Twin-to-Twin Transfusion Syndrome

What is Twin-to-Twin Transfusion Syndrome?

Twin-Twin Transfusion Syndrome (TTTS) is a condition that may occur in twins that share a single placenta. This issue underlines why it’s necessary to know the number of placentas and amniotic sacs (fluid-filled sacs where the fetus grows in the uterus) for all twins, as it influences how they are managed.

Twins can have either two placentas and two amniotic sacs (dichorionic diamniotic), one placenta and two amniotic sacs (monochorionic diamniotic), or one placenta and one amniotic sac (monochorionic monoamniotic).

If a fertilized egg (zygote) splits into two within the first three days, it results in dichorionic diamniotic twins. If the split happens between day 3 and day 8, it leads to monochorionic diamniotic twins. If it happens between day 8 and day 13, it results in monochorionic monoamniotic twins. When the split occurs after day 13, it can result in conjoined twins.

An ultrasound may show a ‘lambda sign’ for dichorionic twins and a ‘T sign’ for monochorionic twins. The ‘T sign’ indicates a thin dividing membrane between the two amniotic sacs when there’s only one placenta for both twins. For this to be confirmed, there mustn’t be a ‘lambda’ or ‘twin peak’ sign, which indicates each twin has its placenta.

The highest risk for TTTS is in monochorionicity, which is more common in monochorionic diamniotic twins than monochorionic monoamniotic twins.

To diagnose TTTS before birth, an ultrasound needs to show one placenta, one twin with too little amniotic fluid (oligohydramnios), and the other with too much amniotic fluid (polyhydramnios). Oligohydramnios is normally defined as a fluid measure of less than 2 cm, while polyhydramnios is a measure of more than 8 cm. Differences in growth rates can occur between the twins, but it’s not needed to diagnose TTTS. In monochorionic monoamniotic twins, the signs include polyhydramnios and differences in the amount of fluid in the fetal bladder.

What Causes Twin-to-Twin Transfusion Syndrome?

Twin-to-twin transfusion syndrome (TTTS) mainly happens because there are too many connections between the arteries and veins deep in the placenta. These connections occur in the and allow blood to pass between them. However, when they are not balanced, blood can be sent more to one twin and less to the other.

There are also connections found at the surface of the placenta which can flow in both directions. These are thought to help protect against TTTS, and are often less common in twins experiencing this syndrome. Some twins are believed to have more of these protective connections, which may explain why TTTS rates are lower in these twins.

One twin experiencing low blood volume can cause less blood to flow to the kidneys, activating the body’s system for blood pressure and fluid balance. This can lead to less urine production and low levels of amniotic fluid. The other twin, with too much blood volume, can experience heart stretch. This triggers the release of peptides that decrease the system for blood pressure and fluid balance, leading to too much urine and amniotic fluid production.

One twin (the recipient) can have heart valve insufficiency, difficulties with heart filling, and narrowed or closed off pulmonary valves. On the other hand, the donor twin can experience changes in blood vessels due to increased collagen synthesis and overgrowth of the blood vessel wall and smooth muscle layers.

Risk Factors and Frequency for Twin-to-Twin Transfusion Syndrome

Twins make up about 2% to 4% of births worldwide. In the United States, according to data from the Centers for Disease Control and Prevention, twins accounted for about 3% of all live births in 2018. This is a significant increase from 1.8% in the year 1980. Types of twin pregnancies differ, with about 67% being two-egg twins (dizygotic), and 33% being identical twins (monozygotic). Of these identical twins, roughly 75% are MCDA twins.

The Twin-to-Twin Transfusion Syndrome (TTTS), a serious condition that can affect identical twin pregnancies, is found in about 8-10% of MCDA twin pregnancies and about 6% of MCMA twin pregnancies. Overall, TTTS affects around 1 to 3 in every 10,000 births.

