Acardiac twin: too many invasive treatment options—the problem and not the solution

Twin reversed arterial perfusion sequence resulting in an acardiac twin is a condition for which numerous prenatal interventions have been described, ranging from termination of pregnancy to in-utero surgical vascular ablation in order to ‘save’ the normal co-twin1, 2. In general, the number of treatment options available for a disease is inversely related to the effectiveness of such interventions, no one therapeutic technique having been demonstrated as unequivocally optimal. A letter published in this issue of the Journal reporting the failure of intrafetal alcohol injection for ablating an acardiac twin3 provides a timely opportunity to revisit the two main controversial topics in the management of this condition once the decision to intervene has been made: firstly, the timing, and secondly, the technique, of intervention. Acardiac twinning, one of the most severe congenital malformations seen in humans, is unique to monochorionic placentation and occurs with a reported prevalence of 1% of monozygotic twins and one in every 35 000 pregnancies. Its most distinctive feature, and the main focus of our attention, is the presence of a structurally normal ‘pump’ twin, which provides a blood supply to the parasitic acardiac twin in a retrograde, paradoxical fashion through a single superficial artery-to-artery anastomosis4. Either this vessel courses on the surface of the placenta or, occasionally, the single umbilical artery of the acardiac twin connects directly with the umbilical cord of the pump twin. The acardiac twin, therefore, lacks a functional placenta and its entire fetoplacental blood volume is confined to its own vascular tree. In a significant number of cases the continuous growth of the acardiac twin and the associated ‘vascular steal’ phenomenon may lead to cardiac insufficiency, polyhydramnios and even death of the pump twin. A review of 184 cases published in the literature5 and a large series of 49 pregnancies with an acardiac twin6 collected mostly from the pre-ultrasound era, revealed that this condition is associated with a perinatal mortality rate ranging from 35% to 55%. Although there are several methodological criticisms of using this information for counseling patients, such as retrospective analysis of predominantly referral cases or those ascertained at the time of delivery or autopsy, it has the merit of being representative of the natural history of the disease. The studies clearly indicate that about half of all pregnancies complicated with an acardiac twin result in a liveborn pump twin without the need of any invasive prenatal intervention. Reinforcing this conservative approach, a recently published report by Sullivan et al.7 advocates that expectant management should be considered in all cases. Based on their experience with 10 pregnancies with an acardiac twin managed expectantly, these authors reported an overall survival rate for the pump twin of 90%. A critical analysis of the available data, however, revealed that in four cases the size of the acardiac twin was clinically insignificant because, at the time of the delivery, the acardiac-to-pump twin (A/P) weight ratio was less than 3%. In the remaining six pregnancies, the A/P weight ratio ranged from 32% to 282% and half of the pump twins had severe complications, including one case of intrauterine death (A/P weight ratio of 86%), one of severe intrauterine growth restriction requiring delivery at 29 weeks (A/P weight ratio of 282%) and one of severe premature delivery at 31 weeks (A/P weight ratio > 50%). In retrospect, these three cases were undoubtedly candidates for prenatal intervention, although no information on the size of the acardiac twin or prenatal ultrasound features at the time of the diagnosis and follow-up are available from the report. The inevitable lesson from these reports5-7 is that invasive treatment should be restricted to those pregnancies which would potentially benefit from prenatal intervention, i.e. in those where the pump twin is at significant risk of prematurity, cardiac insufficiency or death. We therefore suggest that in-utero invasive treatment should be considered only in cases in which poor prognostic factors are detected, including the development of polyhydramnios, ultrasound markers of cardiac insufficiency (i.e., tricuspid regurgitation, pulsatile umbilical vein and abnormal ductus venosus waveforms in the pump twin's circulation), large acardiac twin and rapid growth of, or evidence of substantial blood flow perfusion through the umbilical vessel supplying, the parasitic mass8-10. If none of these features is present, conservative management is recommended, because spontaneous cessation of blood supply to the acardiac twin occurs in many cases, or the size of the acardiac twin may remain significantly smaller than the size of the pump twin despite a persisting blood supply from the pump twin; even if deterioration is subsequently detected, treatment could be carried out later in gestation11. One exception to this conservative approach may be the treatment of an acardiac twin in a monochorionic–monoamniotic pregnancy. In such cases, ablation of the acardiac twin's vasculature together with transection of the umbilical cord to prevent death of the pump twin due to entanglement of the cord should be considered12. Regarding the treatment options, it has become evident from early clinical experience that management with indomethacin and digoxin to treat polyhydramnios and cardiac insufficiency, respectively, is not efficacious since it only delays definitive treatment and, as such, should be discouraged. Similarly, the less invasive option of amniodrainage to treat polyhydramnios, and hence prolong pregnancy, should not be performed as a single procedure because it does not correct the underlying hemodynamic pathophysiology that leads to progressive cardiovascular demand on the pump twin. At the other end of the interventional spectrum, a rather extreme alternative treatment is selective delivery of the acardiac twin through hysterotomy (sectio parva)13-15, but its invasiveness