Twin reversed arterial perfusion (TRAP) sequence

INTRODUCTION — Twin reversed arterial perfusion (TRAP) sequence refers to a rare pregnancy complication unique to monochorionic twin pregnancies in which a severely anomalous twin with an absent or rudimentary heart ("acardiac twin") is perfused by its co-twin ("pump twin") via aberrant arterio-arterial anastomoses. The acardiac twin is wholly dependent upon circulatory support from the pump twin, and its upper body and head are often poorly developed, if not altogether absent. Thus, the acardiac twin has no potential for ex utero survival. As a result of the circulatory burden of supporting its acardiac co-twin, the pump twin is at risk of developing heart failure and other complications that may lead to preterm birth or death, which are common complications in the absence of intervention. TRAP may also occur in monochorionic triplet and higher-order multiple gestations.

This topic will discuss issues related to TRAP sequence. More common complications of monochorionic twinning, such as twin-twin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), and selective fetal growth restriction (sFGR) are reviewed separately.

●(See "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis" and "Twin-twin transfusion syndrome: Management and outcome".)

●(See "Twin anemia-polycythemia sequence (TAPS)".)

●(See "Selective fetal growth restriction in monochorionic twin pregnancies".)

INCIDENCE — A 2015 study estimated the incidence of TRAP sequence to be 1 in 38 (2.6 percent) monochorionic twin pregnancies and 1 in 9500 to 11,000 (0.01 percent) pregnancies, based on mathematical models [1].

TRAP sequence had historically been reported to occur in approximately 1 percent of monochorionic twin pregnancies and 1 in 35,000 (0.003 percent) pregnancies [2]. These historic figures are widely cited but based on data available up to 1953. In contemporary obstetrics, the incidence appears to be higher due to factors such as the use of first-trimester obstetric ultrasound examination, which can detect early twin demises, and assisted reproductive technology, which has increased the incidence of multiple gestations, including monochorionic twins.

PATHOPHYSIOLOGY

Normal fetal circulation — In the normal fetal circulation, relatively oxygen-rich blood from the placenta flows through the umbilical vein toward the fetal liver; however, the ductus venosus shunts 80 percent of this blood flow into the inferior vena cava, allowing it to bypass the liver and mix with venous return from the lower extremities and kidneys before entering the right atrium (figure 1). Once the blood enters the right atrium, the two sides of the fetal heart act in parallel through intra- and extra-cardiac shunts (foramen ovale, ductus arteriosus) to fill the aorta and provide the systemic circulation. The distal aorta terminates in the left and right common iliac arteries, which each divide into internal and external iliac branches. The umbilical arteries carry relatively deoxygenated blood from the internal iliac arteries back to the placenta.

Fetal circulation in TRAP — In TRAP sequence, the pump twin maintains the normal fetal circulatory pattern described above. Additionally, a portion of its cardiac output travels through one or more mostly placental arterio-arterial anastomoses and then continues retrograde into one or both umbilical arteries and into the systemic circulation of the acardiac twin, thus creating "reversed" circulatory perfusion. While the arterio-arterial anastomoses between twin circulations in TRAP sequence usually exist along the placental surface, a range of vascular atypia has been described, and other abnormalities, such as direct umbilical artery-to-umbilical artery communications that bypass the chorionic plate, are possible [3,4]. Veno-venous anastomoses may also be present but play a minor role.

Reversed circulation involving relatively deoxygenated blood from the pump twin contributes to the development of a wide range of gross structural abnormalities in the acardiac twin [5]. The lower half of the acardiac twin is believed to receive a preferential share of the pump twin's circulatory support, and this may be the reason for relatively better development of the fetal abdomen, pelvis, and lower extremities than the torso, upper extremities, and head, which often demonstrate various degrees of necrosis, maldevelopment, or absence.

