Twin-to-twin transfusion syndrome (TTTS) is a severe complication of multiple monochorionic pregnancy, in which due to anastomoses in the vascular network of the placenta, an imbalance of blood flow occurs in fetuses. The manifestations are the disproportion of the development of twins, polyhydramnios in the bladder of the “recipient” with little water in the “donor”, a number of serious malformations of both fetuses, their intrauterine death. Diagnosis is made based on the pattern of ultrasound examinations, echocardiography and dopplerography, usually performed in the second half of pregnancy. To preserve pregnancy, laser coagulation of placental anastomoses, periodic amniodrenation, and occlusion of the umbilical cord of a more affected fetus are performed to preserve another one.
O43.0 Placental transfusion syndromes
Twin-to-twin transfusion syndrome occurs exclusively in monozygotic twins (extremely rare – triplets), when twins are united by a common chorion. Official statistics show that this complication occurs in 17.5% of women whose pregnancy is monochoriatic in nature. A number of researchers believe that the incidence of the syndrome is much higher, but it often leads to spontaneous abortion in the early stages of childbearing (“hidden mortality”). The level of perinatal mortality in TTTS is high and in some regions reaches 65-100%, approximately 12-15% of all cases of intrauterine death in multiple pregnancies are due to this condition.
The morphological prerequisite for the development of fetal-fetal transfusion syndrome is the presence of anastomoses in the chorion between the vascular networks of both fetuses. In monochorionic pregnancy, they are detected in 60-90% and can be superficial and deep. Superficial veno-venous and arterio-arterial anastomoses are able to transport blood in both directions (depending on pressure) and equalize blood volumes between twins. The structure of deep anastomoses is such that arterial blood entering the placental cocyledon from the system of one child passes into the venous network of another. It is assumed that the prevalence of the number of deep vascular connections in the chorion over the number of superficial ones causes the appearance of the syndrome.
The factors leading to the occurrence of more deep anastomoses are currently unknown. It is assumed that they arise due to the pathology of the formation of the placenta of the “donor”, as a result of which vascular resistance in it increases, and shunts are formed connecting it with the vessels of the “recipient”. The possibility of the influence of late separation of twins, teratogenic factors, insufficient blood supply to the uterus of a woman is discussed. Finding out the exact causes of TTTS is complicated by the late diagnosis of this condition and the unpredictability of its appearance.
It is believed that the occurrence of fetal-fetal transfusion syndrome can occur at different periods of gestation, and the later occurrence of complications is more favorable in prognostic terms. Another point of view is that the prerequisites for TTTS arise even at the stage of separation of fetuses (4-12 days of gestation), and the severity and duration of the appearance of further disorders depends on the number of deep anastomoses and the degree of imbalance in the circulation of twins. Initially, there is a simple flow of blood from the “donor” to the “recipient”, which does not affect the rate of development and other characteristics of both fetuses.
A decrease in the volume of circulating blood in a donor twin gradually leads to the phenomena of placental insufficiency – intrauterine hypoxia, developmental delay. The work of the kidneys is disrupted and urine excretion decreases, which causes a decrease in the volume of the bladder and the appearance of lack of water. The latter factor affects the rate of development of lung tissues, slowing down the formation of the respiratory system. In the absence of treatment, intrauterine fetal death occurs due to hypoxia and severe underdevelopment of the main organs and systems.
At the same time, the recipient twin experiences a significant blood rush, his BCC level increases, which increases the load on the cardiovascular system and kidneys. This leads to hypertrophy of the right parts of the heart, general cardiomegaly, intrauterine tricuspid valve insufficiency. The volume of the bladder increases, there is polyhydramnios. The change in the volume of amniotic fluid in twins may be imperceptible in the case of a common fetal bladder (monochorionic monoamniotic pregnancy). Intrauterine or intranatal death of the “recipient” in the absence of treatment occurs due to heart and kidney defects.
There are several degrees of development of fetal-fetal transfusion syndrome, based on the severity of the fetal condition and the difference in their main indicators (CT, amniotic fluid volume). As TTTS progresses, pregnancy disorders increase in such a way that each stage includes pathologies of all previous stages of the disease. The modern classification identifies five stages of the development of the syndrome:
- Stage 1. Ultrasound studies record only the difference in the volume of amniotic fluid between the donor twin (lack of water) and the recipient (polyhydramnios). An early consequence of this is the appearance of folds of the amniotic septum, which is registered already at 11-17 weeks of gestation (the earliest sign of TTTS). In the case of monoamniotic pregnancy, the 1st stage may not be determined.
- Stage 2. Against the background of the difference in the volume of amniotic fluid in the donor fetus, the filling of the bladder is not determined, its noticeable lag in development is diagnosed (CRT and weight are less than 20% less than in the “recipient”). In the latter, a bladder with a significant volume and echogenicity is visualized.
- Stage 3. Progressive disorders of the cardiovascular system occur in both fetuses, which is manifested by a change in the Doppler and echocardiographic picture. The recipient has cardiomegaly, tricuspid valve insufficiency, pulmonary trunk dilation.
- Stage 4. Signs of dropsy of the recipient fetus develop – swelling of the whole body, an increase in the size of the liver, spleen, accumulation of fluid in the cavities.
- Stage 5. It is diagnosed with intrauterine death of one or both fetuses.
