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Keywords:

  • pregnancy outcome;
  • trisomy 21;
  • ultrasound;
  • umbilical cord;
  • varix

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. REFERENCES

Objectives

Fetal intra-abdominal umbilical vein (FIUV) varix is a focal dilatation of the intra-abdominal portion of the umbilical vein, which has been reported to be associated with intrauterine death and other anomalies. Our aim was to examine our experience with this diagnosis at a single tertiary-care center and to correlate it with clinical outcome.

Methods

This was a retrospective case series study. Our ultrasound database was searched for all cases with a diagnosis of FIUV varix identified at our facility between 1997 and 2007. We reviewed all ultrasound examinations, maternal antenatal records, delivery records and newborns' medical records.

Results

We identified 52 cases of FIUV among a population of approximately 68 000. Three cases of trisomy 21 were identified, all of which were accompanied by other anomalies. There was intrauterine death of one fetus with trisomy 21 at 35 weeks of gestation. We did not find an association between FIUV varix and other obstetric complications.

Conclusions

The outcome of pregnancies with FIUV varix is generally favorable. The finding of a FIUV varix should prompt the search for other anomalies, especially markers of aneuploidy. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. REFERENCES

Fetal intra-abdominal umbilical vein (FIUV) varix is a focal dilatation of the umbilical vein of the fetus. This lesion was first described in autopsies of stillborn infants1. FIUV varix is diagnosed on ultrasound examination by visualizing a dilated intra-abdominal, usually extrahepatic, portion of the umbilical vein. Color-flow imaging that displays continuity with the umbilical vein aids in the diagnosis (Figures 1 and 2). Diagnostic criteria include an umbilical vein diameter greater than 9 mm or an enlargement of the varix to at least 50% more than the diameter of the intrahepatic umbilical vein2.

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Figure 1. Gray-scale ultrasound image showing a fetal intra-abdominal umbilical vein varix (VAR) adjacent to the fetal bladder (BL) in a 32-week fetus.

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Figure 2. Color-flow imaging of the fetal intra-abdominal umbilical vein varix in the case shown in Figure 1.

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Earlier case series have reported an association of FIUV varix with intrauterine death (IUD), and some investigators have suggested that it may represent a significant risk factor for IUD3. A correlation between FIUV varix with other anomalies, aneuploidies, fetal hydrops and other adverse pregnancy outcomes has also been suggested3–7. In the present study we report our experience over a 10-year period with the outcome of pregnancies diagnosed with FIUV varix antenatally at a university tertiary-care center.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. REFERENCES

This study was performed as a retrospective case series. The study protocol was approved by the Institutional Review Board of the University of Texas Medical Branch. The University of Texas Medical Branch is a tertiary-care referral center and provides obstetric care to a large population of primarily indigent women in south-east Texas. Our obstetric ultrasound unit performs an average of 8500 examinations yearly. Approximately 85% of the obstetric ultrasound examinations are performed on women receiving prenatal care at one of our 15 Regional Maternal Child Health Program clinics in south-east Texas. Another 10% are from our private practice group. The indications for these examinations include: dating, anatomical survey, diabetes, hypertensive disorders, growth scan, advanced maternal age, abnormal maternal serum screening and family history of congenital defects. An additional 5% of the sonographic examinations are referrals from local private physicians for previously detected fetal anomalies. The finding of FIUV varix has been reported routinely at our institution since 1997.

All cases of FIUV varix on prenatal ultrasound examinations performed between 1 January 1997 and 30 December 2007 were identified through a search of our computerized database. A total of 67 949 ultrasound examinations on 51 799 individual patients were performed during the study period. The racial/ethnic makeup of the entire obstetric population was 63% Hispanic, 23% Caucasian, 11% African–American, 1% Asian and 2% other. Ultrasound examinations, using a convex abdominal transducer at a frequency of either 3.5 or 5 MHz, were performed with one of the following three ultrasound models (in chronological order): ATL HDI 3000, ATL HDI 5000 or Philips IU22 (Philips, Amsterdam, The Netherlands). Evaluation for FIUV varix was performed on all anatomy ultrasound examinations regardless of gestational age. When focal dilatation was suspected, confirmatory color-flow imaging was performed in all cases.

