The aim of this study was to describe the neonatal management and outcome in monochorionic twins with twin-to-twin transfusion syndrome (TTTS) not treated with fetoscopic laser surgery. All... Show moreThe aim of this study was to describe the neonatal management and outcome in monochorionic twins with twin-to-twin transfusion syndrome (TTTS) not treated with fetoscopic laser surgery. All consecutive live-born neonates with TTTS managed at our center between 2002 and 2021 were included in this retrospective study. Neonatal outcome was assessed in 44 twin pairs with TTTS not treated with laser (nonlaser group) compared to a control group of 88 twin pairs with TTTS successfully treated with laser (laser group), matched for gestational age at birth. Primary outcome was adverse neonatal outcome, a composite outcome including neonatal mortality or severe neonatal morbidity. The incidence of adverse neonatal outcome in the nonlaser group and laser group was 30% (26/88) and 11% (19/176), respectively (relative risk = 3.46, 95% CI [1.79, 6.71]). In the nonlaser group, 11% had necrotizing enterocolitis (vs. 2% in the laser group) and 24% had hypotension (vs. 10% in the laser group). Recipients in the nonlaser group had, compared to recipients in the laser group, significantly more severe cerebral injury (18% vs. 5%) and more polycythemia at birth (21% vs. 1%). Donors in the nonlaser group had, compared to donors in the laser group, more severe growth restriction (71% vs 42%), renal failure (11% vs 1%), and anemia at birth (25% vs. 7%). Thus, the risk for neonatal mortality and/or severe morbidity is three-fold higher in TTTS not treated with laser than in TTTS treated with laser, which highlights the fact that these neonates with TTTS are very sick at birth, requiring accurate and prompt intensive treatment. Show less
Monochorionc twin pregnancies carry a high risk for adverse pregnancy outcome. The unique placenta angioarchitecture in monochorionic twin pregnancies might cause specific complications such as... Show moreMonochorionc twin pregnancies carry a high risk for adverse pregnancy outcome. The unique placenta angioarchitecture in monochorionic twin pregnancies might cause specific complications such as twin-to-twin transfusion syndrome (TTTS) and selective intrauterine growth restriction (sIUGR). The hemodynamic challenges in these complications require specific adaptation of the fetal heart. Subsequently, a higher risk for fetal demise and acquired cardiac abnormalities is present in these cases.In part one of this thesis we focused on the risk for fetal demise. We investigated possible predictors for fetal demise after laser therapy for TTTS, and found that abnormal Doppler profiles and the presence and absence of certain anastomoses are associated with this complication. Beside this, we investigated the possible relation between proximate cord insertion and fetal deterioration.In part two we investigated possible predictors for the development of right ventricular outflow tract obstruction (RVOTO), and found that an early gestational age at onset of TTTS and cardiac dysfunction are associated with this complication. We described that postnatal RVOTO is not only found in recipients, but also in donors and sIUGR cases. We described the spectrum of prenatal RVOTO in relation to postnatal RVOTO. Lastly we introduced a new modality to detect fetal cardiac dysfunction. Show less
Eschbach, S.J.; Gijtenbeek, M.; Geloven, N. van; Oepkes, D.; Haak, M.C. 2019
This thesis presents a number of articles studying the placental angioarchitecture of both TTTS and TAPS to investigate the pathogenesis of these diseases.
The incidence of spontaneous twinning in the Netherlands is approximately 1%, of which are 70% dizygotic and 30% monozygotic twins. Dizygotic twinning occurs after fertilization of two eggs (non... Show moreThe incidence of spontaneous twinning in the Netherlands is approximately 1%, of which are 70% dizygotic and 30% monozygotic twins. Dizygotic twinning occurs after fertilization of two eggs (non-identical twins). Dizygotic twins almost invariably have two separate placentas (dichorionic) and two separate amnions (diamniotic). Monozygotic twinning occurs after fertilization of one egg that splits into two embryos (identical twins). In 70-75%, these twins share one common placenta (monochorionic) and have two separate amnions (diamniotic). The incidence of monochorionic twinning is 1 in every 400 pregnancies. During gestation, monochorionic twins compared to dichorionic twins are at increased risk of several complications, such as intrauterine