Among the protean acardiac twin presentations, a common subtype is acardius acephalus, in which the acardiac twin possesses well-formed lower limbs and pelvis but a severely dysmorphic head and thorax. In other manifestations, the acardiac twin may have no normally identifiable structures and instead appear as an amorphous tissue mass. Due to abnormal circulatory patterns and lack of a normally functioning excretory system, acardiac twins are also at risk for subcutaneous edema, which can be dramatic.

Since the pump twin has to perfuse its own body as well as that of its acardiac co-twin, the resultant hemodynamic burden places it at risk for high-output heart failure. Pump twin heart failure may result in cardiomegaly, polyhydramnios, ascites and other pathologic fluid collections, hydrops fetalis, preterm birth, and perinatal death. The pump twin is also at increased risk for congenital malformations, which is true for all monochorionic twins, with a particular increase in risk for cardiovascular anomalies.

PATHOGENESIS — The precise pathogenesis of TRAP sequence is unknown, and two theories exist. In one, abnormal arterio-arterial anastomoses in early embryogenesis supply deoxygenated blood to an acardiac fetus with no direct placental perfusion. In the other, an acardiac twin with defective early cardiac embryogenesis has low systemic arterial pressure, permitting retrograde flow of blood from its co-twin (pump twin). Regardless of the exact cause, the net result is that the acardiac twin is dependent upon the pump twin for circulatory support from early in the first trimester.

The presence of placental vascular anastomoses alone is not sufficient for the development of TRAP sequence, as nearly all monochorionic twins have some degree of inter-twin placental anastomoses, whereas TRAP remains a rare phenomenon. It is the retrograde blood flow through an arterio-arterial anastomosis that is necessary to make a TRAP sequence diagnosis in a monochorionic twin gestation with an anomalous fetus.

ULTRASOUND FINDINGS — TRAP sequence only occurs in monochorionic multiple gestations and typically with twins. Although very rare, TRAP sequence can occur in a monochorionic-triamniotic triplet pregnancy; a literature review identified 11 case reports of this phenomenon [6]. In monochorionic triplet pregnancies, there may be more than one pump fetus or more than one acardiac fetus.

Acardiac fetus — The following findings can be seen in the acardiac fetus:

●The heart is either absent or a rudimentary pump structure.

●The cranium may be absent or present with major defects, such as anencephaly, holoprosencephaly, or other major neuroanatomic malformations.

●The lower extremities, pelvis, and abdomen may be well developed, or limb defects and anterior abdominal wall defects may be present.

●The lungs, kidney, spleen, and/or liver may be present or absent.

●The head (if present), trunk, and upper extremities (if present) may be severely edematous, in excess of that which might be attributable to autolysis after fetal demise.

●An amorphous tissue mass may be the only finding, with no readily recognizable fetal parts.

●The umbilical cord contains two vessels in 70 percent of cases [7,8].

Pump fetus — The pump fetus may be normal or have signs of high-output cardiac failure, such as:

●Polyhydramnios

●Cardiomegaly

●Pericardial effusions

●Pleural effusions

●Ascites

●Subcutaneous edema/anasarca

●Hydrops fetalis

●Tricuspid regurgitation

PRENATAL (FETAL) DIAGNOSIS — TRAP sequence is diagnosed prenatally based on the characteristic ultrasound findings described above plus Doppler. The three key findings are:

●Monochorionic multiple gestation.

●One fetus with either absent cardiac activity or a rudimentary pump structure (image 1).

●Color Doppler interrogation of the umbilical artery of the acardiac fetus showing blood flowing toward, rather than away from, the acardiac twin (image 2) [7]. This reversed flow is pathognomonic and required for sonographic demonstration of TRAP sequence. Doppler can be used to trace the fetal vessels and demonstrate arterio-arterial anastomosis [9].

Prenatal diagnosis can be made as early as the first trimester [9]. In a classic vignette of an early TRAP presentation, a patient diagnosed with a first-trimester "vanishing" (demised) twin on ultrasound returns for midtrimester fetal anatomic survey only to discover that the presumed fetal demise has continued to grow, at which time TRAP sequence is diagnosed.

