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Transplantation of liver organoids has been investigated as a treatment alternative to liver transplantation for chronic liver disease. Transportal approach can be considered as a method of delivering organoids to the liver. It is important to set the allowable organoid amount and verify translocation by intraportal transplantation. We first examined the transplantation tolerance and translocation of porcine fetal liver-derived allogeneic organoids using piglets. Fetal liver-derived organoids generated from the Kusabira Orange-transduced pig were transplanted to the 10-day-old piglet liver through the left branch of the portal vein. All recipients survived without any observable adverse events. In contrast, both local and main portal pressures increased transiently during transplantation. In necropsy samples, Kusabira Orange-positive donor cells were detected primarily in the target lobe of the liver and partly in other areas, including the lungs and brain. As we confirmed the transplantation allowance by porcine fetal liver-derived organoids, we performed intraportal transplantation of human-induced pluripotent stem cell (iPSC)-derived liver organoid, which we plan to use in clinical trials, and portal pressure and translocation were investigated. Human iPSC-derived liver organoids were transplanted into the same 10-day-old piglet. Portal hypertension and translocation of human iPSC-derived liver organoids to the lungs were observed in one of two transplanted animals. Translocation occurred in the piglet in which patent ductus venosus (PDV) was observed. Therefore, a 28-day-old piglet capable of surgically ligating PDV was used, and after the PDV was ligated, human iPSC-derived liver organoids with the amount of which is scheduled in clinical trials were transplanted. This procedure inhibited the translocation of human iPSC-derived liver organoids to extrahepatic sites without no portal hypertension. In conclusion, human iPSC-derived liver organoids can be safely transplanted through the portal vein. Ligation of the ductus venosus prior to transplantation was effective in inhibiting extrahepatic translocation in newborns and infants.

The fetal circulation has unique shunts, including the ductus venosus (DV), the tone of which dictates how much substrate‐rich blood returning from the placenta is streamed preferentially away from the liver and instead towards the heart. Herein, we aimed to use clinically relevant MRI techniques in sheep to measure indirectly induced changes in DV tone and the consequences of this on DV shunting, expressed as a ratio of umbilical vein (UV) flow [DV:UV (as a percentage)], and its impact on oxygen delivery to the fetal brain. At 116–117 days gestational age (term = 150 days), fetal sheep (n = 11) underwent surgery to implant vascular catheters. Fetal MRI scans were performed at 120–123 days gestational age. Phase contrast MRI and T2 MRI oximetry were performed to measure blood flow and oxygen saturation within the fetal circulation during states of fetal normoxaemia, hypoxaemia and hypoxaemia + systemic α‐adrenergic blockade (fetal infusion of the α‐adrenergic antagonist, phentolamine). Hypoxaemia reduced both overall fetal and cerebral oxygen delivery but did not impact either systemic or cerebral oxygen consumption. Fetal hypoxaemia alone did not impact DV shunting. However, addition of α‐adrenergic blockade to acute hypoxaemia significantly decreased DV shunting. Neither fetal hypoxaemia nor the addition of the α‐adrenergic blockade impacted left ventricular cardiac output or blood flow to the brain and the placenta. At the gestational age studied, systemic α‐adrenergic signalling is required to maintain DV shunting during fetal hypoxaemia. However, reduced DV shunting during the systemic α‐adrenergic blockade was not accompanied by a further deficit in cerebral oxygen delivery. What is the central question of this study? Ductus venosus (DV) tone is dynamic, in that it can dilate or constrict to allow more or less blood to be streamed preferentially towards the left heart and brain. We set out to use clinically relevant MRI techniques in sheep to confirm that indirect manipulation of DV tone via α‐adrenergic blockade is possible and determine the impact of this on cerebral oxygen delivery. What is the main finding and its importance? Without increased DV shunting, cerebral oxygen delivery falls during periods of acute hypoxaemia. Delineating the relationship between the extent of DV shunting and preservation of cerebral oxygen delivery might provide valuable insight during assessment of at‐risk fetuses.

