Twin-to-twin transfusion syndrome
|Twin-to-twin transfusion syndrome|
|Classification and external resources|
A pair of newborn twins affected by TTTS. Both the recipient (left) and donor (right) survived.
|ICD-10||O43.0, P02.3, P50.3|
|ICD-9||762.3 , 772.0|
Twin-to-twin transfusion syndrome (TTTS, also known as Feto-Fetal Transfusion Syndrome (FFTS) and Twin Oligohydramnios-Polyhydramnios Sequence (TOPS)) is a complication of pregnancy where two or more babies are expected. Unequal distribution of blood between babies results in differences in their growth and development, sometimes resulting in stillbirth. In particular, it is caused by aberrant placental blood vessel growth in monochorionic multiples, that is, multiple pregnancies where two or more fetuses share a chorion and hence a single placenta.
Twin-twin transfusion syndrome (TTTS) is diagnosed prenatally by ultrasound imaging. The diagnosis requires that certain symptoms be present in an identical twin, or higher-order multiple pregnancy in which 2 or more babies share a single placenta. They are, for the "Monochorionic-Diamniotic" pregnancies, with Individual Amnions: The presence of oligohydramnios (defined as a maximal vertical pocket [MVP] of <2 cm) in one sac, and of polyhydramnios (a MVP of >8 cm) in the other sac. MVP of 2 cm and 8 cm represent the 5th and 95th percentiles for amniotic fluid measurements, respectively, and the presence of both is used to define stage I TTTS. If there is a subjective difference in amniotic fluid in the 2 sacs that fails to meet these criteria, progression to TTTS occurs in <15% of cases. Although growth discordance (usually defined as >20%) and intrauterine growth restriction (IUGR) (estimated fetal weight <10% for gestational age) often complicate TTTS, growth discordance itself or IUGR itself are not diagnostic criteria. The differential diagnosis may include selective IUGR, or possibly an anomaly in 1 twin causing amniotic fluid abnormality. Twin anemia-polycythemia sequence (TAPS) has been recently described in MCDA gestations, and is defined as the presence of anemia in the donor and polycythemia in the recipient, diagnosed antenatally by middle cerebral artery (MCA)–peak systolic velocity (PSV) >1.5 multiples of median in the donor and MCA PSV <1.0 multiples of median in the recipient, in the absence of oligohydramnios-polyhydramnios. Further studies are required to determine the natural history and possible management of TAPS. TTTS can occur in a MCDA twin pair in triplet or higher-order pregnancies.
The most commonly used TTTS staging system was developed by Quintero et al. in 1999, and is based on sonographic findings. The TTTS Quintero staging system includes 5 stages, ranging from mild disease with isolated discordant amniotic fluid volume to severe disease with demise of one or both twins. This system has some prognostic significance and provides a method to compare outcome data using different therapeutic interventions. Although the stages do not correlate perfectly with perinatal survival, it is relatively straightforward to apply, may improve communication between patients and providers, and identifies the subset of cases most likely to benefit from treatment.
The Quintero staging of twin-twin transfusion syndrome 
|Stage||Ultrasound parameter||Categorical criteria|
|I||MVP of amniotic fluid||MVP <2 cm in donor sac; MVP >8 cm in recipient sac|
|II||Fetal bladder||Symptoms of Stage I except Donor has no measurable fluid, Nonvisualization of fetal bladder in donor twin over 60 min of observation|
|III||Symptoms of Stage II with Doppler anomalies in the Umbilical artery, ductus venosus, and umbilical vein||Absent or reversed umbilical artery diastolic flow, reversed ductus venosus a-wave flow, pulsatile umbilical vein flow|
|IV||Symptoms of Stage III with Fetal hydrops||Hydrops Fetalis in one or both twins|
|V||Single or Double Loss||Fetal demise of one or both twins|
MVP = maximal vertical pocket
Since the development of the Quintero staging system, much has been learned about the changes in fetal cardiovascular physiology that accompany disease progression (discussed below). Myocardial performance abnormalities have been described, particularly in recipient twins, including those with only stage I or II TTTS. Several groups of investigators have attempted to use assessment of fetal cardiac function to either modify the Quintero TTTS stage or develop a new scoring system. While this approach has some benefits, the models have not yet been prospectively validated. As a result, a recent expert panel concluded that there were insufficient data to recommend modifying the Quintero staging system or adopting a new system. Thus, despite debate over the merits of the Quintero system, at this time it appears to be a useful tool for the diagnosis of TTTS, as well as for describing its severity, in a standardized fashion.
