Clinical Pathology Conference: Acute Twin-to-Twin in Utero Transfusion

This clinical pathology conference discusses a case of monochoriontic twins with chronic twin-to-twin transfusion based on unequal venous return and a large arterial communication. Polyhydramnios resulted in preterm labor, fetal distress, and a reversed acute twin-to-twin transfusion through the arterial shunt.     

Monochorionic twin fetuses showing a reversal of donor-recipient phenotypes in severe twin–twin transfusion syndrome without oligo-polyhydramnios sequence

ABSTRACT   Antenatal sonographic diagnosis of twin–twin transfusion syndrome (TTTS) is based on findings of a twin oligo-polyhydramnios sequence (TOPS) observed in monochorionic twin fetuses. However, TTTS can develop without a significant characteristic intertwin discordance in the amniotic fluid volumes. We report an uncommon form of TTTS without TOPS showing severe anemia in one twin and polycythemia in the other. Based on sonographic findings, it is considered that the recipient twin became the donor later in gestation, and vice versa. It is concluded therefore that even in the absence of TOPS, the possibility of severe TTTS with a suspected reversal of donor-recipient phenotypes during pregnancy should not be excluded, and serial Doppler studies including the measurement of the middle cerebral artery peak systolic velocity should be routinely performed even in seemingly uncomplicated monochorionic twin fetuses without TOPS.     

Twin Transfusion: Pathological Studies of the Monochorionic Placenta in Liveborn Twins and of the Perinatal Autopsy in Monochorionic Twin Pairs

Vascular injections of 21 monochorionic placentas from liveborn twins were scored for chorionic surface vessel anastomoses and for venous return areas. The results were correlated with neonatal birth weight and first hematocrit. Weight and hematocrit differences did not correlate with each other or with placental anastomoses. There was a relationship between weight and placental area to the individual twin. In some cases, weight differences between monochorionic twins may be the result of placental differences rather than chronic transfusion. Seventeen perinatal autopsies of monochorionic twin pairs were reviewed for plethora/pallor and for organ and body weights. Cardiac hypertrophy was present in three autopsies. Cardiac hypertrophy may be a measure of chronic twin transfusion in the recipient. The lighter twin was as likely to be plethoric as the heavier. Plethora postmortem is a poor measure of chronic transfusion because of confounding factors, particularly acute twin transfusion. As a result of these studies, placental anatomy is speculated to be complexly rather than directly related to clinical outcome.     

Pathology of Intragestational Intervention in Twin-to-twin Transfusion Syndrome

Selective intervention in multiple pregnancy is being used to enhance the chances of survival of at least one conceptus when the risks for the combined conceptuses and mother are considered too great. These procedures have been applied to induced polyembryonic conceptions (selective continuance) and discordant dichorionic twins (selective birth). We report attempts at selective intervention in three monochorionic twin gestations affected by twin-to-twin transfusion syndrome. In all three cases, both fetuses seemed doomed and the mother was in significant distress. The selected survivor in the first case is doing well; both twins were stillborn in the second case; in the third case, the selected survivor died as a neonate but the other twin survived and is doing well. We suggest possible explanations for the clinical outcome of each case based on detailed pathologic examination of the delivered placentas and autopsy examination of the nonsurviving twins. The shared chorionic circulation is the source of both the clinical disorder and the potential complications of any attempt to alleviate the disorder. This situation is unique to monochorionic twins, and we discuss the implications of this for intrauterine therapy of twin-to-twin transfusion syndrome.     

Twin–twin transfusion syndrome,coarctation of the aorta and hypoplastic aortic arch: A case series report

Aim: The twin–twin transfusion syndrome (TTTS) complicates 10–30% of monochorionic pregnancies. The incidence of pulmonary stenosis and endocardial fibroelastosis is especially high in the recipient twin. We report a novel finding of four cases of coarctation of the aorta and hypoplastic aortic arch in the donor to raise awareness of cardiac lesions in twins affected by TTTS. Method: Retrospective review of both neonatal database and mortality data from 2002 to 2007 with cross‐validation from the local tertiary cardiology unit data (1998–2006) to identify children presenting with coarctation who were also twins. Results: We identified four monochorionic twin pairs affected by the TTTS, delivered between 25 weeks and 36 weeks' gestation, where the donor was found to have coarctation of the aorta or a hypoplastic aortic arch. In addition, two of the four recipients also had cardiac abnormalities. There was a high mortality rate of 30% for both twins, and a high morbidity rate, especially for neurological sequelae. Conclusion: We believe that the types of abnormalities seen may be explained by the altered fetal blood flow and haemodynamics in TTTS. Given the increased prevalence of congenital heart disease in TTTS, with an increased risk of coarctation in the donor twin and pulmonary stenosis in the recipient, intra‐uterine surveillance and a post‐natal comprehensive cardiac assessment for both twins is warranted.     

