Fetal and neonatal neuroimaging in twin-twin transfusion syndrome.

OBJECTIVES: To describe the types of brain injury and subsequent neurodevelopmental outcome in fetuses and neonates from pregnancies with twin-twin transfusion syndrome (TTTS). Additionally, to determine risk factors for brain injury and to review the use of neuroimaging modalities in these cases. METHODS: This was a retrospective cohort study of consecutive TTTS pregnancies treated with laser surgery in a single fetal therapy center between January 2010 and January 2020. The primary outcome was the incidence of brain injury, classified into predefined groups. Secondary outcomes included adverse outcome (perinatal mortality or neurodevelopmental impairment), risk factors for brain injury and the number of magnetic resonance imaging (MRI) scans. RESULTS: Cranial ultrasound was performed in all 466 TTTS pregnancies and in 685/749 (91%) liveborn neonates. MRI was performed in 3% of pregnancies and 4% of neonates. Brain injury was diagnosed in 16/935 (2%) fetuses and 37/685 (5%) neonates and all predefined injury groups were represented. Four fetal and four neonatal cases of cerebellar hemorrhage were detected. Among those with brain injury, perinatal mortality occurred in 11/16 (69%) fetuses and 8/37 (22%) neonates. Follow-up was available for 29/34 (85%) long-term survivors with brain injury and the mean age at follow-up was 46 months. Neurodevelopmental impairment was present in 9/29 (31%) survivors with brain injury. Adverse outcome occurred in 28/53 (53%) TTTS individuals with brain injury. The risk of brain injury was increased after recurrent TTTS/post-laser twin anemia-polycythemia sequence (TAPS) (odds ratio (OR), 3.095 (95% CI, 1.581-6.059); P = 0.001) and lower gestational age at birth (OR per 1-week decrease in gestational age, 1.381 (95% CI, 1.238-1.541); P < 0.001). CONCLUSIONS: Based on dedicated neurosonography and limited use of MRI, brain injury was diagnosed in 2% of fetuses and 5% of neonates with TTTS. Adverse outcome was seen in over half of cases with brain injury. Brain injury was related to recurrent TTTS/post-laser TAPS and a lower gestational age at birth. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Epidural analgesia and emergency delivery for presumed fetal compromise: post-hoc analysis of RAVEL multicenter randomized controlled trial.

OBJECTIVE: To investigate the association between epidural analgesia (EDA) vs patient-controlled remifentanil analgesia (PCRA) and emergency delivery for presumed fetal compromise, in relation to birth-weight quintile. METHODS: This was a post-hoc per-protocol analysis of the RAVEL multicenter equivalence randomized controlled trial. Non-anomalous singleton pregnancies between 36 + 0 and 42 + 6 weeks' gestation were randomized at the time of requesting pain relief to receive EDA or PCRA. The primary outcome was emergency delivery for presumed fetal compromise. Secondary outcomes included mode of delivery and neonatal outcomes. Analysis was performed according to birth-weight quintile and was corrected for relevant confounding variables. RESULTS: Of 619 pregnant women, 336 received PCRA and 283 received EDA. Among women receiving EDA, 14.8% had an emergency delivery for presumed fetal compromise, compared with 8.3% of women who received PCRA. After adjusting for parity, women receiving EDA had higher odds of presumed fetal compromise compared to those receiving PCRA (odds ratio, 1.69 (95% CI, 1.01-2.83)). A statistically significant linear-by-linear association was observed between presumed fetal compromise and birth-weight quintile (P = 0.003). The incidence of emergency delivery for presumed fetal compromise was highest in women receiving EDA and delivering a neonate with a birth weight in the lowest quintile. CONCLUSIONS: Intrapartum EDA is associated with a higher rate of emergency delivery for presumed fetal compromise compared to treatment with PCRA. Birth-weight quintile is a strong predictor of this outcome, independent of pain management method. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal outcome after selective fetal reduction in monochorionic twin pregnancies: A comparison of techniques over a 20-year period.

