Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

Early pregnancy assessment in multiple

pregnancies
Francesco D’Antonio, MD, Amar Bhide, MD *
Fetal Medicine Unit, Division of Developmental Sciences, St George’s University of London,
London SW17 0RE, UK

Keywords:
Early ultrasound assessment and accurate determination of cho-
twin pregnancy rionicity is crucial so that appropriate care of multiple pregnancy
ultrasound can be provided. It is best achieved in the first trimester of preg-
prenatal diagnosis nancy using the Lambda ‘l’ and ‘T’ signs. Accurate labelling of the
twins is needed to ensure that the same individual fetus is
measured through the pregnancy so that the longitudinal growth
pattern can be correctly assessed. Discrepancy in crown–rump
length indicates a possibility for future development of selective
intrauterine growth restriction. Careful early ultrasound assess-
ment is needed to identify structural and chromosomal anomalies,
as twin pregnancies are at increased risk. Twin-to-twin transfusion
syndrome, selective intrauterine growth restriction and congenital
abnormalities represent the major determinants of perinatal loss
in monochorionic pregnancies, and diagnosis and prognosis are
discussed in detail. Treatment of twin reverse arterial perfusion
sequence is more effective in early pregnancy, so early identifica-
tion is needed. Outcome of conjoined twins is guarded, and is
dependent on the extent of fusion, degree of sharing of organs,
associated anomalies, and presence of cardiac failure in utero.
Ó 2013 Elsevier Ltd. All rights reserved.

Introduction

Multiple pregnancies are at increased risk of neonatal mortality and morbidity compared with
singleton pregnancies, This may result from preterm birth, congenital abnormalities, growth problems,
and unique complications related to monochorionicity, such as twin-to-twin transfusion syndrome
(TTTS) and twin reversed arterial perfusion (TRAP) sequence. Early ultrasound assessment is crucial, so

* Corresponding author. Tel.: þ44 20 87250009; Fax: þ44 20 87250079.

E-mail address: abhide@sgul.ac.uk (A. Bhide).

1521-6934/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bpobgyn.2013.11.006
202 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214

that appropriate care of these pregnancies can be provided. Determination of chorionicity in the first
trimester allows stratification of the obstetric risk and the planning of subsequent scans, whereas
accurate labelling of twins is fundamental for the evaluation of the longitudinal growth pattern of
twins, especially when discordance is observed.
Early ultrasound assessment of congenital anomalies is important because congenital anomalies are
more frequent in multiple gestations, and the presence of a structural or chromosomal abnormality
leading to intrauterine demise may profoundly affect survival and neurological outcome of the sur-
viving co-twin, particularly in monochorionic pregnancies.
In this manuscript, we provide an up-to-date review of the role of early ultrasound assessment in
twin pregnancies, with particular focus on determination of chorionicity, twin labelling, early diagnosis
of complication related to monochorionicity, and prediction of adverse outcomes.

Assessment of chorionicity

The pregnancy loss rate in monochorionic twins is significantly higher than that of dichorionic
pregnancies, especially because of complications related to monochorionic placentation, such as TTTS
[1–3]. Previous studies estimating pregnancy loss in twin pregnancies have found that most of these
deaths take place before 24 weeks of gestation, when the likelihood of developing TTTS is significantly
higher than in the third trimester of pregnancy [4–6].
Accurate determination of chorionicity is, therefore, mandatory in the routine care of twin preg-
nancies to distinguish which pregnancies are at risk and to allow the early detection of these specific
complications. Several methods of chorionicity determination have been reported, such as the number
of placentas, fetal sex, the presence and thickness of the inter-twin membrane, and the presence of
‘lambda’ or ‘twin peak’ sign in case of dichorionic and ‘T’ sign in case of monochorionic twins [7–11].
Ultrasound determination of chorionicity is best achieved in the first trimester of pregnancy using the
Lambda (l) and T signs. ‘l’ or ‘twin peak’ sign refers to the classical appearance of the inter-twin
membrane at its placental attachment. In the case of dichorionic placentation, the presence of a
triangular tissue projection extending from the base of the inter-twine membrane gives the latter a
characteristic appearance of the Greek letter ‘l’. This projection is produced by extension of chorionic
villi into the inter-chorionic space of the twin membrane at the point where it encounters the chorion
and placenta of the co-twin (Fig. 1a). In the case of monochorionic placentation, the lack of tissue
projection into the inter-twin membrane prevents the formation of ‘l’ sign, and the inter-twin
membrane inserts perpendicularly in the placental plate (Fig. 1b) [12]. These two signs are mutually
exclusive in twins with a single placental mass [13].
The largest study on the accuracy of the l and T signs, and the number of placental in determining
chorionicity in first-trimester diagnosis of chorionicity reported a sensitivity and specificity of 100%