There are several second- and even first-trimester sonographic findings that have been associated with TTTS.
- Crown-rump length discordance
- Nuchal translucency >95th percentile or discordance >20% between twins
- Reversal or absence of ductus venosus A-wave
- Abdominal circumference discordance
- Membrane folding
- Velamentous placental cord insertion (donor twin)
- Placental echogenicity (donor portion hyperechoic)
TTTS was first described by a German obstetrician, Friedrich Schatz, in 1875. Once defined by neonatal parameters—differences in birth weight and cord hemoglobin at the time of delivery—TTTS is now defined differently. Today, it is known that discordant fetal weights will most likely be a late manifestation, and fetal hemoglobin through cordocentesis is often equivalent in the twin pair even in severe TTTS.
TTTS in art
A painting known as the De Wikkellkinderen (The Swaddled Children), from 1617, is thought to represent a depiction of TTTS. The drawing shows twins that appear to be identical, but one is pale (possibly anemic), while the other is red (possibly polycythemic). Analysis of the family histories of the owners of the painting suggests that the twins did not survive to adulthood, although whether that is due to TTTS is uncertain.
Although somewhat of a stretch, due to the detail of "magical birthgiving" in the folklore, an example of TTTS might have been noted ages before Schatz classified it or the painting "De Wikkellkinderen" illustrated, as an old Norse fairy tale, "Tatterhood", seemed to explain it, with one of the two girls being lovely but weak (pale skin and delicacy of anemia has often associated with how girls were most expected to be at the time) and the other one, the title heroine, was considered hideous and too strong (polycythemia has a higher blood cell count and often includes unsightly blemishes). Of course, with both twins growing up to be healthy adults, the debate of truth in fiction is still a mystery.
||This article's use of external links may not follow Wikipedia's policies or guidelines. (October 2013)|
- Twins and Multiple Births Association, Tamba
- The Twin to Twin Transfusion Syndrome Foundation
- Fetal Health Foundation
- Dr. Rubén Quintero at Jackson Memorial Hospital Miami, FL
- Texas Fetal Center (UTHealth Medical School and Children's Memorial Hermann Hospital) Twin to Twin Transfusion Syndrome
- The International Institute for the Treatment of TTTS
- Texas Children's Fetal Center, Twin-Twin Transfusion Syndrome
- TTTS Educational Video – Texas Children's Fetal Center
- Los Angeles Fetal Therapy, Children's Hospital Los Angeles - University of Southern California Fetal Therapy Program-TTTS
- The Center for Prenatal Pediatrics at Columbia University Medical Center- TTTS Evaluation & Laser Photocoagulation Therapy
- Twin-Twin Transfusion Syndrome – Children's Hospital Boston
- The Children's Hospital of Philadelphia
- The Brown Fetal Treatment Program – What is TTTS?
- Ohio State's Maternal Fetal Medicine
- St. Louis Fetal Care Institute TTTS Survivor Stories
- Skupski, Daniel W. MD, Twin-To-Twin Transfusion Syndrome, 2013. Jp Medical Ltd.
- Quintero, Ruben A. (editor), Twin-Twin Transfusion Syndrome, 2007. CRC Press
- Simpson LL . Twin-twin transfusion syndrome . In: Copel JA editors. Obstetric imaging . 1st ed.. Philadelphia: Elsevier; 2012
- Quintero RA , Morales WJ , Allen MH , Bornick PW , Johnson PK , Kruger M . Staging of twin-twin transfusion syndrome . J Perinatol . 1999;19:550–555
- Huber A , Diehl W , Zikulnig L , Bregenzer T , Hackeloer BJ , Hecher K . Perinatal outcome in monochorionic twin pregnancies complicated by amniotic fluid discordance without severe twin-twin transfusion syndrome . Ultrasound Obstet Gynecol . 2006;27:48–52
- Danskin FH , Neilson JP . Twin-to-twin transfusion syndrome: what are appropriate diagnostic criteria? . Am J Obstet Gynecol . 1989;161:365–369
- Gandhi M , Papanna R , Teach M , Johnson A , Moise KJJ . Suspected twin-twin transfusion syndrome: how often is the diagnosis correct and referral timely? . J Ultrasound Med . 2012;31:941–945
