Intertwin Membrane Perforation and Umbilical Cord Entanglement after Laser Surgery for Twin-Twin Transfusion Syndrome: Prevalence, Risk Factors, and Outcome.

INTRODUCTION: Perforation of the intertwin membrane can occur as a complication of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). Data on the occurrence and the risk of subsequent cord entanglement are limited. The objective of this study was to assess the prevalence, risk factors and outcome of intertwin membrane perforation, and cord entanglement after laser surgery for TTTS. METHODS: In this multicenter retrospective study, we included all TTTS pregnancies treated with laser surgery in two fetal therapy centers, Shanghai (China) and Leiden (the Netherlands) between 2002 and 2020. We evaluated the occurrence of intertwin membrane perforation and cord entanglement after laser, based on routine fortnightly ultrasound examination and investigated the risk factors and the association with adverse short- and long-term outcomes. RESULTS: Perforation of the intertwin membrane occurred in 118 (16%) of the 761 TTTS pregnancies treated with laser surgery and was followed by cord entanglement in 21% (25/118). Perforation of the intertwin membrane was associated with higher laser power settings, 45.8 Watt versus 42.2 Watt (p = 0.029) and a second fetal surgery procedure 17% versus 6% (p < 0.001). The group with intertwin membrane perforation had a higher rate of caesarean section (77% vs. 31%, p < 0.001) and a lower gestational age at birth (30.7 vs. 33.3 weeks of gestation, p < 0.001) compared to the group with an intact intertwin membrane. Severe cerebral injury occurred more often in the group with intertwin membrane perforation, 9% (17/185) versus 5% (42/930), respectively (p = 0.019). Neurodevelopmental outcome at 2 years of age was similar between the groups with and without perforation of the intertwin membrane and between the subgroups with and without cord entanglement. CONCLUSION: Perforation of the intertwin membrane after laser occurred in 16% of TTTS cases treated with laser and led to cord entanglement in at least 1 in 5 cases. Intertwin membrane perforation was associated with a lower gestational age at birth and a higher rate of severe cerebral injury in surviving neonates.

Neonatal Outcome in Twin-to-Twin Transfusion Syndrome Not Treated with Fetoscopic Laser Surgery.

The aim of this study was to describe the neonatal management and outcome in monochorionic twins with twin-to-twin transfusion syndrome (TTTS) not treated with fetoscopic laser surgery. All consecutive live-born neonates with TTTS managed at our center between 2002 and 2021 were included in this retrospective study. Neonatal outcome was assessed in 44 twin pairs with TTTS not treated with laser (nonlaser group) compared to a control group of 88 twin pairs with TTTS successfully treated with laser (laser group), matched for gestational age at birth. Primary outcome was adverse neonatal outcome, a composite outcome including neonatal mortality or severe neonatal morbidity. The incidence of adverse neonatal outcome in the nonlaser group and laser group was 30% (26/88) and 11% (19/176), respectively (relative risk = 3.46, 95% CI [1.79, 6.71]). In the nonlaser group, 11% had necrotizing enterocolitis (vs. 2% in the laser group) and 24% had hypotension (vs. 10% in the laser group). Recipients in the nonlaser group had, compared to recipients in the laser group, significantly more severe cerebral injury (18% vs. 5%) and more polycythemia at birth (21% vs. 1%). Donors in the nonlaser group had, compared to donors in the laser group, more severe growth restriction (71% vs 42%), renal failure (11% vs 1%), and anemia at birth (25% vs. 7%). Thus, the risk for neonatal mortality and/or severe morbidity is three-fold higher in TTTS not treated with laser than in TTTS treated with laser, which highlights the fact that these neonates with TTTS are very sick at birth, requiring accurate and prompt intensive treatment.

Neurodevelopmental Trajectories of Preterm Born Survivors of Twin-Twin Transfusion Syndrome: From Birth to 5 Years of Age.

