Asli Umur

Monoamniotic-versus diamniotic-monochorionic twin placentas: anastomoses and twin-twin transfusion syndrome.

OBJECTIVE The purpose of this study was to compare monoamniotic-monochorionic and diamniotic-monochorionic twin placentas and to estimate the incidence of twin-twin transfusion syndrome in monoamniotic-monochorionic twin pregnancies. STUDY DESIGN We analyzed the angioarchitecture and cord insertion distance in 24 monoamniotic-monochorionic and 200 diamniotic-monochorionic placentas. RESULTS Compared with diamniotic-monochorionic placentas, monoamniotic-monochorionic placentas had significantly more arterioarterial anastomoses (20/20 vs 159/200, respectively; P=.013), significantly less opposite arteriovenous anastomoses (10/20 vs 165/200, respectively; P=.002), similar venovenous anastomoses (6/20 vs 46/200, respectively; P=.323), and arteriovenous anastomoses (20/20 vs 187/200 respectively; P=.279) and significantly shorter umbilical cord distances (median [+/-SD], 5.0+/-6.9 cm vs 17.5+/-6.8 cm; P<.001). CONCLUSION Monoamniotic-monochorionic and diamniotic-monochorionic placentas have different anastomotic patterns. The (virtually) 100% incidence of arterioarterial anastomoses in monoamniotic-monochorionic placentas explains the reason that twin-twin transfusion syndrome rarely occurs in monoamniotic-monochorionic twin pregnancies and predicts that twin-twin transfusion syndrome manifestations are approximately 5 times less often recognized in monoamniotic-monochorionic pregnancies than in diamniotic-monochorionic pregnancies.

Twin–twin transfusion syndrome: mathematical modelling

Twin–twin transfusion syndrome (TTTS) represents a pregnancy complication with a high risk for perinatal mortality and postnatal morbidity. Mathematical models have been utilized to examine the mechanisms of disease and potential treatment modalities. We developed four consecutive models based on pathophysiology mechanisms. Conceptually, these models remained simple, but with increased complexity in details. We present our models tutorially with the necessary equations expressed in words. The aetiology of TTTS was related to AV anastomoses from donor to recipient and their growth commensurate with placental growth. We assessed that natural growth of placenta and foetuses causes the diameter and length of the AV, as well as the AVs pressure gradient, to increase proportional to gestational age. The AV transfusion then increases faster than natural foetal growth. A progressively increasing discordance subsequently develops, not compensated for by foetal growth. A simulation is performed to show how this discordance in blood volumetric development causes successive discordances in other functions, particularly renal, circulatory, and cardio‐vascular, resulting in disease progression to the various stages of TTTS. In conclusion, mathematical modelling of TTTS has provided an understanding of the sequence of events that leads to the various presentations of TTTS stages as well as the efficacy of therapies. Copyright

Modeling acardiac twin pregnancies.

Abstract:  Acardiac twin pregnancies are a rare but severe complication of monochorionic twinning, where the acardiac twin lacks cardiac function but nevertheless grows during pregnancy because it is perfused by the pump twin through a set of placental arterioarterial and venovenous anastomoses. Because the acardiac twins body is only perfused by the pump twins arterial blood, acardiac twins have reduced blood oxygen saturation (SO2) levels. Furthermore, the pump twin has reduced blood oxygen saturation because the anastomoses merge the blood of the two twins. We suggested that angiogenesis from hypoxia mediated neovascularization increases the capillary density in the acardiac twin and causes a continuously decreasing vascular resistance of the acardiac body. The pump twin therefore has a continuously increasing cardiac output and decreasing oxygen saturation, which may cause a vicious circle of increasing levels of pump twin complications, often leading to intrauterine fetal death. Our aim in this article was twofold. First, to summarize our previous modeling work of acardiac twin pregnancies, and add an estimate of the capillary density in mammals at different levels of SO2 from a literature search on angiogenesis related to SO2, Hypoxia Inducible Factor, and Vascular Endothelial Growth Factor. Second, to speculate that combination of these efforts and our most recent model of monochorionic twin pregnancies and twin–twin transfusion syndrome may result in an improved computational model for acardiac twin pregnancies, aimed at identifying early clinical prognostic markers for pump twin complications.

Increasing cardiac output and decreasing oxygenation sequence in pump twins of acardiac twin pregnancies.

An acardiac twin pregnancy is a rare but serious complication of monochorionic twinning and consists of an acardiac twin and a pump twin. The acardiac twin is a severely malformed fetus that lacks most organs, particularly a heart, but grows during pregnancy because it is perfused by the developmentally normal pump twin via a set of arterioarterial and venovenous placental anastomoses. Pump twins die intrauterine or neonatally in about 50% of the cases. Because the effects of an acardiac mass on the pump twins development are incompletely known, methods for outcome prognosis are currently not available. We sought to derive simple relations for the pump twins excess cardiac output and decreased oxygenation and to use available clinical cases for a preliminary test of the model. As a method, we used a theoretical flow model to represent the fetoplacental circulation of an acardiac twin pregnancy and estimated blood deoxygenation and reoxygenation following perfusion of the two bodies and placentas, respectively. The results show the pump twins excess cardiac output and decrease of venous oxygen saturation to depend on the ratio of pump twin to acardiac twin umbilical blood flow, whose ratio can be measured by ultrasonography. The clinical cases show a decreasing umbilical flow ratio with gestation. In conclusion, prospective serial study is necessary to test whether measurement of umbilical flow ratios allows monitoring the pump twins pathophysiologic development, possibly resulting in a guideline for prognosis of pump twin survival.

