Twin-to-twin transfusion syndrome
Encyclopedia
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 fetus
es share a chorion
and hence a single placenta
. Severe TTTS has a 60–100% mortality rate.
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. Depending on the number, type and direction of the interconnecting blood vessel
s (anastomoses
), blood can be transferred disproportionately from one twin (the "donor") to the other (the "recipient"). The 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
).
In early pregnancy (before 26 weeks), TTTS can cause both fetuses to die, or lead to severe disabilities
. If TTTS develops after 26 weeks, the babies can usually be delivered
alive and have a greater chance of survival without disability.
Other than requiring a monochorionic-diamniotic twin (or higher multiple) pregnancy, the causes of TTTS are not known. It is not known to be hereditary or genetic.
/ high-protein diet is effective.
Research into TTTS is ongoing and best medical practices change quickly with respect to this condition. For the most up-to-date information, consult with a maternal-fetal medicine specialist.
, which involves periodically draining amniotic fluid from around the recipient twin in an effort to reduce the pressure of the amniotic fluid. Because serial amniocentesis increases the risk of premature delivery, it has limited success when performed early in pregnancy, especially before fetal viability. TTTS can also be treated by surgery during pregnancy, using fetoscopy
, pioneered by Kypros Nicolaides
, to find the interconnecting blood vessels, and a laser
beam to coagulate the blood in these vessels, blocking them. This is called fetoscopic laser ablation, and is only performed in a few hospitals worldwide. Outcomes vary widely from case to case, but as of this writing statistics of fetoscopic laser ablation indicate a 90% chance that at least one twin will survive and 70% for both.
Treatments practiced worldwide currently include the following. They can be placed in three different categories: Non-treatment, treatment through adjustment of amniotic fluid, and treatment through adjustment of blood supply:
Non-Treatment
Expectant Management
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.
Treatment through 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% chance 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.
Treatment through adjustment of blood supply
Laser Therapy
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 5% risk of cerebral palsy and average delivery occurring at 33–39 weeks' gestation.
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.
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.
Multiple birth
A multiple birth occurs when more than one fetus is carried to term in a single pregnancy. Different names for multiple births are used, depending on the number of offspring. Common multiples are two and three, known as twins and triplets...
where two or more fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
es share a chorion
Chorion
The chorion is one of the membranes that exist during pregnancy between the developing fetus and mother. It is formed by extraembryonic mesoderm and the two layers of trophoblast and surrounds the embryo and other membranes...
and hence a single placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
. Severe TTTS has a 60–100% mortality rate.
Incidence
TTTS occurs in approximately 5.5–17.5% of all monochorionic pregnancies. Based on 2003 CDC data, the theoretical incidence of TTTS would be 1.38 to 1.86 cases in every 1,000 live births or an estimated near 7,500 cases each year in the United States. One Australian study, however, noted an occurrence of only 1 in 4,170 pregnancies or 1 in 58 twin gestations. This distinction could be party 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.Etiology
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
supplies of monochorionic
Chorion
The chorion is one of the membranes that exist during pregnancy between the developing fetus and mother. It is formed by extraembryonic mesoderm and the two layers of trophoblast and surrounds the embryo and other membranes...
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. Depending on the number, type and direction of the interconnecting blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s (anastomoses
Anastomosis
An anastomosis is the reconnection of two streams that previously branched out, such as blood vessels or leaf veins. The term is used in medicine, biology, mycology and geology....
), blood can be transferred disproportionately from one twin (the "donor") to the other (the "recipient"). The transfusion causes the donor twin to have decreased blood volume, retarding the donor's development and growth, and also decreased urinary
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
output, leading to a lower than normal level of amniotic fluid
Amniotic fluid
Amniotic fluid or liquor amnii is the nourishing and protecting liquid contained by the amniotic sac of a pregnant woman.- Development of amniotic fluid :...
(becoming oligohydramnios
Oligohydramnios
Oligohydramnios is a condition in pregnancy characterized by a deficiency of amniotic fluid. It is the opposite of polyhydramnios.-Diagnosis:Diagnosis is made by ultrasound measurement of the amniotic fluid index...