Severe retinopathy of prematurity with retinal detachment in monozygotic twins

We report a monochorionic diamniotic twin pair born at 29 weeks of gestation in which both twins developed severe retinopathy of prematurity (ROP) with retinal detachment. The pregnancy was terminated due to reversal of donor‐recipient phenotypes in possible TTTS. Both twins had unstable cardiopulmonary status during the first week, and developed chronic lung disease. The larger twin, born at 1372 g, developed stage 4a ROP in both eyes, and the smaller twin, born at 1168 g, developed stage 4a ROP in the left eye. Genetic analysis of NDP, FZD4, LRP5, TSPAN12 genes revealed no mutations; however, VEGF gene polymorphism analysis showed heterozygous carrier state of the VEGF 936T allele in both twins, which is a risk factor for threshold ROP in Japanese newborn infants. We speculate the synergistic effects of unstable perinatal cardiopulmonary status and genetic predisposition due to VEGF 936C>T polymorphism caused the development of severe ROP with retinal detachment.     

Twin–twin transfusion syndrome: cerebral ischemia is not the only fetal MR imaging finding

Background Twin–twin transfusion syndrome (TTTS) is a complication of monochorionic/diamniotic twin pregnancies. An imbalance of blood flow occurs through placental anastomoses, causing potentially significant morbidity and mortality in both twins. Although the sonographic findings of TTTS are well documented, we believe that MR imaging is a valuable adjunct. Objective We describe the fetal MR imaging findings associated with TTTS. Materials and methods From 2003 to 2005, 37 consecutive MR imaging studies were performed on multiple-gestation pregnancies. Of the 37, 25 were consistent with TTTS, correlated and confirmed by sonographic criteria. MR fetal abnormalities were documented. Results Cerebral ischemia, which could not be demonstrated by sonography, was delineated well by MR imaging. New findings noted on fetal MR imaging were enlargement of cerebral venous sinuses in both twins, dilatation of the renal collecting system in the recipient, lung lesions in the recipient and cerebral malformations in the donor. Conclusion MR imaging is an important adjunct in TTTS imaging. Its benefit over sonography is its clear definition of cerebral pathology, which is important for intervention and counseling. The new findings, particularly in the urinary tract and cerebral venous sinuses, also help support the diagnosis of TTTS and might reveal additional consequences of the altered hemodynamics that occur in TTTS.     

Rapid Onset of Severe Twin–Twin Transfusion Syndrome Caused by Placental Venous Thrombosis

We report a case of rapid onset of severe twin–twin transfusion syndrome (TTTS) at 25 weeks gestation in a monochorionic twin pregnancy that was uneventful before that time. Thrombosis of a main venous branch draining several arteriovenous (AV) anastomoses to the donor changed the previous hemodynamic balance that existed between multiple bidirectional AV anastomoses. The opposing AVs became hemodynamically uncompensated and, despite amnioreductions, severe TTTS developed. At 27 weeks a cesarean section was performed because of worsening cardiotocography parameters of both fetuses. Birth weights were 750 and 1840 g, and initial hemoglobin concentrations were 9.2 and 13.4 mmol/liter for donor and recipient, respectively. The recipient twin died 5 months later of an ischemic, necrotic, and perforated small intestine due to a thrombosed superior mesenteric artery. The donor is well at 2.5 years. No abnormalities in several factors associated with thrombophilia, including factor V Leiden mutations, were found in the parents. Received September 25, 2001; accepted January 22, 2002.     

