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WHAT
IS TWIN-TO-TWIN TRANSFUSION SYNDROME?
Twin-to-twin transfusion occurs
in a monochorionic pregnancy (i.e., identical twins
who share a single placenta) when blood from one fetus circulates
to the other twin. In general, identical twins normally exchange
some blood during gestation; this exchange is usually balanced,
so that one twin will act as the 'blood donor' one moment, and
as the 'recipient' the next. The twin-to-twin transfusion syndrome
occurs when one twin always 'donates' blood to the other, because
the communication between the two is unbalanced.
Twin-to-twin transfusion syndrome
does not occur in non-identical twin fetuses, where each fetus
has its own placenta. It is also much less likely to occur if
both twins are not only identical, but share a common amniotic space (so-called mono-amniotic twins). The latter is the least
common form of twin pregnancies, but is associated with other
potentially life-threatening problems.
In the twin-to-twin transfusion
syndrome, one twin (donor) will have to pump blood, not only
for himself, but also to transfuse the recipient twin. The donor
has to do more work, thereby having less energy to grow; he will
show signs of intrauterine growth retardation, will produce
less amniotic fluid (oligohydramnios), and eventually become almost
wrapped in its amniotic membranes: there is now so little
fluid surrounding him that he is 'stuck.' Hence, twin-to-twin
transfusion syndrome is sometimes referred to as 'stuck twin'
syndrome.
The recipient twin, on the other
hand, ends up with too much blood and fluids, which forces him
to eliminate it through the urine: a recipient twin will therefore
often be seen with a full bladder. The excess fluid causes polyhydramnios,
the excess accumulation of amniotic fluid in this fetus's amniotic
space. The fetus himself will tend to swell (become edematous),
and may go into heart failure, or 'hydrops'. The combination of polyhydramnios in the recipient and oligohydramnios in the donor is also referred
to as 'poly-oli' syndrome, another term for twin-to-twin transfusion
syndrome.
Figure 1 illustrates a normal
situation, where blood flows in either direction. Figure 2A illustrates
the onset of twin-to-twin transfusion syndrome, where blood preferentially
flows from one fetus (the donor) to the other (the recipient).
In figure 2B, the full-blown syndrome ("stuck twin")
develops.
Figure 1: Twins A
and B each have their own amniotic cavity, but a single placenta.
Blood can flow from twin A to twin B, or vice-versa: there is
balanced transfusion.
Figure 2A: Twin A
(donor) is transfusing twin B (recipient), without counterbalanced
transfusion from B to A.
Figure 2B: Twin A
remains smaller, develops less amniotic fluid (becomes the 'stuck'
twin). Twin B develops hydrops (swelling) and large amounts of amniotic
fluid (polyhydramnios).
HOW
COMMON IS TWIN-TO-TWIN TRANSFUSION SYNDROME?
It happens in 5 to 15% of all
identical twins, and puts about 6,000 babies at risk in the United
States each year.* It can happen anytime during the pregnancy.
It can also affect triplet and higher order pregnancies.
WHAT
IS THE RISK TO THE TWINS?
If twin-to-twin transfusion syndrome
occurs late in gestation, the risks are usually minimal; if one
fetus is threatening to develop hydrops or failure, delivery of the babies
might be the best option. If this occurs earlier, before the
babies are mature enough to survive out of the womb, the options
are fewer and the risks greater.
Preterm, premature rupture of the membranes
(PPROM) and premature
labor are often a threat to the twin pregnancy, possibly due
to increased pressure and increased amounts of amniotic fluid
(polyhydramnios in the 'recipient' fetus).
If the babies are born prematurely, they may be at a higher risk
of suffering serious complications, or even dying in infancy.
One or the other twin is at a
high risk of suffering severe heart- or brain problems (due to
insufficient or inappropriate blood flow caused by the transfusion).
The donor twin is usually the sickest; he will often be anemic (not enough red blood cells), and is
the one at highest risk of dying in utero.
The recipient twin may suffer
as well, and develop hydrops (heart failure) due to fluid and blood
overload. In addition, chronic transfusion may make the recipient's
blood thicker (more viscous). This, in combination with somewhat
sluggish blood flow because of heart failure, may place the recipient
at risk for "vascular accidents" whereby a blood vessel
becomes blocked. This may theoretically affect any organ, or
an entire limb, causing necrosis. As a result, the organ may
be damaged or even absent. Examples of this are an absent kidney,
an interruption in the intestinal tract or a severely abnormal
leg.
Once a fetus dies, the remaining
twin is at a very high risk of dying within days. If he survives,
he is very likely to develop very severe heart or brain damage.
If twin-to-twin transfusion syndrome
develops early in pregnancy (before 20 weeks) and nothing is
done, there is a very high likelihood that both twins will die.
ARE ALL
CASES OF TTTS THE SAME?
