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Twin to Twin Transfusion Syndrome: Overview and Summary

by Mary Slaman-Forsythe

• Twin to twin transfusion syndrome (TTTS) is a disease of the placenta (or afterbirth) that affects identical twin pregnancies.
  
  
• TTTS affects identical twins (or higher multiple gestations), who share a common monochorionic placenta.
  
  
• The shared placenta contains abnormal blood vessels, which connect the umbilical cords and circulations of the twins.
  
  
• The common placenta may also be shared unequally by the twins, and one twin may have a share too small to provide the necessary nutrients to grow normally or even survive.
  
  
• The events in pregnancy that lead to TTTS - the timing of the twinning event, the number and type of connecting vessels, and the way the placenta is shared by the twins - are all random events that have no primary prevention (see section on The Monochorionic Placenta), is not hereditary or genetic, nor is it caused by anything the parents did or did not do. TTTS can happen to anyone.

• Depending on the number, type and direction of the connecting vessels, blood can be transfused disproportionately from one twin (the donor) to the other twin (the recipient).
  
  
• The transfusion causes the donor twin to have decreased blood volume. This in turn leads to slower than normal growth than its co-twin, and poor urinary output causing little to no amniotic fluid or oligohydramnios (the source of most of the amniotic fluid is urine from the baby).
  
  
• The recipient twin becomes overloaded with blood. This excess blood puts a strain on this baby's heart to the point that it may develop heart failure, and also causes this baby to have too much amniotic fluid (polyhydramnios) from a greater than normal production of urine.
  
  
• TTTS can occur at any time during pregnancy, even while a mother is in labor at term. The placental abnormalities determine when and to what degree a transfusion occurs between the twins.
  
  
• Chronic TTTS describes those cases that appear early in pregnancy (12-26 weeks' gestation). These cases are the most serious because the babies are immature and cannot be delivered. In addition, the twins will have a longer time during their development in the womb to be affected by the TTTS abnormalities. Without treatment, most of these babies would not survive and of the survivors, most would have handicaps or birth defects.
  
  
• Acute TTTS describes those cases that occur suddenly, whenever there is a major difference in the blood pressures between the twins. This may occur in labor at term, or during the last third of pregnancy whenever one twin becomes gravely ill or even passes away as a result of the abnormalities in their shared placenta. Acute TTTS twins may have a better chance to survive based on their gestational age, but may have a greater chance of surviving with handicaps.

How Often Does Twin to Twin Transfusion Syndrome Occur?

• Based on 1998 USA statistics (from the CDC), the rate of multiple births per year is now 1:36 (2.81%) births or approximately 111,000 twins or higher multiples.
  
  
• The majority of identical twins share the placenta (monochorionic), and of these approximately 15% go on to develop TTTS.
  
  
• By extrapolating the number of expected identical twins (about one-third) from the annual twin births, and from the number of expected monochorionic identical twins (about two-thirds), and from these the number thought to develop TTTS (about 15%), there are at least 3,600 TTTS cases per year in the U.S. alone with over 7,200 babies affected:

110,700 X .33 X .66 X .15 = 3,600 cases of TTTS per year in U.S.

• Since spontaneous pregnancy loss (spontaneous abortion) and pregnancy terminations (elective abortions) that occur prior to 20 weeks go uncounted by the CDC, 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 often produces. Studies show a higher rate of identical twins than occur naturally in patients having these treatments

What Happens to the Twin Babies Affected by TTTS?

• The tragedy of TTTS is that there are two babies (at least) who begin the pregnancy healthy, without genetic defects, who suffer consequences related to their placenta type.
  
  
• The historic twin survival rate with chronic TTTS was less than 10% before doctors could make the diagnosis in the womb by ultrasound. With the introduction of ultrasound (in 1980), the survival odds greatly improved because treatment of the TTTS was now made possible while the mother was still pregnant (see Warning Signs for the babies below).
  
