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Twin reversed arterial perfusion sequence, or TRAP sequence, is a rare complication affecting identical twins. In approximately 1 in 35,000 births, an abnormal twin that may have an absent or abnormal heart, develops and receives blood flow directly from a normally developed twin or what is called a "pump" twin. Because the pump twin's heart must supply blood for itself as well as for the abnormal twin, it may lead to heart failure and complications for the pregnancy.
As a parent, learning your babies may have TRAP sequence can be frightening. But the Colorado Fetal Care Center (CFCC) is at the forefront of treatment and care for this condition.
Twin reversed arterial perfusion sequence, or TRAP sequence, occurs in twin pregnancies in which one of the babies does not fully form and has either a malformed or absent heart (acardiac twin). This then puts stress on the heart of the sibling twin, called the "pump" twin, because his or her heart is working for two.
In an acardiac twin pregnancy, the normal twin's heart must work harder in order to pump blood to not only the placenta, but also to the acardiac twin. This blood flow is the reverse of what occurs in a normal twin pregnancy, where oxygenated blood is provided by the placenta, with the baby returning unoxygenated blood to the placenta. In this condition, the acardiac twin adds an additional burden on the normal twin’s heart which may lead to heart failure.
The type of TRAP sequence babies have is determined by how developed the abnormal twin is. For example, he or she may have a very abnormal heart or no heart at all. Some have a partial formation of the upper body and head and others may have none. Additionally, each TRAP sequence needs to be evaluated to determine what risk it places on the normal twin.
TRAP sequence occurs in 1 in 35,000 pregnancies and in less than 1 percent of identical twin pregnancies. TRAP sequence is caused by the development of one abnormal twin in an identical twin set, or in what is called a monochorionic twin pregnancy. The normal twin then supplies the blood flow for the abnormal twin, which may lead to heart failure and death.
Because so much work is required for the healthy twin to pump blood to the acardiac twin, it leaves the healthy twin at risk for heart failure and death.
Other complications can include polyhydramnios (excess amniotic fluid), which can cause swelling for the mother, as well as preterm labor and delivery. This has been documented in 46 percent of all TRAP sequence twins.
TRAP sequence can be diagnosed through a routine ultrasound. Because they are identical twins that share a placenta, they need to be more closely monitored throughout gestation for a number of potential complications.
Indicators of TRAP sequence by ultrasound include:
Further examination of the blood flow between the twins can aid in the diagnosis of TRAP sequence.
Once TRAP sequence is diagnosed, it's critical that both the mother and babies are closely monitored to quickly catch complications that could put their health or lives at risk. At the Colorado Fetal Care Center, we select treatment options depending on the severity of the condition to improve outcomes for our tiniest patients.
The Colorado Fetal Care Center is one of the leading care centers for TRAP sequence in twin pregnancies and we have successfully treated more than 100 cases at our facility.
Treatment for TRAP sequence depends greatly on the severity of the impact on the normal twin. At the Colorado Fetal Care Center, we treat each patient as an individual and make recommendations based on what is best for that patient and his or her needs.
Treatment for TRAP sequence is needed only when there is risk to the normal twin's health. This risk is determined by how large the acardiac twin is in relation to the normal twin. In addition, we complete a thorough evaluation of how well the normal twin's heart is functioning. Treatment for TRAP sequence includes monitoring and possibly fetal intervention to save the life of the larger twin.
In the absence of any risk to the normal twin, we will recommend following the pregnancy closely by ultrasound. The ultrasound surveillance will ensure that the acardiac twin remains small and heart function of the normal twin remains strong throughout your pregnancy.
If the acardiac twin is large and there are signs of impending heart failure in the normal twin, we will recommend treatment. Treatment involves stopping blood flow to the acardiac twin to relieve the burden on the normal twin. This is accomplished by a procedure called radiofrequency ablation, or RFA. This procedure involves a small needle that is able to generate heat and is used to seal the blood vessels leading to the acardiac twin. In our experience, the "pump" twin survives 98 percent of the time following RFA for TRAP sequence.
