twin-twin transfusion syndrome

双胎输血综合征
  • 文章类型: Multicenter Study
    背景:双胎输血综合征(TTTS)的胎儿镜激光手术可能会发生双胎膜穿孔。关于随后脐带缠结的发生和风险的数据有限。这项研究的目的是评估患病率,TTTS激光手术后双膜间穿孔和脐带缠结的危险因素和结局。
    方法:在这项多中心回顾性研究中,我们纳入了在两个胎儿治疗中心接受激光手术治疗的所有TTTS妊娠,2002年至2020年期间,上海(中国)和莱顿(荷兰)。我们评估了激光后双膜穿孔和脐带缠结的发生,基于常规的每两周超声检查,并调查了危险因素以及与不良短期和长期结局的关系。
    结果:在接受激光手术治疗的761例TTTS妊娠中,118例(16%)发生双胎膜穿孔,其次是21%(25/118)的脐带缠结。孪生膜的穿孔与更高的激光功率设置有关,45.8瓦特对42.2瓦特(p=0.029)和第二次胎儿手术程序17%对6%(p<0.001)。双膜间穿孔组剖宫产率较高(77%对31%,p<0.001)和较低的出生胎龄(妊娠30.7周与33.3周,p<0.001)与具有完整孪生膜的组相比。严重脑损伤更常见于双膜间穿孔组,分别为9%(17/185)和5%(42/930)(p=0.019)。有和没有双膜穿孔的组之间以及有和没有脐带缠结的亚组之间,两岁时的神经发育结果相似。
    结论:用激光治疗的TTTS病例中,有16%发生激光后双膜穿孔,并导致5例中至少1例脐带缠结。双胎膜穿孔与出生时的胎龄较低和存活新生儿的严重脑损伤发生率较高有关。
    BACKGROUND: Perforation of the intertwin membrane can occur as a complication of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). Data on the occurrence and the risk of subsequent cord entanglement are limited. The objective of this study was to assess the prevalence, risk factors and outcome of intertwin membrane perforation, and cord entanglement after laser surgery for TTTS.
    METHODS: In this multicenter retrospective study, we included all TTTS pregnancies treated with laser surgery in two fetal therapy centers, Shanghai (China) and Leiden (the Netherlands) between 2002 and 2020. We evaluated the occurrence of intertwin membrane perforation and cord entanglement after laser, based on routine fortnightly ultrasound examination and investigated the risk factors and the association with adverse short- and long-term outcomes.
    RESULTS: Perforation of the intertwin membrane occurred in 118 (16%) of the 761 TTTS pregnancies treated with laser surgery and was followed by cord entanglement in 21% (25/118). Perforation of the intertwin membrane was associated with higher laser power settings, 45.8 Watt versus 42.2 Watt (p = 0.029) and a second fetal surgery procedure 17% versus 6% (p < 0.001). The group with intertwin membrane perforation had a higher rate of caesarean section (77% vs. 31%, p < 0.001) and a lower gestational age at birth (30.7 vs. 33.3 weeks of gestation, p < 0.001) compared to the group with an intact intertwin membrane. Severe cerebral injury occurred more often in the group with intertwin membrane perforation, 9% (17/185) versus 5% (42/930), respectively (p = 0.019). Neurodevelopmental outcome at 2 years of age was similar between the groups with and without perforation of the intertwin membrane and between the subgroups with and without cord entanglement.
    CONCLUSIONS: Perforation of the intertwin membrane after laser occurred in 16% of TTTS cases treated with laser and led to cord entanglement in at least 1 in 5 cases. Intertwin membrane perforation was associated with a lower gestational age at birth and a higher rate of severe cerebral injury in surviving neonates.
