Fetal-fetal transfusion syndrome: causes, signs, treatment

Feto-fetal syndrome is a fairly common phenomenon, although not everyone has heard of it. First of all, this symptom concerns pregnancy, in which the mother is expecting twins. To know the main risk factors for this pathology, you need to understand how it occurs and how it manifests itself.

Epidemiology

Statistics show that this syndrome is quite common. Monozygotic twins occur in 3-5 out of 1000 pregnancies. Approximately 75% of monozygotic twins are monochorionic. And the development of twin-to-twin syndrome occurs in 5-38% of monochorionic twins. Severe twin-to-twin transfusion syndrome accounts for 60-100% of fetal or neonatal mortality. The fatal death of one twin is associated with neurological consequences in 25% of surviving twins.

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Causes fetal-fetal syndrome

Many have heard of such a concept as twin-to-twin transfusion syndrome or twin-to-twin transfusion syndrome. What is it?

Twin-to-twin syndrome is a disorder of the placenta, the organ that develops in the uterus during pregnancy, connecting the mother's blood supply to the fetuses and providing nutrition to her offspring. Developing twins are usually normal until abnormalities in the blood flow within the placenta cause a disease process.

The syndrome results from intrauterine blood transfusion from one twin (donor) to the other twin (recipient). Blood transfusion from the donor twin to the recipient twin occurs through placental vascular anastomoses. The most common vascular anastomosis is a deep anastomosis of an artery and vein through a common placental lobe. This syndrome occurs only in monozygotic (identical) twins with a monochorionic placenta. The donor twin is often smaller and has a birth weight 20% less than the recipient twin.

The pathology is a specific complication of monozygotic twins with monochorionic placenta. Monozygotic twins who have dichorionic placentation are not at risk.

The causes of twin-twin syndrome are not completely clear. However, it is known that abnormalities during division of the mother's egg after fertilization lead to abnormalities of the placenta, which can eventually lead to 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. During 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 pregnancy, eventually develop into two individuals (monozygotic twins) who have nearly identical genetic makeup.

However, in some cases of monozygotic twins, the zygote takes more than three days to divide into two complete embryos. Scientists have noticed that the longer it takes for the zygote to divide, the more problems may arise in twin pregnancies. If the zygote takes four to eight days to divide, the twins share a placenta (monochorionic), and the membrane that separates the two fetal amniotic sacs is thin (diamniotic). If the fertilized egg divides over eight to 12 days, the twins share a placenta (monochorionic), and there is no separating membrane; therefore, the two fetuses essentially share one amniotic sac (monoamniotic). Twin-to-twin transfusion syndrome has been reported to occur in both of these types of pregnancies (monochorionic-diamnionic and monochorionic-monoamniotic). It is not clear why the zygote divides into twins and why in some cases it takes longer than usual. Twin feto-fetal syndrome is more common in monochorionic diamniotic pregnancies. Therefore, risk factors are precisely this type of pregnancy, especially if there are similar cases in the family.

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Pathogenesis

The pathogenesis of the syndrome lies in the peculiarities of the blood supply to the babies in utero. Most identical twins share a common placenta, in which blood vessels connect the umbilical cords and the fetal circulation (placental anastomoses). The umbilical cords connect the fetal twins to the placenta. In most cases, the blood flow is balanced between the twins through these connecting blood vessels. However, when double transfusion syndrome occurs, the blood begins to flow unevenly through the connecting blood vessels. As a result, one fetal twin receives too much blood (the recipient), while the other receives too little (the donor). The twins, even if they have been developing normally up to this point, may now begin to show different symptoms, depending on when during the pregnancy the imbalance in blood flow occurred (twin transplant). Twin transplants can occur at any time during pregnancy. If the imbalance in blood flow occurs early in pregnancy (first trimester), one of the twin fetuses may simply stop developing; as a result, only one fetus will be found for the remainder of the pregnancy. If the transfusion occurs shortly before or during labor, the twins may exhibit symptoms related to the sudden lack or excess of blood supply. However, if twin transfusion syndrome occurs during pregnancy (second trimester), a variety of symptoms may occur.