OBJECTIVE: To assess the perinatal outcome after fetal reduction in complicated monochorionic (MC) twin pregnancies by comparing different techniques. METHODS: A retrospective cohort study at a national referral center comparing data between four techniques: interstitial laser coagulation, radiofrequency ablation (RFA), fetoscopic laser coagulation (FLC) and bipolar cord coagulation (BCC). The primary outcome was the mortality of the co-twins. Secondary outcomes were preterm pre-labor rupture of membranes (PPROM), gestational age at delivery and neonatal morbidity. RESULTS: 259 MC twin pregnancies underwent selective fetal reduction: 29 IL, 64 RFA, 85 FLC and 81 BCC. The perinatal mortality rate was 29% and fetal demise of the co-twins occurred in 19%. The lowest mortality rate was seen after BCC (17%, p = 0.012). PPROM occurred in 18% patients without significant differences between techniques. The mean gestational age at delivery in liveborn children was 35 weeks and did not differ between techniques. Severe cerebral injury and neonatal morbidity were reported in 4% and 14%, respectively, without significant differences between techniques. CONCLUSIONS: Selective fetal reductions in MC twins are precarious procedures with an increased risk of perinatal mortality of the co-twins. Our results show the lowest mortality rates after BCC. However, high PPROM rates were seen irrespective of the technique.

Prevalence of placental dichotomy, fetal cardiomegaly and starry-sky liver in twin anemia-polycythemia sequence.

OBJECTIVE: To investigate the prevalence of three additional ultrasound markers, placental dichotomy, cardiomegaly and 'starry-sky' liver, in monochorionic twin pregnancy with twin anemia-polycythemia sequence (TAPS). METHODS: All monochorionic twin pregnancies, diagnosed antenatally with TAPS at our center between 2006 and 2019, were reviewed retrospectively for the presence of placental dichotomy, cardiomegaly in the donor twin and a starry-sky liver in the recipient twin. TAPS was diagnosed based on delta middle cerebral artery (MCA) peak systolic velocity (PSV) > 0.5 multiples of the median. The primary outcome was the prevalence of placental dichotomy, cardiomegaly, starry-sky liver and at least one of these markers in both spontaneous and post-laser TAPS. The secondary outcome was the prevalence of these ultrasound markers according to the antenatal stage of TAPS. RESULTS: A total of 91 monochorionic twin pregnancies with TAPS were eligible for analysis. Placental dichotomy was observed in 44% (40/91) of TAPS cases. A total of 70% (64/91) of the TAPS donors developed cardiomegaly and a starry-sky liver was identified in 66% (53/80) of the TAPS recipients. The prevalence of cardiomegaly and starry-sky liver was roughly comparable between spontaneous and post-laser TAPS (69% (33/48) vs 72% (31/43) and 64% (25/39) vs 68% (28/41), respectively). Pregnancies with spontaneous TAPS showed a higher prevalence of placental dichotomy compared with post-laser TAPS (63% (30/48) vs 23% (10/43)). At least one of the three ultrasound markers was detected in 86% (78/91) of TAPS cases, meaning that 14% (13/91) of cases presented solely with discordant MCA-PSV values. There was a trend towards increased prevalence of all three ultrasound markers with increasing antenatal TAPS stage. CONCLUSIONS: Placental dichotomy, fetal cardiomegaly and a starry-sky liver are commonly found in TAPS pregnancy. Investigating the presence of these ultrasound markers can be of additional help in improving antenatal detection of TAPS in monochorionic twin pregnancy. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

High risk of long-term neurodevelopmental impairment in donor twins with spontaneous twin anemia-polycythemia sequence.

