Fetal Prognosis in Varix of the Intrafetal Umbilical Vein
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1 Fetal Prognosis in Varix of the Intrafetal Umbilical Vein Waldo Sepulveda, MD, Antonio Mackenna, MD, Jorge Sanchez, MD, Edgardo Corral, MD, Eduardo Carstens, MD To assess the clinical significance of varix of the intraabdominal portion of the umbilical vein, we reviewed 10 cases diagnosed prenatally by ultrasonography at a median gestational age of 27 weeks. A comprehensive anatomic survey and serial follow-up scans were performed in each case. All three fetuses with associated anomalies died in utero, and prenatal karyotyping revealed that two of them had a chromosomal abnormality. In six of the seven cases with structurally normal fetuses the pregnancy proceeded uneventfully, and no neonatal complications were attributed to the umbilical vein varix. Our experience and the review of the literature revealed 42 cases with information on fetal outcome. Overall, 24% of the fetuses died, 12% had a chromosomal abnormality, and 5% developed hydrops. We conclude that fetuses with varix of the intrafetal umbilical vein should be considered at risk for poor outcome. However, if no other anomalies are present, the prognosis is generally good. KEY WORDS: Umbilical vein varix; Prenatal ultrasonography; Color Doppler ultrasonography. Received September 2, 1997, from the Fetal Medicine Center, Department of Obstetrics and Gynecology, Clinica Las Condes, Santiago (W.S., A.M.); the Ultrasound Unit, Department of Obstetrics and Gynecology, San Jose Hospital, Santiago (J.S., E.C.); and the Department of Obstetrics and Gynecology, Regional Hospital, Rancagua (E.C.), Chile. Revised manuscript accepted for publication November 23, Address correspondence and reprint requests to Waldo Sepulveda, MD, Fetal Medicine Center, Clinica Las Condes, Casilla 268, Santiago 34, Chile. V arix of the umbilical vein is a rare abnormality. In most reported cases the variceal dilation had involved the intraamniotic portion of the umbilical vein, and it was usually detected at postpartum examination of the umbilical cord in stillborn infants. 1,2 Conversely, varix involving the intraabdominal portion has remained largely unrecognized because this vessel normally collapses after the clamping of the cord, leading to spontaneous resolution of any dilation previously present in the fetus. With the advent of high-resolution ultrasonography, however, it is now possible to identify varix of the intrafetal umbilical vein in utero. 3 7 Nevertheless, despite the increasing number of cases detected prenatally, the clinical significance of this finding remains unknown. Indeed, the first two series showed conflicting information regarding perinatal outcome, one series reporting a 44% perinatal loss in nine cases 6 and the other normal fetal outcome in five cases. 7 To better characterize the clinical relevance of varix of the intrafetal umbilical vein, we review our experience and comparable cases reported in the literature. MATERIALS AND METHODS In the 10 month period from September 1996 to June 1997, we prospectively recruited for this study 10 cases in which varix of the intrafetal umbilical vein was detected prenatally by ultrasonography at three 1998 by the American Institute of Ultrasound in Medicine J Ultrasound Med 17: , /98/$3.50
2 172 VARIX OF THE INTRAFETAL UMBLICAL VEIN J Ultrasound Med 17: , 1998 referral centers for high-risk pregnancies. The diagnosis was suspected by the detection of an anechoic area located in the anterior aspect of the fetal abdomen in close relation to the umbilical vein and subsequently confirmed by the demonstration of continuous venous flow within the mass with pulsed Doppler analysis and color flow mapping (Fig. 1). For the purposes of this study, varix of the intrafetal umbilical vein was defined as a focal dilatation of the intraabdominal portion of the umbilical vein, with a transverse diameter at least 1.5 times greater than the diameter of the intrahepatic umbilical vein. A comprehensive anatomic survey and serial follow-up scans were performed in each case. Information on gestational age at diagnosis, indication