Ultrasound Obstet Gynecol 2002; 20: 360 – 363
Management of single fetal death in twin-to-twin transfusion
Blackwell Science, Ltd
syndrome: a role for fetal blood sampling
M.-V. SENAT*, J.-P. BERNARD*, S. LOIZEAU* and Y. VILLE*
*Department of Obstetrics and Gynecology, Paris-Ouest University, CHI Poissy-St-Germain, France
KEYWORDS: Fetal blood sampling, Intrauterine transfusion, Single fetal death, Twin–twin transfusion
ABSTRACT
Objective Intrauterine death of one twin in monochorionic
pregnancies is associated with an increased mortality and mor-
bidity of the cotwin. This is likely to occur as a consequence of
acute hemodynamic changes due to feto–fetal hemorrhage at
the time of death of the cotwin. We assessed the role of fetal
blood sampling and intrauterine transfusion to rescue the
survivor.
Materials and methods We managed 12 cases of single
intrauterine death at between 17 and 26 weeks’ gestation in
monochorionic twins complicated by twin-to-twin transfusion
syndrome (TTTS). All these cases had been treated either by
laser therapy or by serial amniodrainage. When the demise of
one twin occurred, ultrasound-guided fetal blood sampling
was performed in the surviving twin using a 20-gauge needle
within 24 h of death. Intrauterine transfusion was performed
at the same time in cases where the survivor was anemic. All
survivors were assessed in the neonatal period and at 1 year
of age.
Results Six of the 12 surviving fetuses were found to be
anemic and underwent intrauterine transfusion. All fetuses
survived the procedure. Four of these fetuses had normal
neurological development at 1 year of age. Periventricular
leukomalacia developed in one case and the patient under-
went termination of pregnancy at 34 weeks. In one case
delivery occurred at 34 weeks’ gestation and the baby devel-
oped periventricular leukomalacia at 1 month of age. In all
six non-anemic fetuses pediatric examination was normal at
birth and at 1 year of age.
Conclusion Intrauterine death of one monochorionic twin
in TTTS puts the survivor at high risk of intrauterine death or
of developing ischemic/hypoxic lesions. Our results suggest
that fetal blood sampling is a useful diagnostic tool to identify
those fetuses that are not anemic and hence unlikely to be at
risk of developing a cerebral lesion.
Correspondence: Prof Y. Ville, Service de Gynécologie Obstétrique, Hôpital de Poissy, Rue du Champ Gaillard, 78300 Poissy, France
(e-mail: yville@wanadoo.fr)
Accepted 7-5-02
360
INTRODUCTION
Twins have a higher mortality and morbidity than singletons
and among twin pregnancies the risks are even higher when
they are monochorionic1–7. The mechanism of intrauterine
death in one monochorionic twin and its association with
increased mortality and morbidity in the surviving cotwin is
still debated, although two theories have been proposed. The
embolization theory suggests that the injuries observed among
survivors are related to the passage of thromboplastic
material from the dead twin to the live one via the placental
anastomoses leading to the development of disseminated
intravascular coagulation (DIVC)8–10. The second and most
convincing theory involves exsanguination of the survivor
into the dead fetus just before or at the time of death when
its blood pressure drops dramatically11–14. If this mechanism
is mainly responsible for the morbidity seen in the survivor,
it may then be reasonable to assume that early intervention
could largely prevent the morbid consequences. Twin-to-twin
transfusion syndrome (TTTS) is characterized by a more
severe form of hemodynamic imbalance and instability. In
TTTS treated by either laser coagulation15 or amniodrainage
one could argue that occlusion of some anastomoses is totally
lacking with the latter technique, but could still be incomplete
following laser coagulation owing to technical difficulties.
The management of intrauterine death of one twin by fetal
blood sampling and subsequent intrauterine transfusion
(IUT) of the anemic survivors may therefore rescue these
fetuses from prolonged hypovolemia/anemia.
The aim of this study was to assess the role of fetal blood
sampling and IUT to rescue the survivor within 24 h of the
death of one monochorionic cotwin in TTTS.
MATERIALS AND METHODS
Over a 2-year period we reviewed 12 cases of single intrauterine
death in monochorionic pregnancies complicated by TTTS
occurring between 17 and 26 weeks’ gestation. All these
ORIGINAL PAPER
 14690705, 2002, 4, Downloaded from https://obgyn.onlinelibrary.wiley.com/doi/10.1046/j.1469-0705.2002.00815.x by Nat Prov Indonesia, Wiley Online Library on [17/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Single fetal death in TTTS Senat et al.