  
• The excess amniotic fluid (polyhydramnios) would cause over distention of the uterus, and pregnancy loss occurred when the mother went into premature labor or the baby's bag of water broke.
  
  
• In some circumstances the recipient twin may pass away (from heart failure due to the excess blood), or in other cases the donor (from the loss of blood or having a placental share too small to receive the necessary nutrients). This sometimes made the situation better for the other twin, but in half of the cases the other twin also passed away or survived with severe birth defects.

Over the last 20 years, the following factors have come to be thought important in predicting outcomes in TTTS:

Gestation Age at Diagnosis: Prior to 25 weeks is more serious because the babies cannot be delivered at this time, and they will be exposed to the syndrome longer. Most calls to the Foundation are from couples at eighteen weeks' gestation.

Gestational Age at Delivery: At 28 weeks and beyond, or with an estimated birth weight of 1500gm (3lbs. 5oz.) or more, doctors become more optimistic regarding the outcome for the twins with delivery. In TTTS, the doctors are often faced with the question, 'Are the babies better off out than in?' as they trade off the risks of early delivery versus continuing a TTTS pregnancy.

Degree of Growth Discordance: This implies that the babies are found to be different sizes on the ultrasound scan. A difference of over 20% is though significant, but this depends on gestational age that the difference appears (sometimes the difference is given in weeks rather than a percentage). The twin's size difference may be due to either the transfusion of nutrients or unequal sharing of the common placenta or both.

Degree of Discordance in Amniotic Fluid: The recipient may have quarts of excess amniotic fluid (polyhydramnios) and its bladder always appears full on ultrasound scan. The donor may produce so little urine that its amniotic sac may be empty (oligohydramnios) and the baby's bladder impossible to see with ultrasound.

Presence of Hydrops in One Twin: Hydrops implies fluid buildup in the baby's skin and body cavities, and is usually due to heart failure. It can be seen on ultrasound, and it usually involves the recipient twin who is overwhelmed with too much blood.

• TTTS outcomes are ultimately determined by the number and type of connecting blood vessels, and the way the twins share the placenta (which both occur randomly). Since no two placentas are the same, the outcome is always hard to predict.
  
  
• Regardless of the therapy chosen, the majority of TTTS survive and majority of survivors will be normal. However, the various treatments available do differ in their outcomes: the number of survivors, the number of healthy survivors, and the ability to prolong pregnancy (see Treatments below and the section containing Medical Research and Articles).
  
  
• The majority of TTTS twins, with and without treatment, will be born prematurely and need to spend some time in the newborn intensive care unit.

What are the Warning Signs of Twin to Twin Transfusion Syndrome?

Warning signs in the mother include:

• The sensation of a rapid growth of the womb
  
  
• A uterus that measures large for dates
  
  
• Abdominal pain or tightness, or uterine contractions
  
  
• Sudden increases in body weight
  
  
• Hand and leg swelling in early pregnancy

Warning signs in the twins appear on ultrasound scans and include:

• Evidence of a monochorionic or shared placenta
  
  
• A single placenta
  
  
• Same sex twins
  
  
• A thin, hard to see, dividing membrane

Evidence of TTTS

• Polyhydramnios (excess amniotic fluid) in the sac of one twin
  
  
• Oligohydramnios (decreased to no amniotic fluid) in the sac of the other twin
  
  
• Size differences (discordance) in the twins
  
  
• Hydrops fetalis (water in one baby's body from heart failure)

What are the Available Treatments for Twin to Twin Transfusion Syndrome?

Of all the questions that concern TTTS couples, this seems to be the most important so the answer will be the most comprehensive. The treatments for TTTS pregnancies depend, in part, on when in pregnancy the twins become affected. If the twins are mature enough to survive outside the womb (beyond 25 weeks), immediate delivery is an option for TTTS babies. However, the doctors must weigh the health effects of the prematurity on the twins versus the continued effects of the TTTS abnormalities as they try to prevent any handicaps in the survivors.