In two-thirds of cases of twins with TRAP sequence, the pump and acardiac twins are in separate amniotic sacs. However, in one-third of cases, the babies share the same amniotic sac which may change the approach to treatment.
For twins found to be at risk of heart failure, there is a very high risk of losing the pregnancy. With treatment, however, survival is 98 percent and the average delivery occurs at 35 weeks. For those pregnancies that are at low risk for complications, outcomes are even better with term delivery expected.
Antenatal diagnoses of twin reversed arterial perfusion sequence (TRAP sequence) have been reported in the literature since 1980. Ultrasonographic features useful in the diagnosis of acardia include absence of normal cardiac structure and cardiac movement and variable structural abnormalities. Common structural abnormalities identified in the acardiac fetus include anencephaly, omphalocele and absence of upper limbs. Most cases have edematous soft tissue and large cystic hygroma–like spaces are commonly identified in the skin (Mack et al., 1982).
The placentation is most commonly monochorionic diamniotic (74 percent), in which a thin membrane will be seen dividing the sac of the acardiac fetus from the pump fetus (Healey, 1994). Monoamnionicity is present in approximately 24 percent of cases (Healey, 1994). In exceptional cases, dichorionicity may be diagnosed (Healey, 1994). Polyhydramnios is common as are abnormalities in the umbilical cord or in its insertion (Dashe et al., 2001). The umbilical cord will demonstrate a single umbilical artery in approximately two thirds of cases and in one third the number of cord vessels will be normal (Healey, 1994). A velamentous insertion of the cord or a conjoined cord insertion may be present (Dashe et al., 2001).
Measurement of the acardiac twin should be performed because the ratio of the weight of the acardiac twin to that of the pump twin is useful to predict pregnancy outcome. Because of the structural abnormalities, the biometric parameters of biparietal diameter, abdominal circumference and femur length may not be available or reliable in an acardiac fetus. This problem of the antenatal determination of the acardiac twin's weight has been addressed by Moore et al. (1990). The dimensions and weights of 23 acardiac twins were used for the analysis. A second-order regression equation (weight [g] = –1.66 × length + 1.21 × length2) was computed and was predictive of acardiac weight with the use of its longest linear measurement (r = .79; P < 0.001; SEE = 326 g). When the actual and equation-predicted weights were compared, the mean error (±SE) in prediction was 240 ± 156 g. Alternatively, the weight of the acardia can be estimated from the use of the 3-dimensional measurements of the trunk, upper extremities and lower extremities using the formula for an ellipse with cm3 = 1 gram. Careful Doppler examination of the acardiac fetus may also demonstrate reversal of flow in the umbilical artery of the acardiac fetus, with flow going from the placenta toward the acardiac fetus (Benson et al., 1989; Malone and D'Alton, 2000).
The pump twin should have a detailed structural survey performed because trisomy has been reported in up to 9 percent of cases (Healey, 1994) and sonographic features typical of a trisomic fetus may be identified. Fetal echocardiography is helpful in detecting early signs of in utero congestive heart failure in the pump twin. Atrial and ventricular enlargement can be an initial feature of impending cardiac decompensation and can be measured using M-mode by obtaining a transverse view through the cardiac chambers (Allan, 1986; DeVore, 1987). The ventricular fractional shortening capacity can also be calculated using M-mode with the formula (D – S)D × 100, where D is the diastolic and S is the systolic ventricular size. A low value is indicative of poor cardiac contractility. A pericardial effusion may be present and is a sign of congestive heart failure. Tricuspid regurgitation, demonstrated by Doppler studies of the tricuspid valve, is also a sign of congestive heart failure (Shenker et al., 1988; Silverman et al., 1985). Combined ventricular output (CVO) can be measured to determine if the pump twin is in a high output state. In TRAP sequence at a gestational age too early to determine CVO, Kinsel-Ziter et al. have demonstrated a good correlation of increased CVO with increased cardiothoracic ratio (Kinsel-Ziter et al., 2009).
