Embarazo gemelar acta obstetgynecolscand2001

Acta Obstet Gynecol Scand 2001; 80: 287–299 Copyright C Acta Obstet Gynecol Scand 2001
Printed in Denmark ¡ All rights reserved
Acta Obstetricia et
Gynecologica Scandinavica
ISSN 0001-6349
REVIEW ARTICLE
Twin pregnancy: the role of ultrasound in
management
LENE SPERLING1
AND ANN TABOR2
From the Departments of Obstetrics and Gynecology, 1
Juliane Marie Center, Rigshospitalet, Copenhagen, and 2
Hvidovre
Hospital, Hvidovre, Denmark
Acta Obstet Gynecol Scand 2001; 80: 287–299. C Acta Obstet Gynecol Scand 2001
Determination of chorionicity is one of the most important issues in the management of twin
pregnancy.
Modern ultrasound equipment has made it possible to accurately assess placentation already
in the first trimester with the lambda sign. With regard to prenatal diagnosis, it is important
to know the chorionicity in order to calculate the risk of chromosomally abnormal fetuses.
Accurate chorionicity offers the obstetricians the opportunity to observe the monochorionic
twins more intensively than is required for twins with dichorionic placentation. This review
gives an update of the state of the art for clinicians caring for twin pregnancies.
Key words: abortion; amniocentesis; amnion; amnion fluid; brain damage; biochemical
screening; cervix uteri; chorion; chorionic villi sampling; chromosome abnormalities; endo-
scopy; fetal death; fetal growth; fetofetal transfusion; genetic counseling; malformations;
multiple pregnancy; placentation; prenatal; prenatal diagnosis; preterm delivery; twin preg-
nancy; ultrasonography
Submitted 6 July, 2000
Accepted 18 October, 2000
The incidence of multiple gestations is increasing,
primarily because of delayed childbearing and the
use of assisted reproductive technologies. Twin
pregnancies have a higher incidence of compli-
cations than singletons, from the first trimester un-
til the delivery of the second fetus. Ultrasono-
graphic evaluation throughout all three trimesters
has allowed a closer and more differentiated moni-
toring of twin pregnancies.
This paper gives an overview of the management
of twin pregnancies with special emphasis on the
role of ultrasonography.
Abbreviations:
AC: amniocentesis; CVS: chorionic villus sampling; DC: di-
chorionic; DZ: dizygotic; DS: Down’s syndrome; IUGR: intra-
uterine growth retardation; MC: monochorionic; MZ: monozy-
gotic; NT: nuchal translucency; SGA: small for gestational age;
TTTS: twin-twin transfusion syndrome.
C Acta Obstet Gynecol Scand 80 (2001)
Biology
Zygocity, chorionicity and amnionicity
There are two major types of twin gestations: dizy-
gotic (DZ) and monozygotic (MZ). MZ twins oc-
cur sporadically, while the incidence of DZ twins
increases with advancing age, parity and with ovu-
lation induction. The higher rate of DZ twins ob-
served with advancing maternal age may be caused
by an elevation of gonadotrophin levels with age
(1). In some families DZ twinning is apparently
inherited (2). The twinning frequency is 2–45/1 000
deliveries, with a considerable variation between
countries. This variation is largely caused by dif-
ferences in the occurrence of DZ twins, while that
of MZ twins is similar throughout the world. In
Caucasians about 30% of twin pregnancies are MZ
and about 70% DZ.
Zygocity refers to the type of conception: MZ
twins result from the splitting of one fertilized

288 L. Sperling and A. Tabor
ovum during the first two weeks of embryogenesis,
whereas DZ twins are due to the fertilization of
two ova by different spermatozoa (2, 3).
Chorionicity denotes the type of placentation.
Twin placentas are classified into two categories ac-
cording to the number of layers in the septum be-
tween the two amniotic sacs. In the monochorionic
(MC) placenta the septum consists of two layers of
amnion, while in the dichorionic (DC) placenta it
has two layers of both chorion and amnion. DC
placentas may be fused or separate, but when
examined after delivery blood vessel anastomoses
between the two placental vascular beds are sel-
dom found (4).
If two distinct placentas are identified, the preg-
nancy is DC. In the case of a single placenta, how-
ever, the pregnancy may be MC or DC. Chori-
onicity may be determined by looking for the ‘twin
peak sign’ (5) or ‘lambda sign’ (6, 7), which is only
seen in DC pregnancies. This sign reflects the per-
sistence of the chorion frondosum, which is seen
as a triangular projection extending between the
two layers of amniotic membrane. This sign accu-
rately identifies chorionicity in 99–100% of twins
between weeks 10 and 14π6
(8). As pregnancy pro-
gresses, the twin-peak sign becomes more difficult
to visualize and indeed it has disappeared in about
7% of DC pregnancies at 16–20 weeks. Absence of
the twin-peak sign in the second or third trimester
can therefore not exclude dichorionicity (9, 10).
