Twin-twin transfusion syndrome (TTTS) is a rare disorder that sometimes occurs when women are pregnant with identical (monozygotic) twins. It is a rare disease of the placenta, the organ that joins the mother to her offspring and provides nourishment to the developing fetuses. During the development of identical twins, there are always blood vessels in the fetuses' shared placenta that connect their blood circulations (placental anastomoses). In most cases, the blood flows properly through these vessels. However, in twin-twin transfusion syndrome, the blood begins to flow unevenly, with one fetal twin receiving too much blood (recipient) and one receiving too little (donor). The recipient twin may experience heart failure due to continual strain on its heart and blood vessels (cardiovascular system). The donor twin, on the other hand, may experience life-threatening anemia, insufficient nutrition and oxygen due to its inadequate supply of blood. Such an imbalance in blood flow (i.e., twin-twin transfusion) can occur at any time during the pregnancy, including during delivery.

The effects of twin-twin transfusion syndrome can vary in severity from case to case, depending upon when during pregnancy the syndrome occurs, when it is diagnosed, and any treatment that may be given. The cause of this syndrome is not fully understood, although it is known that placental characteristics play an important role.

The twin-twin transfusion may occur at any time during pregnancy. If the imbalance in blood flow occurs early in the pregnancy (first trimester), one of the fetal twins may simply cease developing; as a result, only one fetus will be detected for the remainder of the pregnancy. If the transfusion occurs shortly before or during delivery, the twins may exhibit symptoms related to a sudden lack or excess of blood supply. However, should twin- twin transfusion syndrome occur during mid-pregnancy (second trimester), a variety of symptoms may occur.

For example, the twin that receives extra blood (recipient) begins to produce more urine than normal (polyuria), resulting in excessive amniotic fluid surrounding the fetus within its amniotic sac (hydramnios). Such an excess of amniotic fluid can develop quickly, often over two to three weeks As a result, the mother’s abdomen grows larger than normal for her stage of pregnancy. In most cases, this is the first symptom of twin-twin transfusion syndrome. Left untreated, the excess amniotic fluid can cause preterm labor or rupture the amniotic sac, resulting in potentially very early delivery.

On the other hand, because the other fetal twin (donor) receives too little blood and has abnormally low levels of circulating fluid in its body (hypovolemia), its kidneys may stop producing urine (renal shutdown); there may therefore be very little fluid in the donor twin’s amniotic sac (oligohydramnios). As a result, the sac’s membranes (amnion) may collapse around the fetus. Because this fetal twin may appear stuck or “cocooned” within the collapsed membranes, it is sometimes called the “stuck twin”.

During normal fetal development, most identical (monozygotic) twins grow at approximately the same rate and have similar weights when they are born. However, if fetal twins are affected by twin-twin transfusion syndrome by mid-pregnancy (second trimester), they may begin to vary greatly in development rate and size. While the recipient twin may become larger in size than normal, the donor twin may suffer from severe growth retardation.

Some researchers believe that uneven sharing of portions of the common, shared placenta may also contribute to different rates of growth. The difference in sizes of the twins may persist even after birth through infancy.

Both recipient and donor fetal twins may exhibit other symptoms as well. The extra blood supply to the recipient twin may cause heart failure resulting in fluid to accumulating in some of its body cavities (hydrops), such as in the abdominal cavity (ascites), around the lungs (pleural effusion), and/or around the heart (pericardial effusion). Receiving excess blood places continual strain on the fetus’s heart and blood vessels (cardiovascular system), which may eventually cause congestive heart failure. On the other hand, the donor twin has an inadequate supply of blood, possibly causing a potentially life- threatening anemia and growth restriction. If the recipient twin develops hydrops or the donor twin develops severe growth restriction, inadequate supply of oxygen (hypoxia) to the developing brain may occur during pregnancy or from respiratory distress syndrome (RDS) associated with early (preterm) delivery. As a result, brain damage may occur, potentially causing Cerebral Palsy. (For more information on this disorder, use “Cerebral Palsy” as your search term in the Rare Disease Database.)

