Twin–Twin Transfusion Syndrome

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1015 Twin–twin transfusion syndrome results from intrauterine blood transfusion from one twin to another twin as a serious complication in 10–20% of monochorionic diamniotic twin pregnancies.

GENETICS/BASIC DEFECTS

1. Cause: a serious complication of monozygotic, monochorionic twin pregnancy through placental vascular anastomoses (unilateral arteriovenous anastomoses), resulting in transfusion of blood from one fetal twin to another twin 2. Pathogenesis

a. Imbalance in net blood flow through transplacental fetofetal transfusion, resulting in a discrepancy in blood volume distribution in two twins

b. The donor twin

i. Becoming hypovolemic, hypotensive, and oliguric ii. Leading to oligo/anhydramnios and growth

restriction c. The recipient twin

i. Becoming hypervolemic, hypertensive, and polyuric

ii. Leading to polyhydramnios and congestive heart failure

CLINICAL FEATURES

1. Donor twin

a. Birth weight: small for gestational age b. Pallor and anemic

c. Poor peripheral perfusion

d. Oligohydramnios in the amniotic sac secondary to hypovolemia and decreased urine output

e. Stuck twin phenomenon (the twin appears in a fixed position against the uterine wall) resulting from severe oligohydramnios

f. Hydrops fetalis secondary to anemia and high-output heart failure

2. Recipient twin

a. Birth weight: larger at birth b. Plethoric and ruddy c. Jaundice

d. Polyhydramnios in the amniotic sac secondary to hypervolemia and increased fetal urine output e. Hydrops fetalis secondary to hypervolemia

f. Hypertension

g. Hypertrophic cardiomegaly

h. Right-sided heart failure with tricuspid regurgitation and right ventricular outflow tract obstruction i. Increased risk of cardiac malformations j. Intravascular coagulation

3. Prognosis

a. Premature delivery in case of mild to moderate twin–twin transfusion syndrome

b. Guarded with possible serious maternal and fetal complications

c. Antenatal death as well as neonatal death secondary to preterm delivery

d. Survival rate for those diagnosed before 28 weeks:

20–45%

4. Antenatal factors that predict poor outcome

a. Early gestational age at diagnosis with delivery before 28 weeks of gestation

b. Fetal polyhydramnios requiring multiple therapeutic amniocenteses

c. Fetal hydrops

d. Absent or reversed diastolic flow in umbilical artery Doppler studies

5. Neonatal complications

a. Neurologic sequelae in 25% of surviving twin in case of fetal demise in other twin

b. Divergent intrauterine growth in association with sub- sequent physical and mental deficiencies in the smaller twins

c. Thrombocytopenia suggested as the cause of cataracts, impaired hearing, and growth retardation of the donor twin

d. Intrauterine growth deficiency of the brain and pro- found neonatal hypoglycemia implicated as reasons for cerebral impairment of the donor twin, resulting in sub- sequent lower intelligence compared with its co-twin e. Circulatory overload with heart failure if severe

hypervolemia occurs

f. Occlusive thrombosis due to hyperviscosity

g. Polycythemia that may lead to severe hyperbilirubinemia and kernicterus

h. Brain damage with cerebral palsy, microcephaly, or encephalomalacia

6. Maternal complications

a. Secondary to multiple gestations i. Preeclampsia

ii. Preterm labor iii. Hemorrhage

iv. Diabetes

b. Maternal mirror syndrome

i. A rare complication associated with fetal hydrops ii. Also known as “Ballantyne syndrome” or “triple

edema syndrome”

iii. A syndrome of severe water retention that “mirrors”

fetal hydropic changes

iv. Frequent occurrence in the mid-trimester

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DIAGNOSTIC INVESTIGATIONS

1. Difference in birth weight: inter-twin difference >20%

(heavier twin = 100%)

2. CBC to demonstrate inter-twin differences of hemoglobin level (difference ≥5 g/dL)

a. Anemia: frequently in donor twin at birth b. Polycythemia frequently in recipient twin at birth 3. Blood chemistry

a. Hypoglycemia in either twins

b. Hypocalcemia, hypoproteinemia in donor twin c. High creatinine in either twins with renal dysfunction 4. Thrombocytopenia in either twins

