Cardiac time intervals and myocardial performance index for prediction of twin-twin transfusion syndrome.

OBJECTIVES: To explore whether intertwin discordance in myocardial performance index (MPI) or cardiac time intervals enables the prediction of twin-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) pregnancies with amniotic fluid discordance. METHODS: Prospective cohort study of MCDA pregnancies with amniotic fluid discordance ≥4 cm. Serial ultrasound examinations consisted of evaluation of amniotic fluid, fetal Dopplers and fetal cardiac function. RESULTS: We included 21 "future-TTTS" (group I), 18 selective fetal growth restriction (sFGR; group II) and 20 uncomplicated MCDA twin pairs (group III). Group I had a higher intertwin difference in left ventricle (LV) MPI and right ventricle (RV) MPI compared to group II and III. The intertwin difference in global heart relaxation time was significantly higher in group I compared to group III. Future recipient twins had significantly higher contraction times of the global heart and RV and lower relaxation times of the global heart and RV compared to the "expected recipients" in group II and III. CONCLUSION: Intertwin discordance in LV-MPI and RV-MPI differentiate between TTTS and MCDA pregnancies with transient discordant amniotic fluid volume. Cardiac time intervals identify future recipient twins. The clinical utility of cardiac time intervals and MPI should be investigated in large prospective studies.

Placental Abruption after Fetoscopic Laser Surgery in Twin-Twin Transfusion Syndrome: The Role of the Solomon Technique.

INTRODUCTION: Twin-twin transfusion syndrome (TTTS) is a complication in monochorionic twin pregnancies which is preferably treated with fetoscopic laser surgery. A few small studies suggested a possible association between the Solomon laser technique and placental abruption. METHODS: The objective of this study is to compare the rate of and to explore potential risk factors for placental abruption in TTTS treated with fetoscopic laser surgery according to the Selective and Solomon laser technique. We conducted a large retrospective cohort study of consecutive TTTS-cases treated with fetoscopic laser surgery in Shanghai, China, and Leiden, The Netherlands treated with either the Selective laser technique (Selective group) or Solomon laser technique (Solomon group). RESULTS: The rate of placental abruption in the Selective group versus the Solomon group was 1.7% (5/289) and 3.4% (15/441), respectively (p = 0.184). No risk factors for placental abruption were identified. Placental abruption was associated with lower gestational age at birth (p = 0.003) and severe cerebral injury (p = 0.003). CONCLUSION: The prevalence of placental abruption in TTTS after fetoscopic laser surgery is low, although it appears higher than in the overall population. Placental abruption is associated with a lower gestational age at birth, which is associated with severe cerebral injury. The rate of placental abruption was not significantly increased with the use of the Solomon technique. Continued research of placental abruption in TTTS is necessary to determine why the rate is higher than in the overall population.

Prevalence, risk factors, and outcome of postprocedural amniotic band disruption sequence after fetoscopic laser surgery in twin-twin transfusion syndrome: a large single-center case series.