When twin-twin transfusion syndrome occurs in mid-pregnancy, one of the fetal twins may die due to the effects of receiving too little blood, receiving too much blood, or having too small a share of the common placenta (severe placenta insufficiency). Blood may then pass from the live twin to the deceased twin, and the live twin may experience low blood pressure (hypotension) and/or inadequate blood flow to its tissues (severe hypoxia). Such decreased blood flow to certain areas of this fetal twin could be life-threatening or could result in a variety of developmental abnormalities, which might include malformations of the hands, arms, feet, and/or legs (terminal limb defects); underdevelopment of one side of the face (hemifacial microsomia); obstruction of the intestine (intestinal atresia); tissue damage and loss in the outer layer of the kidney (renal cortical necrosis); and/or a clot blocking an artery in the heart (coronary thrombosis). In some cases, severe injuries to the brain may occur, resulting in cysts or cavities in the brain’s outer layer (porencephaly) and/or absence of the brain’s cerebral hemispheres (hydranencephaly). (For more information on this disorder, choose “Hydranencephaly” as your search term in the Rare Disease Database.)

The exact cause of TTTS is not fully understood. However, it is known that abnormalities during division of the mother’s egg after it has been fertilized lead to the placental abnormalities that can ultimately result in twin-twin transfusion syndrome.

The normal development of identical (monozygotic) twins begins with the fertilization of the mother’s egg (ovum) by the father’s sperm. Within the first three days after fertilization, the fertilized egg (zygote) divides into two complete, identical embryos. These two embryos, which are nourished by separate placentas (dichorionic) during the pregnancy, ultimately develop into two individuals (monozygotic twins) who have almost identical genetic make-ups.

In some cases of monozygotic twin development, however, a zygote takes longer than three days to divide into two complete embryos. Scientists have observed that the longer it takes the zygote to divide, the more problems are likely to occur in identical twin pregnancies. If the zygote takes from four to eight days to divide, the twins share a common placenta (monochorionic) and the membrane that separates the fetal twins’ two amniotic sacs is thin (diamnionic). If the fertilized egg divides in eight to twelve days, the twins share a common placenta (monochorionic) and no dividing membrane is present; therefore, the two fetuses essentially share one amniotic sac (monoamnionic). Twin-twin transfusion syndrome has been reported to occur in both of these types of pregnancies (monochorionic-diamnionic and monochorionic- monoamnionic); however, the vast majority of cases of TTTS occur in monochorionic-diamnionic pregnancies. It is not understood why a zygote divides into twins nor why it takes longer than normal to divide in some cases.

In all monochorionic twin pregnancies, there are blood vessels in the shared placenta that connect the fetuses’ umbilical cords and blood circulations together (anastomoses). The placenta, which is connected to the fetuses by their umbilical cords, links the mother’s blood supply to her offspring’s. This enables the exchange of waste products from the fetuses to the mother for excretion and enables the transfer of oxygen and nutrients from the mother’s blood to the fetuses’. In most cases, the blood flow is relatively balanced through these connecting blood vessels. However, in twin-twin transfusion syndrome, the blood begins to flow unevenly through the anastomoses. Scientists do not understood what causes such an imbalance in blood flow to take place. However, it is believed that several different factors may play a role, including the degree to which the placenta may be unevenly shared by the twin fetuses, the type and number of connecting blood vessels (anastomoses) in the shared placenta, and changes in pressure within the mother’s uterus (such as occurs with polyhydramnios or with uterine contractions during delivery).

The U.S. Food and Drug Administration in 2006 approved a device known as the Karl Storz Rigid TTTS Fetoscopy Instrument Set under its Humanitarian Device Exemption (HDE) program for the treatment of twin-twin transfusion syndrome. These are surgical tools that include a telescopic camera used to view a fetus (fetoscope) or placenta. These tools are used to identify and obstruct (photocoagulate) the connecting blood vessels (anastamoses) on the placenta using a laser thereby separating the flow of blood within the placenta for each of the twins. The instrument set is manufactured by a company headquartered in Germany, Karl Storz Endoscopy, Inc.

TTTS is a rare disorder that sometimes occurs when a mother is pregnant with identical (monozygotic) twins. There have been a few reported cases in which TTTS also affected identical triplets. Twin-twin transfusion syndrome affects approximately 5 to 15 percent of identical twin pregnancies, meaning that approximately 6,000 babies may be affected each year. However, it is difficult to determine the true frequency of TTTS in the general population since many cases are never diagnosed and many go unrecorded.