No, some cases of TTTS are extremely
severe and rapid in onset, while others have a less aggressive
course. There are several ways doctors can describe and classify
the severity of the syndrome, but the most commonly used is the
one devised by Dr. Ruben Quintero. The Quintero classification
(or its modifications) uses ultrasound findings to estimate the
severity of TTTS:
In stage I,
there is severe polyhydramnios around the recipient and severe
oligohydramnios around the donor, but the
donor is still able to produce enough urine to fill his bladder
(which is visible on ultrasound).
In stage II,
the degree of transfusion and dehydration of the donor is such,
that he is no longer able to fill his bladder - the bladder is
now no longer visible on ultrasound.
In stage III,
additional signs of fetal stress are seen: there may be pulsatile (rather than uniform) flow through
the umbilical vein (usually of the recipient), absent or even reversed end-diastolic flow in the umbilical
artery (usually of the donor) or other signs of cardiovascular
stress, such as a leaky heart valve (tricuspid regurgitation, or TR). As a group,
these signs are called "critical dopplers," because
they are usually diagnosed by using Doppler ultrasound (a feature of the ultrasound
machine).
In stage IV,
there are now overt signs of heart failure in one or both twins:
fluid starts to accumulate around the heart (pericardial effusion),
around the lungs (pleural effusions), in the abdomen (ascites) or under the skin (edema, or thickened nuchal fold).
Clearly, stages III and IV are
more severe than stages I and II. In general, surgical intervention
(such as laser) is not recommended in lesser stages, and most
centers will only offer aggressive treatment for stages II, III
or IV. The main reason for this is that the prognosis is better
for stage I than for higher stages (provided that the twins remain
in stage I and do not progress to a higher stage).
Unfortunately, it is very difficult,
at this time, to predict how a particular case will progress:
some twins have been seen to remain in stage I for many weeks,
or even improve on their own; while others have progressed very
rapidly to a higher stage, sometimes even skipping one or more
stage. Much of the current
research in TTTS is now directed at understanding why some
twins develop the syndrome and others don't, and why some progress
more rapidly than others.
WHAT
ARE THE TREATMENT OPTIONS?
1. Observation and bedrest.
If twin-to-twin transfusion syndrome
occurs after 25 to 28 weeks, conservative measures (bedrest,
single amnioreduction) and early delivery are usually
recommended. Amnioreduction means the removal, through
a fine needle, of the excess amniotic fluid from the recipient
twin with polyhydramnios (see below). As the pregnancy
comes closer to term, it may be best to 'wait and see,' and to
plan early delivery if either twin shows signs of distress. In
this situation, the risks associated with (mild to moderate)
prematurity may be smaller than the risk of an intervention in
the womb (such as the ones described below).
2. Amnioreduction.
Removal of excess amniotic fluid
from the recipient twin has been, until recently, the best available
treatment for twin-to-twin transfusion syndrome. The reason for
its effectiveness is not completely clear, but removing the excess
amniotic fluid may help decrease the risk of rupture of the membranes
(PPROM)
and premature labor. It may also be beneficial by relieving the
pressure on the umbilical cord of the twin with excess fluid,
and thus improve blood flow between the fetus and the placenta.
Amnioreduction does not, however, treat the cause of
twin-to-twin transfusion syndrome, only one of its effects. Since
the fluid is likely to accumulate again (usually within a few
days to a week or two), the procedure will have to be repeated.
With each amnioreduction, the risk of bleeding or infection
increases, as does the risk of injury to the membranes.
The results of repeated amnioreduction depend on how often this has
to be done, and how rapidly fluid accumulates again. In general,
the earlier in gestation the syndrome develops and the quicker
polyhydramnios recurs after amnioreduction, the worse the outcome. Whereas
survival of either twin in twin-to-twin transfusion syndrome
is very low if the condition develops early (before 20 weeks
of gestation), repeated amnioreduction can improve survival of at
least one twin to 50-60%. Unfortunately, the risks of severe
complications in the surviving twins may be as high as 20 to
35%, and includes severe heart or brain anomalies.
3. Laser coagulation of the communicating placental
vessels.
This technique, a form of fetal
surgery, was originally described in 1995 by Dr. Julian DeLia,
and is now being performed in several centers world-wide, including
our own. This is the only known form of treatment for twin-to-twin
transfusion syndrome where the likely cause of the condition
is addressed. In essence, a laser fiber is used, through a very
small endoscope (a long telescopic lens) inserted
into the uterus, to block all vessels that run from one twin
to the other (see figure 3)
Figure 3: The blood
vessels that allow transfusion from one twin to the other are
closed
off by laser. The laser is introduced through a very thin
endoscope
into the uterus. As a result, each twin gets a separate portion
of the placenta, and the twins are now completely separated.