DZ twins are always DC and MC twins are al-
ways MZ. Depending on at which stage of the em-
bryogenesis the zygote splits, four different types
of twins may result (Fig. 1). DC diamniotic MZ
twins result from the division of the zygote at the
two-cell and morula stages (less than four days
after fertilization) and represent about 26–28% of
MZ twins. The division of the inner cell mass at
Fig. 1. Four different types of twins.
four to eight days after fertilization causes MC di-
amniotic MZ twins, the most common type (70%).
MC monoamniotic twins occur when the division
takes place more than eight days after the fertiliza-
tion and represent only 2–4% of the MZ twins.
Incomplete division of the embryonic disk after 13
days causes conjoined twins.
Amnionicity in MC pregnancies can accurately
be determined around 8 weeks of gestation, from
which time it is possible to visualize the amniotic
membrane. Earlier in the first trimester, the num-
ber of yolk sacs may be used to diagnose amnionic-
ity. When two yolk sacs are seen in the extraem-
bryonal celoma, the pregnancy will be diamniotic,
while a single yolk sac will in most cases lead to
monoamniotic twins and should prompt a follow
up scan at 9–10 weeks to assign amnionicity de-
finitively (11).
Congenital anomalies
Most studies of congenital anomalies in twins have
not related their incidence to zygocity or placen-
tation. Myrianthopoulos (12) and Baldwin (13)
have both found that congenital anomalies were
1.2–2 times more common in twins than single-
tons. In DZ twins the rate per fetus is the same as
in singletons, whereas in MZ twins the rate is 2–3
times higher. The most common structural abnor-
malities are cardiac, neural tube and brain defects,
facial clefts, gastrointestinal, and anterior abdomi-
nal wall defect (14, 15). Among cardial defects,
especially persistent ductus arteriosus, single ven-
tricle and ventricular septal defect are seen more
often in twins (16, 17).
In a recent international registry study 5572
malformations were diagnosed in 260,865 twins,
giving a 1.25 relative risk (95% confidence interval
1.21–1.28) of congenital anomalies in twins com-
pared to singletons from the same registries (17).
This study confirmed that the anomalies mention-
ed above are significantly more common in twins,
but also suggested that all anatomical systems ap-
pear to be involved (14, 15). The limitation of the
study was that the incidence of malformations was
neither correlated to chorionicity or zygocity, nor
to the children’s sex.
For any given defect the pregnancy may be con-
cordant or discordant in terms of both the type
of abnormality and its severity. The majority of
structural defects are discordant regardless of zyg-
ocity. Discordance in DC twins is usually due to
differences in genetic predisposition, whereas in
MC twins discordance may be a consequence of
the underlying stimulus to zygote splitting, vari-
ation in gene expression, or a consequence of ab-
normal placentation (18). Apart from the struc-

Twin pregnancy 289
tural fetal defects, which also occur in singletons,
there are three types of congenital anomalies
unique to twin pregnancies. The first are midline
structural defects believed to be a consequence of
the twinning process, represented by conjoined
twins. The second are malformations resulting
from vascular anastomoses with the acardiac mon-
ster being the classical example. Malformations
such as microcephaly, periventricular leucomalac-
ia, hydrocephalus, intestinal atresia, renal dys-
plasia and limb amputation may also be secondary
to vascular defects caused by the demise of a co-
twin with subsequent hypotension, vascular
thrombosis and/or ischemia in the surviving fetus.
Thirdly, some defects or deformations may result
from intrauterine crowding including foot deform-
ities, dislocation of the hip and skull asymmetry
(19). While the third group can be seen in MZ as
well as DZ twins, the first two groups are unique
to MZ twins. The congenital malformations
unique to twin pregnancies are very rare.
Conjoined twins may be diagnosed by prenatal
ultrasonography from 12 weeks of gestation. If the
parents consider continuing the pregnancy, it is es-
sential to perform a detailed ultrasound scan to
assess which viscera are shared. Particular empha-
sis should be put on the examination of the fetal
heart, as the prognosis for twins with a shared
heart is very poor.
Risk of chromosome abnormalities in twin
gestations
Because most twins are DZ and most trisomies re-
sult from non-disjunction during meiosis, before
formation of the zygote, it may be assumed that
each twin has an a priori risk of having an aneu-
ploid chromosome complement. This assumes a
probability of non-disjunction in the second twin
independent of the chromosome complement of
the first twin. In DZ twins, therefore, a chromo-
some abnormality will most likely involve only one
of the twins. On the other hand, in MZ twins a
chromosome abnormality will nearly always in-
volve both twins. In very rare instances MZ twins
may have different karyotypes, presumably as a re-
sult of postzygotic nondisjunction. On the basis of
existing tables of estimated risks of chromosome
abnormalities in singleton gestations (20), Rodis et
al. (21) derived tables defining the age-related risks
of chromosomal abnormalities in twin gestations.
The expected risk of having at least one twin
affected by Down’s syndrome (DS) was greater
than that for a singleton of comparable maternal
age. Indeed for a patient at 32 years of age with a
twin gestation, the risk of having at least one twin
affected by DS was similar to that of a 35-year old
woman with a singleton gestation. However, the
observed birth prevalence in 106 twin pregnancies
with DS was only 3% greater than for singletons
(22). A very high miscarriage rate in twins affected
by DS could explain the discrepancy between the
expected and the observed rates of Down’s syn-
drome (22).