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  • 文章类型: Journal Article
    选择性胎儿镜下激光光凝(SFLP)治疗双胎输血综合征(TTTS)对于新的外科医生在学习曲线开始时具有挑战性。我们描述了一种利用远程培训和基于团队的培训的方法,以促进在有限的案例中快速获得安全有效的实践所需的技能。
    我们对初级外科新手团队进行的SFLP进行了一项前瞻性观察性研究,分三个阶段:在专家导师的直接现场监督下(第1组),在该导师(第2组)和独立(第3组)的远程远程指导下,在新加坡的一家三级医院。主要团队对高保真组织模型进行了定期培训,以加速技能获取并补充手术表现。
    对9例诊断为2期TTTS的患者进行手术特征评估,SFLP后的手术结局和围产期生存率。手术时间无显著差异,吻合口消融,分娩时的胎龄或出生体重。观察到的并发症是:复发性TTTS(22.2%的妊娠),双胎贫血红细胞增多症序列(33.3%),早产胎膜破裂(22.2%)和<32周分娩(44.4%)。在88.9%的病例中,≥1对双胞胎是活产的,77.8%的病例发生≥1双胎的产后存活至6个月。
    系统的指导和专业技能培训有助于帮助新外科医生在新实践开始时协商陡峭的学习曲线并取得良好的结果。特别是在低患者人数的背景下。这最好与专门的模型训练配对,以实现和保持这种复杂程序的手术灵活性。
    Selective fetoscopic laser photocoagulation (SFLP) for twin-to-twin transfusion syndrome (TTTS) is challenging for new surgeons at the start of their learning curve. We described an approach utilising telementoring and team-based training to facilitate rapid attainment of the skills required for safe and efficient practice with a limited caseload.
    We conducted a prospective observational study of SFLP performed by the novice primary surgical team in three stages: under direct on-site supervision from an expert mentor (Group 1), with remote tele-guidance from that mentor (Group 2) and independently (Group 3), at an academic tertiary hospital in Singapore. The primary team undertook regular training on high-fidelity tissue models to accelerate skills acquisition and complement the surgical performance.
    9 patients diagnosed with Stage 2 TTTS were assessed for procedural characteristics, surgical outcomes and perinatal survival following SFLP. There were no significant differences in operative duration, anastomoses ablated, gestational age or birth weight at delivery. The complications observed were: recurrent TTTS (22.2% of pregnancies), twin anaemia polycythaemia sequence (33.3%), preterm prelabour membrane rupture (22.2%) and delivery at < 32 weeks (44.4%). ≥ 1 twin was live-born in 88.9% of cases, while postnatal survival to six months of ≥ 1 twin occurred in 77.8% of cases.
    Systematic mentoring and specialised skills training are useful in aiding new surgeons to negotiate the steep learning curve and achieve good outcomes at the start of a new practice, particularly in the setting of low patient numbers. This is best paired with dedicated model training to achieve and maintain surgical dexterity for this complex procedure.
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  • 文章类型: Journal Article
    目的:探讨双胎输血综合征引起的代谢组学紊乱,胎盘组织和脐带血浆中与胎儿镜激光凝固相关的代谢变化,并研究与不同胎儿结局相关的差异代谢物,包括血液动力学状态,出生体重,和心脏功能,活产婴儿。方法:通过高效液相色谱代谢组学分析来自正常足月或无并发症的早产单绒毛膜双胞胎以及合并有或不接受胎儿镜激光凝固术治疗的双胎输血综合征的胎盘组织和脐带血浆样本。对不同的双胞胎组进行了16次比较。偏最小二乘判别分析,代谢途径分析,生物标志物分析,和Spearman的相关性分析是基于用于确定不同比较中潜在生物标志物的差异代谢物以及与新生儿出生体重和左心室射血分数相关的代谢物进行的。结果:这些代谢组学研究表明,脐带血浆代谢组比胎盘组织在区分不同血流动力学组的胎儿方面具有更好的表现。在这两种类型的样本中,双胎-双胎输血综合征的代谢变化集中在脂肪酸和脂质代谢上。胎儿镜激光凝固术改善了这种综合征带来的代谢组学变化,使治疗组的代谢组与对照组和早产组的代谢组难以区分。某些化合物,尤其是脂质和类脂分子,被认为是这种病态疾病的潜在生物标志物,与新生儿出生体重和射血分数有关。结论:胎儿镜下激光凝固术可改善双胎输血综合征引起的胎盘组织和脐带血浆代谢改变,主要参与脂肪酸和类脂分子的代谢。某些脂质和类脂分子有助于区分不同血液动力学状态的同胎,并且与新生儿出生体重或射血分数显着相关。