Doppler studies should be performed in both the acardiac and pump twins. Verification of circulatory reversal by pulsed Doppler sonography of the acardiac twin can be documented with reversed direction of flow in the umbilical artery and vein (Benson et al., 1989; Dashe et al., 2001; Donnenfeld et al., 1991; Langlotz et al., 1991; Pretorius et al., 1988; Sherer et al., 1989). In one recent study by Dashe et al., between 1990 and 1997, Doppler studies were performed in 6 monochorionic pregnancies complicated by the TRAP sequence. Pulsatile vessels in the umbilical vessels of the acardiac and pump twins were insonated. Reversal of flow was demonstrated in all cases. Resistive index values were calculated and the difference in resistive index between the pump and acardiac twin was evaluated. In the acardiac twins, no ratio of systolic to diastolic velocity or resistive index value was associated with a good or with a poor prognosis for the pump twin. In the pump twins, resistive index differences > 0.20 between the pump and the acardiac twins were associated with good outcomes, while resistive index differences < 0.05 were associated with poor outcomes (Dashe et al., 2001).
The acardiac fetus may be mistaken for an anencephalic fetus. The sonographic features of absent trunk region in addition to increased soft tissue in the body aid in the correct diagnosis (Billah et al., 1984).
The TRAP sequence has been mistaken for intrauterine fetal death (IUFD) of one twin in a multiple gestation (Malone and D'Alton, 2000). Evidence of growth in the "dead" fetus and a "twitching" noted on repeat ultrasound examination has allowed the diagnosis of an acardiac twin to be made (Cardwell, 1988). In a severely macerated fetus, the skeletal and visceral forms are more differentiated and the soft-tissue edema is less advanced than in a case of acardia (Mack et al., 1982). The use of color-flow Doppler can assist in differentiating between single IUFD in a co-twin and the TRAP sequence (Malone and D'Alton, 2000). Pulsed Doppler examination has been used to demonstrate reversed flow through the umbilical artery of the acardiac twin (Pretorius et al., 1988).
The principal perinatal problems associated with acardiac twinning are pump twin congestive heart failure, maternal polyhydramnios and preterm delivery. The antenatal diagnosis of TRAP can be made only through sonographic examination and has been reported in the literature only since 1980. Large series of acardiac twins have attempted to identify factors prognostic of favorable outcome for the pump twin (Healey, 1994; Moore et al., 1990).
In the series of 49 cases reported by Moore et al. (1990), one third of fetuses were delivered before they were viable. In this study, viability was defined as delivery at or beyond 25 weeks of gestation. Of the potentially viable 33 cases, 4 (12 percent) ended in death of the pump twin in utero. The overall perinatal mortality was 55 percent and was primarily associated with prematurity (Table 2).
Polyhydramnios was a major maternal complication, occurring in 46 percent of all acardiac pregnancies, and it was strongly associated with preterm labor and congestive heart failure in the pump twin. Eighty-two percent of patients with polyhydramnios experienced preterm labor requiring hospital admission and treatment, as compared with 22 percent of pregnancies with normal amniotic fluid (P < 0.01). Polyhydramnios was observed in 78 percent of pump twins with congestive heart failure as compared with 13 percent of those in whom congestive heart failure was not confirmed (P < 0.001). The perinatal outcome was strongly related to the ratio of the weight of the acardiac twin to that of the pump twin. The mean overall ratio of the twin weights was 52 ± 42 percent. The twin weight ratio was more than 70 percent in 25 percent of cases. When this characteristic was present, the incidence of preterm delivery was 90 percent, polyhydramnios 40 percent and congestive cardiac failure in the pump twin 30 percent, as compared with 75 percent, 30 percent and 10 percent respectively when the ratio was less than 70 percent (Moore et al., 1990).