fetal death, intrauterine growth restriction, discordant fetal anomalies, and, most severe, twin-to-twin transfusion syndrome (TTTS). TTTS complicates 10 to 15% of monochorionic twin pregnancies. With an annual birth rate of 188 000, between 47 and 67 cases of TTTS are expected in the Netherlands per year. In virtually all monochorionic twin placentas, vascular connections between the two twins are present, whereas these almost never occur in dichorionic placentas. Thus, intertwin transfusion is the norm in monochorionic pregnancies and a normal physiological phenomenon as long as blood flow between the fetuses is balanced. TTTS develops when blood flow gets unbalanced. Hypovolemia, oliguria and oligohydramnios develop in the donor twin. The recipient twin suffers from hypervolemia, polyuria and polyhydramnios, which may lead to circulatory volume overload, cardiac failure and, eventually, hydrops. TTTS is diagnosed sonographically by the detection of an oligo/polyhydramnios sequence. Quintero et al. developed a staging system for TTTS based on the oligo/polyhydramnios sequence (Stage 1), and also included absent bladder filling in the donor (Stage 2), pathological Doppler findings in donor or recipient (Stage 3), hydrops (Stage 4), and eventually fetal death (Stage 5). TTTS usually emerges in the second trimester of pregnancy, although first-trimester and early third-trimester cases have been described. Due to massive polyhydramnios, TTTS may lead to maternal discomfort and present with clinical symptoms, such as premature rupture of membranes or contractions. This may result in (extremely) premature birth and high mortality and morbidity rates. If left untreated, mortality rates exceed 80% and survivors are handicapped in 10 to 50%. Since the 1980__s, several forms of treatment have been available, of which fetoscopic laser coagulation of the vascular anastomoses on the monochorionic placenta has been proven to be superior compared to serial amniodrainage in terms of perinatal survival and absence of neurological disease in survivors. Moreover, treatment in the early Quintero stages resulted in better outcome. Since 2000, monochorionic twin pregnancies complicated by TTTS have been treated with fetoscopic laser coagulation of placental anastomoses in the Leiden University Medical Center (LUMC), which is a tertiary medical center in the Netherlands and serves as the national referral center for fetal therapy. Since then, several studies on monochorionic twins with and without TTTS were started. TULIPS, Twins and ULtrasound In Pregnancy Studies, was one of these projects. Between July 2003 and July 2005, 58 monochorionic twins with and without TTTS had an ultrasound examination performed at least biweekly. The aims of our study were to evaluate serial ultrasound examinations combined with patient instructions in achieving timely detection of TTTS in a cohort of monochorionic diamniotic twin pregnancies, and to study the effects of TTTS and fetoscopic laser coagulation of the placental anastomoses on fetal hemodynamics of monochorionic twins. Chapter 1 contains a review of the literature on ultrasound examination in monochorionic twins and twin-to-twin transfusion syndrome during gestation. In part 1 of this chapter, the importance of first-trimester ultrasound examination to diagnose chorionicity is discussed in detail. To assess chorionicity, the intertwin membrane should be imaged at its insertion site to the placental mass. A lambda (_)-, __Y__- or twin peak sign indicates dichorionicity, whereas a __T__ sign must be visualized in monochorionic diamniotic twin pregnancies. The observation of two separate placentas alone is not sufficient to diagnose dichorionicity. A single placental mass does not prove monochorionicity. Thickness of the intertwin membrane and fetal gender are not considered reliable indicators of chorionicity. The complications of monochorionic twinning, such as single intrauterine fetal death, intrauterine growth restriction, discordant fetal anomalies, and TTTS, are outlined in short. Part 2 is focused on ultrasound and TTTS. Current insights in the pathophysiology, diagnosis, treatment and outcome are reviewed. Sonographic markers early in pregnancy that could forecast the development of TTTS are described, such as increased nuchal translucency, abnormal Doppler studies of the ductus venosus, folding of the intertwin membrane, and the sonographic absence of arterioarterial anastomoses. Furthermore, an overview of the most important Doppler studies in TTTS is supplied. Pathological Doppler studies in the donor