Lives in the Balance: Understanding Twin-Twin Transfusion Syndrome

Twin-twin transfusion syndrome (TTTS) has challenged clinicians, researchers and parents since its identification several decades ago. In this video, the staff of the Center for Fetal Diagnosis and Treatment presents a complete overview of the disorder, including evaluation, treatment and the importance of fetal imaging in obtaining an accurate diagnosis of TTTS versus selective intrauterine growth restriction (sIUGR). The team also discusses how advanced prenatal care provides the best hope for positive outcomes.

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About Twin-to-twin Transfusion Syndrome

Dennis Hasson: That day in the ultrasound room when that technician looked at us like you two know you're having twins.

Marie Hasson: On ultrasound you could see a lot of detail because it was a level two ultrasound.

Mark P. Johnson, MD: It's very uncommon. Only 10, 15% of monochorionic twins develop this type of a syndrome.

Marie Hasson: You could tell they were both girls.

Dennis Hasson: And for one moment it was exciting.

Nahla Kalek, MD, MPH: We still don't know the exact reason behind why certain monochorionic pregnancies are affected by twin-to-twin transfusion syndrome.

Marie Hasson: I could see the screen that something was wrong. There wasn't any fluid in the one sac at all.

Nahla Kalek, MD, MPH: It results from an imbalance in the flow between specific blood vessels that are in the placenta of monochorionic pregnancies.

Mark P. Johnson, MD: They don't share the placenta equally.

Dennis Hasson: That doctor came in, took a look at these ultrasounds.

Marie Hasson: He didn't say a word. He just was looking and kind of taking notes. And then he brought us into his office and shut the door and he said, "This is going to be a very difficult pregnancy."

Mark P. Johnson, MD: Twin-twin transfusion syndrome is a complicated disorder.

Joy N. Macdonald, RN: The serious complication of monochorionic or identical twin pregnancies.

Mark P. Johnson, MD: Monochorionic meaning that they share a placenta.

Susan R. Miesnik, MSN: In a monochorionic diamniotic pregnancy there is one chorion, which is the outer sac, and each twin is in its own amnion, so that it's like a single balloon with two filled balloons inside it.

N. Scott Adzick, MD: One twin, the recipient twin, gets too much blood. And the other twin, the donor twin, doesn't get enough blood.

Mark P. Johnson, MD: Because the amount of oxygen and nutrition going to the donor baby is less than to the recipient baby, they grow at different rates.

Susan R. Miesnik, MSN: One twin will end up being very large, having excessive amniotic fluid around it or polyhydramnios.

Mark P. Johnson, MD: The opposite kind of occurs in the smaller baby, or the donor baby.

Susan R. Miesnik, MSN: The other twin on ultrasound will show itself as being very small for gestational age. It will have decreased amniotic fluid or actually no fluid.

Mark P. Johnson, MD: Over time the amniotic fluid around the donor baby shrinks away until literally the baby becomes shrink wrapped along the side of the uterine wall or placenta.

Susan R. Miesnik, MSN: As this disease progresses, you end up seeing cardiac changes in both of the babies.

Jack Rychik, MD: When we begin to see cardiac changes, one can have significant complications as a consequence, which can lead to either residual issues that these fetuses face or even death in either the recipient or the donor. 

'Like a Fingerprint'

N. Scott Adzick, MD: In a way, twin-twin transfusion syndrome is an unsolved problem. We still don't completely understand the underlying pathophysiology, for instance, and that's why research is important.

Jack Rychik, MD: The disease, we think, is related to abnormal connections of vessels that are shared between the two twins.

N. Scott Adzick, MD: Each case is really unique. It's almost — the term we use, "It's almost like a fingerprint."

Jack Rychik, MD: There is an abnormality of the vessels within the placenta such that these abnormal connections lead to a change in volume, a change in blood delivery between the two twins.

Mark P. Johnson, MD: There are no two placentas that are exactly the same. The number of branches of blood vessels, where they are in the placenta, where they go, the number of communications is unique and different for each case.

