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.

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.

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.

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.

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.

Subsequent pregnancy outcome after mid-trimester termination of pregnancy for preeclampsia.

BACKGROUND: In this study we determined the outcome of subsequent pregnancies after termination of pregnancy for preeclampsia, with the purpose of presenting data useful for counselling these women on future pregnancies. STUDY DESIGN: The cohort consisted of 131 women with a history of termination of pregnancy for preeclampsia. RESULTS: Data of 79 pregnancies were available for analysis, including 13 women with chronic hypertension and 16 women with thrombophilia. There were seven miscarriages (8.8%) and 72 ongoing pregnancies. Low-dose aspirin was prescribed for 64 women (89%). The mean gestational age at delivery was 356/7 ± 4 weeks with a mean birth weight of 2571 ± 938 g. Overall recurrence rate for preeclampsia was 29% at a mean gestational age of 32 weeks. Thirty-eight women had an uncomplicated pregnancy (53%). The women with chronic hypertension had the highest recurrence rate of 38%. Neonatal mortality was 4%. CONCLUSION: The course of subsequent pregnancies after mid-trimester termination for preeclampsia is uncomplicated in 53% with a recurrence rate for preeclampsia of 29%. The mean gestational age at delivery was 11 weeks later and birth weight 2000 g higher than in the index pregnancy.

Incidence and Causes of Intentional Fetal or Neonatal Demise in Twin-Twin Transfusion Syndrome.

INTRODUCTION: The aim of this study is to evaluate the incidence and causes of intentional fetal and neonatal demise in twin-twin transfusion syndrome (TTTS). MATERIAL AND METHODS: All TTTS pregnancies managed at our centre between 2000 and 2014 were included. We evaluated incidence and causes of intentional fetal/neonatal demise, defined as termination of pregnancy, selective fetal reduction, or withdrawal of neonatal intensive care. RESULTS: Intentional fetal/neonatal demise occurred in 9.8% (110/1,122) of fetuses and was due to termination of pregnancy (2.2%), selective fetal reduction (4.2%), or withdrawal of neonatal intensive care (3.4%). Reasons for termination of pregnancy included complications of laser treatment (72.0%), severe fetal anomaly (20.0%), and unwanted pregnancy (8.0%). Reasons for selective fetal reduction were technical difficulties to perform laser surgery (51.1%), fetal complications (38.3%), and parental preference for fetal reduction rather than laser treatment (10.6%). Reasons for withdrawal of neonatal intensive care treatment were severe cerebral injury (47.4%), severe pulmonary complications (15.8%), birth asphyxia (5.3%), multiple complications of TTTS and/or prematurity combined (21.1%), or other (10.5%). CONCLUSIONS: Intentional fetal or neonatal demise in TTTS occurs frequently and is often due to complications after laser surgery and/or severe (cerebral) injury in affected fetuses or neonates.

Renal function in neonates with twin-twin transfusion syndrome treated with or without fetoscopic laser surgery.

The aim of this study is to investigate the short-term renal function in neonates with twin-twin transfusion syndrome (TTTS), treated with fetoscopic laser surgery (laser group) or conservatively (non-laser group). Creatinine and urea levels and urine output were recorded in the first week after birth. Primary outcome was short-term renal dysfunction, defined as a creatinine level of >100 µmol/L during the first week postpartum. We evaluated 312 twins (laser group, n = 274; non-laser group, n = 38). Median creatinine and urea levels were lower in the laser group than in the non-laser group (71 versus 82 µmol/L, p = 0.002). Short-term renal dysfunction was lower in the laser group compared to the non-laser group (7.2 versus 34.4%, p < 0.001). Within the laser group, creatinine levels were significantly higher in the subgroup with incomplete laser surgery compared to twins with successful laser surgery (76 versus 69 µmol/L, p = 0.018). No differences were found between donors and recipients except for a higher incidence of oliguria in donors in the non-laser group on day 1. CONCLUSION: Short-term renal dysfunction occurs less frequently in TTTS twins treated with fetoscopic laser coagulation, particularly after complete surgery, suggesting that laser surgery may have a protective effect on renal function. What is Known: • Antenatally, donor twins in TTTS have severe oliguria due to chronic hypovolemia and impaired renal perfusion • Postnatally, donor twins may suffer from severe renal complications, particularly in TTTS twins treated conservatively. What is New: • The incidence of short-term renal failure in TTTS twins treated with complete laser surgery is low. • After incomplete laser surgery, the incidence of short-term renal dysfunction is increased.