Prenatal screening and diagnostic tests
Crown-rump length measurement
A difference in crown-rump length measurement
between the two embryos may be the first sign of
chromosome abnormality, major congenital anom-
alies or imminent demise in the smaller twin (23,
24). At less than eight weeks of gestation a differ-
ence of more than three mm was associated with a
50% risk of intra-uterine death of the smaller twin
(25).
The consequences of intertwin disparity in
crown-rump length were examined in a study of
123 MC and 416 DC twins (26). There was no cor-
relation between intertwin disparity in crown-
rump length and intertwin disparity in birth
weight. In DC pregnancies a significantly higher
intertwin disparity was found in those pregnancies
with chromosomal abnormality, miscarriage or
intrauterine death in one or both fetuses as com-
pared to those pregnancies resulting in two live
births. This was not the case among the MC twin
pregnancies. Previous smaller studies have shown
the same results (23–25). An explanation could be
that in DC pregnancy early-onset growth restric-
tion due to a genetic defect or to impaired placen-
tation occurs in one of the fetuses. In MC pregnan-
cies, on the other hand, the genetic constitution
and trophoblast invasion should be the same for
the two fetuses and there does not seem to be a
significant imbalance in the blood flow through the
placental vascular communications at this stage of
pregnancy (26). To determine the gestational age
in twins, the largest CRL should be used.
Screening for trisomy 21 in twin pregnancies
Genetic counseling and prenatal diagnostic testing
in twin gestation is complicated, because the
methods of screening are less effective and the
techniques of invasive testing may provide uncer-
tain results or may be associated with higher risks
of miscarriage. In addition, the fetuses may be dis-
cordant for an abnormality, in which case one of
the options for the subsequent management of the
pregnancy is selective feticide.

Biochemical screening
In singleton pregnancies screening by alfa-feto-
protein (AFP), human chorionic gonadotropin
(HCG) and unconjugated estriol in the second tri-
mester yields a 70% detection rate for a 5% false-
positive rate. In cases of twins, the underlying as-
sumption is that each fetus contributes 50% of the
analyzed level in maternal serum, but precise bio-
chemical information about each co-twin is lack-
ing. As most twin pregnancies are DZ and most
likely have only one affected fetus, the presence of
an unaffected co-twin will tend to bring the distri-
butions for affected and unaffected twin pregnan-
cies relatively closer together compared with
affected and unaffected singleton pregnancies.
In the second trimester the median level of bio-
chemical markers in unaffected twin pregnancies is
about double that in singletons (27) with perhaps
levels of unconjugated estriol being only 1.7 times
that in singletons. The reported number of twins
where one or both fetuses had DS is too small to
calculate the marker distributions in affected
twins. Using the pseudo-risk correction procedure
outlined by Wald et al. (27) the estimated detection
rate in twins was 52–55%, i.e. some 15% lower than
in singleton pregnancies, for the same false-posi-
tive rate of 5% (28).
In the first trimester few data are available on
the behavior of biochemical markers in twin preg-
nancies. Free beta-HCG levels may be elevated to
about twice the normal level in singletons preg-
nancy, while for pregnancy-associated protein A
(PAPP-A) the level is slightly lower (1.8 MoM).
Whether the detection rate in the first trimester
can be increased above that in the second trimester
remains to be shown.
Ultrasound screening
In singleton pregnancies screening by maternal age
and fetal nuchal translucency (NT) can identify
about 80% of chromosomally abnormal fetuses for
an invasive testing rate of 5% (29).
In the only large twin pregnancy study the NT
was above the 95th centile of the normal range in
65 out of 896 fetuses (7.3%), including seven of
eight with trisomy 21 (30). In the chromosomally
normal twin pregnancies the prevalence of in-
creased NT was higher in fetuses from MC (8.4%)
than DC pregnancies (6.9%). This study thus sug-
gests that the DS detection rate may be similar in
twin and singleton pregnancies, but the false-posi-
tive rate is higher in twin pregnancies, especially in
MC pregnancies.
It may be concluded that it is possible to screen
twin pregnancies for DS in the first as well as in
the beginning of second trimester. The sensitivity
of biochemical screening is 10–15% lower than in
singleton pregnancies for the same false-positive
rate, while NT screening yields the same detection
rate but at a 50% higher false-positive rate than in
singleton pregnancies. The additional advantage of
NT screening is that when one of the fetuses is
found to have a chromosomal abnormality and the
other is normal, the presence of a sonographically
detectable marker ensures the correct identification
of the abnormal twin, should the parents choose
to have a selective termination of pregnancy.
Further data are required regarding the per-
formance of a screening combining biochemistry
and ultrasonography, but the addition of maternal
serum biochemistry to NT could be expected to
increase the detection rate by a further 5–6% (31).