In the series by Healey (1994), of 5 cases at Monash Medical Centre and a review of 184 case reports in the literature from 1960 to 1991, the overall perinatal mortality for the pump fetus was 35 percent in twins and 45 percent in triplets. Factors associated with a significant increase in perinatal mortality for the pump fetus included delivery before 32 weeks of gestation, the acardius anceps form of acardia and the presence of arms, ears, larynx, trachea, pancreas, kidney or small intestine in the acardiac fetus.
Nonetheless, a more recent study questioned the poor prognosis associated with pregnancies complicated by TRAP and explored the role of expectant management (Sullivan, 2003). Ten cases of antenatally diagnosed acardiac twins delivered between 1994 and 2001 in one community were evaluated. All cases were managed expectantly. Nine women delivered healthy pump twins. There was one neonatal death. The mean gestational age at delivery was 34.2 weeks and the mean weights of the pump and acardiac twins were 2279 g and 1372 g, respectively. The authors concluded that neonatal mortality of pump twins in antenatally diagnosed acardiac twin pregnancies may be considerably less than reported, and expectant management with close antepartum surveillance may be an option.
Regarding fetal treatment for twin reserved arterial perfusion sequence (TRAP sequence), many invasive procedures have been described with the goal of interrupting the umbilical circulation of the acardiac twin. There is a great deal of controversy in the literature concerning which cases are candidates for such procedures. It has been recommended that invasive procedures be performed only after heart failure has developed (Platt et al., 1983). Some have recommended surgical intervention only after medical therapy has failed (Ash et al., 1990). Others have suggested intervening before heart failure is present in the pump twin (Platt et al., 1983). Others consider the diagnosis of TRAP the indication for fetal intervention (Tsao et al., 2002).
Various percutaneous procedures have been described to interrupt the umbilical circulation in acardiac twins, including (1) insertion of a thrombogenic coil into the recipient twin's umbilical cord, (2) injection of silk soaked in alcohol into the cord, (3) injection of absolute alcohol into the cord, (4) fetoscopic ligation of the acardiac fetus's cord, (6) bipolar forceps cautery of the acardiac fetus's cord, (7) thermocoagulation of the aorta of the acardiac fetus and (8) intrafetal radiofrequency thermal ablation (Porreco et al., 1991; Holzgreve et al., 1994; Quintero et al., 1994; Sepulveda et al., 1995; Arias et al., 1998; Rodeck et al., 1998; Challis et al., 1999; Tsao et al., 2002; Livingston et al., 2007).
Injection of coils or sclerosants is generally no longer performed because of the unreliability in achieving complete occlusion. Fetoscopic cord ligation may be associated with a failure rate of 10 percent together with a 30 percent risk of preterm rupture of membranes (Challis et al., 1999). Laser and cautery options have the advantage of generally requiring one access port in the uterus and therefore may be associated with less morbidity. No comparative studies are available, however, to suggest one optimal method of selective termination in this setting.
Robie et al. (1989) reported a case of selective delivery by hysterotomy of an acardiac acephalic twin fetus at 22.5 weeks of gestation with the subsequent delivery of the normal twin at 33 weeks of gestation. Fries et al. (1992) subsequently reported 5 cases of selective delivery in 1992. In one case, placental abruption occurred shortly after the procedure, leading to fetal death. Two cases delivered at 35 weeks of gestation and the remaining 2 delivered at 27 and 28 weeks.
Porreco et al. (1991) described the insertion of a helical metal coil under sonographic guidance to induce thrombosis in the umbilical artery of the acardiac twin at 24 weeks. The co-twin delivered at 39 weeks and had a normal course.
Quintero et al. (1994) described a percutaneous fetoscopic procedure that treated this condition at 19 weeks of gestation and was followed by the birth of a normal twin at 36 weeks of gestation. A further case was reported by McCurdy et al. (1993). A trial of maternal digoxin administration failed and was followed by a fetoscopic ligation of the acardiac twin's cord at 19 weeks. Ultrasound examination on the first postoperative day indicated death of the pump twin.
