Twin twin transfusion syndrome with and without selective fetal growth restriction: Predictors of donor demise.

OBJECTIVE: Evaluate survival in twin twin transfusion syndrome (TTTS) with and without selective fetal growth restriction (sFGR) after fetoscopic laser surgery (FLS). METHODS: Retrospective study of monochorionic diamniotic twins undergoing FLS. The cohort was classified as TTTS and TTTS with sFGR. Baseline, intra-operative and postoperative variables were analyzed. Mann-Whitney U, Pearson chi-square, Fisher's exact, t-test and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: Four hundred and ninety-two pregnancies were included, 304 (61.78%) TTTS and 188 (38.22%) TTTS with sFGR. No difference in donor outcomes. TTTS group had higher donor estimated fetal weight (EFW%) percentile (19.7 ± 18.8 vs. 2.2 ± 2.1, p < 0.001). Significant predictors for demise at 30 days were 37% intertwin weight discordance (IWD) with donor EFW% < first (area under ROC curve [AUC] = 0.85, p = 0.001) or IWD >25% and intertwin umbilical artery pulsatility index discordance (DUAPI) ≥0.4 (AUC = 0.71, p = 0.001). CONCLUSION: Combination of IWD of 37% and donor EFW%

North American Fetal Therapy Network: intervention vs expectant management for stage I twin-twin transfusion syndrome.

BACKGROUND: Stage I twin-twin transfusion syndrome presents a management dilemma. Intervention may lead to procedure-related complications while expectant management risks deterioration. Insufficient data exist to inform decision-making. OBJECTIVE: The aim of this retrospective observational study was to describe the natural history of stage I twin-twin transfusion syndrome, to assess for predictors of disease behavior, and to compare pregnancy outcomes after intervention at stage I vs expectant management. STUDY DESIGN: Ten North American Fetal Therapy Network centers submitted well-documented cases of stage I twin-twin transfusion syndrome for analysis. Cases were retrospectively divided into 3 management strategies: those managed expectantly, those who underwent amnioreduction at stage I, and those who underwent laser therapy at stage I. Outcomes were categorized as no survivors, 1 survivor, 2 survivors, or at least 1 survivor to live birth, and good (twin live birth ≥30.0 weeks), mixed (single fetal demise or delivery between 26.0-29.9 weeks), and poor (double fetal demise or delivery <26.0 weeks) pregnancy outcomes. Outcomes were analyzed by initial management strategy. RESULTS: A total of 124 cases of stage I twin-twin transfusion syndrome were studied. In all, 49 (40%) cases were managed expectantly while 30 (24%) underwent amnioreduction and 45 (36%) underwent laser therapy at stage I. The overall fetal mortality rate was 20.2% (50 of 248 fetuses). Of those managed expectantly, 11 patients regressed (22%), 4 remained stage I (8%), 29 advanced in stage (60%), and 5 experienced spontaneous previable preterm birth (10%) during observation. The mean number of days from diagnosis of stage I to a change in status (progression, regression, loss, or delivery) was 11.1 (SD 14.3) days. Intervention by amniocentesis or laser therapy was associated with a lower risk of fetal loss (P = .01) than expectant management. The unadjusted odds of poor outcome were 0.33 (95% confidence interval, 0.09-01.20), for amnioreduction and 0.26 (95% confidence interval, 0.09-0.77) for laser therapy vs expectant management. Adjusting for nulliparity, recipient maximum vertical pocket, gestational age at diagnosis, and placenta location had negligible effect. Both amnioreduction and laser therapy at stage I decreased the likelihood of no survivors (odds ratio, 0.11; 95% confidence interval, 0.02-0.68 and odds ratio, 0.07; 95% confidence interval, 0.01-0.37, respectively). Only laser therapy, however, was protective against poor outcome in our data (odds ratio, 0.29; 95% confidence interval, 0.07-1.30 for amnioreduction vs odds ratio, 0.12, 95% confidence interval, 0.03-0.44 for laser), although the estimate for amnioreduction suggests a protective effect. CONCLUSION: Stage I twin-twin transfusion syndrome was associated with substantial fetal mortality. Spontaneous resolution was observed, although the majority of expectantly managed cases progressed. Progression was associated with a worse prognosis. Both amnioreduction and laser therapy decreased the chance of no survivors, and laser was particularly protective against poor outcome independent of multiple factors. Further studies are justified to corroborate these findings and to further define risk stratification and surveillance strategies for stage I disease.