Cardiac outcomes of hydrops as a result of twin–twin transfusion syndrome treated with laser surgery

Aim:   To determine cardiac outcomes of foetal hydrops as a result of twin–twin transfusion syndrome treated with laser surgery.
Methods:   Hydrops identified in 16 recipient foetuses with twin–twin transfusion syndrome was treated with laser ablation surgery to anastomotic vessels. Prior to laser surgery, the foetuses were assessed by echocardiography for cardiac abnormalities and ventricular and valvular dysfunction. After delivery, echocardiography was performed on 15 of the 16 newborn infants.
Results:   Foetal echocardiography indicated impaired biventricular function in the 16 hydropic foetuses. Five foetuses had little or no forward flow through the pulmonary valve, while four had pulmonary regurgitation. Following laser surgery performed at a mean of 22.9 weeks gestation, hydrops resolved in all cases. Delivery occurred at a mean of 33.6 weeks gestation. Post-natal echocardiography revealed cardiac abnormalities in five neonates, of whom three had right ventricular outflow tract obstruction. One preterm infant with severe pulmonary stenosis died with intractable cardiac failure.
Conclusion:   The majority of hydropic infants with twin–win transfusion syndrome have normal cardiac outcomes following intrauterine laser surgery. As up to one-third may have cardiac abnormalities, cardiological monitoring is recommended during the first year of life.     

双胎贫血-红细胞增多序列征新生儿喂养不耐受3例总结

目的探讨双胎贫血-红细胞增多序列征新生儿喂养情况。方法回顾分析3例喂养不耐受的双胎贫血-红细胞增多序列征新生儿的临床资料。结果 3例生后确诊为双胎贫血-红细胞增多序列征的单绒毛膜双胎早产的供血儿,在喂养过程中都出现了喂养不耐受的临床表现,而3例受血儿的喂养过程顺利。结论单绒毛膜双胎妊娠,若存在宫内慢性双胎输血,产后需密切关注新生儿的喂养问题,尤其双胎供血儿。     

In Utero Development of Pulmonary Artery Calcification in Monochorionic Twins: A Report of Three Cases and Discussion of the Possible Etiology

Pulmonary artery (PA) calcification is unusual in children, reportedly occurring only in conjunction with severe underlying valvular disease. Three newborns were found by chest X-ray study to have thin calcified rings of the PA. Two were pump twins in twin reversed arterial perfusion (TRAP) sequences, each with an acardiac cotwin, and the third was the recipient in a twin transfusion syndrome (TTS). Both twin pairs with TRAP sequence were premature, each pump twin presenting with cardiac decompensation. One remained well at 5 months of age, the other died at 5 1/2 months of age. The third, the premature recipient of twins with TTS, died at 24 h of age, and the donor cotwin died at 2 h of age. The two hearts were structurally normal at autopsy. Subtle intimal wrinkling was seen above the pulmonary valve leaflets, and the media was yellow and granular on cut section. Hyperplasia of the intima and media with disruption and calcification of the elastic fibers of the media was seen microscopically. These three cases of PA calcification occurring in utero were not related to structural valvular abnormalities but were presumably due to increased cardiac output in utero as each occurred in the volume-overloaded twin of the twin pair. Comparison of the weight differences between these three twin pairs with PA calcification suggests a relationship between the presence of PA calcification and the severity of the cardiac volume overload. In utero cardiac damage may contribute to the high morbidity and mortality rate seen in infants with TRAP sequence and TTS.     

Complications of Monochorionic Diamniotic Twins: Stepwise Approach for Early Identification,Differential Diagnosis,and Clinical Management

One in three monochorionic twins may develop complications during pregnancy. Monochorionic twins, especially monochorionic diamniotic (MCDA), present specific problems caused by the presence of interfetal placental anastomoses. The first critical step in the management of MCDA twins is identification in the first trimester. Secondly, close follow-up every 2 weeks is mandatory to allow early diagnosis and timely treatment of twin-twin transfusion syndrome. Other potentially severe complications include selective fetal growth restriction, twin anemia polycythemia syndrome or single fetal death. Thirdly, a correct differential diagnosis is critical to establish the best therapy. This may represent a clinical challenge since MCDA twin complications often overlap. A simple diagnostic algorithm may be of great help to establish the right diagnosis and management option. In this review we summarize the main steps for the clinical follow-up, differential diagnosis, and targeted management of MCDA twins complications.     

