Background: Monochorionic twin pregnancies are at high risk of adverse outcomes, but it is not possible to predict which pregnancies will develop complications. The aim of the study was to evaluate, in monochorionic twin pregnancies, whether first-trimester ultrasound (nuchal translucency [NT], crown-rump length [CRL]), and maternal serum biomarkers (alpha-fetoprotein [AFP], soluble fms-like tyrosine kinase-1 [sFlt-1] and placental growth factor [PlGF]), are prognostic factors for fetal adverse outcome composite, twin-twin transfusion syndrome (TTTS), growth restriction, and intrauterine fetal death (IUFD). Methods: A cohort study of 177 monochorionic diamniotic twin pregnancies. Independent prognostic ability of each factor was assessed by multivariable logistic regression, adjusting for standard prognostic factors. Factors were analysed as continuous data; thus, the reported ORs relate to either 1% change in NT or CRL inter-twin percentage discordance or one unit of measure in each serum biomarker. Results: The odds of the fetal adverse outcome composite were significantly associated with increased NT inter-twin percentage discordance (adjusted OR 1.03 [95% CI 1.01, 1.06]) and CRL inter-twin percentage discordance (adjusted OR 1.17 [95% CI 1.07, 1.29]). TTTS was significantly associated with increased NT discordance (adjusted OR 1.06 [95% CI 1.03, 1.10]) and decreased PlGF (adjusted OR 0.42 [95% CI 0.19, 0.93]). Antenatal growth restriction was significantly associated with increased CRL discordance (adjusted OR 1.20 [95% CI 1.08, 1.34]). Single and double IUFD were associated with decreased PlGF (adjusted OR 0.34 [95% CI 0.12, 0.98]) and (adjusted OR 0.18 [95%CI 0.05, 0.58]) respectively. Conclusions: This study has identified potential individual prognostic factors in the first trimester (fetal biometric and maternal serum biomarkers) that show promise but require further robust evaluation in a larger, prospective series of MC twin pregnancies, so that their usefulness both individually and in combination can be defined. Trial registration: ISRCTN 13114861 (retrospectively registered).

OBJECTIVES: To explore the outcome of monochorionic monoamniotic (MCMA) twin pregnancies affected by twin-to-twin transfusion syndrome (TTTS). METHODS: MEDLINE and EMBASE databases were searched for studies reporting the outcome of MCMA twin pregnancies complicated by TTTS. The primary outcome was intrauterine death (IUD); secondary outcomes were miscarriage, single IUD, double IUD, neonatal death (NND), perinatal death (PND), survival of at least one twin, survival of both twins and preterm birth (PTB) before 32 weeks' gestation. Outcomes were assessed in MCMA twins affected by TTTS not undergoing intervention and in those treated with amniodrainage, laser therapy or cord occlusion. Subgroup analysis was performed including cases diagnosed before 24 weeks. Random-effects meta-analysis of proportions was used to analyze the data. RESULTS: Fifteen cohort studies, including 888 MCMA twin pregnancies, of which 44 were affected by TTTS, were included in the review. There was no randomized trial comparing the different management options in MCMA twin pregnancies complicated by TTTS. In cases not undergoing intervention, miscarriage occurred in 11.0% of fetuses, while the incidence of IUD, NND and PND was 25.2%, 12.2% and 31.2%, respectively. PTB complicated 50.5% of these pregnancies. In cases treated by laser surgery, the incidence of miscarriage, IUD, NND and PND was 19.6%, 27.4%, 7.4% and 35.9%, respectively, and the incidence of PTB before 32 weeks' gestation was 64.9%. In cases treated with amniodrainage, the incidence of IUD, NND and PND was 31.3%, 13.5% and 45.7% respectively, and PTB complicated 76.2% of these pregnancies. Analysis of cases undergoing cord occlusion was affected by the very small number of included cases. Miscarriage occurred in 19.2%, while there was no case of IUD or NND of the surviving twin. PTB before 32 weeks occurred in 50.0% of these cases. CONCLUSIONS: MCMA twin pregnancies complicated by TTTS are at high risk of perinatal mortality and PTB. Further studies are needed in order to elucidate the optimal type of prenatal treatment in these pregnancies. Copyright (c) 2019 ISUOG. Published by John Wiley & Sons Ltd.