for the scan, prenatal ultrasonographic findings, and pregnancy outcome was obtained by chart review or by contacting the referring obstetrician. In addition, a search of the English literature was undertaken to identify similar cases and to determine the fetal prognosis of this condition based on a larger number of cases. RESULTS Table 1 shows the principal clinical and ultrasonographic findings in our 10 cases. Varix of the intrafetal umbilical vein was diagnosed at a median gestational age of 27 weeks (range, 22 to 34 weeks). Primary reasons for referral were routine obstetric ultrasonography (n = 4), abnormal prenatal findings on scans obtained at other centers (n = 3), suspected fetal abdominal cyst (n = 2), and a twin pregnancy complicated by Rh factor incompatibility (n =1). Of the two women referred with the diagnosis of a fetal abdominal cyst, color Doppler imaging showed this to be the dilated portion of the umbilical vein in both cases. Doppler studies at the time of the diagnosis demonstrated normal blood flow velocity waveforms in the umbilical cord in all cases. Ultrasonographic examination confirmed the presence of associated multiple anomalies in three fetuses. Prenatal karyotyping revealed that two fetuses had a chromosomal abnormality, one with trisomy 9 and one with trisomy 18. The former had a vermian cleft, microphthalmia, atrial septal defect, polycystic kidneys with echoic cortex, growth restriction, and severe oligohydramnios noted at 23 weeks gestation. The latter had a strawberry-shaped head, mild ventriculomegaly, diaphragmatic hernia, abnormal posturing of hands with overlapping fingers, growth restriction, and polyhydramnios at 29 weeks gestation. In the euploid fetus hydrocephaly, growth restriction, and echogenic bowel were noted at 27 weeks gestation. These three fetuses died in utero at 33, 30, and 33 weeks gestation, respectively. In the remaining seven cases, a comprehensive anatomic survey demonstrated that the umbilical vein varix was an isolated finding. Of these, six pregnancies proceeded uneventfully, and phenotypically normal infants were born at term, with no postnatal complication noted at pediatric examination. The remaining case was a twin pregnancy complicated by severe Rh factor incompatibility requiring an intrauterine transfusion, which resulted in fetal death shortly after the transfusion in the fetus with the varix. Postmortem examination revealed extensive thrombosis of the umbilical vein. Review of the literature revealed that a prenatal diagnosis of varix of the intrafetal umbilical vein had been reported in 43 cases, including this series (Table 2) Information regarding pregnancy outcome was not available in one case 4 and, therefore, this case was excluded from further analysis. Of the remaining 42 cases, the diagnosis was made before 28 weeks ges- Figure 1 A, Ultrasonographic view of the fetal abdomen shows an anechoic area (arrow) in close relation to the umbilical vein and above the fetal bladder (b). B, Color Doppler imaging confirms varix of the intrafetal umbilical vein. A B
3 J Ultrasound Med 17: , 1998 SEPULVEDA ET AL 173 tation in 12 cases (29%), after 28 weeks gestation in 15 cases (36%), and no information was available as to gestational age in the remaining 15 cases (36%). Overall, an adverse pregnancy outcome occurred in 13 cases, including 10 perinatal deaths. Four fetal deaths were reported in a single series of nine cases in which the umbilical vein varix was the only prenatal ultrasonographic finding. 6 Four fetal deaths were associated with aneuploidy, 6,10 one with hydrops, 3 and one with structural anomalies associated with growth restriction. Three otherwise normal fetuses died with no apparent cause; thrombosis of the varix was documented prenatally before intrauterine death in one case. 6 Thrombosis of the varix, probably as the result of intrauterine transfusion, could also explain the fetal death in the remaining case. Of the 32 survivors, one fetus developed hydrops 2 weeks after the detection of the umbilical vein varix, with spontaneous resolution after birth, 6 one delivered prematurely at 33 weeks gestation, 6 one developed transient cardiomegaly in utero, 7 and another with trisomy 21 had esophageal atresia and underwent surgical correction after birth. 