongiotrophoblast cell marker Tpbpa and the growth retardation of the embryos in DKO mice. Fluorescent immunohistochemistry demonstrated downregulation of a vascular endothelial marker, CD31, in labyrinth embryonic vessels and poor elongation of extra-embryonic mesoderm into the labyrinth layer in DKO placenta, whereas the branching of the DKO chorionic trophoblast was initiated. In addition, allantoic and yolk sac vessels in extra-embryonic tissues were less remodeled in DKO mice. In vitro endothelial cord formation and migration activities of cultured vascular endothelial cells derived from human umbilical vein were downregulated under the inhibition of IP3R. Our results suggest that IP3R1 and IP3R3 are required for extra-embryonic vascularization in the placenta, allantois, and yolk sac. This is the first demonstration of the essential role of IP3/IP3Rs signaling in the development of the vasculature at the embryonic-maternal interface.

Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies.

Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (-17.7±16.4% versus -9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth.

A Benign Anomalous Umbilical Vein: Not All Umbilical Veins That Wander Are Lost.

A rare case of an anomalous umbilical vein with a previously unreported outcome is described. Most reported cases of anomalous umbilical veins are associated with significant concurrent fetal anomalies and poor outcomes. Fetal magnetic resonance imaging was used in this case to confirm normal portal and hepatic venous vasculature. No other fetal anomalies were identified on ultrasound. The infant was delivered at term and is healthy at the age of 8 months. Parental anxiety regarding the diagnosis was the only adverse consequence of this incidental finding.

Hemodynamic studies of isolated absent ductus venosus.

OBJECTIVE: The objective of this article is to evaluate hemodynamic changes among fetuses with isolated absent ductus venosus (IADV) diagnosed by prenatal ultrasonography. PATIENTS AND METHODS: Fetuses with prenatal diagnosis of IADV were recruited and followed. Hemodynamic assessment was performed in all cases, including measurement of cardiac dimensions, shortening fraction, myocardial performance index, preload index in the inferior vena cava and the presence of venous pulsations in the umbilical vein (UV). RESULTS: Nine fetuses of IADV were assessed, including six cases with extra-hepatic UV drainage and three with intra-hepatic drainage. All fetuses with extra-hepatic UV drainage showed an elevated preload index in the inferior vena cava, venous pulsations in the UV and cardiomegaly. Of them, four had hydrops, two showed poor cardiac function and three resulted in perinatal mortality. Three cases with intra-hepatic drainage had continuous flow in the UV, normal in all hemodynamic parameters and all survived. CONCLUSION: Hemodynamic assessment of fetuses with IADV was helpful in predicting the development of hydrops and perinatal mortality. The poor prognostic factors included cardiac overload, cardiomegaly, poor myocardial performance, increased preload, the presence of venous pulsations and extra-hepatic UV drainage. © 2015 John Wiley & Sons, Ltd.

Examination of the twin placenta.

Twin birth rates have increased dramatically over the past three decades, and twins currently account for 3% of all pregnancies. Twin pregnancies of any type are at risk for prematurity. In addition, monochorionic twin pregnancies (25-30% of all twin pregnancies) are predisposed to a specific set of complications, including twin-to-twin transfusion syndrome (TTTS), twin reversed arterial perfusion syndrome (TRAP), malformations, and intertwin growth discordance. This article reviews the basic mechanisms underlying the twinning process, the relationship between zygosity and chorionicity, and the various types of twinning. We describe the major complications of monochorionic twinning in association with their reported placental characteristics (or lack thereof). Finally, a rational, evidence-based approach to examination of the twin placenta is presented. It is essential for the pathologist to understand the value, strengths, and limitations of examination of the twin placenta in order to provide a meaningful clinicopathological correlation in complicated (monochorionic) twin pregnancies.