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Objective: To assess the incidence of and risk factors for adverse long-term neurodevelopmental outcome in complicated monochorionic pregnancies treated with selective feticide at our centre between 2000 and 2011. Design: Observational cohort study. Setting: National referral centre for fetal therapy (Leiden University Medical Centre, the Netherlands). Population: Neurodevelopmental outcome was assessed in 74 long-term survivors. Methods: Children, at least 2 years of age, underwent an assessment of neurologic, motor and cognitive development using standardised psychometric tests and the parents completed a behavioural questionnaire. Main Outcome Measures: A composite outcome termed neurodevelopmental impairment including cerebral palsy (GMFCS II-V), cognitive and/or motor test score of <70, bilateral blindness or bilateral deafness requiring amplification. Results: A total of 131 monochorionic pregnancies were treated with selective feticide at the Leiden University Medical Centre. Overall survival rate was 88/131 (67%). Long-term outcome was assessed in 74/88 (84%). Neurodevelopmental impairment was detected in 5/74 [6.8%, 95% confidence interval (CI), 1.1-12.5] of survivors. Overall adverse outcome, including perinatal mortality or neurodevelopmental impairment was 48/131 (36.6%). In multivariate analysis, parental educational level was associated with cognitive test scores (regression coefficient B 3.9, 95% CI 1.8-6.0). Behavioural problems were reported in 10/69 (14.5%). Conclusions: Adverse long-term outcome in survivor twins of complicated monochorionic pregnancies treated with selective feticide appears to be more prevalent than in the general population. Cognitive test scores were associated with parental educational level. Tweetable Abstract: Neurodevelopmental impairment after selective feticide was detected in 5/74 (6.8%, 95% CI 1.1-12.5) of survivors. [ABSTRACT FROM AUTHOR]

Severe pre-eclampsia and HELLP syndrome developed within 24h after a 31year old nulliparous woman suffered a blunt abdominal trauma with massive fetomaternal hemorrhage and fetal intracranial bleeding. This is the first case reported of fulminating pre-eclampsia and HELLP syndrome following maternal exposure to a large amount of fetal cells and/or fetal cell debris as DNA or microparticles. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the diagnostic accuracy of delta middle cerebral artery peak systolic velocity (MCA-PSV) > 0.5 multiples of the median (MoM) and compare its predictive value with that of the current MCA-PSV cut-off values of > 1.5 MoM in the donor and < 1.0 MoM in the recipient, for the diagnosis of twin anemia-polycythemia sequence (TAPS) in monochorionic twin pregnancy., Methods: This was a retrospective consecutive cohort study comprising all uncomplicated monochorionic twin pregnancies and twin pregnancies with a postnatal diagnosis of TAPS managed between 2003 and 2017 in the Dutch national referral center for fetal therapy. Cases with incomplete MCA-PSV Doppler measurements 1 week prior to delivery or with incomplete hemoglobin measurements within 1 day after birth were excluded. The postnatal diagnosis of TAPS was based on an intertwin hemoglobin difference > 8 g/dL and at least one of the following: reticulocyte count ratio > 1.7 or presence of minuscule anastomoses on the placental surface. We compared the predictive accuracy of the current diagnostic method using MCA-PSV cut-off values of > 1.5 MoM in the donor and < 1.0 MoM in the recipient with that of a new method based on intertwin difference in MCA-PSV > 0.5 MoM for prediction of TAPS., Results: In total, 45 uncomplicated and 35 TAPS monochorionic twin pregnancies were analyzed. The sensitivity and specificity of the cut-off MCA-PSV values (donor > 1.5 MoM, recipient < 1.0 MoM) to predict TAPS was 46% (95% CI, 30-62%) and 100% (95% CI, 92-100%), respectively; positive predictive value was 100% (95% CI, 81-100%) and negative predictive value 70% (95% CI, 58-80%). Delta MCA-PSV showed a sensitivity of 83% (95% CI, 67-92%) and a specificity of 100% (95% CI, 92-100%); the positive and negative predictive values were 100% (95% CI, 88-100%) and 88% (95% CI, 77-94%), respectively. Of the 35 cases with TAPS diagnosed postnatally, 13 twin pairs showed a delta MCA-PSV > 0.5 MoM but did not fulfill the cut-off MCA-PSV criteria. Of these 13 TAPS twins, nine donors and four recipients had normal MCA-PSV values. There was a high correlation between delta MCA-PSV and intertwin difference in hemoglobin level (R = 0.725, P < 0.01)., Conclusion: Delta MCA-PSV > 0.5 MoM has a greater diagnostic accuracy for predicting TAPS compared to the current MCA-PSV cut-off criteria. We therefore propose a new antenatal classification system for TAPS. In monochorionic twin pregnancies with delta MCA-PSV > 0.5 MoM on Doppler ultrasound, but normal MCA-PSV values in the donor or recipient, obstetricians should be aware of the therapeutic implications and neonatal morbidities associated with TAPS. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To evaluate the incidence of residual anastomoses (RA) after laser therapy for twin-twin transfusion syndrome (TTS) and investigate risk factors for incomplete laser surgery., Material and Methods: All available TTS placentas treated with laser at our center between 2002 and 2016 were injected with color dye to assess the presence of RA. We evaluated the incidence of RA over the past 15 years by dividing the cohort into three time periods, and studied the association with risk factors and neonatal outcome., Results: Overall, RA were detected in 21.0% (78/371) of placentas. The incidence of RA decreased from 38.8% (26/67) in the initial period to 11.7% (16/137) in the most recent period (p < 0.001). On multivariate analysis, several risk factors were independently associated with the risk of RA, including Solomon laser technique (odds ratio [OR] 0.17, 95% CI 0.09-0.33) and estimation of surgical success (OR 19.28, 95% CI 8.17-45.49). Premature delivery and neonatal morbidity occurred more often in TTS cases with RA., Conclusions: The incidence of RA after laser therapy for TTS decreased significantly in the past 15 years and is now below 15% due to the use of the Solomon technique., (© 2018 S. Karger AG, Basel.)