Invasive prenatal diagnostic tests
The efficacy and safety of second-trimester amnio-
centesis (AC) and first-trimester chorionic villus
sampling (CVS) will be examined first, the ques-
tion of selective termination later. CVS is as effec-
tive as AC in providing sufficient tissue for accu-
rate diagnosis (32). One concern about CVS is that
there is no method available to confidently assess
the source of chorionic villi. In cases of same-sex
twins sampled by CVS, there is no guarantee that
each twin was individually sampled. Therefore
each chorion frondosum must be accurately and
meticulously identified before and during CVS
sampling. Even so, there is uncertainty in about
5% of CVS procedures that both placentas have
been sampled, as compared to 0.3% of AC (32).
During AC, aspiration of separate gestational sacs
can be confirmed by injecting a coloring agent
such as indigo carmine into the first sac. This dye
has never been associated with any fetal or neo-
natal complications. Another dye, methylene blue,
increased the risk of fetal death by a relative risk
of 8.5 in an Australian study of 262 twins (33).
Furthermore, a causal relationship between in ut-
ero methylene blue exposure and jejunal atresia
was strongly suggested in a study of 89 twin preg-
nancies (34). The advent of real-time ultrasound
has made dye injection obsolete in nearly all cases,
since it allows visually guided amniotic fluid sam-
pling from both sacs.
Sampling MC twin pregnancies presents unique
problems. Although theoretically most MC preg-
nancies require only a single sampling, exceptions
do occur in cases of heterokaryotypic twins or
when the ultrasound impression of a single cho-
rion is incorrect.
The spontaneous abortion rate in ultrasono-
graphically normal twin pregnancies not under-

Twin pregnancy 291
going an invasive procedure is poorly documented
in the literature. Sebire et al. reported that 12.7%
of 102 MC pregnancies detected before 15 weeks
of gestation miscarried at least one fetus, while in
the 365 DC pregnancies the rate was 2.5% (30).
The spontaneous abortion rate in twin pregnancies
thus seems to be higher than in singletons.
The procedure-related risk of fetal loss is about
1% after AC at 16–20 weeks of gestation (35), as
well as after first trimester CVS (36) in singleton
pregnancies. Because twins have a higher spon-
taneous abortion rate than singletons, the most
appropriate control group would consist of twin
pregnancies of the same gestational and maternal
age not undergoing an invasive procedure. The
studies on the risk of invasive prenatal diagnostic
procedures in twin pregnancies all have significant
limitations: some did not have complete follow-up,
most are small-uncontrolled studies or studies
using singleton pregnancies as controls, and a ran-
domized study has not been conducted (37–41).
These factors can explain the wide variation in
reported post-procedural fetal loss rates (Table I).
As the number of instrumental insertions in AC
as well as CVS in singletons has been associated
with an increase in procedure-related fetal losses
(NICHD 1977) (42), it has been suggested that
these procedures in twin pregnancies should be
performed by a single insertion. This was shown
to be successful in 48 of 55 pregnancies having AC
(43), but the study was unfortunately too small to
draw any conclusions concerning the risk of fetal
loss. The risk of an invasive prenatal diagnostic
procedure in twin pregnancies resulting from mul-
ti-fetal pregnancy reduction does not seem to differ
from that in non-reduced twin pregnancies (44,
45).
It may thus be concluded that it is difficult to
judge the extent to which the miscarriage rate fol-
lowing an invasive procedure in twin pregnancies
is causally linked to the test. A cautious estimate
may be that it is between the same and twice the
risk in singleton pregnancies. There does not seem
to be a great difference between the fetal loss rate
Table I. Miscarriage rate following invasive prenatal diagnostic tests in twin pregnancies
Miscarriage rate
Study group Control group
N % N %
Twins with AC compared to singletons without AC37
330 3.6 671 0.6
Twins with AC compared to twins without AC38
101 3.5 108 3.2
Twins with CVS compared to twins without CVS39
104 3.4 101 6.9
Twins with AC compared to twins with CVS40
72 2.9 161 3.2
AC: amniocentesis. CVS: chorionic villus sampling.
after AC and CVS. The fact that sampling accu-
racy in twin pregnancy is higher when AC is
chosen, speaks in favor of AC. However, the
method of choice for invasive prenatal diagnosis
must be seen in relation to the risk associated with
selective termination.
Selective termination
Selective termination is a procedure in which an
abnormal fetus in a multifetal pregnancy is termi-
nated in order to allow the pregnancy to continue
to term with the normal fetus(es). Multifetal preg-
nancy reduction, on the other hand, is the elective
reduction of three or more fetuses to a smaller
number of fetuses in an attempt to reduce the mor-
tality and morbidity of the surviving fetuses. Both
these procedures present complex ethical and
moral dilemmas for the parents and for the obstet-
rician.