Fig. 1. How to differentiate between monochorionic and dichorionic twins. (a) In the case of dichorionic placentation, the presence
of a triangular tissue projection extending from the base of the inter-twine membrane gives the latter a characteristic appearance of
the Greek letter ‘l’; (b) in the case of monochorionic placentation, the lack of tissue projection into the inter-twin membrane
prevents the formation of l sign and the inter-twin membrane inserts perpendicularly in the placental plate (white arrows).
 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214 203

and 99.8%, respectively, when these ultrasound markers are used to diagnose chorionicity between 11
and 14 weeks of gestation [7]. Recently published papers are shown in Table 1.
Although highly predictive of dichorionic placentation in the first trimester of pregnancy, the l-sign
gradually disappears during the second trimester of pregnancy, limiting its predictive accuracy [13]. In
the absence of a clear assignment, the pregnancy should be considered monochorionic and be
monitored as such. It is important to look for the lambda sign at the insertion of the inter-twin
membrane on the placental surface, and not the uterine wall (Fig. 2). Membrane insertion on the
uterine wall gives a false impression of a ‘T’ sign when the pregnancy, in fact, is dichorionic.
The thickness of the inter-twin membrane has been reported to predict chorionicity reliably. Carrol
et al. [10] found that the median thickness of the inter-twin membrane in dichorionic twins was
significantly higher than that of monochorionic twins (2.2 v 0.9 mm), and reported similar sensitivities
of 98% and 93% for l-sign and membrane thickness, respectively. The investigators also found that a
combination of these two ultrasound markers improved sensitivity by 1.3% compared with the use of T
and l-sign or membrane thickness alone. The assessment of the inter-twin membrane, however, is
technically difficult to obtain, and is affected by high inter- and intra-observer variability [14,15].
Other investigators have used ultrasound determination of fetal sex as a marker of chorionicity; the
main limitation of this assessment is that fetal sex cannot be reliably determined by early ultrasound
scans, and that all monochorionic twins and one-third of dichorionic twins are of the same sex
[9,16,17].

Pregnancy dating

Uncertainty about gestational age has been shown to be associated with a significant increase in
perinatal mortality and morbidity, and accurate pregnancy dating is needed to provide optimal
antenatal care of pregnancy [18]. In singleton gestations, evidence shows that accurate pregnancy
dating reduces the number of unnecessary induction of labour, and that the use of CRL is superior to
that of menstrual date [19,20].
The potential concerns associated with pregnancy dating in twin pregnancies are whether CRL
charts derived from singletons pregnancies can be use to assess gestational age reliably, and whether
the pregnancy should be dated according to the larger twin, smaller twin, or to an average of the two.
Several formulae to date singleton pregnancies from CRL have been reported [21–26].
Because no clinically validated twin formulae for fetal growth in the first trimester are available, it
has been questioned whether singleton CRL charts should be used to date twin pregnancies. Martins
et al. [27] showed no significant difference between CRLs of twins and singletons between 7 and 10
weeks of gestation, whereas Wisser et al. [26] showed a maximum discrepancy of 1.6 days between

Table 1
Studies reporting the predictive accuracy of ultrasound in diagnosing monochorionic pregnancy.

Reference Number of Gestational Ultrasound marker Confirmatory test Sensitivity Specificity

pregnancies age (weeks) (%) (%)
Dias et al., 613 11–14 l and T signs, Placental histology 100 99.8
2011 [7] placental masses. or discordant sex at
birth.
Lee (2006) [8] 410 <14 l and T signs, Placental histology 88.9 99.5
placental masses,
fetal sex
Menon, 463 3–14 l and T signs, Placental histology 100 97.9
2005 [9] placental masses,
fetal sex, inter-twin
membrane thickness.
Carrol et al., 150 10–14 l and T signs, placental Placental histology 98.0 97.4
2002 [10] masses. or discordant sex at
birth
Stenhouse et al., 138 7–14 l and T signs, placental Placental histology 100 98.7
2002 [11] masses, fetal sex or discordant sex at
birth
204 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214

Fig. 2. How to differentiate between monochorionic and dichorionic twins. Membrane insertion on the uterine wall (white arrows)
gives a false impression of a ‘T’ sign when the pregnancy, in fact, is dichorionic (red arrows).