Holzgreve et al. (1994) injected multiple pieces of silk suture soaked in 96% alcohol into the umbilical cord of an acardiac twin at 21 weeks of gestation. This resulted in immediate interruption of flow in the cord and the ultimate delivery at term of a 2780 g healthy newborn. The advantage of this approach in comparison to umbilical cord ligation is the use of a much thinner needle. Less operative time is required and there is no need for general anesthesia (Holzgreve et al., 1994).
Other methods of interrupting the circulation in the acardiac twin involve direct coagulation of the umbilical vessels or the aorta, using either laser photocoagulation or diathermy thermocoagulation. Laser photocoagulation of umbilical vessels using a neodymium yttrium aluminum garnet laser has been successfully reported, although this approach appears less likely to be successful when performed after 24 weeks gestation (Arias et al., 1998). This may be because umbilical vessels are too large to adequately photocoagulate when the gestational age is greater than 24 weeks. Thermocoagulation of the aorta of the acardiac fetus using diathermy via a wire passed through an 18-gauge needle has been successfully reported in four cases at 24 weeks' gestation or less (Rodeck et al., 1998). The advantages of this latter approach include avoiding the need for micro-endoscopic instruments or skills and avoiding the difficulties in identifying the target umbilical cord. Intrafetal radiofrequency ablation (RFA) has also been utilized in cases of TRAP. RFA causes thermal injury with high frequency radio waves that denature proteins and initiate cell death through coagulative necrosis. In a series of 23 pregnancies complicated by TRAP and managed with RFA, there was a 91 percent survival rate with a mean gestational age of 35 weeks at delivery (Lee et al., 2004). Livingston and Crombleholme et al. reported a 95 percent survival rate with an ultrasound-guided technique using a 17-gauge radiofrequency LeVeen needle (Boston Scientific) with a mean gestational age at delivery of 36 weeks in a series of 26 patients. Survival rates of 85 percent have been reported with fetoscopic cord coagulation likely as a consequence of two ports being required (Lewi et al., 2003). In a more recent report of TRAP sequence treated by radiofrequency ablation, we reported 54 fetuses in which the acardius to pump twin ratio exceeded 0.7 or there was evidence of increased combined ventricular output or polyhydramnios in the pump twin was successful with 97.3 percent pump twin survival and delivery at a mean gestational age of 36.5 weeks.
It has been suggested that successful interruption of the acardiac circulation after 24 weeks' gestation may require a more invasive approach, such as fetoscopic ligation of the umbilical cord (Arias et al., 1998; McCurdy et al., 1993; Quintero et al., 1994). However, the series reported both by Tsao and Livingston included patients successfully treated after 24 weeks' gestation.
The goal of antepartum management of a pregnancy complicated by twin reversed arterial perfusion sequence (TRAP sequence) is to maximize outcome for the structurally normal pump twin. Management of acardiac twin gestations is controversial. When the diagnosis is made, the gestational age should be documented by maternal history and standard biometric measurements of the pump fetus. The high and low risk factors for perinatal mortality in the pump fetus must be evaluated through sonographic examination. In the absence of poor prognostic features (twin weight ratio > 0.70, elevated CVO, increased C:T ration, congestive cardiac failure, polyhydramnios), expectant management with serial sonographic evaluation is reasonable (Malone and D'Alton, 2000). Additional factors that place the pregnancy at high risk for perinatal mortality include features of acardius anceps demonstrating the presence of arms, ears, larynx, trachea, pancreas, renal tissue and small intestine. Rapid growth of the acardiac twin may also be a sign of poor outcome (Brassard et al., 1999).
Features that indicate a lower risk include features of acardius amorphous with absence of arms, legs, brain, esophagus, trachea and omphalocele (Healey, 1994). Karyotyping of the pump twin should be offered because as many as 9 percent of pump twins have an abnormal karyotype (Healey, 1994).
