Evaluation and management of twin-twin transfusion syndrome: still a challenge
2007; Elsevier BV; Volume: 196; Issue: 5 Linguagem: Inglês
10.1016/j.ajog.2007.01.041
ISSN1097-6868
Autores Tópico(s)Prenatal Screening and Diagnostics
ResumoThe management of twin-twin transfusion syndrome (TTTS) remains a challenge. Untreated, perinatal morbidity and mortality rates are as high as 90-100%. Optimal treatment continues to be debated, although publication of the Eurofetus trial1Senat M.V. Deprest J. Boulvain M. Paupe A. Winer N. Ville Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome.N Engl J Med. 2004; 351: 136-144Crossref PubMed Scopus (1062) Google Scholar in 2004 resulted in the widespread embrace of laser surgery for this disorder. See related article, page 450 See related article, page 450 Essentially all monochorionic twin placentas contain vascular anastamoses, including arterioarterial (AA), arteriovenous (AV), and venovenous connections. Severe TTTS requiring therapy occurs in approximately 8% of unselected monochorionic twin pregnancies2Fick A.L. Feldstein V.A. Norton M.E. Wassel Fyr C. Caughey A.B. Machin G.A. Unequal placental sharing and birth weight discordance in monochorionic diamniotic twins.Am J Obstet Gynecol. 2006; 195: 178-183Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar and is thought to result from twin-to-twin transfusion through uncompensated, unidirectional AV connections. The disorder is associated with vasoactive mediators in both donor and recipient twins and a clinical picture of polyhydramnios/oligohydramnios sequence, cardiac decompensation, neurological abnormalities, intrauterine growth retardation, and preterm delivery. Perinatal mortality can occur in utero or because of severe prematurity. In survivors, neurologic abnormalities, on imaging studies and by clinical evaluation, are reported in 10-69% of subjects.1Senat M.V. Deprest J. Boulvain M. Paupe A. Winer N. Ville Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome.N Engl J Med. 2004; 351: 136-144Crossref PubMed Scopus (1062) Google Scholar, 3Lopriore E. van Wezel-Meijler G. Middeldorp J.M. Sueters M. Vandenbussche F.P. Walther F.J. Incidence, origin, and character of cerebral injury in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery.Am J Obstet Gynecol. 2006; 194: 1215-1220Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar Our understanding of the pathophysiology, diagnostic criteria, and optimal treatment for TTTS have all evolved in recent years. Early studies of therapeutic amniocentesis and septostomy focused on equilibrating the amniotic fluid discordance. More recently endoscopic laser has been used to obliterate the anastamoses, directly interfering with the intertwin transfusion process. All therapeutic modalities have been reported to improve outcomes, with perinatal survival rates of 65-85%.4Quintero R.A. Dickinson J.E. Morales W.J. et al.Stage-based treatment of twin-twin transfusion syndrome.Am J Obstet Gynecol. 2003; 188: 1333-1340Abstract Full Text Full Text PDF PubMed Scopus (272) Google Scholar Recognizing that a randomized trial was needed to determine the optimal treatment, the Eurofetus Consortium reported on a randomized, controlled trial of serial amnioreduction vs laser therapy in 2004.1Senat M.V. Deprest J. Boulvain M. Paupe A. Winer N. Ville Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome.N Engl J Med. 2004; 351: 136-144Crossref PubMed Scopus (1062) Google Scholar The authors concluded that laser therapy resulted in improved survival of at least 1 twin, 76% vs 56% in the amniocentesis group. The laser group also had lower rates of cystic periventricular leukomalacia (6% vs 14%) and improved rates of survival without neurologic complication at 6 months of age (52% vs 31%). That study was concluded early after a planned interim analysis demonstrated improved survival in the laser group. In this issue of the Journal, Dr. Lenclen and colleagues report on a retrospective study comparing neonatal outcomes of treated TTTS cases that delivered between 24 and 34 weeks of gestation, with those of dichorionic preterm twins delivered in the same gestational age range. Their aim was to study the relative contributions of prematurity and treatment modalities to neonatal outcome. The study compares 137 neonates from 79 pregnancies treated for TTTS with 242 neonates from 130 dichorionic twin pregnancies. Of the TTTS cases, about half participated in the Eurofetus trial, including most of the amniocentesis-treated twins (18 of 21 pregnancies). The primary outcome was neonatal death or severe cerebral lesions (cystic periventricular leukomalacia or grade III or IV intraventricular hemorrhage), and they sought to determine which lesions were of antenatal origin. The authors also evaluated failed laser surgery, defined as persistent polyhydramnios/oligohydramnios or marked discordance in hemoglobin levels at birth, as a contributor to adverse outcome. The study provides 3 analyses, comparing the outcomes of amniocentesis (AR) vs laser-treated TTTS twins, AR vs dichorionic twins, and laser-treated TTTS vs dichorionic twins. In the Eurofetus trial, the improved outcomes associated with laser were caused in large part by a prolongation of gestation, with a median gestational age at delivery of 33.3 weeks vs 29.0 weeks in the AR group. In this current study, the authors focused on a subset of preterm infants, with an average gestational age at delivery of 28.9 weeks in the AR group, 30.1 weeks in the laser group, and 30.5 weeks in the dichorionic twin control group. Among TTTS cases, perinatal mortality was higher (47.6% vs 23.3%) and severe cerebral lesions more frequent (37.9% vs 16.2%) in the AR versus laser group; cerebral lesions were more commonly of antenatal origin in the laser group (56% vs 36%). After adjustment for gestational age at birth, adverse neonatal outcome (death or severe cerebral lesions) remained more frequent in neonates treated by AR. The goal of laser is generally