It is not entirely clear why this imbalance occurs. However, it is thought that several different factors may play a role, including the extent to which the placenta may be unevenly shared between the two fetuses, the type and number of connecting blood vessels (anastomoses) in the shared placenta, and changes in pressure in the mother's uterus (such as occurs with polyhydramnios or with uterine contractions during labour).

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Symptoms fetal-fetal syndrome

The symptoms of twin-to-twin syndrome develop when there is already a large blood shunt that causes problems. During normal fetal development, most identical (monozygotic) twins grow at about the same rate and are of similar weight when they are born. However, if twins develop twin-to-twin syndrome by mid-pregnancy (second trimester), they can vary greatly in the rate and size of their growth. While the recipient twin may grow larger than normal, the donor twin may suffer from severe growth retardation.

The extra blood supply to the recipient twin can cause heart failure, resulting in fluid accumulation in certain cavities, such as the abdomen (ascites), around the lungs (pleural effusion), or around the heart (pericardial effusion). Taking in excess blood puts constant stress on the fetal heart and blood vessels, which can eventually cause congestive heart failure. When a fetus is anemic or deprived of enough blood and oxygen, it tries to use what it can most efficiently. This is accomplished by focusing blood flow to the most important organs (the brain and heart) and shutting down less important organs, such as the kidneys. Thus, the “donor” twin will make much less – or sometimes no – urine. Meanwhile, the recipient twin is overloaded with blood and volume, and as a result, has excessive urination. The donor twin is at risk of developing kidney and other organ failure due to insufficient blood flow. Because of the blood vessels that connect the circulation of the two fetuses through a shared placenta, if one twin dies, the other twin faces a serious risk of death or damage to vital organs.

On the other hand, the donor twin has an inadequate blood supply, which can lead to potentially life-threatening anemia and growth restrictions. If the donor twin develops severe growth restriction, inadequate oxygen supply (hypoxia) to the developing brain may occur during pregnancy or from respiratory distress syndrome. This can result in brain damage, which can cause cerebral palsy. Therefore, symptoms may only appear on ultrasound, primarily a large difference in fetal weight.

When monochorionic twins with twin-to-twin transfusion syndrome occur midway through pregnancy, one of the twins may die from receiving too little blood, receiving too much blood, or sharing too little of the placenta (severe placental insufficiency). Blood may then pass from the living twin to the deceased twin. This reduced blood flow to certain areas of that fetus may be life-threatening or may lead to various developmental abnormalities. In some cases, severe brain injury may occur, resulting in cysts or cavities in the outer layer of the brain or absence of the cerebral hemispheres.

But it is important to diagnose the syndrome when the child has not yet died. Therefore, the first signs of the syndrome may be accompanied by such clinical manifestations as a sudden increase in abdominal girth, shortness of breath, abdominal tension, compression and even premature rupture of the placenta.

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Stages

The stages of the syndrome correspond to the degree of severity. They are distinguished based on ultrasound data.

• Stage I: Visible bladder in donor twin with normal Doppler findings. Uneven amniotic fluid volume.
• Stage II: The bladder in the donor twin is empty and cannot be detected by ultrasound.
• Stage III: empty bladder in the donor twin, abnormal blood flow through the umbilical cord and placenta; this is identified by Doppler ultrasound.
• Stage IV: One or both fetuses retain fluid, causing swelling.
• Stage V: Death of one of the fruits.

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Forms

The types of fetal transfusion syndrome depend on when these changes occur, and the later the gestation period, the greater the chance of carrying healthy babies to term. Therefore, a distinction is made between early feto-fetal syndrome and late fetal syndrome.

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Complications and consequences

The consequences of the syndrome are more severe if it develops early in pregnancy. Instability of fetal blood pressure can lead to cerebral ischemia in both donors or recipient twins. Fetal cerebral ischemia can lead to periventricular leukomalacia, microcephaly, and cerebral palsy. The earlier the twins are born, the higher the incidence of postnatal morbidity and mortality.

Neurological complications may also develop in the setting of the syndrome. Intrauterine death of one twin may result in neurological sequelae in the surviving twin. Acute involvement of the surviving twin in the relaxed circulation of the deceased twin may result in intrauterine CNS ischemia.

