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.

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.

Behavioural outcome in twin-twin transfusion syndrome survivors treated with laser surgery.

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.

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.

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.