Peripheral skin necrosis in the recipient of monochorionic twins complicated by twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) complicates approximately 15% of monochorionic, diamniotic twin pregnancies and if untreated carries a high perinatal loss rate of between 80% and 100%, depending on the stage. The underlying pathology in TTTS appears to be an imbalanced intertwin perfusion difference, secondary to functional unidirectional arteriovenous anastomoses within a monochorionic placenta. We report two cases of monochorionic twin pregnancy complicated by TTTS, in which the pregnancies were treated by serial aggressive amnioreduction. However, the recipient twin in each pregnancy developed 'ischemic damage' to a lower limb.     

产前超声监测羊水量不均衡双胎妊娠的临床价值

目的 探讨产前超声监测羊水量不均衡双胎的临床价值.方法 分析270例双羊膜囊双胎中单绒毛膜双羊膜囊双胎(monochorionic-diamniotic twin,MCDA)与双绒毛膜双羊膜囊双胎(dichorionicdiamniotic twin,DCDA)羊水量不均衡的发生率,妊娠过程中羊水量变化趋势及与妊娠结局的关系.结果 共45例双胎间羊水量不均衡,MCDA组37例,其中24例为双胎输血综合征(twin-to-twin transfusion syndrome,TTTS);DCDA组8例,无TTTS发生.MCDA组羊水量不均衡的发生率明显高于DCDA组(P＜0.001).MCDA组中羊水量不均衡的非TTTS双胎,羊水量的差异随孕周增加呈减少趋势,且妊娠结局明显优于TTTS(P＜0.001).结论 MCDA组中羊水量不均衡双胎与TTTS间可能存在一个重叠的临界状态,动态监测羊水量的变化趋势,是产前诊断和判断预后的关键,也是临床干预的重要依据.     

Prognostic factors in severe twin-twin transfusion syndrome treated by endoscopic laser surgery.

OBJECTIVE: The aim of this study was to investigate clinical and sonographic parameters, in particular Doppler blood flow measurements, in severe second-trimester twin-twin transfusion syndrome before and after endoscopic laser coagulation of the placental vascular anastomoses, to correlate these data with fetal outcome and to determine whether fetal blood flow measurements could help to estimate the probability of fetal survival. METHODS: In 121 cases of severe twin-twin transfusion syndrome examined between 17 and 26 weeks of gestation, the following investigations were performed: fetal biometry, placental location, deepest pool of amniotic fluid, echocardiography and Doppler sonography of the umbilical arteries and the ductus venosus of both twins before and after fetoscopic laser ablation of the placental anastomoses. RESULTS: The overall survival rate was 64% (156/242). Both fetuses survived in 48% (58/121) and one fetus survived in 33% (40/121), resulting in 81% (98/121) of pregnancies with at least one survivor. Gestational age at the time of the procedure and placental location had no significant influence on fetal survival. The amniotic fluid volume drained after laser coagulation correlated significantly (p = 0.038) with the risk of miscarriage or extremely premature delivery within 4 weeks of the procedure. Intertwin discrepancy in abdominal circumference showed a significant negative correlation (p = 0.004) with the probability for survival of donor fetuses. Before the procedure, 19% (23/121) of donor twins and 5% (6/121) of recipient twins showed absent or reversed end-diastolic flow in the umbilical artery (p = 0.001). This finding had no significant influence on the survival rate of donors. An increase of waveform indices in the umbilical artery 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability for survival of donors (p = 0.042) and recipients (p = 0.018). Before the procedure, 37% (45/121) of recipient twins and 9% (10/113) of donor twins showed absent or reversed flow during atrial contraction in the ductus venosus (p < 0.0001). This finding had a significant negative influence on the survival rate of recipient fetuses (p = 0.02). Furthermore, an increase of waveform indices in the ductus venosus 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability of survival in recipients (p = 0.005). CONCLUSIONS: Fetoscopic laser coagulation of the placental vascular anastomoses in severe mid-trimester twin-twin transfusion is a potentially corrective and effective, minimally invasive procedure. Doppler investigation of the umbilical and fetal circulations provides important information on the fetal condition, prognosis and therapeutic effects of the intervention. Signs of congestive heart failure in the recipient may reduce the probability of survival, whereas increased placental resistance in the donor before the procedure is not necessarily associated with a reduction in the probability of survival after laser coagulation.     