). 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
Polyhydramnios
Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in 0.2 to 1.6% of pregnancies,,...
).
In early pregnancy (before 26 weeks), TTTS can cause both fetuses to die, or lead to severe disabilities
Disability
A disability may be physical, cognitive, mental, sensory, emotional, developmental or some combination of these.Many people would rather be referred to as a person with a disability instead of handicapped...
. If TTTS develops after 26 weeks, the babies can usually be delivered
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...
alive and have a greater chance of survival without disability.
Other than requiring a monochorionic-diamniotic twin (or higher multiple) pregnancy, the 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 (generally in the form of "protein shakes" such as Boost or Ensure) as a therapy to try to counteract the syndrome. Theories for why this would be effective vary, but some doctors claim to have seen it help. There are, however, no formal clinical trials indicating that the bed restBed rest
Bed rest is a medical treatment involving a period of consistent recumbence in bed. It is used as a treatment for an illness or medical condition, especially when prescribed or chosen rather than resulting from severe prostration or imminent death...
/ high-protein diet is effective.
Research into TTTS is ongoing and best medical practices change quickly with respect to this condition. For the most up-to-date information, consult with a maternal-fetal medicine specialist.
Treatment
There are a number of different therapies used to treat TTTS, with varying rates of success. The oldest, most traditional treatment is through serial amniocentesisAmniocentesis
Amniocentesis is a medical procedure used in prenatal diagnosis of chromosomal abnormalities and fetal infections, in which a small amount of amniotic fluid, which contains fetal tissues, is sampled from the amnion or amniotic sac surrounding a developing fetus, and the fetal DNA is examined for...
, which involves periodically draining amniotic fluid from around the recipient twin in an effort to reduce the pressure of the amniotic fluid. Because serial amniocentesis increases the risk of premature delivery, it has limited success when performed early in pregnancy, especially before fetal viability. TTTS can also be treated by surgery during pregnancy, using fetoscopy
Fetoscopy
Fetoscopy is an endoscopic procedure during pregnancy to allow access to the fetus, the amniotic cavity, the umbilical cord, and the fetal side of the placenta. A small incision is made in the abdomen, and an endoscope is inserted through the abdominal wall and uterus into the amniotic cavity...
, pioneered by Kypros Nicolaides
Kypros Nicolaides
Kypros Nicolaides is an Anglo-Cypriot surgeon, broadcaster and a world expert in ante-natal surgery.Nicolaides was born in 1953 in Paphos, Cyprus...
, to find the interconnecting blood vessels, and a laser
Laser
A laser is a device that emits light through a process of optical amplification based on the stimulated emission of photons. The term "laser" originated as an acronym for Light Amplification by Stimulated Emission of Radiation...
beam to coagulate the blood in these vessels, blocking them. This is called fetoscopic laser ablation, and is only performed in a few hospitals worldwide. Outcomes vary widely from case to case, but as of this writing statistics of fetoscopic laser ablation indicate a 90% chance that at least one twin will survive and 70% for both.
Treatments practiced worldwide currently include the following. They can be placed in three different categories: Non-treatment, treatment through adjustment of amniotic fluid, and treatment through adjustment of blood supply:
Non-Treatment
Expectant Management
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.
Treatment through 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% chance 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.
Treatment through adjustment of blood supply
Laser Therapy
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 5% risk of cerebral palsy and average delivery occurring at 33–39 weeks' gestation.
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.
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.TTTS in art
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
), while the other is red (possibly polycythemic
Polycythemia
Polycythemia is a disease state in which the proportion of blood volume that is occupied by red blood cells increases...
). 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.
External links
- FREE Twin to Twin Transfusion Syndrome Patient Guides from Twins and Multiple Births Association, Tamba. The largest patient support group of its kind in the world
- The Twin to Twin Transfusion Syndrome Foundation
- The 15 Most Important Questions
- 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
- A timelapse movie of a TTTS laser ablation
- 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?
- Fetal Hope Foundation
- Ohio State's Maternal Fetal Medicine