Vascular abnormalities of the umbilical cord

Definition

The human umbilical cord usually develops with two arteries and one vein. A single umbilical artery is the absence of one of the umbilical arteries. [1]

ICD code

Q27.0

Incidence

The reported incidence of SUA varies from 0.5% at the time of second-trimester prenatal ultrasound and in umbilical cord specimens from liveborn infants to 2.1% of fetal deaths, autopsies, or aborted fetuses. In twins its incidence has been reported to be as high as 5% [1]. The left artery is the absent vessel in 60-70% of the SUA cases. 

Pathogenesis/ Etiology

The arterial system forms during the fourth and fifth weeks of embryonic development. The umbilical cord develops later in the region of the body stalk to become the embryo connection to the fetal portion of the placenta. Around 7-8 weeks postmenopausal age, the umbilical cord contains the body stalk with umbilical vessels and other structures that will later regress and disappear entirely. Both umbilical arteries are functionally part of the same segment of fetoplacental circulation. It has been suggested that genetic and persisting environmental factors influence the development of SUA.

Recently, in a prospective study of 6500+ singletons with SUA from a single institution, conception via assisted reproductive technology was identified as an independent risk factor for isolated SUA. The etiology behind this association in this cohort was hypothesized to be due to the invitro development of the chorion which ultimately can affect placental morphological development   and potentially lead to a higher incidence of iSUA. In this study, a higher incidence of SGA and preterm birth was also noted in pregnancies with isolated SUA [22].  This association may have implications for obstetric management, particularly in third trimester surveillance of fetal growth and preterm birth prevention but further support for these associations awaits future prospective studies. 

The most widely accepted underlying explanations for the occurrence of SUA include the following:
(1) Primary agenesis of one umbilical artery, 
(2) Thrombotic atrophy of one umbilical artery 
(3) Persistence of the original single allantoic artery of the body stalk. [2] 

Associated anomalies

Although most of the time, SUA appears to be an isolated finding, one-third of the cases are associated with structural anomalies. The most common structural abnormalities involve the cardiovascular, gastrointestinal, and renal systems. In 10% of cases, SUA is associated with aneuploidy, particularly   Trisomy18 and Trisomy13. SUA occurs more commonly in twins (up to 5 %) and is a common finding in 2/3 of cases of the Twin Reversed Arterial Perfusion Sequence (TRAP). [1]

Recurrence risk

Only one recent study investigated the risk of recurrence of SUA and reported that isolated SUA in the first pregnancy doubled the odds of repetition in the second pregnancy. In contrast, a four-fold increased risk was reported if SUA was combined with malformations in the first pregnancy. [3]

Diagnosis

Colour Doppler imaging through the fetal pelvis in the transverse plane can reveal the single UA adjacent to the urine-filled fetal bladder.  [4]. This approach is preferred to differentiate it from the partially fused UAs, which can be mistaken for a SUA if only a transverse section of the umbilical cord is imaged.

Differential diagnosis  

Fused Umbilical Arteries; can be found in the cord insertion site about 3 cm from the placental insertion. This condition is not associated with structural abnormalities or aneuploidy.[5]

Implications for sonographic diagnosis

When SUA is diagnosed at the time of the mid-trimester scan, a targeted ultrasound is warranted to rule out associated anomalies. [2]

Some studies report that Isolated SUA is associated with perinatal morbidities, while others fail to prove association. One large population -based  study demonstrated  an increased risk of FGR, earlier GA at birth, polyhydramnios, oligohydramnios, placental abruption, placenta previa,  cord prolapse, Caesarean delivery and overall perinatal mortality [5] in SUA fetuses compared to a control group of fetuses with 3 vessel cords , after controlling for other confounders. Studies have been heterogeneous however and   larger prospective studies are needed to delineate specific risks.

Implications for Sonographic screening

As per ISUOG guidelines for imaging in first and second trimesters, the number of cord vessels, cord insertion at the umbilicus, and cord cysts should be noted. A brief evaluation of the paravesical region with colour or power Doppler can help confirm the presence of two umbilical arteries. When a single umbilical artery is identified in the mid-trimester scan, care should be taken not to cause anxiety to the parents if there is no evidence of coexisting structural defects or FGR [6, 7]

Prognosis

The prognosis depends on the presence of associated structural anomalies or aneuploidy.