OBJECTIVE: To investigate the neurodevelopmental outcome at age 2 and 5 years in survivors of twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser surgery and born premature and/or small for gestational age. STUDY DESIGN: At 2 and 5 years of age, standardized neurologic, motor, and cognitive assessments were performed by a neonatologist, a pediatric physical therapist, and a psychologist. Behavior was assessed using a validated questionnaire completed by parents. RESULTS: Neurodevelopmental assessment at both time points was available for 73 survivors of TTTS. Mild to moderate neurodevelopmental impairment (NDI) was detected in 34% of survivors (25 of 73) at 5 years, compared with 25% (18 of 73) at 2 years (P = .178). Severe NDI was observed in 12% (9 of 73) at 5 years and in 3% (2 of 73) at 2 years (P = .035). Mean cognitive score was lower at the 5-year follow-up (90.7 ± 12.3 vs 95.6 ± 13.1 at 2 years; P = .001), and more children were diagnosed with mild cognitive impairment at 5 years (29% vs 11% at 2 years; P = .007). When comparing individual outcomes at both time points, 35% (25 of 71) moved from a normal outcome or mild to moderate impairment at 2 years toward more severe impairment at 5 years. CONCLUSIONS: A high rate of mild to moderate cognitive impairment and severe NDI at age 5 years was not identified at age 2 years. Our data highlight the importance of longitudinal follow-up of survivors of TTTS beyond age 2 years and emphasize the precautions that should be taken when diagnosing an absence of impairment before school age.

Large Hemoglobin Differences at Birth in Monochorionic Twins with a Placental Chorangioma and Delayed Cord Clamping.

We report a case of a monochorionic diamniotic twin with an uncomplicated pregnancy, but with an unexpected large intertwin hemoglobin (Hb) difference at birth. Twin 1 was delivered vaginally and had an uneventful neonatal course. The umbilical cord of Twin 1 was clamped approximately 5 min after birth. After the birth of Twin 1, Twin 2 developed severe bradycardia and showed limited cardiac output on ultrasound, for which an emergency cesarean section was performed. A full blood count revealed an Hb of 20.1 g/dL for Twin 1 and 10.2 g/dL for Twin 2 (intertwin difference 9.9 g/dL). Reticulocyte counts were similar, 40‰ and 38‰, respectively. Placental examination revealed 10 vascular anastomoses, including one arterio-arterial anastomosis with a diameter of 1.4 mm. Additionally, a large chorangioma was present on the placental surface of Twin 2. There was no color difference on the maternal side of the placenta. Based on the reticulocyte count ratio and the placental characteristics, twin anemia polycythemia sequence was ruled out as the cause of the large intertwin Hb difference. In this report, we discuss the various potential causes that could explain the large intertwin Hb difference including the role of delayed cord clamping in Twin 1, and the role of a large chorangioma, which may have attracted blood from the fetal circulation of Twin 2.

Consensus on Training and Assessment of Competence in Performing Chorionic Villus Sampling and Amniocentesis: An International Delphi Survey.

INTRODUCTION: The aim of this study was to obtain expert consensus on the content of a curriculum for learning chorionic villus sampling (CVS) and amniocentesis (AC) and the items of an assessment tool to evaluate CVS and AC competence. METHODS: We used a 3-round iterative Delphi process. A steering committee supervised all processes. Seven international collaborators were identified to expand the breadth of the study internationally. The collaborators invited fetal medicine experts to participate as panelists. In the first round, the panelists suggested content for a CVS/AC curriculum and an assessment tool. The steering committee organized and condensed the suggested items and presented them to the panelists in round 2. In the second round, the panelists rated and commented on the suggested items. The results were processed by the steering committee and presented to the panelists in the third round, where final consensus was obtained. Consensus was defined as support by more than 80% of the panelists for an item. RESULTS: Eighty-six experts agreed to participate in the study. The panelists represented 16 countries across 4 continents. The final list of curricular content included 12 theoretical and practical items. The final assessment tool included 11 items, systematically divided into 5 categories: pre-procedure, procedure, post-procedure, nontechnical skills, and overall performance. These items were provided with behavioral scale anchors to rate performance, and an entrustment scale was used for the final overall assessment. CONCLUSION: We established consensus among international fetal medicine experts on content to be included in a CVS/AC curriculum and on an assessment tool to evaluate CVS/AC skills. These results are important to help transition current training and assessment methods from a time- and volume-based approach to a competency-based approach which is a key step in improving patient safety and outcomes for the 2 most common invasive procedures in fetal medicine.