Sequência anemia-policitemia em gêmeos: definição, classificação e tratamento / Twin anemia-polycythemia sequence: definition, classification and treatment

A presença de anastomoses vasculares placentárias nas gestações gemelares monocoriônicas favorece o surgimento de complicações graves como a Síndrome de Transfusão Feto-Fetal (STFF) e a Sequência Anemia-Policitemia em Gêmeos (TAPS). STFF e TAPS são ambas formas crônicas de transfusão feto-fetal. TAPS, descrita em 2007, é caracterizada por anemia crônica no gêmeo doador e policitemia no gêmeo receptor, na ausência de discordância no volume de líquido amniótico, característica da STFF clássica. O diagnóstico pode ser feito pré- e pós-natal. O critério diagnóstico pré-natal é baseado na discordância intergemelar da medida do Doppler do pico de velocidade sistólica da artéria cerebral média (PSV-ACM). O diagnóstico pós-natal é baseado na grande diferença da hemoglobina intergemelar, ao nascimento, e reticulocitose no gêmeo doador.(AU)

The presence of placental vascular anastomoses in monochorionic twins favors the development of several complications like Twin-Twin Transfusion Syndrome (TTTS) and Twin Anemia-Polycythemia Sequence (TAPS). TTTS and TAPS are both chronic forms of fetofetal transfusion. TAPS, described on 2007, is characterized by chronic anemia in the donor twin and polycythemia in the recipient twin, in the absence of amniotic fluid volume discordances, characteristic of classical TTTS. The diagnostic can be made pree posnatally. The prenatal diagnostic criteria is based on the inter-twin discordance in Doppler measurement of peak systolic velocity in the middle cerebral artery (MCA-PSV). The postnatal diagnosis is based on large intertwin hemoglobin difference at birth and retoculocytosis in the donor twin.(AU)

[TAPS sequence--unknown and underestimated problem of monochorionic pregnancies]. / Zespól TAPS--nieznany i niedoceniany problem ciaz jednokosmówkowych.

Monochorionic twin pregnancy is associated with an increased perinatal morbidity and mortality Placental anastomoses are typical for monochorionic pregnancies and may play a role in the development of severe complications such as twin-twin transfusion syndrome (TTTS) and recently discovered twin anemia-polycythemia sequence (TAPS). Both TTTS and TAPS are the chronic form of feto-fetal transfusion. There is a typical oligohydramnios/polyhydramnios sequence in the TTTS syndrome, whereas TAPS is characterized by large inter-twin hemoglobin difference in the absence of amniotic fluid discordances. The paper presents a case of TAPS at 20 weeks of gestation in a 35-year-old primigravida with monochorionic, diamniotic pregnancy TAPS was the cause of Intrauterine fetal death of one of the twins. In the absence of signs of fetal distress an expectant management was considered. An elective cesarean section was performed at 35 weeks of gestation due to decelerations in CTG. This paper presents a clinical case, as well as diagnostic criteria, classification, perinatal management and outcome in TAPS. The review of the literature is also included, focusing on the diagnostic differences between TAPS and TTTS, two distinct variants of feto-fetal transfusion. This case presents a twin anemia-polycythemia sequence, a rare and heterogeneous disease with a wide range of outcome. TAPS may remain undetected during pregnancy and result in the delivery of two healthy neonates with large inter-twin hemoglobin discordance. Unfortunately TAPS may also lead to intrauterine fetal demise of one or both twins, particularly in cases when it is undetected and untreated.