Nahla Kalek, MD: In addition to being unpredictable, every pregnancy is independent in terms of how rapidly or how stable the condition remains.

N. Scott Adzick, MD: One has to follow the case extremely closely and be prepared for every possible eventuality because that may affect further diagnostic studies and treatment.

Mark P. Johnson, MD: And that's why treating twin-twin transfusion is so challenging.

Susan R. Miesnik, MSN: Every patient presents with a different situation. Every patient progresses through the disease process and the pregnancy with a different sort of scenario.

Lori J. Howell, RN: So all of those scenarios mean we have to tailor the information about possible treatment strategies to those individual findings at the evaluation.

Diagnosis and Decisions

Mark P. Johnson, MD: Many times twin-twin transfusion is first suspected when you have a twin pregnancy that appears to be monochorionic or shares a placenta and there's a size difference between the baby and an amniotic fluid volume difference.

Nahla Kalek, MD: The information that we receive from our referring physicians allows us to be able to ascertain how urgent we would need to evaluate our patients.

Lori J. Howell, RN: So we make arrangements very shortly, usually within one to two days, for them to visit the center.

Nahla Kalek, MD: If we feel that based on the information that we receive that the clinical situation is critical, then we will make certain to see our patients within 24 hours.

Joy N. Macdonald, RN: When I initially talk to families I get a sense of what they understand of the pregnancy. I also try to allay a little bit of their fear by telling them that we're not certain what the diagnosis is and it's important for them to come in for an evaluation so that we can confirm the diagnosis.

N. Scott Adzick, MD: There are other conditions that can mimic the findings. As a matter of fact for every 10 referrals that we get about two out of the 10 prove to be something else.

Lori J. Howell, RN: There's typically five areas we look at. Is there one placenta? Are they the same sex? Is there the same amount of fluid in one sac versus the other sac? How are the cords inserted? And then importantly, what are the cardiac ECHO findings?

Nahla Kalek, MD: When patients arrive to our center for evaluation, part of their evaluation consists of a very detail-oriented ultrasound examination, as well as a detail-oriented fetal echocardiogram.

Jack Rychik, MD: Because we believe the origins of the disease of twin-twin transfusion syndrome are cardiovascular, it is essentially important to begin the evaluation process implementing fetal echocardiography.

Nahla Kalek, MD: Utilizing the results from the examinations, including the ultrasound examination as well as the fetal echocardiogram, we can then create a composite, which allows us to stage the twin-twin transfusion syndrome.

Lori J. Howell, RN: Once that evaluation is complete, that same day we sit down with the family and go over the results of those tests and explain what their options are for the pregnancy and what would most likely be the scenarios that would happen depending upon which option they chose.

Mark P. Johnson, MD: We try to be non-directive. We try to first of all present what the problem is, what we believe the pathologic process is, why it's progressive. We then present all the forms of therapy.

Joy N. Macdonald, RN: The consultation period is a time for families to ask as many questions as they have.

Mark P. Johnson, MD: We really put it out on the table. We educate them about the risks, the potential benefits, what's reported in the literature as to survivals, complications, outcomes. And then we really work in concert with the family to decide what's the best thing for them.

The Importance of Monitoring

Jack Rychik, MD: Twin-twin transfusion syndrome is not simply a phenomenon of a difference in size. It has a cardiovascular origin to it.

Nahla Kalek, MD: There are certain characteristics, which we've come to appreciate, that are the result of each fetus's adaptation or adaptive response to the changes that occur secondary to twin-twin transfusion syndrome. As a result, we've been able to develop a CHOP cardiovascular scoring system.

Jack Rychik, MD: Between fetal cardiologists and maternal-fetal medicine and perinatology experts, it was the combining of their experiences in observing this twin-twin transfusion phenomenon that really has resulted in the development of this very, very unique scoring system.

Joy N. Macdonald, RN: The entire pregnancy has to be monitored extremely closely. It has to be monitored for signs that the babies are developing heart failure.