5. Hyperbilirubinemia in polycythemic recipient twin 6. Imagings

a. Cranial ultrasound: intraventricular hemorrhage and periventricular leukomalacia in premature twins b. Chest radiography; pleural effusions and cardiomegaly

in hydrops fetalis c. Echocardiography

i. Myocardial dysfunction/hypertrophy ii. Valvular insufficiency

iii. Pericardial effusion

d. Renal ultrasound: abnormal renal echogenicity indicat- ing hypoxic-ischemic cortical necrosis

e. Abdominal ultrasound: Ascites in hydrops fetalis 7. Demonstration of transplacental vascular connections: an

important criterion for the diagnosis of the twin–twin transfusion syndrome

a. Donor twin i. Placenta

a) Pale b) Swollen c) Atrophied

ii. Amniotic membrane showing amnion nodosum in the presence of oligohydramnios

b. Placenta of the recipient twin i. Red

ii. Congested iii. Hypertrophied

8. Surgical pathologic assessment of vascular anastomoses in monochorionic placentas with strong clinical correlation of placental types and occurrence of twin–twin transfusion a. Type A (placenta without vascular anastomoses): 0%

b. Type B (placenta with only deep arteriovenous anastomoses): 81%

c. Type C (placenta with only superficial anastomoses):

1%

d. Type D (placenta with combined deep arteriovenous and superficial anastomoses): 18%

9. Sonographic criteria for determining chorionicity a. Dichorionic

i. Separate placentas ii. Well-visualized septum b. Monochorionic diamniotic

i. One placenta

ii. A paper-thin, reflective hair-like septum (only small parts visible)

c. Dichorionic diamniotic: septum readily seen with a thickness similar to one wall of the umbilical cord

GENETIC COUNSELING

1. Recurrence risk

a. Patient’s sib: not increased unless in another pregnancy with monochorionic twinning (twin–twin transfusion syndrome affects 10–15% of monochorionic twins) b. Patient’s offspring: not increased unless in pregnancy

with monochorionic twinning 2. Prenatal diagnosis

a. Ultrasonography

i. Divergent fetal size: striking differences in the sizes of the twins

a) Disparity in size of inter-twin abdominal circumference (difference > 18 mm) b) Disparity in size or in the number of vessels

in the umbilical cords: The donor twin may have a single umbilical artery. The size of the umbilical cord of the recipient twin may be much larger than that of its co-twin ii. Divergent size of amniotic sacs

a) Presence of polyhydramnios (largest pocket

>8 cm) in one sac (the recipient twin persist- ently has a distended bladder and produces a large amount of urine)

b) Presence of oligohydramnios (largest pocket

<2 cm or stuck twin) in other sac (the donor twin produces little urine)

iii. “Stuck twin” sign: a growth-retarded fetus tightly enwrapped within its membrane and trapped or stuck against the uterine wall due to oligohydramnios

iv. Determination of monozygosity a) Like-sex twins

b) Monochorionic/diamniotic placentation (absence of twin-peak sign, thin separating membrane, and single placenta showing divergent echogenicity of the cotyledons supplying the two cords)

v. Evidence of hydrops in either twin

vi. Evidence of congestive cardiac failure in the recipient twin

vii. A sonographic staging classification for twin–twin transfusion syndrome allowing for the grading of the severity of the disease by stan- dardized criteria

a) Stage I: visible bladder of the donor twin, normal Doppler studies

b) Stage II: not visible bladder of the donor twin (during the length of examination, usually 1 hour), not critically abnormal Doppler studies

c) Stage III: critically abnormal Doppler studies in either twin, characterized as absent or reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile umbilical venous flow

d) Stage IV: ascites, pericardial or pleural effusion, scalp edema, or overt hydrops of one or both twins

e) Stage V: presence of one or both demised twins

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b. Echocardiography i. Possible advantages

a) Assessment of cardiovascular adaptation to inter-twin transfusion

b) Early recognition of deterioration c) Evaluation of antenatal management ii. Fetal heart rate monitoring: A silent, sinusoidal

pattern in tracings of the fetal heart rate may indicate signs of fetal anemia.

