The Front Line

Twin-Twin Transfusion Syndrome (TTTS)

by Robert Carpenter, M.D.
Clinical Associate Professor, Obstetrics–Gynecology

Twin-twin transfusion syndrome (TTTS) occurs in 5 percent to 10 percent of monochorionic, diamniotic identical twins (or rarely, in higher order identical pregnancies). TTTS usually is first observed between 10 and 24 weeks of gestation and may vary in severity at different periods throughout the pregnancy. The condition is characterized by a pregnancy in which one fetus (donor) is smaller and is “stuck” inside the amnion, which is devoid of amniotic fluid, while the transfused fetus (recipient) exists in a large volume of amniotic fluid.

The polyhydramnios within the recipient sac is one of the most problematic issues for the obstetrical team. Commonly, the volume of fluid is measured in liters and often is associated with a tense maternal abdomen and a very uncomfortable mother. Complications of untreated polyhydramnios can be preterm labor and premature rupture of membranes; occasionally acute placental abruptions may develop. Traditional treatment has consisted solely of repetitive decompression amniocentesis where volumes of amniotic fluid (1 to 3 liters) may be removed as often as every several days.

Historically, TTTS was considered to have developed from an abnormal anastomosis of a donor artery with a recipient vein and increased blood flow from the donor fetus to the recipient fetus. However, studies in which labeled maternal red cells were injected into the donor umbilical vein have not demonstrated significant transfer of those cells into the recipient fetus several hours later, as determined by fetal blood sampling.

Recent findings have suggested that the renin-angiotensin system, human brain naturetic peptide (hBNP), and endothelin-1 may cause a hypertensive vasculopathy, causing damage to the donor kidneys, which disturbs the regulation of amniotic fluid volumes and urine formation.

Other explanations for the pathophysiology of TTTS concern critical pressures (hemodynamic and/or hydrostatic) rather than the pure “transfusion” volume exchanged between donor and recipient. Those pressures may represent both the abnormal vascular communication present in many identical twins and the hydrostatic forces that apply pressure to the chorionic plate and subjacent vessels by the membranes of the expanded polyhydramniotic recipient sac against the placental or chorionic plate of the donor. In the last 20 years, multiple centers reported resolution of the acute changes normally noted in TTTS after a decompression amniocentesis. Amniotic fluid was subsequently seen in the donor sac with a free-floating amnion between the two fetuses. Following this serendipitous event associated with decompression amniocentesis, the donor twin often demonstrated evidence of improved renal function with urine production and subsequent maintenance of amniotic fluid volume.

A protracted study was performed using septostomy to introduce holes within the intervening membrane either with or separate from decompression amniocentesis. While this procedure was shown to help in some patients, it does not help in all circumstances.

Using laser photocoagulation, Dr. Julian E. De Lia coagulated the traversing vessels found at the interface of the compressed membrane within the polyhydramniotic recipient sac. In some cases, the TTTS process stopped; however, a significant loss of one or both fetuses continued. The Eurofetus Trial demonstrated efficacy of the laser method with improved survival: 76% of treated fetuses compared with 56% of the serial amniocentesis treated group. Additionally, fewer neurological abnormalities (48%) were present in the laser treated group compared with those seen in the amniocentesis treated group (79%) by neuroimaging techniques.

Because of the unacceptably high mortality and morbidity in TTTS, some form of therapy is indicated. Even with treatment, however, the outcome often is death of one or both of the fetuses. If only one fetus dies, cerebral embolic phenomenon may occur in the surviving co-twin (often the donor) with significant destruction of cerebral and other tissues. On the other hand, many recipients die of congestive heart failure, a component part of the increased plasma volume present in that twin.

Most randomized controlled trials have not had the power to definitively state which treatment option is the best to improve fetal outcome (decompression amniocentesis, obliteration by laser photocoagulation of traversing vessels, or septostomy). The most important issues in TTTS are recognizing the disease process, close follow-up, and intensive education of the parents concerning different treatment modalities. For many patients, admission to a randomized therapeutic trial to allow scientific evaluation to determine the best method of treatment is appropriate. Since the gestational age of patients at delivery is 28 to 29 weeks in many patients experiencing TTTS, randomized experimental therapy may provide information that might benefit others who develop this syndrome.