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.

Fetoscopic myelomeningocoele closure: Is the scientific evidence enough to challenge the gold standard for prenatal surgery?

Since the completion of the Management of Myelomeningocoele Study, maternal-fetal surgery for spina bifida has become a valid option for expecting parents. More recently, multiple groups are exploring a minimally invasive approach and recent outcomes have addressed many of the initial concerns with this approach. Based on a previously published framework, we attempt to delineate the developmental stage of the surgical techniques. Furthermore, we discuss the barriers of performing randomized controlled trials comparing two surgical interventions and suggest that data collection through registries is an alternative method to gather high-grade evidence.

Intrauterine fetoscopic laser surgery versus expectant management in stage 1 twin-to-twin transfusion syndrome: an international randomized trial.

BACKGROUND: Selective fetoscopic laser coagulation of the intertwin anastomotic chorionic vessels is the first-line treatment for twin-twin transfusion syndrome. However, in stage 1 twin-twin transfusion syndrome, the risks of intrauterine surgery may be higher than those of the natural progression of the condition. OBJECTIVE: This study aimed to compare immediate surgery and expectant follow-up in stage 1 twin-twin transfusion syndrome. STUDY DESIGN: We conducted a multicentric randomized trial, which recruited from 2011 to 2018 with a 6-month postnatal follow-up. The study was conducted in 9 fetal medicine centers in Europe and the Unites States. Asymptomatic women with stage 1 twin-twin transfusion syndrome between 16 and 26 weeks' gestation, a cervix of >15 mm, and access to a surgical center within 48 hours of diagnosis were randomized between expectant management and immediate surgery. In patients allocated to immediate laser treatment, percutaneous laser coagulation of anastomotic vessels was performed within 72 hours. In patients allocated to expectant management, a weekly ultrasound follow-up was planned. Rescue fetoscopic coagulation of anastomoses was offered if the syndrome worsened as seen during a follow-up, either because of progression to a higher Quintero stage or because of the maternal complications of polyhydramnios. The primary outcome was survival at 6 months without severe neurologic morbidity. Severe complications of prematurity and maternal morbidity were secondary outcomes. RESULTS: The trial was stopped at 117 of 200 planned inclusions for slow accrual rate over 7 years: 58 women were allocated to expectant management and 59 to immediate laser treatment. Intact survival was seen in 84 of 109 (77%) expectant cases and in 89 of 114 (78%) (P=.88) immediate surgery cases, and severe neurologic morbidity occurred in 5 of 109 (4.6%) and 3 of 114 (2.6%) (P=.49) cases in the expectant and immediate surgery groups, respectively. In patients followed expectantly, 24 of 58 (41%) cases remained stable with dual intact survival in 36 of 44 (86%) cases at 6 months. Intact survival was lower following surgery than for the nonprogressive cases, although nonsignificantly (78% and 71% following immediate and rescue surgery, respectively). CONCLUSION: It is unlikely that early fetal surgery is of benefit for stage 1 twin-twin transfusion syndrome in asymptomatic pregnant women with a long cervix. Although expectant management is reasonable for these cases, 60% of the cases will progress and require rapid transfer to a surgical center.

Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases.

BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7-28.8; range, 15.1-35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P=.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4-27.8; P=.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1-45.5; P=.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0-146.4; P=.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7-0.9; P=.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4-43.3; P=.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5-2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins.

Post-Laser Twin Anemia Polycythemia Sequence: Diagnosis, Management, and Outcome in an International Cohort of 164 Cases.

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7-28, range: 1-119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6-33.7; range: 19.0-41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients (p < 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%; 51/118) and recipients (37%; 54/145), p = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, p = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1-8.3, p < 0.001), and GA at birth (OR = 0.8, 95%CI 0.7-0.9, p = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3-1.7, p < 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.