- Slaghekke F , Kist WJ , Oepkes D , et al. Twin anemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome . Fetal Diagn Ther . 2010;27:181–190
- Taylor MJ , Govender L , Jolly M , Wee L , Fisk NM . Validation of the Quintero staging system for twin-twin transfusion syndrome . Obstet Gynecol . 2002;100:1257–1265
- Stamilio DM , Fraser WD , Moore TR . Twin-twin transfusion syndrome: an ethics-based and evidence-based argument for clinical research . Am J Obstet Gynecol . 2010;203:3–16
- Rossi AC , D'Addario V . The efficacy of Quintero staging system to assess severity of twin-twin transfusion syndrome treated with laser therapy: a systematic review with meta-analysis . Am J Perinatol . 2009;26:537–544
- Habli M , Michelfelder E , Cnota J , et al. Prevalence and progression of recipient-twin cardiomyopathy in early-stage twin-twin transfusion syndrome . Ultrasound Obstet Gynecol . 2012;39:63–68
- Michelfelder E , Gottliebson W , Border W , et al. Early manifestations and spectrum of recipient twin cardiomyopathy in twin-twin transfusion syndrome: relation to Quintero stage . Ultrasound Obstet Gynecol . 2007;30:965–971
- Rychik J , Tian Z , Bebbington M , et al. The twin-twin transfusion syndrome: spectrum of cardiovascular abnormality and development of a cardiovascular score to assess severity of disease . Am J Obstet Gynecol . 2007;197:392.e1–392.e8
- Lewi L , Jani J , Blickstein I , et al. The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study . Am J Obstet Gynecol . 2008;199:514.e1–514.e8
- Acosta-Rojas R , Becker J , Munoz-Abellana B , et al. Twin chorionicity and the risk of adverse perinatal outcome . Int J Gynaecol Obstet . 2007;96:98–102
- Blickstein I . Monochorionicity in perspective . Ultrasound Obstet Gynecol . 2006;27:235–238
- Lewi L , Lewi P , Diemert A , et al. The role of ultrasound examination in the first trimester and at 16 weeks' gestation to predict fetal complications in monochorionic diamniotic twin pregnancies . Am J Obstet Gynecol . 2008;199:493.e1–493.e7
- . Sebire NJ , Souka A , Skentou H , Geerts L , Nicolaides KH . Early prediction of severe twin-to-twin transfusion syndrome . Hum Reprod . 2000;15:2008–2010
- Sebire NJ , D'Ercole C , Hughes K , Carvalho M , Nicolaides KH . Increased nuchal translucency thickness at 10-14 weeks of gestation as a predictor of severe twin-to-twin transfusion syndrome . Ultrasound Obstet Gynecol . 1997;10:86–89
- Kagan KO , Gazzoni A , Sepulveda-Gonzalez G , Sotiriadis A , Nicolaides KH . Discordance in nuchal translucency thickness in the prediction of severe twin-to-twin transfusion syndrome . Ultrasound Obstet Gynecol . 2007;29:527–532
- Linskens IH , de Mooij YM , Twisk JW , Kist WJ , Oepkes D , van Vugt JM . Discordance in nuchal translucency measurements in monochorionic diamniotic twins as predictor of twin-to-twin transfusion syndrome . Twin Res Hum Genet . 2009;12:605–610
- Maiz N , Staboulidou I , Leal AM , Minekawa R , Nicolaides KH . Ductus venosus Doppler at 11 to 13 weeks of gestation in the prediction of outcome in twin pregnancies . Obstet Gynecol . 2009;113:860–865
- Matias A , Montenegro N , Loureiro T , et al. Screening for twin-twin transfusion syndrome at 11-14 weeks of pregnancy: the key role of ductus venosus blood flow assessment . Ultrasound Obstet Gynecol . 2010;35:142–148
- De Paepe ME , Shapiro S , Greco D , et al. Placental markers of twin-to-twin transfusion syndrome in diamniotic-monochorionic twins: a morphometric analysis of deep artery-to-vein anastomoses . Placenta . 2010;31:269–276
- Kusanovic JP , Romero R , Gotsch F , et al. Discordant placental echogenicity: a novel sign of impaired placental perfusion in twin-twin transfusion syndrome? . J Matern Fetal Neonatal Med . 2010;23:103–106
- Johnson, A. & Moise, K., J. "Improving Survival in Twin-Twin Transfusion Syndrome. Contemporary OB/GYN December 2006" (PDF).
- Berger H, de Waard F, Molenaar Y (2000). "A case of twin-to-twin transfusion in 1617". Lancet 356 (9232): 847–8. doi:10.1016/S0140-6736(00)02665-9. PMID 11022944.
- Fox, Michael J. "Pg 197." Lucky man. New York: Hyperion, 2002.