Objective: The optimal outcome after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) depends on the successful ablation of all placental anastomoses. The objective of this study was to determine the incidence of and risk factors for recurrent TTTS (rTTTS) or twin anemia-polycythemia sequence (TAPS) after FLS, focusing on the impact of cannula diameter., Methods: This was a secondary analysis of data collected prospectively at two centers from 666 consecutive patients undergoing FLS for TTTS. The main outcomes were rTTTS and TAPS following FLS. Variables assessed included gestational age at intervention, stage of disease, recipient maximum vertical pocket, anterior placenta, number of anastomoses ablated, cannula diameter/operative scopes and use of the Solomon technique. Cannula diameter and corresponding scopes used were as follows: 8 Fr and 1.3 mm/0°; 9 Fr and 2.7 mm/0°; 10 Fr and 3 mm/0°; or 12 Fr and 3.3-3.7 mm/30-70°. Cannula diameter was used as a surrogate for scopes during analysis. Multivariate logistic regression analysis was performed to identify risk factors associated with rTTTS or TAPS after FLS; 'center' was considered an independent variable to account for variations in practice. In a nested cohort of pregnancies in which both fetuses survived, placental dye injection was performed in 315 placentae. Multivariate logistic regression analysis was performed to evaluate variables associated with the presence of residual anastomoses., Results: rTTTS or TAPS occurred in 61 (9%) cases following FLS (rTTTS in eight (1%) and TAPS in 53 (8%)). Factors associated significantly with the risk of rTTTS/TAPS on multivariate analysis were cannula diameter (when an 8-Fr, 9-Fr, 10-Fr or 12-Fr cannula was used, there was rTTTS/TAPS in 24%, 13%, 2% or 0.8% of cases, respectively (P < 0.001)) and use of the Solomon technique (rTTTS/TAPS occurred in 4.2% of those in which it was used vs 18.1% in those in which it was not (P < 0.001)). Only use of the Solomon technique was associated significantly with no residual anastomoses found after delivery., Conclusions: Following FLS for TTTS, a lower incidence of rTTTS/TAPS was seen when the Solomon technique was used, as well as when a 10-Fr or 12-Fr cannula was used. A lower complication rate may be due to the use of a scope with better optics during placental mapping. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: In this study, we aim to evaluate trends in the condition of fetuses and neonates with hemolytic disease at the time of first intrauterine transfusion (IUT) and at birth, in relation to routine first-trimester antibody screening, referral guidelines, and centralization of fetal therapy., Method: We conducted a 30-year cohort study including all women and fetuses treated with IUT for red cell alloimmunization at the Dutch national referral center for fetal therapy., Results: Six hundred forty-five fetuses received 1852 transfusions between 1 January 1987 and 31 December 2016. After the introduction of routine first-trimester antibody screening, the hydrops rate declined from 39% to 15% (OR 0.284, 95% CI, 0.19-0.42, P < 0.001). In the last time cohort, only one fetus presented with severe hydrops (OR 0.482, 95% CI, 0.38-0.62, P < 0.001). Infants are born less often <32 weeks (OR 0.572, 95% CI, 0.39-0.83, P = 0.004) and with higher neonatal hemoglobin (P < 0.001). Neonatal hemoglobin was positively independently associated with gestational age at birth, fetal hemoglobin, and additional intraperitoneal transfusion at last IUT., Conclusion: Severe alloimmune hydrops, a formerly often lethal condition, has practically disappeared, most likely as a result of the introduction of routine early alloantibody screening, use of national guidelines, and pooling of expertise in national reference laboratories and a referral center for fetal therapy., (© 2018 The Authors Prenatal Diagnosis Published by John Wiley & Sons Ltd.)

Objective: Maternal alloimmunization to fetal red-blood-cell antigens is a major cause of fetal anemia, which can lead to hydrops and perinatal death if untreated. The cornerstone of management during pregnancy is intrauterine intravascular blood transfusion (IUT). Although this procedure is considered relatively safe, complications continue to occur. The aim of this study was to evaluate rates of procedure-related complications and perinatal loss following IUT, and their change over time, in order to identify factors leading to improved outcome., Methods: This was a retrospective analysis of all IUTs for red-cell alloimmunization performed at the national referral center for fetal therapy in The Netherlands, from 1988 to 2015. Differences in complication rates and their associations with alterations in transfusion technique after 2001 were assessed., Results: Between 1988 and 2015, 1678 IUTs were performed in 589 fetuses. For IUTs performed in 2001 and onwards, there was significant improvement in survival (88.6% vs 97.0%, P < 0.001) and a decline in procedure-related complications per fetus (9.8% vs 3.3%, P = 0.001) and per procedure (3.4% vs 1.2%, P = 0.003) compared with those performed before 2001. Procedure-related perinatal loss declined from 4.7% to 1.8% per fetus (P = 0.053). Beneficial changes in transfusion technique were routine use of fetal paralysis, increased use of intrahepatic transfusion and avoidance of arterial puncture., Conclusions: IUT has become an increasingly safe procedure in recent years when performed by experienced hands. The chosen technique should be fine-tuned according to the patient's individual situation. The declining complication rates are most likely related to center volume: this rare procedure is best performed in experienced fetal therapy centers. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: Monochorionic twins are at risk of severe complications including twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS) and acute peripartum TTTS. The pathophysiology is based on inter-twin blood transfusion through placental vascular anastomoses. Areas covered: This review focuses on the incidence, management and outcome of neonatal hematological complications at birth in TTTS, TAPS and acute peripartum TTTS. Expert commentary: Hematological disorders are often present at birth in monochorionic twins and include acute or chronic anemia, polycythemia and thrombocytopenia. Routine measurement of complete blood counts in all complicated monochorionic twins is strongly recommended. Increased awareness on these disorders and correct diagnostic tests will lead to prompt and adequate management at birth.

Background: The introduction of the Solomon technique for the treatment of twin-twin transfusion syndrome (TTTS) increased placental exposure to laser energy. This study aims to identify the impact of power and energy used in laser treatment on placental tissue and pregnancy outcome., Methods: Pictures of all dye-injected placentas since the start of the Solomon trial were analyzed. Placental damage was scored using a grading system including visual scar depth and affected proportion of the vascular equator. Parameters analyzed included laser power and total energy, gestational age (GA) at laser, GA at birth, laser-to-delivery interval and preterm prelabor rupture of membranes (PPROM)., Results: We included 122 cases in the analysis. More placental damage occurred more often in the Solomon group (42%) compared to the selective group (15%) (p < 0.001). In multivariate analysis, more placental damage was associated with higher laser energy (regression coefficient B 0.002) but not with higher power setting (regression coefficient B -0.442). More damage was associated with earlier GA at birth (regression coefficient B -0.167), higher incidence of PPROM <32 weeks (regression coefficient B 0.003) and a shorter laser-to-delivery interval (regression coefficient B -0.168)., Conclusions: Placental damage is positively associated with more laser energy but negatively associated with higher power setting. More placental damage was associated with a lower GA at birth, shorter laser-to-delivery interval and higher PPROM rate. Whether these results should lead to a change in surgical technique requires more research, both further ex-vivo experiments on human placentas and clinical studies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: Twin-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are severe complications in monochorionic twin pregnancies associated with high mortality and morbidity risk if left untreated. Both diseases result from imbalanced inter-twin blood transfusion through placental vascular anastomoses., Areas Covered: This review focuses on the differences in antenatal management between TTTS and TAPS. Expert commentary: The optimal management for TTTS is fetoscopic laser coagulation of the vascular anastomoses, preferably using the Solomon technique in which the whole vascular equator is coagulated. The Solomon technique is associated with a reduction of residual anastomosis and a reduction in post-operative complications. The optimal management for TAPS is not clear and includes expectant management, intra-uterine transfusion with or without partial exchange transfusion and fetoscopic laser surgery.