Twins can also occur in in vitro fertilization (IVF) pregnancies, and thus TTTS can also occur in these cases. The prevalence of each stage of TTTS varies, and it’s estimated by the Society for Maternal-Fetal Medicine (SMFM) as follows:

Stage I: 11% to 15%
Stage II: 20% to 40%
Stage III: 38% to 60%
Stage IV: 6% to 7%
Stage V: 2%

Signs and Symptoms of Twin-to-Twin Transfusion Syndrome

In pregnancies where twin-to-twin transfusion syndrome (TTTS) is suspected, certain physical signs in the fetuses can be observed. What exactly is seen will depend on the stage of the illness. However, the minimum expectation is to have low levels of amniotic fluid (oligohydramnios) in one sac and excessive amniotic fluid (polyhydramnios) in the other. Furthermore, in pregnancies where twins share one amniotic sac (monoamniotic), there can be uneven amounts of amniotic fluid present and noticeable differences in the size of the fetuses’ bladders. In severe instances of low amniotic fluid, ultrasound may reveal that the amniotic sac surrounding the ‘donor’ twin (who is providing the blood) seems to be fixed or “stuck” to the twin.

Meanwhile, not all moms carrying twins with TTTS will have symptoms, or they may experience symptoms before or after TTTS is diagnosed. When asked about their experiences, almost half of the women with a TTTS-complicated pregnancy reported having symptoms before a firm diagnosis was made. The most common symptoms reported include:

Rapid weight gain
A sensation of swelling or bloating
Pain
Contractions
Other unspecified symptoms

Testing for Twin-to-Twin Transfusion Syndrome

According to the SMFM Guidelines on Twin-to-Twin Transfusion Syndrome (TTTS), a type of ultrasound that checks for twin viability, chorionicity (the type of placentation in twin pregnancies), crown-rump length (a measurement of the fetal size) and nuchal translucency (the fluid collection at the back of a baby’s neck) is recommended for women carrying twins between the 10th and 13th weeks. Any abnormalities at this stage could be an early indication of TTTS. Other ultrasound findings that might suggest TTTS are abnormalities in the umbilical cord and the intertwin membrane (the membrane between the two babies).

Once twin gestation (pregnancy) is established, women should return for ultrasound appointments every 2 to 4 weeks to check for TTTS. This condition usually develops during the second trimester, commonly between the 16th and 26th weeks.

Starting from the 16th week, the ultrasound appointments will involve checking the fluid amount in each amniotic sac and looking at each baby’s bladder, with repeat scans every two weeks up until delivery. The frequency of this careful monitoring is driven by the fact that TTTS can progress at different speeds depending on the pregnancy.

When it comes to choosing the right time for delivery in pregnancies affected by TTTS, there are many factors to consider. Therefore, it’s usually decided on a case-by-case basis, but if possible, it’s typically recommended to plan for delivery between the 34th and 37th weeks. Considering the higher risk of preterm birth in twins, the SMFM also advises the possibility of using steroids between the 24th and 34th weeks of pregnancy to help mature the babies’ lungs.

While there is limited data on the effectiveness of using Doppler studies (a type of ultrasound that uses sound waves to measure and assess blood flow) of the umbilical artery as a screening tool for TTTS, the SMFM still suggests that it can be useful when there’s an observed size and/or fluid discrepancy. When TTTS is diagnosed, these Doppler studies become even more critical in understanding the condition’s stage.

The SMFM recommends fetal echocardiography (an ultrasound of the baby’s heart) in twin gestations due to the increased risk of congenital heart disease, especially in TTTS situations, which can put more strain on the recipient twin’s heart. Furthermore, due to the increased risk of preterm labor, miscarriage, and shortened cervix in twins and TTTS affected pregnancies, regular checks on the cervical length are also advised.

The mother and her partner should also receive appropriate counseling regarding this condition and its implications.

Treatment Options for Twin-to-Twin Transfusion Syndrome

Once twin-to-twin transfusion syndrome (TTTS) is diagnosed, there are several ways to manage it. These include careful monitoring, removing excess amniotic fluid (amnioreduction), creating a hole in the barrier separating the twins (septostomy, which isn’t commonly done nowadays), using a laser to seal off problematic blood vessels (fetoscopic laser photocoagulation), reducing the number of fetuses (selective reduction), and ending the pregnancy.

