Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study.

BACKGROUND: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. METHODS: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015-2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. RESULTS: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015-2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). CONCLUSION: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

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.

Complications of intrauterine intravascular blood transfusion: lessons learned after 1678 procedures.

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.

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.

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.

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.

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.

Laser surgery as a management option for twin anemia-polycythemia sequence.

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.

Iatrogenic perforation of intertwin membrane after laser surgery for twin-to-twin transfusion syndrome.

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.

Increased perinatal loss after intrauterine transfusion for alloimmune anaemia before 20 weeks of gestation.

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.

Perinatal outcome after selective feticide in monochorionic twin pregnancies.

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.

Management of twin anemia-polycythemia sequence using intrauterine blood transfusion for the donor and partial exchange transfusion for the recipient.

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.