FIUV varix diameter was measured from one outer edge to the opposite inner edge with electrical calipers on axial images immediately cephalad to the insertion of the umbilical vein into the fetal abdomen3. FIUV varix was diagnosed based on previously described criteria. If the focal dilatation was greater than 9 mm, or at least 50% larger than the intrahepatic umbilical vein, then FIUV varix was diagnosed2. In our analysis, gestation-specific criteria were used to verify the proper diagnosis3. All FIUV varices were ≥ 2 SD above the mean umbilical vein diameter for each gestational age.

We initiated antenatal testing at 32 weeks of gestation with non-stress tests twice weekly and amniotic fluid index measurements once weekly. Antepartum testing was performed on 94.2% of cases, and delivery was indicated in 19.2% because of non-reassuring fetal testing. The presence of FIUV varix was the indication for labor induction in seven (13.5%) cases. No case remained undelivered past 40 weeks of gestation.

We reviewed the complete electronic and paper medical records for each case of FIUV varix diagnosed, including all ultrasound examinations, maternal outpatient and inpatient charts, amniocentesis reports, and delivery and postpartum infant records. Descriptive statistics were used and reported as mean ± SD and range. Categorical data were analyzed using Chi-square tests.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. REFERENCES

Overall, we identified 58 cases of FIUV varix in our study population. The incidence was 1.1 per 1000 pregnancies. Six cases were excluded from the analysis because the patients were not delivered at our institution and outcome data were not available. Fifty-two mother–infant pairs were therefore included in the study. Fifty cases (96%) involved singleton gestations and two (4%) were twin pregnancies. Both twin pregnancies were monochorionic–diamniotic. Twenty-eight (53.8%) fetuses were male. All cases had been delivered at the time of writing. Table 1 summarizes the demographic characteristics of the study population.

Table 1. Basic demographic information
ParameterValue
Maternal age (years, mean ± SD (range))27.2 ± 6.1 (18–43)
Age ≥ 35 years (n (%))5 (9.6)
Gravidity (mean ± SD (range))2.9 ± 1.4 (1–7)
Gestational age at initial diagnosis (weeks, mean (range))29.8 (18–35)
 Diagnosis at < 24 weeks (n (%))3 (5.8)
 Diagnosis at < 30 weeks (n (%))23 (44.2)
Hispanic ethnicity (n (%))46 (88.5)
Singleton gestation (n (%))50 (96.1)
Male fetus (n (%))28 (53.8)

The mean FIUV varix diameter in our subjects was 12.8 ± 2.9 (range, 7–21) mm. Fifteen (28.8%) cases of FIUV varix were accompanied by other abnormalities on ultrasound examination. The urological system was most commonly involved, accounting for six (40%) of these abnormalities. Seven cases of FIUV varix (13.5% of all cases) were not seen on the initial ultrasound examination, but were found on follow-up examinations carried out for other abnormalities. There were two cases of FIUV varix associated with a single umbilical artery. Table 2 lists the coexisting sonographic abnormalities in our study population. Some 56% of the FIUV varix cases were first diagnosed after 30 weeks of gestation. The frequency of coexisting fetal anomalies was not associated with the gestational age at initial FIUV varix diagnosis (χ2 = 0.55; P = 0.52).

Table 2. Ultrasound findings
ParameterValue
  1. FIUV, fetal intra-abdominal umbilical vein; TRAP, twin reversed arterial perfusion.

Maximum FIUV varix size (mm, mean ± SD (range))12.79 ± 2.92 (7–21)
Amniotic fluid index at diagnosis (cm, mean ± SD (range))14 ± 3 (8–21)
Overall cases with coexisting abnormalities (n (%))15 (28.8)
 Monochorionic twins with TRAP1 (1.9)
  sequence 
 Single umbilical artery1 (1.9)
 Beckwith–Wiedemann syndrome1 (1.9)
 Unilateral club foot1 (1.9)
 Echogenic dilated bowel1 (1.9)
 Bilateral moderate pyelectasis2 (3.8)
 Widened cisterna magna (1.2 cm)1 (1.9)
 Cardiomegaly, short long bones, clinodactyly, macroglossia, absent nasal bone, placenta previa, atrioventricular canal defect1 (1.9)
 Unilateral choroid plexus cyst (10 mm)1 (1.9)
 Right pelvic kidney and single umbilical artery1 (1.9)
 Right renal agenesis1 (1.9)
 Monochorionic–diamniotic twins with twin–twin transfusion syndrome1 (1.9)
 Bilateral pyelectasis with right renal cyst1 (1.9)
 Ventriculomegaly, echogenic bowel, pyelectasis, ventricular septal defect1 (1.9)