10 None of the remaining 28 fetuses had prenatal complications, and all had a normal postnatal outcome. Overall, chromosomal abnormality was confirmed in five of the 42 cases (12%), including two fetuses with trisomy 21, two with trisomy 18, and one with trisomy 9. DISCUSSION In the fetus, the intraabdominal portion of the umbilical vein courses cephalad from the cord insertion, enters the liver, and anastomoses with the portal vein. This portion of the umbilical vein is routinely seen during prenatal ultrasonography, as it is an important landmark to obtain abdominal circumference measurements and to document intactness of the anterior abdominal wall, allowing the opportunity to detect anatomic variants and anomalies of this vessel in utero. In view of the paucity of reports in the pediatric literature, it seems that varix of the intrafetal umbilical vein, if present in the neonate, is clinically irrelevant, probably because of spontaneous resolution after the clamping of the cord. In the fetus, however, this condition has been associated with intrauterine death and hydrops fetalis. 3,6 Recently, it was suggested that this prenatal finding should also be considered as a soft marker of aneuploidy. 10 Our experience and the review of comparable cases reported in the literature revealed that intrafetal umbilical vein varix is associated with a perinatal mortality rate of 24%. Moreover, fetal aneuploidy was found in 12% of the cases, and 5% of the fetuses developed hydrops. Nevertheless, large discrepancies on the prevalence of these complications exist, and, therefore, confident information for prenatal counseling and pregnancy management is still lacking. Table 1: Varix of the Intrafetal Umbilical Vein Gestation Reason for Other Ultrasonographic Case (wk) Referral Findings Remarks 1 22 Routine None Normal neonate 2 23 Routine None Normal neonate 3 23 Routine None Normal neonate 4 34 Routine None Normal neonate 5 31 Abdominal cyst None Normal neonate 6 32 Abdominal cyst None Normal neonate 7 30 Twin pregnancy, None Intrauterine transfusion, Rh factor incompatibility IUD at 32 weeks 8 23 Fetal anomalies Multiple anomalies, IUGR Trisomy 9, IUD at 33 weeks 9 27 Fetal anomalies Multiple anomalies, IUGR Normal karyotype, IUD at 33 weeks Fetal anomalies Multiple anomalies, IUGR Trisomy 18, IUD at 30 weeks IUD, Intrauterine death; IUGR, Intrauterine growth restriction.
4 174 VARIX OF THE INTRAFETAL UMBLICAL VEIN J Ultrasound Med 17: , 1998 Table 2: Fetal Outcome in Varix of the Intrafetal Umbilical Vein. Review of the Literature Author n GA at Diagnosis (wk) Fetal Outcome Fuster and coworkers Hydrops, fetal death Rizzo and Arduini Normal neonate Mahony and associates , 31, 34, Normal neonates 19, 22, 23*, 24 Fetal deaths 32 Hydrops 33 Premature delivery Estroff and Benacerraf , 29, 32, 37, 38 Normal neonates White and Kofinas 8 7 Not stated Normal neonates Moore and associates Normal neonate Challis and colleagues 10 8 Not stated 6 normal neonates; 2 abnormal fetuses: one died, one lived* Current report 10 22, 23, 23, 31, 32, 34 Normal neonates 23, 27, 29, 30 Fetal deaths GA, Gestational age. *Trisomy 21. Hydrops resolved after birth. Transient cardiomegaly in utero. Trisomy 18. Trisomy 9. Differences in fetal outcome between series can be explained by several factors. First, the prevalence of associated anomalies in each series can strongly influence the final outcome. In one of the largest series, Mahony and associates 6 noted four intrauterine deaths in nine fetuses, with umbilical vein varix as the only abnormality. Conversely, our experience shows that most perinatal deaths are associated with structural anomalies, including chromosomal defects and growth retardation. This finding is in keeping with a recent series of eight fetuses with umbilical vein varix in which poor outcome occurred only in the two fetuses with aneuploidy. 10 On the other hand, no cases of poor outcome were noted in another two series in which the umbilical vein varix was an isolated finding. 