iii. Doppler studies

a) Detection of arterio–arterial anastomoses in monochorionic twins

b) Doppler velocimetry of the umbilical arter- ies: inter-twin differences in systolic/diastolic ratio > 0.4 predicting growth discordan- cy of at least 350 g

iv. Ultrasound-guided fetal blood sampling

a) Establishing the diagnosis of monozygosity when blood group studies are performed on both twins

b) Allowing an accurate antenatal assessment of the inter-twin hemoglobin difference and consequently establishing the diagnosis of twin–twin transfusion

c) Revealing the degree of fetal anemia in the donor twin

c. Fetoscopy

i. Plethora donor twin ii. Pale recipient twin 3. Management

a. General approach

i. Monochorionic twining at high risk for twin–twin transfusion syndrome

ii. Requiring close obstetrical monitoring

iii. Requiring specialized care in neonatal intensive care unit

b. Post-partum therapies

i. Directed towards the problems of each twin, such as prematurity, anemia, polycythemia, and hydrops fetalis

ii. Severely anemic donor twin: requires packed red blood cell transfusions or partial exchange transfusions

iii. Polycythemic recipient twin: requires partial exchange transfusion to lower serum hematocrit c. Prenatal therapies

i. Treating the mother with digoxin with favorable results when the recipient twin is showing signs of cardiac failure

ii. Serial amniodrainage (amnioreduction): currently the most widely used therapy because it is simple and requires commonly available skills and equipment a) Removing large volumes of amniotic fluid

from the recipient twin’s sac

b) Reducing the amniotic fluid volume, thereby reducing the risk of preterm labor or rup- tured membranes

c) Overall perinatal survival with serial aggressive amnioreduction: about 60% in uncon- trolled published series

d) Double survival rate (50%) and single survival rate (20%) in severe twin–twin transfusion syndrome presenting before 28 weeks of gestation

e) Fail to address the underlying cause of twin–twin transfusion syndrome

f) Complications: uterine contractions, premature rupture of membranes, chorioamnionitis, abruptio placenta, and inadvertent septostomy resulting in iatrogenic monoamniotic twins

iii. Amniotic septostomy: intentionally puncturing the intertwine septum

a) To create a hole in the intertwine membrane between the anhydramniotic donor’s sac and the hydramniotic recipient’s sac

b) Restoring normal amniotic fluid pressure gradient, allowing fluid to move along a hydrostatic gradient from the hydramnios sac into the oligohydramnios sac

c) Also an inadvertent occurrence during amnioreduction procedure

d) Limited experience

iv. Endoscopic laser coagulation of all placental vascular anastomoses

a) Reduces and abolishes intertwine transfusion by ablating chorionic plate anastomoses, producing functionally dichorionic pregnancies

b) Proponents arguing that the procedure reduces the risk of neurological injury in survivors

c) Overall survival rate (58%) with single survival of 32% and double survival of 42% for cases presenting prior to 18 weeks

d) Rare fetal complications (relationship to the procedure not established): aplasia cutis, limb necrosis, amniotic bands, and microph- thalmia/ anophthalmia

v. Selective feticide by cord occlusion (umbilical cord ligation): used as a last resort in cases in which both twins are at risk because of the serious condition of one twin

a) Considered in case of monochorionic twin pregnancy in which one twin is a nonviable fetus, especially the condition is compro- mising the nonaffected fetus

b) A typical example in twin reversed arterial perfusion sequence. The relatively normal twin risks high-output cardiac failure, compli- cations of polyhydramnios and death in utero.

c) Another example of twin–twin transfusion syndrome, in which one fetus has major con- genital anomalies or in utero acquired abnormality, such as demonstrable cerebral lesions, terminal cardiac failure, or other conditions with a poor prognosis

d) Benefits of selective termination of the affected twin: arrest the fetofetal transfusion process and protect the survivor

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vi. In general, twin–twin transfusion syndrome diagnosed before 26 weeks of gestation has sig- nificantly better survival rates and fewer neurological sequelae after laser ablation therapy than amnioreduction. Twin–twin transfusion syndrome diagnosed after 26 weeks can best be treated by amnioreduction or delivery.

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Fig. 1. Diamniotic monochorionic twin placenta with features of twin–twin transfusion (the placental discs are not fused in this case):

The placenta corresponding to the recipient twin (right) is small but plethoric and dark in color. The placenta of the donor twin (left) is large but anemic, pale and edematous. The amniotic sacs were removed at the margins of the placental discs. The root of the thin monochorionic septum between the two sacs is shown on the fetal surface (first picture).

The color difference between the two placentas is better shown on the maternal surface (second picture).

Fig. 2. The donor twin (right) showing smaller and pallor and the recipient twin (left) showing larger and plethoric at birth.