OBJECTIVES: To evaluate the long-term neurodevelopmental and behavioral outcomes in surviving infants of pregnancies with spontaneous twin anemia-polycythemia sequence (TAPS), to compare outcome between donors and recipients, and to investigate potential risk factors for neurodevelopmental impairment (NDI). METHODS: This was a retrospective study of a consecutive cohort of spontaneous-TAPS survivors delivered between 2005 and 2017 at the Leiden University Medical Center, The Netherlands. Neurological, motor, cognitive and behavioral development were assessed at a median age of 4 years. The primary outcome was NDI, which was a composite outcome of cerebral palsy, deafness, blindness and motor and/or cognitive delay. NDI was subdivided into two grades of severity: mild-to-moderate and severe NDI. Outcome was compared between surviving donor and recipient twins. Logistic regression analysis was used to assess risk factors for NDI. RESULTS: Forty-nine twin pregnancies complicated by spontaneous TAPS were eligible for inclusion. The perinatal survival rate was 83% (81/98) of twins. Neurodevelopmental assessment was performed in 91% (74/81) of surviving twins. NDI occurred in 30% (22/74) of TAPS survivors, and was found more often in donors (44%; 15/34) than in recipients (18%; 7/40) (odds ratio (OR), 4.1; 95% CI, 1.8-9.1; P = 0.001). Severe NDI was detected in 9% (7/74) of survivors and was higher in donors compared with recipients (18% (6/34) vs 3% (1/40)), although the difference did not reach statistical significance; P = 0.056). Donors demonstrated lower cognitive scores compared with recipients (P = 0.011). Bilateral deafness was identified in 15% (5/34) of donors compared with 0% (0/40) of recipients (P = 0.056). Parental concern regarding development was reported more often for donor than for recipient twins (P = 0.001). On multivariate analysis, independent risk factors for NDI were gestational age at delivery (OR, 0.7; 95% CI, 0.5-0.9; P = 0.003) and severe anemia (OR, 6.4; 95% CI, 2.4-17.0; P < 0.001). CONCLUSION: Surviving donor twins of pregnancies complicated by spontaneous TAPS have four-fold higher odds of NDI compared with recipient cotwins, are at increased risk of cognitive delay and have a high rate of deafness. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Improved prediction of twin anemia-polycythemia sequence by delta middle cerebral artery peak systolic velocity: new antenatal classification system.

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.

Incidence of and Risk Factors for Residual Anastomoses in Twin-Twin Transfusion Syndrome Treated with Laser Surgery: A 15-Year Single-Center Experience.

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.

Impact of cannula size on recurrent twin-twin transfusion syndrome and twin anemia-polycythemia sequence after fetoscopic laser surgery.

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.

Labour pain with remifentanil patient-controlled analgesia versus epidural analgesia: a randomised equivalence trial.

OBJECTIVE: To distinguish satisfaction with pain relief using remifentanil patient-controlled analgesia (RPCA) compared with epidural analgesia (EA) in low-risk labouring women. DESIGN: Randomised controlled equivalence trial. SETTING: Eighteen midwifery practices and six hospitals in the Netherlands. POPULATION: A total of 408 pregnant women at low risk for obstetric complications initially under the care of primary-care midwives. METHODS: Women randomised before active labour to receive analgesia with RPCA or EA, if requested. MAIN OUTCOME MEASURES: Primary outcome was satisfaction with pain relief measured hourly using a visual analogue scale and summed as area under the curve (AUC). Secondary outcomes were overall satisfaction with pain relief, pain intensity scores during labour, mode of delivery, and maternal and neonatal outcomes. RESULTS: We randomised 418 women, of whom 409 could be followed for the primary endpoint. Analgesia was received by 46% (94/203) in the remifentanil group and 37% (76/206) in the epidural group. The AUC for satisfaction with pain relief was 32 in the remifentanil group and 31 in the epidural group (mean difference -0.50; 95% CI -6.8 to 5.9). Among women who actually received analgesia, these values were 23 and 35, respectively (mean difference -12; 95% CI -22 to -1.5). Secondary outcomes were comparable. CONCLUSIONS: In low-risk labouring women, we could not demonstrate equivalence between a strategy with RPCA to EA with respect to satisfaction with pain relief assessed during the total duration of labour. However, once applied satisfaction was higher in women who received epidural analgesia. TWEETABLE ABSTRACT: Satisfaction with pain relief is higher in women receiving epidural analgesia compared with Remifentanil PCA.

