Abstract
Introduction: Fetal extrahepatic portosystemic venous shunt (FEPSVS) is vascular malformations that divert placental and bowel blood from the liver into the systemic circulation. When uncorrected, it can lead to severe pathologic consequences after birth. In this study, we aim to report our method of prenatal diagnosis, the developing insight regarding prenatal counseling, and postnatal treatment. Methods: Retrospective review of fetuses diagnosed with FEPSVS, classified into Abernethy type I or II based on the absence or existence of intrahepatic portal venous system (IHPVS) flow. Two different counseling periods were compared regarding pregnancy management and postnatal outcome. Results: In the first period (2000–2010), 5 cases were diagnosed; 4 were type I with an 80% termination rate. In the second period (2011–2021), 6 cases were diagnosed; with only a 16% termination rate in type I cases. Two type II cases were reclassified to type I postnatally and corrected successfully. Of the 6 born alive, 5 had early surgical/endovascular corrections, and 1 experienced spontaneous closure. All the cases resulted in a successful rescue of the IHPVS with good outcomes. Conclusion: During our developing insights we realized that: (1) the adult classification according to the IHPSVS is not relevant for prenatal prognostic counseling; (2) prenatal diagnosis of FEPSVS is essential in promoting early postnatal investigation and corrective intervention, which might prevent the appearance of postnatal complications.
Plain Language Summary
Fetal extrahepatic portosystemic venous shunt (FEPSVS) is vascular malformations that divert placental and bowel blood from the liver into the systemic circulation. When uncorrected, it can lead to severe pathologic consequences after birth. Cumulative experience in the diagnosis has changed the counseling and clinical management of this vascular anomaly. Originally considered as a highly lethal condition, our experience has shown that hepatic reperfusion can develop maintaining a normal liver function after surgical closure of the shunt. Accurate prenatal characterization of FEPSVS is crucial for precise multidisciplinary counseling and programming of the postnatal intervention, thus preventing long-term pathological complications.
Introduction
Congenital extrahepatic portosystemic venous shunts, as called in the adult literature, are rare vascular malformations in which the portal flow is diverted from the liver into the systemic veins [1]. In utero, any part of the three components that compose the conducting vascular complex from the placenta to the heart: the umbilical vein (UV), portal vein, and the ductus venosus (DV) can create an extrahepatic shunt. In our experience, the DV extrahepatic systemic shunts were all associated with completely normal intrahepatic umbilcal-portal vascular anatomic configuration and thus were excluded due to lack of counseling dilemma as an isolated factor. The main prenatal prognostic factor regarding postnatal liver function is related to the absence or partial existence of Doppler intrahepatic portal venous system (IHPVS) flow [2]. Persisting and untreated may lead to life-threatening complications such as pulmonary hypertension, hypoxemia from hepatopulmonary syndrome, and benign or malignant hepatic tumors [3‒5,3, 5]. First described 200 years ago by John Abernethy [6], most of the literature is related to children and adult populations, describing clinical manifestation, methods of diagnosis, and treatment possibilities [7‒12].
Morgan and Superina [13] were the first to classify postnatal CEPSVS into two types: Abernethy Type I, a complete diversion of the portal flow into the systemic circulation with the absence of IHPVS, and Type II in which any component of the IHPVS exists in the liver. Currently, at least four additional anatomical classifications of CEPSVS have been proposed [14‒17]; however, the prevailing prognostic one for prenatal counseling, is still the traditional Abernethy type I and II classification. Prenatal determination of the type of shunt is essential for counseling and planning postnatal treatment. In the early period of our learning curve, based on the literature known to us [7, 18, 19], it was customary in our department to counsel patients with Abernethy type I that liver transplant would be suggested as the first-line postnatal therapeutic approach.
Although prenatal investigation and diagnosis of the fetal venous system and shunts have been reported more often in the last 2 decades, the data on the natural history of extrahepatic shunts are still very limited [19‒23]. Even the most updated International Observational Study reported only 2 cases among 66 with a prenatal diagnosis of fetal extrahepatic portosystemic venous shunt (FEPSVS) [24]. In this study, we aimed to report our evolving experience with FEPSVS from the fetus to infancy and to assess the impact of prenatal diagnosis on postnatal management.
Methods
We performed a retrospective review of our database of tertiary prenatal diagnosis unit in a large referral academic medical center, covering a period between 2000 and 2021. The data were collected from computerized textual, and visual files including volume files, clips, and pictures stored on the 4D view system. Only cases with available documented outcomes were included.