Modelling the influence of amnionicity on the severity of twin-twin transfusion syndrome in monochorionic twin pregnancies.

Clinical treatment for diamniotic-monochorionic twin-twin transfusion syndrome (TTTS) may include conversion of diamniotic pregnancies to a monoamniotic-monochorionic state by disrupting the amnion septum. We sought to test the underlying hypothesis, i.e. that a monoamniotic state reduces the severity of TTTS. With use of our previously developed mathematical model of two equal fetoplacental circulatory units connected by various sizes and types of placental anastomoses, we compared the haemodynamic and amniotic fluid dynamics of monoamniotic and diamniotic twins that develop TTTS. We used three anastomotic patterns that produce severe, moderate or mild forms of TTTS, respectively, in our diamniotic-monochorionic twin model. Monoamnionicity was modelled by adding the two amniotic fluid volumes and using the volume-averaged amniotic fluid osmolality. The results were as follows: for severe TTTS, small differences develop between diamniotic and monoamniotic donor twins in fetal urine production, swallowed volume, blood volume, blood pressures, net fetofetal transfusion, and blood and amniotic fluid osmolality. However, the circulatory imbalance between the monoamniotic twins deteriorates similar to that of diamniotic twins. The pathophysiological differences tend to disappear for milder TTTS. In conclusion, our model suggests that the uncommon finding of TTTS in monoamniotic twins is not due to the presence of a single amniotic sac. Rather, clinically significant differences in anastomotic patterns and the delayed or lack of identification of manifestations in monoamniotic twins account for the reduced rate of TTTS diagnosis. Based on these results we expect the clinical disruption of the amnion septum in diamniotic-monochorionic TTTS pregnancies to have only minimal benefits.

Does amniotic fluid volume affect fetofetal transfusion in monochorionic twin pregnancies? Modelling two possible mechanisms

Clinical evidence suggests that increased amniotic fluid volume due to polyhydramnios increases placental vascular resistance. We have sought to model the possible effects of an increased amniotic fluid volume on the net fetofetal transfusion in monochorionic twin pregnancies. We wanted to compare these effects with the results of previous simulations, which aimed to explain why the twin-twin transfusion syndrome (TTTS) placentas more often include bidirectional arteriovenous (AV) rather than AV plus arterioarterial (AA) anastomoses. We extended our mathematical model of TTTS by simulating two different mechanisms that increase the placental vascular resistance as a consequence of polyhydramnios. First, there is an increase in the placental capillary resistance and hence in deep AV and opposite AV (denoted as VA) resistances due to polyhydramnios. Second, there is an increase in the resistance of chorionic veins due to polyhydramnios, assuming that these veins act as Starling resistors. We then simulated the effects of polyhydramnios on different placental anastomotic patterns. The results were as follows. In the first mechanism (polyhydramnios affects AV-VA resistances), an increased amniotic fluid volume hardly affected bidirectional AV, but slightly decreased fetofetal transfusion in AV plus AA anastomoses. However, for these effects to change the natural development of the pregnancy, polyhydramnios needed to persist for approximately 4 weeks, and by comparing the effects of polyhydramnios with the effects of amnioreduction, amnioreduction was more beneficial for normalizing the donor amniotic fluid volume. Therefore, these beneficial effects due to polyhydramnios have no practical clinical significance. In the second mechanism (Starling resistor for chorionic veins), polyhydramnios slightly increased fetofetal transfusion and hence slightly increased TTTS severity in bidirectional AV and AV plus VV, but did not affect AV plus AA anastomoses. In conclusion, we hypothesize that the simulated effects of polyhydramnios are not the primary cause of the fact that TTTS placentas more often include bidirectional AV than AV plus AA anastomoses. Rather, the more likely explanation is the previously identified larger range of AA than VA anastomotic diameters that adequately compensate for the effects of the AV.

Haemodynamic resistance model of monochorionic twin pregnancies complicated by acardiac twinning

An acardiac twin is a severely malformed monochorionic twin fetus that lacks most organs, particularly a heart. It grows during pregnancy, because it is perfused by its developmentally normal co-twin (called the pump twin) via a set of placental arterioarterial and venovenous anastomoses. The pump twin dies intrauterine or neonatally in about 50% of the cases due to congestive heart failure, polyhydramnios and prematurity. Because the pathophysiology of this pregnancy is currently incompletely understood, we modified our previous haemodynamic model of monochorionic twins connected by placental vascular anastomoses to include the analysis of acardiac twin pregnancies. We incorporated the fetoplacental circulation as a resistance circuit and used the fetal umbilical flow that perfuses the body to define fetal growth, rather than the placental flow as done previously. Using this modified model, we predicted that the pump twin has excess blood volume and increased mean arterial blood pressure compared to those in the acardiac twin. Placental perfusion of the acardiac twin is significantly reduced compared to normal, as a consequence of an increased venous pressure, possibly implying reduced acardiac placental growth. In conclusion, the haemodynamic analysis may contribute to an increased knowledge of the pathophysiologic consequences of an acardiac body mass for the pump twin.