Impact of Laser Power and Firing Angle on Coagulation Efficiency in Laser Treatment for Twin-Twin Transfusion Syndrome: An ex vivo Placenta Study.

OBJECTIVE: To assess the impact of laser power and firing angle on coagulation efficiency for closing placental anastomoses in the treatment of twin-twin transfusion syndrome. METHODS: We used an ex vivo blood-perfused human placenta model to compare time to complete coagulation using 30 vs. 50 W of neodymium-doped yttrium aluminum garnet laser power and using a firing angle of 90° vs. 45°. Placentas were perfused with pig blood at 5 mL/min. Differences were analyzed using independent-samples t test, Mann-Whitney U test, or χ2 test as appropriate. RESULTS: Coagulation took less time and energy using 50 W (n = 53) compared to 30 W (n = 52), 11 vs. 22 s (p < 0.001), and 557 vs. 659 J (p = 0.007). Perpendicular coagulation (n = 53) took less time and energy compared to a 45° angle (n = 21), 11 vs. 17 s (p = 0.004), and 557 vs. 871 J (p = 0.004). Bleeding complicated 2 (3%) measurements in the 50-W group, 5 (10%) in the 30-W group, and 3 (14%) in the 45° group. DISCUSSION: In a highly controlled model, a 50-W laser power setting was more energy efficient than 30 W in coagulating a placental vein. A more perpendicular laser firing angle resulted in more efficient coagulation. Furthermore, bleeding due to vessel wall disruption occurred more often with lower power and a more tangential approach.

Neurodevelopmental outcome at 2 years in twin-twin transfusion syndrome survivors randomized for the Solomon trial.

BACKGROUND: The preferred treatment for twin-twin transfusion syndrome is fetoscopic laser coagulation of inter-twin vascular anastomoses on the monochorionic placenta. Severe postoperative complications can occur when inter-twin vascular anastomoses remain patent including twin-anemia polycythemia sequence or recurrent twin-twin transfusion syndrome. To minimize the occurrence of residual anastomoses, a modified laser surgery technique, the Solomon technique, was developed in which the entire vascular equator is coagulated. In the Solomon randomized controlled trial (NTR1245), the Solomon technique was associated with a significant reduction in twin-anemia polycythemia sequence and recurrence of twin-twin transfusion syndrome when compared with the standard laser surgery technique. Although a significant improvement in perinatal outcome was shown after the Solomon technique, the clinical importance should also be ascertained with long-term follow-up evaluation of the surviving children. OBJECTIVE: The purpose of this study was to compare the long-term neurodevelopmental outcome in surviving children with twin-twin transfusion syndrome who were included in the Solomon randomized trial and treated with either the Solomon technique or standard laser surgery technique. STUDY DESIGN: Routine standardized follow-up evaluation in survivors, at least 2 years after the estimated date of delivery, was performed at 2 of the 5 centers that participated in the Solomon trial: Buzzi Hospital Milan (Italy) and Leiden University Medical Center (The Netherlands). The primary outcome of this follow-up study was survival without long-term neurodevelopmental impairment at age 2 years. Neurodevelopmental impairment was defined as cerebral palsy, cognitive and/or motor development score of <85, bilateral blindness, or deafness. Cognitive and motor development was evaluated with the use of Bayley-III. All analyses per fetus, neonate, or child were conducted with the generalized estimated equation module to account for the effect that observations between co-twins are not independent. RESULTS: The primary outcome (survival without neurodevelopmental impairment) was detected in 95 of 141 cases (67%) in the Solomon group and in 99 of 146 cases (68%) in the standard group (P = .92). Neurodevelopmental impairment in long-term survivors who were included for follow-up evaluation was detected in 12 of 107 cases (11%) in the Solomon and in 10 of 109 cases (9%) in the standard group (P = .61). Neurodevelopmental impairment was due to cerebral palsy in 1 case (1%; spastic unilateral) in the Solomon group and in 2 cases (2%; spastic unilateral and spastic bilateral) in the standard group (P = .58). Cognitive development <85 cases was detected in 2 of 105 children (2%) in the Solomon group and in 6 of 106 children (6%) in the standard group (P = .23). Motor development <85 occurred in 8 of 103 children (8%) in the Solomon group and 3 of 104 children (3%) in the standard group (P = .23). CONCLUSION: We found no difference in survival without neurodevelopmental impairment between the Solomon and standard laser techniques. In view of the reduction of short-term complications and the absence of increased adverse long-term effects, these data support the use of the Solomon technique in the treatment of twin-twin transfusion syndrome.

