Fetal brain imaging following laser surgery in twin-to-twin surgery.

OBJECTIVE: To describe the incidence and nature of prenatal brain damage following fetoscopic laser selective coagulation (FLSC) of placental vessels for twin-to-twin transfusion syndrome (TTTS). DESIGN: Retrospective observational study. SETTING: Single center cohort. POPULATION: All consecutive cases referred for TTTS treated by FLSC between 2003 and 2015. METHODS: After the FLSC, patients were followed weekly by ultrasound. Fetal magnetic resonance imaging (MRI) scans were systematically planned at 30-32 weeks of gestation. MAIN OUTCOME MEASURES: Brain damage diagnosed prenatally by ultrasound or MRI. RESULTS: In total, 1023 cases were reviewed. Brain damage was diagnosed prenatally in 22/1023 (2.1%) cases. Diagnosis was performed by ultrasound prior to MRI in 18 (82%) cases. All lesions were within the spectrum of ischaemic haemorrhagic lesions. Postoperative twin anaemia polycythaemia sequence and recurrence of TTTS were significantly associated with brain damage. CONCLUSION: The incidence of prenatal brain damage is low following FSLC, and is strongly associated with incomplete surgery. TWEETABLE ABSTRACT: Following FSLC for TTTS, prenatal brain damage occurs in 2% of cases and is associated with incomplete surgery.

[Outcome of triplet pregnancies managed for twin-to-twin transfusion syndrome: A single center experience]. / Issues des grossesses triples compliquées d'un syndrome transfuseur-transfusé : expérience d'un centre.

OBJECTIVES: Study the outcomes of triplet pregnancies (GGG) complicated with twin-to-twin transfusion syndrome (TTTS) treated with laser fetoscopy. METHODS: Retrospective study of interventions, outcomes and perinatal follow-up of GGG treated for TTS. RESULTS: Between 2002 and 2013, 25 GGG complicated by TTTS were seen in our center, 20 dichorionic and 5 monochorionic. The mean gestational age (GA) at diagnosis of TTTS was 19.7 GW (±2.4) with 2, 4, 16 and 1 pregnancies at Quintero's stage I, II, III and V, respectively. They had a fetoscopy at an average GA of 19 GW and 6 days. There were 3 (13.0%) late miscarriages. The average GA at delivery was of 29.6 GW overall (26.3 GW and 31.1 GW in monochorionic and dichorionic pregnancies respectively). The overall fetal survival rate was 57.97% (40% and 66.7% in the group of monochorionic dichorionic pregnancies, respectively). However, neonatal mortality (<28 days) is 17.5%. CONCLUSION: GGG operated by fetoscopy for TTTS have a survival rate of three, at least 2 and at least 1 fetus of 21.7%, 69.6% and 82.6% respectively. The overall fetal survival rate is 59.97%. There is a tendency for better survival rates in dichorionic GGG compared to monochorionic GGG (P=0.079).

Pulmonary stenosis in complicated monochorionic twin pregnancies: prevalence, management and outcome.

OBJECTIVE: To review prevalence, management and prognostic factors of pulmonary stenosis (PS) in monochorionic diamniotic (MCDA) pregnancies complicated by twin-to-twin transfusion syndrome (TTTS). METHODS: Retrospective study over the last 10 years in a single referral center. We reviewed fetal echocardiography data of all MC twin cases with diagnosis of isolated PS. We assessed fetoscopy characteristics of those that underwent laser coagulation. We collected data regarding perinatal outcome, neonatal echocardiography and cardiac management. RESULTS: We found 24 cases of isolated PS among 2091 MCDA pregnancies. Among 1052 complicated MCDA that underwent fetal laser surgery, 22 (2.09%) developed PS of which 20 were diagnosed prenatally. Two cases were diagnosed in uncomplicated MCDA pregnancies (0.2%). Four of 22 (18.18%) cases with TTTS showed in utero regression after laser treatment. Thirteen newborns (65%) required valvular dilatation. Peak systolic velocities in the pulmonary artery trunk (PSV-PA) at diagnosis and the interval between the diagnosis of TTTS and that of PS were significantly different (p < 0.001 and p = 0.05 respectively) between PS requiring cardiac intervention and those who did not. CONCLUSION: An elevated PSV-PA at the time of PS diagnosis and a short time-interval between fetoscopic laser surgery and PS diagnosis are predictive of the need for interventional treatment after birth.

Monozygotic twins discordant for 18q21.2qter deletion detected by array CGH in amniotic fluid.

