A Twin-to-Twin Transfusion Syndrome (V QuinteroÃ¢â¬â¢s stage): A Case Report and LiteratureÃ¢â¬â¢s Review

Case report

Open Access

Genovese F¹, Marilli I¹, Benintende G² , Carbonaro A¹, Leanza V¹, Vizzini S¹, Leanza G¹ and Pafumi C^1*

¹Institute of Pathology, Obstetrics and Gynecology, University Hospital - Vittorio Emanuele, Catania, Italy

²Complex Operative Unit of Prenatal Diagnosis and Medical Genetics, University Hospital - Vittorio Emanuele, Catania, Italy

^*Corresponding authors:

Pafumi C
Institute of Pathology
Obstetrics and Gynecology
University Hospital-Vittorio Emanuele, Catania, Italy
E-mail: pafumi@unict.it

Received July 06, 2012; Published September 03, 2012

Citation: Genovese F, Marilli I, Benintende G, Carbonaro A, Leanza V, et al. (2012) A Twin-to-Twin Transfusion Syndrome (V Quintero’s stage): A Case Report and Literature’s Review. 1:292. doi:10.4172/scientificreports.292

Copyright: © 2012 Genovese F, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Abstract

Background: Monochorionic twins have a risk of developing a Twin-to-twin transfusion syndrome (TTTS) between 10 and 15%. The pathogenesis of the twin-to-twin transfusion syndrome is still unknown, and the mortality reaches 80-90% if not treated. TTTS is characterized by the presence of multiple vascular placental anastomoses. The diagnosis of TTTS is primarly ultrasonographic, through the identification of peculiar signs: no intertwin dividing membrane, same sex, polyhydramnios of the recipient, oligo/anhydramnios of the donor, donor Intra-Uterine Growth Restriction (IUGR), permanently filled bladder in the recipient and slightly filled or empty bladder in the donor. The severity of the syndrome is established using the Quintero’s staging system.

Case: We report the case of a 36 year old patient with one set of monochorionic female twins and a male fetus with its own placenta. The one set of female twins was complicated by Quintero stage V twin-to-twin transfusion syndrome, with death of the donor twin.

Methods: Review of the literature based mainly on PubMed search using specific keywords.

Results: TTTS should be treated in specialized centers. There are several treatment options for the management of twin-to-twin transfusion syndrome: fetoscopic laser coagulation of placental vascular anastomoses and serial amniodrainage; selective feticide by cord occlusion; septostomy with or without amniodrainage.

Conclusions: Appropriately timed diagnosis of twin-to-twin transfusion syndrome is crucial because a delay in diagnosis may result in a delay in treatment and consequent increased perinatal mortality and morbidity. At the moment the best treatment seems to be fetoscopic laser coagulation of placental vessel anastomoses, which showed survival rates between 76-88%.

Keywords

Monochorionic twins; Placenta; TTTS; Quintero’s staging system

Introduction

Monochorionic twins account for about 10 - 20% of twin pregnancies [1]. A monochorionic pregnancy occurs when a single fertilised ovum splits into identical twins after 3 days of ova fertilisation. This condition has an increased risk of perinatal morbidity and mortality compared to dichorionic twin pregnancies. The placenta in monochorionic twins contains several inter-fetal vascular anastomoses. The abnormality of a single placenta serving two twins can lead to: Twin to Twin Transfusion Syndrome (TTTS), Twin Anemia-Polycythemia Sequence (TAPS), selective intrauterine growth restriction or Twin Reversed Arterial Perfusion sequence (TRAP) [2].

Case Report

We report the case of a 36 year old patient with a natural dichorionic triiamniotic triplet pregnancy, with one set of monochorionic biamniotic female twins and a male fetus with its own placenta and amniotic sac. The set of female twins was complicated by Quintero stage V twin-to-twin transfusion syndrome, with death of the donor twin which occurred probably at 13 weeks (between 12 and 17 weeks of gestational age), and the survival of the recipient twin till birth at term.

We began to suspect a twin to twin transfusion syndrome for the first time at 10 weeks, when we detected, during an ultrasound (US) examination, beside a regular singleton pregnancy, a monochorionic biamniotic twin pregnancy, with an antero-fundal location of the placenta. The US showed an early discrepancy between the measures of the two twins. The bi-test performed at 12weeks+3days also confirmed this suspect. During this exam the second twin, the one we called donor, showed an increase of the Nuchal Translucency (NT), 2.5 mm (around the 95° percentile), meanwhile the recipient’s NT was 1.9mm. The Nucal translucency of the singleton male fetus was 1.6mm. The maternal Pregnancy-associated plasma protein A (PAPP-A) was 24.60 UI/mL. A normal fetal heart rate was present in all three fetuses.

