Johanna M. Middeldorp

Twin Anemia-Polycythemia Sequence: Diagnostic Criteria, Classification, Perinatal Management and Outcome

Monochorionic twins share a single placenta with intertwin vascular anastomoses, allowing the transfer of blood from one fetus to the other and vice versa. These anastomoses are the essential anatomical substrate for the development of several complications, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of fetofetal transfusion. TTTS is characterized by the twin oligopolyhydramnios sequence, whereas TAPS is characterized by large intertwin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in up to 5% of monochorionic twins and may also develop after incomplete laser treatment in TTTS cases. This review focuses on the pathogenesis, incidence, diagnostic criteria, management options and outcome in TAPS. In addition, we propose a classification system for antenatal and postnatal TAPS.

Fetoscopic laser coagulation of the vascular equator versus selective coagulation for twin-to-twin transfusion syndrome: an open-label randomised controlled trial

BACKGROUND Monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome are typically treated with fetoscopic laser coagulation. Postoperative complications can occur due to residual vascular anastomoses on the placenta. We aimed to assess the efficacy and safety of a novel surgery technique that uses laser coagulation of the entire vascular equator (Solomon technique). METHODS We undertook an open-label, international, multicentre, randomised controlled trial at five European tertiary referral centres. Women with twin-to-twin transfusion syndrome were randomly assigned by online randomisation (1:1) with permuted blocks to the Solomon technique or standard laser coagulation. The primary outcome was a composite of incidence of twin anaemia polycythaemia sequence, recurrence of twin-to-twin transfusion syndrome, perinatal mortality, or severe neonatal morbidity. Analyses were by intention to treat, with results expressed as odds ratios (ORs) and 95% CIs. This trial is registered with the Dutch Trial Registry, number NTR1245. FINDINGS Between March 11, 2008, and July 12, 2012, 274 women were randomly assigned to either the Solomon group (n=139) or the standard treatment group (n=135). The primary outcome occurred in 94 (34%) of 274 fetuses in the Solomon group versus 133 (49%) of 270 in the standard treatment group (OR 0·54; 95% CI 0·35-0·82). The Solomon technique was associated with a reduction in twin anaemia polycythaemia sequence (3% vs 16% for the standard treatment; OR 0·16, 95% CI 0·05-0·49) and recurrence of twin-to-twin transfusion syndrome (1% vs 7%; 0·21, 0·04-0·98). Perinatal mortality and severe neonatal morbidity did not differ significantly between the two groups. Outside of the common and well-known complications of twin-to-twin transfusion syndrome and its treatment, no serious adverse events occurred. INTERPRETATION Fetoscopic laser coagulation of the entire vascular equator reduces postoperative fetal morbidity in severe twin-to-twin transfusion syndrome. We recommend that fetoscopic surgeons consider adopting this strategy for treatment of women with twin-to-twin transfusion syndrome. FUNDING Netherlands Organization for the Health Research and Development (ZonMw 92003545).

Placental characteristics in monochorionic twins with and without twin anemia-polycythemia sequence.

OBJECTIVE: To study the placental angioarchitecture of monochorionic placentas with and without twin anemia–polycythemia sequence. METHODS: Eligible were all placentas from monochorionic twin gestations, not complicated by twin-to-twin transfusion syndrome and resulting in double survival. The study was conducted at two European Fetal Therapy Centers between 2002 and 2008. Placental angioarchitecture was evaluated using colored dye injection. Diagnosis of twin anemia–polycythemia sequence was based on the presence of large intertwin hemoglobin difference without the degree of amniotic fluid discordance that is required for the diagnosis of twin transfusion syndrome. RESULTS: Three-hundred thirteen monochorionic twin pregnancies were eligible for the study but placental data could not be completed for 62 placentas (20%). This left 251 monochorionic twin pregnancies of which 11 (4%) fulfilled the criteria for twin anemia–polycythemia sequence. The median number of anastomoses in monochorionic placentas with and without twin anemia–polycythemia sequence was 3 (range: 2–5) and 7 (range: 0–25), respectively (P<.001). Small anastomoses were present in 91% (10/11) of twin anemia–polycythemia sequence-placentas compared with 5% (12/240) of cases without twin anemia–polycythemia sequence (P<.001). Arterioarterial anastomoses were absent in twin anemia–polycythemia sequence-placentas and present in 89% (213/240) of placentas without twin anemia–polycythemia sequence (P<.001). CONCLUSION: Monochorionic twin placentas with twin anemia–polycythemia sequence are characterized by a paucity of anastomoses and the absence of arterioarterial anastomoses. The few anastomoses that are present in twin anemia–polycythemia sequence placentas are mostly small arteriovenous anastomoses. LEVEL OF EVIDENCE: II

Risk Factors for Neurodevelopment Impairment in Twin-Twin Transfusion Syndrome Treated With Fetoscopic Laser Surgery

