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A Cohort Analysis of Patients with Stage I Twin-to-Twin Transfusion Syndrome from a Major Referral Hospital in Northern China

Yang, Jing1; Yuan, Peng-Bo1; Wei, Yuan1; Li, Hong-Tian2; Wang, Xue-Ju1; Li, Lu-Yao1; Jiang, Yuan-Hui1; Wang, Jing3; Gong, Xiao-Li1; Zhao, Yang-Yu1,*

Section Editor(s): Guo, Chun-Ying; Pan, Yang

doi: 10.1097/FM9.0000000000000021
Original Article
Open

Objective: To describe the outcomes of Stage I twin-to-twin transfusion syndrome among patients treated with expectant management (EM), amnioreduction (AR), or fetoscopic laser occlusion of chorioangiopagous vessels (FLOC).

Methods: A cohort of 89 cases was studied. Based on the initial management strategy, patients were classified into three groups: the EM, AR, and FLOC. We assessed perinatal survival to 28 days of age and categorized pregnancy outcomes as good (twin live birth at ≥30.0 weeks), mixed (single fetal demise or delivery between 26.0 and 29.9 weeks), or poor (double fetal demise or delivery at <26.0 weeks).

Results: 26 (29.2%) patients underwent EM, 35 (39.3%) underwent AR, and 28 (31.5%) underwent FLOC therapy. Of those managed expectantly, 19.2% experienced spontaneous abortion, 50% progressed in stage, and 30.8% remained stable or regressed. After adjusting for potential confounders including maternal age, nulliparity, placenta location, and recipient maximum vertical pocket, and so on, FLOC therapy and AR were associated with significantly [odds ratio (OR) = 0.09] and borderline significantly (OR = 0.20) reduced risks of poor pregnancy outcomes and of no survivors to 28 days of age after birth (OR = 0.04 and OR = 0.20, respectively) compared with EM.

Conclusion: About 70% of those treated with EM progressed in stage or experienced fetal loss. Compared to EM, intervention may decrease the risk of poor pregnancy outcomes and improve the perinatal survival rate.

1Obstetrics & Gynecology Department, Peking University Third Hospital, Beijing 100191, China

2Institute of Reproductive and Child Health, Peking University Health Science Center, Beijing 100191, China

3Obstetrics & Gynecology Department, Peking University International Hospital, Beijing 102206, China.

Corresponding author: Yang-Yu Zhao, Department of Obstetrics & Gynecology, Peking University Third Hospital, No. 49 North HuaYuan Road, HaiDian District, Beijing 100191, China. E-mail: zhaoyangyu001@163.com

Jing Yang and Peng-Bo Yuan contributed equally to this study.

Received April 7, 2019

Online date: October 15, 2019

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

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Introduction

Twin-to-twin transfusion syndrome (TTTS) is a unique complication of monochorionic placentation where intertwin anastomoses located along the vascular equator allow unequal sharing of blood volume1 Untreated TTTS is associated with substantial risk for perinatal death, preterm birth, and neurological impairment among survivors2 The perinatal mortality rate is as high as 90% for untreated TTTS occurring before 26 weeks of gestation3 and 17%–33% of surviving neonates suffer from neurodevelopmental impairments.4 Fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) therapy has been recommended as the first-line treatment for Stage II to IV TTTS in pregnancies under 26 weeks of gestation.5 For Stage I TTTS; however, the optimal treatment strategy is highly debated.

The Society for Maternal-Fetal Medicine Clinical Guideline proposed that patients with Stage I TTTS should be managed expectantly.5 A meta-analysis including 18 studies from 1999 to 2016 assumed that the rate of progression diverged from 10% to 50% for Stage I TTTS managed expectantly and the preferred management of Stage I TTTS remains pending.6 With the accumulation of more relevant research evidence, the Green-top Guideline on the Management of Monochorionic Twin Pregnancy recommended that fetoscopic laser ablation should be considered in cases of Quintero Stage I TTTS with significant polyhydramnios (8 cm or more) or cervical shortening (less than 25 mm).7 In a recent retrospective analysis of 124 Stage I TTTS patients managed before 30 weeks of gestation in 30 hospitals in the United States and Canada between 2005 and 2014, Emery et al. concluded that 60% of patients who were managed expectantly progressed in stage and that pregnancy outcomes were significantly improved by FLOC treatment compared to expectant management (EM) and amnioreduction (AR),8 suggesting that FLOC may be considered a first-line strategy for the management of Stage I TTTS. Sago et al. had a review of studies reporting on the applications of FLOC for TTTS. The conclusion suggested that laser therapy can be expected for all stages of TTTS whereas the conservative management exhibited less attractive as a therapeutic option for Stage I TTTS.9