To avoid this initial misdiagnosis, color Doppler study should be performed for all early cases of suspected "vanishing" twins within early monochorionic twin gestations. The finding of reversed perfusion to a presumably demised twin enables early detection of TRAP sequence. Importantly, when conducting color Doppler studies in first-trimester pregnancies, the goal should be to focus the interrogation on the potential acardiac fetus and to limit exposure to the viable co-twin as much as practically possible. (See "Overview of ultrasound examination in obstetrics and gynecology", section on 'Safety'.)

Differential diagnosis — Upon real-time ultrasound examination of monochorionic twins (or higher-order multiple gestation), the differential diagnosis of TRAP sequence includes a severely anomalous co-twin and co-twin demise. An anomalous twin unrelated to TRAP can be excluded by Doppler assessment of the arterial flow pattern to that twin: it will be reversed in TRAP but normal in a purely anomalous twin. A demised twin will not have limb movement, will not have retrograde arterial flow observed on color Doppler imaging, and will not continue to grow on serial ultrasound examinations, whereas an acardiac twin may demonstrate some or all of these findings.

Rarely, the severely amorphous "acardiac" tissue mass of the cotwin may be mistaken for a placental mass, such as a chorioangioma, in a singleton pregnancy. Chorioangiomas are usually well-circumscribed, rounded, vascular lesions next to the chorionic surface near the cord insertion site. Color Doppler ultrasound should demonstrate the low-resistance pulsatile blood flow in the aberrant fetal vessels perfusing the lesion. (See "The placental pathology report", section on 'Mass lesions of the parenchyma'.)

PROGNOSIS — Among TRAP sequence cases with poor prognostic features that are expectantly managed, pump twin perinatal mortality rates of ≥50 percent were reported in two series [10,11]. Notably, interpretation of these data is limited, as one series [10] described cases from over three decades ago and the second series [11] had only small numbers of expectantly managed cases.

The principal reasons for high mortality are development of heart failure, which may lead to pregnancy loss in any trimester, and sequelae of preterm birth, which may be iatrogenic or spontaneous.

In utero treatment improves survival rates to approximately 80 percent or higher. (See 'Outcome' below.)

Poor prognostic factors — One or more of the following poor prognostic factors raise the risk of pump twin mortality [10-13]:

●Pump twin hydrops or high-output heart failure.

●Abnormal pump twin Doppler velocimetry studies including persistently absent or reversed end-diastolic blood flow in the umbilical artery, pulsatile blood flow in the umbilical vein, and/or reversed a-wave in the ductus venosus Doppler waveform (which may be indicative of evolving or overt cardiac failure).

●Ratio of weight of the acardiac twin to weight of the pump twin greater than 0.70 (ie, the calculated weight of the acardiac twin is ≥70 percent of the weight of the pump twin). This can be estimated subjectively or by using a regression equation [10]:

In one study, when the ratio of the weight of the acardiac twin to that of the pump twin exceeded 0.70, the risks of cardiac failure, preterm birth, and polyhydramnios were 30, 90, and 40 percent, respectively [10]. By comparison, when this ratio was below 0.70, the risks of cardiac failure, preterm birth, and polyhydramnios were 10, 75, and 30 percent, respectively.

Other formulas have been proposed for the sonographic assessment of acardiac twin weight since conventional biometric formulas are not applicable when evaluating the size of an acardiac fetus. Given the many different possible acardiac twin body shapes, no single formula can accurately estimate weight for all acardiac twins. Therefore, subjective assessment is also important in the assessment of acardiac twin size.

●Polyhydramnios (defined as maximum vertical pocket of amniotic fluid ≥8 cm).

●Monoamniotic pregnancy (which carries additional risk of cord entanglement).