7,8 Second, gestational age at diagnosis also may have an impact in fetal prognosis. Indeed, some authors attributed the good outcome in their series to the relatively late presentation of the varix. 7 Based on the review of the literature, it seems that detection of a varix of the intraabdominal portion of the umbilical vein in the third trimester in an otherwise normal fetus is not associated with adverse outcome. Last, the criteria for prenatal diagnosis and severity are not established fully. As no standard criteria for the in utero diagnosis exist, in most series the diagnosis has been somehow subjective, and, therefore, some authors probably had included cases with mild enlargement of the intraabdominal umbilical vein. Recently, Challis and coworkers 10 used the objective criterion of an umbilical vein diameter larger than 9 mm. The main limitation with this approach, however, is that an absolute measurement could lead to misdiagnosis, as the size of the umbilical vein normally depends on gestational age. 6 Therefore, by using a single measurement, only severe cases would be detected at earlier gestational ages and many mild cases at term. Using an increase in the varix of at least 50% larger than the diameter of the intrahepatic umbilical vein (because the size of this vessel normally increases in size as pregnancy progresses) would provide a more rational approach for the diagnosis. The mechanism by which varix of the intrafetal umbilical vein leads to fetal death in apparently normal fetuses is unknown. One possible cause is cardiac failure, which is supported by the fact that among the three fetuses who developed signs of cardiac failure, one died and in another the hydrops only resolved after birth. 3,6 An alternative explanation is thrombosis of the varix, which has been noted prenatally in two cases. 4,6 This complication can also explain the fetal death in one of our cases, in which a fetus died after intravascular intrauterine trans-
5 J Ultrasound Med 17: , 1998 SEPULVEDA ET AL 175 fusion. It could be possible that the administration of packed red blood cells directly into the umbilical vein was the predisposing factor for thrombosis of the varix, leading to intrauterine death. In summary, according to the cases pooled from the present series and those reported in the literature, it seems that varix of the intrafetal umbilical vein carries an increased risk for fetal demise, chromosomal abnormality, and hydrops fetalis and should, therefore, be considered as a warning sign for poor pregnancy outcome. Nevertheless, the prognosis in fetuses with no other associated findings is generally good, especially in those in whom serial follow-up scans demonstrate neither developing hydrops nor thrombosis of the varix. REFERENCES 1. Konstantinova B: Malformations of the umbilical cord. Acta Genet Med Gemellol 26:259, Ghosh A, Woo JSK, MacHenry C, et al: Fetal loss from umbilical cord abnormalities: A difficult case for prevention. Eur J Obstet Gynecol Reprod Biol 18:183, Fuster JS, Benasco C, Saad I: Giant dilatation of the umbilical vein. J Clin Ultrasound 13:363, Jeanty P: Fetal and funicular vascular anomalies: Identification with prenatal US. Radiology 173:367, Rizzo G, Arduini D: Prenatal diagnosis of an intraabdominal ectasia of the umbilical vein with color Doppler ultrasonography. Ultrasound Obstet Gynecol 2:55, Mahony BS, McGahan JP, Nyberg DA, et al: Varix of the fetal intra-abdominal umbilical vein: Comparison with normal. J Ultrasound Med 11:73, Estroff JA, Benacerraf BR: Fetal umbilical vein varix: Sonographic appearance and postnatal outcome. J Ultrasound Med 11:69, White SP, Kofinas A: Prenatal diagnosis and management of umbilical vein varix of the intra-amniotic portion of the umbilical vein. J Ultrasound Med 13:992, Moore L, Toi A, Chitayat D: Abnormalities of the intraabdominal fetal umbilical vein: Reports of four cases and a review of the literature. Ultrasound Obstet Gynecol 7:21, Challis D, Trudinger BJ, Moore L, et al: Intra-abdominal varix of the umbilical vein: Is it an indication for fetal karyotyping? [Abstract] Am J Obstet Gynecol 176:S93, 1997
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