to ablate all anastamoses and “dichorionize” the placenta, so perhaps the most interesting comparison in this study is between laser-treated TTTS twins and dichorionic twins. The gestational ages of these 2 groups were comparable, as was neonatal mortality. The perinatal mortality rate was higher in the laser-treated TTTS group (23.3% vs 12.3%), as was neonatal neurologic morbidity (16.2% vs 8.0%). Severe cerebral lesions were of antenatal origin in 56% of the laser group but only 10.5% of the dichorionic twin group. Interestingly, logistic regression showed no relationship between adverse neonatal outcome and group, steroid therapy, intrauterine fetal demise of a cotwin, and intertwin birthweight discordance. Following the publication of the Eurofetus trial, an ongoing National Institutes of Health–funded, multicenter trial in the United States was suspended, in part because many felt that the question had been answered. It is now estimated that 10-15 perinatal centers in the United States are offering endoscopic laser for TTTS, and many more are working to establish programs. Data from the relatively small number of patients that were randomized in the United States trial (n = 40), however, found no difference in 30 day survival between those treated with AR vs laser. In cases with stage III and IV disease, 30 day survival was only 12.5% in the laser group.5Crombleholme T. Shera D. Porter F. et al.NIH sponsored prospective randomized clinical trial o f amnioreduction vs selective fetoscopic laser photocoagulation for twin-twin transfusion syndrome.Am J Obstet Gynecol. 2007; 195: A44Google Scholar Differences in case selection and varying skill or experience of the operators, as well as small numbers, are possible explanations for the poorer outcomes in this study. Although laser ablation appears to result in better outcomes than AR in most published series, the outcomes of TTTS pregnancies clearly remain suboptimal. Demise of at least 1 infant occurs in 38% of cases, even following intervention6Cavicchioni O. Yamamoto M. Robyr R. Takahashi Y. Ville Y. Intrauterine fetal demise following laser treatment in twin-to-twin transfusion syndrome.BJOG. 2006; 113: 590-594Crossref PubMed Scopus (65) Google Scholar and preterm premature rupture of membrane complicates approximately 28% of cases.7Yamamoto M. El Murr L. Robyr R. Leleu F. Takahashi Y. Ville Y. Incidence and impact of perioperative complications in 175 fetoscopy-guided laser coagulations of chorionic plate anastomoses in fetofetal transfusion syndrome before 26 weeks of gestation.Am J Obstet Gynecol. 2005; 193: 1110-1116Abstract Full Text Full Text PDF PubMed Scopus (145) Google Scholar In the Eurofetus trial, just 52% of laser-treated infants were alive and free of neurological complications at 6 months of age, and only 36% of pregnancies resulted in 2 survivors. This current study also reports a higher rate of severe cerebral lesions in TTTS twins as compared with their dichorionic counterparts, regardless of treatment modality. Counseling of women considering treatment for severe TTTS still requires circumspection regarding outcomes. The results of this study confirm several other important points. The authors note that survivors have as good an outcome as dichorionic twins of the same gestational age, when surgery is successful and the pregnancy reaches at least 30 weeks’ gestational age. However, treatment failures continue to occur and were responsible for preterm delivery in 25.8% of cases in this series. In neonates with severe cerebral lesions following laser, more than half were felt to have occurred antenatally, although the timing and mechanisms of such injury are unknown. The relationship of placental angioarchitecture and TTTS outcomes also remains incompletely understood. It appears that the presence of an AA anastomosis decreases the chance of developing TTTS and improves survival in those who do develop the disease.8Tan T.Y. Taylor M.J. Wee L.Y. Vanderheyden T. Wimalasundera R. Fisk N.M. Doppler for artery-artery anastomosis and stage-independent survival in twin-twin transfusion.Obstet Gynecol. 2004; 103: 1174-1180Crossref PubMed Scopus (53) Google Scholar Should an attempt be made to investigate the pattern of anastamoses sonographically prior to deciding on the most appropriate treatment approach? And in cases in which there is severe growth discordance and the smaller twin unlikely to survive, is selective fetocide a more appropriate intervention with better outcomes for the cotwin? Like so many of our interventions in obstetrics, endoscopic laser for the treatment of TTTS is a train that is quickly leaving the station. Although the technique is frequently referred to as minimally invasive, maternal complications can and do occur. Like many techniques, there is a learning curve, and complications and success rates are operator dependent. Best patient care may be provided by a limited number of skilled and experienced practitioners with the expertise to select the best candidates and the volume to continue to accumulate data on clinical outcomes. I would hope that the lessons of electronic fetal monitoring would temper our enthusiasm for widespread adoption of incompletely studied high-tech interventions. We should remain cautious in our approach to the introduction of new techniques and continue to focus research on improvement of our clinical outcomes. Neonatal outcome in preterm monochorionic twins with twin-to-twin transfusion syndrome after intrauterine treatment with amnioreduction or fetoscopic laser surgery: comparison with dichorionic twinsAmerican Journal of Obstetrics & GynecologyVol. 196Issue 5PreviewThe purpose of this study was to compare neonatal outcome in preterm neonates after twin-to-twin transfusion syndrome (TTTS) that was treated by amnioreduction or fetoscopic laser surgery (FLS) and in dichorionic neonates who were matched for gestational age at birth. Full-Text PDF
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