Outcome of pregnancies complicated by twin-twin transfusion syndrome in King Chulalongkorn Memorial Hospital.

OBJECTIVE: To study perinatal outcomes of pregnancies complicated by twin-twin transfusion syndrome (TTTS), which were treated with the authors' intervention modalities. Maternal outcomes of these populations were also explored. MATERIAL AND METHOD: All pregnancies diagnosed TTTS that delivered in King Chulalongkorn Memorial Hospital between January 2000 and November 2009 were enrolled in this descriptive study Patients' data before August 2008 were retrospectively assessed. Perinatal survival, neonatal morbidities, and maternal outcomes were recorded and analyzed. Antenatal ultrasonographic findings were also analyzed to determine prognostic factors on perinatal outcomes. RESULTS: Twenty-five cases of TTTS were recruited in the present study. Overall perinatal survival was 58% (29/50) with no significant difference in perinatal in among various stages of disease (p = 0.19). Survival in stage I-II, stage III, and stage IV were 64.3%, 45.8%, and 75%, respectively. There was no maternal mortality in the present study The most common maternal morbidity was preeclampsia (6/25; 24%). Progression of disease was the only significant prognostic fact or for perinatal mortality (p < 0.001). CONCLUSION: Overall perinatal mortality rate of TTTS in the presented populations was still high (42%). Progression of disease was the only significant prognostic factor for poor perinatal outcome in the preset study Since the case number of the present study was too small, the conclusion that the prognosis of the conservatively treated TTTS was unrelated to the staging cannot be drawn.

Síndrome de transfusão feto-fetal / Twin-twin transfusion syndrome

A síndrome de transfusão feto-fetal (STFF) é uma das complicações mais graves que pode ocorrer em gestações gemelares monocoriônicas. Sua incidência varia de 1:40 a 1:60 em gestações gemelares e de 10 a 20 das gemelares monocoriônicas. Sua fisiopatologia é explicada pelo desequilíbrio das anastomoses vasculares placentárias e a resposta cardiovascular a essa alteração. A taxa de mortalidade sem tratamento é de 70 a 100 para pelo menos um dos gêmeos e não existe consenso bem definido sobre qual o melhor momento para se realizar o tratamento nem sobre a técnica a ser utilizada.

Twin-twin transfusion syndrome (TTTS) is one of the most serious complications that can occur in monochorionic twin pregnancies. The incidence of TTTS ranges from 1:40 to 1:60 in twin pregnancies and 10-20 in monochorionic twin pregnancies. The pathophysiology of the disease is explained by the imbalance of placental vascular anastomoses and the cardiovascular response to this alteration. The mortality rate without treatment is 70-100 for at least one of the twins and there is no clear consensus about the best time to perform the treatment or wich technique shoud be used.

Twin anemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome.

Monochorionic twins share a single placenta with intertwin vascular anastomoses, allowing the transfer of blood from one fetus to the other and vice versa. These anastomoses are the essential anatomical substrate for the development of several complications, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of fetofetal transfusion. TTTS is characterized by the twin oligopolyhydramnios sequence, whereas TAPS is characterized by large intertwin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in up to 5% of monochorionic twins and may also develop after incomplete laser treatment in TTTS cases. This review focuses on the pathogenesis, incidence, diagnostic criteria, management options and outcome in TAPS. In addition, we propose a classification system for antenatal and postnatal TAPS.

Short- and long-term outcome in stage 1 twin-to-twin transfusion syndrome treated with laser surgery compared with conservative management.

