Outcome of twin-twin transfusion syndrome according to the Quintero stage of the disease: a systematic review and meta-analysis

OBJECTIVES: To report the outcomes of twin-twin transfusion syndrome (TTTS) according to Quintero staging system. METHODS: Medline, Embase and Cinahl databases were searched for studies reporting outcomes of TTTS stratified by Quintero staging (I-V). The primary outcome was the survival rate according to TTTS stage. The secondary outcomes were gestational age at birth (weeks), preterm birth (PTB) <34, 32 and 28 weeks of gestation and neonatal morbidity. Outcomes were reported according to different management options (expectant, laser therapy or amnioreduction) for stage I, including only cases treated with laser therapy for stages II-IV and only those managed expectantly for stage V. Random-effect head-to-head meta-analyses were used to analyze the extracted data. RESULTS: Twenty-six studies (2699 twin pregnancies) were included. 610 (22.6%) were diagnosed at Quintero stage I, 692 (25.6%) at stage II, 1146 (42.5%) at stage III, 247 (9.2%) at stage IV and 4 (0.1%) at stage V. Survival of at least one twin occurred in 86.9% (95% CI 84.0-89.7; 456 cases) of pregnancies at stage I, 85% (95% CI 79.1-90.1; 514 cases) at stage II, 80.6% (95% CI 75.7-85.1; 865 cases) at stage III, 82.8% (95% CI 73.6-90.4; 172 cases) at stage IV and 54.6% (95% CI 24.8-82.6; 5 cases) at stage V. The rate of pregnancies with no survivor was 11.8% (95% CI 8.4-15.8; 69 cases) at stage I, 15% (95% CI 9.9-20.9; 76 cases) at stage II, 18.6% (95% CI 14.2-23.4; 165 cases) at stage III, 17.2% (95% CI 9.6-26.4; 33 cases) at stage IV and 45.4% (95% CI 17.4-75.2; 4 cases) at stage V. Gestational age at birth was similar in stage I-III TTTS, and gradually decreases in stage IV and V. Overall, the incidence of PTB and neonatal morbidity increases as the severity of TTTS increases, but data on these two outcomes were limited by the small sample size of the included studies. When stratifying the analysis of stage I TTTS according to the type of intervention, perinatal survival of at least one twin was 84.9% (95% CI 70.4-95.1; 94 cases) in cases managed expectantly, 86.7% (95% CI 82.6-90.4; 249 cases) in those undergoing laser therapy and 92.2% (85% CI 84.2-97.6; 56 cases) in those after amnioreduction, while double survival was 67.9% (95% CI 57.0-77.9; 73 cases), 69.7% (95% CI 61.6-77.1; 203 cases) and 80.8% (95% CI 62.0-94.2; 49 cases) in the three groups, respectively. CONCLUSION: The overall survival in MCDA pregnancies affected by TTTS is higher at earlier Quintero stages (I-II), but perinatal survival rates are reasonable even at stage III and IV when treated with laser therapy. Gestational age at birth was similar in stage I-III TTTS, and gradually decreases in stage IV and V treated with laser. In pregnancies affected by stage I TTTS, amnioreduction was associated with a slightly higher survival compared to laser therapy and expectant management, although these findings might only be confirmed by future head-to-head, randomized trials.