Monochorionic twins share a single placenta and are connected with each other through vascular anastomoses. Unbalanced inter-twin blood transfusion may lead to various complications, including twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). TAPS was first described less than a decade ago, and the pathogenesis of TAPS results from slow blood transfusion from donor to recipient through a few minuscule vascular anastomoses. This gradually leads to anemia in the donor and polycythemia in the recipient, in the absence of twin oligo-polyhydramnios sequence (TOPS). TAPS may occur spontaneously in 3-5% of monochorionic twins or after laser surgery for TTTS. The prevalence of post-laser TAPS varies from 2% to 16% of TTTS cases, depending on the rate of residual anastomoses. Pre-natal diagnosis of TAPS is currently based on discordant measurements of the middle cerebral artery peak systolic velocity (MCA-PSV; >1.5 multiples of the median [MoM] in donors and 8 g/dL), and at least one of the following: reticulocyte count ratio >1.7 or minuscule placental anastomoses. Management includes expectant management, and intra-uterine blood transfusion (IUT) with or without partial exchange transfusion (PET) or fetoscopic laser surgery. Post-laser TAPS can be prevented by using the Solomon laser surgery technique. Short-term neonatal outcome ranges from isolated inter-twin Hb differences to severe neonatal morbidity and neonatal death. Long-term neonatal outcome in post-laser TAPS is comparable with long-term outcome after treated TTTS. This review summarizes the current knowledge after 10 years of research on the pathogenesis, diagnosis, management, and outcome in TAPS.

Objective: Single fetal demise (SFD) occurs in up to 20% of monochorionic pregnancies treated with laser coagulation for twin-twin transfusion syndrome (TTTS). We aimed to determine the independent factors associated with SFD to improve outcome in the care of TTTS pregnancies in the future., Methods: This was a case-control study on twin pregnancies treated for TTTS between 2007 and 2013. Data on ultrasound, laser surgery and outcome were retrieved from our monochorionic twin database. We analyzed separately cases of SFD in donor and recipient twins, and compared them with treated pregnancies that resulted in two live births., Results: Of the 273 TTTS pregnancies treated with laser coagulation, SFD occurred in 30 donors (11.0%) and 27 recipients (9.9%). In 67% of pregnancies with SFD, the death occurred within 1 week after laser treatment. For SFD in donors, absent/reversed end-diastolic flow in the umbilical artery was the strongest predictor (odds ratio (OR), 3.0 (95% CI, 1.1-8.0); P = 0.01), followed by the presence of an arterioarterial anastomosis (OR, 4.2 (95% CI, 1.4-13.1); P = 0.03) and discordance in estimated fetal weight (OR, 1.0 (95% CI, 1.0-1.1); P = 0.04). For SFD in recipients, independent predictors were absent/reversed A-wave in the ductus venosus (OR, 3.6 (95% CI, 1.2-10.5); P = 0.02) and the absence of recipient-to-donor arteriovenous anastomoses (OR, 10.6 (95% CI, 1.8-62.0); P < 0.01)., Conclusions: Our findings confirm earlier reports that suggest that abnormal blood flow is associated with SFD after laser treatment for TTTS. The association of SFD with the type of anastomoses is a new finding. We speculate that the type of anastomoses present determines the degree of hemodynamic change during laser therapy. Future strategies should aim at stabilizing fetal circulation before laser therapy to decrease the vulnerability to acute preload and afterload changes. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess the incidence of and risk factors for adverse long-term neurodevelopmental outcome in complicated monochorionic pregnancies treated with selective feticide at our centre between 2000 and 2011., Design: Observational cohort study., Setting: National referral centre for fetal therapy (Leiden University Medical Centre, the Netherlands)., Population: Neurodevelopmental outcome was assessed in 74 long-term survivors., Methods: Children, at least 2 years of age, underwent an assessment of neurologic, motor and cognitive development using standardised psychometric tests and the parents completed a behavioural questionnaire., Main Outcome Measures: A composite outcome termed neurodevelopmental impairment including cerebral palsy (GMFCS II-V), cognitive and/or motor test score of <70, bilateral blindness or bilateral deafness requiring amplification., Results: A total of 131 monochorionic pregnancies were treated with selective feticide at the Leiden University Medical Centre. Overall survival rate was 88/131 (67%). Long-term outcome was assessed in 74/88 (84%). Neurodevelopmental impairment was detected in 5/74 [6.8%, 95% confidence interval (CI), 1.1-12.5] of survivors. Overall adverse outcome, including perinatal mortality or neurodevelopmental impairment was 48/131 (36.6%). In multivariate analysis, parental educational level was associated with cognitive test scores (regression coefficient B 3.9, 95% CI 1.8-6.0). Behavioural problems were reported in 10/69 (14.5%)., Conclusions: Adverse long-term outcome in survivor twins of complicated monochorionic pregnancies treated with selective feticide appears to be more prevalent than in the general population. Cognitive test scores were associated with parental educational level., Tweetable Abstract: Neurodevelopmental impairment after selective feticide was detected in 5/74 (6.8%, 95% CI 1.1-12.5) of survivors., (© 2015 Royal College of Obstetricians and Gynaecologists.)