Management

Demonstration of a SUA is an indication for a detailed ultrasound to detect possible coexisting structural anomalies. If other abnormalities are found, more testing should be considered, such as  fetal echo and genetic testing [8]. Isolated SUA in an otherwise low-risk pregnancy does not significantly increase the fetal aneuploidy risk. However, some studies have associated isolated SUA with fetal growth restriction and perinatal death. The studies addressing the relationship between the isolated SUA and fetal growth have been heterogeneous. Without strong evidence (large cohort studies), reaching definitive conclusions regarding serial surveillance frequency is difficult.

Definition 

Persistent right umbilical vein (PRUV): Embryologic right umbilical vein (UV) remains open. The left UV may regress or stay patent. [9]

Incidence 

The prevalence of intrahepatic PRUV has been reported to be 0.13% [10]

Etiology/Pathogenesis

In early embryonic life, there are two umbilical veins. At week four, the right umbilical vein undergoes atresia and disappears. The left umbilical vein remains the only vein. In the cases of PRUV, the right umbilical vein remains patent either alone or with the left umbilical vein. [11]
The cause of PRUV remains unknown. 
Possible explanations include:
-    Thrombus obstruction,
-    Teratogens or folic acid deficiency [12]

Pathology

Usually, the right umbilical vein regresses around the fourth week of pregnancy and completely disappears by the seventh week of gestation. In two-thirds of cases, the right umbilical vein replaces the left. When both veins persist, they are named “supernumerary” umbilical vessels. [9]
Two variants of PRUV are recognized:
Type 1 –intrahepatic PRUV; in this type, reported in 95% of cases, the UV passes lateral to the right side of the gallbladder, connects to the right portal vein, and bends toward the stomach. The DV is usually present, and there is little interference in hemodynamics. This type has a good prognosis. 
Type 2 - extrahepatic PRUV: where the UV connects directly to the right atrium or the IVC. This type is associated with DV agenesis and a poorer prognosis. If the DV is absent, the blood returns directly to the heart. That creates an increase in the hemodynamic burden. The affected fetuses suffer from volume overload and severe hemodynamic effects that can result in fetal hydrops. There are several case reports of agenesis of the DV with fetal hydrops. [9]

Associated anomalies

PRUV may be an isolated anomaly or part of more complex visceral and venous system abnormalities, particularly in fetuses with situs inversus visceralis, situs ambiguous, and heterotaxy (left and right isomerism). The most frequent associated anomalies were cardiovascular (60.3%), gastrointestinal (12.8%), renal (15.4%), cerebral (15.4%), and limb abnormalities (7.7%). [12]

Diagnosis

The diagnosis is made in the transverse section at the AC measurement level. There are two simple sonographic landmarks which facilitate the diagnosis; (1) where the portal vein curves towards the stomach in a transverse section of the fetal abdomen; and (2) where the fetal gall bladder is located medially to the umbilical vein (between the umbilical vein and the stomach). Colour Doppler facilitates demonstration of the type of PRUV, according to its drainage. [13] 

Differential diagnosis

Differential diagnoses of PRUV include umbilical vein varix, gallbladder duplication, aberrant course of the portal vein and its branches and intrahepatic cysts. [12]

Implications for sonographic diagnosis

Upon diagnosis, a detailed anatomy scan and fetal echo are advised. With the presence of anomalies, genetic testing is recommended. Trisomy 18 and Noonan syndrome have been reported in many cases. [11]

Implications for Sonographic screening

The congenital absence of DV, which may coexist with PRUV, can result in hemodynamic dysregulation and subsequent volume overload. In severe cases, cardiomegaly, polyhydramnios, and fluid accumulation may occur. PRUV is an uncommon antenatal finding, and a definitive diagnosis remains challenging. The widespread use of colour Doppler and 3D US applications has facilitated the in-utero diagnosis of abnormalities in fetal circulation, including those in the umbilical cord or the fetal portal system. [11]

Prognosis

Isolated PRUVs (76.3–98.6%) have a good prognosis. [9] In general, the prognosis will depend on the presence of other anomalies and the underlying diagnosis. 