N. Scott Adzick, MD: The fetal heart is sort of the motor that makes the fetus run and the placenta run. And that's usually the end stage pathophysiologic event that leads to either death or neurologic complications. So it's important that we follow the fetal heart closely.

Jack Rychik, MD: There are five domains that exist within the twin-twin transfusion score. The first four domains relate to characteristics of the recipient and the fifth relates to characteristics in the donor.

Lori J. Howell, RN: By looking specifically at the heart of both twins, they are able to tell subtle changes, when a heart might be going into cardiac failure, when to intervene with a laser before going into cardiac failure, and in some instances some prediction of heart disease.

Jack Rychik, MD: Not only is the score helpful in our decision tree in understanding who can benefit from intervention, it also is a means potentially for prognosis.

Nahla Kalek, MD: We have actually utilized the same system to gauge the response postoperatively. And what we've come to appreciate and what is extraordinarily remarkable is that the cardiac changes that we see preoperatively as a result of twin-twin transfusion syndrome can be reversed or resolved postoperatively when we apply the same scoring system.

Jack Rychik, MD: It's still unclear exactly how many patients are going to have residual, long-standing, permanent changes. But what we do know through the use of the score is that the vast majority in fact have fairly good resolution of the cardiovascular findings.

Lori J. Howell, RN: So it really takes very experienced and focused talents just looking at fetal echocardiograms.

Treatment Options

Susan R. Miesnik, MSN: Patients who have twin-twin transfusion syndrome, especially if they have polyhydramnios in the one twin, can become very uncomfortable physically with this pregnancy because the uterus gets stretched beyond what is normal for that gestational age.

Nahla Kalek, MD: For our moms that are carrying twins affected with twin-twin transfusion syndrome that have been classified as Stage I and are demonstrating signs or symptoms of maternal discomfort, or are having irregular uterine contractions or are demonstrating shortening of the cervix, then amnioreduction is a therapy that can be offered. The idea behind amnioreduction is primarily as a temporizing measure where we can actually draw off the excessive amount of amniotic fluid that's in the recipient fetus's sac in order to provide not only maternal comfort, but also to avoid preterm contractions which can lead to preterm delivery.

Mark P. Johnson, MD: A needle is passed into the amniotic sac under ultrasound guidance just like an amniocentesis would be. Amniotic fluid is then able to be removed so that this excessive fluid is drawn down into more normal range.

Nahla Kalek, MD: Nowadays amnioreduction has a very limited place in the management of twin-twin transfusion syndrome. For our moms who are excluded as operative candidates, either because they are Stage I or for other maternal indications, amnioreduction can be utilized. And when applied to these particular pregnancies can actually demonstrate a halting of the progression of twin-twin transfusion syndrome.

Mark P. Johnson, MD: But sometimes you see progression. You'll see that the heart of the recipient baby is becoming more affected, that the ability to pump blood is worse, that the leaking of the valves is getting worse.

Nahla Kalek, MD: If a pregnancy progresses in terms of upstaging even after amnioreduction, continued ultrasound surveillance is warranted. And at that point a discussion is held with families regarding the next option or next management strategy that can be employed. If gestational age allows for it, then a selective laser can be performed even after an amnioreduction has been utilized.

Susan R. Miesnik, MSN: That's a procedure that's much more invasive to the patient. It requires that the patient go to the operating room.

Nahla Kalek, MD: What happens with our moms is that they are admitted to the Hospital early in the morning. They're taken to the operating room. And under conscious sedation as well as local anesthetic that's applied to the abdomen we can introduce a fetoscope, which then allows direct visualization of these communications so that we can perform a targeted and focused ablation.

Mark P. Johnson, MD: There are blood vessel communications or vascular communications that occur along the surface of the placenta. And the challenge is to be able to recognize where those communications are. And so now using sophisticated endoscopic approaches, we're able to go into the sac of the recipient baby, identify where the umbilical cord inserts into the placenta, and then we literally map every single blood vessel arising from that point out.

