The Twin-to-twin Transfusion Syndrome Research Articles

Maternal Complications After Laser Surgery for Twin-to-Twin Transfusion Syndrome, a Cohort Study.

To assess maternal complications after fetoscopic laser surgery (FLS) for the twin-to-twin transfusion syndrome (TTTS). All consecutive cases treated with FLS for TTTS between 2008 and 2021 at the Leiden University Medical Center (LUMC) were included. We allocated complications in three timeframes: "Admission for laser surgery," "pregnancy after laser," and "delivery and third stage of labor." Maternal complications were graded according to the Maternal and Fetal Adverse Event Terminology (MFAET) and for intra-abdominal hemorrhage, the Common Terminology Criteria for Adverse Events (CTCAE). In the study period, 637 mothers were treated for TTTS with FLS. There were 1559 occurrences of maternal complications. The rate of severe maternal complications (grade 3 or 4) was 8.0%. Severe complications consisted of six cases of severe intra-abdominal hemorrhage, nine cases of severe hemorrhage in pregnancy, one with severe chorioamnionitis, 10 with severe preeclampsia/HELLP syndrome, and 25 with a severe postpartum hemorrhage. Even though it is the gold standard for treating TTTS, FLS comes at a risk to the mother which should not be neglected. And even though not all complications have serious consequences to the mother, the severe maternal complication rate of 8.0% should be added to the inherent risks for the fetus, and should be discussed with patients eligible for surgery in order to make an informed decision on treatment options.

Handheld Active Add-On Control Unit for a Cable-Driven Flexible Endoscope.

The instruments currently used by surgeons for in utero treatment of the twin-to-twin transfusion syndrome (TTTS) are rigid or semi-rigid. Their poor dexterity makes this surgical intervention risky and the surgeon's work very complex. This paper proposes the design, assembly and quantitative evaluation of an add-on system intended to be placed on a commercialized cable-driven flexible endoscope. The add-on system is lightweight and easily exchangeable thanks to the McKibben muscle actuators embedded in its system. The combination of the flexible endoscope and the new add-on unit results in an easy controllable flexible instrument with great potential use in TTTS treatment, and especially for regions that are hard to reach with conventional instruments. The fetoscope has a precision of 7.4% over its entire bending range and allows to decrease the maximum planar force on the body wall of 6.15% compared to the original endoscope. The add-on control system also allows a more stable and precise actuation of the endoscope flexible tip.

Application of Umbilical Artery Classification in Complicated Monochorionic Twins.

We report our experience on the application of Gratacos' classification in a cohort of monochorionic pregnancies complicated by selective intra-uterine growth retardation based on the Doppler assessment of the umbilical artery. A retrospective study was conducted on 52 cases of monochorionic twin pregnancies, in which one twin presented an abdominal circumference at or below the 10th percentile for gestational age. Cases were classified into three types according to the umbilical artery Doppler in the smaller twin. Subsequently, patients were divided into two groups: the selective IntraUterine Growth Retardation group and the Twin-to-Twin Transfusion Syndrome (TTTS) group. Of the total 52 cases, 37 were classified as Type I, 12 as Type II, and 3 as Type III cases. In the total group, progressive fetal deterioration of the smaller fetus requiring active management was observed in 66.7% of Type II and 11.1% of Type I cases (p < .001), and in no Type III case. Unexpected fetal death of the smaller twin was observed more frequently in Type III (two cases, 66.7%) than in Types I and II cases (5% and 33%, respectively). Among the 52 cases, TTTS with oligo-polyhydramnios sequence was diagnosed in 10 cases. The remaining 42 cases were therefore defined as selective intra-uterine growth retardation. In the selective IntraUterine Growth Retardation group, results were similar to those obtained for the whole population. Classification of complicated monochorionic twins based on the umbilical artery Doppler is particularly important for counseling, even when we include TTTS cases, and permits the prediction of clinical evolution and perinatal outcome.