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Diagnostics fetal-fetal syndrome

Diagnosis of twin-twin syndrome is based on instrumental methods. Twin-twin syndrome can be detected during pregnancy (second trimester) using ultrasonography, a method that creates an image of the fetus by measuring the reflection of sound waves. In ultrasound examination, the syndrome can be suspected when one twin has oligohydramnios and the other has hydramnios.

General signs of the syndrome can be diagnosed based on some data.

1. Same-sex twins sharing a placenta.
2. Thin (two-layer) dividing membrane between the amniotic sacs. No double peak sign.
3. Combined polyhydramnios and oligohydramnios. The maximum vertical pocket (MVP) is greater than 8 cm around the recipient twin and less than 2 cm around the donor twin. The donor twin may become “stuck” due to oligohydramnios.
4. Signs of overhydration or heart failure in both fetuses. This is most common in the larger recipient.
5. A significant size discrepancy between twins is not always present. When a discrepancy occurs, the donor is the smaller twin and the recipient is the larger twin.

Early signs of twin-twin syndrome, before a twin actually becomes "stuck," include a fetus with a persistently distended bladder compared to the other twin.

To further evaluate the severity of twin-twin syndrome, fetal echocardiography is often performed. Fetal echocardiograms are specialized, targeted ultrasound examinations of the heart performed by pediatric cardiologists. Early changes in heart failure are usually seen first in the recipient, as their heart has difficulty pumping the extra blood. These imaging studies may reveal an increase in the size of some heart chambers and changes in flow through the heart valves (eg, tricuspid regurgitation). If the stress and strain in the recipient remain untreated, progressive changes may include decreased function of the heart chambers and possible narrowing of one of the heart valves (pulmonic stenosis).

The instrumental diagnostics are not limited to these methods. Finally, using information from both the echocardiogram and the obstetric ultrasound, we look for blood flow patterns in the umbilical artery and vein and other large fetal blood vessels. Blood in the umbilical artery normally flows away from the fetus and toward the placenta, attempting to obtain fresh oxygen and nutrients from the mother’s circulation. If the condition of the placenta deteriorates, it becomes increasingly difficult for blood to flow into and within the placenta. With each heartbeat, the fetus pushes blood toward the placenta (in the systolic phase) through the umbilical artery, and usually this rhythm is strong enough to keep the blood flowing forward toward the placenta even as the heart fills again for the next. In some cases, as twin-twin syndrome progresses, forward flow in the donor umbilical artery may decrease between heartbeats. If the condition worsens, there may be no flow during refilling of the fetal heart.

All echocardiogram and ultrasound examination results are taken into account when determining the severity of feto-fetal pregnancy for each individual pregnancy.

The tests are not specific for this syndrome, so a woman should take all scheduled tests according to the schedule.

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Differential diagnosis

The differential diagnosis of twin-to-twin syndrome includes syndromes that may have symptoms similar to twin transfusion syndrome. Acardiac twinning is a rare disorder that sometimes occurs when women are pregnant with identical (monozygotic) twins. A few cases have also been reported in identical triplets. In acardiac twinning, there is a direct connection from one of the two umbilical arteries of one twin to the other twins, who share only one umbilical artery and vein. Some researchers believe that the twins may initially experience normal early embryonic development. However, very early in pregnancy, blood begins to flow abnormally through the connecting umbilical artery of the fetus to the connecting artery, and one twin begins to provide circulation to both fetuses.

Depending on when during pregnancy this imbalance in blood flow occurs, the developing heart of the other twin may not develop normally, resulting in no cardiac structure or very primitive cardiac structures. In all cases, this twin (the acardiac twin) also exhibits other major abnormalities, such as no head structures or brain. In most cases, the twin does not exhibit any developmental abnormalities; however, the permanent strain on the heart from having to supply blood to the other twin may cause heart failure in the twin. In acardiac twinning, there may be excess amniotic fluid (hydramnios), causing the mother's uterus to grow faster than normal for her stage of pregnancy. The cause of acardiac twinning is unknown.

Treatment fetal-fetal syndrome

There are currently six therapeutic options for treating twin-twin syndrome:

1. conservative management without intervention;
2. termination of pregnancy;
3. selective feticide;
4. therapeutic amnioreduction;
5. amniotic septostomy;
6. endoscopic ablation of communicating vessels.

Of these methods, therapeutic amnioreduction is probably the most widely used and accepted treatment, although endoscopic laser ablation is gaining popularity.