This research aims to summarize the ultrasound features and pregnancy outcomes of closure of ductus venosus, providing a basis for prenatal consultation and clinical management. A retrospective cohort study was conducted at the Hunan Provincial Maternal and Child Health Care Hospital in China, involving pregnant patients diagnosed with ductus venosus closure between January 2020 and December 2023. Data on maternal age, gestational age, ultrasound findings, timing and method of pregnancy termination, and pregnancy outcomes were collected. Twenty-five pregnant women were diagnosed with ductus venosus closure during the study period. Among them, 12 cases (48%, 12/25) were associated with other abnormalities. Of these, 4 cases (33.33%, 4/12) resulted in live births, while 8 cases (66.67%, 8/12) led to induced labor due to major abnormalities. The remaining 13 cases (52%, 13/25) involved isolated ductus venosus closure, with 1 case (7.69%, 1/13) of intrauterine fetal death and 12 cases (92.31%, 12/13) of successful delivery. The closure of the ductus venosus was primarily characterized by the tramline sign (52%, 13/25) and the cord sign (48%, 12/25) on two-dimensional ultrasound, with no detectable blood flow on Doppler ultrasound imaging. Ductus venosus closure can occur as an isolated finding (52%) or in conjunction with other abnormalities (48%), with cardiac anomalies being the most common. The closure of ductus venosus can occur during the second and third trimesters of pregnancy. The two-dimensional ultrasound showing tramline sign or cord sign, along with the absence of blood flow on Doppler ultrasound imaging, should raise suspicion of closure of ductus venosus.

The fetal circulation is characterized by the presence of three physiological vascular shunts — the ductus arteriosus, the foramen ovale and the ductus venosus. Acting in concert, these shunts preferentially stream blood flow in a pattern that maximizes efficiency of blood oxygenation by the maternofetal unit. Shortly following the transition to extrauterine life, a quick and predetermined succession of events results in closure of these embryological structures with consequent establishment of postnatal vascular flow patterns. While this transition is often seamless, the physiological shunts of the fetus occasionally fail to regress. Such failure to regress can occur in isolation or in association with other congenital malformations. This failed regression challenges the circulatory physiology of the neonate and might have implications for the optimum functioning of several organ systems. When symptomatic, these shunts are treated. Interventions, when undertaken, might be medical, endovascular or surgical. The radiologist’s role continues to expand in the assessment of these shunts, in providing a roadmap for treatment and in prompt identification of treatment-related complications. This review is to familiarize radiologists with the embryology, pre- and post-treatment imaging appearances, and associated complications of persistent fetal vascular shunts.

Placental-based complications of pregnancy can be classified as acute and chronic. An example of acute placental complication is abruptio placenta. The chronic placental complications include pregnancy induced hypertension (PIH) and idiopathic Intrauterine growth restriction (IUGR). The fetus is at risk for perinatal complications in both acute and chronic conditions. Here we take a look at the natural history of the Doppler parameters in chronic conditions. The techniques used for assessing the fetal well-being include, clinical methods, biophysical tests, conventional ultrasonography, and fetal Doppler studies. Arterial Doppler studies are used to assess the well-being of the fetus and to determine the timing of delivery. However, arterial Dopplers predict only the subset of fetuses at risk of having perinatal complications. Venous Dopplers have been used to improve upon the prognostication. However, by the time the commonly used venous Doppler signs, that is, ′A′ wave reversal in ductus venosus (DV) is present, the fetus is likely to be already compromised. The fetus tries to adapt to the environment of deprivation by making a series of changes in the umbilical artery circulation, cerebral circulation, and hepatic circulation. As a result of these adaptations, the fetus overcomes the state of chronic hypoxia. This article takes a look at these changes and also the effect of these adaptations. It is suggested that serial comparisons of the venous flow characteristics of the DV and inferior vena cava (IVC) can provide an early indication of the impending decompensation and can be used to predict the time the delivery.

Background: The biochemical features of portosystemic venous shunt with high flow volume are hypergalactosaemia, hyperammonaemia, prolonged blood coagulation time, and raised serum bile acid concentration. The ductus venosus remains open with shunt flow in most neonates for a certain period after birth. However, the effects of blood flow through the ductus venosus on neonatal liver function remain unclear. Objective: To elucidate the effect of patency of the ductus venosus on liver function in early neonates. Methods: Subjects were divided into three groups by gestational age (group I, 29–32 weeks; group II, 33–36 weeks; group III, 37–41 weeks). The shunt flow volume through the ductus venosus was examined serially using ultrasonography, and correlations between flow volume and liver function in the respective groups were calculated during the first week after birth. Results: Group I had a higher flow volume and later functional closure than the other two groups. Plasma ammonia and serum total bile acid concentrations correlated with flow volume in groups I and II, and blood galactose and galactose 1-phosphate concentrations correlated significantly with flow volume in group III. Percentage hepaplastin also correlated significantly with flow volume in all groups, but plasma vitamin K concentration did not in any group. Conclusions: Patent ductus venosus has a considerable effect on crucial liver functions such as ammonia detoxification, blood coagulation, and regulation of serum total bile acid concentration in early neonates.

