Clinical experience of Umbilical Cord cysts from a Chinese single centre


 BackgroundThe aim of this series was to guide the prenatal management of umbilical cord cysts by summarizing their clinical datas.MethodsA retrospected study from Jan 2012 to May 2019 was conducted in our centre from Women’s Hospital, School of Medicine, Zhejiang University. Clinical datas and pregnancy outcomes of women with umbilical cord cysts were reviewed from the hospital’s electronic record and descriptive information about the umbilical cord cysts were depicted from both the sonograms and macrography.ResultsTwenty-eight women were diagnosed with umbilical cord cysts during the last six years,of whom only three had therapeutic abortion for fetal malformations and twenty-three were diagnosed between 12 + and 38 + gestational week(GW). Eight had only maternal serum screening, six had non-invasive prenatal testing (NIPT) directly and six had both tests. Three had karyotype analysis while five cases had no record.With maternal serum screening,one had high risk and the other one had middle risk and they both further had NIPT low risk.Still another one had a HCG multiple of median (MoM) up to 2.9 whose fetal had left kidney cyst.Except umbilical cord cysts, six fetus had other sructural defects including multiple malformation,single umbilical artery,acromphalus and kidney absence or cyst.There were still two cases had fetal arrhythmia and atrial premature beats.The mean delivery week was 39 + GW, six women had successful vaginal delivery and the remaing had cesarean section. The mean birth weight was 3120 g and the majority had a good pregnancy outcome.ConclusionsUmbilical cord cysts were rare but might warn fetal structural defects or chromosomal abnormality. Systematic ultrasound assessment and karyotype analysis or NIPT at least should be suggested in their prenatal counseling. More attention should be paid to fetal distress during pregnancy and vaginal delivery could be a choose unless they had other contraindication.


Abstract Background
The aim of this series was to guide the prenatal management of umbilical cord cysts by summarizing their clinical datas.

Methods
A retrospected study from Jan 2012 to May 2019 was conducted in our centre from Women's Hospital, School of Medicine, Zhejiang University. Clinical datas and pregnancy outcomes of women with umbilical cord cysts were reviewed from the hospital's electronic record and descriptive information about the umbilical cord cysts were depicted from both the sonograms and macrography.

Results
Twenty-eight women were diagnosed with umbilical cord cysts during the last six years,of whom only three had therapeutic abortion for fetal malformations and twenty-three were diagnosed between 12 + and 38 + gestational week(GW). Eight had only maternal serum screening, six had non-invasive prenatal testing (NIPT) directly and six had both tests. Three had karyotype analysis while ve cases had no record.With maternal serum screening,one had high risk and the other one had middle risk and they both further had NIPT low risk.Still another one had a HCG multiple of median (MoM) up to 2.9 whose fetal had left kidney cyst.Except umbilical cord cysts, six fetus had other sructural defects including multiple malformation,single umbilical artery,acromphalus and kidney absence or cyst.There were still two cases had fetal arrhythmia and atrial premature beats.The mean delivery week was 39 + GW, six women had successful vaginal delivery and the remaing had cesarean section. The mean birth weight was 3120 g and the majority had a good pregnancy outcome.

Conclusions
Umbilical cord cysts were rare but might warn fetal structural defects or chromosomal abnormality.
Systematic ultrasound assessment and karyotype analysis or NIPT at least should be suggested in their prenatal counseling. More attention should be paid to fetal distress during pregnancy and vaginal delivery could be a choose unless they had other contraindication.

Background
Umbilical cord cysts were a rare entity, de ned as an echolucent area within the umbilical cord. They were classi ed as true cysts and pseudocysts, with the former orignated from embryonic remnants including the allantoic duct and omphalomesenteric duct while the latter represented only localized edema or degeneration of the Wharton's jelly.That is, the essential difference between true cysts and pseudocysts was whether to have an epithelial lining inside the cyst wall or not,thus it was di cult to distinguish them prenataly [1].
Regardless of true cysts or pseudocysts,they both presented a challenge to obstetrician due to their association with adverse pregnancy outcoms. A number of cases indicated that umbilical cord cysts had no clinical signi cance when they were detected as early as 8-9 weeks menstrual age [2].However, multiple cycsts while not single detected in rst trimesters had been reported to be associated with miscarriage and aneuploidy [3] and cycsts detected in the 2nd and 3rd trimesters were associated with fetal abdominal wall defects or chromosomal anomalies especially trisomy 13 and 18 [1]. Their relation with obstructive uropathy had also been observed in some cases [4,5]. It was very necessary to exclude fetal malformation and chromosomal anomalies for these pregnant women. In this series we summarized twenty-eight cases of umbilical cord cysts detected during the 2nd and 3rd trimester. The prenatal datas and pregnancy outcomes were also reviewed from the hospital's electronic record.