twins and singletons. When comparing the CRL of the smaller and larger twin with that of singleton
pregnancies, Salomon et al. [28] and Chaudhuri et al. [29] reported that the CRL of the smaller twin was
closest to the actual gestational age, whereas Dias et al. [30] found no significant difference between
both smaller and mean CRL in twins with that of singleton gestations.
A difference in twin CRLs is a common finding in twin gestations. It is not related to chorionicity, and
seems to reflect a physiological variation rather than a pathological condition [31]. A policy of dating
twin pregnancy according to the smaller CRL would minimise parental anxiety about apparent reduced
growth in the first trimester. Reduced fetal growth, however, might be linked with chromosomal or
structural abnormalities, and it is difficult to be confident whether the small twin is normally or
pathologically small during the early stages of pregnancy.
A policy of dating by using the larger CRL may be more effective because it is relatively infrequent
for a twin to be pathologically large. This policy, however, may exaggerate the relative smallness of the
other twin, and may increase parental anxiety. Dating by mean CRL may be a reasonable alternative,
limiting parental anxiety without compromising accuracy.

Twin labelling

Multiple pregnancies are scanned frequently because of the increased risk for congenital anomalies,
aneuploidy, and growth restriction compared with singleton pregnancies [4,5]. Accurate labelling of
the twins is needed to ensure that the same individual fetus is measured through the pregnancy so that
the longitudinal growth pattern can be assessed.
Standardised and reliable labelling is also mandatory at first-trimester Down’s syndrome risk
assessment in case invasive prenatal diagnosis is subsequently required. Twin order and presentation
are relevant information for obstetricians planning timing and mode of delivery. Birth order is also
especially important in twin pregnancies discordant for fetal abnormalities that are not immediately
evident on external examination at birth (e.g. if one twin is affected by a duct-dependent cardiac
lesion).
A variety of protocols for labelling twins have been used by different units and even individual
operators. These include fetal presentation, sac position, and placental site. The lack of consistency in
labelling predisposes to errors in twin identification.
Identifying each fetus by the position of its placenta is of limited value, as the placental position
change with advancing gestation, and technique cannot be used with twin pregnancies where the
placenta is either monochorionic or fused dichorionic. Antenatal determination of fetal sex is difficult
in early pregnancy, and is of no value in same-sex twin pregnancies.
The position of each twin relative to maternal cervix is often used to label twin pregnancies;
however, the position of either fetus relative to the cervix can change considerably, especially in early
pregnancy, thus limiting the clinical applicability of this method.
 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214 205

A recent study proposed a consistent method of twin identification throughout pregnancy based on
the relation between the gestational sac and maternal cervix [32]. In this study at the 11–14-week
ultrasound assessment, the fetus contained in the gestational sac closest to the internal os was
designated as Twin 1. The relative orientation of the fetuses to each other (Fig. 3) was then defined as
either lateral (left/right) or vertical (top/bottom). Lateral fetal orientation was associated with an inter-
twin membrane running vertically along the longitudinal axis of the uterus, whereas vertical fetal
orientation was associated with an inter-twin membrane running horizontally across the longitudinal
axis of the uterus (Fig. 3).
The reproducibility of this method is likely to be good because the position of the gestational sac
relative to the cervix remains constant throughout the pregnancy, allowing objective differentiation
between the two fetuses. This assignment should be clearly documented so that it is consistently
followed. Furthermore, using multiple criteria (e.g. left and right, upper and lower, gender, placental
location, presence of discordant anomaly) is likely to reduce the error.
Interestingly, 16% of the twins changed presentation when the scan orientation was compared with
the birth order, and this change in twin order was significantly higher for twins delivered by caesarean
section compared with those delivered vaginally (Fig. 4) [32]. This finding was subsequently confirmed
in a large cohort of twin pregnancies [33]. The finding that antenatal ultrasound labelling does not
predict twin birth order reliably in a significant proportion of twin deliveries, has huge clinical
implication. It is often assumed by obstetricians, neonatologists, and parents alike, that the prenatal
nomenclature used to identify twins will also apply to the birth order and postnatal nomenclature.
Obstetricians need to be aware of the poor association between antenatal ultrasound labelling and
twin birth order when planning delivery of twins discordant for fetal growth or for non-cephalic
presentation of the leading twin. Obstetricians and neonatologists should also be aware of the likeli-
hood of a discrepancy between pre- and post-natal twin order when delivering babies with discordant
anomalies where immediate postnatal intervention is required at birth. For example, when delivering
twins discordant for cardiac abnormalities or diaphragmatic hernia, dedicated perinatal assessment is
required in order to quickly identify the affected twin after delivery. Correct and consistent identifi-
cation of antenatal and postnatal twins is also important in studies on perinatal outcomes.