    Objectives: To investigate metabolomic perturbations caused by twin-twin transfusion syndrome, metabolic changes associated with fetoscopic laser coagulation in both placental tissue and cord plasma, and to investigate differential metabolites pertinent to varying fetal outcomes, including hemodynamic status, birth weight, and cardiac function, of live-born babies. Methods: Placental tissue and cord plasma samples from normal term or uncomplicated preterm-born monochorionic twins and those complicated by twin-twin transfusion syndrome treated with or without fetoscopic laser coagulation were analyzed by high-performance liquid chromatography metabolomic profiling. Sixteen comparisons of different co-twin groups were performed. Partial least squares-discriminant analysis, metabolic pathway analysis, biomarker analysis, and Spearman\'s correlation analysis were conducted based on differential metabolites used to determine potential biomarkers in different comparisons and metabolites that are pertinent to neonatal birth weight and left ventricular ejection fraction. Results: These metabolomic investigations showed that the cord plasma metabolome has a better performance in discriminating fetuses among different hemodynamic groups than placental tissue. The metabolic alteration of twin-twin transfusion syndrome in these two types of samples centers on fatty acid and lipid metabolism. The fetoscopic laser coagulation procedure improves the metabolomic change brought by this syndrome, making the metabolomes of the treated group less distinguishable from those of the control and preterm birth groups. Certain compounds, especially lipids and lipid-like molecules, are noted to be potential biomarkers of this morbid disease and pertinent to neonatal birth weight and ejection fraction. Conclusions: Fetoscopic laser coagulation can ameliorate the metabolomic alteration caused by twin-twin transfusion syndrome in placental tissue and cord plasma, which are involved mainly in fatty acid and lipid-like molecule metabolism. Certain lipids and lipid-like molecules are helpful in differentiating co-twins of different hemodynamic statuses and are significantly correlated with neonatal birth weight or ejection fraction.
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  • 文章类型: Journal Article
    目的:本研究旨在确定单绒毛膜双胎(MCT)妊娠的选择性胎儿生长受限(sFGR)。
    方法:回顾性分析北京大学第三医院2015年1月至2019年12月sFGR病例。我们根据国际妇产科超声学会诊断标准纳入sFGR。我们排除了那些严重胎儿结构异常的病例,双反向动脉灌注(TRAP),遗传综合征或非整倍性;因产妇并发症或个人原因而终止的病例;有胎儿干预的怀孕,例如用于血管吻合的胎儿镜激光光凝(FLP),通过射频消融(RFA)和微波消融(MVA)减少胎儿。我们没有排除那些接受羊膜减灭术治疗的病例。根据发病时的胎龄(24周之前或之后),我们对数据进行了分析,以确定与胎儿预后结局相关的危险因素.主要结果包括至少一个双胞胎和两个双胞胎的存活。次要结局包括分娩的胎龄,活产体重,Apgar<7in5min,入院新生儿病房和新生儿死亡。Kruskal-Wallis秩检验用于比较非正态分布数据,而分类数据使用Fisher精确检验或χ2检验进行匹配。方差分析用于比较正态分布数据,接下来是事后Bonferroni分析。采用多元二元logistic回归分析确定与宫内死亡相关的因素。
    结果:有119例怀孕符合调查条件,75(63.0%)被归类为早发性sFGR,44(37.0%)被归类为晚发性sFGR。至少一个双胞胎的存活率(82.7%vs.95.5%),双胞胎的存活率(73.3%vs.88.6%)在早发性sFGR组均降低,与晚发型sFGR组相比。胎儿生长受限(FGR)和适当的胎龄生长(AGA)胎儿存活的婴儿在两组出生体重方面表现出相似的结果,5分钟Apgar评分<7,新生儿死亡,和28天生存率。多变量模型用于预测至少一个双胞胎的宫内死亡。重叠双胎输血综合征(TTTS)的比值比(OR17.915,95CI3.699~86.756)和Ⅱ/Ⅲ型sFGR(OR4.619,95CI1.074~19.869)明显更高。
    结论:在MCT妊娠中,早发性sFGR至少有一个或两个双胞胎的存活率较差,但是活产后的预后没有统计学差异,无论是FGR婴儿还是AGA婴儿。叠加TTTS和Ⅱ/Ⅲ型sFGR的围产期结局较差。这些信息可以在产前咨询期间提供给父母。
    OBJECTIVE: This study aimed to identify selective fetal growth restriction (sFGR) in monochorionic twin (MCT) pregnancy with expectant management.