OBJECTIVE: To assess the role of first- and early second-trimester markers in the prediction of twin-to-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies. METHODS: Electronic databases MEDLINE, EMBASE and ClinicalTrials.gov were searched from inception to April 2014, using the MeSH term 'fetofetal transfusion' in combination with phrases 'predictive value', 'sensitivity', 'specificity', 'false positive', 'false negative', 'screening', 'accuracy' and 'ROC'. Study quality was assessed using the PRISMA guidelines and QUADAS-2 tool. A meta-analysis was planned for the following predictive factors: intertwin nuchal translucency (NT) discrepancy; NT > 95(th) percentile in at least one twin; intertwin crown-rump length (CRL) discrepancy as a percentage of the larger CRL; abnormal ductus venosus (DV) flow in at least one twin. The outcome assessed was TTTS, defined according to the presence of a twin oligohydramnios-polyhydramnios sequence. The diagnostic performance of the predictive factors was evaluated for each included study. RESULTS: The electronic search identified 152 records, of which 23 were assessed in full for eligibility. We identified 13 eligible studies that reported the predictive accuracy of ultrasound parameters, measured before 16 weeks, for the development of TTTS, including a total of 1991 pregnancies, of which 323 developed TTTS. An increased risk of TTTS was associated with: intertwin NT discrepancy (positive likelihood ratio (LR+), 1.92 (95% CI, 1.25-2.96); negative likelihood ratio (LR-), 0.65 (95% CI, 0.50-0.84)); NT > 95(th) percentile (LR+, 2.63 (95% CI, 1.51-4.58); LR-, 0.85 (95% CI, 0.75-0.96)); CRL discrepancy > 10% (LR+, 1.80 (95% CI, 1.05-3.07); LR-, 0.92 (95% CI, 0.81-1.05)); abnormal DV flow (LR+, 4.77 (95% CI, 1.33-17.04; LR-, 0.49 (95% CI, 0.17-1.41)). The highest sensitivities were observed for intertwin NT discrepancy (52.8% (95% CI, 43.8-61.7%)) and abnormal DV flow (50.0% (95% CI, 33.4-66.6%)). CONCLUSION: Monochorionic twin pregnancies with intertwin NT discrepancy, NT > 95(th) percentile, intertwin CRL discrepancy > 10% or abnormal DV flow on first-trimester ultrasound examination are at significantly increased risk of developing TTTS. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd.

Sonographic evaluation of the fetal venous system in normal and abnormal conditions has drawn increasing interest in recent years. Whereas the assessment of the fetal heart and the related arteries is standardized using well-defined planes, the fetal venous system is still lacking a systematic approach. In this article we present a novel sonographic algorithm for a systematic examination of the fetal venous system using six planes of transverse and oblique views of the fetal abdomen and chest. These planes, using two-dimensional and color Doppler, enable a targeted demonstration of the typical veins to include the umbilical vein, ductus venosus, portal veins, hepatic veins, inferior vena cava, azygos vein, pulmonary veins, coronary sinus, superior vena cava and brachiocephalic vein. We postulate that integrating such a sequential stepwise algorithm for the evaluation of the venous system into targeted fetal cardiac imaging may improve the detection of isolated and combined anomalies of the fetal systemic and pulmonary veins.

The accuracy of in-vivo detection of arterio-arterial anastomoses (AAA) in monochorionic (MC) twins and its predictive value for twin-twin transfusion syndrome (TTTS) was assessed in 105 consecutive MC twins scanned at fortnightly intervals. AAA were sought using spectral and colour energy Doppler and ultrasound findings were compared with placental injection studies. AAA were identified in vivo in 59 (56%) pregnancies and at injection study in 68 (65%). The overall sensitivity and specificity was 85 and 97.3% respectively for the detection of AAA. Detection rates were higher at later gestations, with anterior placentae and with larger diameter AAA. The median insonation time to detect an AAA was 10 min (range 1-30). Where an AAA was identified, 15% of pregnancies (nine of 59) developed TTTS compared to 61% (28 of 46) when no AAA was seen (odds ratio 8.6). We conclude that AAA can be detected in vivo with high sensitivity and specificity without undue prolongation of scanning times and have a role in risk stratification in the antenatal assessment of MC twins.