Discrepancy in biometry

Size discordance represents one of the major determinants of adverse perinatal outcomes in twin
pregnancies [34]. Although a degree of discordance in fetal size is invariably present in all twin

Fig. 3. Twin labelling. The relative orientation of the fetuses to each other is then defined as either lateral (left/right) or vertical (top/
bottom). (a) Lateral fetal orientation is associated with an inter-twin membrane running vertically along the longitudinal axis of the
uterus, whereas (b) vertical fetal orientation is associated with an inter-twin membrane running horizontally across the longitudinal
axis of the uterus (Adapted from Dias et al. [32]).
206 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214

Fig. 4. Twin labelling. Perinatal switch in twin order at birth (Adapted from Dias et al. [32]).

pregnancies, inter-twin discordance in size has been associated with a multitude of adverse outcomes
including stillbirth, neonatal death, preterm birth, respiratory distress and admission to neonatal
intensive care unit [35–44]. On the assumption that discordant growth in twins begins as early as the
first trimester of pregnancy, it has consequently been suggested that discordance in CRL may have a
role in predicting birth-weight discordance. Discordance is most often expressed as a difference in
measurements (biometry or estimated weight) expressed as a percentage of the larger fetus. A total of
12–15% discordance is typically the 95th centile.
Discordance in early fetal growth has been associated with other adverse outcomes, such as
pregnancy loss, chromosomal abnormalities, and structural malformations, leading to the widely held
belief that discordance in size in the first trimester may have a role in predicting fetal growth
discordance and adverse perinatal outcomes [28,45–62].
Discordance in CRL is a factor commonly taken into consideration in counselling parents about the
outcome of the pregnancy, and different thresholds have been investigated. The role of CRL discor-
dance in predicting the outcome in twin pregnancies is still conflicting, with different studies reporting
contrasting results (Table 2).
The largest study exploring the role of CRL discrepancy detected at the time of the 11–14 weeks scan
shows that inter-twin CRL discordance is not a particularly good predictor of early fetal loss, perinatal
loss, birth weight discordance or preterm birth once chromosomal or structural abnormalities and
TTTS are excluded [31]. In this study, chorionicity, abnormal nuchal translucency, nuchal translucency
discordance, and small CRL were not independently associated with the occurrence of an adverse fetal
outcome [31].
Although surprising, this finding can be explained on the basis of the peculiar pathophysiology of
fetal growth in twin pregnancies. The uterine milieu is usually able to supply the metabolic demands of
both twins during the second and early third trimester, until about 28–32 weeks, after which twin
growth usually diverges from that of singletons. Evidence also shows that, even in cases of severe
discordant growth, the utero-placental unit supplies 50–75% more than that for the average singleton
gestation. This suggests that delayed growth in one twin during the first trimester is unlikely to occur
as the result of dysfunction in the utero-placental unit [63].
Bora et al. [52] and Papaioannou et al. [64] al found that CRL discordance of 17–18%, detected at 6–9
weeks of gestation, was highly predictive of subsequent fetal loss later in the first or second trimester of
pregnancy. Studies carried out in singletons have shown that a smaller than expected CRL detected
early in pregnancy is predictive of subsequent fetal loss in the first trimester [65,66]. In this scenario, a
discrepancy in size during the embryonic and early fetal stages might reflect a pathological condition,
potentially leading to the loss of the fetus. Conversely, a discrepancy in fetal size in the late first
trimester is more likely to represent a state of physiological variation. Most losses will have already
occurred in the early stages of pregnancy, hence its weaker association with subsequent fetal loss.
Chromosomal and structural malformations are usually associated with aberrant fetal growth.
Previous studies have also reported that CRL discordance can predict adverse fetal outcome when
chromosomal abnormalities and structural malformations are included in the population studied, or
considered as primary outcomes of the analysis, thus suggesting a potential role for counselling pa-
tients about the possible occurrence of these conditions (Table 2).
Table 2
Published studies that include data on crown– rump length discordance and adverse pregnancy outcomes.

Structural or chromosomal abnormalities included

References Chorionicity Number of Crown–rump Number of Early mortality Perinatal Birth weight Preterm birth
pregnancies length discordance pregnancy mortality discordance and sIUGR