Amnioreduction is often used to correct excessive levels of amniotic fluid and can be done any time after 14 weeks of gestational age. Selective reduction is usually only considered if the TTTS has advanced to stage III or IV.

Fetoscopic laser photocoagulation is a procedure performed under ultrasound guidance, typically between 15 and 26 weeks of gestation, to create separate supplies of blood for each twin. The operation can be done outside this timeframe, but there are increased risks: before 16 weeks, there’s a higher risk of preterm premature rupture of the membranes (PPROM), and after 25 weeks, the procedure becomes harder due to the increased size of blood vessels.

The “Solomon technique” of fetoscopic laser photocoagulation was developed to reduce the chance of TTTS recurrence and increase the survival of the fetuses, though there is a higher risk of the placenta separating from the uterus wall prematurely (placental abruption). A 2019 study recommended a modified version of this technique which balances the need to seal off enough blood vessels with preserving a healthy placenta.

How TTTS is managed depends on the stage of the condition and how far the pregnancy has progressed.

– Stage I: Here, the usual recommendation is careful monitoring, as the outcomes are similar to other interventions. Weekly ultrasound checks can be considered. Only about 25% of Stage I TTTS worsens, and with careful monitoring, the survival of at least one twin happens in a majority of pregnancies.

– Stage II, III, IV: In these stages, fetoscopic laser photocoagulation is recommended if the gestational age is less than 26 weeks. A study showed better results with this technique, including increased survival rates for one or both twins, delivery at a later gestational age, and improved neurological outcomes. However, this study did not include Stage I TTTS, so its results should not guide the management of Stage I TTTS.

– Stage V: There is currently no evaluated intervention for this stage.

Physicians must consider several conditions when diagnosing Twin-to-twin transfusion syndrome (TTTS). Some possible conditions include:

Preliminary rupture of membranes (PPROM)
Premature rupture of membranes
Anomalies causing difference in amniotic fluid levels between the twins
Selective fetal growth restriction (sIUGR), where one twin is less than 10% of the expected weight for their stage of development
Twin Anemia Polycythemia Sequence (TAPS), either spontaneously occurring or due to complications from laser therapy treatment

To recognize these conditions, the mother is often asked if she has experienced symptoms like fluid leakage with or without contractions, indicating potential membrane rupture.

It’s also relevant to note that growth differences and TAPS can occur as part of TTTS, or independently from it. The presence of TAPS is often indicated by unusual blood flow readings in the twins’ middle cerebral arteries, revealing anemia in the donor twin and polycythemia (excess red blood cells) in the recipient twin when checked via ultrasound.

What to expect with Twin-to-Twin Transfusion Syndrome

The outcome for patients can vary greatly depending on the stage and severity of their disease, and the point in the pregnancy when the diagnosis is made. A diagnosis made earlier in a pregnancy, and if the disease is at a higher stage, can mean a worse outcome. The survival rate for one twin can be anywhere between 15% to 70%. About half the time, both twins survive, even with treatment.

The brightest outlook is for those diagnosed at Stage I. Among these patients, about 86% survive, and about 75% of these cases remain stable or even improve over time. There isn’t much information for Stages II to IV, but the death rate for babies at Stage III or higher is estimated to be between 70% to 100%.

Concerning Stage V, after the death of one twin, the other twin has a 10% chance of dying and a 10 to 30% chance of having a neurological complication. Some studies suggest that the surviving twin may have a better neurological outcome if they were treated earlier in the pregnancy with a procedure called fetoscopic laser photocoagulation.