Arterioarterial (AA) and venovenous (VV) anastomoses in monochorionic (MC) placentas lie on the placental surface and are termed as superficial anastomoses. The purpose of this study is to report the occurrence of an atypical form of superficial anastomoses which are partially hidden. Partially-hidden superficial anastomoses were defined as vascular anastomoses without visible direct connection on placental surface but with clear mixing of dye after colored dye injection. With analyzing 270 MC placentas, we found a prevalence of partially-hidden AA and VV anastomose of 3% and 5%, respectively. In conclusion, partially-hidden superficial anastomose are not infrequent in MC placentas., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the effect of a newly developed training curriculum on the performance of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS) using an advanced high-fidelity simulator model., Methods: Ten novices were randomized to receive verbal instructions and either skills training using the simulator (study group; n = 5) or no training (control group; n = 5). Both groups were evaluated with a pre-training and post-training test on the simulator. Performance was assessed by two independent observers and comprised a 52-item checklist for surgical performance (SP) score, measurement of procedure time and number of anastomoses missed. Eleven experts set the benchmark level of performance. Face validity and educational value of the simulator were assessed using a questionnaire., Results: Both groups showed an improvement in SP score at the post-training test compared with the pre-training test. The simulator-trained group significantly outperformed the control group, with a median SP score of 28 (54%) in the pre-test and 46 (88%) in the post-test vs 25 (48%) and 36 (69%), respectively (P = 0.008). Procedure time decreased by 11 min (from 44 to 33 min) in the study group vs 1 min (from 39 to 38 min) in the control group (P = 0.69). There was no significant difference in the number of missed anastomoses at the post-training test between the two groups (1 vs 0). Subsequent feedback provided by the participants indicated that training on the simulator was perceived as a useful educational activity., Conclusions: Proficiency-based simulator training improves performance, indicated by SP score, for fetoscopic laser therapy. Despite the small sample size of this study, practice on a simulator is recommended before trainees carry out laser therapy for TTTS in pregnant women., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Introduction: Twin anemia-polycythemia sequence (TAPS) is a newly described disease in monochorionic twin pregnancies, characterized by large inter-twin hemoglobin differences. Optimal management for TAPS is not clear. One of the possible treatment modalities is intrauterine blood transfusion (IUT) in the donor with or without combination of partial exchange transfusion (PET) in the recipient., Methods: We applied a computational model simulation to illustrate the mechanism of IUT with and without PET in TAPS occurring after laser surgery for twin-twin transfusion syndrome (TTTS). Model simulations were performed with the representative anastomotic pattern as observed during laser intervention, and after placental dye injection., Results: The model was tested against different cases where IUT was combined with PET for the treatment of post-laser TAPS. Model simulations using the observed anastomotic pattern showed a significant reduction of hyperviscosity in the recipient after IUT/PET compared to IUT without PET., Discussion: In this model simulation we show that the addition of PET to IUT reduces the severity of polycythemia in the recipient. PET may thus be important to prevent complications of hyperviscosity., Conclusion: This model simulation shows the beneficial effect of PET for the recipient in TAPS cases treated with IUT., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To determine, by expert consensus, the essential substeps of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) that could be used to create an authority-based curriculum for training in this procedure among fetal medicine specialists., Methods: A Delphi survey was conducted among an international panel of experts (n = 98) in FLS. Experts rated the substeps of FLS on a five-point Likert-type scale to indicate whether they considered them to be essential, and were able to comment on each substep, using a dedicated online platform accessed by the invited tertiary care facilities that specialize in fetal therapy. Responses were returned to the panel until consensus was reached (Cronbach's α ≥ 0.80). All substeps that were rated  ≥ 4 by 80% of the experts were included in the evaluation instrument., Results: After the first iteration of the Delphi procedure, a response rate of 74% (73/98) was reached, and in the second and third iterations response rates of 90% (66/73) and 81% (59/73) were reached, respectively. Among a total of 81 substeps rated in the first round, 21 substeps had to be re-rated in the second round. Finally, from the initial list of substeps, 55 were agreed by experts to be essential. In the third round, the 18 categorized substeps were ranked in order of importance, with 'coagulation of all anastomoses that cross the equator' and 'determination of fetoscope insertion site' as the most important., Conclusions: A total of 55 substeps of FLS for TTTS were defined by a panel of experts to be essential in the procedure. This list is the first authority-based evidence to be used in the development of a final training model for future fetal surgeons., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To evaluate differences between international fetal centers in their treatment of twin-twin transfusion syndrome (TTTS) by fetoscopic placental laser coagulation., Methods: Fetal therapy centers worldwide were sent a web-based questionnaire. Participants were identified through networks and through scientific presentations and papers. Questions included physician and center demographics, treatment criteria, operative technique and instrumentation. Laser treatment was compared between low-volume (< 20 procedures/year) and high-volume (≥ 20 procedures/year) centers. Data were analyzed using descriptive statistics., Results: Of 106 fetal therapy specialists approached, 76 (72%) from 64 centers in 25 countries responded. Of these, 48% (31/64) of centers and 63% (48/76) of operators performed fewer than 20 laser procedures annually. Comparison of low- and high-volume centers showed differences in technique, gestational age limits for treatment and geography. High-volume centers more often used the Solomon technique and applied wider gestational age limits for treatment. Europe and Asia had more high-volume centers, whereas South America, the Middle East and Australia had mainly low-volume centers., Conclusion: This survey revealed significant differences between fetal centers in several aspects of fetoscopic placental laser therapy for TTTS. Increasing awareness of TTTS, and of laser coagulation as its preferred treatment, will lead to an increase in centers offering this modality, especially in Asia, Africa, South America and the Middle East. Considering the rarity of TTTS and the relative complexity of the procedure, developing international guidelines for techniques, instrumentation and suggested minimum volumes per center may aid in optimizing perinatal outcome., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Introduction: Not much is known on the definition, occurrence and characteristics of proximate umbilical cord insertions (PCI) in monochorionic (MC) placentas. The purpose of this study was to establish a reference range for the distance between cord insertions and to evaluate the prevalence and angio-architecture of MC placentas with PCI., Methods: All MC placentas not treated with laser surgery were included in this study. The reference range of distance between cord insertions was created using the standard methodology proposed by Royston and Wright. We defined PCI as a cord insertion distance below the 5th centile., Results and Discussion: A total of 369 MC placentas were analyzed during this study period. The 5th centile was calculated by the equation: 0.027 × gestational age (weeks) +2.91 (cm), and ranged from 3.3 to 4 cm throughout gestation. Accordingly, 18 of the 369 (5%) MC placentas fulfilled the definition criteria for PCI. PCI occurred frequently in MC monoamniotic placentas (53%, 9/17) but were rare in MC diamniotic placentas (3%, 9/352). The prevalence of arterio-arterial and veno-venous anastomoses in MC placentas with and without PCI was respectively 100% versus 80% (P = .12) and 56% versus 26% (P = .01). PCI may be representative of later splitting of inner cell mass., Conclusion: The threshold for PCI (5th centile) is approximately 4 cm throughout gestation. PCI are rare in MC diamniotic placentas, but are quite common in MC monoamniotic placentas. MC placentas with PCI are characterized by higher rates of superficial AA and/or VV anastomoses., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to assess the perinatal outcome of pregnancies with twin-twin transfusion syndrome (TTTS) treated with laser therapy over the past 25 years, and in relation to different techniques used in this time period., Methods: A systematic review of studies reporting on perinatal outcome according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines was conducted. The MEDLINE, Embase and Cochrane Library databases were systematically searched. Comparisons were made in respect to time period and laser technique and Quintero stages., Results: In total, 34 studies reporting on 3,868 monochorionic twin pregnancies were included. The mean survival of both twins increased from 35 to 65% (p = 0.012) and for at least one twin from 70 to 88% (p = 0.009) over the past 25 years. Mean gestational age at birth remained stable over the years at 32 weeks gestation. Also, we showed a significantly improved perinatal survival with the evolution of the laser technique from non-selective to selective, selective sequential and the Solomon technique (p = 0.010)., Discussion: Since the introduction of laser therapy for TTTS more than two decades ago, perinatal survival improved significantly. Improved outcome is probably associated with several factors, including evolution of the laser technique, learning curve effect, better referral and improved early neonatal care., (© 2015 S. Karger AG, Basel.)