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.

Twin-twin transfusion syndrome in the era of fetoscopic laser surgery: antenatal management, neonatal outcome and beyond.

Introduction: Twin-twin transfusion syndrome (TTTS) is a devastating complication of monochorionic twin pregnancy and remains a major challenge for worldwide fetal medicine specialists. In TTTS, intertwin transfusion through vascular anastomoses in the shared placenta leads to severe hemodynamic imbalance. This review summarizes the current knowledge of TTTS.Areas covered: The most recent insights concerning the management of TTTS, as well as fetal and neonatal complications are described. Relevant articles were selected based on a Pubmed search using the keywords below. Understanding of the underlying pathophysiology has improved greatly as a result of placental injection studies. Advancements in antenatal management have led to increased perinatal survival and a decreased incidence of neonatal complications, including brain injury and neurodevelopmental impairment.Expert opinion: Further opportunities for improvement comprise technological innovations in laser procedures and the prevention of preterm rupture of membranes with subsequent prematurity. A noninvasive treatment such as high-intensity focused ultrasound (HIFU) seems to hold promise for the future treatment of TTTS. Fetal MRI studies are important to improve our understanding of fetal brain injury and should relate their findings to long-term neurodevelopment. International collaboration and centralization of care are of paramount importance to ensure the best care for our patients.

Long-Term Neurodevelopmental Outcome in Twin-to-Twin Transfusion Syndrome: Is there still Room for Improvement?

Despite many developments in its management, twin-to-twin transfusion syndrome (TTTS) remains an important risk factor for long-term neurodevelopmental impairment (NDI). Our objective was to compare the incidence of severe NDI in a recent cohort of TTTS survivors, treated with laser surgery from 2011 to 2014, with a previous cohort treated from 2008 to 2010. Neurological, cognitive, and motor development were assessed at two years of age. We determined risk factors associated with Bayley-III scores. Severe NDI occurred in 7/241 (3%) survivors in the new cohort compared to 10/169 (6%) in the previous cohort (p = 0.189). Disease-free survival (survival without severe impairment) did not significantly differ. Low birth weight and being small for gestational age (SGA) were independently associated with lower cognitive scores (both p < 0.01). Severe cerebral injury was related to decreased motor scores (B = -14.10; 95% CI -3.16, -25.04; p = 0.012). Children with severe NDI were born ≥32 weeks' gestation in 53% of cases and had no evidence of cerebral injury on cranial ultrasound in 59% of cases. Our results suggest that improvement in outcome of TTTS has reached a plateau. Low birth weight, SGA, and cerebral injury are risk factors for poor neurodevelopmental outcome. Neither gestational age above 32 weeks nor the absence of cerebral injury preclude severe NDI.

Twin-Twin Transfusion Syndrome with Anemia-Polycythemia: Prevalence, Characteristics, and Outcome.

The aim of this study was to estimate the prevalence of co-existing anemia-polycythemia (AP) in twin pregnancies with twin-twin transfusion syndrome (TTTS) prior to laser surgery, and to evaluate the characteristics and outcomes in TTTS twins with and without AP. All TTTS cases treated with laser between 2001 and 2019 were retrospectively reviewed for the presence of AP before surgery. AP was defined as delta middle cerebral artery-peak systolic velocity > 0.5 multiples of the median. The primary outcome was a composite of perinatal survival and severe neurodevelopmental impairment (NDI). Secondary outcomes included procedure-related characteristics, severe neonatal morbidity, and disease-free survival. In total, 66% (461/696) of TTTS twin pregnancies were eligible for analysis. AP was detected in 15% (70/461) of the TTTS twins prior to laser surgery. Gestational age at laser was higher in the TTTS+AP group compared to the TTTS-only group-21.0 weeks (interquartile rage (IQR): 18.8-24.0) versus 19.3 weeks (IQR: 17.3-21.9), respectively (p < 0.0001). Fewer placental anastomoses were detected in the TTTS+AP group than in the TTTS-only group-five (IQR: 4-6) versus six (IQR: 5-8), respectively (p < 0.0001). Perinatal survival was 77% (599/782) in the TTTS-only group and 83% (118/142) in the TTTS+AP group (p = 0.130). Severe NDI was 8% (28/370) in TTTS-only and 3% (2/74) in TTTS+AP. TTTS-only twins showed more severe neonatal morbidity than twins with TTTS+AP-23% (132/575) versus 11% (13/115), respectively (p = 0.005). Disease-free survival was lower in the TTTS-only group compared to the TTTS+AP group-62% (341/548) versus 73% (72/98), respectively (p = 0.046). Thus, AP complicates 15% of TTTS twins prior to laser. TTTS+AP twins show a different placental angioarchitecture, a later time of onset of the disease, and a more favorable outcome.