With the incidence of multiple pregnancy rising in China, there is an urgent need to answer the critical questions regarding what is a first-line treatment for Stage I TTTS and whether laser therapy benefits specifically apply to Stage I. The previously mentioned evidence on Stage I TTTS came primarily from Western populations. In this study, we aimed to provide updated evidence about the natural history, pregnancy outcomes, and neonatal survival status of Stage I TTTS undergoing three initial management strategies by analyzing a cohort of 89 Stage I TTTS cases at a major referral institution in northern China.

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Materials and methods

All monochorionic twin pregnancies with possible TTTS included in this retrospective study were referred to the Center for Maternal-Fetal Medicine at Peking University Third Hospital between July 2009 and December 2016. This study was approved by the Institutional Review Board (IRB00006761-2016145). All cases underwent a systematic ultrasound evaluation including chorionicity, detailed anatomic survey, biometry, arterial and venous fetal Doppler studies, measurement of amniotic fluid maximum vertical pocket (MVP), and endovaginal cervical length by professional senior doctors.

Standard prenatal ultrasound criteria for diagnosis of TTTS consisted in oligohydramnios in the donor's sac (maximal vertical pocket ≤2 cm) and polyhydramnios in the recipient's sac (maximal vertical pocket ≥8 cm). Quintero staging system defined severity of TTTS according to sonographic criteria as follow: Stage I: visualization of donor's bladder in the donor twin, and the absence of critically abnormal Doppler measurements; Stage II: bladder not visualized in the donor twin; Stage III: abnormal Doppler of the umbilical artery and/or ductus venosus in one or both twins; Stage IV: hydrops in one or both twins; Stage V: intrauterine demise of one or both twins.10

The inclusion criteria were monochorionic diamniotic twin pregnancies diagnosed with Stage I TTTS at less than 30 weeks’ gestational age (GA). The exclusion criteria included TTTS above Stage I, insufficient polyhydramnios or oligohydramnios to make the diagnosis of Stage I TTTS, fetal malformations unrelated to TTTS, monoamniotic twins, complicated twin pregnancy including selective intrauterine growth restriction (sIUGR), twin anemia-polycythemia sequence, twin reversed arterial perfusion, therapeutic amniocentesis prior to referral, elective pregnancy termination in the absence of progression to higher stage TTTS, and incomplete information and insufficient follow-up to determine the critical study outcome.

A standardized protocol was followed for the treatment of Stage I TTTS based on the indications and contraindications of intervention combining with the patient's symptoms and choices. For Stage I TTTS prior to 26 weeks of gestation, patients were treated with FLOC or AR if clinical symptoms of polyhydramnios were present such as respiratory distress or preterm contractions from polyhydramnios. Patients without above conditions were managed expectantly or treated with FLOC (Fig. 1A). In cases of gestation age at diagnosis of >26 weeks, patients with clinical symptoms of polyhydramnios underwent AR and those were managed expectantly without any symptoms (Fig. 1B). Patients and family members were fully communicated and informed the related information by two fetus medical experts including pros and cons of various treatments, the evaluation of difficulty and feasibility concerning FLOC operation and the risk of preterm birth or abortion. Cases were retrospectively divided into three groups including EM, AR, and FLOC group according to the initial management strategies.

Figure 1

Figure 1

The patients in the EM group were routinely followed with weekly ultrasound evaluation. In cases of stage progression, the patients willingly chose FLOC therapy or pregnancy termination. When clinical symptoms of polyhydramnios were present, such as contractility and shortening of the cervix, AR or FLOC therapy was offered. Patients with stabilization or improvement in disease stage delivered at our center or returned to their referring hospitals for further surveillance, management, and delivery.