and the high rate of maternal complications inevitably restrict this option to the medical history books. Minimally invasive intrauterine treatment to interrupt the blood supply to the acardiac twin, and hence treat the underlying anatomical defect, is currently the main strategy to prevent perinatal death of the pump twin1, 2. Although the rationale behind this modality is easy to understand, its practical achievement is more difficult. Platt et al.16, in 1983, were the first to suggest occlusion of the circulation to the acardiac twin as the definitive treatment for this condition. Only in 1991 did this option became clinically available when Porreco et al.17 described in the English-language literature the novel approach of ultrasound-guided insertion of a helical metal coil to induce thrombosis in the umbilical artery of the acardiac twin. Three years later, Quintero et al.18 reported the successful ligation of an acardiac twin's umbilical cord under fetoscopic guidance. Although highly effective, endoscopic techniques are more invasive, lengthy and cumbersome compared with ultrasound-guided needle techniques. In addition, they are associated with serious inherent risks, including rupture of membranes in up to 30% of cases. Furthermore, they frequently require additional procedures such as a second port entry for amnioinfusion and septostomy to access the acardiac fetus's umbilical cord through the pump twin's sac, with the additional risk of cord entanglement due to iatrogenic pseudoamnionicity. Technical difficulties in visualizing the umbilical cord also led to ligation of the pump twin's cord in one case19 and the overall experience with 16 pregnancies in which the acardiac twin was managed with fetoscopy-assisted umbilical cord ligation demonstrated a perinatal mortality rate of 38% and a preterm delivery rate of 70%2, 20. Fetoscopy-assisted laser coagulation instead of ligation of the umbilical cord may theoretically appear less demanding, but this technique can only be carried out in early pregnancy for technical reasons21, hence increasing the number of overtreated cases. The main limitations of all the fetoscopy-guided techniques, either cord ligation or laser coagulation of the umbilical vessels, are that they require expensive equipment and skilled operators which are only available in a few specialist centers around the world, mainly in Europe and the USA. Although fetal endoscopic surgery is currently available in our center in Chile, clinical practice in most developing countries is often constrained by substantial practical, technical and financial limitations for referring patients to such centers; therefore, the availability of simpler, less invasive techniques for achieving vascular occlusion in this complex disorder are needed. Targeting the intrafetal rather than the umbilical cord vessels provides such an alternative option22. This approach has been greatly facilitated with the use of color Doppler ultrasound, which allows the clear identification of the acardiac twin's feeding vessel and its main intra-abdominal branches, making these vessels easier to access compared with the umbilical cord using ultrasound-guided needle techniques22. In 1995, the intrafetal technique for ablation of acardiac twins using absolute alcohol was described22. Subsequently, several authors have reported successful pregnancy outcomes after using this approach11, 23, 24. In the case reported by Ozeren et al. in this issue3, the authors attempted unsuccessfully to ablate the circulation of an acardiac twin at 16 and at 24 weeks. Of note, they injected a large amount (8 and 12 mL, respectively) of absolute alcohol ‘…into the intrafetal part of the umbilical artery…’, with persistence of blood flow within the acardiac mass on both occasions. It is likely that the treatment failed due to the inability to achieve intravascular injection of the sclerosant agent. A multicenter study examining intrafetal vascular chemosclerosis with alcohol in acardiac fetuses revealed that failure of the technique is often the result of inadvertent injection of the sclerosant into the pump twin's circulation, resulting in bradycardia during the procedure and fetal demise shortly after25. Recently, several other modifications to the technique of intrafetal vascular ablation have been developed, including monopolar coagulation26, laser coagulation27 and radiofrequency ablation28. This so-called intrafetal approach has several advantages over the cord occlusion techniques in terms of its simplicity, safety and efficacy, not least the fact that it can be carried out in any fetal medicine unit with facilities to perform fetal blood sampling with needles commonly used for standard cytogenetic diagnostic procedures. Although some criticisms have been raised regarding the use of case reports and small series to build up a meta-analysis29, it is evident from a recent large review of the literature on treatment of acardiac twins that the ultrasound-guided intrafetal needle approach is consistently easier, is far less invasive and has a higher rate of clinical success than do the ultrasound- and fetoscopy-guided cord occlusion procedures2. In summary, pregnancies complicated by acardiac twinning should be managed and, if required, treated, in referral centers by fetal medicine specialists familiar with invasive procedures. Treatment should be instituted in cases selected on the basis of objective criteria and serial ultrasound surveillance is critical to determine which cases would potentially benefit from prenatal intervention. Once treatment is indicated, the intrafetal approach appears to be superior to cord occlusion techniques. If available, ultrasound-guided laser coagulation, or radiofrequency ablation, of the intrafetal vessels should be the first line of treatment based on the currently available experience. If referral to fetal surgery centers is not possible, chemosclerosis of the intrafetal arterial vessels with alcohol should be attempted. This work was supported by Sociedad Profesional de Medicina Fetal “Fetalmed” Limitada and a grant from the Direccion Academica, Clinica Las Condes, Santiago, Chile.