Feto-fetal transfusion syndrome: what is it, causes, symptoms, treatment, prognosis

What is Feto-Fetal Transfusion Syndrome?

Feto-fetal transfusion syndrome (FFTS), also known as fetal-fetal transfusion syndrome (SFT) is a rare condition that sometimes occurs when women are pregnant with identical (monozygotic) twins. It is a rare disease of the placenta, the organ that connects the mother to her offspring and provides nutrition to the developing fetus. During the development of identical twins, there are always blood vessels in the common placenta of the fetus that connect their circulation (placental anastomoses). In most cases, blood flows correctly through these vessels. However, with fetal transfusion syndrome between twins, blood flows unevenly: one fetal twin receives too much blood (recipient) and the other too little (donor). The recipient twin may experience heart failure due to the constant stress on the heart and blood vessels (cardiovascular system). On the other hand, the donor twin may be experiencing life-threatening 

anemia, malnutrition and oxygen starvation due to insufficient blood supply. This imbalance in blood flow (such as FFTS) can occur at any time during pregnancy, including during childbirth.

The consequences of FFTS can vary in severity from case to case, depending on when the during pregnancy the syndrome occurs when it is diagnosed and from any treatment that may be assigned. The cause of this syndrome is not fully understood, although the characteristics of the placenta are known to play an important role.

Signs and symptoms

Feto-fetal transfusion syndrome (FFTS) is a rare condition that sometimes occurs when women are pregnant with identical (monozygous) twins. FFTS is a disease of the placenta, an organ that develops in the uterus during pregnancy, connects the mother's blood supply to the fetus and provides nutrition for her offspring. Developing fetal twins usually remain normal until blood flow disturbances in the placenta cause disease to develop.

Most identical twins share a common placenta, in which blood vessels connect the umbilical cord and the fetal circulation (placental anastomoses). The umbilical cord connects the twin fetuses to the placenta. In most cases, blood flow between twins is balanced through these connecting blood vessels. However, when PFTS occurs, blood begins to flow unevenly through the connective blood vessels. As a result, one fetal twin receives too much blood (recipient) and the other too little (donor). Fetal twins, although they have developed normally up to this point, can now begin to show different symptoms depending on when the blood flow imbalance occurred during pregnancy.

Feto-fetal transfusion syndrome can occur at any stage of pregnancy. If an imbalance in blood flow occurs early in pregnancy (first trimester), one of the fetal twins may simply stop developing; as a result, only one fetus will be found for the remainder of the pregnancy. If a blood transfusion occurs shortly before or during childbirth, twins may develop symptoms related to a sudden lack or excess of blood supply. However, if FFTS occurs in the middle of pregnancy (second trimester), various symptoms may occur.

For example, a twin receiving extra blood (recipient) begins to produce more urine than usual (polyuria), as a result of which the fetus in the amniotic fluid is surrounded by an excessive amount of amniotic fluid (hydramnios). This excess of amniotic fluid can develop rapidly, often within two to three weeks. As a result, the mother's belly becomes larger than normal for her gestational age. In most cases, this is the first symptom of fetal transfusion syndrome. If left untreated, excess amniotic fluid can cause premature labor or rupture of the amniotic sac, potentially leading to very early labor.

On the other hand, because the other fetal twin (donor) receives too little blood and has abnormally low level of circulating fluid in his body (hypovolemia), his kidneys may stop producing urine (renal failure); therefore, there may be very little fluid in the amniotic sac of the donor twin (oligohydramnios). As a result, the sac membranes (amnion) can break down around the fetus. Because this embryonic twin may appear to be stuck or "cocooned" within ruptured membranes, it is sometimes referred to as a "stuck twin."

During normal fetal development, most identical (monozygotic) twins grow at about the same rate and have the same birth weight. However, if fetal twins suffer from fetal transfusion syndrome by mid-pregnancy (second trimester), they can vary greatly in developmental speed and size. Although the recipient twin may grow larger than usual, the donor twin may suffer from severe growth retardation.

Some researchers believe that uneven distribution of a portion of a single, common placenta may also contribute to different growth rates. The difference in size between twins can persist even after birth in infancy.

Fetal twin recipients and donors may show other symptoms as well. Additionally, the FFTS may call heart failure, as a result of which fluid will accumulate in some body cavities (dropsy), for example, in the peritoneum (abdominal ascites), around the lungs (pleural effusion) and / or around the heart (pericardial effusion). Excess blood puts a constant strain on the fetus's heart and blood vessels (cardiovascular system), which can ultimately cause congestive heart failure. On the other hand, the donor twin has insufficient blood supply, which can cause potentially life-threatening anemia and limiting growth. If the recipient twin develops dropsy or the donor twin has severe growth restriction, an inadequate supply may occur. oxygen (hypoxia) of the developing brain during pregnancy or as a result of respiratory distress syndrome (RDS) associated with early (premature) delivery. As a result, brain damage can occur, which can cause cerebral palsy.