Patients in the AR and FLOC groups admitted to the hospital were assessed and treated by two Maternal-Fetal Medicine specialists within 24–48 hours. AR was performed under ultrasound guidance using an 18-gauge needle, and the fluid was drained to reduce the deepest vertical pocket to 6–8 cm. AR was repeated within 7 days, or FLOC was offered when polyhydramnios recurred. In the FLOC group, cervical length (CL) and dilation were measured with endovaginal ultrasound. Patients with a CL <2.5 cm were offered cerclage placement at the time of laser surgery. All procedures in the FLOC group were performed percutaneously, with the patient under local or regional anesthesia. The site of entry on the maternal abdomen was chosen to allow access to the insertion of the intertwin membrane on the placental surface through the recipient's sac with the use of a 3.0-mm cannula with a trocar under continuous ultrasonographic guidance. A 2-mm fetoscope and a neodymium:yttrium-aluminum-garnet or diode laser with a 600-μm-diameter fiber were used. Vessels crossing the membranes were followed to identify the anastomotic vessels in the recipient's sac; these vessels were left intact if the examination confirmed that they belonged to just one twin but were otherwise coagulated using a nontouch technique at an output of 15–20 W. Amniotic fluid was subsequently drained through the cannula until the deepest pool was at most 5–6 cm on ultrasonography. In the AR and FLOC groups, all the women were kept in the hospital for 24–72 hours after the procedure and then treated as outpatients with weekly ultrasonographic follow-up. Operative details, perioperative, and postoperative complications, as well as pregnancy outcomes, were reviewed.

The natural history of Stage I TTTS includes spontaneous abortion (pregnancy loss before 28 weeks of gestation), progression, stabilization, and regression. Progression was defined as an increase in stage (from Stage I to Stage II or higher). Regression was defined as the absence of the sonographic features of Quintero Stage I TTTS. The primary outcome measures included perinatal survival rate and pregnancy outcome. The perinatal survival rates are expressed as the percentages of all survivors, no survivors, one survivor, two survivors, or at least one survivor to 28 days of age after birth. Pregnancy outcomes based on twin survival and GA at delivery were categorized as good (survival of both twins and delivery at ≥30 weeks), mixed (single twin demise or delivery at 26–29.9 weeks), or poor (demise of both twins or delivery at <26 weeks) according to the research by Emery et al.8 Furthermore, intervention-related complications were assessed.

A database was established to collect detailed information including maternal demographics, treatment options, and sonographic characteristics, maternal and neonatal complications, delivery information, and perinatal and neonatal outcome. For patients who delivered at the study hospital, perinatal and neonatal outcomes were collected from electronic medical records. For those who delivered elsewhere, related information was collected by telephone follow-up.

Continuous variables with a normal distribution are presented as the mean ± standard deviation (SD). Comparisons among groups were performed using univariate analysis of variance, and post hoc analyses of between-group comparisons were performed using the LSD (least significant difference) or SNK (Student-Newman-Keuls) method. Data with a nonnormal distribution are presented as the median and interquartile range, and the nonparametric test was conducted. Count data are expressed as frequencies and ratios. Comparisons among groups were performed using the chi-square test or Fisher's exact probability method. Multivariate multinomial logistic regression analysis was performed to compare the treatment outcome between groups, with adjustments for maternal age, nulliparity, GA, CL, placenta location, coexisting sIUGR, and MVP at the time of Stage I diagnosis. Backward stepwise logistic regression was applied to estimate the odds ratio (OR) of mixed and poor pregnancy outcomes for the FLOC and AR groups compared to the EM group. In the multivariable-adjusted model, maternal age, recipient MVP, and GA at diagnosis and so on were included as confounding variables. All analyses were performed using SPSS, version 20 (SPSS, Inc., Chicago, IL, USA). A P value of <0.05 indicated statistical significance.

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Results

A total of 120 women with Stage I TTTS were identified at our center from July 2009 to December 2016. One hundred and nine cases followed the standardized protocol for diagnosis and treatment after excluding 11 cases of spontaneous abortion. The assessment of disease severity and management strategies did not change during the study period. 36 (33.0%) pregnancies were expectantly managed, 44 (40.4%) pregnancies received therapeutic AR, and 29 (26.6%) pregnancies underwent FLOC. In all, 45 patients had definite pregnancy outcomes at the study hospital, while 64 patients returned to their referring hospital with the ability to treat premature neonates. Of these 64 patients, 20 were excluded due to incomplete documentation of prenatal (n = 7) and insufficient follow-up (n = 13) (Fig. 2). A total of 89 patients with a GA of ≤30 weeks at diagnosis remained for further analysis; these patients were referred from 11 provinces in China (Fig. 3).