Table 1 Summary of clinical and hematological characteristics of the 12 survivors following intrauterine death of their monochorionic cotwin in twin-
to-twin transfusion syndrome

Treatment L L L L L L A A A A A+L L+C

GA at treatment (weeks) 22 21 21 23 20 18 26 24 20 17 (22,24) (20,25)

Dead twin (D/R) R R R D R D R R D D D R
Ultrasound markers of fetal anemia minor minor minor none none none none major none none major none
(1) (1) (1) (2) (2)
Hb pretransfusion (g /dL) 16 11 12 14 6.8 20 6.1 5.1 13.2 3.8 7.0 8.0
Hb post-transfusion (g /dL) NA NA NA NA 11.5 NA 12.6 12.8 NA 11.9 13 12
Intrauterine transfusion no no no no yes no yes yes no yes yes yes
GA at delivery (weeks) 38 37 35 34 36 38 28 34 37 34 PVL 36 29
TOP
Morbidity at 1 year of age no no no no no no no PVL no no no

L, laser; A, amniodrainage; C, cord coagulation; GA, gestational age; R, recipient; D, donor; Hb, hemoglobin concentration; PVL, periventricular
leukomalacia; TOP, termination of pregnancy; (1) frontal edema, echogenic bowel; (2) ascites and/or generalized edema.

pregnancies had been treated either with laser coagulation or
with serial amniodrainage following prenatal diagnosis
(Table 1). When the demise of one twin occurred, fetal blood
sampling was performed in the surviving twin with a 20-gauge
needle within 24 h. IUT was performed under ultrasound
guidance in cases where the survivor was anemic, with the aim
of correcting the effect of hypovolemia/anemia in the devel-
opment of tissue ischemia. The site of sampling was the placental
cord insertion in all cases. Fetal hematology was assessed
with hemo-cue and compatible ORh-irradiated adult blood
was used for IUT when indicated. Confirmation of fetal
hematology was obtained later through the usual techniques
from the hematology laboratory. Weekly anomaly scans
and Doppler investigations were performed following IUT
and magnetic resonance imaging (MRI) was performed at
32 weeks’ gestation. At the time of delivery the neonates under-
went a complete clinical examination as well as transfont-
anellar ultrasound at birth. All survivors were re-assessed
at the age of 1 year. Placentae all underwent histological
examination.
RESULTS
Amniodrainage was performed in four cases at 17, 20, 24 and
26 weeks’ gestation, respectively. Laser coagulation alone
was performed in six cases at 18–23 weeks’ gestation. One
patient had an amniodrainage at 22 weeks and a laser pro-
cedure 2 weeks later. One patient had a laser procedure at
20 weeks’ gestation followed by cord coagulation in one twin
at 25 weeks’ gestation. Seven recipients and five donors died.
All deaths occurred within 3 days of the procedure. Six of the
12 surviving fetuses were found to be anemic and IUT was
then performed (Figure 1). The volume of blood that was
transfused was calculated according to the concentration of
the donor blood, the fetal hemoglobin concentration and the
estimated fetal weight16. Of these six fetuses only two had
major ultrasound markers of fetal anemia with an otherwise
normal biophysical profile: frontal edema, mild ascites,
hyperechogenic bowel, absent or reversed flow during atrial
contraction in the ductus venosus. All fetuses survived the
procedure. In one case ultrasound and MRI follow-up
showed periventricular leukomalacia at 34 weeks’ gestation
and the patient underwent termination of pregnancy. In two
cases delivery was close to term and these fetuses had a
normal neurological development at 1 year of age. In two
cases delivery occurred 2 and 4 weeks following IUT. These
fetuses were born prematurely at 28 and 29 weeks’ gestation,
respectively. They also had normal neurological development
at 1 year of age. In one case delivery occurred at 34 weeks’
gestation and the baby developed periventricular leukomalacia
at the age of 1 month, despite normal weekly ultrasound and
MRI antenatal follow-up and normal antenatal MRI. The
neonatal brain scan was also normal in that case. In the six
non-anemic fetuses follow-up anomaly scans and Doppler
remained normal and the pregnancies were uneventful.
Spontaneous delivery occurred between 34 and 38 weeks of
gestation. Pediatric examination was normal at birth and at
1 year of age. There was no evidence of hypoxic or ischemic
brain injury. Results are summarized in Table 1.
Histological examination of the placentae confirmed
monochorionicity in all cases.