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

OBJECTIVES: 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. METHODS: Timely detection of TTTS was defined as diagnosis before severe complications of TTTS occurred, such as preterm prelabor rupture of membranes, very preterm delivery (24-32 weeks of pregnancy), fetal hydrops, or intrauterine fetal death. During a 2-year period, a prospective series of 23 monochorionic twin pregnancies was monitored from the first trimester until delivery. At least every 2 weeks we performed ultrasound and Doppler measurements (nuchal translucency thickness, presence of membrane folding, estimated fetal weight, deepest vertical pocket, bladder filling, and Doppler waveforms of the umbilical artery, ductus venosus and umbilical vein). Measurements of TTTS cases were compared with those of non-TTTS cases matched for gestational age. Furthermore, patients were informed about the symptoms caused by TTTS, and instructed to consult us immediately in case of rapidly increasing abdominal size or premature contractions. RESULTS: In all four TTTS cases, the diagnosis was timely. At the time of diagnosis, one case was at Quintero Stage 1, two at Quintero Stage 2, and one at Quintero Stage 3. Two of the TTTS cases became apparent after the patients' feeling of rapidly increasing girth. The identification of TTTS predictors was successful with respect to one parameter: isolated polyhydramnios in one sac, without oligohydramnios in the other, preceded the ultimate diagnosis of TTTS in two of the four TTTS cases. All other ultrasound measurements of TTTS cases, prior to the diagnosis of TTTS, were within the range of measurements of non-TTTS cases. CONCLUSION: Biweekly ultrasound examinations, with special attention to the amniotic fluid compartments of both fetuses, combined with detailed patient instructions to report the onset of symptoms resulted in timely diagnosis of all TTTS cases and appears to be a safe program for monitoring monochorionic twin pregnancies.     

Selective feticide in monochorionic twin pregnancies by ultrasound-guided umbilical cord occlusion.

OBJECTIVES: To evaluate the feasibility and the follow-up of three different ultrasound-guided procedures of selective feticide in monochorionic twin pregnancies. METHODS: This was a retrospective observational study of patients who underwent percutaneous umbilical cord occlusion between July 1993 and January 2002 after diagnosis of previable, abnormal, monochorionic twin pregnancy, with imminent cardiac failure of one of the fetuses. Selective feticide was performed under general anesthesia using three different ultrasound-guided techniques: cord ligation using a suture (four cases), cord coagulation using bipolar forceps (five cases) and cord compression by squeezing the cord against the uterine wall (two cases). RESULTS: During the study period, 11 patients underwent selective feticide before 28 weeks' gestation in our department (eight recipient twins with twin-twin transfusion syndrome (TTTS), one of which also had a congenital diaphragmatic hernia, and three acardiac twins). One procedure failed due to maternal hemorrhage following insertion of the trocar (both fetuses died after emergency Cesarean section). One cotwin died a few minutes after the procedure and one survivor died within the neonatal period. The mean gestational age at the time of the procedure was 24 weeks of gestation and the mean gestational age at delivery was 31.1 weeks. Premature rupture of membranes occurred in four cases. Eight babies were alive and well at the time of writing. CONCLUSIONS: Ultrasound guidance can enable selective feticide to be performed via a single port. Although bipolar coagulation seemed to be the easiest technique, the choice of procedure depends on local conditions.     

Measurement of fetal surfactant production by fluorescence polarization of amniotic fluid in complicated pregnancies

The results are presented of fluorescence polarization as a method for measurement of surfactant production in 159 specimens of amniotic fluid collected from pregnant women with diabetes, hypertension, Rh immunization, premature rupture of membranes (for more than 48 h prior to delivery) and intrauterine growth retardation (IUGR). The predictability of the development of respiratory distress syndrome has been assessed by this assay. Its specificity, sensitivity and overall accuracy were similar to the lecithin/sphingomyelin (L/S) ratio. The influence of the conditions detailed on fetal lung maturation was determined, lung development being enhanced until near term by Rh immunization, rupture of membranes and hypertension with IUGR.     

Fetal arterial Doppler studies in twin-twin transfusion syndrome.