Introduction Cerebroplacental ratio (CPR) has been shown to be an independent predictor of adverse perinatal outcome at term and a marker of failure to reach the growth potential (FRGP) regardless of fetal size, being abnormal in compromised fetuses with birthweight above the 10th centile. The main aim of this study was to propose a risk‐based approach for the management of pregnancies with normal estimated fetal weight (EFW) and abnormal CPR near term. Material and methods This was a retrospective study of 943 pregnancies, that underwent an ultrasound evaluation of EFW and CPR at or beyond 34 weeks. CPR values were converted into multiples of the median (MoM) and EFW into centiles according to local references. Pregnancies were then divided into four groups: normal fetuses (defined as EFW ≥10th centile and CPR ≥0.6765 MoM), small for gestational age (EFW <10th centile and CPR ≥0.6765 MoM), fetal growth restriction (EFW <10th centile and CPR <0.6765 MoM), and fetuses with apparent normal growth (EFW ≥10th centile) and abnormal CPR (<0.6765 MoM), that present FRGP. Intrapartum fetal compromise (IFC) was defined as an abnormal intrapartum cardiotocogram or pH requiring cesarean delivery. Risk comparisons were performed among the four groups, based on the different frequencies of IFC. The risks of IFC were subsequently extrapolated into a gestational age scale, defining the optimal gestation to plan the birth for each of the four groups. Results Fetal growth restriction was the group with the highest frequency of IFC followed by FRGP, small for gestational age, and normal groups. The “a priori” risks of the fetal growth restriction and normal groups were used to determine the limits of two scales. One defining the IFC risk and the other defining the appropriate gestational age for delivery. Extrapolation of the risk between both scales placed the optimal gestational age for delivery at 39 weeks of gestation in the case of FRGP and at 40 weeks in the case of small for gestational age. Conclusions Fetuses near term may be evaluated according to the CPR and EFW defining four groups that present a progressive risk of IFC. Fetuses in pregnancies complicated by FRGP are likely to benefit from being delivered at 39 weeks of gestation. Near term fetuses may be evaluated with CPR and EFW, defining four groups that present different risks of IFC. Based on earlier consensus, extrapolation of risk suggests that the optimal gestation for delivery of fetuses with normal EFW but abnormal CPR might be around 39 weeks.

PurposeAbnormal flow in the ductus venosus (DV) has been reported to be associated with adverse perinatal outcome, chromosomal abnormalities, and congenital heart defects (CHD). Aneuploid fetuses have increased risk of CHD, but there are discrepancies on the performance of this markers in euploid fetuses. The aim of this meta-analysis was to establish the predictive accuracy of DV for CHD.MethodsMEDLINE, EMBASE, and CINAHL were searched from inception to February 2022. No language or geographical restrictions were applied. Inclusion criteria regarded observational and randomized studies concerning first-trimester DV flow as CHD marker. Random effect meta-analyses to calculate risk ratio (RR) with 95% confidence interval (CI), hierarchical summary receiver-operating characteristics (HSROC), and bivariate models to evaluate diagnostic accuracy were used. Primary outcome was the diagnostic performance of DV in detecting prenatal CHD by means of area under the curve (AUROC). Subgroup analysis for euploid, high-risk, and normal NT fetuses was performed. Quality assessment of included papers was performed using QUADAS-2.ResultsTwenty two studies, with a total of 204.829 fetuses undergoing first trimester scan with DV Doppler evaluation, fulfilled the inclusion criteria for this systematic review. Overall, abnormal DV flow at the time of first trimester screening was associated to an increased risk of CHD (RR 6.9, 95% CI 3.7–12.6; I2 = 95.2%) as well in unselected (RR: 6.4, 95% CI 2.5–16.4; I2 = 93.3%) and in euploid (RR: 6.45, 95% CI 3.3–12.6; I2 = 95.8%) fetuses. The overall diagnostic accuracy of abnormal DV in detecting CHD was good in euploid fetuses with an AUROC of 0.81 (95% CI 0.78–0.84), but it was poor in the high-risk group with an AUROC of 0.66 (95% CI 0.62–0.70) and in the unselected population with an AUROC of 0.44 (95% CI 0.40–0.49).ConclusionsAbnormal DV in the first trimester increases the risk of CHD with a moderate sensitivity for euploid fetuses. In combination with other markers (NT, TV regurgitation) could be helpful to identify fetuses otherwise considered to be at low risk for CHD. In addition to the improvement of the fetal heart examination in the first trimester, this strategy can increase the detection of major CHD at earlier stage of pregnancy.