This study protocol was reviewed by the Helsinki Committee of the Sheba Medical Center Board which approved the study as a retrospective observational-descriptive nonclinical review (study number 534-18-SMC, 1/11/2018) and was exempted from requiring written informed consent. All patients were contacted by telephone, gave verbal consent to participate in the study, and shared by telephone their children’s medical data with us.
Ultrasound examinations were performed using various equipment: ATL HDI 9 (Advanced Technology Laboratories, Bothell, WA, USA) Voluson 730 Expert, E8 Expert, and E10 Expert (GE Medical Systems, Zipf, Austria) system, equipped with a 4–8 MHz transabdominal and a 5–9 MHz or 6–12 MHz transvaginal transducers. Three- and four-dimensional (3D/4D) color Doppler technology with high‐definition flow was used depending on the equipment used.
All fetuses underwent detailed anatomical examination, including echocardiographic evaluation, by one of the two observers (R.A., Z.K.), each with more than 30 years of experience in the field of fetal ultrasound. Genetic counseling and fetal karyotyping/chromosomal microarray analysis/whole exome sequencing analysis were offered to all women involved depending on availability at the time of examination.
In our obstetrics ultrasound unit, fetal abdominal venous system evaluation is an integral part of the routine antenatal anatomical survey. Methodological details regarding anatomic imaging were described previously [20, 25]. The diagnosis of FEPSVS was based on three main sonographic criteria: (1) abnormal communication between the main portal vein (MPV) or the UV at the level of portal sinus; (2) absence or abnormality of either or all of the intrahepatic UV – portal and DV systems; (3) triphasic Doppler waveform on the precordial afferent veins: MPV, the UV, the splenic vein, and the superior mesenteric vein draining into the hepatic vein, right heart atria, or the inferior vena cava (IVC).
The presence or absence of the IHPVS and the DV were recorded in each case. The absence of Doppler evidence of IHPVS was classified as type I and the presence of partial or complete IHPVS as type II.
In the first period, between 2000 and 2010, counseling during pregnancy in cases with FEPSVS type I was based on the, then known to us, adult literature and our lack of experience with surgical therapeutic interventions. It emphasized the most probable need for a postnatal liver transplant, and hence, termination of pregnancy was suggested to the parents in all cases. In the second period from 2011 to 2021, as a consequence of our developing experience and others [26], counseling raised the possibility that Doppler nonvisible intrahepatic portal vascularity may reappear after birth following surgical closure of the shunt and reperfusion of the liver hypoplastic portal vessels, with fair function and prognosis. Termination of pregnancy was offered only as an option since no certainty for the postnatal portal regeneration in all cases could be assured.
All cases were examined after birth by pathology, postmortem venography, or neonatal imaging, including ultrasound, venography, and computed tomographic angiography (CT-angio). All live-born fetuses were examined shortly after delivery by certified neonatologists and pediatric gastroenterologists who performed meticulous physical examinations. Liver metabolic functions including blood ammonia level and abdominal ultrasound have been performed before discharge from the hospital. Long‐term follow‐up was carried out by pediatric gastroenterologists and surgeons.
Results
During the study period, we identified eleven fetuses with a diagnosis of FEPSVS. Four cases had also been included in an interim analysis of fetuses with umbilical-portal-systemic venous shunts reported previously [23] (Table 1). The mean gestational age at diagnosis was 24 weeks (range 14–35). The collected data were analyzed with a focus on two main areas: (1) in utero sonographic presentation and management and (2) postnatal findings, treatment, and outcomes.
