Color Doppler, HDlive, and HDlive Silhouette features of an umbilical cord cyst before 11 weeks of gestation: Diagnostic value

We describe transvaginal color Doppler, HDlive, and HDlive Silhouette features of an umbilical cord cyst (UCC) before 11 weeks of gestation.


| INTRODUC TI ON
2][3][4][5][6][7] The incidence of UCC detected in the first trimester was 0.4%-3.4%. 2,3,6,7Four studies showed that pregnancy outcomes were noneventful. 1,2,4,5However, Ross et al. 3 reported that 26% of UCCs are associated with fetal abnormalities, such as chromosomal or structural defects.Ghezzi et al. 6 showed that all UCCs with single cysts led to healthy neonates, whereas five of six UCCs with multiple cysts led to miscarriage or fetal abnormality.Bonilla et al. 8 reported that differentiation between true and pseudocysts may be possible using different three-dimensional ultrasound modes.However, the incidence, nature, origin, and pregnancy outcome of UCCs in the first-trimester is still unknown.In addition, there have been only two studies to focus on UCC outcomes at less than 12 weeks of gestation. 4,5In the current study, we evaluated UCCs using transvaginal color Doppler, HDlive, and HDlive Silhouette to elucidate the nature and origin of UCCs detected before 11 weeks of gestation.
Moreover, the clinical characteristics, pregnancy courses, and outcomes were investigated.

| MATERIAL S AND ME THODS
In this cohort study, examinations were planned for research purposes.During the 9-month period from November 2021 to July 2022, 135 transvaginal dating scans were performed randomly at 7 to 10 + 6 weeks of gestation.The data were collected on a basic lowrisk population in the outpatient department of an obstetrics and gynecology clinic at a local district in Japan.All examinations were performed using Voluson SWIFT (GE Healthcare) and Voluson E10 BT21 (GE Healthcare) with a transvaginal transducer (GE RIC5-9-RS, 3.8-9.3MHz).One experienced examiner (T.H.) conducted all transvaginal two-dimensional sonographic, color Doppler, HDlive, and HDlive Silhouette examinations.UCC was defined as single or multiple echo-free spaces adjacent to and/or inside the umbilical cord (UC), and the number and the location of UCCs were determined.Crossexamination of the whole UC was conducted.Moreover, the zoom-up function (maximum 3.4-times zooming) was used to observe the whole UC.Seventeen UCCs (12.6%) were identified at 7 to 10 + 6 weeks of gestation (two at 7, seven at 8, seven at 9, and one at 10 weeks), and were evaluated using color Doppler, HDlive, and HDlive Silhouette.
Detection and diagnosis of UCC and midgut herniation and their evaluations were examined by two examiners (T.H. and T.K.), with complete agreement between them.The clinical courses and outcomes such as maternal age, para, birth age, birth weight, sex ratio, Apgar score, umbilical artery blood pH (UApH), delivery method, incidence of neonatal abnormality, incidence of maternal complication, and placental weight between control (non-UCC) and study (UCC) groups were also investigated.The researcher (M.K.) blinded to UCC diagnosis collected outcomes.Missing outcome data in the lost to follow-up cases were excluded from the statistical analysis.The study was conducted following approval by the ethics committee of Miyake Clinic, Okayama, Japan.All participants provided informed consent after a full explanation of the aim of the study.

| Statistical analysis
Maternal age, birth age, birth weight, UApH, and placental weight between the control and study groups were examined by unpaired t tests.Para and Apgar score values between groups were examined by Mann-Whitney U tests.The sex ratio, delivery method, incidence of neonatal abnormality, and incidence of maternal complication were compared between the two groups using χ 2 test.All analyses were performed with Mathematica 13.0.0.0 (Wolfram Research).A P value <0.05 was considered significant.

| RE SULTS
A normal UC depicted by two-dimensional sonography, HDlive, and HDlive Silhouette at 8 weeks and 2 days of gestation is shown in Figure 1.
The mean crown-rump length was 18.7 mm (SD, ±2.1 mm).The incidence of UCC was 12.6% at 7 to 10 + 6 weeks of gestation (two at 7, seven at 8, seven at 9, and one at 10 weeks).There were 10 multiple and seven single cysts (Figures 2-5).Cyst diameters ranged from 3.3 to 11.3 mm (mean, 5.6 mm; SD, ±2.1 mm).UCC location was on the fetal side in six cases (Figure 2a), at the free loop in 10 cases (Figures 3a and 4a), and on the placental side in one case (Figure 5a).Blood flow was noted in three cases (17.6%) (Figure 4b).Nuchal translucency thickness was 1.4 (mean) ± 0.5 (SD) mm, and ductus venosus flow was normal on the first-trimester fetal ultrasound scan (at 11 to 13 + 6 weeks of gestation) (Table 1).All except two cases (lost to follow-up) involved noneventful pregnancy courses and resulted in healthy neonates (Table 1).
Figure 6 presents a flow diagram of participants with or without outcomes in the control and study groups.

