Twin-to-twin transfusion syndrome

As a result of sharing a single placenta, the blood supplies of monochorionic twin fetuses can become connected, so that they share blood circulation: although each fetus uses its own portion of the placenta, the connecting blood vessels within the placenta allow blood to pass from one twin to the other. It is thought that most monochorionic placentae have these "shared connections" that cross the placenta, with the net flow volumes being equal between them. This state is sometimes referred to as "flow balance". When the placenta has deep veinartery connection, this can cause blood flow to become unbalanced. • Embolic Theory: The demise of the donor twin allows necrotic tissue, presumably thrombosis-plastin like material, to pass through the vasculature of the surviving twin via the placental vessels. The necrotic tissue embolizes the surviving twin's mesenteric artery, resulting in bowel atresia, the renal artery, resulting in renal agenesis, or the peripheral arteries, resulting in limb ischemia and skin abnormalities. • Ischemic Theory: The demise of the donor twin creates a low-pressure state resulting in the shunting of blood into the low-resistance vascular system of the dead fetus. This state of low pressure acutely causes hypovolemia, resulting in ischemia and poor end-organ perfusion. • Placentation Theory: The incidence of velamentous cord insertion, an abnormal insertion of the umbilical cord into the placenta, is higher in TTTS. The exact mechanism of effect this has on fetal damage is unknown. ==Diagnosis==

Quintero stages A staging system is commonly used to classify the severity of TTTS. Stage I: A small amount of amniotic fluid (oligohydramnios) is found around the donor twin and a large amount of amniotic fluid (polyhydramnios) is found around the recipient twin. Stage II: In addition to the description above, the ultrasound is not able to identify the bladder in the donor twin. Stage III: In addition to the characteristics of Stages I and II, there is abnormal blood flow in the umbilical cords of the twins. Stage IV: In addition to all of the above findings, the recipient twin has swelling under the skin and appears to be experiencing heart failure (fetal hydrops). Stage V: In addition to all of the above findings, one of the twins has died. This can happen to either twin. The risk to either the donor or the recipient is roughly equal & is quite high in Stage II or higher TTTS. The Quintero staging does not provide information about prognosis, and other staging systems have been proposed. ==Treatment==

Various treatments exist for TTTS. Non treatment This is equivalent of zero intervention. It has been associated with almost 100% mortality rate of one or all fetuses. Exceptions to this include patients that are still in Stage 1 TTTS and are past 22 weeks' gestation. Adjustment of amniotic fluid Serial amniocentesis This procedure involves removal of amniotic fluid periodically throughout the pregnancy under the assumption that the extra fluid in the recipient twin can cause preterm labor, perinatal mortality, or tissue damage. In the case that the fluid does not reaccumulate, the reduction of amniotic fluid stabilizes the pregnancy. Otherwise, the treatment is repeated as necessary. There is no standard procedure for how much fluid is removed each time. There is a danger that if too much fluid is removed, the recipient twin could die. This procedure is associated with a 66% survival rate of at least one fetus, with a 15% risk of cerebral palsy, and average delivery occurring at 29 weeks' gestation. Septostomy, or iatrogenic disruption of the dividing membrane This procedure involves the tearing of the dividing membrane between fetuses such that the amniotic fluid of both twins mixes, under the assumption that pressure is different in either amniotic sac and that its equilibration will ameliorate progression of the disease. It has not been proven that pressures are different in either amniotic sac. Use of this procedure can preclude use of other procedures as well as make difficult the monitoring of disease progression. In addition, tearing the dividing membrane has contributed to cord entanglement and demise of fetuses through physical complications. Adjustment of blood supply Laser therapy (fetoscopic laser photocoagulation) and laser ablation of connecting vessels in twin-to-twin transfusion syndrome This procedure involves endoscopic surgery using laser to interrupt the vessels that allow exchange of blood between fetuses under the assumption that the unequal sharing of blood through these vascular communications leads to unequal levels of amniotic fluid. Each fetus remains connected to its primary source of blood and nutrition, the placenta, through the umbilical cord. This procedure is conducted once, with the exception of all vessels not having been found. The use of endoscopic instruments allows for short recovery time. This procedure has been associated with 85% survival rate of at least one fetus, with a 6–7% risk of cerebral palsy and average delivery occurring at 32–33 weeks' gestation. Twin anemia–polycythemia sequence (TAPS) may occur after laser surgery for TTTS (post-laser form). The spontaneous form of TAPS complicates approximately 3–5% of monochorionic twin pregnancies, whereas the post-laser form occurs in 2–13% of TTTS cases. The pathogenesis of TAPS is based on the presence of few, minuscule arterio-venous (AV) placental anastomoses (diameter <1mm) allowing a slow transfusion of blood from the donor to the recipient and leading gradually to highly discordant Hb levels. A 2014 review found that laser coagulation resulted in fewer fetal and perinatal deaths than amnioreduction and septostomy, and recommended its use for all states of TTTS. Selective reduction Selective termination of one of the fetuses is usually not considered until TTFS has reached either stage III or IV, and is indicated when the death of one twin is imminent, but the fetus is too premature to deliver, as the death of one twin will cause the death of the second twin due to the shared blood supply if not immediately delivered. Use of this treatment has decreased as TTTS is identified and treated in earlier stages and with better outcomes. When used, it is associated with an 85% survival rate of the remaining fetuses with 5% risk of cerebral palsy and a 33–39 weeks of gestation at delivery. Voluntary termination Some women choose to have an abortion of both fetuses as the health of both fetuses is impacted by TTFS. ==Epidemiology==

Based on recent (2005) US NCHS data, the rate of multiple births is now approximately 3.4% (4,138,349 total births, of which 139,816 were twins or higher-order multiple births). The majority of identical twins share a common (monochorionic) placenta, and of these approximately 15% go on to develop TTTS. By extrapolating the number of expected identical twins (about one-third) from annual multiple births, and the number of twins with monochorionic placentae (about two-thirds), and from these the number thought to develop TTTS (about 15%), there are at least 4,500 TTTS cases per year in the U.S. alone: 139,816 × 0.33 × 0.66 × 0.15 = 4,568 cases of TTTS per year in U.S. (involving more than 9,000 babies.) Since spontaneous pregnancy losses and terminations that occur prior to 20 weeks go uncounted by the C.D.C., this estimate of TTTS cases may be very conservative. Although infertility treatments have increased the rate of multiple birth, they have not appreciably diluted the expected incidence of identical twins. Studies show a higher rate of identical twins (up to 20 times with IVF) using these treatments versus spontaneous pregnancy rates. One Australian study, however, noted an occurrence of only 1 in 4,170 pregnancies, or 1 in 58 twin gestations. This distinction could be partly explained by the "hidden mortality" associated with MC multifetal pregnancies—instances lost due to premature rupture of membrane (PROM) or intrauterine fetal demise before a thorough diagnosis of TTTS can be made. ==History==

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. The drawing shows twins that appear to be identical, but one is pale, while the other is red. 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. ==See also==