Figure 2

Figure 2

Figure 3

Figure 3

Thirty-six patients were managed conservatively with a mean of 4.2 ± 2.1 ultrasound evaluations. Twenty-seven (75.0%) patients returned to their referring hospital when a sonogram identified no evidence of progression. Ten cases were excluded due to a lack of sufficient perinatal data (three cases) or loss to follow-up (seven cases). Of the remaining 17 patients, five regressed, three remained at Stage I, three experienced spontaneous abortion, and six cases progressing in stage underwent pregnancy termination. Nine patients were followed until delivery at the study hospital. Two patients experienced spontaneous abortion within a week after diagnosis. The seven cases that progressed did this to Stage 2 (n = 2), Stage 3 (n = 2), and Stage 4 (n = 3). Eventually, 26 cases of EM were analyzed. Thirteen patients (50%) advanced in Stage, 5 (19.2%) experienced spontaneous abortion, 5 (19.2%) regressed, and three (12.5%) remained at Stage I (Fig. 4). Of the 13 patients who advanced in stage, two advanced to Stage II, five advanced to Stage III, four advanced to Stage IV, and two advanced to Stage V.

Figure 4

Figure 4

Three of the 13 patients underwent laser surgery after advancing to Stage II (n = 2) and III (n = 1), and the other 10 patients requested pregnancy termination.

Of the 35 patients in the AR group, 21 cases were diagnosed prior to 26 weeks of gestation and 14 cases were diagnosed after 26 weeks of gestation. Among 21 cases, eight (38.1%) underwent two or more procedures; of these, four (19%) underwent FLOC due to progression in stage after two to four ARs. The pregnancy outcomes of these four patients were as follows: one case of double intrauterine death at Day 1 post-FLOC, two cases of single intrauterine death within 7 days post-FLOC, and one case of delivery at 35 weeks with dual survivors. Six patients (42.9%) underwent more than two ARs among 14 cases with GA at diagnosis of ≥26 weeks.

Of the 28 patients in the FLOC group, one was offered cerclage placement at the time of FLOC with CL = 1.3 cm and delivered at 32 weeks of gestation with the survival of both twins. One patient with CL = 0.6 cm experienced preterm premature rupture of membranes (PPROM) 16 days after FLOC and cerclage placement.

There were significant differences in recipient MVP, GA at diagnosis, the number of days from diagnosis to delivery, and GA at delivery among the three groups (all P < 0.05). The GA at diagnosis was higher in the AR group (25.9 ± 2.3 weeks) than in the FLOC group (22.3 ± 2.3 weeks) and the EM group (22.4 ± 2.5 weeks) (P < 0.001). The GA at delivery was higher in the FLOC group (33.4 ± 4.3 weeks) than in the AR group (30.6 ± 3.7 weeks) and the EM group (29.1 ± 5.5 weeks) (P = 0.002). The median number of days from diagnosis to delivery was 33 (12–84) in the EM group, 34 (11–56) in the AR group, and 91 (45–110) in the FLOC group (P < 0.001) (Table 1), which that in FLOC group was longer than AR and EM group. No differences were found among the three groups in terms of maternal age, nulliparity, receipt of ART, coexisting sIUGR or CL.

Table 1

Table 1

Subjects with poor outcomes accounted for 17.9% of the FLOC group and 17.1% of the AR group; both of these percentages were lower than 61.5% of the EM group (P = 0.002). The perinatal survival rates of two survivors to 28 days of age in the EM, AR, and FLOC groups were 30.8%, 77.1%, and 71.4%, respectively. The incidence rates of no survivors in the three groups were 61.5%, 17.1%, and 10.7%, respectively. The perinatal survival rates of at least one survivor in the three groups were 38.5%, 82.9%, and 89.3%, respectively (P < 0.001) (Table 2).