F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214
cut-off (% or mm) losses (%)
Sebire et al., 1998 [45] Monochorionic and 539 Not stated 36 (6.7) Associated – Not associated –
dichorionic
Kalish et al., 2004 [47] Dichorionic only 159 10% 9 (5.6) Associated – Associated with birth –
weight discordance >20%
Bartha et al., 2005 [48] Monochorionic and 57 Not reported 5 (8.5) – – Associated with birth Associated
dichorionic weight discordance  25%
and sIUGR
Salomon et al., 2005 [28] Monochorionic and 182 11.4–14.3% 14 (7.7) Not associated Not associated Not associated Not associated
dichorionic
Fajardo-Exposito et al., Monochorionic and 46 – – – – Not predictive –
2011 [58] dichorionic
Bhide et al., 2011 [51] Monochorionic and 507 12.2–19.3% 39 (7.7) Associated – Associated (dichorionic –
dichorionic (monochorionic only)
only)
Harper et al., 2012 [57] Dichorionic only 610 11% 28 (4.6) Associated Not associate Not associated Not associated
(<20 wks)
Kalish et al., 2003 [46] Dichorionic only 130 10% – Associated – Associated (sensitivity –
18.8% specificity 92.1%)
Banks et al., 2007 [50] Dichorionic 108 5% – – – Not associated –
Tai and Grobman, 2007 [49] Monochorionic and 178 11.1% 19 (10.7) – Not associated Predictive of birth weight Not associated
dichorionic discordance > 20% (area
under curve: 0.72)
El Kateb, et al., 2007 [59] Monochorionic only 239 10% 16 (15.5) Associated Not associated –
Kagan et al., 2007 [60] Monochorionic only 512 Not reported 42 (8.2) Associated with Not associated Not associated
fetal loss 18
wks)
Fareeduddin et al., 2010 [53] Dichorionic only 78 9% – – – Not associated Associated
Fratelli et al., 2011 [61] Monochorionic only 135 5–20% 4 (3.0) – – Predictive (area under –
curve: 0.77)
Matias et al., 2011 [62] Monochorionic only 237 – – – – Not associated –
Shahshahan et al., 2011 [54] Dichorionic only 118 11% 10 (8.5) – Associated Associated with birth Not associated
weight discordance
>20% and sIUGR
Memmo et al., 2011 [55] Monochorionic only 242 7.1% – – – Predictive of sIUGR <26 –
weeks (area under curve:
0.89)
D’Antonio, et al., 2013 [31] Monochorionic and 2155 Not found 65 (3.0) Not associated Not associated Not associated Not associated

207
dichorionic

sIUGR, selective intrauterine growth restriction.

208 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214

First-trimester detection of congenital abnormalities

Twin pregnancies are at an increased risk for structural anomalies and aneuploidy compared with
singleton pregnancies [67,68]. Thus, a thorough ultrasound evaluation of pregnancy is warranted.
About 1–2% of multiple pregnancies are discordant for congenital abnormalities and an increased risk
of adverse perinatal outcome. No large studies have assessed the accuracy of ultrasound in diagnosing
congenital anomalies in the first trimester in twin pregnancies, but it is not unreasonable to apply the
results in singletons. Screening studies typically detect 40–70% of abnormalities at 11–14 weeks [69–71].
Allen et al. [72] found that prenatal ultrasound with cardiac screening limited to the four-chamber
view in the second trimester provided detection of 39% of all major anomalies, 55% of non-cardiac
major anomalies, but none of the cardiac lesions, and 69% of the major anomalies for which routine
prenatal management should be altered. Edwards et al. [73] reported a sensitivity and specificity of 82%
and 100% for ultrasound in prenatal diagnosis of congenital anomalies. In a recent prospective study,
Sperling et al. [74] found an incidence of congenital anomalies of 2.6% in twin pregnancies and reported
that combining nuchal translucency with an early scan at 19 weeks of gestation gave a detection rate of
83% for the diagnosis of congenital anomalies.
On the basis of these data, it seems clear that ultrasound assessment of twin pregnancies in centers
with high levels of expertise in fetal medicine is therefore warranted.

Prediction of complications in monochorionic twin pregnancies: twin-to-twin transfusion