Management

After the diagnosis, a referral to have a detailed anatomy scan and fetal echo is advised. [10]
 

Definition 

Fetal intra-abdominal Umbilical vein varix (FIUVV) is a dilation of the intraabdominal, extrahepatic portion of the umbilical vein. [14]
There have been a few case reports of extra-abdominal varices, typically identified as a postnatal diagnosis, most of which are diagnosed retrospectively during an autopsy. 

Incidence

Its prevalence is reported to be 1.1 to 2.8/per 1000 pregnancies. [15]

Pathogenesis

The weakest part of the umbilical vein is the extrahepatic intraabdominal part. That part dilates quickly with any increase in venous pressure. [15]

Etiology

Any condition that increases umbilical venous pressure could lead to dilatation of the extrahepatic portion of the umbilical vein. [14]

Pathology

FIUV varix is a developmental lesion rather than a congenital anomaly because more than two-thirds of the cases are diagnosed after 30 weeks of gestation. It is seen as a cyst-like structure in the upper fetal abdomen containing venous flow upon colour Doppler imaging. The extrahepatic portion is the weakest and can quickly dilate under high venous pressure. That high venous pressure could be due to structural anomalies or signs of aneuploidy. [14]

Associated anomalies

70%–80% of cases of umbilical vein varix are isolated findings. Only 5-10% of the cases of FIUVV reported have associated anomalies. [16] Aneuploidy is present in 5%–10% of all cases of umbilical vein varix. [17]

Recurrence risk

The recurrence risk depends on the underlying cause, e.g., it can recur when associated with chromosomal anomalies. No reported recurrence risk for isolated cases. 

Diagnosis

In ultrasound, FIUVV can be seen as a hypoechoic, cyst-like space at the cord insertion site in the upper abdomen, with the venous flow on Doppler interrogation. Measurement of varix dimension is usually done on the axial image of the fetal abdomen, immediately cephalad to umbilical vein insertion. No standard criteria exist for defining umbilical vein varix; it can be determined in the third trimester using one of the following criteria: a portion of intra-abdominal umbilical vein that is at least 50% wider than the non-dilated portion; a dilatation of ≥ 9 mm; or a dilatation greater than 2 SD above the mean value for gestational age. [18]

 Differential diagnosis

- Distended gallbladder, Mesenteric cyst. [19]

- Umbilical cord cyst [20]  
Colour Doppler imaging should rule out other intraabdominal cystic masses (dilated gallbladder, mesenteric, urachal, hepatic cysts, or enteric duplication) because it shows the continuity with the umbilical vein and distinguishes vascular structures from other cystic lesions, for example, the distended gallbladder or cysts in other structures. 

Implications for sonographic diagnosis

After FIUV varix has been diagnosed, detailed ultrasound to rule out associated anomalies is advised. If additional abnormalities are detected, fetal genetic testing should be offered since the risk of chromosomal abnormalities increases with findings of other sonographic abnormalities. A formal fetal echocardiogram should be performed. Serial scans to monitor for signs of impending hydrops or thrombus formation are advised. [16]

Implications for Sonographic screening

With the advance of ultrasound scanning with colour Doppler capability, diagnosing FIUV varix is no longer difficult. [16]

Prognosis

The significance of antenatal FIUVV detection remains unclear. The spectrum in outcomes varies from normal to high rates of complications and fetal mortality. This could be due to the rarity of this anomaly. A recent review reported a good prognosis when isolated, even if diagnosed early in pregnancy. In such cases, an antenatal follow-up to term is sufficient. [21] Close monitoring for developing complications such as thrombosis is advised. The frequency of follow-up is varied in the literature.

Management

After the diagnosis of FIUVV, a detailed scan is advised to check for associated anomalies. Should other abnormalities be detected, genetic screening/testing and Fetal echo should be considered to rule out aneuploidy and cardiac anomalies. Close monitoring for the development of complications such as thrombosis is advised. [18]  More extensive prospective trials should be performed to determine the significance of the antenatal finding of FIUV varix on obstetric management and fetal outcome. [14]