are consistent with decreased venous return due to hypovolemia and increased cardiac afterload due to increased placental resistance. Pathological Doppler studies in the recipient are caused by congestive heart failure due to hypervolemia. Fetoscopic laser ablation of the placental anastomoses in TTTS affects the fetal and fetoplacental circulation in various ways, such as transient volume overload in donors and improvement of cardiac function in recipients, resulting in changed Doppler studies after therapy. Finally, the fetal heart in TTTS is discussed. Particularly recipients may be affected by prenatal cardiac failure. Donors show no or little cardiac pathology. The exact cause of cardiac dysfunction is unclear, however, primary cardiac pathology, increased preload, or increased afterload are suggested to play a role. In conclusion, most twin pregnancies have an uneventful course, although twins are at greater risk than singletons, particularly those that are monochorionic. TTTS is the most severe complication during gestation. TTTS is diagnosed sonographically, and that is why ultrasound examination is an essential tool in prenatal care for monochorionic twins. In chapter 2 we undertook a study to report the occurrence of bipartite monochorionic twin placentas. Examination of 109 monochorionic placentas delivered at our institution between June 2002 and June 2005 was performed. Placental characteristics on prenatal ultrasound were studied, including single or double appearance and type of intertwin membrane-placental junction (__T__ sign or lambda sign). Monochorionicity was confirmed by postnatal histologic confirmation (diamniotic intertwin membrane without chorionic tissue within the dividing septum). Bipartition was diagnosed when two separate placental masses attached by membranes were identified. Of the 109 monochorionic placentas, three were composed of two separate placental masses. Prenatal ultrasound examination showed two separate placental masses in each case. Monochorionicity was suspected on prenatal ultrasound due to the presence of __T__ sign in two cases and TTTS in another case. Microscopic examination of the dividing septum was consistent with monochorionicity in each case. Vascular anastomoses were present in two of the three placentas, and led in both cases to the development of TTTS. We concluded that two separate placental masses in twin pregnancies are not per se dichorionic and may occur in almost 3% of monochorionic placentas. Second-trimester twin-to-twin transfusion is well known, but first-trimester cases have been rarely described. In chapter 3 we present the case of a monochorionic twin at 11+0 weeks of gestation with single increased nuchal translucency and normal karyotypes. At 12+5 weeks of gestation, double intrauterine death was diagnosed, followed by delivery of a strikingly red and white fetus. In conclusion, TTTS can be seen in various ways at different gestational ages. Besides the well-known risks of severe second-trimester TTTS, we believe that TTTS can cause fetal death or neurological damage, even in the first trimester of pregnancy. The only presenting symptom may be a single increased nuchal translucency. In chapter 4 we assessed the value of serial ultrasound examinations together with patient instructions to report the onset of symptoms in achieving timely detection of TTTS in a cohort of monochorionic diamniotic twin pregnancies, and to evaluate sonographic TTTS predictors. 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 two-year period, a prospective series of 23 monochorionic twin pregnancies was monitored from the first trimester until delivery. At least every two 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 to 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. 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. We concluded that biweekly ultrasound examinations, with special attention to 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. In chapter 5 we investigated fetal hemodynamics in monochorionic twins with TTTS before and after fetoscopic laser therapy, focusing on the renal and cerebral blood flow. In a prospective study, we performed Doppler studies in monochorionic twin pregnancies with TTTS. The pulsatility index (PI) and end-diastolic flow (EDF) of the umbilical artery (UA) (recorded as present, absent or reversed); the PI and the peak systolic velocity of the middle cerebral artery (MCA PSV); the maximum flow velocity (V max) and flow pattern of the intrahepatic part of the umbilical vein (UV) (classified as pulsatile or non-pulsatile); the