Surgical treatment is advantageous because the speed of the outcome can save the lives of babies. Because transfusion syndrome is a progressive disorder, early treatment can prevent complications, including preterm labor and premature rupture of membranes due to excess fluid (polyhydramnios). The choice of treatment for the syndrome depends on the severity of the condition and the current stage of your pregnancy. All patients with stage II, III, or IV, and some patients with stage I, should be evaluated and considered for fetal intervention. In most cases, fetoscopic laser intervention will be the appropriate and optimal therapy.

Amnioreduction or amniocentesis is a procedure that involves draining excess amniotic fluid. Using ultrasound guidance, a needle is inserted into the recipient sac and 2-3 liters of fluid are gently removed. This therapy aims to prevent the risk of preterm labor from excessive uterine distension. In addition, by reducing the volume of fluid, a decrease in the pressure of the intra-amniotic and placental vasculature is obtained, which improves placental blood flow. As the underlying cause of the syndrome continues, the fluid in the sac re-accumulates. Therefore, amnioreduction may need to be repeated several times during pregnancy.

Amniocentesis can be combined with a “septostomy.” In this procedure, fluid is first drained from the amniotic sac and then a needle is used to create a small hole in the membrane between the twins’ amniotic sacs. This allows amniotic fluid to pass into the donor twin’s sac. A septostomy allows the amniotic fluid volumes to be equalized between the twins. Amniotic fluid surgery, such as amnio drainage or septostomy, can relieve symptoms and may alleviate problems in some patients. However, because the anastomoses remain open, the risks of unbalanced volume exchange also remain – the underlying problem is not addressed.

Laser coagulation of placental anastomoses is performed by inserting a thin fiber-optic tube through the mother's abdominal wall and through the uterine wall into the amniotic cavity of the recipient twin. By examining the blood vessels on the surface of the placenta directly, abnormal vascular connections between twins can be found and eliminated by directing a laser beam at them. Only those vessels that go from one twin to the other are coagulated by the laser beam. Normal blood vessels that help feed each twin are left intact.

A detailed ultrasound before the procedure shows where the umbilical cords attach to the common placenta and can help detect abnormal inter-cordial connections, allowing for quicker and easier identification of the process with a fetoscope. After the laser procedure is completed, amniocentesis (removal of excess amniotic fluid) is performed to reduce the chance of early labor and help make the pregnancy more comfortable.

Childbirth after twin-twin syndrome is usually planned by cesarean section.

Selective feticide involves interrupting the blood transfusion by deliberately killing one twin. It is recommended for use in the early stages when other methods are ineffective and one baby could cause the death of the other, and then both could be lost. This process requires that all vascular connections be occluded simultaneously, which is done by umbilical cord occlusion.

Cord occlusion is a procedure that is performed inside the womb through a membrane placed by an ultrasound guide in the sac of one twin, usually the donor (smaller). Special tweezers grasp the cord and an electric current passes between the tweezers, coagulating the blood vessels of that fetus's umbilical cord. This stops the blood flow and that baby dies.

The surviving baby usually has no long-term effects. As with any invasive intrauterine procedure, short-term complications may occur, including premature birth, ruptured membranes, infection, or bleeding. But in more than 90% of cases, the procedure results in one live baby born in the near future with no permanent defects. The procedure is technically feasible and usually short, so maternal surgical complications are very rare.

Folk remedies and homeopathy are not used for feto-fetal syndrome.

Prevention

Prevention of the development of the syndrome is a very complex issue, since there are no specific methods.

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Forecast

The prognosis of twin-twin syndrome depends on the stage and severity of discordance of the fetuses. The average survival rate is 50-65%; this figure is 77% if treatment is started during stage I. When comparing the prognosis after different treatment methods, it was found that 76% survival of at least one fetus and 36% survival of both twins using laser, compared to 51% survival of at least one fetus and 26% survival of both twins with amnioreduction.

Twin-twin syndrome is a relatively common and serious complication of monochorionic pregnancy. The diagnosis should be suspected in any pregnancy with a sudden increase in abdominal girth, and can be confirmed by ultrasound. However, there are treatments, and it is worth remembering that the earlier treatment is started, the greater the chance of saving both fetuses.

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