Twin-Twin Transfusion Syndrome with and without Selective Fetal Growth Restriction Prior to Fetoscopic Laser Surgery: Short and Long-Term Outcome.

As twin-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are both prevalent complications of monochorionic (MC) twin pregnancies, its coexistence is not uncommon. The aim of this study is to evaluate the short and long-term outcome in TTTS with and without sFGR prior to fetoscopic laser coagulation. All TTTS cases treated with laser surgery at our center between 2001-2019 were retrospectively reviewed for the presence of sFGR, defined as an estimated fetal weight (EFW) <10th centile. We compared two groups: TTTS-only and TTTS + sFGR. Primary outcomes were perinatal survival and long-term severe neurodevelopmental impairment (NDI). Of the 527 pregnancies eligible for analysis, 40.8% (n = 215) were categorized as TTTS-only and 59.2% (n = 312) as TTTS + sFGR. Quintero stage at presentation was higher in the TTTS + sFGR group compared to the TTTS-only group (57% compared to 44% stage III). Separate analysis of donors showed significantly lower perinatal survival for donors in the TTTS + sFGR group (72% (224/311) compared to 81% (173/215), p = 0.027). Severe NDI at follow-up in long-term survivors in the TTTS-only and TTTS + sFGR group was present in 7% (13/198) and 9% (27/299), respectively (p = 0.385). Both sFGR (OR 1.5;95% CI 1.1-2.0, p = 0.013) and lower gestational age at laser (OR 1.1;95% CI 1.0-1.1, p = 0.001) were independently associated with decreased perinatal survival. Thus, sFGR prior to laser surgery is associated with a more severe initial presentation and decreased donor perinatal survival. The long-term outcome was not affected.

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.

What is the impact of placental tissue damage after laser surgery for twin-twin transfusion syndrome? A secondary analysis of the Solomon trial.

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

Antenatal management of twin-twin transfusion syndrome and twin anemia-polycythemia sequence.

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

Solomon Technique Versus Selective Coagulation for Twin-Twin Transfusion Syndrome.

Monochorionic twin pregnancies can be complicated by twin-to-twin transfusion syndrome (TTTS). The best treatment option for TTTS is fetoscopic laser coagulation of the vascular anastomoses between donor and recipient. After laser therapy, up to 33% residual anastomoses were seen. These residual anastomoses can cause twin anemia polycythemia sequence (TAPS) and recurrent TTTS. In order to reduce the number of residual anastomoses and their complications, a new technique, the Solomon technique, where the whole vascular equator will be coagulated, was introduced. The Solomon technique showed a reduction of recurrent TTS compared to the selective technique. The incidence of recurrent TTTS after the Solomon technique ranged from 0% to 3.9% compared to 5.3-8.5% after the selective technique. The incidence of TAPS after the Solomon technique ranged from 0% to 2.9% compared to 4.2-15.6% after the selective technique. The Solomon technique may improve dual survival rates ranging from 64% to 85% compared to 46-76% for the selective technique. There was no difference reported in procedure-related complications such as intrauterine infection and preterm premature rupture of membranes. The Solomon technique significantly reduced the incidence of TAPS and recurrent TTTS and may improve survival and neonatal outcome, without identifiable adverse outcome or complications; therefore, the Solomon technique is recommended for the treatment of TTTS.