OBJECTIVE: We sought to compare short- and long-term outcome in Quintero stage 1 twin-to-twin transfusion syndrome (TTTS), managed with laser surgery or conservatively. STUDY DESIGN: We conducted a retrospective study of all monochorionic twin pregnancies with stage 1 TTTS referred to our center. Primary outcomes were perinatal survival, neonatal morbidity, and long-term neurodevelopmental outcome. RESULTS: Fifty women presented with stage 1 TTTS of which 40% (20/50) was treated with laser and 60% (30/50) was managed conservatively. Perinatal survival of both or at least 1 twin was 65% (13/20) and 85% (17/20) in the laser group, and 77% (23/30) and 97% (29/30) in the conservatively managed group (P = .52 and P = .29), respectively. Long-term neurodevelopmental impairment of the surviving infants was found in 0% (0/21) vs 23% (7/30), respectively (P = .03). CONCLUSION: In this retrospective study, long-term outcome in stage 1 TTTS was better after laser surgery than with conservative management, suggesting the need for a randomized controlled trial.

The efficacy of Quintero staging system to assess severity of twin-twin transfusion syndrome treated with laser therapy: a systematic review with meta-analysis.

Severity of twin-twin transfusion syndrome (TTTS) is classified in five stages according to Quintero staging. However, the efficacy of such staging was recently debated. We reviewed the efficacy of Quintero staging to predict survival rate in TTTS treated with laser therapy. Articles reporting survival rate for each stage in TTTS treated with laser therapy were reviewed. Number of twins alive per pregnancy (NAP) was compared between early (I + II) and advanced (III + IV) stages and within stages. Meta-analysis was performed according to Meta-analysis Of Observational Studies in Epidemiology guidelines. Heterogeneity was tested with chi-square for heterogeneity at a significance level of P < 0.10, and random or fixed models were generated as appropriate. A P value < 0.05 was considered statistically significant. NAP was similar between early (zero survivors: 34/228, 15%; one survivor: 49/228, 21%; two survivors: 145/228, 63%) and advanced stages (zero survivors: 38/214, 18%; one survivor: 64/214, 30%; two survivors: 112/214, 52%; P > 0.05) except for one survivor ( P < 0.05). A trend for increased NAP was observed in all stages. Because clinically relevant differences were not observed, laser therapy is the optimal treatment for all stages. As Quintero staging does not provide information about prognosis, a new staging system is proposed.

Maternal-fetal surgery: where are we and how did we get here?

Using the criteria proposed in 1982 to justify consideration of in utero surgical treatment of fetal disorders, the development of maternal-fetal treatment is described, and an assessment of current status is provided. Significant issues remain, and many questions are unanswered. By using three different disorders, congenital diaphragmatic hernia, open spina bifida, and twin-to-twin transfusion, the complexity and sophistication of the field are explored, as well as the existing gaps in understanding.

Validation of Quintero stage III sub-classification for twin-twin transfusion syndrome based on visibility of donor bladder: characteristic differences in pathophysiology and prognosis.

OBJECTIVE: To validate the Quintero stage III subclassification for twin-twin transfusion syndrome (TTTS) based on visibility of the bladder of the donor twin. METHODS: Between July 2002 and August 2006, there were 131 pregnant Japanese women affected by severe TTTS before 26 weeks' gestation, treated with fetoscopic laser surgery at five centers in Japan, whose pregnancies continued beyond 22 weeks. Outcome data were available in all cases and surviving infants were followed up for at least 6 years. This study focused on the Stage III TTTS patients. These were subclassified into Stage III atypical (abnormal Doppler flow with visible donor bladder) and Stage III classical (abnormal Doppler flow with non-visible donor bladder) groups. Perioperative data and postnatal outcomes were compared between the groups. RESULTS: Seven Stage I, 22 Stage II, 82 Stage III and 20 Stage IV pregnancies continued beyond 22 weeks. There was a significantly higher incidence of absent or reversed end-diastolic velocity in the umbilical artery (UA-AREDV) of the donor in Stage III atypical than in Stage III classical patients (83.8% vs. 53.3%, P = 0.004). Stage III atypical cases also had a significantly higher incidence of arterioarterial (AA) anastomoses (72.9% vs. 17.8%, P < 0.001) and intrauterine fetal demise (IUFD) of the donor (43.2% vs. 13.3%, P = 0.002). However, there were no differences in overall survival or in abnormal brain scans of surviving infants. Donors with both UA-AREDV and AA anastomoses had a significantly higher incidence of IUFD compared with the others (53.3%, P < 0.001). CONCLUSIONS: Quintero stage III atypical was characterized by a high incidence of AA anastomoses and UA-AREDV of the donor, resulting in IUFD. Subclassification of Stage III based on visibility of the bladder of the donor twin was adequate for and compatible with differentiating prognosis and pathophysiology.