syndrome and selective intrauterine growth restriction

Complications related to monochorionicity, such as TTTS and Selective intrauterine growth re-
striction, represent the major determinants of perinatal mortality and morbidity in monochorionic
twin pregnancies [5]. Early identification of these conditions is, therefore, warranted to plan proper
perinatal management and improve outcome.
Twin-to-twin transfusion syndrome affects 10–15% of all monochorionic twin pregnancies, and is
responsible for most of the fetal losses occurring before 24 weeks of gestation (Fig. 5) [5]. Although the
pathophysiology of TTTS has not been completely elucidated yet, it is thought to be the result of an
unbalanced haemodynamics through the circulations of the two fetuses leading to the hypo-perfusion,
hypovolaemia and oliguria in one fetus (donor) and hyperperfusion, hypervolaemia and congestive
heart failure in the other (recipient). It may develop at any time in gestation, but the risk is highest
between 16 and 24 weeks of gestation.
Bi-weekly ultrasound assessment in monochorionic twins, combined with prenatal instructions to
report the onset of maternal symptoms such as abdominal discomfort, has been show to provide a
prompt diagnosis of the condition and to guide prenatal intervention [75].
Diagnosis of TTTS is usually made in the second trimester of pregnancy, and the Quintero staging system
is widely used [76]. Other ultrasonographic parameters, such as myocardial performance indices, inter-
twin membrane folding, discrepancy in abdominal circumference, or amniotic fluid and abnormalities in
the umbilical cord insertion have been reported to be useful for the early prediction of the condition.
Some investigators have attempted to correlate first-trimester ultrasound findings (i.e. CRL and
nuchal translucency discrepancy) with the early prediction of TTTS, based on the assumption that TTTS
is a chronic progressive condition that starts early in pregnancy [59–61,74,77–80].
Lewi et al. [80] found that discrepancy in CRL and amniotic fluid volume increased the risk of
developing TTTS later in gestation, but other studies failed to corroborate this association [55,59,60].
Twin-to-twin transfusion syndrome is essentially a condition of haemo-dynamic imbalance be-
tween the circulations of the twins. A degree of unequal placental sharing is often present, thus leading
to the discrepancy in size that is usually noticed in this condition. The cardiac overload of the recipient
does not lead to the occurrence of polyhydramnios in the first trimester of pregnancy, because the
production of amniotic fluid by fetal kidneys consistently starts from 16 weeks of gestation. However,
the evidence of congestive cardiac failure may be present from the first trimester of pregnancy, and
may reflect an increase in the nuchal translucency or an abnormal ductus venosus flow pattern.
Sebire et al. [81] was the first to investigate the role of nuchal translucency in predicting TTTS, and
found that the presence of a nuchal translucency above the 95th centile for singleton pregnancy had a
 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214 209

Fig. 5. Survival trend in MC and DC twin pregnancies through gestation (adapted from D’Antonio et al. [5]).

positive predictive value and a negative predictive value of 38% and 91%, respectively, for future
development of TTTS. Kagan et al. [60] found that discordance in nuchal translucency of 20% or more
had a detection rate of 52% for severe TTTS for a false positive rate of 20%. Several investigators have
reported similar results [60,77–79,82], although others [61,74] have failed to find a strong association
between TTTS and abnormal nuchal translucnecy.
Matias et al. [82] reported an abnormal flow in the ductus venosus in at least one fetus between 11
and 14 weeks of gestation, resulting in a relative risk of 11 for the developing of TTTS, with a sensitivity
of 75% and a specificity of 92%. They also reported a combination of an inter-twin nuchal translucency
discordance of 0.6 mm or greater, and an increase in abnormal flow in the ductus venosus increased
this relative risk up to 21. Maiz et al. [83] found that the occurrence of TTTS increased from 15–30% if
there was a reversed a-wave in one of the fetuses, and reduced to 10% if the ductus venosus flow was
normal in both fetuses at 11–13 weeks.
Selective intrauterine growth restriction (sIUGR)is a condition with a unique set of risks to mon-
ochorionic twins occurring in 10–15% of these pregnancies.
A recent study found that a discrepancy in CRL 7.1 mm or more at 11–14 weeks had a sensitivity of
92% and specificity 76% for the detection of this condition [55]. It is biologically plausible that the
imbalance in placental sharing for sIUGR is evident from early pregnancy, and is manifested as
discrepant CRL measurements. In contrast, the vascular imbalances characteristic of TTTS may not
cause discrepant early growth, although the haemodynamic compromise of the recipient may manifest
as increased nuchal translucency, nuchal translucency discordance, or abnormal flow pattern in the
ductus venosus. The transient nature of nuchal translucency enlargement precludes its reliability in
predicting TTTS, thus limiting its use as a screening test.

Unusual complications of twins: monochorionic monoamniotic twins, conjoined twins and

twin reversed arterial perfusion sequence

Monochorionic monoamniotic twins represent a rare variant of monochorionic pregnancies,

characterised by the presence of a single placenta and a single amniotic sac. They are the result of the
division of the fertilised oocyte between 8 and 12 days after conception, and represent 1% of mono-
zygotic gestations. They are considered to be at increased risk of perinatal mortality, especially as the
result of congenital abnormalities, conjoined twins, spontaneous miscarriage, preterm birth, cord
entanglement, and acute transfusion events [84,85]. Although the presence of a single amniotic sac
precludes consistent labelling of the twins and the longitudinal assessment of fetal growth, antenatal
identification of these pregnancies is needed to plan proper perinatal management.
Prenatal diagnosis of monochorionic, monoamniotic (MCMA) twin pregnancies is usually possible
in the first trimester of pregnancy, and is suspected by the identification of a single yolk sac and a single
gestational sac [86]. Identification of two yolk sacs does not always preclude a MCMA twin pregnancy
210 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214