Summary list of cases diagnosed with fetal extrahepatic umbilical-portal systemic shunts in a single tertiary obstetric ultrasound unit between 2000 and 2021
Case . | Abernethy type of shunt . | GA at diagnosis . | Origin and drainage of the shunt . | Intrahepatic portal venous system . | Associated findings . | Postnatal outcome . |
---|---|---|---|---|---|---|
1 | I | 22 | UV-LA | No | Mitral stenosis | TOP |
2 | I | 22 | MPV-IVC | No | Cleft lip | TOP |
Male XX | ||||||
3 | I | 23 | UV-RA | No | No | TOP |
4 | I | 14 | UV-RA | No | No | TOP |
5 | II | 26 | UV-Iliac | Only right branch | No | Open surgery closure at 6 years old after 2 failed radiologic closure |
Spleno-left renal shunt | Healthy | |||||
6 | II | 22 | MPV-IVC | Both right and left branches | No | Open surgery partial closure at 6 months |
Definite REX operation at 9 months | ||||||
Healthy | ||||||
7 | I | 28 | MPV-IVC | No | No | TOP |
8 | 1 | 29 | MPV-IVC | No | BPS | Spontaneous closure after birth |
In utero laser ablation | Healthy | |||||
9 | I | 35 | MPV-IVC | No | No | Open surgery closure at 22 months |
Healthy | ||||||
10 | I | 17 | MPV-IVC | No | No | Endovascular stage closure at 10 months |
Healthy | ||||||
11 | I | 17 | MPV-IVC | No | No | Endovascular stage closure at 7 months |
Healthy |
Case . | Abernethy type of shunt . | GA at diagnosis . | Origin and drainage of the shunt . | Intrahepatic portal venous system . | Associated findings . | Postnatal outcome . |
---|---|---|---|---|---|---|
1 | I | 22 | UV-LA | No | Mitral stenosis | TOP |
2 | I | 22 | MPV-IVC | No | Cleft lip | TOP |
Male XX | ||||||
3 | I | 23 | UV-RA | No | No | TOP |
4 | I | 14 | UV-RA | No | No | TOP |
5 | II | 26 | UV-Iliac | Only right branch | No | Open surgery closure at 6 years old after 2 failed radiologic closure |
Spleno-left renal shunt | Healthy | |||||
6 | II | 22 | MPV-IVC | Both right and left branches | No | Open surgery partial closure at 6 months |
Definite REX operation at 9 months | ||||||
Healthy | ||||||
7 | I | 28 | MPV-IVC | No | No | TOP |
8 | 1 | 29 | MPV-IVC | No | BPS | Spontaneous closure after birth |
In utero laser ablation | Healthy | |||||
9 | I | 35 | MPV-IVC | No | No | Open surgery closure at 22 months |
Healthy | ||||||
10 | I | 17 | MPV-IVC | No | No | Endovascular stage closure at 10 months |
Healthy | ||||||
11 | I | 17 | MPV-IVC | No | No | Endovascular stage closure at 7 months |
Healthy |
BPS, bronchopulmonary sequestration; IHPVS, intrahepatic portal venous system; IVC, inferior vena cava; GA, gestational age; LA, left atria; MPV, main portal vein; RA, right atria; TOP, termination of pregnancy; UV, umbilical vein.
In utero Presentation and Management
Among the eleven cases, four were referred to our center for consultation and seven were identified by us. The common denominator of all the eleven fetuses was an abnormal abdominal umbilical-portal course, failing to identify the normal liver umbilical-portal-DV complex at the axial plane. This led us to explore the integrity of the fetal venous system.
Seven fetuses (cases 2, 6, 7, 8, 9, 10, 11) demonstrated an abnormal course of a dilated UV merging with the MPV into a common vessel draining into the IVC (Fig. 1a–c) or both separately draining into the hepatic segment of the IVC (Fig. 2a, b), instead of the subdiaphragmatic infundibulum. In all these cases, the DV could not be delineated as a separate anatomic structure. In the remaining four fetuses, the UV had various abnormal communications with the right atria, the left atrium, and the Iliac vein (Table 1).
Type I portosystemic extrahepatic shunt. a Axial plane demonstrates the communication between the MPV and the UV merging into a common truncus draining into the IVC. Note the absence of visible normal portal intrahepatic branches and the DV. b The oblique abdominal plane demonstrates the confluence of the superior mesenteric vein and the splenic vein into the MPV, draining into the common truncus and the IVC. In the inserted figure, note the characteristic triphasic Doppler waveform in the superior mesenteric vein. c Schematic representation. Dao/Ao, descending aorta; DV, ductus venosus; HA, hepatic artery; IVC, inferior vena cava; MPV, main portal vein; LPV, left portal vein; LPVm, left portal vein medial branch; LPVi, left portal vein inferior branch; LPVs, left portal vein superior branch; RAPV, right anterior portal vein; RPPV, Right posterior portal vein; SMV, superior mesenteric vein; SplV/SV, splenic vein; Sp, spine; St, stomach; UV, umbilical vein.
