Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome in the eurofoetus trial


      To investigate long-term neuro-developmental outcome of children born in the Eurofoetus RCT comparing endoscopic laser surgery and serial amnioreduction in twin-to-twin transfusion syndrome (TTTS).

      Study design

      Survivors beyond 6 months were followed-up and evaluated by standardized examination (Amiel-Tison and Gosselin) and by the Ages and Stages questionnaires (ASQ). Primary outcome was the incidence of severe neurological abnormalities leading to permanent disability. In addition children were subjected to cognitive evaluation using Wechsler Intelligence Scale for Children (WISC-IV) at the age of 6.


      120 children (73 treated with laser (L) and 47 with amnioreduction (A)) survived beyond 6 months. Six were lost to follow-up. 114 children (69 L and 45 A) were examined at a median (25-75 percentile) of 5.3 (4.4-6.1) years. Incidence of major neurological problems was 15/114 (13.1%). Univariate analysis is summarized in Table 1. Multivariate analysis showed that only gestational age at delivery, 1-minute Apgar score and Quintero staging were predictive factors. Neurological evaluation changed over time with improvement or worsening in 4/114 and 5/114 cases but remained stable from the age of 2. Normal ASQ scores were found in 72% and 89% and in 72% and 80% of cases at 2 and 4 years in the L and A groups respectively (NS). IQ was below 85 in 0/10 and 2/9 children in L and A groups at the age of 6.


      Among TTTS survivors, the risk of developing long-term major neurological impairment depends upon perinatal factors but not of fetal treatment.
      Table 1Prediction of severe neurological impairment
      VariableOdd Ratiop-value
      Laser/amnio reduction0.940.92
      Quintero Staging (3-4/1-2)3.170.0170
      Gestation at delivery, (weeks)0.760.0024
      Birthweight, SD1.010.98
      Apgar 1min0.690.0018
      Apgar 5min0.590.0106
      Arterial pH0.050.51