This cross-sectional study investigates the circulatory profile of the donor and recipient fetuses in pregnancies with twin-twin transfusion syndrome manifested by acute polyhydramnios during the second trimester of pregnancy. Doppler investigations of the umbilical arteries and of the fetal descending thoracic aortas and middle cerebral arteries were performed in both fetuses of 27 pregnancies with twin-twin transfusion syndrome at 18 to 25 (mean, 21.7) weeks' gestation. Significant differences from normal values were increased umbilical artery pulsatility index and decreased aortic mean velocity in both donor and recipient fetuses, decreased middle cerebral artery pulsatility index in recipients and decreased middle cerebral artery mean velocity in donors. Increased umbilical artery pulsatility index in some donor and recipient fetuses may be the consequence of abnormal placental development and polyhydramnios-related compression, respectively. Doppler findings in the fetal circulation are compatible with hypovolemia in the donor and hypervolemia with congestive heart failure in the recipient.     

Intrauterine death of one twin, with rescue of the other, in twin-twin transfusion syndrome.

Single intrauterine death may occur in twin-twin transfusion syndrome. We investigated why the outcome of the surviving twin is fairly good when the donor twin dies first compared with when the recipient twin dies first. A detailed hemodynamic study was performed using Doppler ultrasound in a twin pregnancy affected by twin-twin transfusion syndrome before and after a single intrauterine death that occurred in the donor twin at 26 weeks' gestation. The recipient twin was expected to die due to severe right cardiac failure with functional stenosis of the pulmonary artery 2 days before the cotwin's death. The donor twin's death caused a prompt resolution of cardiac failure and improvement in other indices, including flow velocity waveform patterns of the umbilical vein, the middle cerebral artery and the ductus venosus. A healthy, premature female neonate weighing 1630 g with a hemoglobin concentration of 17.8 g/dL was delivered by Cesarean section following rupture of the fetal membranes 28 days after the episode. Hemorrhaging from the surviving twin to the dead twin that occurred just before or after the cotwin's death may have contributed to the decrease in volume overload in the recipient twin, leading to a prompt amelioration of the critical hemodynamic indices. The early death of the donor twin may thus have played a significant role in improving the status of the recipient twin in this case of twin-twin transfusion syndrome.     

Middle cerebral artery peak systolic velocity in monochorionic and dichorionic twin pregnancies.

OBJECTIVE: The purpose of this study was to compare middle cerebral artery (MCA) peak systolic velocity (PSV) values in monochorionic (MC) and dichorionic (DC) twin pregnancies. METHODS: This was a prospective cohort study in which MCA Doppler evaluation was performed in unselected twin pregnancies at time of routine sonography between 28 and 32 weeks. Pregnancies with known fetal anomalies, twin-twin transfusion syndrome, and red cell alloimmunization or other conditions associated with anemia were excluded. The intertwin MCA PSV difference, defined as the larger minus smaller PSV value within a pair, was compared in MC and DC pregnancies and was correlated with estimated fetal weight and birth weight discordance. Statistical analyses included Spearman correlation, analysis of variance, a t test, and a chi(2) test. RESULTS: Doppler indices were analyzed from 48 twin pregnancies, of which 32 (67%) were DC and 16 (33%) were MC. There was no difference in proportion of values above or below the singleton median for either the larger or smaller DC or MC twins (all P > or = .3). The median intertwin MCA PSV difference was 4.9 cm/s in MC pregnancies and 4.5 cm/s in DC pregnancies (P = .6). There was no significant correlation between the MCA PSV difference and either estimated fetal weight discordance or birth weight discordance in either MC or DC pregnancies (all P > or = .3). CONCLUSIONS: Middle cerebral artery PSV values in uncomplicated twin pregnancies are comparable with published singleton norms, with a median intertwin MCA PSV difference of approximately 5 cm/s. We found no significant correlation between the intertwin MCA PSV difference and discordance in MC or DC twin gestations.     

Controlled fetal blood-letting of the recipient twin as a new method for the treatment of severe twin-twin transfusion syndrome: preliminary results.