Legal Briefs

Twins (31 3/7 weeks) were born to a 31-year-old healthy mother with a pregnancy remarkable for an accidental administration of epinephrine at 10 3/7 weeks. The mother was experiencing severe hyperemesis gravidarum for which her physician ordered intravenous (IV) dolasetron mesylate (Anzemet®, sanofi-aventis, Bridgewater, NJ), but the outpatient nurse unintentionally administered epinephrine instead. The nurse gave the mother 1 mL of the 1:1,000 concentration of IV epinephrine. In adults, the dose of epinephrine for anaphylaxis is 1 mL of 1:1,000 solution intramuscularly or subcutaneously, and for cardiac arrest, it is 1 mL of 1:10,000 intravenously. The plaintiff experts pointed out that this mother received a concentration of epinephrine 10-fold higher than that used for cardiac arrest; for the 10-week fetuses, they were likewise exposed to a mega-dose. The mother immediately became pale and dizzy and developed chest pain, shortness of breath, tachycardia, and hypertension. An electrocardiograph showed a subendocardial myocardial infarction. A perinatologist closely observed the twins before and subsequent to this event. The twins were diamniotic monochorionic (DiMo) males as a result of in vitro fertilization (IVF). A week after the epinephrine administration, the mother experienced vaginal bleeding and an ultrasound showed a “possible subchorionic hematoma.” At 14 5/7 weeks’ gestation, 30 days after the epinephrine mishap, discordance was noted in the twin size (121 g and 96 g). The larger twin had polyhydramnios, for which 220 mL of red-brown amniotic fluid was removed. Both bladders were visible. No further amnioreduction was needed for the remainder of the pregnancy. The twin-to-twin transfusion syndrome (TTTS) met the least severe grade of the Quintero grading system (I of V). At 30 4/7 weeks’ gestation, the mother experienced a mild brownish discharge. On external monitoring, regular uterine contractions were occurring. The mother was admitted for IV tocolysis and antenatal steroids, …

Akutes fetofetales Transfusionssyndrom - Fallbericht und Literaturübersicht

The perinatal morbidity and mortality risk in monochorionic twin pregnancies are 3-5-fold increased compared to those of dichorionic twin pregnancies. Partially, this is due to the higher rate of preterm delivery but also to the twin-to-twin transfusion syndrome (TTTS). Caused by unidirectional blood flow via placental anastomoses, the TTTS leads to weight differences of more than 20% between monochorial twins. The blood donor often shows oligohydramnios, whereas the recipient shows polyhydramnios. Lewi et al. demonstrated, in a study with 202 monochorionic twin pregnancies, a 9% rate of severe TTTS. The mortality of this complication is about 90% when untreated. In contrast to the chronic TTTS, little is known about the acute intrapartal one, which is characterised by anaemia and hypovolaemia of the donor and polyglobulia of the recipient without significant weight differences between the two. In most cases, anaemia occurred after normal delivery of the first twin. Still, there are no means or signs for early detection. We describe the case of a 30-year-old primigravida with a monochorionic diamniotic twin pregnancy. During pregnancy, no evidence of TTTS could be detected. At 37 + 1 weeks gestation labour was induced with prostaglandin-containing gel. Both foetuses showed cephalic presentation. The CTG of the first twin showed a conspicuous heart rate. After labour the first twin presented with anaemia and hypovolaemic shock, the APGAR was 2/7/8. The infant's haemoglobin was 13.7 g/dL. After delivery, the second twin with APGAR 10/10/10 showed a haemoglobin of 19.6 g/dL, which is in the upper normal range. Their birth weights differed by merely 10.4%. Acute TTTS is frequently characterised by anaemia and hypovolaemia of the second twin. In our case of a monochorionic twin delivery with acute TTTS the donor was born first. Early diagnosis and neonatal intervention is essential for reducing postnatal morbidity and mortality.

