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Embargoed for release at 5 p.m.
July 7, 2004
Summary: Performing laser
surgery in utero on identical twins suffering from twin-to-twin
transfusion syndrome leads to significantly better outcomes than
traditional treatment, according to a study that involves physicians
from Rhode Island Hospital, Women & Infants' Hospital and
Brown Medical School. The results of the study, which was led
by investigators in France and Belgium, will appear in the July
8 issue of New England Journal of Medicine. The Rhode Island
site is the only one in North America that performed fetal surgery
as part of the study.
Proof of efficacy of laser therapy
for Twin-Twin Transfusion Syndrome (TTTS), a complication unique
to identical twins
Providence, RI/Paris, France/Leuven,
Belgium - The majority of identical twins have only one placenta.
In a number of these, blood may flow disproportionately from
one baby to the other through connecting blood vessels in their
shared placenta. This condition is called Twin-Twin Transfusion
Syndrome, and has an incidence of about 1 per 1,000 pregnancies.
If it occurs early in pregnancy and is left untreated, it is
likely to cause loss of both babies. Until recently, the only
available treatment consisted in repeated drainage of excess
amniotic fluid (a consequence of the condition), but the results
of this method are less than optimal. A new, more cause-oriented
approach was therefore introduced, whereby a surgical separation
of the connecting vessels on the placenta is performed by means
of laser. Pioneering centers in keyhole surgery inside the womb
("fetoscopic surgery"), together with a number of "Fetal
Treatment" centers throughout Europe, just finished a study
comparing the two treatments. Using the most powerful form of
medical research, whereby patients are randomly assigned by a
computer to one or the other therapy, they have demonstrated
that fetoscopic laser coagulation improves survival chances by
25 % and reduces the risks of neurologic problems by half, compared
with drainage of amniotic fluid alone. These results will be
published this week in the New England Journal of Medicine and
are expected to have an impact on modern management of this disease.
TWINS OF DIFFERENT KINDS
There are two types of twin pregnancies.
Those resulting from two fertilized eggs are called fraternal
twins: they are like any other siblings, who just happen to occupy
the same womb at the same time. They may or may not have a different
gender. Twins resulting from the fertilization of a single egg
or "zygote" are called identical or "monozygotic"
twins. These children look identical and always have the same
gender.
While most people are only interested in whether twins are identical
or not, this is irrelevant from an obstetrical viewpoint. In
terms of outcome of the pregnancy, the number of placentas is
the most important factor. Fraternal twins always have their
own placenta, but monozygotic or identical twins each have their
own placenta in only 30 % of cases. 70 % of identical twins will
have to share a single placenta throughout pregnancy, a situation
that is much riskier.
Figure 1: Schematic drawing of TTTS. The smaller
fetus is the donor, who has almost no amniotic fluid and is stuck
to the wall of the womb, whereas the larger fetus is the recipient,
who has too much amniotic fluid. Both babies share a single placenta.
THE TWIN-TWIN TRANSFUSION SYNDROME
Most identical twins experience
no problems from the shared circulation and placenta. This remains
true as long as the exchange of blood between the fetuses is
well balanced. In 15%, however, more blood flows from one fetus
towards the other, leading to what is called Twin-Twin Transfusion
Syndrome (TTTS). The first fetus is called the "donor,"
as he pumps blood into the second fetus, who is therefore called
the "recipient." This leads to too little blood (anemia),
too little urine production and too little amniotic fluid production
in the donor, who is frequently smaller. Doctors can document
the lack of urine and amniotic fluid production using ultrasound,
showing a nearly empty gestational sac, which may eventually
not be visible at all. The recipient receives too much blood
and eliminates the excess fluid by increasing his urine production
(Figure.1). This leads to too much amniotic fluid around the
recipient (polyhydramnios) and a rapid and excessive distension
of the womb, leading to early delivery or rupture of the membranes.
The condition itself can be easily demonstrated by ultrasound.
Figure 2: Drawing of the shared placenta
in TTTS. Multiple vessels connect both fetuses through so-called
"anastomoses" (open circles). These anastomoses are
the sites for laser coagulation.
Importantly, TTTS is essentially a disease of the placenta, while
the twins themselves are normal. However, unborn babies are fully
dependent on the placenta for oxygen and nutrition, and any disease
of the placenta will invariably affect their well-being. When
TTTS occurs before 26 weeks gestational age (the normal duration
of pregnancy is 40 weeks), it will have dramatic implications.
It is estimated that the chance of survival is less than 1 in
5. Of the surviving fetuses, approximately 25% will sustain severe
damage of the brain, liver, kidneys or other organs.
Given this high risk for losing the entire pregnancy, treatment
is highly desirable. Certainly, the excess of amniotic fluid
should be evacuated. This is done by needle puncture of the mother's
pregnant uterus and is called amniodrainage. Amniodrainage does
not remove the cause of the disease (the communicating blood
vessels on the placenta), but it reduces the pressure in the
womb and the risk of early delivery. The removal of fluid is
repeated as often as required, usually 5 to 6 times. In the study
that is to be published, one or both babies survived in only
half the mothers who were treated with amniodrainage only. Babies
were also born very prematurely, i.e. at 29 weeks on average.
While this is certainly better than without any therapy at all,
it leaves room for improvement.
Figure 3: Illustration of fetoscopic laser
treatment. A cannula has been placed through the abdominal wall,
through which a telescope and laser beam have been passed. The
connecting vessels are identified and subsequently destroyed.
In 1995 an operation to separate the two blood circulations was
introduced. By means of an endoscope (a tiny telescope of 3 mm
diameter) the physician inspects the placenta and uses a laser
to separate the connecting blood vessels on the placenta (Figure
2). This operation usually lasts less than an hour and causes
no pain to the fetuses, who are not touched by it. At the end
of the operation, the excess amniotic fluid is evacuated, down
to normal levels; thus, it combines laser with the previously
described therapy. In the study, 76 % of pregnancies ended up
with one or two babies; this is an improvement of 25 % when compared
with amniodrainage alone. In addition to that, laser therapy
reduced the occurrence of serious brain damage by the age of
6 months from 10.3 to 4.5 %. This may be in part due to the later
gestational age at birth (babies in the laser group were born
at a mean of 33 weeks).
With this study, a long-lasting quarrel between "believers"
and "non-believers" in this new method may be settled
in favor of the more modern and causative approach to this disease.
At this stage there are only a limited number of centers that
have enough experience with the operation. The results of this
study suggest that patients diagnosed with severe TTTS should
be offered laser intervention, or should be offered the option
to travel to a center familiar with this form of therapy.
For further information contact:
François I.
Luks, MD, Rhode Island Hospital, Brown Medical School, Providence,
RI
Stephen R. Carr, MD,
Women & Infants' Hospital, Brown Medical School, Providence,
RI
Prof Yves
Ville, C.H.R. de Poissy-St Germain Paris, Dept. of Obstetrics
and Gynaecology (Principal Investigator)
Prof Jan Deprest,
University Hospital Leuven, Dept. of Obstetrics and Gynaecology
(Eurofoetus General Project Manager)
Figures: K Dalkowski, with permission
of Karl Storz Endoskope.
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