BACKGROUND: Postprocedural amniotic band disruption sequence is a condition that is associated with intrauterine interventions, and it is characterized by a constriction of the limbs or umbilical cord by fibrous strands, leading to edema, amputation, and/or fetal demise. OBJECTIVE: To evaluate the prevalence of, risk factors for, and the outcome of postprocedural amniotic band disruption sequence after fetoscopic laser surgery in twin-twin transfusion syndrome cases. STUDY DESIGN: All consecutive cases of twin-twin transfusion syndrome treated with fetoscopic laser coagulation of the vascular anastomoses at our center between January 2002 and March 2019 were included in the study. The occurrence of postprocedural amniotic band disruption sequence in these cases was recorded, and the potential risk factors were analyzed. RESULTS: Postprocedural amniotic band disruption sequence was detected, at birth, in 2.2% (15/672) of twin-twin transfusion syndrome cases treated with fetoscopic laser surgery, in both the recipients (10/15, 67%) and the donors (5/15, 33%). Postprocedural amniotic band disruption sequence primarily affected the lower extremities (11/15, 73%) and, less frequently, the upper extremities (2/15, 13%), both the upper and lower extremities (1/15, 7%), or the umbilical cord (1/15, 7%). Postprocedural amniotic band disruption sequence led to the amputation of toes in 5 of 15 cases (33%) and resulted in fetal demise because of constriction of the umbilical cord in 1 case (7%). The independent risk factors identified for postprocedural amniotic band disruption sequence were lower gestational age at laser surgery (odds ratio per week, 1.43; 95% confidence interval, 1.12-1.79; P=.003) and the presence of postprocedural chorioamniotic membrane separation on antenatal ultrasound examination (odds ratio, 41.66; 95% confidence interval, 5.44-319.25; P<.001). CONCLUSION: The prevalence of postprocedural amniotic band disruption sequence is low, but, when present, it may lead to severe consequences, with amputation of extremities or fetal demise occurring in more than one-third of the cases. Lower gestational age at the time of laser therapy and chorioamniotic membrane separation are independent risk factors for the postprocedural amniotic band disruption sequence.

Perioperative fetal hemodynamic changes in twin-twin transfusion syndrome and neurodevelopmental outcome at two years of age.

OBJECTIVE: To investigate whether perioperative fetal hemodynamic changes in twin-to-twin transfusion syndrome (TTTS) are associated with neurodevelopmental impairment (NDI) at two years. METHODS: Doppler parameters of three sonograms (day before, first day after and 1 week after laser surgery for TTTS) were assessed for correlation with neurodevelopmental outcome at two years (2008-2016). NDI was defined as: cerebral palsy, deafness, blindness, and/or a Bayley-III cognitive/motor developmental test-score > 2SD below the mean. RESULTS: Long-term outcome was assessed in 492 TTTS survivors. NDI was present in 5% (24/492). After adjustment for severe cerebral injury (present in 4%), associated with NDI were: middle cerebral artery peak systolic velocity (MCA-PSV) >1.5 multiples of the median (MoM) 1 day after surgery (odds ratio [OR] 4.96; 95% confidence interval [CI]: 1.17-21.05, P = .03), a change from normal umbilical artery pulsatility index (UA-PI) presurgery to UA-PI >p95 postsurgery (OR 4.19; 95% CI: 1.04-16.87, P = .04), a change from normal to MCA-PSV >1.5MoM (OR 4.75; 95% CI: 1.43-15.77, P = .01). CONCLUSION: Perioperative fetal hemodynamic changes in TTTS pregnancies treated with laser are associated with poor neurodevelopmental outcome. Prospective research on the cerebrovascular response to altered hemodynamic conditions is necessary to further understand the cerebral autoregulatory capacity of the fetus in relation to neurodevelopmental outcome.

The value of echocardiography and Doppler in the prediction of fetal demise after laser coagulation for TTTS: A systematic review and meta-analysis.

This study aimed to investigate the value of echocardiography and Doppler before fetoscopic laser coagulation for twin-twin transfusion syndrome (TTTS) in the prediction of intrauterine fetal demise (IUFD). We performed a systematic review and meta-analysis to compare preoperative parameters between fetuses with and without demise after laser surgery. Eighteen studies were included. Recipient twins have an increased risk of demise in case of preoperative absent/reversed flow (A/REDF) in the umbilical artery (odds ratio [OR] 2.76, 95% confidence interval [CI], 1.78-4.28), absent or reversed a-wave in the ductus venosus (OR 2.32, 95% CI, 1.70-3.16), or a middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) (OR 7.59, 95% CI, 2.56-22.46). In donors, only A/REDF in the umbilical artery (OR 3.40, 95% CI, 2.68-4.32) and absent or reversed a-wave in the ductus venosus (OR 1.66, 95% CI, 1.12-2.47) were associated with IUFD. No association was found between donor-IUFD and preoperative myocardial performance index (MPI). Two studies found an association between abnormal MPI and recipient demise. With this study, we have identified a set of preoperative Doppler parameters predictive of fetal demise after laser surgery. More research is needed to assess the utility of preoperative echocardiographic parameters such as the MPI in predicting IUFD.