Syndrome transfuseur-transfusé : physiopathologie, diagnostic et traitement chirurgical

Multiple pregnancies represent 2% of all pregnancies but account for 20% of admissions to neonatal intensive care units. The outcome of multiple pregnancies is mainly dependent on chorionicity. Most perinatal complications are 3 to 12 times more prevalent in monochorionic pregnancies. The increased mortality and morbidity in this setting are mainly related to vascular anastomoses on the chorionic plate, joining the two fetal circulations. Intrauterine death of a monochorionic twin leads to exsanguination of the survivor, with fatal outcome in 20 to 30% of cases and a similar rate of severe ischemic complications. The most severe and acute complication is the twin-to-twin transfusion syndrome (TTTS). The main clinical manifestations of TTTS are the polyuric polyhydramnios--oliguric oligohydramnios sequence in the recipient and donor twin, respectively. TTTS is associated with a perinatal mortality rate of around 90%, and neurological sequelae are present in 20-40% of survivors born at around 25 weeks. Serial amnioreduction was long the only fetal therapy for TTTS, improving the survival rate to around 50% for at least one twin delivered at around 28 weeks, and reducing the risk of sequelae to around 20% among survivors. We have developed an intrauterine fetoscopic surgical treatment for TTTS. A 2-mm endoscope and a diode laser fiber are introduced percutaneously, under local anesthesia, through a single 3-mm trocard Coagulation of feto-fetal anastomoses on the chorionic plate leads to the survival of at least one twin in around 80% of cases at 33 weeks. Fewer than 10% of survivors have sequelae, mainly related to prematurity. We conducted a randomized controlled trial that confirmed the superiority of laser therapy over amnioreduction. The long-term outlook of these infants is good, with up to 6 years of follow-up.

Commentary

This issue of NeoReviews is devoted largely to disorders of the placenta. In two earlier reviews, Dr Kurt Benirschke provided excellent overviews of the normal and abnormal placenta (see the June 2004 and September 2005 issues of NeoReviews ). The articles in the current issue provide more detail about recent advances in investigations of placental pathology, offering information that should be understood by all neonatologists to help them interpret pathologists’ reports and explain findings better to parents. In addition to expanding our understanding of chorioamnionitis and “demystifying” villitis and fetal thrombotic vasculopathy, this issue includes an extensive discussion of the twin-to-twin transfusion syndrome (TTTS). Although relatively uncommon, this disorder is …

Case Report: Twin-to-Twin Transfusion Syndrome Resulting from Placental Collateral Artery Development

Background The twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies, caused by a net inter-twin transfusion of blood from one fetus (the donor) towards the other fetus (the recipient) through placental anastomoses. TTTS is driven by unidirectional arterio-venous anastomoses, and mitigated by bidirectional arterio-arterial or veno-venous anastomoses which reduce the net inter-twin transfusion. In contrast to these accepted concepts, cases have been described paradoxically devoid of arterio-venous anastomoses but including arterio-arterial anastomoses. We hypothesized that TTTS may develop in such cases as a consequence of a stenosed chorionic artery in the recipient placenta that connects with the arterio-arterial anastomosis. Clinical cases We describe two cases of monochorionic twin placentae without arterio-venous anastomoses but with only an arterio-arterial and veno-venous anastomosis. In one case severe TTTS developed. There, the arterio-arterial anastomosis connected to a stenosed chorionic artery in the recipient placenta and showed a tortuous appearance. The other case developed uneventful. It lacked a stenosed chorionic artery and the arterio-arterial anastomosis was non-tortuous. Conclusion We present evidence that the arterio-arterial anastomosis represented a functional collateral artery whose outgrowth was driven by an increased shear-stress caused by an increased flow to a lower pressure vascular bed in the placenta of the recipient. The lower arterial pressure occurred from the moment that a chorionic artery which was connected to the anastomosis developed a significant stenosis. The resulting collateral flow through the anastomosis maintained blood supply to the lower pressure placental bed, the beneficial function of collaterals, but also resulted in an increasing net inter-twin transfusion which triggered onset of severe TTTS.

Twin‐to‐twin transfusion syndrome: Is the future getting brighter?