Background and Objective: To investigate the efficacy of sequential laser coagulation in the treatment of twin-to-twin transfusion syndrome (TTTS)., Data Sources: MEDLINE, EMBASE and the Cochrane Library were systematically searched for comparative studies on the efficacy of sequential versus standard selective laser coagulation for TTTS. The primary outcome measure in these studies was survival of at least one twin, both twins and fetal demise., Results: Three cohort studies comparing the selective laser treatment technique (n = 120) versus the sequential technique (n = 224) in 344 monochorionic twin pregnancies were included. Mean survival of at least one twin was 88% in the selective group versus 92% (p = 0.22) in the sequential group. Mean survival of both twins was lower in the selective group (52%) than in the sequential group (75%) (p = 0.002). Donor fetal demise decreased from 34% in the selective to 10% in the sequential group (p < 0.01), and recipient fetal demise decreased from 16 to 7% (p = 0.02)., Conclusion: Limited evidence suggests improved double neonatal survival as well as decreased donor and recipient fetal demise with the use of the sequential technique. However, these results are based on small non-randomized studies with evident forms of bias and methodological limitations. A randomized controlled trial to assess the efficacy of sequential laser technique is therefore required., (© 2014 S. Karger AG, Basel.)

Objective: To evaluate management and outcome of iatrogenic monoamniotic twins (iMAT) compared with twins with intact intertwin dividing membranes after laser surgery for twin-to-twin transfusion syndrome (TTTS)., Methods: This was a retrospective analysis of twins with and without iatrogenic rupture of the intertwin membranes that had been treated for TTTS with laser surgery at our center between 2004 and 2012. Primary outcomes were perinatal survival and severe neonatal morbidity. Secondary outcomes were mode of delivery, gestational age at birth and cord entanglement., Results: In total, 338 pregnancies were included. In 67/338 (20%) pregnancies, iMAT was suspected antenatally. In 47 of these 67 (70%), a preterm Cesarean section was performed for monoamnionicity. Perinatal survival was 108/134 (81%) vs 396/542 (73%) in twins with intact intertwin membranes (P = 0.13). Mean gestational age at birth in iMAT was 31 completed weeks, compared to 33 weeks in twins with intact membranes (P < 0.01). At birth, cord entanglement was present in 8/67 (12%) iMAT pregnancies. Severe neonatal morbidity was assessed in 106/110 (96%) in iMAT cases and 392/416 (94%) in controls. The incidence of severe neonatal morbidity was 28/106 (26%) in iMAT vs 72/392 (18%) in controls (P = 0.25). Severe cerebral injury was significantly increased in the iMAT group as compared with controls, at 16/106 (15%) vs 18/392 (5%) (P < 0.01)., Conclusions: Iatrogenic rupture of intertwin membranes was suspected in 20% of pregnancies treated with laser therapy for TTTS and was associated with a lower gestational age at birth and increased neonatal morbidity., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Residual anastomoses after fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS) may lead to severe postoperative complications, including recurrent TTTS and twin anemia-polycythemia sequence (TAPS). A novel technique (Solomon technique) using laser coagulation of the entire vascular equator was recently investigated in a randomized controlled trial (Solomon trial) and compared with the Standard selective laser technique. The aim of this secondary analysis was to evaluate the occurrence and characteristics of residual anastomoses in placentas included in the Solomon trial., Study Design: International multicenter randomized controlled trial in TTTS, randomized 1:1 ratio to either the Solomon laser technique or Standard laser technique. At time of laser, surgeons recorded whether they considered the procedure to be complete. Placental dye injection was performed after birth in the participating centers to evaluate the presence of residual anastomoses., Results: A total of 151 placentas were included in the study. The percentage of placentas with residual anastomoses in the Solomon group and Standard group was 19% (14/74) and 34% (26/77), respectively (P = .04). The percentage of placentas with residual anastomoses in the subgroup of cases where the procedure was recorded as complete was 8/65 (12%) and 22/69 (32%) in the Solomon group and Standard group, respectively (P < .01)., Conclusion: The Solomon laser technique reduces the risk of residual anastomoses. However, careful follow-up remains essential also after the Solomon technique, as complete dichorionization is not always achieved., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: To evaluate the effectiveness of laser treatment for antenatally detected twin anemia-polycythemia sequence (TAPS) compared with intrauterine transfusion or expectant management., Methods: All monochorionic twin pregnancies with TAPS managed between 2005 and 2013 in two European fetal therapy centers were evaluated. The outcomes of TAPS cases treated primarily with laser surgery were compared with the outcomes of cases managed expectantly or treated with intrauterine transfusion., Results: In this retrospective study 52 cases of TAPS were detected antenatally and were managed with either laser surgery (n=8; 15%) or intrauterine blood transfusion (n=17; 33%) or expectantly (n=27; 52%). Perinatal survival in the laser group was 94% (15/16) vs 85% (29/34) in the intrauterine-transfusion group and 83% (45/54) in the expectant-management group (P=0.30). The rates of severe neonatal morbidity in liveborn neonates in the laser, intrauterine-transfusion and expectant-management groups were 7% (1/15), 38% (12/32) and 24% (12/50), respectively (P=0.17). There was a significant reduction in respiratory distress syndrome in cases treated by laser. No severe postnatal hematological complications were detected in the laser group compared with 72% (23/32) in the intrauterine-transfusion group and 52% (26/50) in the expectant-management group (P<0.01). Median time between diagnosis and birth was 11 weeks in the laser group compared to 5 weeks after intrauterine transfusion and 8 weeks after expectant management (P<0.01). After injection of colored dye no residual anastomoses were found in the laser group., Conclusions: Laser surgery for TAPS appears to improve perinatal outcome by prolonging pregnancy and reducing respiratory distress syndrome. Larger, adequately controlled studies are needed to reach firm conclusions on the optimal management of TAPS., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To identify a learning curve and monitor operator performance for fetoscopic laser surgery for twin-to-twin transfusion syndrome using cumulative sum analysis., Design: Retrospective cohort study., Setting: National tertiary referral center for invasive fetal therapy., Population: A total of 340 consecutive monochorionic pregnancies with twin-to-twin transfusion syndrome treated with fetoscopic laser coagulation between August 2000 and December 2010., Methods: A learning curve was generated using learning curve cumulative sum analysis and cumulative sum methodology to assess changes in double survival across the case sequence. Laser surgery was initially performed by two operators, joined by a third and fourth operator after 1 and 2 years, respectively., Main Outcome Measures: Individual operator performance, double perinatal survival at 4 weeks., Results: Overall survival of both twins occurred in 59% (201/340), median gestational age at birth was 32.0 weeks. Cumulative sum graphs showed that level of competence for double survival for the operators was reached after 26, 25, 26, and 35 procedures, respectively. Two operators kept their competence level and continued to improve after completing the initial learning process; two others went out of control at one point in time, according to the cumulative sum boundaries. A difference in learning effect was associated with number of procedures performed annually and previous experience with other ultrasound-guided invasive procedures., Conclusions: This study shows that all operators reached a level of competence after at least 25 fetoscopic laser procedures and confirms the value of using the cumulative sum method both for learning curve assessment and for ongoing quality control., (© 2014 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome are typically treated with fetoscopic laser coagulation. Postoperative complications can occur due to residual vascular anastomoses on the placenta. We aimed to assess the efficacy and safety of a novel surgery technique that uses laser coagulation of the entire vascular equator (Solomon technique)., Methods: We undertook an open-label, international, multicentre, randomised controlled trial at five European tertiary referral centres. Women with twin-to-twin transfusion syndrome were randomly assigned by online randomisation (1:1) with permuted blocks to the Solomon technique or standard laser coagulation. The primary outcome was a composite of incidence of twin anaemia polycythaemia sequence, recurrence of twin-to-twin transfusion syndrome, perinatal mortality, or severe neonatal morbidity. Analyses were by intention to treat, with results expressed as odds ratios (ORs) and 95% CIs. This trial is registered with the Dutch Trial Registry, number NTR1245., Findings: Between March 11, 2008, and July 12, 2012, 274 women were randomly assigned to either the Solomon group (n=139) or the standard treatment group (n=135). The primary outcome occurred in 94 (34%) of 274 fetuses in the Solomon group versus 133 (49%) of 270 in the standard treatment group (OR 0·54; 95% CI 0·35-0·82). The Solomon technique was associated with a reduction in twin anaemia polycythaemia sequence (3% vs 16% for the standard treatment; OR 0·16, 95% CI 0·05-0·49) and recurrence of twin-to-twin transfusion syndrome (1% vs 7%; 0·21, 0·04-0·98). Perinatal mortality and severe neonatal morbidity did not differ significantly between the two groups. Outside of the common and well-known complications of twin-to-twin transfusion syndrome and its treatment, no serious adverse events occurred., Interpretation: Fetoscopic laser coagulation of the entire vascular equator reduces postoperative fetal morbidity in severe twin-to-twin transfusion syndrome. We recommend that fetoscopic surgeons consider adopting this strategy for treatment of women with twin-to-twin transfusion syndrome., Funding: Netherlands Organization for the Health Research and Development (ZonMw 92003545)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to analyze perinatal outcome in monoamniotic (MA) pregnancies that underwent antenatal surgical interventions for fetal complications., Methods: Review of all MA pregnancies treated with antenatal surgical interventions in three fetal treatment centers between 2000 and 2013. Indications were twin-twin transfusion syndrome, twin reversed arterial perfusion sequence, discordant anomalies, or elective reduction. We analyzed associations between indication, type of intervention, perinatal survival, and gestational age (GA) at birth and compared our results with a systematic review of the literature., Results: Fifty-eight MA pregnancies were included. Median GA at treatment was 18.0 weeks (range: 13.1-33.0). Procedures included cord coagulation plus transection (n = 42), cord coagulation without transection (n = 7), laser coagulation of placental anastomoses (n = 7), and one case each with interstitial laser and radiofrequency ablation. Median GA at birth was 34 weeks (range 16.0-41.0), and 75% (53/71) of fetuses intended to survive indeed survived. Literature review included 20 articles, reporting on a total of 45 cases of surgically treated MA pregnancies, showing similar outcome results., Conclusion: We present the largest series concerning surgical interventions in complicated MA pregnancies. Despite being rare in experienced hands, a 75% survival is achieved. Collaboration between centers, data sharing, and benchmarking may further improve outcome., (© 2014 John Wiley & Sons, Ltd.)