Various techniques have been used to interrupt the vascular communication between the twins in an effort to improve outcome of the normal pump twin. These methods have included hysterotomy with physical removal of the acardiac twin, ultrasound-guided injection of thrombogenic materials into the umbilical circulation of the acardiac twin, ligation of the umbilical cord of the acardiac twin under fetoscopic guidance and intrafetal radiofrequency cord ablation (Ash et al., 1990; Holzgreve et al., 1994; Porreco et al., 1991; Quintero et al., 1994; Robie et al., 1989; Simpson et al., 1983; Van Allen et al., 1983; Challis, 1999; Tsao, 2002; Livingston et al., 2007). Steroids should be given if delivery is expected between 24 and 34 weeks of gestation (NIH Consensus Development Panel, 1995). Preterm labor should be suppressed with tocolytic agents.
Delivery at a tertiary care hospital is recommended because of the risk of preterm delivery and congestive cardiac failure in the pump twin. The vaginal route is the preferred mode of delivery. The indications for cesarean include the standard obstetric reasons. In the series by Moore et al. (1990), abnormal presentation and fetal distress necessitated cesarean delivery in more than half of the potentially viable pregnancies.
Medical management with maternal administration of digoxin or indomethacin has been reported but there are no significant case series on these management strategies. The use of maternal digitalization to treat cardiac failure in the pump twin was reported by Simpson et al. in 1983. Marked edema of the trunk in the normal twin was present. Fetal ascites, pleural effusion or cardiomegaly was not demonstrated. Serial ultrasound examinations demonstrated resolution of the edema and continued normal growth of the viable fetus. Delivered at 34 weeks, the normal twin weighed 1860 g. The acardiac twin weighed 1810 g. No subsequent reports of this digoxin therapy for acardia have been reported.
Ash et al. (1990) reported the use of indomethacin in an acardiac pregnancy complicated by polyhydramnios at 21 weeks. No evidence of cardiac failure was visualized in the pump twin. Indomethacin, 50 mg daily, was given to treat the symptomatic polyhydramnios because of the high risk of premature labor. The indomethacin was continued for 8.5 weeks. Oligohydramnios at 34 weeks prompted induction of labor and spontaneous vaginal delivery occurred. The normal twin weighed 1865 g at birth and the acardiac twin weighed 785 g (Ash et al., 1990).
A neonatologist should attend the delivery of babies with twin reversed arterial perfusion sequence (TRAP sequence). In the Moore et al. (1990) series, admission to a newborn intensive care unit was required in 41 percent of the pregnancies and 59 percent of those reaching viability. Five of 29 live-born pump twins died during the newborn period. There is little information in the literature on the neonatal course of the pump twin. The main problems for the pump twin include complications of prematurity and congestive heart failure (Moore et al., 1990; Van Allen et al., 1983).
Other frequent neonatal findings include massive hepatosplenomegaly, ascites with hypoplasia of abdominal musculature, edema and hypoalbuminemia due to inadequate liver synthesis of albumin (Van Allen et al., 1983).
Respiratory assistance as well as support of myocardial function with inotropic medication may be required. Early administration of surfactant therapy is indicated when premature delivery at less than 30 weeks of gestation is anticipated. Postnatal consultation with a pediatric cardiologist and echocardiography are recommended.
There is no information in the literature concerning long-term outcome for the pump twin. Considerations for the long-term prognosis must include the degree of prematurity, the severity of the neonatal course the degree of prematurity, the severity of the neonatal course and the degree of congestive heart failure.
Genetics and recurrence risk
Estimates of the recurrence risk of acardiac twin pregnancy are on the order of 1 in 10,000 (Van Allen et al., 1983). This recurrence risk is calculated from the recurrence risk for monoamniotic twinning, which is 1 percent (Myrianthopoulos, 1970), multiplied by the frequency of the occurrence of the TRAP sequence, which is approximately 1 percent of all monozygous twins (Gillim and Hendricks, 1953; Napolitani and Schreiber, 1960).
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