The twin-to-twin transfusion syndrome (TTTS) continues to pose a major challenge in the area of fetal therapy. Untreated, the mortality and morbidity are extremely high, and the fact that there are two structurally normal fetuses at risk makes the case for effective in utero therapy even more compelling. Advances in therapeutic procedures, in particular the development of selective laser photocoagulation of intertwin vascular anastomoses, have improved outcomes, both in terms of survival and survival free of disability. This review examines the pathophysiology, diagnosis, surveillance, contemporary therapies, expected outcomes and ongoing challenges in TTTS.

Septostomy with amniodrainage in the treatment of twin-to-twin transfusion syndrome: a 16-case report

To report the treatment results of 16 monochorionic and diamniotic gestations cases, which had complications due to the twin-to-twin transfusion syndrome (TTTS), the neonatal and other possible complications of the septostomy associated to the amniodrainage. Based on ultrasonographic findings, 16 pregnant women were diagnosed with the twin-to-twin transfusion syndrome (TTTS). These cases were divided in two groups: one of them included the fetuses without hydrops and the second included the "recipient" fetuses with hydrops. The therapy measures included septostomy with or without amniodrainage. The following parameters were evaluated: gestational age at the time the septostomy was performed, volume of drained amniotic fluid, gestational age at delivery, birth weight, postnatal evolution, and procedure complications. The average gestational age for this procedure was of 23.6 weeks (from 14 weeks and 1 day to 33 weeks). The gestational age for the septostomy until the delivery was of 8.18 weeks (from 1.0 to 21.3 weeks). The survival rate in the group without hydrops was of 68.7%, while in the second group it was of 25%. Some of the complications were as follows: two cases of premature membrane rupture and one case of preterm labor. Septostomy with amniodrainage, when performed on the initial stages and on earlier gestational ages has good perinatal results.

Management of the twin-to-twin transfusion syndrome (TTTS)

Twin-to-twin transfusion syndrome (TTTS) is a severe complication of multiple pregnancy occurring in 10–12% of monochorionic twins. This complication is mainly due to the presence of unbalanced arterio-venous anastomoses between placental branches of the umbilical circulations. The natural history of TTTS is variable. It is often difficult to predict whether a patient will show stable rather than rapidly progressive disease. A formal staging system has been suggested based on the sonographic time sequence of cases with progressive deterioration and poorer outcome. The mortality of untreated TTTS has been quoted to be more than 80% with advances in neonatal care the mortality rate may have decreased. The three most commonly used therapies for mid-trimester TTTS are amnioreduction, fetoscopic laser coagulation of the vascular anastomoses and septostomy. Outcome for fetuses with TTTS treated with amnioreduction depends on several antenatal variables which may help in counseling patients. Fetoscopic laser coagulation of vascular anastomoses represents an important evolution in the surgical treatment of TTTS. The management of the TTTS according to stage should be corroborated with an appropriate clinical trial.

Management of the twin-to-twin transfusion syndrome (TTTS)

Twin-to-twin transfusion syndrome (TTTS) is a severe complication of multiple pregnancy occurring in 10–12% of monochorionic twins. This complication is mainly due to the presence of unbalanced arterio-venous anastomoses between placental branches of the umbilical circulations. The natural history of TTTS is variable. It is often difficult to predict whether a patient will show stable rather than rapidly progressive disease. A formal staging system has been suggested based on the sonographic time sequence of cases with progressive deterioration and poorer outcome. The mortality of untreated TTTS has been quoted to be more than 80% with advances in neonatal care the mortality rate may have decreased. The three most commonly used therapies for mid-trimester TTTS are amnioreduction, fetoscopic laser coagulation of the vascular anastomoses and septostomy. Outcome for fetuses with TTTS treated with amnioreduction depends on several antenatal variables which may help in counseling patients. Fetoscopic laser coagulation of vascular anastomoses represents an important evolution in the surgical treatment of TTTS. The management of the TTTS according to stage should be corroborated with an appropriate clinical trial.

