Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome
Classification and external resources
A pair of newborn twins affected by TTTS. Both the recipient (left) and donor (right) survived.
ICD-10	O43.0, P02.3, P50.3
ICD-9	762.3 , 772.0
DiseasesDB	32064
MedlinePlus	001595
eMedicine	med/3410
MeSH	D005330

Twin-to-twin transfusion syndrome (TTTS, also known as Feto-Fetal Transfusion Syndrome (FFTS) and Twin Oligohydramnios-Polyhydramnios Sequence (TOPS)) is a complication of disproportionate blood supply, resulting in high morbidity and mortality. It can affect monochorionic multiples, that is, multiple pregnancies where two or more fetuses share a chorion and hence a single placenta. Severe TTTS has a 60–100% mortality rate.

Incidence

Based on 2005 USA National Center for Health Statistics (4,138,349 total births), the rate of multiple births per year is now 1:30 (3.4%), or approximately 139,816 twins or higher multiples. The majority of identical twins share a common (monochorionic) placenta, and of these approximately 15% go on to develop TTTS. By extrapolating the number of expected identical twins (about one-third) from annual multiple births, and the number of twins with monochorionic placentas (about two-thirds), and from these the number thought to develop TTTS (about 15%), there are at least 4,500 TTTS cases per year in the U.S. alone: 139,816 X .33 X .66 X .15 = 4,568 cases of TTTS per year in U.S. (involving 9,500 or more babies) Since spontaneous pregnancy loss (spontaneous abortion) and pregnancy terminations (elective abortions) that occur prior to 20 weeks go uncounted by the C.D.C., our estimate of TTTS cases may be very conservative. Although infertility treatments have increased the rate of multiple birth, they have not diluted the expected incidence of identical twins even though multiple embryos are often produced and implanted. Studies show a higher rate of identical twins (up to 20 times with IVF) in women having these treatments than occur naturally.

There is approximately a 1 in 1000 chance of having TTTS in a given pregnancy.

One Australian study, however, noted an occurrence of only 1 in 4,170 pregnancies or 1 in 58 twin gestations. This distinction could be partly explained by the "hidden mortality" associated with MC multifetal pregnancies—instances lost due to premature rupture of membrane (PROM) or intrauterine fetal demise before a thorough diagnosis of TTTS can be made.

Etiology

Twin to twin transfusion syndrome

Fetoscopy and laser ablation of connecting vessels in TTTS

As a result of sharing a single placenta, the blood supplies of monochorionic twin fetuses can become connected, so that they share blood circulation: although each fetus uses its own portion of the placenta, the connecting blood vessels within the placenta allow blood to pass from one twin to the other. Depending on the number, type and direction of the interconnecting blood vessels (anastomoses), blood can be transferred disproportionately from one twin (the "donor") to the other (the "recipient"). The transfusion causes the donor twin to have decreased blood volume, retarding the donor's development and growth, and also decreased urinary output, leading to a lower than normal level of amniotic fluid (becoming oligohydramnios). The blood volume of the recipient twin is increased, which can strain the fetus's heart and eventually lead to heart failure, and also higher than normal urinary output, which can lead to excess amniotic fluid (becoming polyhydramnios).

In early pregnancy (before 26 weeks), TTTS can cause both fetuses to die, or lead to severe disabilities. If TTTS develops after 26 weeks, the babies can usually be delivered alive and have a greater chance of survival without disability.

Other than requiring a monochorionic-diamniotic twin (or higher multiple) pregnancy, the causes of TTTS are not known. It is not known to be hereditary or genetic.

Imbalance in development

Some doctors recommend complete bed-rest for the mother coupled with massive intakes of protein (generally in the form of "protein shakes" such as Boost or Ensure) as a therapy to try to counteract the syndrome. Research completed shows these nutritional supplements do work. Diet supplementation was associated with lower overall incidence of TTTS (20/52 versus 8/51, P = 0.02) and with lower prevalence of TTTS at delivery (18/52 versus 6/51, P = 0.012) when compared with no supplementation. Nutritional intervention also significantly prolonged the time between the diagnosis of TTTS and delivery (9.4 +/- 3.7 weeks versus 4.6 +/- 6.5 weeks; P = 0.014). The earlier nutritional regimen was introduced, the lesser chance of detecting TTTS ( P = 0.001). Although not statistically significant, dietary intervention was also associated with lower Quintero stage, fewer invasive treatments, and lower twin birth weight discordance. Diet supplementation appears to counter maternal metabolic abnormalities in DiMo twin pregnancies and improve perinatal outcomes in TTTS when combined with the standard therapeutic options.

Stages

A staging system proposed by fetal surgeon Dr. Ruben Quintero is commonly used to classify the severity of TTTS.

Stage I: A small amount of amniotic fluid (oligohydramnios) is found around the donor twin and a large amount of amniotic fluid (polyhydramnios) is found around the recipient twin.

Stage II: In addition to the description above, the ultrasound is not able to identify the bladder in the donor twin.

Stage III: In addition to the characteristics of Stages I and II, there is abnormal blood flow in the umbilical cords of the twins.

Stage IV: In addition to all of the above findings, the recipient twin has swelling under the skin and appears to be experiencing heart failure (fetal hydrops).

Stage V: In addition to all of the above findings, one of the twins has died. Usually the donor twin is the twin to die first, but it can happen to either.