pulsatility index for veins (PIV) and A-wave of the ductus venosus (DV) (recorded as present, absent or reversed); and the PI and PSV of the renal artery (RA) were measured within 24 h before, 12 to 24 h and 4 to 10 days after laser therapy. At each examination, the presence or absence of tricuspid regurgitation (TR) and of hydropic signs (pleural effusion, ascites, pericardial effusion, or skin edema) was recorded. Hemoglobin values and reticulocyte counts were determined at birth. Long-term follow-up was assessed at the age of 2 years. In donor twins (n=34), DV PIV increased significantly 12 to 24 h after laser therapy, however returned to pre-operative values within 4 to 10 days. A significant decrease in UA PI and increase in UV V max was detected after laser treatment. Twenty percent (6/30) showed signs of TR 12 to 24 h after laser therapy, which was resolved completely after 4 to 10 days. The MCA PI and RA PI were significantly decreased 12 to 24 h after laser treatment, however returned to pre-operative values within 4 to 10 days. MCA and RA PSV values were unchanged by fetoscopic laser therapy. In recipient twins (n=32), DV PIV decreased significantly 4 to 10 days after laser therapy. The RA PI increased non-significantly after laser treatment; RA PSV values were unchanged. MCA PI and MCA PSV values increased significantly after laser therapy. After birth, mean hemoglobin values of donors (17.3 _ 4.9 g_/dL) and recipients (16.1 _ 4.2 g_/dL) were comparable (p=0.43). At the age of 2 years, neurodevelopmental impairment was diagnosed in 15% (4/26) of donors and in 10% (2/21) of recipients and was not related to abnormal MCA flow. None of the children suffered from chronic renal failure. We concluded that fetoscopic laser ablation of the placental anastomoses in TTTS affects the fetal and fetoplacental circulation in various ways, such as transient volume overload in donors and improvement of cardiac function in recipients. Cerebral and renal flow changes occur after laser therapy. Whether these are permanent or temporarily fetal adaptations needs further investigation with prolonged follow-up. In our studies, the changes found were not associated with long-term neurological or renal sequelae. In chapter 6 the influence of fetoscopic laser therapy on fetal cardiac size in monochorionic twins complicated by TTTS was evaluated. In a longitudinal, prospective study, we assessed sonographically the fetal cardiac size in monochorionic diamniotic twins with TTTS treated with laser therapy and in monochorionic twins without TTTS. The fetal cardiothoracic ratio (cardiac circumference divided by thoracic circumference) of TTTS twins was determined within 24 h before, 12 to 24 h after and 1 week after laser treatment, and from then on every 2 to 4 weeks until birth. TTTS twins were classified at Quintero Stage 1-2 (n=18) and Stage 3-4 (n=16) and measurements were compared to biweekly measurements of non-TTTS monochorionic twins matched for gestational age (n=38). Cardiomegaly was defined as a cardiothoracic ratio above the 97.5th percentile. Before laser treatment, cardiomegaly was observed in 44% (8/18) and in 50% (8/16) of recipients at Quintero Stage 1-2 and Stage 3-4, respectively. Cardiomegaly occurred in none of the donors before treatment. After laser treatment, cardiomegaly was observed in 76% (13/17) and 50% (7/14) of recipients at Stage 1-2 and Stage 3-4, respectively. Cardiomegaly was found in 17% (3/18) and 13% (2/15) of donors at Stage 1-2 and Stage 3-4, respectively. Non-TTTS monochorionic twins and singletons showed cardiomegaly in 18% (7/38) and 8% (2/25). After laser therapy, cardiothoracic ratios of recipients at Stage 1-2 and Stage 3-4 were not significantly changed (p=0.34 and 0.67, respectively). Cardiothoracic ratios of donors at Stage 1-2 and Stage 3-4 were increased compared to their cardiothoracic ratios before laser therapy (p-values 0.0002 and 0.005, respectively). Cardiothoracic ratios of non-TTTS monochorionic twins were not significantly different from our reference range in singletons throughout gestation, and were smaller as compared to both recipients and donors after laser therapy. It was concluded that recipients show cardiomegaly both before as well as after fetoscopic laser therapy for TTTS. Donors develop cardiomegaly only after laser treatment for TTTS. Our findings emphasize the significant effect of TTTS and fetoscopic laser therapy on the fetal hearts of both recipient and donor twins. In chapter 7 we compared fetal cardiac output (CO) in donor and recipient twins of TTTS pregnancies after fetoscopic laser