Perinatal outcomes of twin pregnancies affected by early twin-twin transfusion syndrome: A systematic review and meta-analysis

Introduction: Twin-to-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal mortality and morbidity if not treated. However, the optimal timing and management in case of early (occurring < 18 weeks) TTTS has not been established yet. Material and methods: This is a systematic review and meta-analysis aiming at evaluating the outcomes of monochorionic diamniotic twin pregnancies complicated by early (ie before 18 weeks) TTTS according to different management options (expectant, laser therapy, amnioreduction or cord occlusion). The primary outcome was mortality, including single and double intrauterine, neonatal and perinatal death. Secondary outcomes were: composite morbidity, neuromorbidity, respiratory distress syndrome, admission to neonatal intensive care unit, intact survival (defined as survival free from neurological complications) and preterm birth < 32 weeks of gestation. All outcomes were reviewed according to the different management options (expectant, laser therapy, amnioreduction or cord occlusion) and reported FOR the overall population of twins, and for the donor and recipient separately. Subgroup analysis for TTTS occurring before 16 weeks of gestation was performed. Random-effect meta-analyses of proportions were used to analyse the data. Results: Thirteen studies were included. Early TTTS occurred in 14.3% (95% confidence interval [CI] 11.9-17.0) of cases. The incidence of intrauterine death was 19.0% (95% CI 2.6-45.5) in twins managed expectantly, 32.4% (95% CI 16.5-50.7) in those who received laser treatment and 12.5% (95% CI 4.8-23.0) in those treated with amnioreduction. The incidence of neonatal death was 22.6% (95% CI 4.2-49.8) in twins managed expectantly, 24.7% (95% CI 0.5-80.3) in those who received laser and 20.2 (95% CI 5.8-43.4) in those who had amnioreduction; it was not possible to compute the incidence of these outcomes in twins undergoing cord occlusion because of insufficient sample and lack of reporting of most of the observed outcomes. Overall, the incidence of perinatal death was 43.9% (95% CI 5.9-87.7) in twins managed expectantly, 47.3% (95% CI 21.4-70.0) in those treated with laser and 28.5% in those who had amnioreduction. Conclusions: Twin pregnancies affected by early TTTS are at substantial risk of perinatal mortality and morbidity; however, the data come from very small studies with a high risk of selection bias.