OBJECTIVE: To investigate the feasibility of withdrawal of blood from the recipient twin as a new method for the treatment of severe twin-twin transfusion syndrome. METHODS: Seven consecutive monozygotic monochorionic twin pregnancies affected by severe twin-twin transfusion syndrome were treated. Fetal blood was withdrawn from the recipient twin using cordocentesis. The volume of blood to be removed was determined using the formula for intrauterine blood transfusion of anemic fetuses. Fetal outcome was evaluated in relation to changes in the amniotic fluid and in growth curves (comparing the differences between the centiles of the estimated fetal weight before the procedure and the centiles of weight at birth), fetal mortality, gestational age at delivery, neonatal weight and neurological damage. RESULTS: Overall, seven of the 14 (50%) fetuses survived; at least one fetus survived in five (71%) pregnancies, both fetuses survived in two (29%) pregnancies, while in two (29%) pregnancies there were no survivors. No maternal complications were observed. At follow-up, one (14%) baby had minor neurological damage. CONCLUSIONS: Withdrawal of blood from the recipient twin in the treatment of severe twin-twin transfusion syndrome was associated with survival similar to that of the alternative techniques of serial amniodrainage and fetoscopic laser surgery, with some possible advantages such as reduced neurological damage compared with serial amniodrainage. It is also less invasive compared with fetoscopic laser surgery.     

Early manifestations and spectrum of recipient twin cardiomyopathy in twin-twin transfusion syndrome: relation to Quintero stage.

OBJECTIVES: To examine cardiac structural and functional changes in twin-twin transfusion syndrome (TTTS), relative to Quintero stage, as a means of evaluating the spectrum of cardiomyopathy in TTTS. METHODS: This was a cross-sectional, retrospective study of 42 consecutive cases of TTTS referred to a single fetal therapy center. Quintero stages were assigned by standard criteria. Presence of ventricular hypertrophy, cardiomegaly, atrioventricular valve regurgitation (AVVR), ventricular systolic dysfunction and right ventricular outflow tract obstruction on fetal echocardiography were noted. The Doppler myocardial performance index (MPI), an index of global ventricular function, was calculated for both ventricles in subjects with adequate Doppler data. We compared cardiac changes across Quintero stages. RESULTS: There was no cardiomyopathy observed in donor twins. The majority of subjects presented at Quintero Stage I (n = 14), II (n = 14) or III (n = 11), with fewer at Stages IV (n = 2) or V (n = 1). As early as Quintero Stages I and II, a significant proportion of recipient twins had ventricular hypertrophy (17/28, 61%), AVVR (6/28, 21%) or quantitative abnormalities in either right (12/24, 50%) or left (14/24, 58%) ventricular function. Increasing prevalence of biventricular systolic dysfunction and cardiomegaly accompanied advancing Quintero stage. CONCLUSIONS: Changes in cardiac structure and function not reflected in Quintero staging occur in recipient twins early in the evolution of TTTS. Incorporation of cardiac findings into assessment of TTTS severity may prove useful in stratification of risk and treatment selection.     

Early oxidative stress in amniotic fluid of pregnancies with Down syndrome

OBJECTIVE: Some evidence suggests that oxidative stress, due to an imbalance between oxidants and antioxidants, occurs in babies with Down syndrome (DS). This study tests the hypothesis that oxidative stress occurs early in DS pregnancies. DESIGN AND METHODS: Isoprostanes (IPs), a new marker of free radical-catalyzed lipid peroxidation, were measured in amniotic fluid from pregnancies with normal, growth restricted and DS fetuses, diagnosed by karyotype analysis of amniotic cells cultured. RESULTS: A nine-fold increase in IP concentrations was found in amniotic fluid of pregnancies with DS fetuses. This increase (595.15; 542.96-631.64 pg/ml, median; 95% CI), was greater than in pregnancies with fetal growth-restricted fetuses (155; 130.57-172.23 pg/ml, median; 95% CI) and normal fetuses (67; 49.82-98.38 pg/ml, median; 95% CI; p<0.0001). CONCLUSIONS: The study reveals that oxidative stress occurs early in pregnancy and supports the idea of testing whether prenatal antioxidant therapy may prevent or delay the onset of oxidative stress diseases in the DS population.     

Stage I twin-twin transfusion syndrome: rates of progression and regression in relation to outcome.