1.    Voskamp, B.J., et al., Relationship of isolated single umbilical artery to fetal growth, aneuploidy and perinatal mortality: systematic review and meta-analysis. Ultrasound Obstet Gynecol, 2013. 42(6): p. 622-8.
2.    Geipel, A., et al., Prenatal diagnosis of single umbilical artery: determination of the absent side, associated anomalies, Doppler findings and perinatal outcome. Ultrasound Obstet Gynecol, 2000. 15(2): p. 114-7.
3.    Ebbing, C., et al., Isolated single umbilical artery and the risk of adverse perinatal outcome and third stage of labor complications: A population-based study. Acta Obstet Gynecol Scand, 2020. 99(3): p. 374-380.
4.    Bosselmann, S. and G. Mielke, Sonographic Assessment of the Umbilical Cord. Geburtshilfe Frauenheilkd, 2015. 75(8): p. 808-818.
5.    Burshtein, S., et al., Is single umbilical artery an independent risk factor for perinatal mortality? Arch Gynecol Obstet, 2011. 283(2): p. 191-4.
6.    Salomon, L.J., et al., ISUOG practice guidelines: performance of first-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol, 2013. 41(1): p. 102-13.
7.    Salomon, L.J., et al., ISUOG Practice Guidelines (updated): performance of the routine mid-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol, 2022. 59(6): p. 840-856.
8.    Rembouskos, G., et al., Single umbilical artery at 11-14 weeks' gestation: relation to chromosomal defects. Ultrasound Obstet Gynecol, 2003. 22(6): p. 567-70.
9.    Krzyzanowski, A., et al., Prenatal diagnosis of persistent right umbilical vein - Incidence and clinical impact. A prospective study. Aust N Z J Obstet Gynaecol, 2019. 59(1): p. 77-81.
10.    Dagdeviren, G., et al., Prenatal diagnosis of the persistent right umbilical vein, incidence and clinical significance. J Obstet Gynaecol, 2022. 42(3): p. 443-446.
11.    Li, J., et al., Ultrasonic detection of fetal persistent right umbilical vein and incidence and significance of concomitant anomalies. BMC Pregnancy Childbirth, 2020. 20(1): p. 610.
12.    Weichert, J., et al., Persistent right umbilical vein: a prenatal condition worth mentioning? Ultrasound Obstet Gynecol, 2011. 37(5): p. 543-8.
13.    Wolman, I., et al., Persistent right umbilical vein: incidence and significance. Ultrasound Obstet Gynecol, 2002. 19(6): p. 562-4.
14.    Byers, B.D., et al., Pregnancy outcome after ultrasound diagnosis of fetal intra-abdominal umbilical vein varix. Ultrasound Obstet Gynecol, 2009. 33(3): p. 282-6.
15.    Gowda, S., et al., Large fetal intra-abdominal umbilical vein varix: Antenatal sonographic diagnosis and follow-up. J Obstet Gynaecol Res, 2019. 45(9): p. 1936-1940.
16.    Fung, T.Y., et al., Fetal intra-abdominal umbilical vein varix: what is the clinical significance? Ultrasound Obstet Gynecol, 2005. 25(2): p. 149-54.
17.    Grin, L., et al., Is umbilical vein varix associated with changes in cerebroplacental ratio? J Matern Fetal Neonatal Med, 2020. 33(1): p. 162-166.
18.    di Pasquo, E., et al., Fetal intra-abdominal umbilical vein varix: retrospective cohort study and systematic review and meta-analysis. Ultrasound Obstet Gynecol, 2018. 51(5): p. 580-585.
19.    Lee, S.W., et al., Clinical characteristics and outcomes of antenatal fetal intra-abdominal umbilical vein varix detection. Obstet Gynecol Sci, 2014. 57(3): p. 181-6.
20.    Sherer, D.M., et al., Current Perspectives of Prenatal Sonography of Umbilical Cord Morphology. Int J Womens Health, 2021. 13: p. 939-971.
21.    Pamplona-Bueno, L., et al., Fetal Intra-Abdominal Umbilical Vein Varix: A Case Report and Literature Review. J Obstet Gynaecol India, 2015. 65(6): p. 420-2.
          Diagnostic Imaging Obstetrics 1.pdf
22.    Siargkas, A., et al., Prenatal Diagnosis of Isolated Single Umbilical Artery: Incidence, Risk Factors and Impact on Pregnancy Outcomes. Medicina (Kaunas), 2023. 59(6)

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