The aim of this study was to investigate the independent role of veno-venous (VV) anastomoses in the development of twin-twin transfusion syndrome (TTTS). Thirty TTTS placentas and 41 non-TTTS placentas, routinely injected with colored dye, were enrolled in this study. We excluded all cases with arterio-arterial (AA) anastomoses and TTTS cases treated with laser surgery. The prevalence of VV anastomoses was significantly higher in TTTS cases compared to non-TTTS cases, 37% (11/30) and 7% (3/41), respectively (P < .01; odds ratio 7.3; 95% confidence interval: 1.8-37.1). Our findings suggest that, in the absence of AA anastomoses, VV anastomoses may enhance the development of TTTS., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To estimate the prevalence of proximate cord insertions in twin-twin transfusion syndrome (TTTS) and evaluate the outcome after fetoscopic laser coagulation surgery., Methods: We included all TTTS cases treated with laser at our center between 2002 and 2013. Placentas were examined after birth and injected with colored dye. TTTS cases without complete placental injection study were excluded. We recorded the presence of proximate cord insertions (distance < 5 cm) after birth and the presence and types of residual anastomoses. We compared the clinical outcome and placental findings in cases with and without proximate cord insertions., Results: The prevalence of proximate cord insertions in TTTS placentas was 2% (4/252). Perinatal mortality in the TTTS group with and without proximate cord insertions was 13% (1/8) and 12% (61/496), respectively (P = 1.0). Residual anastomoses were detected in all placentas with proximate cord insertions (100%, 4/4) compared to 27% (66/248)(P < .01) in TTTS placentas without proximate cord insertions., Conclusion: Fetoscopic laser coagulation in TTTS cases with proximate cord insertions is challenging due to technical difficulties in visualizing the vascular equator and results in an increased risk of incomplete laser treatment., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate and compare perinatal outcome after intrauterine transfusions (IUT) performed before and after 20 weeks of gestation. To analyse contributing factors., Design: Retrospective analysis., Setting: The Dutch referral centre for fetal therapy., Population: IUTs for fetal alloimmune anaemia., Methods: Fetuses were divided into two groups: fetuses requiring the first IUT before 20 weeks of gestation (Group 1) and those in which the IUTs started after 20 weeks (Group 2). The cause of perinatal loss was classified as procedure-related (PR) or not procedure-related (NPR). The cohort was divided into two periods to describe the change of perinatal loss over time., Main Outcome Measures: Perinatal loss of fetuses requiring the first IUT before 20 weeks of gestation, compared with perinatal loss later in gestation., Results: A total of 1422 IUTs were performed in 491 fetuses. Perinatal loss rate in Group 1 was higher (7/29 24% versus 35/462 8%, P = 0.002). Especially NPR was higher for IUTs performed before 20 weeks (4/37 11% versus 19/1385 1%, P < 0.001). Kell alloimmunisation was overrepresented in Group 1 (7/29 24% versus 52/462 11%, P = 0.04). In a multivariate regression analysis, only hydrops was independently associated with perinatal loss (P = 0.001). In recent years, a decline in total perinatal loss was found (36/224 16% versus 6/267 2%, P < 0.001), but perinatal loss in Group 1 did not decline (4/224 1.8% versus 3/267 1.1%, P = 0.5)., Conclusions: Perinatal loss after IUT performed before 20 weeks of gestation is increased compared with loss after IUT performed later in gestation. In addition, we confirmed earlier observations that hydrops is a major contributor to adverse outcome. Early and timely detection and treatment may prevent hydrops and improve outcome., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Objective: To evaluate the incidence and risk factors of adverse perinatal outcome in complicated monochorionic twin pregnancies treated with selective feticide., Methods: This was a retrospective analysis of prospectively collected data from a consecutive, national cohort. All monochorionic twin pregnancies treated with selective feticide at Leiden University Medical Center between June 2000 and November 2011 were included. Obstetric and neonatal data were recorded. The primary outcome measure was adverse perinatal outcome, including fetal or neonatal demise or severe neonatal morbidity., Results: Data on perinatal outcome were obtained in all cases (n = 131). Overall perinatal survival rate was 67.2% (88/131). Median gestational age at delivery was 34 (interquartile range, 23-38) weeks. Neonatal mortality and morbidity rate in liveborn children was 4.3% (4/92) and 12.0 % (11/92), respectively. Severe cerebral injury was detected in three children. The overall incidence of adverse perinatal outcome was 41.2% (54/131). Median gestational age at occurrence of preterm prelabor rupture of membranes (PPROM) was 19.0 weeks and 32.0 weeks in cases with and without adverse perinatal outcome, respectively (P = 0.017). Liveborn children with adverse perinatal outcome were born at a lower median gestational age (29.0 weeks) than were children without adverse perinatal outcome (38.0 weeks) (P < 0.001)., Conclusions: The risk of adverse perinatal outcome after selective feticide is high and associated with low gestational age at occurrence of PPROM and low gestational age at delivery. Long-term follow-up to assess neurodevelopmental outcome in survivors is required., (Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.)