Methods
This was a retrospective study involved 28 pregnancy women with umbilical cord cysts delivered in our department during the period of September 2012 to March 2019. The diagnosis of umbilical cord cysts was made by routine B-mode ultrasound examinations. Pathological examination or macrography of the placentas ultimately con rmed the ultrasound diagnosis for all cases.The data were collected by searching on medical records and department of pathology databases.
This research conformed to the provisions of the Declaration of Helsinki and was approved by the ethics committee of Women's hospital Zhejiang University.The patients were informed and provided their written informed consent.

Results
During the six years period, twenty-three cases were diagnosed with umbilical cord cysts by ultrasound at mid-late pregnancy(range,12+W-38+W) and ve cases were found during delivery. Among the total twenty-eight cases, twenty-ve patients successfully delivered at last and three had induced abortion for fetal malformations. The average age was thirty-one years old (range,24-38years)with 10 primipara and 18 multipara,of whom 4 primipara fertilized by IVF. As gestation proceeded, ve cases had cysts diameter increased signi canly and the largest one was 15cm in diameter. 7 cases were more than 5 cm when diagnosed while increased to that diameter at delivery. As to cycst location,placenta, fetal and central occurred equally and cycst were seen more(showed in Table 1 and 2).
Almost all cases had at least one type of prenatal screening except 5 cases with no record. 11 patients had maternal serum screening low risk and 5 had NIPT low risk as well. 1 had middle and the other had high risk but both had NIPT low risk eventually while there was still 1 had high HCG mom 2.9 though with biochemical screening low risk. 6 cases had NIPT test directly. Of the 3 cases having karyotype analysis, 1 had 46XN,15S+ and the other two had normal karyotype(shown in Table 3 . Except umbilical cord cysts,eight cases had other fetal abnormality. One fetal was diagnosed with multiple malformation especially multiple cardiac anomalites at 16+GW while the other one was diagnosed with lobular whole forebrain. The third one was diagnosed with 4cm umbilical cord cysts at 25+GW but the cycst enlarged to 10 cm at 32+W and the fetal had multiple malformation. The forth case had single umbilical artery and acromphalus and the remaining two had left kidney absence or cyst.There were still two cases had fetal arrhythmia and atrial premature beats inspite inspite of no sructural defects(showed in Table 4). The mean delivery week was 39+W, six women had successful vaginal delivery and no fetal distress happened including the case with cycst diameter up to fteen centimeter. Seven had emergency cesarean section for higher S/D, fetal distress or breech position while the other twelve had selective cesarean section for scarred uterus, intrauterine infection, or IVF. The birth weight ranged from 1420g to 4220g with the average 3120g and only one fetal's weight was lower than the 10 percentage. All these datas were summarized in Table 1,2 and 3.

