Twin-to-twin transfusion syndrome (TTTS), also known as feto-fetal transfusion syndrome (FFTS) and twin oligohydramnios-polyhydramnios sequence (TOPS) is a complication of disproportionate blood supply, resulting in high morbidity and mortality. It can affect monochorionic multiples, that is, multiple pregnancies where two or more fetuses share a chorion and hence a single placenta. Severe TTTS has a 60–100% mortality rate.
Symptoms of the recipient twin:
- very large amount of urine in the bladder
- too much amniotic fluid in the sac (polyhydramnios)
- larger than the donor twin and possibly swollen with too much blood
- congenital heart failure from an excess of blood
Symptoms of the donor twin:
- little or no urine in the bladder
- too little amniotic fluid in the sac (oligohydramnios)
- much smaller than the recipient twin
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". Depending on the number, type and direction of the interconnecting blood vessels (anastomoses), blood can be transferred disproportionately from one twin (the "donor") to the other (the "recipient"), due to a state of "flow imbalance" imparted by new blood vessel growth across the placental "equator", the line that divides each baby's proportion of the shared placenta. This state of transfusion causes the donor twin to have decreased blood volume, retarding the donor's development and growth, and also decreased urinary output, leading to a lower than normal level of amniotic fluid (becoming oligohydramnios). The blood volume of the recipient twin is increased, which can strain the fetus's heart and eventually lead to heart failure, and also higher than normal urinary output, which can lead to excess amniotic fluid (becoming polyhydramnios).
TTTS usually develops during the period of peak placental growth, starting in week 16 and proceeding through week 25; after this point, the placenta's growth decelerates, essentially stopping just after week 30. While TTTS has occasionally been detected beyond this timepoint, it is thought that its occurrence beyond week 30 may be due to a placental embolism that upsets the flow balance of the shared connections between the babies. TTTS is potentially lethal to either or both twins, no matter when it is detected. However, when detected past week 25, emergency delivery may be considered to rescue the babies if the TTTS is severe.
Other than requiring a monochorionic twin (or higher multiple) pregnancy, the underlying causes of TTTS are not known. It is not known to be hereditary or genetic.
Imbalance in development
Some doctors recommend complete bed-rest for the mother coupled with massive intakes of protein as a therapy to try to counteract the syndrome. Research completed shows these nutritional supplements do work. Diet supplementation was associated with lower overall incidence of TTTS (20/52 versus 8/51, P = 0.02) and with lower prevalence of TTTS at delivery (18/52 versus 6/51, P = 0.012) when compared with no supplementation. Nutritional intervention also significantly prolonged the time between the diagnosis of TTTS and delivery (9.4 ± 3.7 weeks versus 4.6 ± 6.5 weeks; P = 0.014). The earlier nutritional regimen was introduced, the lesser chance of detecting TTTS ( P = 0.001). Although not statistically significant, dietary intervention was also associated with lower Quintero stage, fewer invasive treatments, and lower twin birth weight discordance. Diet supplementation appears to counter maternal metabolic abnormalities in monochorionic twin pregnancies and improve perinatal outcomes in TTTS when combined with the standard therapeutic options. Nutritional therapy appears to be most effective in mitigating cases that are caught in Quintero Stage I, little effect has been observed in those that are beyond Stage .
An ultrasound showing the combination of oligohydramnios and polyhydramnios in a monochorionic twin pair indicates the diagnosis of TTTS. True TTTS is diagnosed when ultrasound examination shows that the deepest pocket of amniotic fluid in one twin's sac measures less than 2 centimeters, while the deepest pocket of amniotic fluid measures greater than 8 centimeters in the other twin's sac.
Although TTTS is diagnosed based on the amniotic fluid levels in each sac, the twins may also differ significantly in weight and size. Some of the size differences may be due to the TTTS process. However, much of it is due to the different portion of the placenta devoted to each twin, or unequal placental sharing.
Most monochorionic twins that develop TTTS also have some unequal placental sharing, with a smaller portion of the placenta assigned to the donor twin. Many twins that only have unequal placental sharing, but are not transfusing one another, may be incorrectly diagnosed as having TTTS. Differences may be subtle, but outcomes are dependent on accurate diagnosis, and the treatment and management are different for each condition.
Various treatments for TTTS include:
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.
Adjustement of amniotic fluid
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 divinng 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.
Adjustement of blood supply
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 to 5% of monochorionic twin pregnancies, whereas the post-laser form occurs in 2 to 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 recent 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.
Umbilical cord occlusion
This procedure involves the ligation or otherwise occlusion of the umbilical cord to interrupt the exchange of blood between the fetuses. The procedure is typically offered in cases where one of the fetuses is presumed moribund and endangering the life or health of the other twin through resultant hypotension. 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 fetus(es) with 5% risk of cerebral palsy and a 33–39 weeks of gestation at delivery.