Discordant chromosomal anomalies in monozygotic twins may be caused by various timing issues of erroneous mitosis and twinning events. Here, we report a prenatal diagnosis of heterokaryotypic monozygotic twins discordant for phenotype. In a 28-year-old woman, ultrasound examination performed at 26 weeks of gestation, detected intrauterine growth restriction and unilateral cleft lip and palate in twin B, whereas twin A had normal fluid, growth and anatomy. Molecular karyotyping in twin B identified a 18q21.2qter deletion, further confirmed by FISH analysis on amniocytes. Interestingly, in twin A, cytogenetic studies (FISH analysis and karyotype) on amniocytes were normal. Genotyping with microsatellite markers confirmed the monozygosity of the twins. At 32 weeks of gestation, selective termination of twin B was performed by umbilical cord coagulation and fetal blood samples were taken from the umbilical cord in both twins. FISH analyses detected mosaicism in both twins with 75% of cells being normal and 25% harboring the 18qter deletion. After genetic counseling, the parents elected to terminate the second twin at 36 weeks of gestation. In postmortem studies, FISH analyses revealed mosaicism on several tissues in both twins. Taking into account this observation, we discuss the difficulties of genetic counseling and management concerning heterokaryotypic monozygotic twins.

Active management of selective intrauterine growth restriction with abnormal Doppler in monochorionic diamniotic twin pregnancies diagnosed in the second trimester of pregnancy.

OBJECTIVE: This study aims to compare outcomes of active management of monochorionic diamniotic twin pregnancies complicated with severe intrauterine growth restriction (IUGR) of one twin before 24 weeks with continuous or intermittent absent or reversed end-diastolic flow (AREDF) in the umbilical artery, with or without twin-to-twin transfusion syndrome (TTTS). METHOD: This study is a retrospective comparison of 45 consecutive cases of severe selective IUGR (s-IUGR) defined as an estimated fetal weight at or below the fifth centile with a >25% weight discordance and AREDF in the umbilical artery before 24 weeks and 166 consecutive cases of TTTS stage III, with AREDF in the donor (TTTS3D) and also with s-IUGR. These were treated by either selective laser photocoagulation of chorionic vessels (SLPCV) or cord coagulation (CC). RESULTS: The 166 cases of TTTS3D were treated by SLPCV, whereas 23 and 22 cases of s-IUGR were treated by SLPCV and CC, respectively. Overall survival was 52.17% or 45.45% in s-IUGR treated by SLPCV or CC, respectively, and 48.49% in TTTS3D. The survival of appropriately grown for gestational age (AGA) twins following CC (90.9%) was higher than that following SLPCV in s-IUGR (74%) or in recipient twins of TTTS3D (55.42%) (p = 0.001). Survival of the IUGR twin was 30% and 41.56% with SLPCV in s-IUGR and TTTS3D, respectively. CONCLUSIONS: Active management of severe IUGR with AREDF in the umbilical artery seems beneficial. Survival rates with SLPCV were similar in s-IUGR and TTTS3D. However, there was a trend for higher survival rates in the AGA twin for CC. The choice of the technique should be driven by objective counseling on survival of both IUGR and AGA twins and therefore by the utility-based ethical values expressed by the pregnant woman.

A nomogram for perioperative prognostic risk-assessment in twin-twin transfusion syndrome.

OBJECTIVE: Prognostic assessment in twin-to-twin transfusion syndrome (TTTS) is ill-defined. The objective of this study is to define a perioperative prognostic score for TTTS treated by percutaneous laser coagulation. METHODS: Consecutive cases of TTTS treated by percutaneous fetoscopic laser coagulation over a 6-year period were reviewed. Twin survival at 28 days was considered using a 3-level polytomous variable defined by 0, 1, or 2 fatal events. A multivariate prognostic analysis with internal validation was conducted using gestational age at diagnosis, weight discordance, umbilical artery, and ductus venosus abnormalities in the donor and the recipient respectively, cervical length, selectivity of surgery, and transplacental approach. RESULTS: On the basis of 507 cases, the perinatal survival rate of 2 and 1 twin was 46.2% and 31.5%, respectively. Statistically significant factors included umbilical artery abnormalities in the donor, gestational age, and transplacental approach, but with different effects regarding survival of 0, 1, or 2 twins. A scoring chart was subsequently constructed together with a nomogram for both a preoperative and immediate post-operative prognostic assessment. CONCLUSION: Part of the prognosis can be anticipated by perioperative findings. Although further validation is required, the presented nomogram should help unify the prognostic assessment in TTTS.