OBJECTIVE: To estimate the risk factors for adverse long-term neurodevelopment outcome in twin–twin transfusion syndrome treated with laser surgery. METHODS: Twin–twin transfusion syndrome cases treated with laser surgery at three European centers from August 2000 to December 2005 were included in this case-control study. Neurological, mental, and psychomotor development (using the Bayley Scales of Infant Development, 2nd edition) was evaluated at 2 years of age. RESULTS: A total of 212 twin–twin transfusion syndrome pregnancies were treated with laser surgery during the study period. Overall mortality rate was 30% (129 of 424). Seventeen children (6%) were lost to follow-up. Long-term outcome was assessed in 278 infants. The incidence of neurodevelopment impairment was 18% (50 of 278). Four risk factors were found to be significantly associated with increased risk for neurodevelopment impairment: greater gestational age at laser surgery (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.00–1.69; P=.05), higher Quintero stage (OR 3.55 for each increment in stage, 95% CI 1.07–11.82, P=.04), lower gestational age at birth (OR 1.39 for each week, 95% CI 1.06–1.81; P=.01), and lower birth weight (OR 1.18 for each 100-g decrease, 95% CI 1.05–1.32; P<.01). In a multivariable analysis, lower gestational age at birth was the only factor independently associated with neurodevelopmental impairment (OR 1.33 for each week, 95% CI 1.05–1.67, P=.02). CONCLUSION: Neurodevelopment impairment in twin– twin transfusion syndrome survivors treated with laser surgery is associated with advanced gestational age at laser surgery, low gestational age at birth, low birth weight, and high Quintero stage. LEVEL OF EVIDENCE: II

Fetoscopic Laser Surgery in 100 Pregnancies with Severe Twin-to-Twin Transfusion Syndrome in the Netherlands

Objective: In this prospective cohort study, we evaluated the initial results of fetoscopic laser surgery for severe second trimester twin-to-twin transfusion syndrome (TTTS) treated at our centre. Method: A total of 100 consecutive pregnancies with severe second trimester TTTS treated at our centre with selective fetoscopic laser coagulation of vascular anastomoses on the placental surface between August 2000 and November 2004 were included in the study. Perinatal survival was analysed in relation to Quintero stage. Results: Median gestational age was 20 weeks at fetoscopy (range: 16–26) and 33 weeks at delivery (range: 18–40). Perinatal survival rate was 70% (139/200). The treatment resulted in at least one survivor at the age of 4 weeks in 81% of pregnancies. Perinatal survival was significantly higher when treatment was performed in the early Quintero stages (95% in stage 1, 76% in stage 2, 70% in stage 3, 50% in stage 4) (p = 0.02). Conclusion: Results of fetoscopic laser surgery for TTTS in our centre are similar to those in specialised centres in other countries. Diagnosis and treatment in the early Quintero stages resulted in significantly higher perinatal survival.

Residual anastomoses in twin-to-twin transfusion syndrome treated with selective fetoscopic laser surgery: localization, size, and consequences

OBJECTIVE To study the localization and size of residual anastomoses in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery and correlate the findings with outcome. STUDY DESIGN Placental injection in twin-to-twin transfusion syndrome placentas treated with laser was performed by using colored dye. RESULTS A total of 77 twin-to-twin transfusion syndrome placentas were included in the study. Residual anastomoses (n = 48) were found in 32% (25/77) of lasered placentas. Most residual anastomoses were localized near the margin of the placenta. The majority of residual anastomoses (67%; 32/48) were very small (diameter, < 1 mm). Eleven of the 25 cases (44%) in the residual anastomoses group developed twin anemia-polycythemia sequence. CONCLUSION Most residual anastomoses in twin-to-twin transfusion syndrome placentas treated with laser are very small and localized near the placental margin. Almost half of cases with residual anastomoses developed twin anemia-polycythemia sequence after laser surgery.

Timely diagnosis of twin‐to‐twin transfusion syndrome in monochorionic twin pregnancies by biweekly sonography combined with patient instruction to report onset of symptoms

To assess the value of serial ultrasound examinations together with patient instructions to report the onset of symptoms in achieving timely detection of twin‐to‐twin transfusion syndrome (TTTS) in a cohort of monochorionic diamniotic twin pregnancies, and to evaluate sonographic TTTS predictors.

Twin-to-twin transfusion syndrome after 26 weeks of gestation: is there a role for fetoscopic laser surgery?

Objective  To compare fetoscopic laser surgery with amniodrainage in the treatment of twin‐to‐twin transfusion syndrome (TTTS) diagnosed after 26 weeks of gestation.

Hematological characteristics in neonates with twin anemia-polycythemia sequence (TAPS).

To evaluate the neonatal hematological features of monochorionic twins with twin anemia–polycythemia sequence (TAPS) and to determine the additional diagnostic value of reticulocyte count measurement.

Short- and long-term outcome in stage 1 twin-to-twin transfusion syndrome treated with laser surgery compared with conservative management.

OBJECTIVE We sought to compare short- and long-term outcome in Quintero stage 1 twin-to-twin transfusion syndrome (TTTS), managed with laser surgery or conservatively. STUDY DESIGN We conducted a retrospective study of all monochorionic twin pregnancies with stage 1 TTTS referred to our center. Primary outcomes were perinatal survival, neonatal morbidity, and long-term neurodevelopmental outcome. RESULTS Fifty women presented with stage 1 TTTS of which 40% (20/50) was treated with laser and 60% (30/50) was managed conservatively. Perinatal survival of both or at least 1 twin was 65% (13/20) and 85% (17/20) in the laser group, and 77% (23/30) and 97% (29/30) in the conservatively managed group (P = .52 and P = .29), respectively. Long-term neurodevelopmental impairment of the surviving infants was found in 0% (0/21) vs 23% (7/30), respectively (P = .03). CONCLUSION In this retrospective study, long-term outcome in stage 1 TTTS was better after laser surgery than with conservative management, suggesting the need for a randomized controlled trial.