Early manifestations and spectrum of recipient twin cardiomyopathy in twin-twin transfusion syndrome: relation to Quintero stage.

OBJECTIVES: To examine cardiac structural and functional changes in twin-twin transfusion syndrome (TTTS), relative to Quintero stage, as a means of evaluating the spectrum of cardiomyopathy in TTTS. METHODS: This was a cross-sectional, retrospective study of 42 consecutive cases of TTTS referred to a single fetal therapy center. Quintero stages were assigned by standard criteria. Presence of ventricular hypertrophy, cardiomegaly, atrioventricular valve regurgitation (AVVR), ventricular systolic dysfunction and right ventricular outflow tract obstruction on fetal echocardiography were noted. The Doppler myocardial performance index (MPI), an index of global ventricular function, was calculated for both ventricles in subjects with adequate Doppler data. We compared cardiac changes across Quintero stages. RESULTS: There was no cardiomyopathy observed in donor twins. The majority of subjects presented at Quintero Stage I (n = 14), II (n = 14) or III (n = 11), with fewer at Stages IV (n = 2) or V (n = 1). As early as Quintero Stages I and II, a significant proportion of recipient twins had ventricular hypertrophy (17/28, 61%), AVVR (6/28, 21%) or quantitative abnormalities in either right (12/24, 50%) or left (14/24, 58%) ventricular function. Increasing prevalence of biventricular systolic dysfunction and cardiomegaly accompanied advancing Quintero stage. CONCLUSIONS: Changes in cardiac structure and function not reflected in Quintero staging occur in recipient twins early in the evolution of TTTS. Incorporation of cardiac findings into assessment of TTTS severity may prove useful in stratification of risk and treatment selection.

Intertwin discordance in umbilical venous volume flow: a reflection of blood volume imbalance in twin-to-twin transfusion syndrome.

OBJECTIVES: To compare umbilical venous volume flow (UVVF) between donor and recipient twins in twin-to-twin transfusion syndrome (TTTS) using an index that is independent of gestational age and to correlate changes in this index with outcome following endoscopic laser surgery. METHODS: UVVF was calculated in 84 cases of TTTS by multiplying the umbilical vein cross-sectional area at its entry into the fetal abdomen by time averaged blood velocity. All cases were classified according to the Quintero staging system. The ratio between UVVF in recipients and donors (R/D-UVVF) in each pair of twins was calculated before and 48 h after laser treatment, and changes in R/D-UVVF were correlated with pregnancy outcome. Intraobserver and interobserver UVVF measurement reliability was assessed in 19 singletons, and 13 donor and recipient twins before laser treatment using the intraclass correlation coefficient (ICC). RESULTS: Twenty-five, 32, 21 and six cases presented as Quintero Stages 1, 2, 3 and 4, respectively, at a median gestational age of 20 (range, 15-26) weeks. Intraobserver and interobserver ICC for UVVF measurement in twins were 0.97 and 0.67, respectively. UVVF was a median of 2.13-fold (range, 0.3-19-fold) higher in recipients than in donors (137 mL/min vs. 64 mL/min, P < 0.001) and increased with gestational age (r = 0.58, P < 0.001 for recipients, r = 0.62, P < 0.001 for donors). From 68 cases in which R/D-UVVF could be measured 48 h following laser surgery, cases with a favorable outcome showed a significant decrease in R/D-UVVF from a median of 1.97 to 1.27 (P < 0.01) and cases with recurrent TTTS (n = 6) did not (decrease in R/D-UVVF from a median of 2.32 to 2.19, P = 0.17). Using a cut-off of < 30% reduction of R/D-UVVF, 66% of the cases with recurrence could be predicted, and the odds ratio for recurrence was 3.13 (95% CI, 0.52-18.29). A significant UVVF imbalance between recipient and donor twins was found in cases with Quintero Stages 1-3 but not in those with Stage 4. CONCLUSIONS: In TTTS, UVVF is significantly higher in recipients than in their donor cotwins and the R/D-UVVF seems adequately to indicate the flow imbalance between twins, regardless of gestational age. A decrease in R/D-UVVF could be predictive of a favorable evolution following laser treatment.