    METHODS: We retrospectively analyzed cases of sFGR between January 2015 and December 2019 in Peking University Third Hospital. We included sFGR according to the International Society of Ultrasound in Obstetrics and Gynecology diagnostic criteria. We excluded those cases where a significant fetal structural abnormality, twin reversed arterial perfusion (TRAP), genetic syndrome or aneuploidy; cases terminated for maternal complications or for personal reasons; pregnancies that had a fetal intervention, such as fetoscopic laser photocoagulation (FLP) for vascular anastomoses, fetal reduction by radiofrequency ablation (RFA) and microwave ablation (MVA). We didn\'t excluded those cases that had amnioreduction therapy. According to the gestational age at onset (before 24 weeks or after), data were analyzed to identify the risk factors associated with fetal prognostic outcomes. Primary outcomes included survival of at least one twin and both twins. Secondary outcomes included gestational age of delivery, live birth weight, Apgar <7 in 5 min, admission to the neonatal unit and neonatal death. Kruskal-Wallis rank tests were used to compare non-normally distributed data, whereas categorical data were matched using Fisher\'s exact test or χ2 tests. ANOVA was used to compare normally distributed data, followed by a post-hoc Bonferroni analysis. Multivariate binary logistic regression was used to identify the factors connected with intrauterine death.
    RESULTS: There were 119 pregnancies that qualified for investigation, 75 (63.0%) were categorized as early-onset sFGR and 44 (37.0%) as late-onset sFGR. The rate of survival of at least one twin (82.7% vs. 95.5%), survival of both twins (73.3% vs. 88.6%) were all reduced in the early-onset sFGR group, compared to the late-onset sFGR group. Babies born alive of fetal growth restriction (FGR) and appropriate growth for gestational age (AGA) fetuses showed similar results in the two groups regarding birth weight, 5-min Apgar score <7, neonatal death, and 28-day survival rate. A multivariable model was used to predict the intrauterine death of at least one twin. The odds ratio were significantly higher for superimposed twin-twin transfusion syndrome (TTTS) (OR 17.915, 95%CI 3.699∼86.756) and Types Ⅱ/Ⅲ sFGR (OR 4.619, 95%CI 1.074∼19.869).
    CONCLUSIONS: In MCT pregnancies, early-onset sFGR had a poorer survival of at least one or both twins, but there was no statistical difference in the prognosis after live birth, neither for FGR babies nor those of AGA. Superimposed TTTS and Types Ⅱ/Ⅲ sFGR had a worse perinatal outcome. This information could be provided to the parents during prenatal counselling.
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  • 文章类型: Journal Article
    Twin-to-twin transfusion syndrome (TTTS) could be treated with fetoscopic laser photocoagulation. For patients with placenta located on the anterior wall of uterus, surgical procedures are difficult. To solve this problem, a flexible fetoscope was designed in our department.
    The flexible fetoscope was made up of polyurethane, fiberglass and stainless steel coils. The specular body was soft and could bend encountering obstacles, which reduced the possibility of injury to the fetus and placenta. The distal tip of the body could curve from -180° to +270° with the control of the handweel. Three pregnant women of TTTS with anterior placenta was operated with this instrument.
    All pregnant women were treated smoothly and gave live twins birth at term. Through angiography, it was demonstrated that the vascular connections on the surface had been coagulated.
    The flexible fetoscope was a novel instrument in treating TTTS, especially for the anterior placenta.
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  • 文章类型: Journal Article
    BACKGROUND: Twin-twin transfusion syndrome (TTTS) is a complication in monochorionic twin pregnancies which is preferably treated with fetoscopic laser surgery. A few small studies suggested a possible association between the Solomon laser technique and placental abruption.
    METHODS: The objective of this study is to compare the rate of and to explore potential risk factors for placental abruption in TTTS treated with fetoscopic laser surgery according to the Selective and Solomon laser technique. We conducted a large retrospective cohort study of consecutive TTTS-cases treated with fetoscopic laser surgery in Shanghai, China, and Leiden, The Netherlands treated with either the Selective laser technique (Selective group) or Solomon laser technique (Solomon group).
    RESULTS: The rate of placental abruption in the Selective group versus the Solomon group was 1.7% (5/289) and 3.4% (15/441), respectively (p = 0.184). No risk factors for placental abruption were identified. Placental abruption was associated with lower gestational age at birth (p = 0.003) and severe cerebral injury (p = 0.003).