Discordant Fetal Growth Patterns in Monochorionic Twin Pregnancies Described by Simple Algebraic Relations

Objective: To test whether twin-twin transfusion syndrome (TTTS) and non-TTTS cases that were suspect but not confirmatory for developing the syndrome (non-TTTS-with-symptoms) have discordant fetal growth patterns that correlate with our previously derived algebraic relations. Methods: In 25 monochorionic twin pregnancies, fetal growth was determined by standard ultrasonography. The difference between estimated fetal weights (dEFW) as well as the difference divided by the average of the two weights, the difference average ratio (DAR), were fitted to the predicted trends of discordant fetal growth for TTTS and non-TTTS pregnancies. The best fits were compared with the clinical data. Results: Out of 13 TTTS cases, dEFW analysis correctly correlated with 8 (62%) and DAR analysis correctly with 10 (77%). Out of 12 non-TTTS-with-symptoms cases, dEFW analysis correctly correlated with 7 (58%) and DAR analysis correctly with 9 (75%). If TTTS correlated best, dEFW analysis was correct in 8/12 (67%), and DAR analysis in 10/11 (91%) cases. If non-TTTS correlated best, dEFW analysis was correct in 7/9 (78%), and DAR analysis in 9/12 (75%). The likelihood ratios of TTTS and non-TTTS were 1.9 and 0.26, respectively, with dEFW analysis, and 9.2 and 0.31 with DAR analysis. Conclusion: The simple algebraic relations derived to identify trends of fetal discordant growth show evidence that clinical TTTS and non-TTTS manifestations are quantifiable. The relations may contribute to future risk stratification in monochorionic twin pregnancies, e.g., by prospectively distinguishing between cases that will develop TTTS and those that will not, despite presenting with symptoms.

Trends of discordant fetal growth in monochorionic twin pregnancies

We derived simple analytical relations representing trends of discordant fetal growth in monochorionic twins developing the twin-twin transfusion syndrome from an approximation of previously developed model equations. In severe twin-twin transfusion syndrome cases, the difference between the estimated fetal weights of both twins increases proportional to (t - 5)5 (t denotes gestational age in weeks) and the sum of both weights increases proportional to t3. Hence, the ratio between the difference of estimated fetal weights and the average of the two weights (difference average ratio) increases in proportion to (t - 5)5/t3. In mild cases, the difference between estimated fetal weights as well as the sum of the two weights increases proportional to t3. Therefore, the difference average ratio becomes a constant. Comparison with clinical data of severe and mild cases showed surprisingly good agreement except after laser coagulation of placental anastomoses. These relations may therefore enable us to distinguish between severe and mild developing twin-twin transfusion syndrome cases.

Mathematical modeling of twin–twin transfusion syndrome

Twin-twin transfusion syndrome (TTTS) is a unique complication of monochorionic twin pregnancies, diagnosed by discordant amniotic fluid volume (oligo/anhydramnios-polyhydramnios sequence). Often, but not always, serious cardiovascular sequelae develop, resulting in the assessment of TTTS as having a widely variable and unpredictable clinical presentation. TTTS is a consequence of placental anastomoses, which can be arteriovenous from donor to recipient (AVDR), arteriovenous from recipient to donor (AVRD), arterioarterial (AA), and venovenous (VV). These anastomoses allow a net fetofetal transfusion to develop from one twin (the donor) to the other (the recipient). While about 96% of all monochorionic placentas have anastomoses, only 5-10% of them develop TTTS (see Chapter 3). TTTS severity has been classified.1 Stage I includes the oligo-polyhydramnios sequence without further complications. Stage II also includes lack of donor bladder filling. Stage III includes critically abnormal arterial or umbilical venous flow and/or ductus venosus patterns in either twin. Stage IV includes hydrops, and stage V intrauterine fetal demise in either or both twins. Although ultrasonography can study the fetal and placental anatomy, and Doppler sonography the blood flow of major fetal, umbilical, and placental vessels, other parameters contributing to TTTS presentation and sequelae cannot be studied directly (i.e. the fluid flows responsible for the amniotic fluid discordance, cardiovascular parameters including fetal blood pressures, and the net fetofetal transfusion). Because an animal model of TTTS is not available, understanding the complex pathophysiology of TTTS to its full extent is problematic. As an alternative, mathematical models of monochorionic twin pregnancies have been developed with the hope that they can aid in identifying and understanding the sequence of events that leads to the various TTTS manifestations and the potential efficacy of therapies.