Comparison Between Monochorionic and Dichorionic Placentas With Special Attention to Vascular Anastomoses and Placental Share.

Placental vascular anastomoses in twins lead to a shared circulation and may subsequently enable the development of severe complications such as twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). The presence of vascular anastomoses has frequently and systematically been studied in monochorionic (MC) placentas, but only rarely in dichorionic (DC) placentas. The aim of this study was to compare the prevalence of vascular anastomoses and evaluate the sharing discordance in MC and DC placentas. All consecutive placentas of MC and DC twins delivered at the Leiden University Medical Center (the Netherlands) and Medical University of Warsaw (Poland) from 2012 to 2015 were routinely injected with colored dye and included in the study. We excluded twin pregnancies treated with fetoscopic laser surgery. A total of 258 placentas were analyzed in this study, including 134 MC placentas and 124 DC placentas. Vascular anastomoses were present in 99% (133/134) of MC placentas and 0% of DC placentas (p < .01). Placental share discordance between MC twins was significantly larger compared to DC twins, 19.8 (interquartile range [IQR] 8.1-33.3) and 10.8 (IQR 6.2-19.0), respectively (p < .01). Vascular anastomoses associated complications occurred in 16% (22/134) MC twins. Our findings show that vascular anastomoses are almost ubiquitous in MC placentas, but non-existent in DC placentas. In addition, unequal placental sharing appears to be more common in MC than in DC placentas.

Long-Term Neurodevelopmental Outcome in Survivors of Twin-to-Twin Transfusion Syndrome.

Twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic (MC) twin pregnancies associated with high perinatal mortality and morbidity rates. Management in TTTS is a major challenge for obstetricians and neonatologists. Twins with TTTS are often born prematurely after an extremely distressing and highly hazardous fetal period. Follow-up studies report varying rates of cerebral palsy (CP) and long-term neurodevelopmental impairment (NDI). This review discusses the latest findings on the long-term outcome of TTTS survivors, possible risk factors for long-term impairment, and provides recommendations for future research.

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.

Hemoglobin Differences in Uncomplicated Monochorionic Twins in Relation to Birth Order and Mode of Delivery.

