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 AV's 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 © 2008 John Wiley & Sons, Ltd.     

Perinatal hepatic infarction in twin–twin transfusion

We report a case of a twin pregnancy which was complicated by a twin–twin transfusion in which the recipient twin was noted to have an intra-abdominal echogenic mass. This twin died at two days of age of hepatic infarction. The donor twin was healthy at birth, at thirty weeks' gestation, and did not have any subsequent problems. Fetal intra-abdominal echogenicity may be a marker of hepatic infarction. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of renal agenesis in a twin gestation

Bilateral renal agenesis is a lethal congenital anomaly. It appears to be transmitted in a polygenic pattern. The prenatal ultrasound findings consist of severe oligohydramnios, absence of the fetal bladder, and failure to identify fetal kidneys. Twin gestations with renal agenesis have been described in the paediatric literature. We detail a case of a patient with two prior affected pregnancies with bilateral renal agenesis. Her latest pregnancy was diagnosed prenatally, with one fetus with bilateral and the other fetus with unilateral renal agenesis. The ultrasound findings should be differentiated from the stuck twin phenomenon.     

Central nervous system damage and other anomalies in surviving fetus following second trimester antenatal death of co-twin. Report of four cases and literature review

Four cases of multiple gestation with second trimester death of one fetus and subsequent damage to a survivor are reported. Monochorionic placentation was documented in three of the cases. Central nervous system lesions occurred in all cases, and bowel injury was noted in two of the damaged fetuses. Although rare maternal clotting problems have been reported in similar situations, none was noted in any of these four cases. Prior reports have indicated that losses in the first half of gestation were of no consequence to the surviving fetuses. These four cases contradict this suggestion, and indicate that close sonographic observation of the survivors is important in any multiple gestation where one fetus has died.     

Genetic amniocentesis in biamniotic twin pregnancies by a single transabdominal insertion of the needle

We present a technique to aspirate amniotic fluid from both sacs in biamniotic twin pregnancies using a single abdominal insertion with a spinal needle. It was successful in 48 out of 55 cases of biamniotic twin pregnancies referred to our perinatal unit between 1985 and 1994. The single insertion technique was used when the inter-amniotic membrane was clearly evident and two separate free amniotic fluid pools could be reached by the operator with a single puncture. An adequate amount of amniotic fluid was sampled from both sacs to make a cytogenetic diagnosis in all cases. There were four fetuses with trisomy 21 in three twin pregnancies. In two cases, only one twin was affected whilst the co-twin was normal, so that a selective feticide was performed. No miscarriages due to genetic amniocentesis were reported. After 1990, all genetic amniocenteses in biamniotic twin pregnancies (except for one case due to late booking) were performed between 14 and 15 weeks of gestation and with all cases except one, it was possible to sample both twins by a single puncture. We suggest that early amniocentesis (14–15 weeks) by a single abdominal puncture could be a reliable and safe alternative to first-trimester chorionic villus sampling in twin pregnancies.     

Acardiac anomaly: current issues in prenatal assessment and treatment

Acardiac anomaly is a rare condition affecting monochorionic multiple pregnancies. We review this condition with emphasis on its prenatal diagnostic features and treatment options. Due to the parasitic hemodynamic dependence of the acardiac twin on the pump twin, it is important to monitor the pump twin for signs of decompensation and, if indicated, intervene by interrupting vascular supply to the acardiac twin. The goal of treatment is to maximize the pump-twin's chance of survival. To assist with the decision of when to treat, we suggest a new classification system based on prognostic factors, specifically the size and growth of the acardiac twin and the cardiovascular condition of the pump twin. When the acardiac twin is small and no signs of cardiovascular impairment in the pump twin are present, we suggest serial ultrasound surveillance to detect any worsening of the condition. In cases with a large acardiac twin or rapid growth of the acardiac mass, we recommend prompt intervention. Once treatment is indicated, the intrafetal approach to interrupt the vascular supply to the acardiac twin appears to be superior to cord occlusion techniques as it is simpler, safer and more effective. The first line of treatment, if available, should be ultrasound-guided laser coagulation or radiofrequency ablation of the intrafetal vessels. Copyright © 2005 John Wiley & Sons, Ltd.     

Twin–twin transfusion syndrome—possible roles for doppler ultrasound and amniocentesis

A 29-year-old woman was referred for suspicion of twin-twin transfusion syndrome (TTTS). Several ultrasonographic and neonatal criteria of TTTS were encountered in this twin pregnancy. The peculiar observations in this case were, firstly, the demonstration of superficial anastomosis by Doppler ultrasound and, secondly, that one single therapeutic amniocentesis could have been sufficient to partially correct the progression of the syndrome, as after amniocentesis it was no longer possible to demonstrate the vascular communication. This observation suggests that superficial anastomoses could also have a role in the genesis of TTTS. Their effect could be monitored by Doppler ultrasound and could be more easily corrected by therapeutic amniocentesis.     

Insights into the pathophysiology of twin–twin transfusion syndrome

Twin–twin transfusion syndrome (TTTS) is attributed to trans-anastomotic transfusion between twins. Anastomoses are ubiquitous in monochorionic (MC) placentae, yet TTTS develops in only 15%. Although ex vivo and in vivo studies fail to identify a unique anastomotic signature, TTTS placentae are typically associated with an imbalance in unidirectional arteriovenous anastomoses with absent bidirectional anastomoses. Doppler detection of an artery-artery anastomosis reduces the chance of TTTS, whereas, in those that develop the disease, it improves stage-independent survival. Selective laser is often curative, but an increasingly recognized risk of persistent or reverse TTTS may be attributable to atypical arteriovenous anastomoses not identifiable from the chorionic plate. Simple dysvolaemia fails to explain several phenotypic features, including haematological concordancy, recipient hypertension, and reversibly absent end diastolic flow in the donor. The renin-angiotensin system is upregulated in the donor and downregulated in the recipient's kidneys, while paradoxically raised renin levels in the recipient may contribute to raised afterload along with endothelin. Although research is limited in humans by therapy and the lack of a suitable experimental model, further studies of placental and vascular pathophysiology may not only refine current treatment modalities but may also, in addition, suggest further avenues for downstream management such as genetic predisposition testing or pharmacological intervention. Copyright © 2005 John Wiley & Sons, Ltd.     

Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death

To assess the role of fetal blood sampling and intrauterine transfusion in monochorionic (MC) multiple pregnancy complicated by single intrauterine death (IUD), we reviewed ten cases over a 4-year period in a tertiary referral centre which underwent fetal blood sampling within 24 h of death of its MC co-twin. Intrauterine rescue transfusion was performed in all seven anaemic fetuses (hematocrit; Hct<30%) to raise the fetal Hct to ≥40%. The rationale was to prevent death and/or brain injury. Two fetuses, which were severely acidaemic at blood sampling, died in utero within 24 h of the procedure. In two cases, the surviving twins manifested abnormal sonographic findings of the fetal brain 2–5 weeks later and underwent late termination. In two cases, the pregnancies continued uneventfully until delivery at 35 and 40 weeks' gestation with good neonatal outcome. In one case the co-twin delivered 1 week later at 29 weeks but died within 12 h. Fetuses without anaemia were not transfused and had normal clinical outcomes. We suggest that intrauterine rescue transfusion before the development of severe acidaemia in anaemic surviving MC co-twins may prevent fetal death, but does not necessarily prevent brain injury. Until its role becomes clearer, we recommend that its use be restricted to situations in which the parents and the local jurisdiction allow late termination as an option if brain injury subsequently manifests on ultrasound. Copyright © 2001 John Wiley & Sons, Ltd.