Twin-to-Twin Transfusion Syndrome 

Updated: Aug 03, 2018
Author: Terence Zach, MD; Chief Editor: Ronald M Ramus, MD 

Overview

Background

Twin-to-twin transfusion syndrome (TTTS) is the result of an intrauterine blood transfusion from one twin (donor) to another twin (recipient). TTTS only occurs in monozygotic (identical) twins with a monochorionic placenta. The donor twin is often smaller with a birth weight 20% less than the recipient's birth weight. The donor twin is often anemic and the recipient twin is often plethoric with hemoglobin differences greater than 5 g/dL.

Pathophysiology

TTTS is the result of transfusion of blood from one fetal twin to another twin. The blood transfusion from the donor twin to the recipient twin occurs through placental vascular anastomoses. The most common vascular anastomosis is a deep, artery-to-vein anastomosis through a shared placental cotyledon.[1]

TTTS is a specific complication of monozygotic twins with monochorionic placentation. Monozygotic twins that have a dichorionic placentation are not at risk for TTTS. Monozygotic twins with monochorionic, diamniotic placentation or monochorionic, monoamniotic placentation are at risk for TTTS (see images below).[2]

Monozygotic twins with monochorionic, diamniotic p Monozygotic twins with monochorionic, diamniotic placentation.
Monozygotic twins with monochorionic, monoamniotic Monozygotic twins with monochorionic, monoamniotic placentation.

The clinical features of TTTS are the result of hypoperfusion of the donor twin and hyperperfusion of the recipient twin.

The donor twin becomes hypovolemic and oliguric or anuric. Oligohydramnios develops in the amniotic sac of the donor twin. Profound oligohydramnios can result in the stuck twin phenomenon in which the twin appears in a fixed position against the uterine wall. Ultrasonography typically fails to visualize the fetal bladder because of absent urine.

The recipient twin becomes hypervolemic and polyuric. Polyhydramnios develops in the amniotic sac of the recipient twin.

Either twin can develop hydrops fetalis. The donor twin can become hydropic because of anemia and high-output heart failure. The recipient twin can become hydropic because of hypervolemia. The recipient twin can also develop hypertension, hypertrophic cardiomegaly, disseminated intravascular coagulation, and hyperbilirubinemia after birth.

Epidemiology

Frequency

United States

Monozygotic twins occur in 3-5 per 1000 pregnancies. Monozygotic twins can be monochorionic or dichorionic. Approximately 75% of monozygotic twins are monochorionic. Only monochorionic twins are at risk for TTTS. TTTS occurs in 5-38% of monochorionic twins.

Thus, TTTS only occurs in same sex, monozygotic twins with monochorionic placentation.

Prognosis

Outcome is dependent upon gestational age at birth and whether intrauterine fetal brain ischemia occurred. The lower the gestational age at birth the greater the risk for long-standing neurologic or pulmonary sequelae. Catch-up growth occurs postnatally in most of the smaller donor twins.

Morbidity/mortality

Severe TTTS has a 60-100% fetal or neonatal mortality rate. Mild-to-moderate TTTS is frequently associated with premature delivery. Fetal demise of one twin is associated with neurologic sequelae in 25% of surviving twins. Fetal blood pressure instability can lead to brain ischemia in either the donor or recipient twin. Ischemia of the fetal brain can result in periventricular leukomalacia, porencephaly, microcephaly and cerebral palsy. The more premature the twins are at birth, the higher the incidence of postnatal morbidity and mortality.

In a review of 135 monochorionic twin pregnancies with single intrauterine death (sIUD), whether spontaneous or procedure related, O'Donoghue et al found that death of the co-twin followed in 22.9% of cases. In the pregnancies that continued after sIUD, the frequency of antenatally acquired brain injury in the co-twin was significantly lower after procedure-related than spontaneous sIUD: 2.6% versus 22.2% (P = 0.003). The investigators conclude that the risk of brain injury is reduced but not negated by procedures that restrict inter-twin transfusion.[3]

Complications

Neurologic sequelae

Intrauterine demise of one twin can result in neurologic sequelae in the surviving twin. Acute exsanguination of the surviving twin into the relaxed circulation of the deceased twin can result in intrauterine CNS ischemia.