Either an artery from one baby connecting straight into the arterial system of the other baby. It can be veins connected to veins directly. Or the most common is when a vessel from one baby enters into the placenta and then comes out of the placenta and goes to the opposite baby.

And then using a laser fiber we're actually able to coagulate, or kind of spot weld, those communications shut.

Susan R. Miesnik, MSN: Effectively separating the single placenta into two separate components, one for each fetus.

Mark P. Johnson, MD: Then each twin has its own placental mass. There's no longer this communication. And hopefully that will interrupt the twin-twin transfusion process and stabilize the situation until you can get out to a gestational age to deliver the babies where there's a good chance of survival.

Nahla Kalek, MD: Although fetoscopic laser coagulation is a minimally invasive procedure, it is a surgical procedure, and as such carries with it specific risks. Those risks include preterm contractions that could ultimately lead to preterm labor and delivery. There's also the risk of preterm rupture of membranes. And the third risk is of membrane separation. The sort of cumulative risks for any one of those complications occurring after laser surgery is in the neighborhood of 10 to 15 percent. Alternatively the risk of not moving forward with an intervention when formally diagnosed with Twin-to-Twin Transfusion Syndrome carries with it a risk of 80 to 85 percent of loss of the pregnancy.

Mark P. Johnson, MD: And so you really have to weigh the risks against the potential benefits.

Nahla Kalek, MD: We are incredibly fortunate to be operating in a center that has allowed for the reception of a tremendous volume of families who are referred to us for twin-twin transfusion syndrome specifically. As a result we've been able to develop a multidisciplinary program that incorporates all levels of care that are specifically targeted towards the care of families affected by twin-twin transfusion syndrome.

Difficult Choices

Martha Hudson, MSW: I think the most difficult thing about twin-to-twin transfusion syndrome is the fact that you have two babies competing for the same thing and that you're trying to make a decision to benefit both babies, but you may not be in a position, the babies may not medically allow that.

Susan R. Miesnik, MSN: In this disease process with the shared placenta the risk becomes if one of the fetuses dies it can have a really negative impact on the other fetus.

Mark P. Johnson, MD: Because the fates of the two babies are linked, if one were to die it puts the other baby at extremely high risk for either death or injury. In those cases you can selectively cut off the blood supply to the baby who's going to die anyway and thus preserve the placenta and the risk of death, or prevent the risk of death or a neurologic injury to the other baby.

Susan R. Miesnik, MSN: Sacrificing that really ill twin for the sake of the other twin. And that's a tremendously agonizing decision for families to have to make. It's almost a Sophie's Choice for them.

Martha Hudson, MSW: I don't think any other anomaly that we deal with is as difficult as that.

Susan R. Miesnik, MSN: The fact that we've worked with them through the pregnancy and we have a relationship with them enables us to help them through that really, really terrible time.

Support When a Family Needs It Most

Martha Hudson, MSW: There is nothing more difficult for a family to cope with than the unknown. And if they are faced with a situation that is very nebulous, that can go either way without good understanding of what the possibilities are, the family will have a much more difficult time coping and making a decision.

Susan R. Miesnik, MSN: Giving parents a sense of control is vital, but it's really very difficult to do.

N. Scott Adzick, MD: When you think about it, if you're a mom in St. Louis and you go to see the obstetrician to find out how the fetus looks, whether you're going to have a boy or a girl, and you're told that the baby has a devastating birth defect, I mean, that's a big load. Then to be told, well, you need to go to Philadelphia to be assessed and possibly receive fetal therapy. I mean, you can imagine what that's like for the families.

Susan R. Miesnik, MSN: One of the vital things about this center is that we have the time and the desire to really provide every detail of information that we can for families so that they have the entire picture of what they're dealing with, what the diagnosis is, what the prognosis is, what options are available for them for treatment, and then what the complications and risks of those treatments could be, and what the potential outcomes will be.

N. Scott Adzick, MD: We try and craft things so that the families' needs are met.

Martha Hudson, MSW: To look at any barriers that might exist in terms of their ability to make a decision about which procedure or if any procedure to have, and what might be the best for them.