Intrauterine growth restriction in monochorionic twins

Intrauterine growth restriction (IUGR) occurs in approximately 3–10% of singleton pregnancies, in 9.1% of all twins, and in 9.9% of monochorionic twins. Spontaneous demise of the IUGR twin may occur and may result in concomitant demise or severe neurological handicap of the other twin. Currently, monochorionic twins with selective IUGR (SIUGR) are managed expectantly. Alternatively, all adverse consequences resulting from the potential demise of the SIUGR twin could be averted by unlinking the circulations between the two fetuses. The latter can be achieved by laser photocoagulation of communicating vessels or by umbilical-cord occlusion. The purpose of this chapter is to review this important entity in obstetrics.     

Association of Cloacal Anomalies, Caudal Duplication, and Twinning

Cloacal anomalies exhibit a wide variety of morphologic types and accompanying clinical severity. The association of malformations of the cloaca with partial, complete, or conjoined twinning has been appreciated for some time, but, with the advent of prenatal ultrasound technology, appears to occur with a greater frequency than once thought. This observation has important implications for pathogenesis. We present 2 representative cases, a 19-week-old female fetus with duplication of several caudal structures and a 21-week-old male fetus with cloacal exstrophy variant and demised co-twin with lower abdominal wall defect, extruded intestinal tract, absent external genitalia, and imperforate anus. These findings and previously published theories suggest that certain models of monozygotic twinning may apply to the pathogenesis of cloacal anomalies. Specifically, the partial or complete duplication of the organizing center within a single embryonic disc may increase the risk of mesodermal insufficiency and thus account for the failure of complete development of the cloacal membrane and consequent exstrophy or other aberration.     

Twin–twin transfusion syndrome – What we have learned from clinical trials

Monochorionic twin pregnancies are at increased risk for adverse outcome compared to dichorionic twin pregnancies and singletons. Monochorionic-specific complications include twin–twin transfusion syndrome (TTTS), twin anemia–polycythemia sequence, single intrauterine fetal demise and its consequences on the co-twin, and selective intrauterine growth restriction. Whereas the natural history of monochorionic-specific complications carries a high risk of fetal death or severe neurologic disability, a framework now exists, based on well-designed clinical trials, for optimal treatment of these entities. Fetoscopic selective laser coagulation of anastomotic vessels on the chorionic plate has been clearly demonstrated to improve survival and neurologic outcomes for Quintero stage ≥2 TTTS. However, many challenges remain unsolved, the most important of which is preterm premature rupture of membranes. Further improvement in the outcomes of monochorionic pregnancies will require improvements in the rate of premature delivery, and improved diagnosis and treatment strategies for early and late onset TTTS.     

Parasitic Conjoined Twins with Omphalocele and Tetralogy of Fallot

Human parasitic twins are very rare. Here we report a unique case of a partial twin attached to the host in the midline at the forehead, chin, chest, and epigastrium. The parasite lacked thoracic organs and major neural tube derivatives. However, it had small peripheral nerves and ganglia within perirenal and pericolonic connective tissue. Also present were a well-developed small intestine, colon, and appendix with normal submucosal and myenteric plexuses. These findings may represent either the initial presence of a neural tube that later regressed or migration of autosite neural crest cells. The parasite had a mature, functioning kidney with its ureter opening to skin and complete absence of urinary bladder or genital organs. This raises questions about the embryological development of the ureteric bud, which is an outgrowth of the mesonephric duct. The host had tetralogy of Fallot and omphalocele containing the parasitic kidney and bowel. Parasitic twinning occurs at 3 weeks of gestation, tetralogy of Fallot at 3-7 weeks, and omphalocele at 6-10 weeks. A single noxa acting at 3 weeks could have caused sequential malformations that initially seem unrelated.     

Acardiac acephalic twin gestation with transposition of great arteries in pump twin

We report here a case of twin reversed arterial perfusion sequence with transposition of great arteries in the pump twin. Color Doppler and fetal echocardiographic examination revealed an acardiac, anencephalic twin without upper limbs and a pump twin with transposition of great arteries. To our knowledge despite multiple anomalies reported in the acardiac twin, major anomalies, especially of a cardiac type are extremely rare and not reported in the pump twin, which maintains circulation. Management is directed at saving the pump fetus; therefore, we believe that during sonographic exam, emphasis should be placed on associated organ anomalies or complications that may hamper viability of the pump.