Twin anemia-polycythemia sequence (TAPS) is a rare condition which may occur either spontaneously in uncomplicated monochorionic twin pregnancies or may develop after laser treatment in twin-twin transfusion syndrome. TAPS is characterized by a large intertwin discordance in hemoglobin levels without discordance in amniotic fluid levels, and may lead to severe complications including fetal hydrops, hematological morbidity and perinatal mortality. Several treatments have been proposed including intrauterine transfusion, laser surgery, elective delivery and expectant management. The optimal treatment remains unclear. In this case series we report 3 TAPS cases managed recently at our center with a combination of intrauterine blood transfusion for the anemic twin and intrauterine partial exchange transfusion for the polycythemic twin. In 1 case, the donor was found to have severe cerebral injury on neuroimaging examination. We propose etiologic mechanisms for cerebral injury in TAPS, discuss the rationale behind this treatment alternative, and evaluate the pros and cons of the various management options., (Copyright © 2013 S. Karger AG, Basel.)

Objective: To compare perinatal outcome in monochorionic (MC) triplets with twin-to-twin transfusion syndrome (TTTS) versus dichorionic (DC) triplets with TTTS., Study Design: Retrospective analysis of all triplets with TTTS treated at our center and all cases reported in the literature between 1990 and 2010. Survival and gestational age at birth of MC and DC triplets were compared and stratified by type of intervention. We excluded triplets with one or more fetal deaths <16 weeks' gestation and those with one or more fetuses with congenital anomalies., Results: MC triplets were affected by TTTS in a total of 27 cases, and overall survival was 51% (38/75 fetuses) compared to 105 DC triplets with a survival of 76% (220/291 fetuses) (p < 0.05). Mean gestational age at birth in MC triplets was 28 weeks, compared to 31 weeks in DC triplets (p < 0.05). Perinatal survival of at least one fetus in MC triplet and DC triplet pregnancies was 70% (19/27) and 91% (96/105) (p < 0.05). In DC triplets, survival after laser therapy was significantly improved compared to expectant management, amniodrainage or selective feticide (p < 0.05)., Conclusion: MC triplets with TTTS are at a considerably higher risk for perinatal mortality and preterm birth than DC triplets. The optimal strategy to manage MC triplets with TTTS, including the role of selective feticide and laser therapy of all anastomoses, is still to be established., (Copyright © 2012 S. Karger AG, Basel.)

The presence of placental vascular anastomoses is a conditio sine qua non for the development of twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS)(1,2). Injection studies of twin placentas have shown that such anastomoses are almost invariably present in monochorionic twins and extremely rare in dichorionic twins(1). Three types of anastomoses have been documented: from artery to artery, from vein to vein and from artery to vein. Arterio-venous (AV) anastomoses are unidirectional and are referred to as "deep" anastomoses since they proceed through a shared placental cotyledon, whereas arterio-arterial (AA) and veno-venous (VV) anastomoses are bi-directional and are referred to as "superficial" since they lie on the chorionic plate. Both TTTS and TAPS are caused by net imbalance of blood flow between the twins due to AV anastomoses. Blood from one twin (the donor) is pumped through an artery into the shared placental cotyledon and then drained through a vein into the circulation of the other twin (the recipient). Unless blood is pumped back from the recipient to the donor through oppositely directed deep AV anastomoses or through superficial anastomoses, an imbalance of blood volumes occurs, gradually leading to the development of TTTS or TAPS. The presence of an AA anastomosis has been shown to protect against the development of TTTS and TAPS by compensating for the circulatory imbalance caused by the uni-directional AV anastomoses(1,2). Injection of monochorionic placentas soon after birth is a useful mean to understand the etiology of various (hematological) complications in monochorionic twins and is a required test to reach the diagnosis of TAPS(2). In addition, injection of TTTS placentas treated with fetoscopic laser surgery allows identification of possible residual anastomoses(3-5). This additional information is of paramount importance for all perinatologists involved in the management and care of monochorionic twins with TTTS or TAPS. Several placental injection techniques are currently being used. We provide a simple protocol to accurately evaluate the presence of (residual) vascular anastomoses using colored dye injection.

Background: The optimal approach for venous thrombosis (VTE) prophylaxis during pregnancy and postpartum in women with an increased risk of VTE is not established., Objectives: To evaluate the effectiveness, represented as the incidence of pregnancy-related VTE, and safety, represented as incidence of postpartum hemorrhage (PPH), of a protocol recommending prophylaxis with low-dose low-molecular-weight heparin (LMWH) in women at intermediate to high risk of VTE., Patients/methods: In this retrospective cohort study, we analyzed 34 women (44 pregnancies) with intermediate risk of VTE who received low-dose LMWH for 6 weeks postpartum and 57 women (82 pregnancies) with high risk of VTE who received low-dose LMWH during pregnancy and for 6 weeks postpartum. Pregnancy-related VTE was defined as VTE during pregnancy or ≤ 3 months postpartum. PPH was defined as blood loss >500 mL and severe PPH as blood loss > 1000 mL., Results: The incidence of pregnancy-related VTE was 5.5% (95% CI, 2.4-12.3) despite prophylaxis with low-dose LMWH. All events occurred in women at high risk, with a postpartum incidence of 7.0% (95% CI, 2.9-16.7) and antepartum incidence of 1.8% (95% CI, 0.4-9.2). The risk of PPH was 21.6% (95% CI, 14.3-31.3) and severe PPH 9.1% (95% CI, 4.7-16.9), which was not different in women who started LMWH postpartum and those who used LMWH during pregnancy., Conclusions: Although prophylaxis with low-dose LMWH during pregnancy and postpartum proved to be safe, the risk of pregnancy-related VTE is considerable in women with a high risk of VTE. VTE prophylaxis with low-dose LMWH may not be sufficiently effective in these women., (© 2011 International Society on Thrombosis and Haemostasis.)