[87]. Absence of the inter-twin membrane may be difficult to confirm, especially in the first trimester of
pregnancy. The presence of cord entanglement as shown by colour Doppler is diagnostic of MCMA twin
pregnancies, and the assessment of umbilical cord insertion usually shows their proximity to one
another. Although cord entanglement has been proposed as one of the major factors responsible for
mortality in MCMA, a recent meta-analysis has shown the presence of cord entanglement does not
contribute significantly to perinatal mortality and morbidity in these pregnancies [88].
Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic preg-
nancies, which is characterised by the presence of an acardiac mass perfused by an apparently normal
(pump) twin [89]. The perfusion occurs in a retrograde fashion through arterio-arterial anastomoses
(Fig. 6), usually through a common cord insertion site. [90] This vascular arrangement, characteristic of
TRAP sequence pregnancies, predisposes to a hyperdynamic circulation and progressive high output
cardiac failure in the pump twin [91]. The latter is presumably the cause of pregnancy loss noted in
cases with TRAP sequence [90].
Early diagnosis of TRAP sequence is needed to guide an early intervention.
In fact, as there seem to be no reliable ultrasound or Doppler markers to predict pump twin demise.
In view of the high spontaneous early pregnancy loss rate, elective therapeutic intervention seems to
be indicated in all cases of TRAP sequence pregnancy. A recent meta-analysis indicates that expectant
management of this condition carries a high rate of spontaneous pregnancy loss, and that performing
intra-fetal laser therapy before 16 weeks’ gestation reduces the risk of an adverse outcome [92].
Prenatal diagnosis of TRAP sequence is usually possible in the first trimester of pregnancy, and
involves the visualisation of a dysmorphic fetal mass showing no cardiac activity and the presence of a
reverse blood flow through the umbilical artery. The pump twin may show signs of high output cardiac
failure (polyhydramnios, cardiomegaly, pericardial effusions, tricuspid regurgitation, abnormal flow in
the ductus venosus, ascites and hydrops). The TRAP twin frequently has a single umbilical artery,

Fig. 6. (a) Twin reversed arterial perfusion (TRAP) sequence; (b) ‘reverse’ arterial perfusion through the TRAP mass; (c) increased
nuchal translucency in the ‘pump’ twin, indicating cardiac de-compensation; and (d) TRAP mass.
 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214 211

whereas the pump twin is at increased risk for structural abnormalities. It is important to remember
that TRAP sequence may be easily misdiagnosed as a single early fetal death in the context of a
monochorionic pregnancy. The outcome of the pump twin is dependent of the gestational age in which
the treatment is performed. The use of color Doppler in all those monochorionic pregnancies pre-
senting with absent cardiac activity of one fetus is mandatory to make the correct diagnosis [92].
Conjoined twins result from the cleavage of the fertilised oocyte after 12 days of conception, thus
resulting in different degrees of fusion between the two fetuses. Conjoined twins represent 1% of MCMA
twins [93]. Prenatal diagnosis of conjoined twins has been reported in the early first trimester of
pregnancy by using transvaginal ultrasound [94]. Perinatal outcome of conjoined twins is mainly
dependent on the degree of fusion, the presence of intrauterine cardiac de-compensation, and structural
abnormalities. Stillbirth occurs in about 40% of these fetuses [95]. Conjoined twins may present with
first-trimester increased nuchal translucency or fetal hydrops, especially when a single or abnormal
heart is shared by the two fetuses, thus leading to high output cardiac failure and eventually death [95].

Conclusion

Early ultrasound assessment in twins allows planning of appropriate management of these preg-
nancies. Accurate determination of chorionicity is crucial to stratify the obstetric risk and to plan
further scans. Reproducible labelling of the twins is needed to ensure that the same individual fetus is
measured through the pregnancy so that the longitudinal growth pattern can be correctly assessed.
Discrepancy in crown–rump length is a relatively common finding in twins. However, recent data
suggest that its use as a screening test for adverse pregnancy outcome has a disappointing predictive
accuracy. Careful early ultrasound assessment is needed to identify structural and chromosomal
anomalies, as twin pregnancies are at increased risk. Treatment of twin reverse arterial perfusion
sequence is more effective in early pregnancy, so early identification is needed. Outcome of conjoined
twins is guarded, and is dependent on the extent of fusion, degree of sharing of organs, associated
anomalies, and presence of cardiac failure in utero.