Possible Complications When Diagnosed with Twin-to-Twin Transfusion Syndrome

As previously mentioned, Twin to Twin Transfusion Syndrome (TTTS) carries a risk of one or both twins not surviving, with the survival rates of both twins at about 50%. There can also be heart issues in both twins such as abnormal heart valve function, difficulty in filling the heart chambers, narrow or closed lung artery in the recipient twin; and changes in the blood vessels due to excess protein synthesis and thickening of the vessel and muscle layers in the donating twin. Generally, twins have a higher chance of being born prematurely, which is also a risk in TTTS. There can be neurological issues arising from TTTS and premature birth, causing cerebral palsy and long-term brain development issues.

Various complications can emerge based on how TTTS is managed. For instance, expecting the condition to resolve on its own could lead to the condition progressing further, particularly if it’s advanced at diagnosis; 75% cases of stage one TTTS stay the same or get better without treatment. Possible complications from a procedure known as amnioreduction include the risk of one or both twins not surviving (with survival rates post-procedure ranging from 50% to 65%), needing repeat amnioreductions, premature rupture of membranes (PPROM), premature labor, placental detachment, infection, and lower success of potential future laser photocoagulation. There’s also an increased risk of poor brain outcomes after amnioreduction, compared to a procedure known as fetoscopic laser photocoagulation.

While fetoscopic laser photocoagulation is the recommended treatment for stages II-IV, it too has potential complications like premature membrane rupture, preterm delivery, leakage of amniotic fluid outside the womb, placental detachment, vaginal bleeding, infection, fetal death, recurring TTTS, and twin anemia-polycythemia sequence (TAPS). However, this method has a lower risk of causing cerebral injury, cerebral palsy, and brain developmental issues compared to amnioreduction.

Risks of TTTS:

Increased risk of Twin Mortality
Cardiac complications
Premature delivery
Neurological deficits
Poor brain outcomes after amnioreduction

Risks of various TTTS management:

Expectant management: progression of the condition
Amnioreduction: repeat amnioreductions, PPROM, premature labor, placental detachment, infection
Fetoscopic laser photocoagulation: premature membrane rupture, preterm delivery, leakage of amniotic fluid, placental detachment, vaginal bleeding, infection, fetal death, recurring TTTS, twin anemia-polycythemia sequence (TAPS)

Preventing Twin-to-Twin Transfusion Syndrome

It’s important for patients to understand that certain symptoms could signal a condition called twin-to-twin transfusion syndrome (TTTS). These symptoms could include things like contractions or a sudden increase in size. If these symptoms occur, patients should immediately report them to their healthcare provider. This would aid in detecting TTTS sooner. Once TTTS is diagnosed, the healthcare provider should explain the patient about the outlook of the condition. This would be based on the stage of the condition, possible treatments they could consider, and how one might manage it. They would also talk about any risks and benefits attached to these treatment options and explain how the condition might progress. The healthcare provider should also discuss the chances of the child having health problems after birth, most importantly, any issues related to the nervous system.

Frequently asked questions

The prognosis for Twin-to-Twin Transfusion Syndrome (TTTS) can vary depending on the stage and severity of the disease, as well as the timing of the diagnosis. The survival rate for one twin can range from 15% to 70%, and about half the time, both twins survive with treatment. The prognosis is brightest for patients diagnosed at Stage I, with an 86% survival rate and a 75% chance of remaining stable or improving over time. However, for babies at Stage III or higher, the death rate is estimated to be between 70% to 100%.

Twin-to-Twin Transfusion Syndrome (TTTS) mainly happens because there are too many connections between the arteries and veins deep in the placenta.

The signs and symptoms of Twin-to-Twin Transfusion Syndrome (TTTS) can vary depending on the stage of the illness and whether the twins share one amniotic sac or not. However, some common signs and symptoms include: 1. Low levels of amniotic fluid (oligohydramnios) in one sac and excessive amniotic fluid (polyhydramnios) in the other sac. 2. Uneven amounts of amniotic fluid and noticeable differences in the size of the fetuses' bladders in pregnancies where twins share one amniotic sac (monoamniotic). 3. In severe cases of low amniotic fluid, the amniotic sac surrounding the "donor" twin (who is providing the blood) may appear fixed or "stuck" to the twin. 4. Rapid weight gain. 5. A sensation of swelling or bloating. 6. Pain. 7. Contractions. 8. Other unspecified symptoms. It is important to note that not all moms carrying twins with TTTS will have symptoms, or they may experience symptoms before or after TTTS is diagnosed. Almost half of the women with a TTTS-complicated pregnancy reported having symptoms before a firm diagnosis was made.