When a structural malformation or chromo-
somal abnormality is diagnosed in one twin, the
parents have the options of continuing the entire
pregnancy, terminating the entire pregnancy or of
selective termination of the affected fetus. With
rare exceptions, a selective termination is not offer-
ed when the fetal anomaly is lethal, as selective
termination has the potential of causing loss of the
entire pregnancy. On the other hand the presence
of a fetus with a major anomaly seems to increase
the risk of preterm delivery (46). Twin pregnancies
complicated by a fetus with a major anomaly will,
on average, be delivered two weeks earlier than
other twin pregnancies, resulting in a lower birth
weight and associated risks of prematurity for the
unaffected twin. Therefore selective termination
should be included in the management options in
cases of non-lethal, major anomalies in one twin.
The failure of the initial attempts at performing
selective termination may have been due to the fact
that they were performed in MZ twins with a
shared placenta. In such cases the death of one
fetus results in exsanguination of the remaining
fetus. Currently selective termination in MC twins

can be achieved by umbilical cord ligation under
ultrasound guidance or by fiber-optic fetoscopy
(47). Obviously selective termination for DC twins
has a better chance of succeeding, and has been
shown to be technically successful in virtually
100% of cases (48). In DC pregnancies the benefits
expected from selective termination should be
weighed against the potential risk of the procedure
concerning the unaffected twin (49). Selective ter-
mination can be done by several methods, intra-
cardiac or intrafunic injection of KCl appears to
cause a lower miscarriage rate (8.3%) than air em-
bolization (41.7%) (48).
In 1994 a collaborative report from 9 centers on
169 twins (48) showed that the gestational age at
the time of the procedure correlated positively with
loss rate and inversely with gestation at delivery.
In fact when the procedure was performed before
16 weeks 5.4% of the pregnancies were lost, while
14.4% of the pregnancies were lost when the pro-
cedure was performed after 17 weeks. In 1999 a
larger collaborative report, partly from the same
centers (50), presented data on 345 selective ter-
minations in twins from 8 centers. The spon-
taneous abortion rate before 24 weeks was 7.0%
and 80% of all viable deliveries occurred after 33
weeks. There was no longer any correlation be-
Fig. 2. Cumulative fetal loss rates in monochorionic (solid line)
and dichorionic (dashed line) twin pregnancies, from week 12
of gestation (With permission) (52).
tween the gestational age at the time of the pro-
cedure and the loss rate, nor with the gestational
age at delivery.
It thus seems that, with increasing experience,
there has been a plateauing of risks and flattening
of the gestational age curve. This underlines the
importance of centralizing these procedures. Early
prenatal diagnosis may still be optimal, however,
to ensure the correct diagnosis of chorionicity
without which selective termination cannot be
done safely.
Miscarriage and perinatal mortality
In a large registry study, which could not distin-
guish between DC and MC pregnancies, the peri-
natal mortality rate was 5–6% higher in twins than
in singletons (51). Perinatal statistics will, however,
underestimate the contribution of MC placen-
tation to fetal death, since the highest mortality
rate in MC pregnancies is before 24 weeks (Fig. 2).
In a prospective study (52), at least one fetal loss
occurred before 24 weeks of gestation in 12.7% of
the 102 MC and 2.5% of the 365 DC pregnancies,
and there was at least one perinatal loss after 24
weeks in 4.9% of MC and 2.8% of DC pregnancies.
This study confirms that the miscarriage rate, as
well as the perinatal mortality, is higher in twins
than in singletons, and especially among MC
twins.
Preterm delivery
Preterm delivery is the major cause of mortality
and morbidity in twin pregnancies. In a large Cali-
fornian multicenter study the preterm delivery rate
(Ͻ32 weeks) was 15–17% among 432 twin preg-
nancies as compared to 1–2% in 33,451 singleton
pregnancies. Furthermore, although only 2.6% of
the fetuses were twins, they accounted for 9.5% of
all stillbirths, 15.4% of all neonatal deaths and
12.2% of all perinatal deaths (53).
There is some evidence that sonographic assess-
ment of the cervix can predict singleton pregnan-
cies at high risk of preterm delivery. Iams et al.
conducted (54) a multicenter study measuring cer-
vical length at 24 and 28 weeks gestation in 2915
unselected women. The relative risk of preterm de-
livery increased with decreasing length of the cer-
vix. The sensitivity of the test does, however, ap-
pear to be lower in symptom-free low-risk patients
than in patients with symptoms of preterm labor
(55).
In 215 twin pregnancies assessed in week 23 (56)
the risk of preterm delivery increased exponen-
tially with decreasing cervical length, just as in
singletons (54, 57). Two studies have tried to find

Twin pregnancy 293
the optimal cut-off in cervical length. In 85 women
with twin pregnancies, the positive predictive value
of a cervical length greater than 35 mm at 24–26
weeks for delivery at term was 97%. A cervical
length of Æ25 mm, however, only identified 31%
of those who delivered preterm at or before 33
weeks (58). Similarly Goldenberg and co-workers
(59) found that the specificity for preterm delivery
of a cervical length Ͻ25 mm in week 23 was 86%
in 147 twin pregnancies, while the sensitivity was
54%. When the ultrasound scan was done in week
27 the sensitivity increased to 63%, but the speci-
ficity decreased to 69%. A single transvaginal ex-
amination at 23–26 weeks thus seems able to iden-
tify most twin gestations at low risk of preterm
birth. However, the most important issue is to be
able to detect those pregnancies at high risk of de-
livering preterm, and the sensitivity may increase
with gestational age. In women admitted with signs
of preterm labor between 23 and 33 weeks of ges-
tation, the cervical length was a better predictor of
preterm delivery than funneling or digital exami-
nation in singletons as well as twin pregnancies
(60). Measurement of cervical length may thus be
useful not only as a screening but also as a diag-
nostic method.