therapy to monochorionic twins without TTTS and to normal singletons. In a longitudinal, prospective study, we sonographically assessed fetal CO in donors (n=10) and recipients (n=10) with TTTS after fetoscopic laser therapy, in monochorionic twins without TTTS (n=20) and in 20 normal singleton pregnancies. The fetal CO of TTTS twins was determined 1 day and 1 week after laser treatment, and from then on every 2 to 4 weeks until birth. Twins without TTTS were examined biweekly until birth. Singletons were examined twice with an 8-week interval at different gestational ages between 17 and 35 weeks. Absolute CO increased exponentially with advancing gestational age (p<0.001), and was significantly related to fetal weight for all groups (p<0.0001). The median CO/kg in donors after laser therapy, recipients after laser therapy, and non-TTTS monochorionic twins was significantly higher compared to singletons (all p-values <0.001). Median CO/kg in donors after laser therapy, recipients after laser therapy, and non-TTTS monochorionic twins was not significantly different from each other. It was concluded that monochorionic twins with TTTS have an increased CO/kg after laser treatment as compared to normal singletons. These results may be of importance in view of the increasing awareness of fetal origins of adult disease. In conclusion, knowledge about monochorionic twinning and its complications such as TTTS is crucial for clinicians participating in the care of pregnant women and for children born as monochorionic twins. With the studies described in this thesis, we aimed at designing a framework that is helpful in providing high quality prenatal care for monochorionic twins. A first-trimester scan to establish chorionicity is vital and should be followed by biweekly ultrasound examinations and patient instructions. Specific __guidelines__ that may be used both before and after fetoscopic laser treatment for TTTS are provided in the recommendations for clinical practice. We hope that the studies presented in this thesis will contribute to increased awareness of the potential problems and optimization of management of this unique subset of pregnancies: the monochorionic twins. Show less
Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Placental vascular anastomoses,... Show moreTwin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the development of TTTS. TTTS is thought to result from unbalanced inter-twin blood flow between the donor twin and the recipient twin through the vascular anastomoses, leading to hypovolemia and oligohydramnios in the donor and hypervolemia and polyhydramnios in the recipient. Despite significant developments in the diagnosis, staging and management of TTTS, the pathogenesis of TTTS is still poorly understood and, most importantly, perinatal mortality and morbidity in TTTS remain strikingly high. In this thesis, several studies on TTTS are presented regarding various aspects of this disease, including studies on monochorionic placentas to investigate the pathogenesis of TTTS, description of a new form of chronic TTTS and the short and long-term outcome in TTTS treated with fetoscopic laser surgery. In Chapter 2, an overview of the literature is presented. This review analyzes the possible pathophysiologic mechanisms involved, discusses the latest findings in diagnosis, therapy and prognosis, and focuses on neonatal and pediatric morbidity associated with TTTS. In Chapter 3 we describe a novel technique to calculate the net feto-fetal blood flow through placental arterio-venous anastomoses in a case of TTTS treated with laser surgery and subsequent intrauterine transfusion. In this study we determined that the net blood flow through the five unidirectional arterio-venous anastomoses was approximately 28 ml/24h, much lower than previously measured with Doppler ultrasound. This finding may also explain the inaccuracy of Doppler flow measurements, as such low flow velocities cannot possibly be detected with current Doppler techniques. Measurements of anastomotic blood flow are of major importance for the validation and development of accurate computer modeling in TTTS. In Chapter 4 we studied the role of velamentous cord insertion and discordant placental sharing in the pathogenesis of TTTS by comparing monochorionic placentas with and without TTTS. Previously, several studies reported an increased incidence of velamentous cord insertions in TTTS placentas and suggested a direct relation between velamentous cord insertion, unequal placental sharing and the development of TTTS. In this study we examined 76 monochorionic