To the best of our knowledge, this study has the largest sample of prenatal ultrasound diagnoses of fetal PRUV to date, including 756 PRUV fetuses. This study analyzed and summarized 10 years of data from the prenatal ultrasound center of our hospital to find the incidence of PRUV (0.17%) and of other concomitant anomalies found on prenatal ultrasound examination of PRUV fetuses (13.5%). The most common types of anomalies in PRUV fetuses were cardiovascular anomalies, followed by nervous system, urinary system, skeletal, and other anomalies. PRUV was associated with a higher incidence of any fetal anomalies, and when these anomalies were classified by systems, PRUV was associated with a higher incidence of cardiovascular, nervous, urinary, skeletal, digestive, and respiratory system anomalies. When a PRUV fetus has SUA at the same time, the risk of any concomitant anomalies and the risk of fetal cardiovascular anomalies are further increased.
The prenatal ultrasound detection rate of fetal PRUV differs among studies. Several studies have shown detection rates similar to our rate of 0.17%.1,6,8,12 Retrospective studies in Spain and Germany had lower detection rates of 0.1% and 0.08%.2,10 Two studies showed much higher detection rates of 0.46% and 0.5%, but the authors have attributed this to the private system and referrals in one study and the prospective study design and small sample size in the other.9,11 The actual incidence may be slightly higher than 0.17% because our data includes late pregnancy and emergency cases. Given the limitations of fetal position and limited examination time, PRUV may be missed in such examinations. If the PRUV was associated with a significant anomaly, demise may have occurred before detection, thereby lowering the detection rate.
PRUV can appear in isolation or concomitantly with anomalies in other systems. Our study shows that approximately 13.5% of PRUV fetuses have anomalies in other systems, similar to the concomitant malformation rate of 13% reported by Blazer et al.12 or 17.9% reported by Adiego-Calvo et al.6, and was lower than the rate of 23.5–40.9% reported by other researchers.1,2,9,10 The lower proportion of PRUV fetuses with concomitant anomalies observed in our study may be due to the following: first, our study included cases at late gestation, while some fetuses with PRUV and concomitant serious anomalies might have been aborted during early or mid-gestation or had stopped growing in utero. Other studies focused on the second trimester window which may have detected more serious anomalies. Second, fetuses with isolated SUA were not included in the concomitant anomaly group in our study. By comparison, some studies included fetuses with isolated SUA in the concomitant anomaly group, thus increasing the proportion of fetuses with anomalies. Third, the discrepancy may be explained by different sample sizes.
Our study shows that compared with the control group, the risk of fetal anomalies increased, and when these anomalies were classified by systems, PRUV also increased the risk of cardiovascular, nervous, urinary, skeletal, digestive, and respiratory system anomalies. The most common anomalies in PRUV fetuses were cardiovascular system anomalies, followed by nervous system, urinary system, skeletal, and other anomalies. Similar to our study, Adiego-Calvo et al. 6 found a statistically significant association between isolated PRUV and the presence of congenital malformations, but in their series, only malformations of the genitourinary system showed this positive association. The difference in sample size may be the main reason for the different results.
When both PRUV and SUA occurred, the risk of any fetal anomalies and cardiovascular anomalies is further increased. Our study is the first to report this significant finding, which suggests that when PRUV and SUA coexist, detailed examination of other fetal systems, especially the cardiovascular system, should be conducted.
In this study, the presence of the most common anomalies suggest that PRUV may not only be a variation of the anatomy of the umbilical vein, but it may also be a link to developmental abnormalities of the fetal cardiovascular system, or it may be regulated by a common mechanism controlling the development of the nervous system, urinary system, and skeletal system; these speculations must be validated by in-depth studies. Other proposed causes in the literature include thromboembolism or external compression in early pregnancy leading to early occlusion of the left umbilical vein, preserving the blood supply to the right umbilical vein1, insufficient folic acid supplementation, or effects of specific teratogenic drugs in early pregnancy.7
In previous reports, chromosomal abnormalities in PRUV fetuses include trisomy 21, trisomy 18, Turner mosaicism, Noonan’s syndrome, and so on. Wolman et al. reported a case of a PRUV fetus with trisomy 18,1 Bradley et al. reported a case of a PRUV fetus with Noonan’s syndrome, 13 Weichert et al. reported a case of PRUV fetus with Turner mosaicism and another with trisomy 18,10 Krzyżanowski et al. reported a case of a 69, XXX PRUV fetus,9 and Canavan et al. reported five cases of PRUV fetuses with chromosomal abnormalities (three cases of trisomy 18 and two cases of trisomy 21). Of these cases, only one case with trisomy 21 and one case with Turner mosaicism had no additional abnormal sonographic findings. In our cohort of patients, two cases of trisomy 18 were found, both of which had multiple malformations. Collectively, these reports and our results demonstrate that PRUV fetuses with chromosomal abnormalities usually have malformations of other systems, and isolated PRUV does not have a high risk of chromosomal abnormalities. PRUV fetuses with additional abnormal sonographic findings should undergo fetal chromosome examination.
This study has some limitations. First, this study has a retrospective design. Thus, some cases of fetal PRUV may not be detected due to the limitations of the fetal position during the third trimester and limited time during emergency ultrasound examination, which may result in an underestimated PRUV detection rate. Second, the abnormalities were found by ultrasonography, not the results of pathological examinations.