When FFTS occurs in mid-pregnancy, one of the fetal twins may die due to the consequences of getting too little amount of blood, too much blood being drawn, or too little of the total placenta (severe placenta). The blood can then pass from the living twin to the deceased twin, and the living twin can have low blood pressure (hypotension) and / or insufficient blood flow to tissues (severe hypoxia). This decrease in blood flow to certain areas of this fetal twin can be life-threatening or lead to various developmental abnormalities, which may include:

• malformations of the hands, arms, feet and / or legs (limb malformations);
• underdevelopment of one side of the face (hemifacial microsomia);
• intestinal obstruction (intestinal atresia);
• damage and loss of tissue in the outer layer of the kidney (renal cortical necrosis);
• a blood clot (blood clot) that blocks an artery in the heart (coronary thrombosis).

In some cases, severe brain injuries can occur, resulting in cysts. or cavities in the outer layer of the brain (porencephaly) and / or the absence of cerebral hemispheres (hydranencephaly).

Causes and risk factors

The exact cause of fetal transfusion syndrome is not fully understood. However, it is known that abnormalities during the division of the mother's egg after it has been fertilized lead to abnormalities in the placenta, which can ultimately lead to PFTS.

The normal development of identical (monozygous) twins begins with the fertilization of the mother's egg with the father's sperm. During the first three days after fertilization, the fertilized egg (zygote) divides into two full identical embryos. These two embryos, which feed on a separate (dichorionic) placenta during pregnancy, end up eventually develop into two individuals (monozygous twins), which have an almost identical genetic composition.

However, in some cases of development of monozygotic twins, the zygote takes more than three days to divide into two full embryos. Scientists have noticed that the longer the zygote divides, the more problems can arise during pregnancy with identical twins. If it takes 4 to 8 days to divide the zygote, the twins have a common placenta (monochorionic), and the membrane separating the two amniotic sacs in twin fetuses is thin (diamnion). If a fertilized egg divides in 8-12 days, the twins have a common placenta (monochorionic) and there is no dividing membrane; therefore, the two fetuses essentially share one amniotic sac (monoamniotic sac). It has been reported that fetal transfusion syndrome occurs in both types of pregnancies (monochorionic-diamnion and monochorionic-monoamnion); However, the vast majority of FFTS cases occur during monochorionic diamnion pregnancies. It is unclear why the zygote divides into twins and why in some cases it takes longer than usual to divide.

In all monochorionic twin pregnancies, there are blood vessels in the common placenta that connect the fetal umbilical cord and circulation together (anastomoses). The placenta, which is connected to the fetus by their umbilical cord, connects the mother's blood supply to the blood of her offspring. This makes possible the exchange of waste products of the fetus with the mother for excretion from the body, as well as the transfer of oxygen and nutrients from the mother's blood to the fetus. In most cases, blood flow through these connective blood vessels is relatively balanced. However, with fetal transfusion syndrome, blood begins to flow unevenly through the anastomoses. Scientists do not understand what causes this imbalance in blood flow. However, several different factors are thought to play a role, including the extent to which the placenta may be unevenly distributed by twin fetuses, the type and the number of connecting blood vessels (anastomoses) in the common placenta, as well as changes in pressure in the mother's uterus (for example, with polyhydramnia or with uterine contractions during childbirth).

Affected populations

FFTS is a rare condition that sometimes occurs when a mother is pregnant with identical (monozygotic) twins. There have been several reported cases in which the FFTS also affected identical triplets. Feto-fetal transfusion syndrome affects about 5-15 percent of identical twin pregnancies, which means that about 6,000 babies can be affected each year. However, it is difficult to determine the true incidence of FFTS in the general population, as many cases are never diagnosed and many are not reported.