PREGNANCY MANAGEMENT — Following a diagnosis of TRAP sequence, patients should be referred to a fetal diagnosis and therapy center with experience managing these pregnancies for further assessment and to discuss management strategies. The option of pregnancy termination should be offered. For continuing pregnancies, strategies include conservative management or targeted cord occlusion of the acardiac twin.

Assessment for genetic abnormalities — Pregnancies complicated by TRAP sequence appear to be at increased risk of genetic abnormalities (aneuploidy) [14,15]; therefore, an invasive procedure (eg, amniocentesis, chorionic villus sampling) to obtain fetal cells for genetic testing (karyotype, microarray) is recommended. This information may influence patient decisions regarding pregnancy continuation; acardiac twin cord occlusion; and/or other aspects of prenatal, intrapartum, or postnatal care.

Ultrasound monitoring — There are no robust data to support any specific evidence-based surveillance strategy for monitoring pregnancies complicated by TRAP sequence. Based on our clinical experience, we suggest close sonographic assessment following diagnosis of TRAP sequence, with serial sonographic examinations typically every one to two weeks depending upon the perceived severity of clinical presentation and gestational age.

For example, we would monitor a relatively small acardiac mass with a normal pump twin in the early midtrimester on alternating weeks since substantial deterioration between studies is unlikely. We would recommend weekly monitoring for patients with a relatively large acardiac twin, those in whom we have concerns about development of poor prognostic factors, and those at or approaching a gestational age where ex utero survival is likely, because poor prognostic factors or a deterioration in fetal status may prompt consideration for cord occlusion therapy or, in some instances, delivery. In other scenarios, such as cases in which we suspect evolving very early pump twin compromise before our usual gestational age cutoff for cord occlusion therapy, we may offer twice weekly monitoring to optimize the timing of the therapeutic intervention.

Antenatal corticosteroids — Pregnancies complicated by TRAP sequence may be considered for antenatal corticosteroid administration if the clinician is concerned about delivery occurring in the next seven days based on signs of threatened preterm labor, the presence of preterm prelabor rupture of membranes (PPROM), or sonographic findings of compromise of the pump twin that might necessitate delivery (eg, abnormal Doppler velocimetry). (See 'Poor prognostic factors' above and "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery".)

Cord occlusion therapy — The goal of cord occlusion therapy for the management of TRAP sequence is to interrupt the vascular communication(s) between twins, thereby relieving the pump twin of the hemodynamic burden of supporting its acardiac co-twin. As the acardiac twin has no potential for any meaningful long-term independent survival, treatment for TRAP sequence is entirely focused on optimizing pump twin outcomes.

Intervention confers a better prognosis than conservative management, especially in pregnancies with one or more poor prognostic features. In a meta-analysis including 26 retrospective studies of TRAP sequence, intervention by cord occlusion or ablation was associated with a greater chance of live birth than conservative management (odds of miscarriage/fetal death with conservative management versus intervention: odds ratio [OR] 2.22, 95% CI 1.23-4.01), with the greatest benefit in pregnancies with poor prognostic factors (odds of miscarriage/fetal death with conservative management versus intervention: OR 8.58, 95% CI 1.47-49.96) [16]. (See 'Poor prognostic factors' above.)

Cord occlusion procedures are only available at a small number of institutions due to the need for highly specialized training and equipment. Patients with pregnancies complicated by TRAP sequence should be offered referral to these centers for further evaluation and care. A list of many such centers worldwide can be found on the North American Fetal Therapy Network website (www.naftnet.org).

Candidates — Candidates for cord occlusion therapy generally include TRAP sequence with at least one of the poor prognostic factors described above. (See 'Poor prognostic factors' above.)

Although a ratio of the estimated weight of the acardiac twin to that of the pump twin exceeding 0.70 is one such poor prognostic factor, many centers now offer cord occlusion therapy for ratios exceeding 0.50 or with evidence of a rapidly growing acardiac twin. Ultimately, the decision to intervene must be individualized to the specifics of each pregnancy and must balance maternal and obstetric risks against potential pump twin benefits. Local legal regulations regarding termination may be an additional factor, although it should be reiterated that acardiac twins often lack hearts and heads and are universally acknowledged to have no chance for ex utero survival.