Right ventricular outflow tract obstruction in complicated monochorionic twin pregnancy.

OBJECTIVES: Severe right ventricular outflow tract obstruction (RVOTO) is a potential complication in recipient twins of twin-to-twin transfusion syndrome (TTTS) that requires postnatal follow-up or treatment. We aimed to evaluate pregnancy characteristics of neonates with RVOTO from complicated monochorionic twin pregnancies, determine the incidence of RVOTO in TTTS cases and construct a prediction model for its development. METHODS: This was an observational cohort study of all complicated monochorionic twin pregnancies with a postnatal diagnosis of RVOTO examined at our center. Cases were referred for evaluation of the need for fetal therapy or intervention because of TTTS, selective intrauterine growth restriction (sIUGR) or multiple congenital malformations in one of the twins. Ultrasound data were retrieved from our monochorionic twin database. Among liveborn TTTS recipients treated prenatally with laser therapy, those with RVOTO were compared with those without RVOTO (controls). We describe four additional cases with RVOTO that were not TTTS recipients. RESULTS: A total of 485 twin pregnancies received laser therapy for TTTS during the study period. RVOTO was diagnosed in 3% (11/368) of liveborn TTTS recipients, of whom two showed mild Ebstein's anomaly. Before laser therapy, pericardial effusion was seen in 45% (5/11) of RVOTO cases (P < 0.01) and abnormal A-wave in the ductus venosus (DV) in 73% (8/11) (P = 0.03), significantly higher proportions than in controls. Mean gestational age at laser therapy was 17 + 3 weeks in RVOTO cases compared with 20 + 3 weeks in controls (P = 0.03). A prediction model for RVOTO was constructed incorporating these three significant variables. One TTTS donor had RVOTO after the development of transient hydrops following laser therapy. Three larger twins in pregnancies complicated by sIUGR developed RVOTO, the onset of which was detectable early in the second trimester. CONCLUSIONS: RVOTO occurs in TTTS recipient twins but can also develop in TTTS donors and larger twins of pregnancies complicated by sIUGR. Abnormal flow in the DV, pericardial effusion and early gestational age at onset of TTTS are predictors of RVOTO in TTTS recipients, which suggests increased vulnerability to hemodynamic imbalances in the fetal heart in early pregnancy. These findings could guide diagnostic follow-up protocols after TTTS treatment. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Operator competence in fetoscopic laser surgery for twin-twin transfusion syndrome: validation of a procedure-specific evaluation tool.

OBJECTIVES: Fetoscopic laser surgery for twin-twin transfusion syndrome is a procedure for which no objective tools exist to assess technical skills. To ensure that future fetal surgeons reach competence prior to performing the procedure unsupervised, we developed a performance assessment tool. The aim of this study was to validate this assessment tool for reliability and construct validity. METHODS: We made use of a procedure-specific evaluation instrument containing all essential steps of the fetoscopic laser procedure, which was previously created using Delphi methodology. Eleven experts and 13 novices from three fetal medicine centers performed the procedure on the same simulator. Two independent observers assessed each surgery using the instrument (maximum score: 52). Interobserver reliability was assessed using Spearman correlation. We compared the performance of novices and experts to assess construct validity. RESULTS: The interobserver reliability was high (Rs = 0.974, P < 0.001). Checklist scores for experts and novices were significantly different; the median score for novices was 28/52 (54%), whereas that for experts was 47.5/52 (91%) (P < 0.001). The procedure time and fetoscopy time were significantly shorter (P < 0.001) for experts. Residual anastomoses were found in 1/11 (9%) procedures performed by experts and in 9/13 (69%) procedures performed by novices (P = 0.005). Multivariable analysis showed that the checklist score, independent of age and gender, predicted competence. CONCLUSIONS: The procedure-specific assessment tool for fetoscopic laser surgery shows good interobserver reliability and discriminates experts from novices. This instrument may therefore be a useful tool in the training curriculum for fetal surgeons. Further intervention studies with reassessment before and after training may increase the construct validity of the tool. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of single fetal demise after laser therapy for twin-twin transfusion syndrome.

