Twin-to-twin transfusion syndrome (TTTS)

Overview

In single pregnancies, one placenta supports a single fetus. While fraternal twins — twins that come from two eggs and two sperm — are always surrounded by their own sacs and have their own individual placentas, 70 percent of identical twins may share a single placenta. These are called monochorionic twins.

Because there is no barrier separating the two fetuses in monochorionic twin pregnancies, there are almost always blood vessel connections in the placenta shared by the two fetuses. In about 10 to 15 percent of monochorionic twins, abnormal or imbalanced blood vessel connections in the shared placenta can cause an imbalance in the circulations of the fetuses. There may be significant transfer of blood from one twin — the so-called "donor twin" — to the other twin, called the "recipient." This results in twin-to-twin transfusion syndrome, or TTTS. TTTS is a serious, progressive disorder.

In TTTS, an artery branches off from the donor twin's umbilical cord, entering the placenta to obtain oxygen and nutrients from the mother's circulation. Unfortunately, the corresponding vein that would normally bring the now nutrient-rich blood back to that same fetus is instead directed toward the other twin via this abnormal arterio-venous connection. If there are no connections flowing in the opposite direction, one twin receives too much blood, and the other too little.

Diagnosis

When a fetus doesn't have enough blood and oxygen, it tries to use what it has most efficiently. Blood is shunted preferentially to the most important organs, the brain and the heart, and away from less vital organs like the kidneys.

This causes the kidneys to partially shut down, and the fetus makes less urine. Because amniotic fluid is mostly comprised of fetal urine, the reduced urine output causes low amniotic fluid levels, called oligohydramnios. As the kidneys make less and less urine and the oligohydramnios worsens, the fetal bladder may empty and will no longer be visible by ultrasound, since it is not being filled with urine.

Meanwhile, the recipient becomes overloaded with fluid as a result of the ongoing blood transfusion from the donor twin, and responds by producing large amounts of urine. This leads to very large amounts of amniotic fluid in the recipient's sac, called polyhydramnios.

An ultrasound showing this 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.

Careful ultrasound is crucial for correctly detecting and diagnosing TTTS. At the UCSF Fetal Treatment Center, ultrasounds are performed by specialists widely renowned for their diagnostic skills and expertise in this field, who have written textbooks and many scientific articles about fetal conditions such as TTTS and unequal placental sharing.

Evaluating the Severity of TTTS

The severity of TTTS is partially based on when the condition becomes evident. The earlier it presents, the more serious the problem. In addition, the degree of fluid imbalance between the twins is important in staging TTTS.

A bladder that remains empty in the donor twin is a concerning sign, indicating a more advanced stage of TTTS. The situation worsens further when, in addition to the abnormal discrepancy in fluid volumes, ultrasound shows abnormal blood flow patterns in the umbilical cord vessels of either one or both of the twins. Finally, evidence of heart failure and tissue swelling, called hydrops, in either twin — usually the recipient — indicates a very serious, advanced stage.

Many patients in whom TTTS is suspected may, on further investigation, be found to have twins with discrepant fluid volumes that do not meet the definition for stage I TTTS. Still, all patients carrying monochorionic twins with significantly unequal amniotic fluid volumes or fetal weights should be evaluated and followed very carefully for changes, as true TTTS can develop and worsen rapidly.

Fetal Echocardiography

To further evaluate the severity of TTTS, UCSF often performs fetal echocardiography. Fetal echocardiograms are specialized ultrasound studies of the fetal heart, performed by pediatric cardiologists with special expertise in this area.

Early signs of heart failure are usually seen first in the recipient twin, as its heart must work hard to pump the extra blood. These exams may reveal increased size of some of the heart chambers, and changes in flow across the heart valves. If the stress and overload on the recipient continues untreated, progressive changes may include decreased function of the heart chambers and possibly narrowing of one of the heart valves, called pulmonary stenosis.

Umbilical Artery Blood Flow

Finally, using information from both the echocardiogram and ultrasound exam, we look for blood flow patterns in the umbilical artery and vein and other major fetal blood vessels.

Blood in the umbilical artery normally flows away from the fetus and toward the placenta to obtain fresh oxygen and nutrients from the mother's circulation. If a placental condition worsens, it becomes harder for the blood to flow toward and within the placenta. With each heartbeat, the fetus pushes blood toward the placenta (the systole phase) through the umbilical artery, and normally, that beat is strong enough for blood to keep flowing forward, toward the placenta, even as the heart re-fills for its next beat (the diastole phase).