Introduction: Intravascular intrauterine transfusion (IUT) is an effective and relatively safe method for the treatment of fetal anemia. Although implemented in centers all over the world in the 1980s, the length and strength of the learning curve for this procedure has never been studied. Cumulative sum (CUSUM) analysis has been increasingly used as a graphical and statistical tool for quality control and learning curve assessment in clinical medicine. We aimed to test the feasibility of CUSUM analysis for quality control in fetal therapy by using this method to monitor individual performance of IUT in the learning phase and over the long term., Methods: IUTs performed in the Dutch referral center for fetal therapy from 1987 to 2009 were retrospectively classified as successful or failed. Failed was defined as no net transfusion or the occurrence of life-threatening procedure-related complications. The CUSUM statistical method was used to estimate individual learning curves and to monitor long-term performance. Four operators who each performed at least 200 procedures were included., Results: Individual CUSUM graphs were easily assessed. Both operators pioneering IUT in the late 1980s had long learning phases. The 2 operators learning IUT in later years in an experienced team performed acceptably from the start and reached a level of competence after 34 and 49 procedures., Discussion: CUSUM analysis is a feasible method for quality control in fetal therapy. In an experienced setting, individual competence may be reached after 30 to 50 IUTs. Our data suggest that operators need at least 10 procedures per year to keep a level of competence., (Copyright © 2011 S. Karger AG, Basel.)

Objective: To evaluate the efficacy and safety of thromboprophylaxis with a low of low-molecular-weight heparin (LMWH) in women with an intermediate to high risk of pregnancy-related venous thromboembolism (VTE)., Design: Retrospective cohort study., Methods: We collected data from all pregnant women with an intermediate or high risk of VTE in the period 1996-2009. In accordance with protocol, pregnant women with an intermediate risk of VTE were treated with a prophylactic dose of LMWH for 6 weeks post partum, and pregnant women with a high risk were treated with a prophylactic dose of LMWH during the pregnancy and for 6 weeks post partum. Efficacy was defined as the incidence of VTE during pregnancy or < 3 months post partum, and safety as the incidence of post-partum haemorrhage (PPH) (> 500 ml blood loss) or severe PPH (> 1,000 ml blood loss)., Results: We analysed 34 women (44 pregnancies) with an intermediate risk and 57 women (82 pregnancies) with a high risk of VTE. The incidence of pregnancy-related VTE despite thromboprophylaxis was 5.5% (95% CI: 2.4-12.3). All VTEs occurred in high-risk women, and risk was higher post partum than ante partum: 7.0% (95% CI: 2.9-16.7) and 1.8% (95% CI: 0.4-9.2%), respectively. The risk of PPH was 21.6% (95% CI: 14.3-31.3) and of severe PPH 9.1% (95% CI: 4.7-16.9) and was comparable in women who used LMWH during pregnancy and those who started LMWH post partum., Conclusion: There was a considerable risk of pregnancy-related VTE in high-risk women despite a prophylactic dose of LMWH during pregnancy and in the post partum period. For these women thromboprophylaxis with a low, prophylactic dose of LMWH appeared to be insufficient.

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., (Copyright 2010 S. Karger AG, Basel.)

Monochorionic twins share a single placenta with inter-twin 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 severe complications, including twin-twin transfusion syndrome (TTTS) and twin-anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of feto-fetal transfusion. TTTS is characterized by the twin oligo-polyhydramnios sequence (TOPS), whereas TAPS is characterized by large inter-twin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in a minority of monochorionic twins or in TTTS cases after laser treatment. This review focuses on the differences between TAPS and TTTS in terms of pathogenesis, incidence, diagnostic criteria, treatment modalities, perinatal outcome and long-term outcome.

Bronchopulmonary sequestration (BPS) is sometimes associated with hydrothorax and hydrops in utero. In the absence of fetal hydrops, perinatal outcome is favorable and justifies expectant management. In the presence of fetal hydrops, perinatal outcome is reported to be extremely poor and intervention should be considered. Therapeutic options include open fetal surgery, minimally invasive coagulation of the blood supply and thoracoamniotic shunting. We present the first case of fetal hydrops and a large hydrothorax due to BPS treated successfully with one ultrasound-guided thin needle insertion, through which both laser coagulation of the feeding artery and drainage of the hydrothorax were performed. Following the procedure the hydrothorax and hydrops gradually disappeared and the BPS diminished in size. A healthy neonate was delivered uneventfully at term. We describe the case and discuss the different therapeutic options.

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.

Objective: To study the localization and size of residual anastomoses in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery and correlate the findings with outcome., Study Design: Placental injection in twin-to-twin transfusion syndrome placentas treated with laser was performed by using colored dye., Results: A total of 77 twin-to-twin transfusion syndrome placentas were included in the study. Residual anastomoses (n = 48) were found in 32% (25/77) of lasered placentas. Most residual anastomoses were localized near the margin of the placenta. The majority of residual anastomoses (67%; 32/48) were very small (diameter, < 1 mm). Eleven of the 25 cases (44%) in the residual anastomoses group developed twin anemia-polycythemia sequence., Conclusion: Most residual anastomoses in twin-to-twin transfusion syndrome placentas treated with laser are very small and localized near the placental margin. Almost half of cases with residual anastomoses developed twin anemia-polycythemia sequence after laser surgery.

Background and Objectives: Kell haemolytic disease in pregnancies has been suggested to be associated with decreased fetal platelet counts. The aim of this study was to evaluate the incidence and clinical significance of fetal thrombocytopenia in pregnancies complicated by Kell alloimmunization., Materials and Methods: In this retrospective cohort study, fetal platelet counts were performed in 42 pregnancies with severe Kell alloimmunization prior to the first intrauterine blood transfusion. Platelet counts from 318 first intrauterine transfusions in RhD alloimmunized pregnancies were used as controls., Results: Fetal thrombocytopenia (platelet count < 150 x 10(9)/l) was found in 4/42 (10%) in the Kell group and in 84/318 (26%) in the RhD group. None of the fetuses in the Kell alloimmunized pregnancies, including 15 with severe hydrops, had a clinically significant thrombocytopenia defined as a platelet count < 50 x 10(9)/l. In the RhD alloimmunized pregnancies, 2/230 (1%) of the non-hydropic fetuses and 7/30 (23%) of the severely hydropic fetuses had a clinically significant thrombocytopenia., Conclusion: In contrast to fetuses with severe anaemia and hydrops due to RhD alloimmunization, fetuses with severe anaemia due to Kell alloimmunization are generally not at risk for substantial thrombocytopenia.