Enrico Lopriore

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.

Long-term neurodevelopmental outcome in twin-to-twin transfusion syndrome

OBJECTIVE The purpose of this study was to determine the long-term neurodevelopmental outcome in children after twin-to-twin transfusion syndrome. STUDY DESIGN Maternal and neonatal medical records of all twin-to-twin transfusion syndrome patients who were admitted to our center between 1990 and 1998 were reviewed. Neurologic and mental development at school age was assessed during a home visit in all twin-to-twin transfusion syndrome survivors. RESULTS A total of 33 pregnancies with twin-to-twin transfusion syndrome were identified. Four couples opted for termination of pregnancy. All other pregnancies were treated conservatively, 18 pregnancies (62%) with serial amnioreductions and 11 pregnancies (38%) without intrauterine interventions. Mean gestational age at delivery was 28.6 weeks (range, 20-37 weeks). The perinatal mortality rate was 50% (29/58 infants). The birth weight of the donor twins was less than the recipient twins (P<.001). Systolic blood pressure at birth was lower in donors than in recipients (P=.023), and donors required inotropic support postnatally more frequently than did recipients (P=.008). The incidence of hypertension at birth was higher in recipients than in donors (P=.038). Abnormal cranial ultrasonographic findings were reported in 41% of the neonates (12/29 neonates). All long-term survivors (n=29 neonates) were assessed during a home visit. Mean gestational age at birth of the surviving twin was 31.6 weeks (range, 25-37 weeks). The mean age at follow-up was 6.2 years (range, 4-11 years). The incidence of cerebral palsy was 21% (6/29 infants). Five of 6 children with cerebral palsy had an abnormal mental development. The incidence of cerebral palsy in the group of survivors who were treated with serial amnioreduction was 26% (5/19 infants). Four children were born after the intrauterine fetal demise of their co-twin, 2 of which had cerebral palsy. CONCLUSION The incidence of adverse neurodevelopmental outcome in twin-to-twin transfusion syndrome survivors is high, especially after the intrauterine fetal demise of a co-twin.

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).

The pregnancy and long-term neurodevelopmental outcome of monochorionic diamniotic twin gestations: a multicenter prospective cohort study from the first trimester onward

OBJECTIVES We sought to document the pregnancy and neurodevelopmental outcome in monochorionic diamniotic twin pregnancies and to identify risk factors for death and impairment. STUDY DESIGN We conducted a prospective cohort study of 136 monochorionic twins followed up from the first trimester until infancy. RESULTS A total of 122 (90%) pregnancies resulted in 2 survivors, 6 (4%) in 1 survivor and 8 (6%) in no survivor. In all, 230 (92%) of 250 surviving infants were assessed at a mean age of 24 months. Neurodevelopmental impairment was present in 22 (10%) infants. Death or impairment of 1 or both infants occurred in 28 (22%) of 126 pregnancies. Twin-to-twin transfusion syndrome and assisted conception increased the risk of both death and impairment, whereas early-onset discordant growth only increased the risk of death. CONCLUSION The mortality in this prospective series was 8% and neurodevelopmental impairment occurred in 10% of infants.

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.

Rhesus haemolytic disease of the newborn: Postnatal management, associated morbidity and long-term outcome

Rhesus haemolytic disease of the newborn can lead to complications such as hyperbilirubinaemia, kernicterus and anaemia. Postnatal management consists mainly of intensive phototherapy, exchange transfusion and blood transfusion. During the last decades, significant progress in prenatal care strategies for patients with Rhesus haemolytic disease has occurred. New prenatal management options have led to a remarkable reduction in perinatal mortality. As a result of the increase in perinatal survival, attention is now shifting towards short-term and long-term morbidity. This review focuses on the management of neonatal and paediatric complications associated with Rhesus haemolytic disease, discusses postnatal treatment options and summarizes the results of studies on short-term and long-term outcome.

Noninvasive antenatal management of fetal and neonatal alloimmune thrombocytopenia: safe and effective.

Objective  To describe the outcome of pregnancies with fetal and neonatal alloimmune thrombocytopenia (FNAIT) in relation to the invasiveness of the management protocol.