The Quintero staging does not provide information about prognosis, and other staging systems have been proposed.

Treatment

Various treatments for TTTS include:

Non-Treatment

Expectant Management

This is equivalent of zero intervention. It has been associated with almost 100% mortality rate of one or all fetuses. Exceptions to this include patients that are still in Stage 1 TTTS and are past 22 weeks gestation.

Treatment through adjustment of amniotic fluid

Serial Amniocentesis

This procedure involves removal of amniotic fluid periodically throughout the pregnancy under the assumption that the extra fluid in the recipient twin can cause preterm labor, perinatal mortality, or tissue damage. In the case that the fluid does not reaccumulate, the reduction of amniotic fluid stabilizes the pregnancy. Otherwise the treatment is repeated as necessary. There is no standard procedure for how much fluid is removed each time. There is a danger that if too much fluid is removed, the recipient twin could die. This procedure is associated with a 66% survival rate of at least one fetus, with a 15% chance of cerebral palsy and average delivery occurring at 29 weeks gestation.

Septostomy, or Iatrogenic Disruption of the Dividing Membrane

This procedure involves the tearing of the dividing membrane between fetuses such that the amniotic fluid of both twins mixes under the assumption that pressure is different in either amniotic sac and that its equilibration will ameliorate progression of the disease. It has not been proven that pressures are different in either amniotic sac. Use of this procedure can preclude use of other procedures as well as make difficult the monitoring of disease progression. In addition, tearing the dividing membrane has contributed to cord entanglement and demise of fetuses through physical complications.

Treatment through adjustment of blood supply

Laser Therapy

This procedure involves endoscopic surgery using laser to interrupt the vessels that allow exchange of blood between fetuses under the assumption that the unequal sharing of blood through these vascular communications leads to unequal levels of amniotic fluid. Each fetus remains connected to its primary source of blood and nutrition, the placenta, through the umbilical cord. This procedure is conducted once, with the exception of all vessels not having been found. The use of endoscopic instruments allows for short recovery time. This procedure has been associated with 85% survival rate of at least one fetus, with a 5% risk of cerebral palsy and average delivery occurring at 33–39 weeks' gestation.

Umbilical Cord Occlusion

This procedure involves the ligation or otherwise occlusion of the umbilical cord to interrupt the exchange of blood between the fetuses. The procedure is typically offered in cases where one of the fetuses is presumed moribund and endangering the life or health of the other twin through resultant hypotension. Use of this treatment has decreased as TTTS is identified and treated in earlier stages and with better outcomes. When used, it is associated with an 85% survival rate of the remaining fetus(es) with 5% risk of cerebral palsy and a 33–39 weeks of gestation at delivery.

A recent review found that laser coagulation resulted in less fetal and perinatal deaths than aminoreduction and septostomy, and recommended its use for all states of TTTS.

History

TTTS was first described by a German obstetrician, Friedrich Schatz, in 1875. Once defined by neonatal parameters—differences in birth weight and cord hemoglobin at the time of delivery—TTTS is now defined differently. Today, it is known that discordant fetal weights will most likely be a late manifestation, and fetal hemoglobin through cordocentesis is often equivalent in the twin pair even in severe TTTS.

TTTS in art

De Wikkellkinderen (The Swaddled Children), 1617, by an unknown artist, is thought to depict TTTS.

A painting known as the De Wikkellkinderen (The Swaddled Children), from 1617, is thought to represent a depiction of TTTS. The drawing shows twins that appear to be identical, but one is pale (possibly anemic), while the other is red (possibly polycythemic). Analysis of the family histories of the owners of the painting suggests that the twins did not survive to adulthood, although whether that is due to TTTS is uncertain.

Although somewhat of a stretch, due to the detail of "magical birthgiving" in the folklore, an example of TTTS might have been noted ages before Schatz classified it or the painting "De Wikkellkinderen" illustrated, as an old Norse fairy tale, "Tatterhood", seemed to explain it, with one of the two girls being lovely but weak (pale skin and delicacy of anemia has often associated with how girls were most expected to be at the time) and the other one, the title heroine, was considered hideous and too strong (polycythemia has a higher blood cell count and often includes unsightly blemishes). Of course, with both twins growing up to be healthy adults, the debate of truth in fiction is still a mystery.^{[citation needed]}

See also

• Vanishing twin

External links

• The Twin to Twin Transfusion Syndrome Foundation
• The 15 Most Important Questions
• FREE Twin to Twin Transfusion Syndrome Patient Guides from Twins and Multiple Births Association, Tamba. The largest patient support group of its kind in the world
• The International Institute for the Treatment of TTTS
• Texas Children's Fetal Center, Twin-Twin Transfusion Syndrome
• TTTS Educational Video – Texas Children's Fetal Center
• A timelapse movie of a TTTS laser ablation
• Children's Hospital Los Angeles- University of Southern California Fetal Therapy Program-TTTS
• The Center for Prenatal Pediatrics at Columbia University Medical Center- TTTS Evaluation & Laser Photocoagulation Therapy
• Twin-Twin Transfusion Syndrome – Children's Hospital Boston
• The Children's Hospital of Philadelphia
• The Brown Fetal Treatment Program – What is TTTS?
• Fetal Hope Foundation
• Ohio State's Maternal Fetal Medicine
• St. Louis Fetal Care Institute TTTS Survivor Stories