At the time of amniocentesis, performed at 17w+1d, the death of the donor twin was diagnosed. The amniotic fluid of both twins presented a brown pigmentation and levels of alpha-fetoprotein >30000 ng/mL (n. v. 5900-15100 ng/mL). The aspect of the amniotic fluid and its level of alpha fetoprotein were normal in the singleton pregnancy. The cytogenetic study of both twin was normal, instead that of the male fetus showed a de novo balanced translocation T(3;5) (q13;q14), confirmed with a DNA molecular test, while the parents’ cariotypes didn’t show any genetic anomaly. During the gestation the woman was strictly followed every month (Figure 1).

Figure 1: The donor twin inside the gestational sac still intact.

The birth occurred at term (39w+1d), with a cesarean-section, after a premature rupture of membranes at home. Actually the two children are alive and in good health (Figure 2).

Figure 2: The donor stillbirth twin.

Risk factors for developing a TTTS

Monochorionic twin pregnancies have a risk of developing a TTTS between 10 and 15%. This complication occurs in about 1 out of 2000 pregnancies [3,4]. The pathogenesis of the twin-to-twin transfusion syndrome is still unknown, and the mortality reaches 80-90% if not treated. TTTS is characterized by the presence of multiple placental vascular anastomoses, most commonly Arterio- Venous (AV), formed by a ‘‘shared’’ cotyledon, with arterial supply from one twin and venous drainage going to the other fetus; Arterio- Arterial (AA), Veno- Venous (VV) and direct vascular connections also have been described leading to the development of an unbalanced chronic blood transfer from one twin, defined donor, to the other twin called recipient [2,4].

TTTS is associated with patterns of vascular anastomoses which steal a variable amount of blood flow from the donor in favor of the recipient. These patterns seem characterized by predominance in size and/or number of AV anastomoses from the donor to the recipient, in combination with paucity of AA anastomoses [4].

Although TTTS may develop at every gestational age, a good number of cases occur in the second trimester between the 15^th and 25^th week [5]. If untreated TTTS is associated with an high percentage of severe complications, going from the spontaneous death of one twin to the risk of an exsanguination into the dead twin and its placenta. Other commons complications are miscarriage and very preterm delivery. Additionally, severe alterations of the fetal hemodynamic such as abnormal venous doppler, cardiac hypertrophy, bivalvular regurgitation, right outflow tract obstruction and, eventually, heart failure and fetal hydrops have been observed in the recipient twin. Sometimes, suppression of the renal renin-angiotensin system (RAS) characterizes the recipient twin, due to the increased production of these chemical mediators by both placenta and donor twin, who has an hyperactivation of the RAS. An elevation of vascular proteins, such as endothelin, has been observed too in both twins [4].

Sonographic signs of TTTS

Peculiar signs of twin to twin transfusion syndrome are monochorionic placenta, with no intertwin dividing membrane and the T sign at the ultrasonographic exam, instead of the classic lambda sign of dichorionic placenta, same sex, polyhydramnios of the recipient (maximum vertical pocket >8 cm or >10 cm respectively ≤20 weeks or >20 weeks) and oligo/anhydramnios of the donor (maximum vertical pocket <2 cm), donor Intra-Uterine Growth Restriction (IUGR), permanently filled bladder in the recipient and slightly filled or empty bladder in the donor [3,6,7]. The echocardiography usually shows a specific hypertrophic cardiomyopathy in the recipient [8]. The severity of the syndrome is widely valued by a staging system proposed by Quintero et al. based on ultrasounds and doppler measurements. Significant variations in Peek Systolic Velocity (PSV) in the Middle Cerebral Artery (MCA) have been found in monochorionic twins with TTTS [9].

For completeness we report the Quintero’s staging system:

- Stage I The bladder is still visible in the donor twin;

- Stage II The bladder is no longer visible in the donor;

- Stage III Critically abnormal Doppler in either twin: absentreverse diastolic flow in the donor or recipient umbilical artery and/or absent/reverse flow in the ductus venosus or pulsatile flow in the umbilical vein of the recipient;

- Stage IV Hydrops in either fetus;

- Stage V Demise of one or both twins [4].