Long-Term Neurodevelopmental and Respiratory Outcome after Intrauterine Therapy for Fetal Thoracic Abnormalities.

INTRODUCTION: The aim of this study is to evaluate long-term neurodevelopmental and respiratory outcome after fetal therapy for fetal pleural effusion, congenital cystic adenomatoid malformation, and bronchopulmonary sequestration. METHODS: Children ≥18 months of age underwent an assessment of neurologic, motor, and cognitive development. Medical records were reviewed to determine respiratory outcome. Behavioral outcome was assessed using the Child Behavioral Checklist. RESULTS: Between 2001 and 2016, 63 fetuses with fetal hydrops secondary to thoracic abnormalities were treated at our center. Overall perinatal survival was 64% (40/63). Twenty-six children were included for follow-up (median age 55 months). Severe neurodevelopmental impairment (NDI) was detected in 15% (4/26). Three out of 4 children with severe NDI had associated causes contributing to the impairment. Overall adverse outcome, including perinatal mortality or NDI, was 55% (27/49). Fifteen percent (4/26) had severe respiratory sequelae. Parents did not report more behavioral problems than Dutch norms. DISCUSSION: Our results suggest that severe NDI in this specific high-risk cohort occurs in 15%, which is above the range of the incidence of NDI reported in case series treated with other fetal therapies (5-10%). Large multicenter studies and an international web-based registry are warranted to prospectively gather outcome data at fixed time points.

Fatal Umbilical Cord Strangulation in the Remaining Co-Twin after Selective Foeticide with Radiofrequency Ablation for Twin-Twin Transfusion Syndrome.

We report a case of a monochorionic diamniotic twin diagnosed with twin-twin transfusion syndrome (TTTS; stage 3) with co-existing severe cerebral damage in the donor twin at 18 + 4 weeks' gestation. After counselling, the parents opted for selective foeticide of the donor twin. For the procedure, radiofrequency ablation (RFA) was used. Serial ultrasound examinations at 20 + 1 and 21 + 1 weeks' gestation showed good recovery of the ex-recipient, after which the patient was sent back to the referring hospital. At 29 + 5 weeks' gestation, an unexpected foetal death was diagnosed. On macroscopic placental examination, (iatrogenic) monoamnionicity was detected. In addition, the umbilical cord of the recipient was found to be constricted by the macerated umbilical cord of the ex-donor. This case demonstrates that iatrogenic monoamnionicity can be a serious complication of RFA in monochorionic twins complicated by TTTS, with a subsequent risk for cord entanglement leading to a fatal outcome for the remaining co-twin. Although the actual incidence of iatrogenic monoamnionicity after RFA remains unknown, increased attention to the intactness of the inter-twin membrane even weeks after the RFA may be required.

The near disappearance of fetal hydrops in relation to current state-of-the-art management of red cell alloimmunization.

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.

Acquired right ventricular outflow tract obstruction in twin-to-twin transfusion syndrome; a prospective longitudinal study.