Fifty-one of the FIUV varix subjects delivered liveborn infants. There was one case of IUD in a 43-year-old mother at 35 weeks of gestation. The FIUV varix in this fetus, diagnosed at the initial ultrasound examination at 28 weeks, measured 15.6 mm in diameter. In addition to the FIUV varix, this fetus had multiple other antenatally detected anomalies including cardiomegaly, a shortened left humerus, an absent nasal bone, macroglossia and an atrioventricular canal defect. Postmortem cytogenetic analysis of fetal tissue revealed trisomy 21.

Trisomy 21 was also diagnosed in two other fetuses. Both were born alive at term. The first case was diagnosed after birth by the attending pediatricians based on the phenotypic features of the neonate. A neonatal chromosome analysis confirmed the diagnosis. This infant had findings of a 10-mm FIUV varix as well as significant bilateral renal pyelectasis noted on a 33-week ultrasound examination. The FIUV varix was not seen on an earlier ultrasound examination at 21 weeks. The mother had been counseled regarding these findings and did not desire fetal karyotyping. The second case was diagnosed antenatally by genetic amniocentesis. The initial ultrasound examination of this fetus, at 26 weeks of gestation, revealed a 21-mm FIUV varix, a ventricular septal defect, hyperechogenic bowel loops, bilateral renal pyelectasis and ventriculomegaly. The overall incidence of trisomy 21 was 5.8%.

Other pregnancy complications were encountered in 17 (32.6%) cases. Oligohydramnios was the most common complication, occurring in five (9.6%) cases. Most (88%) of the infants were born at term. The two twin pregnancies, both monochorionic–diamniotic, had significant complications. The first was complicated by twin reversed arterial perfusion sequence. The normal fetus displayed the FIUV varix. The second twin gestation was affected by twin–twin transfusion syndrome. In this case the recipient twin had the FIUV varix. Non-reassuring fetal testing was the delivery indication in 10 (19.2%) cases. Neonatal intensive care unit (NICU) admission was necessary in six (11.5%) of the newborns. Table 3 shows the pregnancy complications and perinatal outcomes in our study subjects.

Table 3. Perinatal outcomes of 52 cases of fetal intra-abdominal umbilical vein varix
ParameterValue
  1. NICU, neonatal intensive care unit.

Gestational age at delivery (weeks, mean ± SD (range))38.3 ± 2.3 (28–41)
Preterm delivery (n (%))6 (11.5)
 28–33 weeks3 (5.8)
 34–37 weeks3 (5.8)
Delivery route (n (%)) 
 Vaginal37 (71.1)
 Cesarean section15 (28.8)
Overall cases with pregnancy complications (n (%))17 (32.7)
 Intrauterine fetal death1 (1.9)
 Oligohydramnios5 (9.6)
 Intrauterine growth restriction1 (1.9)
 Rhesus isoimmunization1 (1.9)
 Pre-eclampsia2 (3.8)
 Pyelonephritis1 (1.9)
 Intrauterine growth restriction, anti-E isoimmunization, preterm rupture of the membranes1 (1.9)
 Gestational diabetes mellitus4 (7.7)
 Complete placenta previa1 (1.9)
Birth weight (g, mean ± SD (range))3200 ± 654 (1136–4580)
Birth weight < 10th percentile (n (%))2 (3.8)
5-min Apgar score (mean ± SD (range))8.8 ± 1.5 (7–10)
Umbilical cord arterial pH (mean (range))7.25 (7.1–7.4)
Trisomy 21 (n (%))3 (5.8)
NICU admission (n (%))6 (11.5)
 Delivery at 39 weeks: meconium aspiration syndrome1 (1.9)
 Delivery at 38 weeks: postpartum trisomy 21 diagnosis, respiratory distress syndrome1 (1.9)
 Delivery at 39 weeks: clinical sepsis1 (1.9)
 Delivery at 39 weeks: large undiagnosed atrial septal defect1 (1.9)
 Delivery at 33 weeks: twin–twin transfusion syndrome recipient; indicated delivery for worsening diabetes1 (1.9)
 Delivery at 38 weeks: Beckwith–Wiedemann syndrome1 (1.9)