Management of TTTS

There are several treatment options for the management of Twinto- twin transfusion syndrome: fetoscopic laser coagulation of placental anastomoses and serial amniodrainage; selective feticide by cord occlusion; septostomy with or without amniodrainage [4].

The best treatment of cases presenting before 26 weeks of gestation is fetoscopic laser ablation of the intertwin anastomoses on the chorionic plate [10]. There are no formal contraindications of laser therapy, although a short cervical length (<15 mm) may indicate an higher-risk of preterm delivery. Preliminary evidence suggests that cervical cerclage might reduce this risk [11]. In the absence of complications after laser treatment, planned delivery is recommended from 34 weeks and no later than 37 weeks [12]. With this procedure the survival rates for at least one twin is 76-88%, the incidence of severe neurodevelopmental impairment at 2 to 5-year of age is 13-17% [13,14].

Serial amniodrainage is a palliative treatment, it consists in removing the amniotic fluid from the recipient’s sac. The procedure can be repeated if required. In cases of severe TTTS before 26 weeks’ gestation, amniodrainage has been reported to be associated with survival rates of 51-60% for at least one fetus and rate of neurological handicap of 29% [15,16,17].

Cord occlusion is not a first option therapy for TTTS, but it may be chosen when one fetus presents with a malformation or clear evidence of brain injury [18]. Septostomy is an intentional perforation of the intervening twin membrane. A randomized trial of amnioreduction versus septostomy in the treatment of twin-twin transfusion syndrome showed that survival was similar in the amnioreduction group compared to the septostomy group (78% vs 80% of pregnancies, respectively; RR= 0.94, 95%CI 0.55–1.61; P=0.82), but patients treated with septostomy were more likely to require a single procedure for treatment (64% vs 46%; P=0.04) [19].

Management of a twin pregnancy after in utero death

In the case of monochorionic pregnancy, anastomoses on the chorionic plate may lead, as previously explained, to morbidity and perhaps death of the cotwin. The risks of fetal death and neurological abnormalities of the surviving twin are about 12% and 18% respectively, with an increased risk of preterm delivery. Evidence so far suggests that damage to the surviving twin mainly derives from consequences of hemodynamic disturbance secondary to acute hemorrhage into the demised fetus through vascular communications [20]. A possible cerebral lesion (associated with hypovolemic shock) can generally be detected only 3 weeks to a month after the death of the other twin. Ultrasound evaluation and fetal cerebral Magnetic Resonance Imaging (MRI) are recommended to look for these cerebral lesions in survivors. However early delivery in hours or days after the death of one twin is not recommended, because it will not prevent in any case the potential cerebral lesions [12]. Fichera et al. [21] studied the perinatal outcome and neurological follow up of the cotwins in 10 dichorionic and 13 monochorionic diamniotic pregnancies complicated by single intrauterine death. In the monochorionic group one cotwin died in utero and one in the neonatal period with a perinatal survival rate of 83.4%; in the dichorionic group survival rate was 100%. In all monochorionic cases at the diagnosis of fetal demise of one twin and during subsequent ultrasonographic follow up there were no signs of ischemic brain lesions in the surviving cotwins. In monochorionic pregnancies prenatal MRI, when performed, was negative for signs of brain damage in the surviving cotwins. Gestational age at delivery was not statistically different between monochorionic and dichorionic pregnancies [36 (range, 28.4–40.2) vs. 34.6 (range, 28.2-41.3) weeks] (p= 0.6) and the rate of early preterm delivery before 32 weeks was 23.8% (5/21) independently from chorionicity (18.2% vs. 30%, p= 0.5). Neurodevelopmental follow up was available for 18/20 live born survivors (85%) and was normal in all but one twin; this case was born from a dichorionic pregnancy with a suspect of congenital infection [21].

Conclusion

Appropriately timed diagnosis of twin-twin transfusion syndrome is crucial because a delay in diagnosis may result in a delay in treatment and increased perinatal mortality and morbidity. The management of TTTS should be perform in specialized centers. At the moment the best treatment seems to be fetoscopic laser coagulation of placental vascular anastomoses, which showed survival rates between 76-88%.

In our case it was not possible planning an invasive treatment, such as fetoscopic laser coagulation, because of the early in-utero death of one of the monochorionic twins occurred about 13 weeks of gestation.

References