OBJECTIVE: The pathophysiology of right ventricular outflow tract obstruction (RVOTO) in twin-to-twin transfusion syndrome (TTTS) recipients is incompletely understood. We aimed to investigate the development and spectrum of RVOTO in TTTS recipients. METHODS: A prospective longitudinal cohort study was conducted between 2015 and 2017. Echocardiographic assessment was performed in recipients from TTTS diagnosis until the neonatal period. RESULTS: Prenatal RVOTO, defined as abnormal flow velocity waveforms across the pulmonary valve (PV), was diagnosed in 12.9% (16/124) of recipients at TTTS diagnosis. Postnatal RVOTO was found in 6.7% (7/105) of surviving recipients. All recipients with severe postnatal RVOTO showed prenatal RVOTO at TTTS diagnosis. In 5.6% (6/108) of cases, prenatal RVOTO appeared only after laser therapy, and in 1.9% (2/108), this progressed to mild postnatal pulmonary stenosis. Elevated peak systolic PV velocities were more frequently associated with postnatal RVOTO compared with prenatal finding of functional pulmonary atresia. Postnatal RVOTO was associated with early manifestation of TTTS but was equally found in all Quintero stages. CONCLUSION: In the spectrum of postnatal RVOTO, severe cases show prenatal RVOTO at TTTS diagnosis. However, RVOTO can develop after laser or even in the neonatal period and in all Quintero stages. A potential risk factor for postnatal RVOTO is early TTTS manifestation.

The effect of breathing on ductus arteriosus blood flow directly after birth.

Spontaneous breathing at birth influences ductus arteriosus (DA) flow. This study quantifies the effect of breathing on DA shunting directly after birth. In healthy term infants born by elective cesarean section, simultaneous measurements of DA shunting and tidal volumes during spontaneous breathing were performed at 2-5, 5-8, and 10-13 min after birth. Eight infants with a mean (SD) gestational age of 40 (1) weeks and 3216 (616) grams were studied. Inspiratory tidal volume was 5.8 (3.3-7.7), 5.7 (4.0-7.1), and 5.2 (4.3-6.1) mL/kg at 2-5, 5-8, and 10-13 min. The velocity time integral of left-to-right shunting significantly increased during inspiration when compared to expiration (8.4 (5.2) vs. 3.7 (2.3) cm, 8.9 (4.4) vs. 5.6 (3.4) cm, and 14.0 (6.7) vs. 8.4 (6.9) cm; all p < 0.0001) at 2-5, 5-8, and 10-13 min, respectively. In contrast, right-to-left shunting was not different between inspiration and expiration at 2-5 and 10-13 min (11.1 (2.4) vs. 11.1 (2.6) cm and 10.7 (2.3) vs. 10.6 (3.0) cm; p > 0.05), but there was a small increase at 5-8 min (12.1 (2.4) vs. 10.8 (2.9) cm; p = 0.001) during expiration. CONCLUSION: Directly after birth, ductal shunting is influenced by breathing effort, predominantly with an increase in left-to-right shunt due to inspiration. What is Known: • Spontaneous breathing at birth influences ductus arteriosus flow and pulmonary blood flow. • Crying causes a significant increase in left-to-right ductus arteriosus shunting. What is New: • Left-to-right ductus arteriosus shunting increases during inspiration compared to expiration. • Breathing is important for ductal shunting and contributes to pulmonary blood flow.

Twin Anemia Polycythemia Sequence: Current Views on Pathogenesis, Diagnostic Criteria, Perinatal Management, and Outcome.

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.

Fetoscopic laser coagulation of the vascular equator versus selective coagulation for twin-to-twin transfusion syndrome: an open-label randomised controlled trial.

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).

Is the Sequential Laser Technique for Twin-to-Twin Transfusion Syndrome Truly Superior to the Standard Selective Technique? A Meta-Analysis.

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.

Twenty-Five Years of Fetoscopic Laser Coagulation in Twin-Twin Transfusion Syndrome: A Systematic Review.

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.

Residual anastomoses in twin-twin transfusion syndrome after laser: the Solomon randomized trial.

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.

Fetal surgery in complicated monoamniotic pregnancies: case series and systematic review of the literature.

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.

Learning curve for fetoscopic laser surgery using cumulative sum analysis.

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.

Monochorionic triplets complicated by fetofetal transfusion syndrome: a case series and review of the literature.

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.

Quality control for intravascular intrauterine transfusion using cumulative sum (CUSUM) analysis for the monitoring of individual performance.

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.