The Foundation continuously reviews the latest medical scientific reports to determine for TTTS couples which treatments appear to lead to the highest survival rates for the babies, the highest number of healthy survivors, and the lowest rates of prematurity for the twins. The Foundation also recognizes that it is impossible to save all TTTS twins and completely eliminate the risk of handicap in survivors regardless of treatment because of the nature of the placental abnormalities in TTTS.

The different treatments for TTTS can be classified into those that address the connecting blood vessels in the monochorionic (shared) placenta, those that treat the symptoms, and, sadly, those that reflect a sense of hopelessness on the part of the doctors. We know that none of the treatments have been evaluated in what doctors call 'randomized studies' or 'comparative trials.' A randomized trial means taking a group of TTTS cases and only treating half, then comparing the outcomes in the treated patients to the untreated patients. Such studies may be reasonable in other diseases, but the well documented, historic TTTS death and morbidity (damage) rates calls into question the ethics of such studies. The Foundation does not support this type of experiment for TTTS parents. A comparative trial takes TTTS cases and treats them with one of two or more available therapies to see which has the best outcomes.

Treating of the Connecting Vessels

Fetoscopic Placental Laser Therapy: Since TTTS does not exist in identical monochorionic (MC) twins without the connecting placental blood vessels, it seems reasonable to find a way to separate the twins' blood streams by destroying the connections. The availability of surgical lasers in the early 1980's led this innovative option, and the first fetoscopic laser occlusion of the connecting vessels was performed in 1988 by Dr. Julian E. De Lia at the University of Utah on a couple from Great Falls, Montana. By linking the laser to fetoscopy (the insertion of a tiny telescope into the pregnant uterus), doctors are able to see and destroy all the connecting vessels. This operation is the only TTTS treatment that can 'disconnect' the twins and stop both the chronic transfusion of blood from the donor to the recipient, and the acute or sudden transfusion should one baby pass away or become suddenly ill.

This laser surgery is now performed in centers throughout the world as more and more doctors are convinced that this will lead to the best outcomes. To the best of our knowledge, placental laser surgery results in the highest numbers of healthy survivors in those patients with previable (i.e., less than 25 weeks' gestation) onset or diagnosis of TTTS. Reports on this therapy currently indicate the following: 80-85% survival of at least one twin, 65-70% overall twin survival, 5% or less significant handicap rates in the survivors, and a treatment to delivery average interval of close to 10 weeks. The results may vary in different centers, and this may reflect different levels of experience or the actual surgical techniques used. The procedure involves general anesthesia for the mother, and the surgical complication rates also vary in different centers. These must be discussed with the individual doctors performing the surgery.

Treating the Symptoms

Therapeutic Reduction Amniocentesis: This is the 'most widely available therapy' and involves draining the excess amniotic fluid (polyhydramnios) by inserting a needle into the amniotic sac of the recipient. It relieves the mother's abdominal discomfort, and prolongs TTTS pregnancies by reducing the risk of spontaneous rupture of the membranes or premature labor from the enlarged uterus. In addition, by reducing the pressure inside the womb, it has been reported to change the nature of the transfusion in some TTTS cases. Survival rates with amniocenteses approach 80% in some centers, but health status of surviving infants are not always reported. Recent reports indicate a 60-75% survival rate with amniocentesis, but 10-30% of the survivors have had neurological (brain) abnormalities when ultrasounds were performed in the nursery. Since the babies remain connected, there is the continuing transfusion process between the twins (both chronic and acute). This may explain the higher rate of medical problems in the surviving babies than methods that disconnect the babies.