Laser therapy for twin-to-twin transfusion syndrome (TTTS).

Monochorionic twins are subjected to specific complications which originate in either imbalance or abnormality of the single placenta serving two twins including twin-to-twin transfusion syndrome. The diagnosis is well established in overt clinical forms with the association of polyuric polyhydramnios and oliguric oligohydramnios. The best treatment of cases presenting before 26 weeks of gestion is fetoscopic laser ablation of the intertwin anastomoses on the chorionic plate. Although subjected to subtle variations, the core technique follows robust guidelines which could help understanding and acquiring the required skills and experience to perform this procedure. However appropriate and tailored hands-on training and appropriate perinatal set-up are critical not only for surgical management but also for the follow-up and management of related complications.

Specific complications of monochorionic twin pregnancies: twin-twin transfusion syndrome and twin reversed arterial perfusion sequence.

Monochorionic twins are subjected to specific complications which originate in either imbalance or abnormality of the single placenta serving two twins. This unequal placental sharing can cause complications including twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), selective intrauterine growth restriction or twin reversed arterial perfusion sequence (TRAP). Monochorionicity also makes the management of these specific complications as well as that of a severe malformation in one twin hazardous since the spontaneous death of one twin exposes the co-twin to a risk of exsanguination into the dead twin and its placenta. The latter is responsible for the death of the co-twin in up to 20% of the cases and in ischemic sequelae in about the same proportions in the survivors. Although the symptoms of all these complications are very different, the keystone of their management comes down to either surgical destruction of the inter-twin anastomoses on the chorionic plate when aiming at dual survival or selective and permanent occlusion of the cord of a severely affected twin aiming at protecting the normal co-twin. This can be best achieved by fetoscopic selective laser coagulation and bipolar forceps cord coagulation respectively.

Evaluation of the CHOP cardiovascular score as a prognostic predictor of outcome in twin-twin transfusion syndrome after laser coagulation of placental vessels in a prospective cohort.

OBJECTIVE: To investigate the prognostic value of cardiac function assessment by the previously reported CHOP (Children's Hospital of Philadelphia) cardiovascular score in twin-twin transfusion syndrome (TTTS). METHODS: All consecutive monochorionic pregnancies presenting with TTTS over a 24-month period were evaluated by preoperative echocardiography before percutaneous laser coagulation of chorionic vessels. Each of the 12 items of the CHOP score was evaluated prospectively and the cardiovascular score was categorized into stages using previously published cut-offs. The outcome considered for this study was neonatal survival of neither, one or both twins. RESULTS: In total, 215 pregnancies were enrolled. Due to technical issues, CHOP evaluation was incomplete in 16% of cases and follow-up was unavailable in 12%. Overall, there was a significant relationship between the CHOP score and the Quintero staging system, although this relationship was significantly reduced when parameters used in the Quintero system were removed from the CHOP score. Based upon neonatal survival, the CHOP score did not show any prognostic value regarding overall pregnancy outcome or individual recipient survival. CONCLUSION: Cardiac function assessment using the CHOP score is not of clinical use as a prognostic marker in TTTS. This suggests that cardiac function may not be of interest for preoperative staging when laser coagulation is the first-line treatment, other than to confirm the diagnosis of TTTS requiring surgery.

Profiling fetal cardiac function in twin-twin transfusion syndrome.

OBJECTIVES: Cardiomyopathy in the recipient twin is a marker of severity in twin-twin transfusion syndrome (TTTS), making it a potentially valuable tool for staging the disease. This study aimed to provide a quantitative description of cardiac function in the recipient twin. METHODS: Consecutive monochorionic pregnancies complicated with TTTS and treated by percutaneous laser coagulation underwent fetal echocardiography before surgery. An unsupervised classification analysis was conducted to identify groups of twins with similar cardiac profiles. The predictive value of the recipient twin's preoperative cardiac function based on these profiles was assessed, using perinatal death of at least one twin as the main outcome. The cardiac function profiles that we identified were compared with the current Quintero staging. RESULTS: A total of 107 pregnancies were included, with six of these lost to follow-up; 63/107 complete cases were available for multivariate description of the recipient's cardiac function. Three different preoperative cardiac profiles were identified with increasing right and left myocardial performance index, decreasing right and left shortening fraction, and increasing ductus venosus pulsatility index. Although the three groups represented progressive stages of the syndrome-related cardiomyopathy, no correlation was found with pregnancy outcome. Of Quintero Stage 1 cases, 55% showed significant alterations of cardiac function in the recipient twin. CONCLUSIONS: Progressive cardiomyopathy can be assessed quantitatively in the recipient twin and does not influence pregnancy outcome when fetoscopic laser coagulation is the first-line treatment. Compared with the current staging, cardiac profiling allows discrimination of cases with significant myocardial dysfunction.