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.

Long-term neurodevelopmental outcome after selective feticide in monochorionic pregnancies.

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.

A worldwide survey of laser surgery for twin-twin transfusion syndrome.

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.

Middle cerebral artery peak systolic velocity to predict fetal hemoglobin levels in twin anemia-polycythemia sequence.

OBJECTIVE: To evaluate the diagnostic accuracy of middle cerebral artery peak systolic velocity (MCA-PSV) Doppler measurements in prediction of hemoglobin levels in twin anemia-polycythemia sequence (TAPS). METHODS: This study involved a consecutive cohort comprising monochorionic twin pregnancies complicated by TAPS managed at three European fetal medicine centers between 2005 and 2013. The accuracy of MCA-PSV, measured immediately prior to fetal hemoglobin (Hb) measurement by fetal or cord blood sampling, for prediction of anemia and polycythemia was assessed using 2 × 2 tables. RESULTS: A total of 116 measurements (74 recorded in donors and 42 in recipients) from 43 twin pregnancies complicated by TAPS were available for analysis. MCA-PSV multiples of the median (MoM) values correlated well with Hb levels (r = - 0.86; P < 0.001). The sensitivity of MCA-PSV ≥ 1.5 MoM to predict severe anemia (Hb deficit > 5 SD below the mean) in TAPS donors was 94% (95% CI, 85-98%); specificity was 74% (95% CI, 62-83%); positive and negative predictive values were 76% (95% CI, 65-85%) and 94% (95% CI, 83-98%), respectively. The sensitivity of MCA-PSV ≤ 1.0 MoM to predict polycythemia (Hb level > 5 SD above the mean) in TAPS recipients was 97% (95% CI, 87-99%); specificity was 96% (95% CI, 89-99%); positive and negative predictive values were 93% (95% CI, 81-97%) and 99% (95% CI, 93-100%), respectively. CONCLUSION: MCA-PSV measurement has high diagnostic accuracy for predicting abnormal Hb levels in fetuses with TAPS.

Simulator training in fetoscopic laser surgery for twin-twin transfusion syndrome: a pilot randomized controlled trial.

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.

Identification of essential steps in laser procedure for twin-twin transfusion syndrome using the Delphi methodology: SILICONE study.

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.

Neurodevelopmental outcome in twin anemia-polycythemia sequence after laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: To evaluate the long-term neurodevelopmental outcome in children who developed twin anemia-polycythemia sequence (TAPS) after fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). METHODS: Neurological, motor and cognitive development was assessed in a consecutive cohort of TTTS survivors treated with laser surgery between 2004 and 2011 and complicated by post-laser TAPS. Primary outcome was neurodevelopmental impairment, a composite outcome including any of the following: cerebral palsy, bilateral deafness, blindness, severe motor and/or cognitive developmental delay (>2 SD below the mean). A risk analysis on cognitive outcome was performed. RESULTS: During the study period, 33/306 (11%) monochorionic twin pairs developed TAPS after laser surgery for TTTS. Survival was 53/66 (80%). Long-term outcome was assessed in 47/53 (89%) children. The incidence of neurodevelopmental impairment was 4/47 (9%), occurring in one donor (1/20; 5%) and three recipients (3/27; 11%) (P=0.63). Mild-to-moderate cognitive delay, i.e. scores below 85, was detected in 8/47 (17%) children. Risk factors for low cognitive scores were low gestational age at birth (P=0.02) and low birth weight (P<0.01). The lowest cognitive scores were detected in the subgroup of TAPS survivors treated with intrauterine transfusion (median score, 82.5). CONCLUSIONS: Neurodevelopmental impairment and cognitive delay were found in almost one in five children surviving post-laser TAPS. Better treatment and, ideally, prevention of this complication after laser treatment for TTTS is urgently needed.