OBJECTIVES: To establish gestational age-specific reference ranges for amniotic fluid measurements in monochorionic diamniotic twin pregnancies, to compare them with previously reported singleton and twin reference ranges and to examine the rationale for using a gestational age-dependent cut-off to define polyhydramnios in twin-twin transfusion syndrome, as is the practice in most European centers. METHODS: We retrospectively evaluated amniotic fluid volume in 32 monochorionic diamniotic twin pregnancies that were followed longitudinally at 2-week intervals from the first trimester until birth. Amniotic fluid volume was assessed by measuring the deepest vertical pocket in both amniotic sacs. We used multilevel modeling to estimate the gestational age-specific reference ranges for deepest vertical pocket measurements. RESULTS: Based on 429 observations in 64 fetuses, we constructed gestational age-specific reference ranges from 11 weeks until term. The deepest pocket increased from the first trimester to reach a maximum at 26 weeks, followed by a gradual decrease towards term. Measurements between 18 and 28 weeks were comparable to those in singleton pregnancies. However, before 18 weeks values were higher, whereas after 28 weeks they were lower, as compared to singleton references. CONCLUSION: In monochorionic twin pregnancies, the deepest vertical pocket is a gestational age-dependent measurement. Therefore, a gestational age-dependent definition of polyhydramnios in twin-twin transfusion syndrome, as used by most European centers, seems a logical approach.

Twin-twin transfusion syndrome (TTTS) complicates 10-15% of monochorionic-diamniotic (MCDA) pregnancies. It originates from unbalanced transfer of fluid and vasoactive mediators from one twin to its co-twin via placental anastomoses. This results in hypovolemia in the donor and hypervolemia and vasoconstriction in the recipient twin. Consequently, the recipient demonstrates cardiovascular alterations including atrioventricular valve regurgitation, diastolic dysfunction, and pulmonary stenosis/atresia that do not necessarily correlate with Quintero-stages. Selective fetoscopic laser photocoagulation of placental vascular anastomoses disrupts the underlying pathophysiology and usually improves cardiovascular function in the recipient with normalization of systolic and diastolic function within weeks after treatment. Postnatal studies have demonstrated early decreased arterial distensibility in ex-donor twins, but 10-year follow up is encouraging with survivors showing normal cardiovascular function after TTTS. However, prediction and appropriate early management of TTTS remain poor. Assessment of the cardiovascular system provides additional insight into the pathophysiology and severity of TTTS and may permit more targeted early surveillance of MCDA pregnancies in future. It should form an integral part of the diagnostic algorithm.

Twin-to-twin-transfusion syndrome (TTTS) is the most important cause of handicap and death in monochorionic twin pregnancies. It is caused by a certain pattern of anastomoses between the two fetal circulations leading to an unbalanced blood and fluid transfer. This leads to severe amniotic fluid discordance and variable degrees of cardiac dysfunction. Untreated, this condition has a very poor survival rate. Fetoscopic laser has been shown to be the best first line treatment, which aims to dichorionise the placenta therefore arresting the inter-twin transfusion. Fetoscopic laser is a causative therapy, which aims to functionally create a dichorionized placenta hence arresting inter-twin transfusion. This is achieved by percutaneous sono-endoscopic coagulation of placental anastomoses. In addition, redundant amniotic fluid is drained. Fetoscopic laser coagulation of chorionic plate anastomoses is safe and effective. There is level I evidence that it is the best treatment modality, in particular when the placental surface is lined along the vascular equator. A recent meta-analysis confirmed an increased fetal survival and decreased risk for neonatal and pediatric neurologic morbidity. Laser therapy is the first line therapy for TTTS. The technique is quite standardized and safe and effective in experienced hands. Herein we describe the technique and current instrumentation used for this procedure.

BACKGROUND: Twin-to-twin transfusion syndrome (TTTS) is a serious complication of 10-15% of twin or triplet pregnancies in which multiple fetuses share a single placenta. Communicating placental vessels allow one fetus (the donor) to pump blood to the other (the recipient). Mortality rates without intervention are high, approaching 100% in some series, with fetal deaths usually due to cardiac failure. Surgical correction using laser photocoagulation of communicating placental vessels was developed in the 1980s and refined in the 1990s. Since it was introduced in Victoria in 2006, laser surgery has been performed in approximately 120 pregnancies. Survival of one or more fetuses following laser surgery is currently > 90%, however the neurodevelopmental outcomes for survivors remain incompletely understood. Prior to laser therapy, at least one in five survivors of TTTS had serious adverse neurodevelopmental outcomes (usually cerebral palsy). Current estimates of neurological impairment among survivors following laser surgery vary from 4 to 31% and long-term follow-up data are limited. METHODS: This paper describes the methodology for a retrospective cohort study in which children aged 24 months and over (corrected for prematurity), who were treated with laser placental photocoagulation for TTTS at Monash Health in Victoria, Australia, will undergo comprehensive neurodevelopmental assessment by a multidisciplinary team. Evaluation will include parental completion of pre-assessment questionnaires of social and behavioural development, a standardised medical assessment by a developmental paediatrician or paediatric neurologist, and age-appropriate cognitive and academic, speech and fine and gross motor assessments by psychologists, speech and occupational therapists or physiotherapists. Assessments will be undertaken at the Murdoch Children's Research Institute/Royal Children's Hospital, at Monash Health or at another mutually agreed location. Results will be recorded in a secure online database which will facilitate future related research. DISCUSSION: This will be the first study to report and evaluate neurodevelopmental outcomes following laser surgery for twin-to-twin transfusion syndrome in Victoria, and will inform clinical practice regarding follow-up of children at risk of adverse outcomes.