| DISCUSS ION
0][11][12][13][14][15][16] In this investigation, HDlive also clearly showed with an increased risk of miscarriage, fetal anomaly, or aneuploidy. 6,7e first study was performed at 7 to 14 weeks of gestation, 6 and the latter was conducted at 11 to 13 + 6 weeks of gestation. 7On the other hand, UCCs detected at less than 12 weeks of gestation were not associated with poor pregnancy outcomes. 4,5In the current study, there were seven single and 10 multiple UCCs before 11 weeks of gestation, and all UCCs except for one case (lost to follow-up) resolved at less than 15 weeks of gestation.In particular, UCCs disappeared at less than 11 weeks of gestation in 12 of 16 cases (75%).All except for two cases (lost to follow-up) involved noneventful pregnancy courses and resulted in healthy neonates.
Therefore, UCCs detected incidentally in early pregnancy may not be an ominous sign.
Sepulveda et al. 17  ascertain the pregnancy outcome with a first-trimester umbilical artery aneurysm-like appearance.
The incidence of UCC detected in the first trimester was 0.4% to 3.4%. 2,3,6,7In the current study in a basic low-risk population, however, the incidence of UCC was 12.6% at 7 to 10 + 6 weeks of gestation (two at 7, seven at 8, seven at 9, and one at 10 weeks).
The reason for this marked difference in the incidence of UCC among the current study and previous investigations is currently unknown.One possible explanation is the difference of the ul-

F I G U R E 3
the spatial relationships among UCC, the UC, midgut herniation, yolk sac, and embryo at 7 to 10 + 6 weeks of gestation.HDlive Silhouette also showed the difference in the internal structure of UCC.Moreover, it clearly demonstrated the sac of midgut herniation in the UC.Color Doppler differentiated vascular from avascular UCC.Therefore, color Doppler, HDlive, and HDlive Silhouette may provide information on the nature and origin of UCC and midgut herniation before 11 weeks of gestation.Single UCCs in the first trimester were associated with a favorable pregnancy outcome, whereas multiple UCCs were associated F I G U R E 2 Multiple umbilical cord cysts (UCCs) located on the fetal side depicted by two-dimensional sonography (a), color Doppler (b), HDlive (c), and HDlive Silhouette (d) at 8 weeks and 6 days of gestation.AM, amniotic membrane; CC, central cyst; MH, midgut herniation; UC, umbilical cord; YS, yolk sac.Multiple umbilical cord cysts (UCCs) located at the free loop depicted by two-dimensional sonography (a), color Doppler (b), HDlive (c), and HDlive Silhouette (d) at 9 weeks of gestation.CC, central cyst; MH, midgut herniation; YS, yolk sac.F I G U R E 4 A single umbilical cord cyst (UCC) located at the free loop depicted by two-dimensional sonography (a), color Doppler (b), HDlive (c), and HDlive Silhouette (d) at 8 weeks and 4 days of gestation.CC, central cyst; F, fetus; MH, midgut herniation; UA, umbilical artery; UC, umbilical cord; UV, umbilical vein; YS, yolk sac.

F I G U R E 6
reported an aneurysm of the umbilical artery in three cases with UCCs, with all resulting in fetuses with trisomy 18.However, these cases were diagnosed in the third trimester of pregnancy.In this investigation, three cases with a dilated umbilical artery were noted as UCC before 11 weeks of gestation, and pregnancy courses and outcomes were noneventful.A firsttrimester umbilical artery aneurysm-like appearance as UCC may be a transient physiological change.However, these results were only from three case reports.Further investigations are needed to F I G U R E 5 Multiple umbilical cord cysts (UCCs) located on the placental side depicted by HDlive (a), and HDlive Silhouette (b, c) at 8 weeks and 6 days of gestation.MH, midgut herniation; UC, umbilical cord; VD, vitelline duct; YS, yolk sac.The flow diagram of participants with or without outcomes in the control and study groups.UCC, umbilical cord cyst.
trasound device used.In our investigation, we used an advanced ultrasound device with a high-resolution transvaginal probe for cross-examination of the whole UC.Moreover, the zoom-up function (maximum, 3.4-times zooming) was used to observe the whole UC.Another possible explanation is the difference in attentiveness of observers to detect UCCs among our study and previous investigations.In previous investigations, UCCs were detected incidentally, whereas we observed the whole UC to detect UCCs in detail.Moreover, the whole UC might not be observable late in the first trimester of pregnancy because of ultrasound penetration of the transvaginal probe.Further studies involving a larger sample size are needed to detect the true incidence of UCC in the first trimester of pregnancy.In conclusion, the incidence of UCC was high compared with those in previous reports in the first trimester of pregnancy.Color Doppler, HDlive, and HDlive Silhouette may provide information on the nature and origin of UCCs before 11 weeks of gestation.UCC before 11 weeks of gestation may be a common, transient, and benign finding in utero.The feasibility of early screening of UCC is to use an advanced ultrasound device with a high-resolution transvaginal probe for cross-examination of the whole UC and to use the maximum zoom-up function to observe the whole UC.

Table 2
shows the comparison of birth age, birth weight, neonatal sex, Apgar score at 1 and 5 min, UApH, delivery method, neonatal abnormality, maternal complications, and placental weight between the control and study groups.The maternal age (mean, 28.47 years; SD, ±4.70) in the study group was significantly younger than in the control group (mean, 31.13 years; SD, ±4.79) (P = 0.044).There were no significant differences in para, birth age, birth weight, sex ratio, Apgar scores at 1 and 5 min, UApH, delivery method, neonatal abnormality, maternal complication, or placental weight between the groups.