Amniotic Septostomy: This is the intentional creation of a hole in the membrane septum between the babies' bags of water with a needle during ultrasound scanning. It allows for some of the excess amniotic fluid in the recipient's bag of water to enter the sac of the donor who usually has no to very little amniotic fluid. In one report of 12 TTTS cases, the septostomy to delivery interval was 8.5 weeks and 83% (20/214) of the twins survived. The health of the surviving twins was not given. The babies remain connected with this, and there is now the additional risks associated with twins who sit in the same sac (monoamnionic) such as possible umbilical cord entanglement.

Medication Therapy: Several drugs have been used in TTTS cases for various purposes. These include:

• Digoxin Therapy for Fetal Heart Failure: Here doctors give this heart medication as pills to the mother, or inject it directly into the twin that is showing signs of heart failure. Giving this medication may help the heart beat stronger when it is overloaded with blood.
  
  
• Indomethacin Therapy to Curtail Amniotic Fluid Production: Here doctors also give this medication to the mother hoping to decrease the urine output in the recipient and lessen the amount of polyhydramious. Indomethacin is an aspirin-like medication (non-steroidal anti-inflammatory drug) with numerous side effects in the baby, one of which is on the kidney where decreased urine production occurs. It is the most powerful drug for treating pre-term labor and is used more often for this purpose in TTTS. When used as a single treatment for TTTS cases, the results have been disappointing.
  
  
• Tocolytic Medications to Stop Premature Labor: In addition to indomethacin, there are several other drugs that are used in TTTS cases to stop labor.

Treatments Which Reflect Hopelessness

Termination of the Entire Pregnancy: When pregnancy termination (induced abortion) is recommended by doctors and counselors, it is done so not as a treatment, per se, but as a reflection of their lack of faith in the available therapies for TTTS. The Twin to Twin Transfusion Syndrome Foundation is a pro-twin and, therefore, a pro-life organization. We are in the business of hope, and there is always hope. Certain doctors refuse to believe that parents would risk any health problems in their surviving TTTS babies, and would terminate all TTTS cases despite the fact that the majority of twins survive and are normal regardless of treatment used. Some physicians accomplish this end by 'passive neglect.' This is where there are signs of significant TTTS on ultrasound, and the doctor asks the patient to return weeks later instead of one week hoping the pregnancy ends in the meantime.

Selective Termination of One Baby by Various Methods: The termination of one twin (with the hope that the pregnancy will continue for the other) is undertaken for various reasons. Perhaps the most justifiable reason is when a severe birth defect baby, known as an acardiac MC twin (here an identical twin is deformed and does not have a formed heart), is kept 'alive' by the normally formed twin who pumps blood to the acardiac twin through the placental blood vessel connections. The normal 'pump' twin may go into heart failure due to the strain. The various techniques to separate these twins include ligation of the umbilical cord with suture, or the cauterization of the cord with laser or electric current. Methods must be used that occlude the umbilical cord or major fetal vessels in the deformed baby to avoid death or damage (especially of the brain) to the other normal baby as a result of an acute transfusion through the connections. Sadly, some doctors use this technique in TTTS when they either fail at attempted laser surgery, or when they feel that one twin may have a poor outlook. We have seen babies in heart failure with hydrops, a chosen baby for cord ligation, have laser surgery and live and be completely healthy.

Is There Anything I Can Do to Help My Babies and Myself?

• With few exceptions the pregnant woman's health status is virtually ignored once the twins are determined to have TTTS. Both the doctors and couples focus on the ultrasound findings and condition of the babies.
  
  
• There are things that mothers can do to benefit the babies and themselves right away, which may play a role in the outcome of TTTS pregnancies. These are related to changes in diet and activity.

  Dietary Changes

• It seems that most women with TTTS at mid-pregnancy are found to be malnourished. Anemia, low blood protein, decreased calorie intake and dehydration are common findings.
  
  
• Many women with multiple gestations have morning sickness or poor appetites that may be worse than that seen with only one baby. It may be frustrating and upsetting not to be able to eat well. This below normal intake of nutrients, combined with the needs of twin babies and some of the mother's changes in TTTS (e.g., a womb that is more than twice the normal size for the time of pregnancy) may all contribute to the development of malnutrition.
  
