Fetal umbilical artery thrombosis: prenatal diagnosis, treatment and follow-up

UAT is a rare but potentially dangerous complication. Because of its rarity and limited research data, there is currently no consensus on the treatment strategy for fetal UAT. Additionally, many obstetricians are unfamiliar with UAT. This study reported the initial experience of our centers. The prediction of fetal prognosis and the treatment response underlie important clinical decisions. Notably, our study indicated that the combination of decreased GA and UC abnormalities was of high value for predicting adverse pregnancy outcomes among fetuses with UAT in our setting. No significant differences in adverse outcomes were found between the urgent or expectant management groups.

Underlying pathogenic factors of fetal UAT. Our data showed that GDM and UC abnormalities were independent risk factors for the occurrence of UAT. Recent findings in two descriptive case series by Li et al. [10] and Zhu et al. [4] also noted that congenital UC dysplasia and maternal abnormal blood glucose could be likely etiologies. Unfortunately, their data did not provide enough statistical support. GDM was the most frequent concomitant disease (20%) found to be associated with UAT. The frequency of GDM in this study was far higher than that in the general pregnant population [11]. Previous case series have also reported that some pregnant women with fetal UAT had GDM [12, 13]. Brown et al. (2019) demonstrated a correlation between maternal diabetes and fetal thrombotic vasculopathy [14]. Although the cause was unknown, it may be explained using Virchow’s hypothesis for thrombosis (blood stasis, endothelial injury, and hypercoagulability) [15]. The UC, which is a cord-like structure connecting the fetal umbilicus and the placenta, is an important channel for nutrient metabolism and material exchange between a fetus and its mother. An abnormal UC anatomy or mechanical injury to the UC, including excessive length, twisting, true knots, hypercoiling, and compression, may be associated with blood flow restriction and the occurrence of umbilical vessel thrombosis [16,17,18,19]. Most UAT cases reported previously were related to UC abnormalities (e.g., Oliveira et al.; Wei et al. [19, 20]). In our study, notable UC abnormalities were present in a large proportion (30.0%) of fetuses with UAT. Umbilical vascular thrombosis may also be linked to other common risk factors, such as abnormal coagulation function and infection [12]. However, consistent with the study by Wei et al., we did not find obvious abnormalities in maternal inflammation or coagulation [20].

Prenatal diagnosis. The prenatal diagnosis of UAT depends mainly on ultrasonography, and UAT is easily detected by color or power Doppler flow tests. Abnormal Doppler waveforms of umbilical vessels may be detected before obvious anomalies of fetal circulation occur [21]. Cook et al. first proposed that prenatal early diagnosis of UAT could be made by ultrasound examination, after which some scholars described it as the "orange grabbed" sign [22, 23]. Our study had similar findings. It is important to maintain high vigilance in high-risk pregnancies, especially those with GDM and UC abnormalities. Interestingly, the left UA was more commonly absent in fetuses with a single umbilical artery, but in fetuses with UAT, the right UA was more frequently involved [24]. Further research is needed to explore these differences and complexities.

Prognosis. Here, we propose a predictive model based on GA and UC abnormalities for evaluating pregnancy outcomes. In this model, fetuses with a smaller GA or structural abnormalities in the UC are more likely to have adverse pregnancy outcomes. For patients hospitalized due to disease, a lower GA tends to be indicative of a poor prognosis [25]. A hospital-based decade-long retrospective study in Taiwan found that umbilical cord pathology, including stricture, true knots, strangulation of the fetus, and prolapse, was the most common cause of third-trimester intrauterine fetal demise [26]. In the present study, among the UCs of the confirmed UAT patients, six patients had hypercoiling, five had severe entanglement, and one had excessive length. Clearly, excessive length would increase the risk of UC entanglement. Moreover, fetuses with an excessive UC length, a non-reassuring sign, have significantly increased rates of respiratory distress and perinatal death than those without this sign [27, 28]. Many studies have emphasized the correlation between abnormal umbilical coiling and adverse perinatal outcomes. A hypercoiled UC was significantly associated with thrombosis in umbilical vessels, preterm delivery, aneuploidy and fetal anomalies, increasing the risk of fetal death [29, 30]. Ernst et al. also suggested that hypercoiled UCs with certain gross patterns might be associated with chronic fetal vascular obstruction and stillbirth [31]. Obstetricians should comprehensively assess GA and whether excessive length, severe entanglement, or hypercoiling exists in the UC by ultrasound. This will help obstetricians better grasp the progression and alleviate the fear and anxiety of pregnant women.

Interventions. Obstetricians might be hesitant to intervene when managing a fetus with UAT. Obstetricians often make treatment choices according to the fetal status and their own understanding and experience [3, 13]. As mentioned in the Methods section, we are sharing our experience with UAT over several years. Fortunately, after implementation of the current screening and therapeutic strategy, the expectant management group did not have worse fetal outcomes than the urgent treatment group. Therefore, the possibility of fetal protection should be considered in fetuses with a very low GA, while urgent delivery is suggested for fetuses with a higher GA to avert unnecessary fetal loss. In addition, combined with the above prognostic predictors, it is suggested that fetuses with obvious UC abnormalities be treated aggressively.

The strengths of this study are the relatively large sample size of patients with fetal UAT, the completeness of the follow-up and the real-world nature of the data. However, the present study has several potential limitations. The major limitation is that the current evidence is based on retrospective studies and registry data, and it is unknown whether our results can be generalized to the broader population with UAT.

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