In some cases, as TTTS progresses, forward flow in the umbilical artery of the donor may diminish between heartbeats. If the condition worsens, there may be no flow or even reversal of flow direction during the re-filling (diastole phase) of the fetal heart.

All the echocardiogram and ultrasound exam findings are considered in determining the severity of TTTS for each individual pregnancy.

Outcomes

In TTTS, the recipient twin's blood can become thick and difficult to pump around the body. This may lead to heart failure, generalized soft tissue swelling, and in some cases, fetal death. The donor twin is at risk for failure of the kidneys and other organs because of inadequate blood flow.

Because of the blood vessels that connect the circulations of the two fetuses across the shared placenta, if one twin dies, the other twin faces significant risk of death or damage to vital organs. If one twin dies, the surviving twin has up to a 40 percent risk of some form of brain injury. Unfortunately, without treatment, about 70 to 80 percent of twins with TTTS will die. Survivors may have injuries to their brains, hearts or kidneys.

With fetoscopic laser intervention, a treatment performed during pregnancy, the outcome is more hopeful. At UCSF's Fetal Treatment Center — one of the first centers in the world to use fetoscopic laser intervention for TTTS — survival rates for at least one twin are greater than 85 percent, and for both twins are approximately 60 percent.

Maternal Mirror Syndrome

In cases of extreme fetal tissue swelling, called hydrops, the pregnant woman may be at risk for maternal mirror syndrome. In maternal mirror syndrome, the mother's condition mimics that of the sick fetus. The mother may develop symptoms similar to pre-eclampsia, such as vomiting, hypertension, body swelling that's greater than usual, excessive protein in the urine and dangerous build-up of fluid in the lungs, called pulmonary edema.

While this is rare, it is imperative that the pregnant woman be carefully followed. Care for TTTS must include continued, optimal obstetric care for the mother with surveillance for such maternal conditions, in addition to managing the complicated twin pregnancy.

Treatment

Because TTTS is a progressive disorder, early treatment may prevent complications such as preterm labor and premature rupture of membranes due to excessive amniotic fluid. Treatment depends on the severity of the TTTS and the stage of the pregnancy.

Fetoscopic Laser Intervention

All patients with stage II, III or IV TTTS, as well as some patients with stage I TTTS, should learn about and consider fetal intervention. In most cases, the optimal treatment is fetoscopic laser intervention. The UCSF Fetal Treatment Center was one of the first in the world to perform fetoscopic laser intervention to treat TTTS. At UCSF, survival rates for at least one twin are greater than 85 percent, and about 60 percent for both twins with this procedure.

The procedure is performed by inserting a thin, fiber-optic scope through the mother's abdominal wall, through the wall of the uterus and into the amniotic cavity of the recipient twin. By examining the blood vessels on the placental surface directly with the scope, the abnormal vascular connections between the twins can be found and eliminated with a laser beam. Only those vessels that go from one twin to the other are coagulated by the laser beam. The normal blood vessels that help nourish each twin are left intact.

Before the procedure, the team performs a detailed ultrasound examination to search for the sites where the umbilical cords attach to the shared placenta and for abnormal inter-twin connections, making it quicker and easier to identify them with the fetoscope. After the laser procedure is complete, an amnioreduction — removal of extra amniotic fluid — is performed, to decrease the risk of early labor and help make the pregnancy more comfortable.

Amnioreduction Versus Fetoscopic Laser Intervention

Many families ask whether amnioreduction — removal of excess amniotic fluid — is a potential treatment option for TTTS.

Some of our most expert European colleagues attempted to address the question of whether laser intervention or amnioreduction was the best therapy for TTTS. In a randomized prospective trial, they found 76 percent survival of at least one fetus and 36 percent survival of both twins with laser intervention, compared with 51 percent survival of at least one fetus and 26 percent survival of both twins with amnioreduction. For many researchers and experts in this field, this study showed that laser was the preferred therapy for TTTS.

At our center, however, we have found a group of patients with early TTTS that respond well to amnioreduction, a less invasive therapy. In a small percentage of TTTS pregnancies, an artery-to-artery connection between the twins on the surface of the placenta can be found using ultrasound. These twins have been shown to have better outcomes overall — in our experience, more than 80 percent survival rates for both twins — after being treated with amnioreduction. Thus, although laser intervention is the appropriate therapy for the vast majority of patients with TTTS, we occasionally offer amnioreduction to patients with TTTS who meet criteria for this therapy.