Spontaneous twin anemia polycythemia sequence: diagnosis, management, and outcome in an international cohort of 249 cases

Abstract

BACKGROUND: Twin anemia polycythemia sequence is a chronic form of unbalanced fetofetal transfusion through minuscule placental anastomoses in monochorionic twins, leading to anemia in the donor and polycythemia in the recipient. Owing to the low incidence of twin anemia polycythemia sequence, data on diagnosis, management, and outcome are limited. OBJECTIVE: This study aimed to investigate the diagnosis, management, and outcome in a large international cohort of spontaneous twin anemia polycythemia sequence. STUDY DESIGN: Data from the international twin anemia polycythemia sequence registry, retrospectively collected between 2014 and 2019, were used for this study. A total of 17 fetal therapy centers contributed to the data collection. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. RESULTS: A total of 249 cases of spontaneous twin anemia polycythemia sequence were included in this study, 219 (88%) of which were diagnosed antenatally and 30 (12%) postnatally. Twin anemia polycythemia sequence was diagnosed antenatally at a median gestational age of 23.7 weeks (interquartile range, 9.7e28.8; range, 15.1e35.3). Antenatal management included laser surgery in 39% (86 of 219), expectant management in 23% (51 of 219), delivery in 16% (34 of 219), intrauterine transfusion (with partial exchange transfusion) in 12% (26 of 219), selective feticide in 8% (18 of 219), and termination of pregnancy in 1% (3 of 219) of cases. Perinatal mortality rate was 15% (72 of 493) for the total group, 22% (54 of 243) for donors, and 7% (18 of 242) for recipients (P<.001). Severe neonatal morbidity occurred in 33% (141 of 432) of twins with twin anemia polycythemia sequence and was similar for donors (32%; 63 of 196) and recipients (33%; 75 of 228) (P¼.628). Independent risk factors for spontaneous perinatal mortality were donor status (odds ratio, 3.8; 95% confidence interval, 1.9e7.5; P<.001), antenatal twin anemia polycythemia sequence stage (odds ratio, 6.3; 95% confidence interval, 1.4e27.8; P¼.016 [stage 2]; odds ratio, 9.6; 95% confidence interval, 2.1e45.5; P¼.005 [stage 3]; odds ratio, 20.9; 95% confidence interval, 3.0e146.4; P¼.002 [stage 4]), and gestational age at birth (odds ratio, 0.8; 95% confidence interval, 0.7e0.9; P¼.001). Independent risk factors for severe neonatal morbidity were antenatal twin anemia polycythemia sequence stage 4 (odds ratio, 7.9; 95% confidence interval, 1.4e43.3; P¼.018) and gestational age at birth (odds ratio, 1.7; 95% confidence interval, 1.5e2.1, P<.001). CONCLUSION: Spontaneous twin anemia polycythemia sequence can develop at any time in pregnancy from the beginning of the second trimester to the end of the third trimester. Management for twin anemia polycythemia sequence varies considerably, with laser surgery being the most frequent intervention. Perinatal mortality and severe neonatal morbidity were high, the former especially so in the donor twins.

Treatment and outcome of 370 cases with spontaneous or post‐laser twin anemia–polycythemia sequence managed in 17 fetal therapy centers

“…missed antenatally) and/or if they were diagnosed with post-laser TAPS within 1 week after laser for TTTS, unless TAPS persisted after 1 week, and/or if they were first diagnosed with TAPS at Stage 5. The outcomes of TAPS cases diagnosed postnatally are presented in two 380 Tollenaar et al other studies investigating perinatal outcome separately in spontaneous and post-laser TAPS 10,11 .…”

“…Severe perinatal morbidity rates were high in all groups, but were significantly increased in cases treated with IUT (± PET) or delivery within 7 days after diagnosis. Notably, TAPS twins managed with IUT (± PET) were delivered at a significantly earlier gestation compared with all other management groups, which is known to have significant impact on short-term outcome 10,11 . However, twins managed with delivery were born at a comparable gestational age to that of twins treated with laser surgery, which suggests that other factors might play a role.…”

“…However, laser surgery was associated with a high diagnosis-to-birth interval, especially in comparison to treatment with IUT (± PET). As prematurity has a profound impact on short-and long-term health in TAPS twins, prolongation of pregnancy is of the utmost importance to improve outcome 6,7,10,11 . Notably, a comparable prolongation of pregnancy was achieved with selective feticide and expectant management.…”

“…On the other hand, in expectant management, prolongation of pregnancy likely results in continuous exposure to the potential detrimental effects of TAPS, as only 16% of cases showed spontaneous resolution. As risk for perinatal mortality and morbidity increases with increasing antenatal TAPS stage, definitive treatment with laser might be the optimal intervention to improve perinatal outcome for this condition 11,24 .…”

“…The management groups differed in terms of GA at diagnosis, severity of TAPS and type of TAPS. Since higher TAPS stage and post-laser TAPS are associated with poorer prognosis, these factors could have influenced significantly the perinatal outcome 10,11 . Moreover, long-term outcome was not investigated in this study.…”