Disorders closely related to symptoms

Symptoms of the following conditions may be similar to those of fetal transfusion syndrome. Comparisons can be useful for differential diagnosis:

• Twin parasite (acardial twin) is a rare condition that sometimes occurs when women are pregnant with identical (monozygotic) twins. Several cases have also been reported in triplets. In a parasitic twin, there is a direct connection of one of the two umbilical arteries of one twin to the artery of the other twin, which has only one umbilical artery and a vein. Some researchers believe that fetal twins may have normal very early embryonic development. However, very early in pregnancy, blood begins to flow improperly through the umbilical artery. the fetus with an artery junction, and one of the twins ("twin-pump") begins to provide blood circulation for both fruits. Depending on when this blood flow imbalance occurs during pregnancy, the developing heart of the other twin may do not develop normally, resulting in a lack of recognizable cardiac structure or the presence of very primitive cardiac structures. In all cases, this twin (acardial twin) will also exhibit other serious abnormalities, such as the absence of head or brain structures (anencephaly). In most cases, the pump twin has no malformations; however, the constant stress on his heart, associated with the need to supply blood to the other twin, can lead to heart failure. With an acardiac twin, excess amniotic fluid (hydramnios) can occur, causing the mother's uterus to grow faster than normal for her stage of pregnancy. Early (preterm) labor is common. Some researchers believe that acardial twin masses are actually an extreme form of fetal transfusion syndrome. The cause of acardial twin is unknown.

Diagnostics

Feto-fetal transfusion syndrome can be detected in mid-pregnancy (second trimester) with ultrasound - a method that creates an image of the fetus by measuring the reflection of sound waves. Ultrasound findings that may indicate FFTS include twins of the same sex; a single common placenta (monochorionic) - a thin membrane that separates the amniotic sacs of the fetus; differences in the amount of amniotic fluid with polyhydramnios (defined as the largest vertical pocket of fluid more than 8 cm in a larger twin) and oligohydramnios (defined as the largest vertical pocket less than 2 cm in the smaller twin), as well as a difference in size of more than 20%.

The current stage or classification of the severity of the disease is currently consistent with that proposed by Quintero in 1999. This staging system has been a useful tool to enable clinicians to compare treatment outcomes and choose between different treatment strategies, since it takes into account the aggravation of the severity of the disease process at each of the increasing stages. However, this gives the impression that the natural history of the FFTS follows an orderly development over time. Unfortunately, clinical experience has shown that this is not the case, and the progression of disease processes is very variable and somewhat unpredictable. This staging system also does not include elements describing fundamental cardiovascular changes that are key to understanding the disease and are present in subtle forms even in the earliest stages of the disease.

Examination of the placenta by doctors after childbirth can confirm the monochorionic status of twins, the presence connecting blood vessels (placental anastomoses), as well as the diagnosis of fetal-fetal syndrome transfusion.

Standard treatments

Treatment of fetal transfusion syndrome depends on the severity of the disease and the gestational age of the fetus and includes:

• Close monitoring with regular ultrasound in less severe cases;
• Laser coagulation of placental anastomoses (LCPA) in severe FFTS.

- Laser coagulation of placental anastomoses (LCPA).

Laser coagulation of placental anastomoses is the standard of care for severe PFTS. This is a minimally invasive surgical procedure that uses a small camera (fetoscope) to detecting abnormal connections of blood vessels in the placenta and their detachment (cauterization) using laser.

LCPA is the preferred treatment for severe cases of fetal transfusion syndrome. The procedure prevents the exchange of blood between fetuses, often stopping the progression of the condition and normalizing blood flow. A thorough examination will be done before deciding whether laser coagulation of placental anastomoses is an appropriate treatment option. Generally, pregnancy should be between 16 and 26 weeks without any other significant abnormalities, and the patient should be healthy.

LKPA is a stationary procedure. Mothers are given intravenous sedation, local anesthesia, and in some cases general anesthesia may be required depending on the location of the placenta. A medicine is given to prevent labor. The fetal surgeon will then make a small incision in the mother's abdomen and insert a small instrument into the uterus. The fetoscope is then passed through an instrument to examine and map the blood vessel connections on the surface of the placenta being shared by the twins. This image is displayed on a large screen and ultrasound is used to continuously monitor the fetal heart rate.

The laser is used to seal the connections between blood vessels and separate them permanently. After sealing the blood vessels between the twins, the surgeon draws a laser line between the joints to coagulate even smaller vessels from one side to the other. The surgeon then drains excess amniotic fluid (amnioreduction) before completing the procedure.

After the procedure, the patient is given medicine for uterine contractions. Although each case is different, most patients stay in the hospital for two to three days. Ultrasound and, in some cases, fetal echocardiography are done 48 to 72 hours after surgery to assess the condition of the fetus.

Although each procedure carries a risk, the likelihood of serious complications from the mother is very rare. Potential complications include premature birth, premature rupture of membranes, infection, and fetal injury.

Forecast

Feto-fetal transfusion syndrome often causes preterm labor, even with successful treatment. In this case, babies need care in the neonatal intensive care unit.

Most babies who are successfully treated for the syndrome live normal and healthy lives. However, some have mild symptoms, such as anemia, that are easily treatable. Other, more serious problems include brain damage, neurological deficits, and heart failure.