North American Fetal Therapy Network: intervention vs expectant management for stage I twin-twin transfusion syndrome

Background Stage I twin-twin transfusion syndrome presents a management dilemma. Intervention may lead to procedure-related complications while expectant management risks deterioration. Insufficient data exist to inform decision-making. Objective The aim of this retrospective observational study was to describe the natural history of stage I twin-twin transfusion syndrome, to assess for predictors of disease behavior, and to compare pregnancy outcomes after intervention at stage I vs expectant management. Study Design Ten North American Fetal Therapy Network centers submitted well-documented cases of stage I twin-twin transfusion syndrome for analysis. Cases were retrospectively divided into 3 management strategies: those managed expectantly, those who underwent amnioreduction at stage I, and those who underwent laser therapy at stage I. Outcomes were categorized as no survivors, 1 survivor, 2 survivors, or at least 1 survivor to live birth, and good (twin live birth ≥30.0 weeks), mixed (single fetal demise or delivery between 26.0-29.9 weeks), and poor (double fetal demise or delivery Results A total of 124 cases of stage I twin-twin transfusion syndrome were studied. In all, 49 (40%) cases were managed expectantly while 30 (24%) underwent amnioreduction and 45 (36%) underwent laser therapy at stage I. The overall fetal mortality rate was 20.2% (50 of 248 fetuses). Of those managed expectantly, 11 patients regressed (22%), 4 remained stage I (8%), 29 advanced in stage (60%), and 5 experienced spontaneous previable preterm birth (10%) during observation. The mean number of days from diagnosis of stage I to a change in status (progression, regression, loss, or delivery) was 11.1 (SD 14.3) days. Intervention by amniocentesis or laser therapy was associated with a lower risk of fetal loss ( P  = .01) than expectant management. The unadjusted odds of poor outcome were 0.33 (95% confidence interval, 0.09–01.20), for amnioreduction and 0.26 (95% confidence interval, 0.09–0.77) for laser therapy vs expectant management. Adjusting for nulliparity, recipient maximum vertical pocket, gestational age at diagnosis, and placenta location had negligible effect. Both amnioreduction and laser therapy at stage I decreased the likelihood of no survivors (odds ratio, 0.11; 95% confidence interval, 0.02–0.68 and odds ratio, 0.07; 95% confidence interval, 0.01–0.37, respectively). Only laser therapy, however, was protective against poor outcome in our data (odds ratio, 0.29; 95% confidence interval, 0.07–1.30 for amnioreduction vs odds ratio, 0.12, 95% confidence interval, 0.03–0.44 for laser), although the estimate for amnioreduction suggests a protective effect. Conclusion Stage I twin-twin transfusion syndrome was associated with substantial fetal mortality. Spontaneous resolution was observed, although the majority of expectantly managed cases progressed. Progression was associated with a worse prognosis. Both amnioreduction and laser therapy decreased the chance of no survivors, and laser was particularly protective against poor outcome independent of multiple factors. Further studies are justified to corroborate these findings and to further define risk stratification and surveillance strategies for stage I disease.