Table 2

Table 2

Compared with the patients in the EM group, those in the AR and FLOC groups had a lower risk of poor outcomes [OR = 0.14, 95% confidence interval (CI), 0.04–0.47; and OR = 0.14, 95% CI, 0.04–0.51, respectively]. After adjustments for maternal age, nulliparity, recipient MVP, coexisting sIUGR, CL, placenta location, and GA at diagnosis, the subjects in the AR group (OR = 0.20, 95% CI, 0.04–0.98) and FLOC group (OR = 0.09, 95% CI, 0.02–0.40) had a lower risk of poor outcomes than those in the EM group (Table 3). In addition, the crude OR of no survivors was 0.11 (95% CI, 0.03–0.38) for the AR group and 0.08 (95% CI, 0.02–0.33) for the FLOC group. The corresponding adjusted ORs were 0.20 (95% CI, 0.04–0.95) and 0.04 (95% CI, 0.01–0.25) after adjusting for the above covariates (Table 3).

Table 3

Table 3

Further comparisons of pregnancy outcomes and complications between the FLOC and AR groups with GA at diagnosis of <26 weeks revealed that interval days from operation to delivery was longer in the FLOC group than AR group (P < 0.001). The incidences of spontaneous abortion and pregnancy loss within 1 week after the procedure were similar for the two groups. The incidence of PPROM within 4 weeks after the procedure was lower in the FLOC group (7.1%) than in the AR group (33.3%) (P = 0.028). Three patients (14.3%) suffered recurrent symptoms of polyhydramnios and one patient (4.8%) was complicated with intrauterine infection in the AR group, but none in the FLOC group (Table 4).

Table 4

Table 4

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Discussion

In this single but major referral-center study, we focused on the natural history and describe the outcomes of Stage I TTTS patients treated with three initial management strategies including EM, AR, or FLOC. Progression in stage or pregnancy termination occurred in approximately two-thirds of cases that were managed expectantly as an initial strategy, which was the leading cause of considerable fetal mortality and poor pregnancy outcome in this study, whereas intervention was associated with better pregnancy outcomes and an improved perinatal survival rate compared to EM.

A 50% rate of progression among Stage I patients in this study was identical to 50% of Duryea et al.'s study11 but lower than 60% reported by Emery et al. Other studies have reported varying rates of progression in Stage I TTTS, from 10%12 to 45%.13,14 The lower incidence of progression may be an effect of AR, as some patients underwent AR prior to EM.15 In two subsequent studies8,11 and our study, which had a much higher incidence of progression, any intervention was not implemented in EM group; thus, this group could reflect the natural course of Stage I disease and may provide a more accurate incidence of progression.

Both AR and FLOC therapy may decrease the risk of poor pregnancy outcomes and improve the perinatal survival rate compared to EM. Multivariate analysis suggested that FLOC therapy and AR were associated with reduced risks of poor pregnancy outcomes (OR = 0.09; 95% CI, 0.02–0.40 and OR = 0.20; 95% CI, 0.04–0.98, respectively) and of no survivors to 28 days of age after birth (OR = 0.04; 95% CI, 0.01–0.25 and OR = 0.20; 95% CI, 0.04–0.95, respectively) compared with EM. As with any observational analysis, this study does not certify causal inferences because many other potential confounding factors, such as family economic conditions, regular perinatal care, were not included. However, the much lower adjusted OR of poor pregnancy outcomes and no perinatal survivors indicated that the protective effect of FLOC was strong. Any confounders that could lead to such a strong association should have an even stronger protective effect, yet we identified no such confounders in the literature. Notably, clinical symptoms and recipient MVP, which may predict poor outcomes, tended to be more severe in the AR and FLOC groups than in the EM group.

The mechanism of TTTS is unbalanced transfusion from the donor to the recipient, mediated at least in part by arteriovenous anastomoses within the placenta. The presence of arteriovenous anastomoses without a compensating anastomosis between pairs of arteries has been suggested to indicate a higher risk for the development of TTTS.16 Fetoscopic laser coagulation of anastomotic vessels on the chorionic plate aims to correct what is known about the pathophysiology of the syndrome and to dichorionize a monochorionic placenta.17 The injection of monochorionic placentas with a dye after laser surgery showed that in the etiology of TTTS, vascular anastomosis could be eliminated by ablating the placental vascular anastomosis.18

AR is hypothesized to decrease intraamniotic and placental intravascular pressure and increase uterine artery blood flow, potentially facilitating placental blood flow and/or reducing the incidence of preterm labor related to polyhydramnios. However, in view of the inability to resolve the etiology of TTTS, the recurrence of polyhydramnios is inevitable, and repeated invasive procedures increase the likelihood of complications such as PPROM, preterm delivery, vaginal bleeding and/or abruption, and chorioamnionitis.19 These factors may explain the higher rate of PPROM within 4 weeks and the shorter interval from operation to delivery in the AR group compared with the FLOC group. This is also the reason why 18 (51.4%) cases underwent two or more AR and the rates of infection were 4.8% in AR group whereas there were no infection cases in FLOC group.