 

Presentation

History

Women with twin pregnancies who develop twin-to-twin transfusion syndrome (TTTS) frequently complain of a rapidly enlarging abdomen over 2-3 weeks as polyhydramnios develops in the amniotic sac of the recipient twin.

Other complaints include preterm labor and premature rupture of membranes.

Physical

TTTS should be considered in a pregnant woman carrying monochorionic twins if she develops a rapidly increasing fundal height. After birth, TTTS can be considered if the twins are monozygotic, and significant differences occur in the size or appearance of the twins.

Donor twin features include the following:

  • Small for gestational age - More than 20% smaller than recipient twin

  • Pallor

  • Poor peripheral perfusion

Recipient twin features include the following:

  • Large for gestational age - More than 20% larger than donor twin

  • Plethoric and ruddy

  • Jaundice

Hydrops fetalis can be present in either twin in TTTS. These infants have subcutaneous edema, a distended abdomen, and respiratory distress.

Causes

TTTS occurs in monozygotic, monochorionic twin pregnancies when an anastomosis between placental vasculature exists.

 

DDx

Diagnostic Considerations

Important considerations

Monochorionic twin pregnancies are considered high-risk situations and require very close obstetrical monitoring. Newborns with twin-to-twin transfusion syndrome (TTTS) may be critically ill at birth and require specialized care in neonatal intensive care units. These infants are at significant risk for neurologic sequelae.

Other problems to be considered

The following conditions should also be considered in the differential diagnosis in cases of suspected TTTS:

  • Hydrops fetalis

  • Polycythemia

  • Polycythemia of the newborn

  • Polyhydramnios

  • Oligohydramnios

  • Anemia of the newborn

 

Workup

Laboratory Studies

After delivery, the newborn work-up should include the following laboratory studies:

  • CBC count: The donor twin is frequently anemic at birth, whereas the recipient twin is frequently polycythemic at birth.

  • Calcium: Hypocalcemia is frequently present in the donor twin.

  • Glucose: Hypoglycemia may be present in either twin.

  • Creatinine: Either twin may have evidence of renal dysfunction.

  • Platelet count: Thrombocytopenia can occur in either twin.

  • Bilirubin: Hyperbilirubinemia may develop in the polycythemic recipient twin.

Imaging Studies

Sonographic findings of TTTS during pregnancy include the following:

  • Significant discrepancy in size of same-sex fetuses

  • Monochorionic placentation

  • Significant disparity in the amount of amniotic fluid between the fetuses with the smaller twin having oligohydramnios

  • Smaller fetus with an absent stomach and bladder

  • These pregnancies are at risk for preterm delivery. This may be related to the uterine overdistention from the twin gestation and polyhydramnios. Cervical shortening is also more common so transvaginal assessment of the cervix should also be done.[4]

Neonatal imaging should include the following:

  • Neonatal brain ultrasonography: Because ischemia of the brain can occur during fetal development in either the donor or recipient twin, brain ultrasonography should be considered in both twins born with TTTS. Twins born prematurely are susceptible to intraventricular hemorrhage and periventricular leukomalacia.

  • Neonatal echocardiography: Myocardial dysfunction, myocardial hypertrophy, valvular insufficiency, and pericardial effusions can be detected in either twin.

  • Neonatal renal ultrasonography: Abnormal renal echogenicity may be present in either twin and indicates hypoxic-ischemic cortical necrosis.

  • Neonatal abdominal ultrasonography: Ascites may be present if hydrops fetalis occurs.

  • Neonatal chest radiography: Pleural effusions and cardiomegaly may be present if hydrops fetalis occurs.