[Prenatal management of uncomplicated monochorionic biamniotic pregnancies]. / Surveillance des grossesses gémellaires monochoriales biamniotiques non compliquées.

Monochorionic pregnancies accounts for only 20% of twins but are responsible for most of their morbidity and mortality. There is no randomized study evaluating management of monochorionic pregnancies. Based on expert opinion, it is recommended that monochorionic pregnancies should be followed-up by practionners working with specialized centers with expertise in monochorionic pregnancies. Optimal follow-up should include a bi-monthly ultrasound evaluation.

Emergency cerclage in cases of twin-to-twin transfusion syndrome with a short cervix at the time of surgery and relationship to perinatal outcome.

OBJECTIVE: To evaluate the impact of emergency cerclage on perinatal outcome in cases presenting with cervical length less than fifth centile at the time of laser surgery. POPULATION AND METHODS: Observational study of severe twin-to-twin transfusion syndrome (TTTS) cases diagnosed before 26 weeks of gestation and treated by fetoscopic selective laser coagulation (FSLC). Transvaginal sonographic measurement of cervical length prior to treatment identified cases with cervical length less than fifth centile (15 mm). Expectant management was followed in these cases prior to 2004, and a McDonald suture was performed immediately after laser surgery from 2004 onwards. Outcome was compared in patients with and without cerclage. RESULTS: Cervical length was a strong predictor for gestational age (GA) at delivery (p = 0.005). Mean GA at laser therapy was comparable [22.4 ( +/- 2.1) and 22.1 ( +/- 2) in patients with (n = 9) and without cerclage (n = 5), respectively, (p = 0.8)], whereas mean (SD) GA at delivery was 30.5 ( +/- 4.3) and 23.1 ( +/- 2.6) weeks in patients with and without cerclage, respectively, (p = 0.004). There were 16 (89%) and 4 (40%) surviving twins in cases with and without cerclage, respectively (p = 0.01). CONCLUSIONS: In TTTS treated by laser, cervical length before treatment is significantly associated with GA at delivery. In cases with cervix < 15 mm, emergency cerclage may prolong the pregnancy and allow for better outcome.

Three-dimensional sonographic assessment of fetal urine production before and after laser surgery in twin-to-twin transfusion syndrome.

OBJECTIVE: Fetal urine production in twin-to-twin transfusion syndrome (TTTS) reflects the hemodynamic imbalance between the donor and recipient twins but it has not been measured in this particular condition. The aim of this study was to measure fetal urine production using three-dimensional (3D) ultrasound in donor and recipient twins before and after laser treatment for TTTS and to correlate this with umbilical venous volume flow (UVVF). METHODS: Urine production rate (UPR) was measured using 3D ultrasound with Virtual Organ Computer-aided AnaLysis (VOCAL) in 106 cases of severe TTTS. The rotation angle was set at 30 degrees . The bladder volume was measured twice in each fetus (V(1) and V(2)), with an interval of 5-30 min between measurements, in order to calculate the UPR. When V(2) > V(1), UPR was calculated using the formula: V(2) - V(1) /time interval. Together with UPR, UVVF was measured before and after treatment. Both parameters were corrected for fetal weight. Inter- and intraobserver variability were calculated in 16 cases using the intraclass correlation coefficient. RESULTS: Before laser treatment, UPR was significantly higher in recipients compared with donors (median, 14.8 and 0 mL/h/kg, mean 23.8 and 2.3 mL/h/kg, respectively, P < 0.001), and UPR was positively correlated with UVVF in both twins. Following laser treatment (48 h later), UPR decreased to 9 mL/h/kg (P < 0.001) in recipients, while there was no change in donors. UVVF increased significantly from a median value of 92 to 132 mL/min/kg (P < 0.01) in donors and decreased significantly from 150 to 99 mL/min/kg (P < 0.001) in recipients. CONCLUSIONS: In TTTS UPR is correlated to UVVF and reflects the hemodynamic imbalance between donor and recipient twins. Following laser treatment, UPR decreases in recipients but is unaffected in donors. However, changes in UVVF occur in both twins. This suggests that although fetal renal function is driven by fetal hemodynamics, there may be a lag in the recovery of renal function in the donor twin.