Preprocedure evaluation and preparation — A comprehensive fetal anatomic assessment, fetal echocardiography, and invasive diagnostic genetic testing are recommended before fetal cord occlusion therapy [17].

There are no robust data to support either clear benefit or harm from perioperative antibiotic prophylaxis for percutaneous cord occlusion therapy. At our center, we administer cephalexin 250 mg orally approximately 1 hour before therapy and continue it every 6 hours for a total of 72 hours. If the patient is not able to take a cephalosporin, we would use clindamycin 900 mg orally.

Choice of procedure — Three contemporary modalities for intrafetal cord occlusion therapy for management of TRAP sequence are radiofrequency ablation (RFA), bipolar cord coagulation, and intrafetal (or interstitial) laser coagulation [18-21]. These procedures can be performed under local or regional anesthesia.

The choice of technique for a given pregnancy should be individualized based on operator experience, center resources, clinical presentation, gestational age, and preference. In the United States, RFA is the most commonly used cord occlusion technique, and the preferred technique at the author's institution. In many treatment centers, RFA and/or bipolar are reserved for candidates with TRAP sequence presentations at least 16 weeks of gestation, and preferably ≥18 weeks of gestation, due to concerns about a higher rate of complications, such as PPROM, with earlier intervention. The optimal management of candidates presenting before 16 to 18 weeks is unclear. Expectant management until later in gestation is an option but has been associated with significant risk for poor obstetric outcomes [22]. Use of intrafetal laser therapy has been suggested for the specific indication of early TRAP presentations, as it can be performed as early as the late first trimester [23].

Because RFA involves a smaller caliber uterine entry than bipolar occlusion to conduct the procedure, RFA proponents believe that it may possess a lower complication rate (and therefore greater efficacy) for achieving midtrimester cord occlusion in complicated monochorionic gestations. However, limited data have been unable to conclusively demonstrate improved outcomes with RFA [24,25], despite its seemingly less invasive nature [26,27]. In a meta-analysis that included 481 cases of bipolar cord occlusion and 320 cases of RFA from 17 studies involving complicated monochorionic gestations, overall survival was 76.8 percent with RFA and 79.1 percent with bipolar occlusion [25]. While PPROM occurred less frequently in the RFA group compared with the bipolar group, (17.7 versus 28.2 percent), mean gestational age at delivery was similar for both groups (34.7±1.7 weeks for RFA; 35.1±1.6 weeks for bipolar).

No randomized trials comparing RFA with other cord occlusion modalities have been completed, but an international trial is underway comparing early intervention with intrafetal laser with later intervention with RFA or fetoscopic photocoagulation of anastomosing vessels [28].

Procedure

●RFA – RFA is used to coagulate the acardiac twin abdominal wall at the level of the umbilical cord insertion, thereby causing cord occlusion. For RFA, a probe (contemporary probes are typically 17-gauge) is percutaneously guided though a small skin incision into the acardiac twin under continuous ultrasound guidance. This procedure can be performed under regional anesthesia or with local anesthetic (ie, lidocaine) block with sedation in a patient who has received preprocedural oral pain medication.

Although different RFA probes exist, a commonly used RFA probe utilizes deployable tines that release in a palm-tree configuration, allowing for a controlled ablation sphere (image 3) that will occlude all umbilical vessels. Ablation is then performed until either specific impedance or temperatures are reached, depending on the device used. Due to significant maternal thermal injuries associated with early RFA experience, grounding pads are required prior to ablation to protect the patient from such injuries. As with the other techniques, cessation of blood flow from the pump twin to the acardiac twin is confirmed by Doppler ultrasound prior to the end of the procedure [20]. Following the RFA procedure, we usually administer a limited course of indomethacin (50 mg oral loading dose followed by 25 mg orally every 6 hours for a total of 48 to 72 hours) to patients with procedure-associated cramping or contractions. (See "Inhibition of acute preterm labor", section on 'Fetal side effects'.)