Comparing previous cohorts,12,20 this study is the largest retrospective review of stage I cases to date (n = 89) among single-center studies to date and the first study to investigate the management strategy and corresponding outcomes for Stage I TTTS in China. In view of the possible selection bias inherent to the retrospective nature of this study, our study has several limitations. First, more patients in the EM group than in the FLOC and AR groups had missing data for the outcomes of interests, which may compromise the between-group comparability and, therefore, introduce bias. However, for patients whose initial treatment strategy was EM, we did not identify any material difference between patients who did and did not remain in the analysis. Additionally, the prognoses of patients in the EM group and the between-group differences regarding the outcomes of interest in our study were highly consistent with previous studies with a rigorous design and more complete data. Second, although our center is a major referral center for TTTS in Northern China, and the patients involved in the study were referred from most of the northern provinces, this single-center, hospital-based study may still allow for selection bias. Additionally, in our study, the cardiac function of twins was not assessed at the time of diagnosis or after treatment. The prognosis of TTTS is closely related to the Quintero stage and fetal cardiac function.21 The current study indicates that the Tei index is appropriate for assessing the severity of cardiac function in early-stage TTTS (I and II).22 Some centers have considered TTTS cardiomyopathy when making treatment recommendations regarding Quintero Stage I and II fetuses.

Green-top Guideline November 2016 of Management of Monochorionic Twin Pregnancy composed by the Royal College of Obstetricians and Gynaecologists supported that Quintero Stage I under specific circumstances should be treated with FLOC in accordance with the protocol in our center. In addition, Wagner et al.'s study followed up a cohort of 20 Stage I TTTS and considered that a long-term outcome in Stage I TTTS was better after laser surgery than with conservative management.20 Roberts et al. had a review including three studies (253 women and 506 babies) to evaluate the impact of treatment modalities in TTTS. Their conclusions were that endoscopic laser coagulation of anastomotic vessels should continue to be considered in the treatment of all stages of TTTS to improve neurodevelopmental outcomes.23 In view that FLOC is the only therapy that directly halts the pathologic process and improved substantially a poor outcome and worse prognosis, it is reasonable to use FLOC for Stage I TTTS unless a randomized clinical trial reveals marked disadvantages associated with FLOC. At present, randomized controlled trial comparing a conservative management and laser surgery (TTTS1) had been conducted since 2011 with clinical Trials.gov Identifier: NCT01220011. This trial may answer an important question and help in the management and tailoring of surgical indications in Stage I TTTS.

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Conclusions

Despite these limitations in this study, our results showed that both AR and laser therapy could decrease the risk of poor pregnancy outcomes and improve the perinatal survival rate and FLOC therapy may be more effective in cases of Stage I TTTS diagnosed before 26 weeks of gestation. Further study is needed to execute the risk stratification integrating more comprehensive indexes including fetal heart function, CL, and placental arteries anastomosis. And besides, whether it is possible to consider FLOC as a first-line treatment for Stage I TTTS prior to 26 weeks of gestation need to be further confirmed in settings where laser ablation expertise is available for Chinese populations.

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Acknowledgments

The authors thank all the clinicians of the Obstetrics & Gynecology Department of Peking University Third Hospital for their excellent assistance.

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Funding

This work was supported by grants from the National Key R&D Program of China (2016YFC1000408).

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Author Contributions

Jing Yang and Peng-Bo Yuan contributed to the data analysis and manuscript drafting. Yuan Wei and Hong-Tian Li participated in revising the article. Xue-Ju Wang and Jing Wang participated in the acquisition of data. Yuan-Hui Jiang, Xiao-Li Gong, and Lu-Yao Li participated in execution. Yang-Yu Zhao contributed to conception or study design and final approval of the version to be published.

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Conflicts of Interest

None.

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References

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Keywords:

Treatment; Twin-to-twin transfusion syndrome; Quintero stage I

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