Other Tests

The risk for aneuploidy in monochorionic twin gestations is not increased compared with a singleton gestation of the same age. Invasive procedures to salvage the pregnancy would not be recommended if lethal aneuploidy (ie, T13 or T18) is seen, so evaluation of the amniotic fluid should be offered to assess for aneuploidy.[5]

Procedures

Amnioreduction can be done immediately once the diagnosis of TTTS is made. This can be performed by placing a 20- or 18-gauge spinal needle into the amniotic cavity of the fetus with polyhydramnios under ultrasonographic guidance and connecting this to 1 L evacuated containers. Several liters of fluid can be removed by this method.

The patient should then be followed weekly to evaluate for evidence of improvement, ie, monitoring the amniotic fluid volume of both fetuses. If there was some improvement in the amniotic fluid of the donor, then repeat amnioreductions can be performed if and when the polyhydramnios recurs around the recipient.

Serial ultrasonography to assess fetal growth are also recommended and these can be done every 2-4 weeks. Once an advanced gestation is obtained nonstress testing can be performed to assess fetal well-being.

If there is any evidence of cardiac failure, ie, cardiac hypertrophy or hydrops, in either fetus or if there is no response to the amnioreduction, then the patient should be referred to a center that can perform fetoscopic laser photocoagulation of the placenta.

A systematic review and meta-analysis by Rossi et al found that a small number of cases with laser therapy are affected with neurologic impairment (cerebral palsy being the most frequent) , signs of which begin in infancy. All infants, even those who appear to be healthy, should be closely followed.[6]

Staging

The most useful staging system for TTTS was developed by Quintero:[7]

Table. TTTS Staging System (Open Table in a new window)

Stage

Oligohydramnios/

Polyhydramnios

Absent Urine in Donor Bladder

Abnormal Doppler Blood Flows

Hydrops Fetalis

Fetal Demise

I

+

-

-

-

-

II

+

+

-

-

-

III

+

+

+

-

-

IV

+

+

+

+

-

V

+

+

+

+

+

 

Treatment

Approach Considerations

The most common procedure to treat TTTS is reduction amniocentesis. This procedure involves draining the amniotic fluid from around the recipient twin. This procedure may improve circulation in the donor twin especially if the anastomosis are superficial in the placenta and the TTTS is a lower stage. This procedure may need to be performed multiple times during the pregnancy.

Fetoscopic laser photocoagulation of chorionic plate vessels is a highly specialized procedure performed in a few centers around the world. This is mostly reserved for more severe cases, especially those that do not respond to amnioreduction. In pregnancies treated with fetoscopic procedures, the overall survival is 75% with 85% having at least 1 fetus survive.[8]  The fetal death rate for the donor is higher that the recipient following this procedure.[9]  A study by Slaghekke et al that included 274 women with TTTS reported that laser coagulation of the entire vascular equator (Solomon technique) was associated with a reduction in twin anaemia polycythaemia sequence (3% vs 16% for the standard treatment) and recurrence of twin-to-twin transfusion syndrome (1% vs 7%).[10]  Another study by Van Klink et al found no difference in the long-term neurodevelopmental outcome in surviving patients with TTTS treated by the Solomon technique compared to the standard laser technique.[11]

 

Timing of delivery depends on multiple factors. The ideal would be for delivery at term; however, evidence of lack of fetal growth or nonreassuring antepartum testing or preterm labor may result in a premature delivery.

Medical care of twins after birth is directed toward problems related to prematurity, anemia, polycythemia, and hydrops fetalis.

  • Severely anemic donor twins may require packed RBC transfusions or partial exchange transfusions.

  • Polycythemic recipient twins may require partial exchange transfusion to lower serum hematocrit levels.

  • Newborns with hydrops fetalis may require mechanical ventilation, thoracocentesis, pericardiocentesis, and paracentesis.

Diet

Nutritional supplementation with commercially available dietary supplements during pregnancies has been reported to reduce the severity and incidence of TTTS. In addition, patients who took dietary supplements required fewer invasive procedures.[12]