placentas with TTTS and 63 monochorionic placentas without TTTS. The incidence of velamentous cord insertion (per fetus) in the TTTS group and the no-TTTS group was 13% and 14% (p = 0.79), respectively. Placental sharing discordance in the TTTS group and the no-TTTS group was 20% in both groups (p = 0.83). In the TTTS group, donor twins had more often a velamentous cord insertion than recipient twins (24% and 3%, respectively, P < 0.001) and smaller placental shares (44% and 56% respectively, p < 0.001)). Our findings suggest that velamentous cord insertion and smaller placental share in donor twins are a consequence of developing TTTS, rather than a cause of TTTS. In Chapter 5 the frequency of residual placental vascular anastomoses after fetoscopic laser surgery for TTTS was studied. Presence of residual anastomoses was investigated in relation to adverse outcome and to intertwin hemoglobin difference at birth. Residual anastomoses were detected in 33% (17/52) of placentas. Adverse outcome (fetal demise, neonatal death or severe cerebral injury) was similar in the groups with and without residual anastomoses, 18% (6/34) and 29% (20/70), respectively (p = 0.23). Large inter-twin hemoglobin differences (> 5 g/dL) were found in 65% (11/17) of cases with residual anastomoses and 20% (7/35) of cases without residual anastomoses (p < 0.01). The first conclusion of this study is that laser treatment needs to be improved as only 2/3 of monochorionic placentas are functionally __dichorionized__. The second conclusion is that residual anastomoses in this study are not associated with adverse outcome. Lack of association between residual anastomoses and adverse outcome may partly be due to the small size of the majority of residual anastomoses (< 1mm diameter in 64% of the cases) and the presence of __protective__ residual superficial anastomoses in 35% of the cases. Finally, we concluded that residual anastomoses are often associated with neonatal hematological complications. In Chapter 6 we describe two pairs of monochorionic twins without TTTS but with marked discordant hemoglobin levels. We named this new form of TTTS, the twin anemia-polycythemia sequence (TAPS). In the two reported TAPS cases, both donor twins were severely anemic requiring blood transfusion and both recipients were polycythemic, one requiring partial volume exchange transfusions. Inter-twin difference in reticulocyte counts was extremely high, suggesting a chronic form of inter-twin blood transfusion. Placental injection studies revealed a preponderance of very small (< 1 mm) arterio-venous anastomoses in one direction. Nowadays, routine prenatal measurements of middle cerebral artery peak systolic velocity using Doppler ultrasound are recommended after laser surgery to rule out fetal anemia or (iatrogenic) TAPS. We suggest that routine Doppler studies also be performed in uncomplicated monochorionic twin pregnancies without TOPS. Signs of fetal anemia in a monochorionic twin should then alert the perinatologist of the possibility of TAPS. TAPS should be diagnosed when a large inter-twin discordance in fetal or neonatal hemoglobin levels and reticulocyte counts is found, in the absence of TOPS. Placental injection studies may then reveal a preponderance of very small arterio-venous anastomoses. Discordant hemoglobin levels occur not only in chronic TTTS and in TAPS, but are also reported to occur in uncomplicated monochorionic pregnancies due to acute peripartum TTTS. In Chapter 7 we studied the inter-twin difference in hemoglobin levels at birth in monochorionic twins without TTTS compared to a control group of dichorionic twins, in relation to birth order and placental vascular anatomy. We found that hemoglobin differences occur more frequently in monochorionic twins without chronic TTTS than in dichorionic twins, but only when measured on the second day of life. Furthermore, hemoglobin differences in monochorionic twins are associated with birth order and with the presence of superficial vascular anastomoses. We found that second-born monochorionic twins have significantly higher hemoglobin values than first-born twins. Our findings support the hypothesis that second-born monochorionic twins are more likely to receive a large placental blood transfusion rather than lose blood into the placenta. We also report that hemoglobin differences in monochorionic twins are greater in the presence of superficial vascular anastomoses. In analogy to acute perimortem TTTS, it is conceivable that superficial vascular anastomoses may also be responsible for rapid placento-fetal blood