|Twin to twin transfusion syndrome and
monochorionic twinning European network
Title of the project
Full title of proposal: TWIN TO TWIN TRANSFUSION SYNDROME AND MONOCHORIONIC TWINNING EUROPEAN NETWORK
Short title or acronym: EURO-TWIN-2-TWIN
Background and rationale - Monochorionic twin pregnancies are high risk pregnancies
The risk for fetal or neonatal death and long term sequellae in twin pregnancies is about five times greater than in singletons. The incidence of twin pregnancies is about 1/90 pregnancies, of which half of them are identical or monozygotic. Identical twins have a higher risk for complications than non-identical twins. At closer look, it is rather chorionicity (number of placentas) than zygositiy (the number of ovocytes fertilised) which determines outcome of pregnancy. About two in three identical twin pairs are monochorionic (MC). Neonatal literature lists for MC twins a twice as high mortality compared to DC twins and four times as high compared singletons. However perinatal statistics underestimate the problem as even more pregnancies are lost prior to viability. Though data are extremely scarce, recent estimates show a 6 times higher risk for fetal loss rate prior to 24 weeks, a nearly double rate of preterm delivery and of perinatal mortality and a four times higher risk for low birthweight, with all its consequences.
These data show clearly that, although rather rare (3/1,000), MC twins are high risk pregnancies, prone to significant morbidity and mortality. Since chorionicity can be determined by ultrasound examination, patients can in theory timely be identified. Given that many pregnancies are complicated prior to viability, it seems warranted to start surveillance early in gestation. However, because of the lack of data, there are at present no guidelines on how this should be donerealized, let be what action should be taken based on the observations made.
Objectives and primary approaches as per initial application
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The most important difference between MC and DC twin pregnancies is that there are vascular connections in (nearly) all MC placentas, which therefore is probably related to the difference in outcome. A certain pattern of intertwin anastomoses can lead to an even rarer (0,5/1,000 life births), yet more dreadful complication of MC twin pregnancy. Twin-to-twin transfusion syndrome (TTS) is based on a chronic and net transfusion of blood of one fetus to the other, leading to a number of problems, such as preterm rupture of the membranes, preterm labour and birth and intra-uterine fetal death (IUFD). Untreated it is associated with an overall fetal loss rate of 80 % and an over 30 % chance for neurological lesions and mental handicap, seriously affecting later quality of life. The condition is therefore usually treated. Until 1995, the mainstay of therapy has been to drain excessive amniotic fluid, with survival rates of about 50 %, however still with a chance of 20 % for neurologic morbidity. More recently, a more causative approach was proposed by two of the applicants of this proposal. By means of a percutaneous “fetoscopic” operation, anastomosing vessels are visualized and coagulated with laser. Survival rates are about 60-68 % per fetus and a more than 80 % chance for at least one survivor, with a striking reduction in neurologic morbidity to 5 % at birth. It remains at present uncertain which of the two therapies is best, and if there would be a place for a stratified approach. It is proposedhave set up a clinical trial in this respectd.
The general public and even medical professionals are still very much unaware of TTS, let bethe risks associated to MC pregnancies in general, and the importance of diagnosing MC status early in gestation. We have addressed this problem. It is believed that with appropiate means, the efficacy of an ultrasound follow up programme for MC twins can be demonstrated. Also the lack of insight into the pathophysiology of the condition could be overcome. With sufficient prospectively collected data, it may be possible to predict which MC twins will develop TTS, at what stage or with which degree of severity, and whether it would be beneficial to treat TTS in its early stages. For that purpose a consortium of leading clinical centers throughout Europa that have a proven expertise in the field of MC twins were gathered with patient organisations and the medical industries, to achieve the following goals:
These are three-fold:
1) To carry out large enough clinical studies to determine the true outcome of MC twin pregnancy, the risk for TTS, what would be the best therapy for TTS and to model MC twin pregnancy in order to predict outcome, the risk for TTS and to improve outcome following therapy;
2) To correlate the most probable underlying cause for the increased risk of MC twins, i.e. the angioarchitecture, to the outcome, in order to use this information for determining best follow up or therapy;
3) To develop new software to complement existing fetal databases for this pathology and new technology for treating selected cases of TTS;
4) to overcome the unawareness of the medical community and the lack of information for citizens about this condition.
The following specific objectives and correlated deliverables are defined:
PATHOPHYSIOLOGY AND IMPROVEMENT OF OUTCOME AND THERAPY.
Since it is believed that most of the risks of MC twin pregnancies are related to the presence and pattern of vascular anastomoses, information on the angio-architecture placenta of these pregnancies is essential.