Type I portosystemic extrahepatic shunt. a Axial plane demonstrates the communication between the MPV and the UV merging into a common truncus draining into the IVC. Note the absence of visible normal portal intrahepatic branches and the DV. b The oblique abdominal plane demonstrates the confluence of the superior mesenteric vein and the splenic vein into the MPV, draining into the common truncus and the IVC. In the inserted figure, note the characteristic triphasic Doppler waveform in the superior mesenteric vein. c Schematic representation. Dao/Ao, descending aorta; DV, ductus venosus; HA, hepatic artery; IVC, inferior vena cava; MPV, main portal vein; LPV, left portal vein; LPVm, left portal vein medial branch; LPVi, left portal vein inferior branch; LPVs, left portal vein superior branch; RAPV, right anterior portal vein; RPPV, Right posterior portal vein; SMV, superior mesenteric vein; SplV/SV, splenic vein; Sp, spine; St, stomach; UV, umbilical vein.
Type II portosystemic extrahepatic shunts. a The axial plane demonstrates the MPV draining directly into the IVC. Although anatomically not normal, the intrahepatic portal system presented both branches. No characteristic DV is seen. The insert demonstrates the characteristic triphasic Doppler waveform of the MPV systemic shunt. b Schematic representation. Ao, descending aorta; IVC, inferior vena cava; MPV, main portal vein; LPV, left portal vein; LPVm, left portal vein medial branch; LPVi, left portal vein inferior branch; LPVs, left portal vein superior branch; RAPV, right anterior portal vein; RPPV, right posterior portal vein; SMV, superior mesenteric vein; SplV, splenic vein; Sp, spine; St, stomach; UV, umbilical vein.
Type II portosystemic extrahepatic shunts. a The axial plane demonstrates the MPV draining directly into the IVC. Although anatomically not normal, the intrahepatic portal system presented both branches. No characteristic DV is seen. The insert demonstrates the characteristic triphasic Doppler waveform of the MPV systemic shunt. b Schematic representation. Ao, descending aorta; IVC, inferior vena cava; MPV, main portal vein; LPV, left portal vein; LPVm, left portal vein medial branch; LPVi, left portal vein inferior branch; LPVs, left portal vein superior branch; RAPV, right anterior portal vein; RPPV, right posterior portal vein; SMV, superior mesenteric vein; SplV, splenic vein; Sp, spine; St, stomach; UV, umbilical vein.
Associated anomalies were found in three type I cases: mitral stenosis in case 1, cleft lip, and 46 male XX in case 2. Both were in the first period and decided to terminate the pregnancy. In case 8, bronchopulmonary sequestration was treated by in utero laser coagulation and pregnancy continued without complications.
Two cases, one in each period (cases 5 and 6) were classified as Abernethy type II. In case 5 (UV-Iliac), it was possible to identify only the right portal branch (online suppl. Fig. 1; for all online suppl. material, see https://doi.org/10.1159/000543529). This case also included a Spleno-left renal shunt which was diagnosed only after birth. In case 6 (MPV-IVC), the two intrahepatic portal branches were identified. The right branch emerged from the portal left branch. The MPV drained into a dilated IVC and gave origin to the left branch (Fig. 2, online suppl. Fig. 2).
Nine fetuses (cases 1–4 in the first period and 7–11 in the second period) were assigned as Abernethy type I (Fig. 1, online suppl. Fig. 3–6). None of them showed IHPVS despite consistent and repetitive efforts to demonstrate it by color Doppler. In all these cases, liver perfusion was compensated by a prominent hepatic artery [27]. In all cases, except for case 5, triphasic Doppler pulsations instead of monophasic flow on the UV, splenic vein, superior mesenteric vein, and MPV verified the connection to the systemic precordial veins.
In all cases, the multidisciplinary counseling team explained to the parents the significance of the findings. In the first period, based on the then-known to us literature, the possibility of a postnatal liver transplant as the probable only option was presented to the couple. As a result, all four type I (cases 1–4) elected to terminate the pregnancy.
On the other hand, in the later period, in which counseling regarding postnatal liver transplant was not an absolute possibility, only one (20%) of the five type I cases (case 7) elected to terminate the pregnancy. Both type II cases in the two periods elected to continue the pregnancy. All six women delivered a spontaneous vaginal delivery at term and immediate pediatric gastrointestinal surveillance was carried out.
Postnatal Findings and Outcome
Of the five couples who opted to terminate the pregnancy, four agreed on postmortem imaging studies: In two, venography through umbilical catheter was performed, and in the other two, CT-angio was performed. In all cases, CEPSVS was confirmed.