Cerclage reduced the risk of preterm labor ten
times in singletons with cervical length below 20
mm at 23 weeks (61). This treatment is now being
evaluated in a randomized controlled trial in
singletons as well as in twin pregnancies.
Monoamniotic twins
Monoamniotic twins are the least common form
of twin placentation (1–2%), but have the highest
fetal mortality rate (30–70%). Cord entanglements
as well as acute forms of TTTS cause the majority
of the fetal losses.
Cord entanglement can be demonstrated by
Doppler examination in the first trimester (62), but
will, however, be present in most cases. It has been
suggested that the larger the fetuses, the smaller
the risk of cord compression causing fetal death.
Stabilization of fetal position has been attempted
by administration of ‘Sulindac’ to the mother in
order to reduce amniotic fluid volume and thereby
the risk of cord compression (63). All six pairs of
twins in this study were delivered without compli-
cations.
When monoamniotic twins are diagnosed, the
parents should be counseled about the high risk of
fetal death. If the pregnancy is continued, it should
be intensively monitored and delivery appropri-
ately timed. Evidence regarding the optimal time
of delivery is lacking, most opt for delivery around
32–34 weeks.
Fetal growth abnormalities
The incidence of fetal growth restriction is signifi-
cantly increased in twins compared to singletons.
The main factors determining fetal growth are gen-
etic potential and placental function, which is
thought to be due mainly to the trophoblast in-
vasion of the maternal spiral arteries. In MC preg-
nancies both the genetic potential and the tropho-
blast invasion should be the same, whereas in DC
pregnancies there may be differences in the genetic
constitution of the fetuses and of the placenta.
Abnormal growth in twin pregnancies may be
detected by identifying growth discordance or
small for gestational age (SGA) children (defined
as birth weight 2 standard deviations or more be-
low the mean for gestational age) (64). The most
accurate assessment of fetal growth discordance is
to compare abdominal circumferences. After 24
weeks an intertwin abdominal circumference dif-
ference of 20 mm or more, irrespective of ges-
tational age, had an 83% positive predictive value
to detect a difference in birth weight of 20% or
more (65–67). Early second-trimester inter-twin
weight discordance, however, was not correlated to
birth weight discordance (26), but may instead be
the consequence of a genetic defect or impaired
placentation.
In order to find the SGA fetuses, their weight
has to be compared to a norm. It is well known
that the fetal weight of twins is close to that of
singletons up to 30 weeks (68). After that time the
overall pattern of fetal growth is slower for twins
compared to singletons (69). Min et al. (69) have
developed a birth weight reference for twins ac-
cording to chorionicity, sex and race on the basis
of longitudinal measurements, which maybe
should be used to assess SGA in twins in the fu-
ture.
The risk of growth retardation was about four
times higher in MC (7.5%) compared to DC (1.7%)
pregnancies (52). This finding is dependent on the
reference or standard used, and the difference may
be smaller if based on a chorionicity-dependent
reference.
In a historic cohort study of 903 twins, Grob-
man & Parilla (70) demonstrated that the positive
predictive value of a 20–24 weeks weight esti-
mation to identify SGA infants was 85%.
Among infants with normal weight the elapsed
time until a growth abnormality was detected was
10 weeks. This underlines the importance of the
20–24 week scan, since it may predict which infants
will become SGA.
Several studies have suggested that discordance
in umbilical artery flow is associated with growth
discordance in twins and can identify those fetuses

at high risk for unfavorable outcome (71, 72).
Studies of the middle cerebral arteries permit as-
sessment of redistribution of blood flow under
conditions of fetal distress, where the brain sparing
effect occurs. MC twins more often had brain-
sparing effect than the DC twins, even in the MC
group without TTTS (73–75). This may be one ex-
planation for the higher mortality and morbidity
seen in the MC group.
Twin-twin transfusion syndrome
The twin-twin transfusion syndrome (TTTS) com-
plicates 5–15% of all MC twin pregnancies (52). It
is one of the most lethal conditions in fetal medi-
cine with an 80–100% mortality rate without treat-
ment (76) and a 15–50% risk of handicap in sur-
vivors (4).
Pathogenesis
Cross circulations may be found in both MC and
DC placentas, but the TTTS is a phenomenon of
MC twins and is only very rarely seen in MZ DC
twins. The classic concept of the pathogenesis has
been that it is caused by a simple shift of blood
from the donor twin to the recipient. More recently
it has, however, been suggested that placental vas-
cular anastomoses in twins with TTTS are fewer,
more often solitary and of the arteriovenous type
than in twins without TTTS (4). This hypothesis is
supported by histopathological studies from Can-
ada, where all MC twins with unidirectional a-v
anastomoses in the absence of superficial anastom-
oses developed TTTS as compared to only 11%
among the twins with several superficial anastom-
oses (77). TTTS may thus be the result of a paucity
of bi-directional superficial anastomoses making
some MC twins unable to compensate for the
hemodynamic imbalance resulting from the unidi-
rectional transfusion along the arterio-venous ana-
stomosis.