Susan R. Miesnik, MSN: Each individual family needs to make a decision on its own as to what works best for them. Do they proceed with a procedure? Do they terminate a pregnancy? Which for some families that may be the option. Do they stay here in Philadelphia? Do they go home to their referring physician in their hometown?

Martha Hudson, MSW: The decision that's best for one family may be completely different than a decision that is made by another family in the exact same situation.

Lori J. Howell, RN: So it's really our job to explain what the options are in a way so that they can make the best choices for themselves and their family.

A Future of Hope

Marie Hasson: We had our twin girls March 29th. And they're now 5 years old and luckily very healthy and beautiful.

Dennis Hasson: Their birthday was in the end of March and they're going to graduate from preschool in June. They played soccer for the first time this year. To see them out there running around in the soccer field or to not be running around, to be standing and picking daisies while the ball's going by, it's nice to just see sweet little girls happy.

Jack Rychik, MD: Five, 10 years ago we had nowhere near the positive results that we have today. We had nowhere near the understanding that we have today. And in essence, we've taken what has been for most sets of twins a lethal disease, we've made it manageable, and we've had tremendous success in creating survivors. And that's incredibly gratifying.

Nahla Kalek, MD: A profoundly remarkable characteristic is the dedication of the center towards the care of families affected by twin-twin transfusion syndrome.

Mark P. Johnson, MD: A lot of our knowledge has just in this area has only come in the last few years of studying, you know, injection studies of placentas.

Nahla Kalek, MD: We collaborate with our referring physicians as well as our families to have the placentas returned to us for formal pathologic examination. Part of that is so that we can gain a deeper appreciation for the mechanisms that are involved in twin-twin transfusion syndrome.

Mark P. Johnson, MD: It becomes certainly a challenge for us to try to recognize what's going on and the best therapy to treat these, to give these families the best outcome possible.

Nahla Kalek, MD: We offer our patients that undergo selective laser the opportunity to return for an extensive neurodevelopmental as well as neonatal cardiac evaluation.

Jack Rychik, MD: This is true translational medicine in that we are learning from our experience in managing these patients and what we learn is very quickly converted into changes in how we make management decisions.

Susan R. Miesnik, MSN: There's a huge debt that we owe to these families. They help us to advance the scientific purpose that we're here for. They help us to advance fetal treatment, and in addition they provide — they're the life of the center.

Mark P. Johnson, MD: Every single family's contribution increases the likelihood of future families having better outcomes.

Susan R. Miesnik, MSN: They just bring such joy and such commitment to this experience even if they're dealing with a situation that's less than optimal.

Mark P. Johnson, MD: By allowing us to care for their pregnancy, care for their children, it's probably the principle reason that we're able to make progress.

N. Scott Adzick, MD: In many cases, the families and the patients teach us.

Nahla Kalek, MD: We learn so much from watching them.

Lori J. Howell, RN: Every family that we take care of adds to that education, adds to that learning.

Mark P. Johnson, MD: The other valuable contribution is that we get feedback from them.

Martha Hudson, MSW: Absolutely the best ideas come from families. And they've been through it and they've had a chance to reflect and they give us feedback that helps us change and improve the program for the better.

Susan R. Miesnik, MSN: They always provide me with a sense of hope.

Joy N. Macdonald, RN: I feel honored to be part of these — the lives of our families.

Lori J. Howell, RN, MS: I think families get a sense for that, how special they are to us.

Mark P. Johnson, MD: We are here to provide medical care, but really the families are here to teach us what we don't know, what we don't understand, for future generations of children with these problems.

When TTTS Isn't TTTS

Mark P. Johnson, MD: Sometimes families come to us with the diagnosis of TTTS and it turns out to be something more like selective intrauterine growth restriction, or sIUGR. TTTS and sIUGR are related because they involve the same common shared placenta between the two babies. What differentiates them is the vascular connections between the two babies.