Perinatal characteristics and outcomes of pregnancies complicated by twin-twin transfusion syndrome.

OBJECTIVE: To assess the outcome of a geographically based cohort of monochorionic twin pregnancies complicated by twin-twin transfusion syndrome managed in a single perinatal center over a 10-year period. METHODS: A prospective cohort design was established in 1992 within a single tertiary obstetric unit. RESULTS: Sixty-nine cases of twin-twin transfusion syndrome were identified during the study period. The median gestation at diagnosis was 22.1 weeks (interquartile range 19.7-25.4). Perinatal outcome was directly related to stage at diagnosis and gestation at delivery. The overall perinatal survival rate was 64.5%. For lesser disease severity (stages I and II) the perinatal survival rate was 76.4%, falling to 51.5% with increasing disease severity (stages III-V) (P =.004). The median gestation at delivery was 29.4 weeks (interquartile range 26.3-33.8). The perinatal survival for those born at less than 28 weeks' gestation was 27.1%, increasing to 84.4% for those born at more than 28 weeks' gestation (P =.001). The incidence of neonatal complications reflected the high preterm birth rate. Amnioreduction was the principal intervention employed in this series, but in 24.6% of cases no therapy was used because of the requirement for immediate delivery or fetal demise. CONCLUSION: Twin-twin transfusion syndrome is a heterogeneous disorder in its clinical manifestations and progress. There remain significant perinatal mortality and morbidity in pregnancies complicated by twin-twin transfusion syndrome, principally related to the high preterm birth rate that typifies this disorder. The severity of disease as assessed by stage and the gestation at delivery are the principal factors in determining perinatal outcome in this condition.

Staging of twin-twin transfusion syndrome.

OBJECTIVE: The purpose of this study was to evaluate the prognostic value of sonographic and clinical parameters to develop a staging classification of twin-twin transfusion syndrome (TTTS). STUDY DESIGN: Severe TTTS was defined as the presence of polyhydramnios (maximum vertical pocket of > or = 8 cm) and oligohydramnios (maximum vertical pocket of < or = 2 cm). Nonvisualization of the bladder in the donor twin (-BDT) and absence of presence of hydrops was also noted. The middle cerebral artery, umbilical artery, ductus venosus, and umbilical vein in both fetuses were assessed with pulsed Doppler. Critically abnormal Doppler studies (CADs) were defined as absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein. TTTS was staged as follows: stage I, BDT still visible; stage II, BDT no longer visible, no CADs; stage III, CADs; stage IV, hydrops; stage V, demise of one or both twins. Laser photocoagulation of communicating vessels (LPCV) or umbilical cord ligation was performed depending on the severity of the condition. The study was approved by the Institutional Review Board of St. Joseph's Hospital in Tampa and by the Fetal Therapy Board at Hutzel Hospital, Detroit, and all patients gave informed consent. RESULTS: A total of 80 of 108 referred patients met criteria for surgery, but only 65 were treated surgically: 48 with LPCV and 17 with umbilical cord ligation. Complete Doppler data were obtainable in 41 of 48 LPCV patients. Survival rates by stage for one or two fetuses were statistically different (chi-squared analysis = 12.9, df = 6, p = 0.044). Neither percent size discordance nor gestational age at diagnosis were predictive of outcome. CONCLUSION: Staging of TTTS using the proposed criteria has prognostic significance. This staging system may allow comparison of outcome data of TTTS with different treatment modalities.