Ultrasonographic classification of 26 cases of fetal umbilical-portal-systemic venous shunts and the correlations with fetal chromosomal abnormalities

For the 26 cases of UPSVS in this study, the earliest gestational weeks at diagnosis was 12 weeks, and the latest was 28 weeks, with an average of 21 weeks. Among them, ten cases (38%) had advanced maternal age (≥ 35 years), and fourteen cases (54%) had advanced paternal age (≥ 35 years).

Clinical data of the 26 cases of UPSVS were shown in Table 1. Among them, twenty cases terminated pregnancies, and six continued pregnancies to term deliveries; twenty received invasive prenatal diagnosis, and nine had fetal chromosomal abnormalities. According to the classification method of UPSVS put forward by Achiron, et al., four cases (15%) were diagnosed as type I, ten (38%) were type II, three (12%) were type IIIA, and nine (35%) were type IIIB [5]. All four cases of type I manifested as fetal heart enlargement and heart failure. Four of ten cases of type II had chromosomal abnormalities (all four were trisomy 21). Among the ten cases of type III who received invasive prenatal diagnosis, five cases of type IIIB had fetal chromosomal abnormalities (two of trisomy 18, one of trisomy 3 mosaicism, one of chromosome 10 micro-deletion, one of chromosome 8 micro-duplication). In UPSVS fetuses, type II and type IIIB were mostly complicated by chromosomal abnormalities, which were 44% (4/9) and 50% (5/10), respectively.

In order to show the frequency of UPSVS in our center, we made statistics on frequency of other structural anomalies in our center in the corresponding period, as shown in Table 2. In this study, the anatomic abnormality that umbilical vein runs on the liver surface and directly connects with right atrium was observed in all four cases of type I (umbilical vein-systemic shunt, USS), as shown in Fig. 1. Meanwhile, the UV-LPV-DV complex was not detected in fetal liver, and intrahepatic portal vein was unclear on ultrasonography. Due to anatomic abnormality, the umbilical vein blood flowed directly into the right atrium without entering the liver, which led to significantly increased blood volume load of the right atrium. This could be the reason why all four cases of type I manifested as heart enlargement and heart failure, and all terminated pregnancies due to the subsequent poor fetal prognosis.

The ten cases of type II (ductus venous-systemic shunt, DVSS) all had intact UV-LPV-DV complexes. However, the ductus venosus did not connect to subdiaphragmatic vestibule, but ectopically connected to the liver segment of inferior vena cava, as shown in Fig. 2. Among cases of type II, six of ten cases terminated pregnancies. Four cases were invasively diagnosed as trisomy 21, with complicated structural malformations as aberrant right subclavian artery, ventricular septal defect, nuchal fold thickening, absence of ossified nasal bone, echogenic bowel, and FGR. One case was monochorionic diamniotic twins, in which fetus A was type II UPSVS and fetus B was acardia malformation, but the couple declined prenatal diagnosis. One case had normal karyotyping and CNV-seq results, but complicated by fetal edema, nuchal translucency thickening, and cervical cystic hygroma. Four of ten cases had isolated type II UPSVS and normal karyotyping and CNV-seq results, and continued pregnancies to term deliveries. The four babies were normal in growth and development in the follow-ups at 33 months after birth.

All the three cases of type IIIA (intrahepatic portosystemic shunt, IHPSS) had complicated structural malformations, and all terminated pregnancies. One case had a communicating branch connecting left portal vein (LPV) and middle hepatic vein, absence of UV-LPV-DV complex, complete transposition of the great arteries, right aortic arch, absence of right lung, right ureter stenosis near the bladder, severe right hydronephrosis, and single umbilical artery, as shown in Fig. 3. One case had a communicating branch connecting right branch of portal vein and right hepatic vein, and right multicystic dysplastic kidney. One case had a communicating branch connecting left lateral lobe portal vein and left hepatic vein, fetal heart enlargement (heart-chest area ratio = 0.44), and mitral and tricuspid regurgitation. Two of them received prenatal diagnosis, and had normal karyotyping and CNV-seq results.

The nine cases of type IIIB (extrahepatic portal-systemic shunts, EHPSS) had common ultrasound characteristics that main portal vein blood flow into the liver was not detected at the first porta hepatis, and the hepatic artery was widened compensatorily. In seven of the nine cases, UV-LPV-DV complex was detected. one case had an abnormal blood vessel originating from portal sinus, tortuously coursing to the right, posterior and inferior, and merging into hepatic segment of inferior vena cava, as shown in Fig. 4. Fetal complicating structural abnormalities included FGR, ventricular septal defect, coarctation of aortic arch, bulging of right diaphragm, and bilateral choroid plexus cysts. The karyotyping result was trisomy 18. One case had abnormal left-hand posture, bilateral choroid plexus cysts, and abnormal karyotype of trisomy 18. One case had absence of ossified nasal bone and abnormal karyotype of 47,XN,+3(8) / 46,XN(44) mosaic. One case had fetal edema, thickened nuchal fold of 7.7 mm, but the couple declined invasive prenatal diagnosis. The other three cases had normal inner diameter of venous duct, well-filled intrahepatic portal vein, and none of other structural abnormalities. Among them, one case had an abnormal blood vessel originating from portal sinus, tortuously coursing to the left, posterior and inferior, and merging into left internal iliac vein; one case had an abnormal blood vessel originating from portal sinus, tortuously coursing to the left, posterior and upper, and merging into the azygos vein, as shown in Fig. 5. These two cases declined invasive prenatal diagnosis, and continued pregnancies to term deliveries. Follow-ups until December 2022, 20 and 33 months after birth respectively, showed that one baby was normal in growth and development, and the other had elevated total bile acid of 31 µmol/L (normal reference range 0–15 µmol/L), while other indicators of liver function test were normal. She has received ursodeoxycholic acid treatment. At present, she had normal intelligence development and a normal body weight of 13 kg and height of 84 cm. However, these two cases of type IIIB UPSVS did not have angiography to confirm the congenital vascular malformations. These two cases were also the only two live births among nine cases of type IIIB. The other case had an abnormal blood vessel originating from portal sinus, tortuously coursing to the right, posterior and inferior, merging into liver segment of inferior vena cava. CNV-Seq result showed an micro-duplication of 46,XY, dup(8)(p23.1), 3.8 Mb, and the pregnancy was terminated by induced labor. Two of nine cases of type IIIB had no UV-LPV-DV complex, complicated with absence of intrahepatic intrinsic portal vein, absence of main portal vein and its blood flow at the first porta hepatis, enlarged hepatic artery, and abnormal intrahepatic portal vein and its branches. One of the cases had normal karyotyping and CNV-Seq results, but the couple chose to terminate pregnancy. The other case was dichorionic diamniotic twins conceived by IVF-ET technology. Fetus A was type IIIB UPSVS, and resulted in stillbirth at 26 gestational weeks. Fetus B was normal on ultrasonography, delivered at full term, and was normal in growth and development in the follow-up at 4 months after birth. Both twin fetuses had normal karyotyping and CNV-Seq results.

The ultrasonographic characteristics, including the complicated cardiac and extracardiac anomalies, CVPS scoring, karyotype and CNV-Seq results, and pregnancy outcomes of the 26 UPSVS fetuses were summarized in Table 3, and the frequency of UPSVS coexistent defects/ anomalies in Table 4.