In two cases, the parents agreed on postmortem pathologic examination. In both, liver histology revealed changes compatible with Abernethy type I CEPSVS as described previously by De Vito [28]: abnormal arterio-biliary dyads, absence of normal portal veins, increased hepatic arterial branches, and the presence of dilated “Portal tracts multiple thin-walled channels.”
In all born alive neonates, abdominal Doppler ultrasound confirmed the existence of an extrahepatic Portal shunt. For those with a prenatal diagnosis of type I, the absence of IHPVS was confirmed, however, for the two who were diagnosed prenatally as type II, the diagnosis was changed to type I due to the disappearance of Doppler-evidenced IHPVS perfusion as a result of the UV occlusion.
Ammonia level was mildly elevated only in 4 cases (5, 6, 10, 11) and controlled by a low protein diet. All others had normal metabolic liver function.
Intravenous catheterization was performed in 5 cases; in case 5 (type II converted to type I after birth), left splenorenal shunt and no IHPVS were observed at 3 weeks of life. Two attempts to close the shunt, at 6 months and 1 year of age, were unsuccessful due to the large fistula. Finally, an open two-stage closure of the shunt was performed at 6 years of age, and at the time of publication, he is 17 years old and healthy.
Case 6 (type II converted to type I after birth) had intravenous catheterization at 3 months of age confirming the portal-IVC shunt. The radiologic intervention to close the shunt was postponed due to the early infant age; however, the parents decided to perform open surgery.
A two-stage operation was performed at 6 months of age. In the first stage, gradual banding of the shunt created a reopening of labyrinthic left portal vein, and 3 months later REX shunt was implanted between the superior mesenteric vein and neo-appeared left portal vein. The child is now 10 years old and healthy.
Case 8 had CT-angio on the fifth day of life and a small extrahepatic shunt was demonstrated. At the age of 2 months, abdominal US confirmed that the shunt closed spontaneously with the appearance of portal liver vascularity. The child is 8 years old and healthy.
Case 9 had catheterization at 18 months of age, revealing a shunt between the superior mesenteric vein draining into the IVC through a short and wide MPV without any intrahepatic branches. During balloon occlusion, moderately and small hypoplastic portal veins appeared. Due to the inability to perform endovascular closure, open surgery shunt banding by two stages was performed at 22 months with the appearance of portal vascularity. The child has developed appropriately without any metabolic disturbances. He is now 4 years old and healthy.
Case 10 presented elevated ammonia and liver enzyme levels at 8 months of age. An endovascular stage closure resulted in the reappearance of hypoplastic portal liver vascularity. A second radiologic intervention after 6 months revealed a normal portal perfusion of the liver the child is at present 3 years old, developing well with normalization of liver function tests.
Case 11 presented elevated ammonia levels after birth. At the age of 7 months old, he had radiologic endovascular catheterization with the closure of the shunt and the consequent appearance of the portal liver’s vascularity and normalization of the ammonia level. Presently he is 1 year old doing well, and on continuing clinical evaluations.
Discussion
Fetal vascular shunts originate from three embryologic systems: The umbilical, vitelline (portal), and the DV. They are divided into four types: the umbilical and the DV are extrahepatic (mostly into the right atria and the IVC), and the portal system shunts are divided into intra and extrahepatic shunts. In the first two types, the shunt is spontaneously closed immediately after birth, and the intrahepatic portal shunts by 12–24 months [23]. However, spontaneous closure of the extrahepatic shunt is rare and when untreated can cause life-threatening complications. In the fetus, the best sonographically demonstrable region for investigation is at the level of the liver and the vessel’s drainage into the precordial vessels: the hepatic veins, the IVC, and the right atria. For all types of shunts, the integrity of the IHPVS (excluding associated malformations) is the most important prenatal prognostic factor regarding postnatal liver function, affecting counseling and pregnancy management.
As in many fields of medicine, the best strategy to improve health is early diagnosis of disease and therapy performance as soon as possible to prevent its consequences. Fetal screening for congenital malformations has been practiced worldwide for more than 30 years, still, the portal system and its intrahepatic connections, are not currently included in any guidelines of the standard fetal examination and thus, the awareness and knowledge regarding possible malformations are the property of only a few.
Neonates with portosystemic extrahepatic shunts have a relatively long asymptomatic window before serious morbidities appear. Indeed, the median age of diagnosis was reported to be 21 years [24]. This report is the first to synchronize in utero diagnosis of FEPSVS with the postnatal outcome, showing how as early as possible closure of the shunt may avoid severe long‐term complications including the need for liver transplantation.