Through the vascular anastomoses, one of the
fetuses becomes a donor and gradually develops
anemia, hypovolemia, hypotension and growth re-
tardation, whereas the recipient becomes hyper-
volemic, hypertensive and macrosomic with in-
creased urinary output. The discrepancy in blood
volume results in oligouria with consequent anhyd-
ramnios in the donor and polyuria with conse-
quent polyhydramnios in the recipient. Signs of hy-
drops fetalis are occasionally found in the recipient
twin, rarely in the donor and seldom in both.
The most bizarre form of intertwin transfusion
is the Reverse arterial perfusion (TRAP): One twin
(the pump) actively perfuses the acardiac co-twin
via retrograde flow. Typically the pump twin is
structurally normal, but at high risk of developing
cardiac failure. The mortality without treatment is
greater than 50% (78).
Diagnosis
The first sign is a marked discordance in amniotic
fluid volume in MC twins (79, 80). An estimation
of amniotic fluid volume is therefore used to assess
the well being of both twins. An amniotic fluid
index above 40 cm or a deepest vertical pocket
above 12 cm in the larger sac seems to select severe
cases (81).
Discordance in size with the larger twin in the
polyhydramniotic sac is usually seen. In most cases
the donor appears as the stuck twin, fixed to the
placenta or uterine wall by the intertwin mem-
brane because of anhydramnios, while the recipient
has polyhydramnios. The donor’s bladder is small
or empty, while the recipient shows signs of poly-
uria with a distended bladder. Doppler ultrasono-
graphy is used to assess fetal well-being. Absent or
low-end diastolic velocities in the umbilical artery
are signs of increased placental resistance. Poor
prognostic factors include reverse flow in the um-
bilical arteries, reduced pulsatility index in the
middle cerebral arteries as a sign of fetal blood
flow redistribution and pulsatile flow in the umbili-
cal vein, reverse flow in the ductus venosus, or pul-
satile flow in the umbilical vein. Decreased ven-
tricular function, tricuspid regurgitation and car-
diac chamber enlargement are commonly seen in
the recipient (82). In severe cases the recipient de-
velops non-immune hydrops and tricuspid incom-
petence (74). Fetal echocardiography (83) should
therefore be performed, since the perinatal prog-
nosis of the recipient twin depends on the severity
of the cardial disease.
Recently a classification of TTTS has been advo-
cated in order to individualize the therapeutic op-
tions and to allow comparison of outcomes from
different centers (84) (Table II).
Prediction
Three methods seem to have the potential to pre-
dict which MC twins are at increased risk of devel-
oping TTTS. As early as in week 10–14 an in-
creased NT may be a sign of TTTS. The likelihood
of developing severe TTTS was 4.4 (95% confi-
dence interval 1.8–9.7) among those MC twins
with a NT above the 95th centile (85).
Identification of arterio-arterial anastomoses by
color Doppler on the placental plate may detect a
low risk group in which only 5% developed TTTS.
In twins without a-a anastomoses, on the other
hand, TTTS was diagnosed in 58% (86). The an-

Twin pregnancy 295
Table II. Staging of TTTS based on sonographic and Doppler findings (modi-
fied after Quintero et al., (ref. no. 84)
Ultrasonographic signs
Stage Donor Recipient
1 Oligohydramnion Polyhydramnios
Bladder still visible
2 Bladder not visible
3 Abnormal Doppler indices*
4 Hydrops Hydrops
5 (Fetal demise) Fetal demise
* Abnormal Doppler indices: absent end-diastolic velocity in the umbilical ar-
tery, reverse flow in the ductus venosus or pulsatile umbilical venous flow
usually with tricuspid regurgitation.
TTTS: Twin-twin transfusion syndrome.
gioarchitecture was confirmed by postnatal injec-
tion. This study confirmed the theory associating
a paucity of superficial anastomoses in MC twins
with TTTS. Further prospective studies are indi-
cated to determine the utility of color Doppler to
predict the risk of TTTS.
The most promising sign may be the folding of
the intertwin membrane at 15–17 weeks, caused by
the disparity in amniotic fluid volume in the two
amniotic sacs (87). In a prospective study of 83
MC twins, there were 23 cases with membrane
folding (28%), half of which developed severe
TTTS, while the rest developed mild TTTS. All 60
pregnancies without membrane folding resulted in
live births without signs of TTTS.
Management
Serial therapeutic amniocenteses may relieve po-
lyhydramnios and thereby prevent preterm labor
(88–91). The reduction in amniotic fluid pressure
may also improve the perfusion to the donor. It
has been suggested removing approximately one
litre of amniotic fluid for every 10 cm the Amniotic
Fluid Index is elevated (91). Serial aggressive am-
nioreduction is associated with an overall perinatal
survival rate around 65% (92), but with a 15–50%
risk of serious handicap in the survivors (93).