BACKGROUND: Twin-to-twin transfusion syndrome (TTTS) is a serious complication of 10-15% of twin or triplet pregnancies in which multiple fetuses share a single placenta. Communicating placental vessels allow one fetus (the donor) to pump blood to the other (the recipient). Mortality rates without intervention are high, approaching 100% in some series, with fetal deaths usually due to cardiac failure. Surgical correction using laser photocoagulation of communicating placental vessels was developed in the 1980s and refined in the 1990s. Since it was introduced in Victoria in 2006, laser surgery has been performed in approximately 120 pregnancies. Survival of one or more fetuses following laser surgery is currently > 90%, however the neurodevelopmental outcomes for survivors remain incompletely understood. Prior to laser therapy, at least one in five survivors of TTTS had serious adverse neurodevelopmental outcomes (usually cerebral palsy). Current estimates of neurological impairment among survivors following laser surgery vary from 4 to 31% and long-term follow-up data are limited. METHODS: This paper describes the methodology for a retrospective cohort study in which children aged 24 months and over (corrected for prematurity), who were treated with laser placental photocoagulation for TTTS at Monash Health in Victoria, Australia, will undergo comprehensive neurodevelopmental assessment by a multidisciplinary team. Evaluation will include parental completion of pre-assessment questionnaires of social and behavioural development, a standardised medical assessment by a developmental paediatrician or paediatric neurologist, and age-appropriate cognitive and academic, speech and fine and gross motor assessments by psychologists, speech and occupational therapists or physiotherapists. Assessments will be undertaken at the Murdoch Children's Research Institute/Royal Children's Hospital, at Monash Health or at another mutually agreed location. Results will be recorded in a secure online database which will facilitate future related research. DISCUSSION: This will be the first study to report and evaluate neurodevelopmental outcomes following laser surgery for twin-to-twin transfusion syndrome in Victoria, and will inform clinical practice regarding follow-up of children at risk of adverse outcomes.

OBJECTIVE: Evaluate the incidence of and risk factors for behavioural problems in twin-twin transfusion syndrome (TTTS) survivors treated with fetoscopic laser coagulation. DESIGN: Observational cohort study. SETTING: National referral center for fetal therapy, Leiden University Medical Center, The Netherlands. PATIENTS: Behavioural outcome was assessed in 417 TTTS survivors, at the age of 2 years. INTERVENTIONS: Parents completed the Child Behavior Checklist for their twins. Antenatal, neonatal and follow-up data including Bayley III and a neurological exam were recorded from the medical database. MAIN OUTCOME MEASURES: The incidence of and risk factors for behavioural problems. RESULTS: 332 twin pregnancies (664 fetuses) were treated with fetoscopic laser for TTTS between 2008 and 2015. For 517 children eligible for follow-up, 417 (81%) Child Behavior Checklist questionnaires were completed. The study group was born at a mean gestational age of 32.8 weeks+/-3.2. Total behavioural problems within the borderline to clinical range were reported in 8% (95% CI 5.9 to 11.2) of survivors, compared with 10% in the general Dutch population (p=0.12). No difference between donors and recipients was detected (p=0.84). Internalising and externalising problems were reported in 9.4% (95% CI 6.9 to 12.6) and 11.5% (95% CI 8.8 to 15.0), respectively. Severe neurodevelopmental impairment was more frequent in the children with behavioural problems. High maternal educational level was associated with lower behavioural problem scores. CONCLUSION: Parents of twins treated with fetoscopic laser therapy for TTTS do not report more behavioural problems compared with general population norms. More behavioural problems are reported in children with severe neurodevelopmental impairment.

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.