D ISC U SSIO N
In the present series of 12 cases of single intrauterine death
Figure 1 Hemoglobin pretransfusion (䉭) and post-transfusion (䉱) in in monochorionic twins complicated by TTTS, there were 10
relation to gestational age. healthy survivors including four anemic fetuses managed

Ultrasound in Obstetrics and Gynecology 361


Single fetal death in TTTS
with IUT and six non-anemic fetuses who underwent fetal
blood sampling without transfusion. One of the anemic
fetuses survived but developed periventricular leukomalacia
at 1 month of age despite IUT within 24 h after the death
of its cotwin. This study supports the data of Nicolini et al.
who found that in non-occlusive management all survivors
sampled within 24 h after death of the cotwin were
anemic14. Okamura et al. also described three of five sur-
vivors with anemia when sampled within 24 h of death of
their cotwin13.
Intrauterine death of one twin is associated with an in-
creased neurological morbidity in the cotwin when it survives17.
Cerebral and renal damage following hemorrhage-related hypo-
tension are the main factors of morbidity17,18. The hypothesis
that there is a passage of thromboplastin-like substances
from the dead twin to the surviving twin through placental
vascular anastomoses, leading to intrauterine DIVC8–10,
has never been shown by fetal or neonatal investigations.
This hypothesis is only based on postmortem findings of
areas of infarction and necrosis in the brain and kidneys
of dead monochorionic twins. Moreover the coagulation
profile in the surviving fetuses after the death of the cotwin
were found to be normal at fetal blood sampling11,13,20.
In constrast, well-documented papers support that morbid-
ity in the surviving fetus is due to acute hemodynamic
decompensation just before or at the time of death of the
cotwin when its blood pressure drops, leading to exsanguina-
tion of the live fetus into the dead one across placental
anastomoses11–14. Consequently acute and profound
hemodynamic changes with hypovolemia and anemia can
occur in the survivor and may be responsible for the develop-
ment of ischemic lesions and particularly periventricular
leukomalacia. This acute phenomenon is probably even more
marked in monochorionic twins with TTTS, and will depend
on the number and size of vascular placental anastomoses
since large quantities of fetal blood can rapidly be transferred
across these vessels. An unfavorable outcome was reported
in monochorionic twins with the association of unidirec-
tional artery–vein anastomoses and artery–artery superficial
anastomoses on monochorionic placentae20. Laser treat-
ment aims at occluding all placental vascular anastomoses,
which is not always entirely feasible, while amniodrainage
should have no occluding effect. The hemodynamic theory
was proposed by Fusi et al. as one of the recipients was
found to be anemic after the death of the donor twin11. This
was later confirmed by Okamura et al.13. In our study the
prognosis of the surviving twin seems to be better than in
other series12–14,22,23. Indeed only two children out of 12
developed periventricular leukomalacia. Only one recent
study reported similar management in single intrauterine
death in seven cases of TTTS22. These fetuses underwent
IUT within 24 h following the demise of the cotwin. Two
fetuses died in utero and two fetuses developed cerebral
lesions and termination of pregnancy was performed. There
was one neonatal death and only two fetuses were born alive
and had a favorable outcome. The main difference with our
series is that laser was performed in eight cases out of 12 and
only three survivors were anemic in this group. One can
therefore assume that laser had completely or partially
362
14690705, 2002, 4, Downloaded from https://obgyn.onlinelibrary.wiley.com/doi/10.1046/j.1469-0705.2002.00815.x by Nat Prov Indonesia, Wiley Online Library on [17/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Senat et al.
occluded placental anastomoses in five and three cases,
respectively. This is likely to prevent at least partly profound
hypovolemia/hypotension from occurring in the survivor.
Indeed in the amniodrainage group, two survivors out of
three developed periventricular leukomalacia despite IUT,
whereas none of the three anemic fetuses did in the laser
group. However, such small numbers do not allow for any
meaningful statistics to be done.
Intrauterine death of one monochorionic twin therefore
puts the survivor at a high risk of intrauterine death or of
developing ischemic/hypoxic lesions. Fetal blood sampling
can be performed to evaluate the hematological condition of
the survivor since ultrasound cannot always show markers of
fetal anemia. Frontal edema and hypoechogenic bowel can be
mistaken for subtle signs of fetal anemia in the context of
intrauterine death of the cotwin. However, when this occurs
after laser coagulation, it is also likely to reflect transient fetal
hypertension following ablation of placental vessels23.
Indeed in our series three non-anemic survivors presented
these ultrasound features following laser therapy. The non-
anemic group had a good outcome. Our results suggest that
fetal blood sampling is a useful diagnostic tool following the
death of a twin in TTTS to identify fetuses that are not anemic
and hence unlikely to be at risk of developing a cerebral
lesion. Fetuses that are anemic remain at high risk, especially
when no occlusive technique has been used initially to de-
crease feto–fetal exsanguination. After extensive counseling
regarding the risks of these invasive procedures, fetal blood
sampling and IUT may therefore prove to be a useful inter-
vention. This observation will need to be confirmed in a
larger series.
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