Early Intertwin Differences in Myocardial Performance During the Twin-to-Twin Transfusion Syndrome

In the twin-to-twin transfusion syndrome (TTTS), pressure rather than volume overload is increasingly considered as a key factor in the pathogenesis of the cardiomyopathy of the recipient twin. If this is the case, cardiac dysfunction should be among the first signs observed with TTTS. The objective of this study was to determine whether intertwin differences in myocardial function are modified early in the course of TTTS and whether they can help to differentiate this condition from intrauterine growth restriction (IUGR). Eight variables were analyzed on the first fetal echocardiography on 21 pairs of twins with TTTS and 11 with IUGR. No difference was found between the 2 groups for the cardiothoracic ratio, pulsatility indices in the umbilical and middle cerebral arteries, and peak velocity of the middle cerebral artery. Significant difference was found for ventricular septal thickness, but with no association with the conditions under study. With TTTS, left ventricular shortening fraction was consistently greater in the donor twins, and myocardial performance indices (MPIs) were elevated in the recipient twins. This increase in MPI was caused by a lengthening of the isovolumic periods compared with those of the donor twin: left ventricular and right ventricular isovolumic periods 0.105+/-0.047 and 0.097+/-0.026 seconds, respectively, for the recipient twins versus 0.0561+/-0.46 and 0.065+/-0.03 seconds, respectively, for the donor twins (P<0.001). These changes in the isovolumic periods were mainly due to significant prolongation of isovolumic relaxation times. A change in left ventricular MPI > or =0.09 combined with a change in right ventricular MPI > or =0.05 would identify a TTTS with a sensitivity of 75% and a false-positive rate of 9%. The observed diastolic function impairment goes along with the pressure-overload pathogenic concept proposed in TTTS. Assessment of intertwin difference in MPI is a valuable tool for early differential diagnosis between TTTS and isolated IUGR.

The Placenta

The human placenta is a discoid organ that has a hemochorial relationship with the mother. That is to say, the trophoblast that covers the villi is in direct contact with the maternal blood. Transfer of substances has to traverse the syncytiotrophoblast, cytotrophoblast, villous basement membrane, fetal capillary bed, and its endothelium. Although the placenta is the most available tissue, it is the least thoroughly investigated organ, and many aspects of its control still are unknown. Especially deficient is our knowledge of the genetic control of its many functions. The placenta also has a different imprinting pattern (paternal imprinting) from that of the embryo. The prevailing sentiment is that once delivery has occurred, it is a superfluous tissue that only needs to be discarded. There are many reasons, however, that knowledge of placental pathology can aid materially in a better understanding of newborns who have anomalies or neonatal problems. Further, a detailed examination of the placenta at birth can provide a better insight into prenatal life and its possible disturbances than is possible from notes in the history of the patient. The shape of the placenta is extremely variable (Fig. 1), probably due to placental location, its interaction with the endometrium, and uterine shape. The placenta implants anywhere in the uterus, but most commonly, it is in an anterior or posterior location. Much less often it is on the fundus. The shape often can be understood best by considering the history of its implantation. The reason for a specific shape can be derived further from the frequently aberrant shapes of twin placentas where competition for space in the uterus, a phenomenon that has been termed “trophotropism,” can be inferred to have existed. This term was used initially in attempts to explain the placental features in the uncommon event of a placenta …

Pulmonary stenosis and reactive right ventricular hypertrophy in the recipient fetus as a consequence of twin-to-twin transfusion.

The present study describes an association between adverse outcome in the twin-to-twin transfusion syndrome (TTTS) and pulmonary stenosis or reactive right ventricular hypertrophy. Six discordant monozygotic twin pregnancies with TTTS are described. Ventricular hypertrophy and atrioventricular valvular regurgitation occurred in all the recipient twins with pulmonary valvular stenosis in three cases and infundibular stenosis in one case. The recipient twin in one pair and both twins in another pregnancy died as a consequence of immaturity but the remaining twins all survived. Surgical intervention was required in one baby for valvular pulmonary stenosis. Our observations suggest that elevated blood pressure in the transfusion recipient may play an important role in pathogenesis. We hypothesise that both pulmonary stenosis and right chamber hypertrophy are secondary to hemodynamic changes. Although we have found valvular pulmonary stenosis in three recipients and infundibular stenosis in only one, this (obstruction to outflow) could be due to right chamber hypertrophy.