Introduction The objective of the study was to compare the accuracy of the ductus venosus pulsatility index (DV PI) with that of the cerebroplacental ratio (CPR) for the prediction of adverse perinatal outcome at two gestational ages: <34 and ≥34 weeks' gestation. Material and methods This was a retrospective study of 169 high‐risk pregnancies (72 < 34 and 97 ≥ 34 weeks) that underwent an ultrasound examination of CPR, DV Doppler and estimated fetal weight at 22–40 weeks. The CPR and DV PI were converted into multiples of the median, and the estimated fetal weight into centiles according to local references. Adverse perinatal outcome was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean delivery, 5′ Apgar score <7, neonatal pH <7.10 and admission to neonatal intensive care unit. Values were plotted according to the interval to labor to evaluate progression of abnormal Doppler values, and their accuracy was evaluated at both gestational periods, alone and combined with clinical data, by means of univariable and multivariable models, using the Akaike information criteria (AIC) and the area under the curve (AUC). Results Prior to 34 weeks' gestation, DV PI was the latest parameter to become abnormal. However, it was a poor predictor of adverse perinatal outcome (AUC 0.56, 95% CI: 0.40–0.71, AIC 76.2, p > 0.05), and did not improve the predictive accuracy of CPR for adverse perinatal outcome (AUC 0.88, 95% CI: 0.79–0.97, AIC 52.9, p < 0.0001). After 34 weeks' gestation, the chronology of the DV PI and CPR anomalies overlapped, but again DV PI was a poor predictor for adverse perinatal outcome (AUC 0.62, 95% CI: 0.49–0.74, AIC 120.6, p > 0.05), that did not improve the CPR ability to predict adverse perinatal outcome (AUC 0.80, 95% CI: 0.67–0.92, AIC 106.8, p < 0.0001). The predictive accuracy of CPR prior to 34 weeks persisted when the gestational age at delivery was included in the model (AUC 0.91, 95% CI: 0.81–1.00, AIC 46.3, p < 0.0001, vs AUC 0.86, 95% CI: 0.72–1, AIC 56.1, p < 0.0001), and therefore was not determined by prematurity. Conclusions CPR predicts adverse perinatal outcome better than DV PI, regardless of gestational age. Larger prospective studies are needed to delineate the role of ultrasound tools of fetal wellbeing assessment in predicting and preventing adverse perinatal outcome. The best prediction of adverse perinatal outcome before and after 34 weeks is achieved evaluating the cerebroplacental ratio. The ductus venosus Doppler does not improve the predictive accuracy. However, prior to 34 weeks, it might provide useful chronological information about fetal hemodynamic progression.

Background The umbilical-ductal-portal system attracts significant interest due to its specific connections in fetal life. Advances in the detailed examination of hepatic circulation have further intensified this interest in recent years. Present study aimed to evaluate the obstetric and perinatal outcomes of patients diagnosed with umbilical-portal-systemic venous shunts (UPSVS) at our clinic. Methods This study involved a retrospective analysis covering the period from September 2019 to June 2024. Detailed anatomical screening, fetal echocardiography, and invasive genetic testing (for patients who consent) were performed on cases of fetal UPSVS. Accompanying anomalies, ductus venosus, the intrahepatic portal system, and hepatic veins were examined in detail. Results During the specified period, 20 patients were identified to have UPSVS, with a mean gestational age of 25 weeks at the time of diagnosis. Of these cases, five (25%) were classified as umbilical-systemic shunt (USS), three (15%) as ductus venosus-systemic shunt (DVSS), twelve (60%) as intrahepatic portal-systemic shunt (IHPSS). Ductus venosus was absent in 70% (n = 14) of the cases. Chromosomal analysis was conducted on 11 fetuses either prenatally or postnatally. Trisomy 21 was detected in two fetuses, 45,X0 in one fetus, a variant of Adams-Oliver syndrome in one fetus, and Adams-Oliver syndrome in another. Pregnancy was terminated in three cases due to chromosomal or additional congenital anomalies. In one case, intrauterine fetal death occurred at 22 weeks of gestation. Sixteen live births were recorded, of which two neonates died due to accompanying congenital anomalies, one at 2 h postnatally and the other on the 10 th postnatal day. Conclusion UPSVS are increasingly detected in the presence of major structural or chromosomal anomalies. The prognosis of isolated cases is generally favorable; however, the exact incidence remains unknown.