●Bipolar coagulation – Bipolar coagulation is performed by percutaneously guiding an operative sheath (approximately 10- to 12-French) under adequate analgesia through a small skin incision into the uterus via Seldinger technique or direct trochar entry to reach the target "acardiac" fetus. Once the uterus is entered, an amnioinfusion can be performed in cases where the target twin has oligohydramnios. A diagnostic fetoscope may then be used to visualize the "acardiac" twin cord and identify an appropriate target site for coagulation. Alternatively, a cord target site can be identified by ultrasound evaluation.

If a fetoscope was used, it is removed, and bipolar forceps are advanced through the sheath and sonographically guided to grasp the target cord site. Once confirmed to be in place, power is applied until successful cord occlusion is achieved. Cord occlusion can be demonstrated using sonography and Doppler studies; fetoscopic visualization may be utilized for confirmation, as well. Similar to RFA, periprocedural indomethacin tocolysis may be used. (See "Inhibition of acute preterm labor", section on 'Fetal side effects'.)

●Laser coagulation – Intrafetal laser coagulation involves a freehand-guided 17- or 18-gauge spinal needle directed into an intrafetal tissue target adjacent to the intrafetal cord vessels. A laser fiber is then passed through the needle, and, over a series of brief controlled bursts, sustained interruption of vascular flow is achieved.

Complications — Major maternal complications from cord occlusion are rare and include severe bleeding, uterine injury, need for laparotomy, thermal injury, chorioamnionitis potentially leading to maternal sepsis, and disseminated intravascular coagulation. Among the 98 patients identified in the North American Fetal Therapy Network Registry of RFA cord occlusion therapy for TRAP, there were no maternal deaths, no patient required a blood transfusion, and most patients were hospitalized for ≤1 day after the procedure [29]. Obstetric complications include PPROM, previable loss, preterm labor, preterm birth, abruption, and intrauterine infection. Perioperative pump twin demise is possible, and there is theoretical risk for direct and indirect pump twin injury [30].

Development of aplasia cutis congenita has been reported as a complication of the intrafetal laser coagulation procedure; further study is required to evaluate the incidence of this complication [31].

Outcome

●Neonatal survival – Across published experiences describing the use of RFA for TRAP, survival of the pump twin ranged from 80 to 100 percent, with mean gestational age at delivery ranging from 33 to 37 weeks [20,29,32,33]. In the North American Fetal Therapy Network review of 98 pregnancies from multiple contributing fetal therapy centers, there was an overall 80 percent pump twin survival rate and median gestational age at birth of 37 weeks [29].

As previously noted, retrospective review suggests comparable efficacy for RFA and bipolar cord occlusion [24,25].

Limited published experience with intrafetal laser coagulation suggests a neonatal survival rate of approximately 80 percent [23,28,34-36]. In the largest series of intrafetal laser for TRAP at a single center (17 cases), the live birth rate was 82 percent at a median gestational age of 37+1 weeks of gestation [34]. An accompanying literature review including data from an additional 10 studies yielded 51 total cases with an 80 percent neonatal survival rate.

●Long-term outcomes – Data on long-term outcomes are sparse. Cases of neurodevelopmental delay have been reported after cord occlusion selective feticide for TRAP [37,38]. In the largest series focused on long-term neurodevelopmental outcomes among pump twin survivors of pregnancies complicated by TRAP sequence that were treated with RFA, information was available for 27 children at median age two years five months and none had neurodevelopmental delay (defined as total developmental quotient <70 points using the Kinder Infant Development Scale, a validated questionnaire) [39]. However, some patients were as young as four months at assessment, only 44 percent were over three years old, and long-term follow-up was not available for another five children who underwent RFA.