A review of the literature on prenatal diagnosis appeared in 2018 by Francois et al. [22]. The authors collected 196 articles between 1982 and 2016 and were able to retrieve a total of 127 cases. Among them, 72 cases had extrahepatic and 51 intrahepatic shunts. This is in contrast to our data, in which the incidence of intrahepatic shunts was two to three times more common [23, 29]. Furthermore, the reliability of the data from 1982 is questionable considering the very limited knowledge of this entity and the limited quality of the Doppler technology existing in that period, which is essential for prenatal diagnosis. In addition, in this article, the results and management are given as one piece with no specifications regarding extra and intrahepatic subtypes and therefore, cannot contribute to the present study.
Three important points arise from the current study: first, accurate in utero diagnosis and anatomic definition of the exact point of origin and drainage of the shunt using multi-planar 3D color Doppler confirmed by triphasic pattern pulse wave Doppler of the precordial systemic circulation.
Second, we evidenced that in two prenatally diagnosed type II, the IHPVS disappeared after birth as a consequence of the UV closure. It is important, therefore, for prenatal counseling and programming of the postnatal restoration of the portal flow to the liver, to take it into consideration. Third, a multidisciplinary prenatal counseling team including neonatologists, pediatric radiologists, surgeons, and hepatologists is essential for comprehensive counseling and an immediate continuity of postnatal medical care.
We have described how the evolution of our knowledge caused us to modify our parental counseling and management approach to pregnancy. The use after birth of venography with balloon occlusion or surgical ligation of the shunt has shown that in utero Doppler invisible portal vessels, diagnosed by us as agenesis of the portal system, existed probably as hypoplastic and expanded progressively [26]. On the other hand, we have realized that the type II cases with apparently “good” prognosis in utero have changed to type I after birth when the UV was the only venous liver’s supplier. With these outcomes, the adult traditional classification regarding the postnatal outcome was revealed of limited prognostic value for the in utero life. Therefore, our pendulum was moved to a more favorable prognosis and counseling in favor of postnatal evaluation and treatment.
This observation is supported by the liver’s histologic study of De Vito et al. [28] who did not find any significant difference in histological changes between the two types of extrahepatic shunts defined by postnatal imaging modalities. However, the prenatal diagnosis of hypoplastic or absent IHPVS is very important since it enables early postnatal intervention and definitive closure rescuing the liver portal circulation before serious long-term complications appear [11].
Indeed, a recent study by Rajeswaran et al. [30] has shown that in 29 patients with extrahepatic portosystemic shunts at the median age of 4.5 years, the use of venography with balloon occlusion demonstrated filling of the portal system in all the shunts and enabled final surgical closure with no need to liver transplantation. Three large multicenter studies by Baiges et al. [24] in 2020, McLin et al. [31] in 2019, and Uchida et al. [32] in 2023 pointed out the importance of prenatal diagnosis in preventing delayed postnatal intervention and emphasized the importance of early occlusion-test in the identification of the hypoplastic liver’s portal system which can be rescued avoiding the need for liver transplantation in most cases. The authors stated that shunt closure must always be considered not only in symptomatic patients but also as an early prophylactic measure to prevent severe life-threatening complications.
Our observation is in concordance with these insights. The continued and immediate postnatal multidisciplinary work-up and treatment are paramount for the rescue of the hypoplastic hepatic portal vessels avoiding significant metabolic complications.
Non-settled issue remains the still existing place for liver transplant as the first line of treatment in complications in which shunt closure cannot improve such as progressing pulmonary disease or liver malignancy [33]. In summary, prenatal characterization of FEPSVS is crucial for precise multidisciplinary counseling and programming of the postnatal intervention, thus preventing long-term pathological complications.
Statement of Ethics
This study was approved by the Ethics Committee of Sheba medical center, as a retrospective observational-descriptive nonclinical review (study no. 534-18-SMC, 1/11/2018), and was exempted from requiring written informed consent. Verbal informed consent was obtained from the participants by telephone prior to the study.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
No sponsor or funder supported this study.
Author Contributions
R.A. and Z.K. conceived the original idea, performed the examinations, and wrote the manuscript. E.K. contributed to the collection and interpretation of the results. R.A.S. performed the postnatal chirurgical interventions.
Additional Information
Reuven Achiron and Zvi Kivilevitch contributed equally to this work.
Data Availability Statement
All data that support the findings of this study are included in this study. The data are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author upon a specific request.