transfusion during delivery. Chapter 8, 9 and 10 focus on the short-term outcome in TTTS treated with fetoscopic laser surgery. The neonatal outcome in TTTS survivors treated with laser at our center is presented in Chapter 8. We compared the outcome in a TTTS group after laser treament with a control group of monochorionic twins without TTTS delivered at our center. We found that neonatal mortality in the TTTS and no-TTTS group was 8% (6/76) and 3% (3/90) respectively (p = 0.03). Overall, the incidence of adverse neonatal outcome (neonatal mortality, major neonatal morbidity or severe cerebral lesions) in the TTTS and no-TTTS group was 26% (20/76) and 13% (12/90), respectively (RR = 1.97, 95% CI = 1.03 to 3.77). We concluded that the risk for adverse neonatal outcome is two-fold increased in TTTS treated with laser than in monochorionic twins without TTTS. Details on the short-term neurological outcome in TTTS survivors treated with fetoscopic laser surgery are presented in Chapter 9. Again we compared the results with a control group of monochorionic twins without TTTS. Incidence of antenatally acquired severe cerebral lesions in the TTTS group was 10% (8/84) and 2% (2/108) in the no-TTTS group (p = 0.02). Incidence of severe cerebral lesions at discharge was 14% (12/84) in the TTTS group and 6% (6/108) in the no-TTTS group (p = 0.04). Antenatal injury was responsible for severe cerebral lesions in 67% (8/12) of the TTTS group. We conclude that the incidence of severe cerebral lesions in TTTS treated with fetoscopic laser surgery is high and results mainly from antenatal injury. Details on the short-term cardiac outcome in TTTS survivors treated with fetoscopic laser surgery are presented in Chapter 10 and compared to a control group of monochorionic twins without TTTS. Echocardiography was performed within one week after delivery. At birth, blood pressure was measured in all survivors and endothelin-1 was determined in umbilical cord blood. Data on right ventricular outflow tract obstruction in TTTS treated with laser surgery at our center but delivered elsewhere were reviewed retrospectively from medical records. We found that the incidence of right ventricular outflow tract obstruction in recipients was 4% (3/75). We found no difference in afterload parameters between donors and recipients after laser treatment. We concluded that the incidence of congenital heart disease in TTTS survivors treated with fetoscopic laser occlusion of vascular anastomoses is around 5%, which is higher than in the general population (0.5%). In particular, the increased risk of right ventricular outflow tract obstruction in recipient twins warrants close cardiac monitoring during fetal and neonatal life. The long-term neurodevelopmental outcome in TTTS is presented in Chapter 11 and 12. Chapter 11 describes the long-term neurodevelopmental outcome in TTTS treated conservatively. All TTTS-cases admitted at our center between January 1990 and December 1998 were included in the study. Perinatal mortality was 50% (29/58). Neurological and mental development at school age was assessed during a home visit in all TTTS-survivors (n = 29). The incidence of adverse neurodevelopmental outcome in TTTS survivors was 21% (6/29) and was due to cerebral palsy (n = 6) and developmental delay (n = 5). The incidence of adverse neurodevelopmental outcome in the group of survivors who were treated with amnioreduction was 26% (5/19). Two of the four children born after intrauterine fetal demise of their co-twin had cerebral palsy. Chapter 12 describes the long-term neurodevelopmental outcome in TTTS treated with fetoscopic laser surgery. All TTTS-cases treated consecutively at our center between August 2000 and December 2003 were included in the study. Perinatal mortality was 30% (49/164). Neurological, mental and psychomotor development at 2 years of age was assessed in all TTTS-survivors (n = 115). Overall, the incidence of neurodevelopmental impairment was 17% (19/115) and was due to cerebral palsy (n = 8), mental developmental delay (n = 9), psychomotor developmental delay (n = 12) and deafness (n = 1). In both long-term follow-up studies, we concluded that neurodevelopmental delay in TTTS, regardless of type of antenatal treatment, is high and warrants long-term follow-up. In conclusion, although laser surgery appears to be the best available treatment option for TTTS, perinatal mortality and morbidity rates in TTTS treated with laser are still significant. More research and new developments are required to further improve the short and long-term outcome in TTTS. Show less