    CONCLUSIONS: The prevalence of placental abruption in TTTS after fetoscopic laser surgery is low, although it appears higher than in the overall population. Placental abruption is associated with a lower gestational age at birth, which is associated with severe cerebral injury. The rate of placental abruption was not significantly increased with the use of the Solomon technique. Continued research of placental abruption in TTTS is necessary to determine why the rate is higher than in the overall population.
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  • 文章类型: Journal Article
    OBJECTIVE: To analyze the discordances of the umbilical artery velocities between pregnancies with twin-twin transfusion syndrome (TTTS) at stage I and those with normal monochorionic-diamniotic (MCDA) twins, and investigate the value of their discordances in predicting TTTS at stage I.
    METHODS: We recruited 58 twin pregnancies with TTTS at stage I and 60 normal MCDA twin pregnancies in a tertiary referral center retrospectively. The umbilical artery velocities and their discordances were compared between the normal and TTTS twins.
    RESULTS: The discordances of umbilical artery mean diastolic velocity (UA-MDV), umbilical artery time-averaged maximum velocity (UA-TAmax), umbilical artery peak systolic velocity (UA-PSV), and umbilical artery end-diastolic velocity (UA-EDV) were higher in the TTTS group than in the normal group. In TTTS co-twins, the UA-MDV, UA-TAmax, UA-PSV, and UA-EDV in recipients were higher than those in donors. The discordances of UA-TAmax and UA-PSV were found to be independent predicting factors for TTTS at stage I.
    CONCLUSIONS: Co-twin umbilical artery velocity discordances were significantly associated with stage I TTTS. The results suggest that UA-TAmax and UA-PSV might be new parameters for predicting TTTS at stage I.
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  • 文章类型: Evaluation Study
    BACKGROUND: Transient donor hydrops (TDH) is defined as donor hydrops developed within days after laser therapy for twin-twin transfusion syndrome (TTTS) followed by resolution later. The purpose of this study was to evaluate the incidence, neonatal outcomes and predisposing factors of post laser therapy TDH in severe TTTS.
    METHODS: A total of 142 patients with severe TTTS who received laser therapy were included into this study. The pre-operative characteristics and neonatal outcomes were compared between TTTS with and without post laser therapy TDH. All live neonates received cranial ultrasound examination after delivery, mild cerebral injury was defined as exhibiting at least one of the following: intraventricular hemorrhage (IVH) grade I and II, lenticulostriate vasculopathy and subependymal pseudocysts; severe cerebral injury comprised at least one among the following: IVH grade III or grade IV, cystic periventriculoleukomalacia (PVL) grade II or more, porencephalic cysts, and ventricular dilatation. Fetal survival was defined as living more than 30 days after delivery.
    RESULTS:
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  • 文章类型: Journal Article
    BACKGROUND: The clinical significance of veno-venous (VV) anastomoses in monochorionic (MC) placentas remains inconclusive and controversial. The purpose of this study was to investigate the correlation between the presence of VV anastomoses and clinical outcome in a large cohort of MC twin pregnancies.
    METHODS: All MC placentas injected with colored dye from 2002 to 2014 were included in the study. We excluded MC pregnancies managed with fetoscopic laser surgery.
    CONCLUSIONS: A total of 384 MC placentas were analyzed. VV anastomoses were detected in 27% (104/384) of MC placentas. The prevalence of twin-twin transfusion syndrome (TTTS) in MC placentas with VV anastomoses was significantly higher compared to MC placentas without VV anastomoses, 20% (21/104) versus 10% (29/280), respectively (P = .01). The overall perinatal mortality in MC twins with and without VV anastomoses was 16% versus 10%, respectively (P = .02). Risk factor analysis showed the presence of VV anastomoses was associated with perinatal mortality (P = .02; odds ratio (OR): 1.76; 95% confidence interval (CI): 1.11-2.79), but was not an independent risk factor for perinatal mortality (P = .26, OR: .66; 95% CI: .33-1.35) in MC twin pregnancies. However, VV anastomoses was associated with and was an independent risk factor for TTTS (P = .00, OR: 3.59; 95% CI: 1.72-7.47). VV anastomoses-related perinatal mortality may be due to the high rate of TTTS in MC twins with VV anastomoses.
    CONCLUSIONS: The presence of VV anastomoses is correlated with TTTS and perinatal mortality, but is not an independent risk factor for perinatal mortality in MC twin pregnancies.
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