Discussion
Umbilical cord cysts were usually detected incidentally on routine obstetric ultrasongraphy with the reported occurrence rate 0.4-3.4% [1,6]. Our department was one of the largest top three specialized hospitals in China and the total number of birth was about two million per year,while only twenty-eight pregnancy women were diagnosed with umbilical cord cysts during the past six years. This, to some extent, explained umbilical cord cysts were really rare.As being detected accidently and no large scale reports, proper prenatal management was di cult to be established.The existing literature had reported that the gestational week of beening diagnosed, number,type and location of umbilical cord cysts were associated with poor fetal outcome.Umbilical cord cysts which occurred in rst trimester and completely resolved before 20 weeks usually had a good outcome [7,8]. However, the percentage of fetal structural defects might increased remarkably to 50% when they persisted to or were diagnosed in second and third trimester [9]. The association of umbilical cord cysts with abdominal wall defect [10] and urinary tract such as omphalocele [11][12][13] had been well documented previously and rare ones including cardiac malformation [14] and single umbilical artery [15] were also reported. Of our case series, six fetus had structural defects and the ratio was about 21%. Besides the above defects,other complicated abnormalities such as lobular whole forebrain,kidney absence or kidney cyst had yet not been reported.
we suggested that women diagnosed with umbilical cord cysts should be given a systematic and comprehensive ultrasound assessment to exclude potential structural defects [16].
Literature also reported that it was the umbilical cord pseudocysts,rather than true cysts that had a higher risk of fetal trisomy 13 and 18 [12].Though classied into true cysts and pseudocysts, it was di cult to distinguish them by prenatal ultrasound and it was very important to choose a relialbe prenatal method to screen fetal chromosomal abnormality for these women.There were three screening methods including maternal serum screening,NIPT and karyotype analysis of amniocentesis at present.The results of serum biochemical markers(AFP,free β-HCG ,PAPP-A) could just be used in general population to screen trisomy 21and 18. Meantime,the maternal serum AFP and free β-HCG levels tended to be signi cantly low in pregnant women with trisomy 18 fetus [17,18] while fetus with abdominal defects,the two levels tend to be signi cantly high [19],then when the two coincidenced,the two levels might be in the normal range. NIPT had been widely used in prenatal screening for trisomy 21,18 and 13 both in high risk and general pupulation [20].In our present series,twenty had maternal serum screening and/or NIPT and three had karyotype analysis while ve cases had no record (showed in Table 3).Of the twenty cases, eight had only maternal serum screening, six had NIPT directly and six had both tests.With maternal serum screening,one had high risk and the other one had middle risk while they both further had NIPT low risk.Still another one had a HCG MoM up to 2.9 whose fetal had left kidney cyst. One fetal had abnormal karyotype of our three karyotype analysis, and fetal mosaic tetrasomy 10p was also reported [21], thus karyotype analysis or NIPT at least was more recommended in these high risk population though half of our cases had low risk of serum screening.
Poor fetal outcomes were also reported to be related with larger ,multiple cysts or cysts located near to the placenta and fetus because of the compression of umbilical vessels or umbilical cord rupture. Limited cases reminded that umbilical cord cystic masses such as hematoma lead to intrauterine fetal death at any stage of pregnancy [22,23], and some authors recommended cesarean section to prevent intrauterine vascular compression of umbilical cord during labor [13]. But so far there was no general consensus whether these women should choose vaginial delivery or elective cesarean section. In the present case series, the majority cases were located to near either placenta or fetus, twelve had the cycst diameter more than 5cm at delivery with the largest up to15cm, ve had multiple cysts. However, all had a relative good outcome.The mean delivery week was 39+W, six women had successful vaginal delivery without fetal distress including the one with cycst diameter up to 15cm. Seven had emergency cesarean section duo to high S/D, fetal distress or breech position while the other twelve also had selective cesarean section for scarred uterus,intrauterine infection, or IVF. So experience from our case series was that more attention should be paid to fetal distress during pregnancy and vaginal delivery could be a choose unless they had other contraindication which was in accordance with Leyre Ruiz Campo's view [24].We also paid close attention to the fetal birth weight and sex,only one fetal's birth weight was lower than the 10 percentage and the femail:mail was 17:11, we still agreed to the view that umbilical cord cysts did not in uence fetal growth while we did not note a male dominance [24].As prenatal ultrasound could not distinguish true cysts from pseudocysts, the pathological examination should be performed after delivery in each case. Unfortunately,only ve cases had pathological examination, among whom 1 was pseudocysts and the remaining 23 cases could not be distinguished.So a limitation of our study was that the low rate of pathological examination.

Conclusions
Umbilical cord cysts were rare but might warn fetal structural defects or chromosomal abnormality.
Systematic ultrasound assessment and karyotype analysis or NIPT at least should be suggested in their prenatal counseling. More attention should be paid to fetal distress during pregnancy and vaginal delivery could be a choose unless they had other contraindication. Abbreviations IVF:in-vitrofertilization;NIPT:no-invasive prenatal testing;AFI:amniotic uid index;AFP:alpha fetoprotein Declarations Acknowledgements No.

Authors' contributions
Wu zaigui collected the clinical data, analysis these data and drafted the manuscript. Dong minyue helped to revised the manuscript. All authors read and approved the nal manuscript.

Funding
This study was supported by the Zhejiang provincial Natural Science Foundation of China(Q19H040050) and Zhejiang provincial Science and Technology Plan projects (2019KY431). Both the two funding body played a role in designing the study and writing the manuscript.

Availability of data and materials
The deta-sets used and /or analyzed during the current study are available from the authors on reasonable request.