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. REFERENCES

FIUV varix is a focal dilatation of the umbilical vein, typically in the intra-abdominal portion. The etiology is uncertain. It is hypothesized by some to be a developed rather than a congenital condition as there are reports of FIUV varices detected between 22 and 33 weeks that were not detected between 16 and 19 weeks3,8. The extrahepatic, intra-abdominal portion of the umbilical vein has the weakest supporting structure of any part of the umbilical circulation. Therefore, any condition that increases umbilical venous pressure could potentially lead to dilatation of the extrahepatic portion of the umbilical vein2. The diameter of the umbilical vein increases linearly from 3 mm at 15 weeks to 8 mm at term. The diameter of most umbilical vein varices is between 6 and 12 SD above the mean umbilical vein diameter for the patient's gestational age3. Extremely large varices up to 85 mm have been reported9. The differential diagnosis for FIUV varices includes normal structures such as the gallbladder or stomach, pathological cystic masses such as urachal cysts, duplication cysts or mesenteric cysts, and other cystic lesions originating from the cord.

The literature on this topic is limited to case reports and case series. The initial case series of FIUV varix was published in 1992 by Mahony et al.3. They found an alarmingly high rate (44%) of IUD in their study population of nine fetuses. One of these fetuses had trisomy 21. Additionally, they reported one fetus with severe fetal hydrops 2 weeks after the detection of the FIUV varix. Estroff and Benacerraf reported five cases of FIUV varix, all without any complications8.

Sepulveda et al. concluded from their study in 1998 that the fetus with FIUV varix should be considered at risk, especially in the presence of additional anomalies6. They reported a 24% rate of IUD, a 12% incidence of aneuploidy and a 5% incidence of fetal hydrops based on the review of literature. Fung et al. reported two IUDs, one trisomy 21 fetus and one small-for-gestational age infant in a cohort of 13 patients4. Rahemtullah and coworkers found a 35% incidence of structural abnormalities among 23 patients5. They concluded that FIUV varix is associated with a high rate of fetal abnormalities and that a detailed evaluation of the fetus should be performed.

The reason for the potential increase in perinatal mortality is uncertain. One suggested mechanism is thrombosis of the dilated varix, which can be identified using color and power Doppler studies of the FIUV varix10. We identified two cases of FIUV varix associated with a single umbilical artery. This has been reported previously in a case report in which the fetus died in utero at 35 weeks of gestation, only 3 days after a reactive non-stress test11.

Our study is the largest case series reported to date. Similar to other studies, we found an association between FIUV varix and aneuploidy (5.8%) and other fetal anomalies (28.8%), although our rates were slightly lower than previously reported3–6. The finding of trisomy 21 in a significant percentage of fetuses with FIUV varix is of special interest. Our study supports the notion of FIUV varix as a marker for fetal aneuploidy.

We did not find an association between FIUV varix and unexplained fetal death, growth restriction, fetal hydrops or admission to the NICU. There did not appear to be a correlation between the maximum FIUV varix size and perinatal complications.

Our study is limited by lack of information on six cases that were lost to follow-up, as well as by the retrospective nature of the study. Additionally, the increased pregnancy surveillance with antepartum fetal testing and obstetric intervention is a potential source of bias. Nonetheless, we conclude from our results that the diagnosis of FIUV varix should prompt the obstetrician to search for other abnormalities and entertain a higher suspicion for aneuploidy. If coexisting abnormalities are not present, the fetal outcome appears to be generally favorable. Based on available data, it may be prudent to initiate antepartum testing on fetuses with FIUV varix between 32 and 34 weeks of gestation. Induction of labor is typically recommended by 40 weeks of gestation or after fetal pulmonary maturity has been established12. Some authors advocate delivery as early as 34 weeks of gestation based on reports of fetal demise despite antenatal testing13. Larger prospective trials should be performed in order to determine the significance of the antenatal finding of FIUV varix on obstetric management and fetal outcome.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. REFERENCES

The authors would like to thank Ms Suzanne Thomas and Ms Shannon Garcia for their assistance with the ultrasound database.

REFERENCES

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. REFERENCES
  • 1
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    Schrocksnadel H, Holbock E, Mittershiffthaler G, Totsch M, Dapunt O. Thrombotic occlusion of an umbilical vein varix causing fetal death. Arch Gynecol Obstet 1991; 248: 213215.
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