Role of amnioreduction — If referral to a center providing acardiac twin cord occlusion is not possible, amnioreduction can decrease polyhydramnios and limit its consequences. However, as amnioreduction does not address the underlying TRAP pathophysiology, it is a temporizing measure at best and not a preferred strategy. Referral to a fetal therapy center experienced with cord occlusion treatment is, therefore, strongly recommended, when possible.

Timing of planned delivery — Although there are no robust data to support optimal delivery timing for pregnancies complicated by TRAP sequence, based on our clinical experience, we believe a reasonable approach is to consider delivering otherwise uncomplicated cases that do not undergo fetal therapy at 34+0 to 36+6 weeks gestational age, and potentially sooner if complications such as pump twin compromise or development of standard obstetric indications for preterm birth occur. Following successful cord occlusion therapy with subsequent reassuring ultrasound and maternal surveillance, full-term delivery is an appropriate goal.

Cesarean birth should be reserved for standard obstetric indications.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Multiple gestation".)

SUMMARY AND RECOMMENDATIONS

●Overview – Twin reversed arterial perfusion (TRAP) sequence refers to a rare, unique complication of monochorionic twin pregnancy in which a twin with an absent or rudimentary heart ("acardiac twin") is perfused by its co-twin ("pump twin") via abnormal placental arterio-arterial anastomoses. (See 'Pathophysiology' above.)

●Prenatal diagnosis – TRAP sequence is diagnosed prenatally based on three key sonographic findings (see 'Prenatal (fetal) diagnosis' above):

•Monochorionic multiple gestation.

•One fetus with either absent cardiac activity or a rudimentary pump structure (image 1).

•Doppler study demonstrating retrograde arterial flow to the acardiac fetus (pathognomonic finding).

●Acardiac phenotype – The acardiac phenotype ranges from well-developed lower extremities, pelvis, and abdomen to a tissue mass that is not readily recognizable as a fetus. The calvarium may be absent or present with intracranial defects, such as anencephaly or holoprosencephaly. Other possible abnormalities include limb defects, anterior abdominal wall defects, and absence of lungs, kidney, spleen, and/or liver. (See 'Acardiac fetus' above.)

●Pump phenotype – The pump twin may have signs of high-output cardiac failure, including polyhydramnios, cardiomegaly, pericardial and pleural effusions, ascites, and tricuspid regurgitation. These findings are poor prognostic factors. The ratio of acardiac-to-recipient twin estimated weight can also be used to assess pump twin prognosis. (See 'Pump fetus' above and 'Poor prognostic factors' above.)

●Prognosis – Among TRAP sequence cases with poor prognostic features that are expectantly managed, pump twin perinatal mortality rates of ≥50 percent were reported in two series; however, one included older data and the other was small. (See 'Prognosis' above.)

●Management

•Referral – Patients with pregnancies complicated by TRAP sequence should be referred to fetal therapy centers for further evaluation and counseling regarding management options, including cord occlusion therapy. (See 'Pregnancy management' above.)

•Genetic testing – Fetal genetic testing is recommended for pregnancies complicated by TRAP sequence, as the risk of genetic abnormalities appears to be increased. (See 'Assessment for genetic abnormalities' above.)

•Cord occlusion

-Pregnancies complicated by TRAP sequence with clinical presentations indicative of a poor prognosis are candidates for intervention via acardiac twin cord occlusion therapy. In utero treatment improves survival rates to 80 percent or higher. (See 'Prognosis' above and 'Outcome' above.)

-Contemporary modalities for cord occlusion therapy for management of TRAP sequence are radiofrequency ablation and bipolar cord coagulation. Intrafetal (or interstitial) laser coagulation is another modality currently being studied for this indication. (See 'Choice of procedure' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Marium G Holland, MD, MPH; Joan M Mastrobattista, MD; and Michael J Lucas, MD, MPH, who contributed to earlier versions of this topic review.