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Figure 4: Laser occlusion of the placental vessels
as seen through the endoscope. |
Fetal surgery is done under epidural
or general anesthesia. A small incision is made on the mother's
abdomen and, under ultrasound guidance, a long and thin instrument
(less than 1/8 " in diameter) is introduced into the amniotic
cavity. This instrument contains an endoscope, which allows the surgeon to directly
look into the uterus; and a laser fiber to coagulate, or block, the blood vessels that
are seen to cross from one twin to the other. All other blood
vessels, that connect the fetus to its own side of the placenta,
are left alone.
The procedure has been performed
hundreds of times since it was first described. It was initially
developed in the United States, but the majority of cases have
been performed in Europe. Today, several centers in the U.S. are offering this
technique.
The results of laser fetal surgery
appear to be better than those of other techniques, when patients
are properly selected. Survival of at least one twin has been
reported to be 70-80%, and survival of both twins is seen in
30-40% of the pregnancies. Also, the complication rate appears
to be much lower. There are much fewer cases of severe heart
and brain damage, and the overall complication rate (including
a few instances of infection and damage to the membranes) is
less than 10%, not including PPROM.
Preterm, premature rupture of
the membranes (PPROM) usually leads to premature delivery; it
is common in twin gestations (5-15%), particularly if TTTS is
present. While decreasing the polyhydramnios (see under Amnioreduction) reduces that risk, it may
still occur as a result of the invasive procedure itself. After
laser coagulation, the incidence of PPROM may be as high as 15%, particularly
if multiple procedures (such as repeated amnioreductions) preceded the endoscopic operation.
Since its first description,
the technique has undergone many improvements. For example, the
use of special endoscopes that can be custom-curved now allows
the treatment of patients with an anterior placenta. The use
of magnetic resonance imaging (MRI) and computerized three-dimensional
reconstruction allows the surgeons to plan the procedures on
a virtual reality model, before the uterus is even entered (figure
5).
Figure 5: Using detailed
MRI images of the fetus (left) and the uterus, a "virtual
patient" can be created and manipulated (center), allowing
the fetal surgeons to better plan the operation on the placenta
(right: green line is the intwertwin membrane on the placental
surface).
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It is important to note that
this is a form of fetal surgery and the most aggressive of the
treatment options for TTTS, and that risks, although reduced
to a minimum, exist for the mother and the fetuses. While the
procedure aims at separating the two blood circulations, communications
may still persist after the operation. As a result, one fetus's
demise could theoretically still affect the other (although that
risk is clearly much reduced compared with any of the other treatment
options). Complications of TTTS, such as fetal death, brain damage,
limb necrosis and others have been reported even when laser therapy
was performed. It is our belief that most of these represented
previously undiagnosed abnormalities (undiagnosed, perhaps, because
of limitations on the ability of ultrasound to detect evolving
problems in their early stages); nevertheless, the possibility
also exists that the treatment may not be successful and the
TTTS may progress.
Until recently,
it had not yet been demonstrated in a scientific way that endoscopic
laser ablation of placental vessels was clearly superior to amnioreduction.
Therefore, our center participated in a randomized, controlled trial involving many
institutions throughout several continents, and administered
by Eurofoetus.
Patients who qualify were offered to enroll in the study, which aimed to compare
serial amnioreduction with endoscopic laser surgery.
The study showed that laser ablation was superior to amnioreduction
for advanced stage TTTS. This is the first time a randomized
controlled study has been performed for fetal treatment of TTTS.
It is also the first study to demonstrate that laser surgery
is superior to amnioreduction.
For more information regarding
the recently completed Eurofoetus study, please contact us or go to the Eurofoetus web site, where a full description
of the trial
protocol is available. The complete results of the study
were published in 2004 in the New England Journal of Medicine. Click
here to read the press release an further information regarding
this study.
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4. Amniotic septostomy.
A few centers have, in the past,
offered an alternative procedure ,whereby one or more small holes
are created between the two amniotic cavities, in the hope that
fluid from the recipient twin (with polyhydramnios) will flow
toward the donor twin (who has oligohydramnios). The reasoning
is that this way, both twins will have a normal amount of amniotic
fluid. Some early results appeared promising, but this technique
has since been abandoned.
SUMMARY:
OUTCOME OF SEVERE TTTS WITH AND
WITHOUT TREATMENT
| |
Untreated |
Amnioreduction |
Laser |
| Survival
of both twins |
0-10% |
26% |
35% |
| Survival
of at least 1 twin |
0-30% |
51% |
76% |
| Maternal
complications |
|
|
|
| |
PPROM
(5-15%) |
PPROM
(5-15%) [1] |
PPROM (5-15%) |
| |
|
Infection
[1] |
Infection |
| |
|
Bleeding |
Bleeding |
| Fetal
complications: |
|
|
|
| Neurologic/Cardiac
damage |
20-35% |
20-35% |
<5% |
| Limb
necrosis |
described |
described |
described |
| Organ
damage/absence |
described |
described |
described |
[1] Risk increases with increasing
number of amnioreductions
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