The stage of twin-to-twin transfusion syndrome does not have a clear link to the term of pregnancy – with unfavorable and early development of complications, signs of stage 1 can be detected at 14-17 weeks. In obstetrics, a period of 25 weeks of gestation is considered an important limit for the syndrome, since the appearance of disorders earlier often leads to termination of pregnancy even with treatment. It is often decided to save only one (more viable) child, then medical intervention can be performed to the detriment of his twin.
There are no subjective manifestations of twin-to-twin transfusion syndrome, it is detected during screening ultrasound examinations. Pregnant women with this pathology are more likely than normal to have uterine hypertension and other conditions that threaten to interrupt the child’s gestation. A number of researchers admit that a significant part of spontaneous abortions in multiple pregnancies is caused by TTTS before its detection. Complications of pathology (intrauterine death) may be manifested by abdominal and chest pain, profuse uterine bleeding or the appearance of bloody discharge from the vagina. In the later stages, a sign of the death of twins is the cessation of their movements (fading).
The most severe complication of fetal-fetal transfusion syndrome is the intrauterine death of both fetuses. The absence of therapeutic measures leads to perinatal death in 100% (with the development of TTTS before 25 weeks of gestation) and in 80-90% – with its later occurrence. Various treatment methods increase the survival rate of at least one child. Complications of the condition also include the risk of developing cerebral palsy in surviving children – the probability of such an outcome ranges from 5 to 20%. Rare complications are intrauterine fetal death with infection or mummification of the corpse.
The detection of twin-to-twin transfusion syndrome occurs during a planned ultrasound of a pregnant woman, already when a monochorionic multiple pregnancy is detected, a woman is included in the risk group. Ultrasound-signs of the disease are detected after the 16th week (extremely rarely – after the 11th–12th), then additional research methods are prescribed to confirm the diagnosis and monitor the condition of the fetuses. With their help, the prognostic prospects of twin-to-twin transfusion syndrome are determined and data are collected for possible treatment.
- Ultrasound screening. With TTTS, it is especially informative in the second and third trimester. Depending on the stage, with its help, in this pathology, polyhydramnios is detected in the recipient (an increase in the depth of the largest pocket of water that does not correspond to the norm in time), an increase in the size of the bladder, at the terminal stages – malformations of organs and dropsy (anasarca). In the donor, low water content is determined by ultrasound (the depth of the pocket of water is not more than 20 mm), a decrease in the size of the bladder.
- Ultrasound fetometry. In a donor twin, there is a lag in growth, a discrepancy in fetometric parameters (frontal-occipital size, circumference of the head, abdomen, chest, length of the tubular bones of the skeleton) to the term of pregnancy. The difference in the main parameters between the fruits with TTTS exceeds 20%.
- Fetal dopplerometry. Pathological changes in blood flow are determined from the 3rd stage of TTTS. These include the difference in systolic-diastolic ratio in fetal umbilical cord arteries over 0.4, reverse end-diastolic flow in the donor. In the recipient fetus, dopplerometry determines abnormal venous blood flow in the umbilical cord, an increase in the blood flow rate in the pulmonary artery.
- Fetal echocardiography. Reveals late manifestations of TTTS, which are determined in the recipient twin. These are hypertrophy of the right parts of the heart, cardiomegaly, tricuspid valve insufficiency, and a decrease in right ventricular ejection.
Conservative treatment with angioprotective agents and drugs for the correction of microcirculation is considered ineffective and can only be used as auxiliary therapy. Specialists adhere to a similar position with regard to hormonal (progesterone preparations) and other medications used in obstetrics to preserve pregnancy. Only fetal surgery methods increase the survival rate of at least one twin:
- Fetoscopic coagulation of placental anastomoses. It is the most effective method of treating fetal-fetal transfusion syndrome – the probability of saving both children is 40-55%, the survival of one is over 85%. There is a fairly low risk of long–term consequences (cerebral palsy in a newborn) – 5-9%. The method requires the use of high-tech equipment and extensive experience of the surgeon.
- Amnioreduction or serial amniodrenage. Repeated removal of amniotic fluid from the bladder of the recipient fetus is necessary to prevent premature birth and perinatal death. The survival rate of one child is 60-66%, the risk of developing cerebral palsy in the future is 13-15%.
- Fetoscopic coagulation of the umbilical cord. A method involving the overlap of one of the umbilical cords (the more affected twin) to reduce transfusion and improve the condition of the other fetus. It is used in the early stages of pregnancy, the probability of saving the child is at least 80%, with a 5% risk of developing cerebral palsy in the future.
- Septostomy. A procedure in which the amniotic septum is damaged to communicate amniotic fluid, equalize their volume and pressure. Many experts question its effectiveness, after the operation it becomes difficult to monitor the progression of TTTS. When performing septostomy, there is a risk of damage to the umbilical cord with the death of fetuses.
Twin-to-twin transfusion syndrome is characterized by an unfavorable prognosis – in the absence of treatment and regular follow-up by an obstetrician-gynecologist, this condition almost always leads to fetal death and spontaneous termination of pregnancy. The effectiveness of surgical intervention depends on many factors: the stage of development of twin-to-twin transfusion syndrome, the duration of pregnancy, the presence or absence of concomitant pathologies in a woman. Quite often, therapeutic measures have to be carried out to the detriment of a more affected child in order to preserve another. Prevention of the development of the syndrome has not been developed, since the causes of its occurrence are unknown.