The types of tests that are needed for Twin-to-Twin Transfusion Syndrome (TTTS) include: 1. Ultrasound: - Type of ultrasound that checks for twin viability, chorionicity, crown-rump length, and nuchal translucency between the 10th and 13th weeks of pregnancy. - Ultrasound appointments every 2 to 4 weeks starting from the 16th week of pregnancy to check for TTTS. - Checking the fluid amount in each amniotic sac and looking at each baby's bladder with repeat scans every two weeks up until delivery. 2. Doppler Studies: - Doppler studies of the umbilical artery can be useful when there's an observed size and/or fluid discrepancy. - These Doppler studies become even more critical in understanding the stage of TTTS once it is diagnosed. 3. Fetal Echocardiography: - Fetal echocardiography, which is an ultrasound of the baby's heart, is recommended in twin gestations due to the increased risk of congenital heart disease, especially in TTTS situations. 4. Cervical Length Checks: - Regular checks on the cervical length are advised due to the increased risk of preterm labor, miscarriage, and shortened cervix in twins and TTTS-affected pregnancies. It is important to note that the specific tests and their timing may vary depending on the stage of TTTS and the gestational age of the pregnancy.

The doctor needs to rule out the following conditions when diagnosing Twin-to-Twin Transfusion Syndrome (TTTS): 1. Preliminary rupture of membranes (PPROM) 2. Premature rupture of membranes 3. Anomalies causing a difference in amniotic fluid levels between the twins 4. Selective fetal growth restriction (sIUGR), where one twin is less than 10% of the expected weight for their stage of development 5. Twin Anemia Polycythemia Sequence (TAPS), either spontaneously occurring or due to complications from laser therapy treatment

The side effects when treating Twin-to-Twin Transfusion Syndrome (TTTS) can vary depending on the specific treatment method used. Here are the potential side effects associated with each treatment: 1. Amnioreduction: - Risk of one or both twins not surviving (survival rates range from 50% to 65%) - Need for repeat amnioreductions - Premature rupture of membranes (PPROM) - Premature labor - Placental detachment - Infection - Lower success of potential future laser photocoagulation - Increased risk of poor brain outcomes compared to fetoscopic laser photocoagulation 2. Fetoscopic laser photocoagulation: - Premature membrane rupture - Preterm delivery - Leakage of amniotic fluid outside the womb - Placental detachment - Vaginal bleeding - Infection - Fetal death - Recurring TTTS - Twin anemia-polycythemia sequence (TAPS) - Lower risk of causing cerebral injury, cerebral palsy, and brain developmental issues compared to amnioreduction It's important to note that the risks and side effects may vary in severity and occurrence depending on individual cases and the stage of TTTS.

A maternal-fetal medicine specialist or a perinatologist.

Twin-to-Twin Transfusion Syndrome affects around 1 to 3 in every 10,000 births.

Twin-to-Twin Transfusion Syndrome (TTTS) can be treated in several ways depending on the stage of the condition and the gestational age of the pregnancy. Treatment options include careful monitoring, amnioreduction to remove excess amniotic fluid, septostomy to create a hole in the barrier between the twins (although this is not commonly done nowadays), fetoscopic laser photocoagulation to seal off problematic blood vessels using a laser, selective reduction to reduce the number of fetuses, and ending the pregnancy. The specific treatment approach will vary based on the severity of TTTS and how far the pregnancy has progressed.

Twin-to-Twin Transfusion Syndrome (TTTS) is a condition that may occur in twins that share a single placenta. It is characterized by one twin having too little amniotic fluid (oligohydramnios) and the other twin having too much amniotic fluid (polyhydramnios).