More recent developments in the management
of TTTS are fetoscopy and laser coagulation to
interrupt the placental vascular anastomoses be-
tween the twins. Under continuous ultrasound and
fetoscopic visualization the chorionic plate along
the inter-twin membrane is examined to identify
the crossing vessels, which are then coagulated
with a laser beam. Subsequently amniotic fluid is
drained to obtain a subjective normalization of the
amniotic fluid volume. Theoretically coagulation
of the specific vessels (a-v anastomosis) should al-
leviate TTTS. However, coagulation of several ves-
sels seems to protect the survivor if the other twin
dies in utero. In a multi-center study endoscopic
laser was carried out at a median of 21 weeks and
the perinatal survival for both twins was 55% and
73% for at least one surviving child (94).
These results are comparable to serial amniocen-
teses, but the handicap rate in survivors appeared
lower. In a more recent German study (95) the re-
sults from one center performing laser surgery in
73 twin TTTS pregnancies were compared to 43
twin TTTS pregnancies treated with amnion drain-
age. The overall survival rate was the same in the
two groups, but there were a significantly higher
proportion of pregnancies with at least one sur-
vivor in the laser group (79% versus 60%). The in-
cidence of abnormal neonatal brain scans was sig-
nificantly lower among survivors in the laser group
(6%) than in the amniocentesis group (18%). This
may be due to the protective effect of coagulating
the communicating vessels, combined with a
higher gestational age at delivery. The results of
laser surgery appear better than serial amniocen-
teses, but have so far only been evaluated in obser-
vational studies. An on-going multi-center Euro-
pean randomized controlled trial will determine
whether the results of laser surgery are superior to
serial amniocenteses.
A new non-invasive technique, focused ultra-
sound surgery, may become a non-invasive method
to occlude placental vessels (96).
Selective feticide of one twin may be considered
in those cases, where one of the twins appears to
be at imminent demise or once other treatment has
failed to try to salvage the co-twin. Selective reduc-
tion should involve an occlusive technique to pre-
vent any possibility of the surviving twin exsan-
guinating into the terminated twin’s circulation.
Intrauterine ligation of one umbilical cord and bi-
polar coagulation have been shown to be feasible,
but these procedures should still be considered in-
vestigational (47, 97–99).
Non steroid anti-inflammatory drugs have been
used as a treatment for polyhydramnios in single-
tons, as they reduce fetal urinary output. They are,
however, contraindicated in twins with TTTS, be-
cause they have a harmful effect on the oligouric
donor twin (100).
Neurological damage in twins
Death of one twin in a MC pregnancy is associated
with a 25% risk of demise for the co-twin or at
least a 25% risk of neurological and/or renal
lesions in the survivor (101, 102). Antenatal ce-
rebral white matter lesions seem to be more com-
mon in MC twins both with and without TTTS

Table III. Recommendations for ultrasonographic evaluation of twin pregnancies
Gestational week Examination
Before week 15 O Determination of chorionicity
O Measurement of nuchal translucency in both twins
O Measurement of CRL in both twins
In week 16 –25 Control of MC twins every other week for:
O Folding sign, and the a-a anastomoses
O Signs of TTTS (Amnion fluid volume, the bladders of the fetuses, hydrops)
In week 18–20 Check for structural anomalies for both MC and DC
In week 21–22 Fetal echocardiography for both MC and DC
In week 23 For both MC and DC:
O Assessment of cervical length
O Measurement of the abdominal circumference of both fetuses
O Determine the weight discordance
From week 28 to delivery Growth assessment and rule out discordance
MC: monochorionic. DC: dichorionic. TTTS: twin-twin transfusion syndrome.
compared to DC twins as well as singletons (103),
and in both the recipient and the donor TTTS twin
(104).
The risk for the co-twin in MC pregnancies to a
large extent depends upon the vascular anatomy of
the monochorionic placenta. The precise mecha-
nism of the co-twin compromise is unclear, but is
probably the consequence of a hemodynamic im-
balance resulting from a lack of placental ana-
stomoses. A dying twin gives rise to a fall in blood
pressure, and blood from the survivor is transfused
into the fetoplacental circulation of the dead twin,
causing severe hypotension and irreversible brain
damage in the survivor (105, 106). Conservative
management (101) after fetal death of one twin in
TTTS has a very poor prognosis and supports the
concept of active management.
At 24 weeks infants with normal weight have a
40% chance of survival, compared to 80% at 28
weeks. The prognosis is much worse, both in re-
lation to perinatal mortality and in relation to
neurological damage, when the fetuses are SGA or
pathological Doppler velocities are found in the
umbilical arteries (107).
In conclusion, this literature review leads us to
suggest the following examination program for
twin pregnancy (Table III).
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Address for correspondence:
Lene Sperling, M.D.
The Ultrasound Clinic
Juliane Marie Center, Rigshospitalet
Copenhagen
Denmark

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