AIM: To determine the differences in hemoglobin (Hb) levels in the first 2 days after birth in uncomplicated monochorionic twins in relation to birth order and mode of delivery. METHODS: All consecutive uncomplicated monochorionic pregnancies with two live-born twins delivered at our center were included in this retrospective study. We recorded Hb levels at birth and on day 2, and analyzed Hb levels in association with birth order, mode of delivery, and time interval between delivery of twin 1 and 2. RESULTS: A total of 290 monochorionic twin pairs were analyzed, including 171 (59%) twins delivered vaginally and 119 (41%) twins born by cesarean section (CS). In twins delivered vaginally, mean Hb levels at birth and on day 2 were significantly higher in second-born twins compared to first-born twins: 17.8 versus 16.1 g/dL and 18.0 versus 14.8 g/dL, respectively (p < .01). Polycythemia was detected more often in second-born twins (12%, 20/166) compared to first-born twins (1%, 2/166; p < .01). Hb differences within twin pairs delivered by CS were not statistically or clinically significant. We found no association between inter-twin delivery time intervals and Hb differences. CONCLUSIONS: Second-born twins after vaginal delivery have higher Hb levels and more often polycythemia than their co-twin, but not when born by CS.

Increased Risk Of Early-Onset Neonatal Sepsis After Laser Surgery For Twin-to-Twin Transfusion Syndrome.

OBJECTIVE: To investigate the occurrence of early-onset neonatal sepsis (EOS) in twin-twin transfusion syndrome (TTTS) managed with laser surgery. STUDY DESIGN: We performed a prospective cohort study of all consecutive TTTS cases treated with laser surgery (TTTS group) delivered at the Leiden University Medical Center. We recorded the occurrence of EOS, defined as a positive blood culture ≤72 hours postpartum (proven sepsis) or administration of a full course of antibiotics due to risk factors or signs of sepsis, in the absence of a positive blood culture (suspected sepsis). Perinatal variables in the TTTS group were compared with uncomplicated monochorionic twins (no-TTTS group). A multivariate model was generated, examining the association between EOS and gestational age at birth, interval between laser surgery and birth, anterior placenta, laser period (first study period: 2002-2008; second study period: 2009-2015), and preterm premature rupture of membranes (PPROM). RESULTS: The rates of combined suspected and proven EOS in the TTTS group and no-TTTS group were 16% (68/416) and 10% (55/542), respectively (relative ratio [RR] 1.74, 95% confidence interval [CI] 1.19-2.55). Multivariate analysis showed that EOS in the TTTS group was independently associated with lower gestational age at birth (odds ratio [OR] 0.75, 95% CI 0.63-0.88), first study period (OR 2.25, 95% CI 1.08-4.67) and PPROM (OR 2.47, 95% CI 1.28-4.75). CONCLUSION: The rate of EOS in the TTTS group is low, but increased compared to the no-TTTS group. EOS in TTTS is independently associated with premature delivery, earlier laser period, and PPROM.

From Postpartum Haemorrhage Guideline to Local Protocol: A Study of Protocol Quality.

Objective Postpartum hemorrhage (PPH) has a continuously rising incidence worldwide, suggesting suboptimal care. An important step in optimizing care is the translation of evidence-based guidelines into comprehensive hospital protocols. However, knowledge about the quality of these protocols is lacking. The objective of this study was to evaluate the quality of PPH-protocols on structure and content in the Netherlands. Methods We performed an observational multicenter study. Eighteen PPH-protocols from 3 University Hospitals (UH), 8 Teaching Hospitals (TH) and 7 Non-Teaching hospitals (NTH) throughout the Netherlands were acquired. The structure of the PPH-protocols was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) Instrument. The content was appraised using previously developed quality indicators, based on international guidelines and Advance-Trauma-Life-Support (ATLS)-based course instructions. Results The quality of the protocols for postpartum hemorrhage for both structure and content varied widely between different hospitals, but all of them showed room for improvement. The protocols scored mainly below average on the different items of the AGREE-II instrument (8 of the 10 items scored <4 on a 1-7 scale). Regarding the content, adoption of guideline recommendations in protocols was 46 %. In addition, a timely indication of 'when to perform' a recommendation was lacking in three-fourths of the items. Conclusion This study shows that the quality of the PPH-protocols for both structure and content in the Netherlands is suboptimal. This makes adherence to the guideline and ATLS-based course instructions difficult.