OBJECTIVES: Twin-twin transfusion syndrome (TTTS) results in high rates of perinatal mortality and neurological morbidity. Fetoscopic laser ablation of placental anastomoses is now established as the treatment of choice for advanced disease. However, there remains controversy about its use in early-stage TTTS, in which laser-related fetal losses need to be balanced against relatively favorable outcomes with more conservative approaches. We investigated rates of progression and regression in Stage I TTTS and determined factors influencing the course of the disease. METHODS: We undertook a retrospective observational study of all TTTS cases referred to our tertiary referral fetal medicine service from 2000 to 2006. In patients presenting with Stage I TTTS, the following variables were evaluated for their ability to predict the course and progression of the disease: gestational age (GA) at presentation, amniotic fluid index, recipient and donor deepest vertical pool, presence of artery-artery anastomoses, small-sized bladder compared to normal donor bladder and fetal size discordance. Study end-points were disease regression or progression, and neonatal survival at 28 days. RESULTS: Among 132 consecutive cases of TTTS, 46 women presented with Stage I disease. In the majority (69.6%), disease remained stable (28.3%) or regressed (41.3%). Of cases that progressed, 79% did so within 2 weeks and 93% progressed to at least Stage III. No factor was significantly linked with progression or regression, although there was a trend towards the absence of an artery-artery anastomosis (P = 0.10) and the presence of a small rather than normal donor bladder (P = 0.10) influencing progression, and later GA at presentation (P = 0.07) influencing regression. At least one infant survived in 83% of cases and there was double survival in 59%. Perinatal outcome was significantly better in cases that regressed (the rates of at least one survivor and double survival being 89% and 89%, respectively) or remained Stage I (77% and 61%, respectively), compared with those cases that progressed (79% and 14%, respectively). Treatment with amnioreduction at first presentation did not influence progression or regression. CONCLUSIONS: This study demonstrates that a high percentage of Stage I TTTS cases regress or remain early stage. Identification of factors predicting progression would facilitate the selection of patients for definitive therapy, while avoiding treatment-related morbidities in mild or transient disease.     

Identification of arterio-venous anastomoses in vivo in monochorionic twin pregnancies: preliminary report.

OBJECTIVE: To determine whether it is possible to identify in vivo placental arterio-venous anastomoses (AVAs) by color Doppler flow mapping. METHODS: Three monochorionic twin pregnancies (one with and two without twin-to-twin transfusion syndrome) underwent placental mapping by color Doppler ultrasound. Placental vessels along the chorionic plate were recorded together with the direction of blood flow and their location in relation to the cord insertions and to superficial arterio-arterial anastomoses. Suggestive AVAs were mapped topographically and results were compared with the findings of formal postnatal placental injection studies. RESULTS: An AVA was identified in each of the three cases. Injection studies showed multiple AVAs. Each antenatally identified AVA was confirmed at placental injection study. Their placental location correlated to other landmarks as predicted by ultrasound. CONCLUSIONS: This preliminary report demonstrates that AVAs can be identified using color Doppler ultrasound. This may facilitate planning for highly selective ablation of AVAs, and shorter procedure times. Formal studies are now indicated to determine the accuracy of this technique.     

Acquired right heart outflow tract anomaly without systemic hypertension in recipient twins in twin-twin transfusion syndrome.

Significant hemodynamic changes are commonly observed in both fetuses in twin-twin transfusion syndrome. In the recipient twin there is cardiac dysfunction with hypertrophy of both ventricles and overall enlargement of the heart. We describe five cases of recipient twins in twin-twin transfusion syndrome with right ventricle hypertrophy, pulmonary stenosis and tricuspid regurgitation acquired in utero. These symptoms developed with no signs of systemic hypertension. Three of the five recipient twins survived and were developing normally at 3-30 months of age. Postnatal outcome is likely to have improved as a result of prenatal diagnosis of right ventricle outflow tract obstruction and timed delivery. These acquired anomalies of the right heart might be related to the particular hemodynamic conditions of the recipient twin. A global heart dilatation is logically expected, but this hypertrophy without dilatation is probably related to the shared plasma of fetuses with opposite hemodynamic conditions. This is what we consider as the hemodynamic-hormonal paradox. These acquired anomalies, though severe, are accessible to neonatal treatment if treated early.