  
• There are two unusual circumstances in TTTS that could make a mother's weight go up despite decreasing her dietary intake. These cause inaccuracies in determinations of nutritional status when one weighs themselves on a scale:
  
  
  1. When the recipient develops polyhydramnious (excess amniotic fluid), this water in the womb adds to the mother's weight.
     
     
  2. The second is also water weight, but this is the effect of swelling or edema that occurs throughout the mother's body whenever her blood protein levels drop to abnormally low levels.
• The Foundation has explored a number of ways for women to help solve this problem and found that the most efficient way to recover the losses, and prepare for the rest of the pregnancy, is to take liquid dietary supplements (e.g., Carnation Instant Breakfast, Ensure Plus, and others that are soy based) sipped slowly, continuously throughout the day in addition to whatever you can eat at meals. If your morning sickness is still present, try your best with the supplements and liquids until it passes.
  
  
• The sensation of thirst is also common, and seems unusual in the face of excess body water. We recommend soy milk or athletic drinks (e.g., Gatorade.) to provide more than just water for you and your babies.

  Activity changes

• The benefits of best rest (or lying on a couch or the floor) in multiple gestation has always been debated by doctors. However, TTTS is a high-risk complication in which all possible beneficial remedies should be utilized to improve outcomes. Horizontal rest should be used.
  
  
• Horizontal rest (on your side) will help your blood flow and oxygen to your womb, and aid in removing some of the excess edema fluid in your body.
  
  
• Work is problematic for many women affected by TTTS. Studies have shown a definite relationship of physically demanding work to adverse outcome in pregnancy. Given the high-risk nature of a TTTS multiple pregnancy, we recommend a leave of absence for the duration, especially if you are undergoing one of the treatments outlined above.

Conclusion and Personal Note From the Foundation

Twin to twin transfusion syndrome affects 15% of monochorionic identical twin pregnancies. We estimate 3,600 cases annually in the U.S. (most definitely much higher) so you are not alone. It occurs from abnormalities in the twins' shared placenta that occur spontaneously and, as far as we know, cannot be prevented. The outlook for twins with TTTS was hopeless over 20 years ago, but now we have the ability to diagnose the condition early (with ultrasound scans) and implement treatments that will ultimately lead to most of the twins surviving and being healthy. TTTS is still regarded, though, as one of the most challenging problems in modern obstetrics. For you, you have been forced into a high risk world that no one ever talks about or that you could ever be prepared for.

We strongly recommend that you create a medical plan of action from the moment your twins are determined to be monochorionic, because the expertise and interest in TTTS varies widely among doctors. It is considered a 'rare disease' so most physicians see only a few cases a year if at all. You have to be your babies' advocate. It is important to have consultations with a high-risk obstetrician (perinatologist or maternal-fetal medicine specialist), to have frequent ultrasound scans, and be aware of the TTTS warning signs. Do not sit back and listen to doctors or nurses who chalk everything up to it being 'just twins'. Begin to educate yourself on the syndrome and the treatment options so if things get worse, or if an immediate decision regarding treatment is necessary, you can choose what you feel is the best for you and your babies. Follow that inner voice inside you, and trust it.

Sadly, some of our TTTS parents have had to fight for their babies all the way with their doctors and insurance companies. You want to know in your heart, now and for the rest of your life, that you did everything possible to save your babies. The Foundation is a pro-twin and pro-life organization that is here to help you and your babies in your fight every step of the way, with educational materials, emotional support, and professional referrals. We are here for you.

Mary Slaman-Forsythe, Founder and President The Twin to Twin Transfusion Syndrome Foundation www.tttsfoundation.org

History of Twin to Twin Transfusion Syndrome

Appendix: Twin to Twin Transfusion Syndrome

Web www.childbirthsolutions.com

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