Jack Rychik, MD: Often the differences between sIUGR and twin-twin transfusion syndrome can in fact be very subtle. Through the use of Doppler ultrasound we can help tease out the facts that support one particular diagnosis versus another. And through Doppler echocardiography we can identify the direction of blood flow, the velocity of blood flow, and also determine patterns of blood flow.

Mark P. Johnson, MD: One of the things that we look at, of course, is cardiac changes. In TTTS there is a very characteristic progressive series of changes that happens in the larger twin due to the extra volume that comes from the smaller twin to the larger twin.

Jack Rychik, MD: Blood is exchanged from one twin, the donor, into the recipient. And then as a consequence there's a huge cascade of hormonal changes that take place that then brings about the cardiovascular manifestations in the recipient.

Mark P. Johnson, MD: In selective IUGR there isn't this transfer of volume. You know, there's not this net shift of volume from twin to the other. It's much more balanced, but that balance, you know, can be a tenuous balance.

Jack Rychik, MD: In the smaller twin there is an abnormality of placental sharing.

Mark P. Johnson, MD: The smaller baby has a much smaller portion of the placenta.

Jack Rychik, MD: And the resistance in the umbilical artery of that particular twin is much higher than normal, resulting in alterations in growth in the smaller twin.

Mark P. Johnson, MD: selective intrauterine growth restriction has been recognized for a long time, but it's only been in the last decade that we've been able to see that there are different forms of it. There's a milder form, which we call type I. There's a more severe form that we call type II. And then there's a new entity that's really only becoming understood, that's come out in the last few years, that's the type III selective IUGR. So if we were to look at a normal placenta there would probably be a large number of connections between both fetuses. There's kind of a sense of balance there. So the shifts in blood in one direction would be offset by shifts in blood in the other direction.

In type I selective IUGR what you notice is perhaps a 60/40 distribution of placental area. But you see a decrease in the number of connections that means that there can't be as dynamic a shift in blood volume between the two twins.

When you go to the type II selective IUGR you start to see a much smaller portion of placenta for the one that develops the intrauterine growth restriction. You also notice that the number of vessels, again, decreases even more. They tend to be balanced so that the number of artery to vein connections from the smaller to the bigger is still offset by artery to veins in the other direction, but the numbers are much, much fewer. And so, again, it's this idea of dynamic sharing that is more restrictive. And that forces the fetus with the smaller portion of placenta to really try to survive on what its got as far as placental mass. And the less volume of the placenta it has, the more it struggles.

In the type III selective IUGR they have just a small, small proportion of the placenta. There tends to be a higher proportion of arteries connecting to veins from the normal baby to the smaller baby, but it's a very small placental area. And that's led to the concept of rescue transfusion, the larger baby being able to send blood to the other side of the placenta. And so those connections are absolutely vital for the smaller baby's survival.

The other characteristic feature in type III selective IUGR is a very big artery to artery connection. There can be rapid shifts in blood in either direction. These high volume shifts of blood from one baby to the other results in the blood pressure going up and going down and going up and going down, and that appears to result in injury. So while this connection is vital to keeping the smaller baby alive, it can potentially result in a brain injury to the normal baby and it can actually kill the smaller baby because of this just sudden rapid shift in blood pressure and volume. So in type III selective IUGR, it's a very, very dependent and very, very dynamic relationship between the two twins and the connections in the placenta.

Jack Rychik, MD: The science and the practice of managing twin complications such as twin-twin transfusion syndrome or sIUGR perhaps, in effect, has only existed for about a decade.

Mark P. Johnson, MD: Understanding the TTTS story has been vital in our understanding of how to differentiate that problem from the selective IUGR problem.

Jack Rychik, MD: High volume exposure to these patients is critical in being able to learn what to expect.

Mark P. Johnson, MD: That high volume, that experience, and that collaboration is what makes us a really good place and allows us to really tailor management for each individual patient to optimize and try to achieve the best outcome possible.

Topics Covered: Twin-Twin Transfusion Syndrome (TTTS)

Related Centers and Programs: Richard D. Wood Jr. Center for Fetal Diagnosis and Treatment