Practice points

 The number of placentas and the presence of l and T-signs seem to be the most useful ul-
trasound marker in determining chorionicity.
 Singletons CRL charts can be used to date twin pregnancies. Dating twin pregnancy by the
CRL of the larger twin or by the mean CRL is reasonably accurate.
 Labelling twin pregnancies by left-right or top-bottom orientation appears to be reliable and
reproducible.
 Antenatal ultrasound does not reliable predict birth order in a considerable percentage of
twin pregnancies.
 Once structural anomalies, aneuploidy and complications related to monochorionicity are
excluded, CRL discrepancy is not a good predictor of adverse perinatal outcome in twin
pregnancies.
 Early detection of congenital anomalies is warranted in twins in order to plan a proper
management of the pregnancy.
 Ultrasound seems to be e less reliable in twins for detecting anomalies.
 Discordance in CRL is not reliable in predicting the occurrence of TTTS, whereas it may
indicate the possibility for future development of sIUGR.
 Discordance in nuchal translucency and abnormal ductus venosus increase the risk of
developing TTTS.
 The presence of cord entanglement is not associated with an increased risk of perinatal loss.
 Early identification of TRAP sequence is important, because intervention is more effective in
the early stages of pregnancy.
 Outcome of conjoined twins is guarded
212 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214

Research agenda

 Test the accuracy of CRL discordance in predicting fetal anomalies in large cohorts.
 Validation of the use of small and mean CRL size for pregnancy date in an unselected
spontaneous population.

References

[1] Rossi AC, D’Addario V. Neonatal outcomes of assisted and naturally conceived twins: systematic review and meta-
analysis. J Perinat Med 2011;39:489–93.
[2] Martin JA, Hamilton BE, Sutton PD, et al. Births: final data for 2003. Natl Vital Stat Rep 2005;54:1–116.
[3] Scottish Perinatal and Infant Mortality and Morbidity Report (SPIMMR), Scottish Health Statistics, ISD Scottish Division,
and Scottish Programme for Clinical Effectiveness and Reproductive Health (SPCERH) Edinburgh 2002; www.isdscotland.
org/isd/info.
*[4] Sebire NJ, Snijders RJ, Hughes K, et al. The hidden mortality of monochorionic twin pregnancies. Br J Obstet Gynaecol
1997;104:1203–7.
[5] D’Antonio F, Khalil A, Dias T, et al. Early fetal loss in monochorionic and dichorionic twin pregnancies: analysis of the
Southwest Thames Obstetric Research Collaborative (STORK) multiple pregnancy cohort. Ultrasound Obstet Gynecol
2013;41:632–6.
*[6] Southwest Thames Obstetric Research Collaborative (STORK). Prospective risk of late stillbirth in monochorionic twins: a
regional cohort study. Ultrasound Obstet Gynecol 2012;39:500–4.
[7] Dias T, Arcangeli T, Bhide A, et al. First-trimester ultrasound determination of chorionicity in twin pregnancy. Ultrasound
Obstet Gynecol 2011;38:530–2.
[8] Lee YM, Cleary-Goldman J, Thaker HM, et al. Antenatal sonographic prediction of twin chorionicity. Am J Obstet Gynecol
2006;195:863–7.
[9] Menon DK. A retrospective study of the accuracy of sonographic chorionicity determination in twin pregnancies. Twin
Res Hum Genet 2005;8:259–61.
[10] Carroll SG, Soothill PW, Abdel-Fattah SA, et al. Prediction of chorionicity in twin pregnancies at 10–14 weeks of gestation.
BJOG 2002;109:182–6.
[11] Stenhouse E, Hardwick C, Maharaj S, et al. Chorionicity determination in twin pregnancies: how accurate are we? Ul-
trasound Obstet Gynecol 2002;19:350–2.
[12] Bessis R, Papiernik E. Echographic imagery of amniotic membranes in twin pregnancies. Prog Clin Biol Res 1981;69A:183–
7.
[13] Sepulveda W, Sebire NJ, Hughes K, et al. The lambda sign at 10–14 weeks of gestation as a predictor of chorionicity in twin
pregnancies. Ultrasound Obstet Gynecol 1996;7:421–3.
[14] Stagiannis KD, Sepulveda W, Southwell D, et al. Ultrasonographic measurement of the dividing membrane in twin
pregnancy during the second and third trimesters: a reproducibility study. Am J Obstet Gynecol 1995;173:1546–50.
[15] Bracero LA, Byrne DW. Ultrasound determination of chorionicity and perinatal outcome in twin pregnancies using
dividing membrane thickness. Gynecol Obstet Invest 2003;55:50–7.
[16] Scardo JA, Ellings JM, Newman RB. Prospective determination of chorionicity, amnionicity and zygosity in twin gestations.
Am J Obstet Gynecol 1995;173:1376–80.
[17] Efrat Z, Perri T, Ramati E, et al. Fetal gender assignment by first-trimester ultrasound. Ultrasound Obstet Gynecol 2006;27:
619–21.
[18] Hall MH, Carr-Hill RA. The significance of uncertain gestation for obstetric outcome. Br J Obstet Gynaecol 1985;92:452–
60.
[19] Whitworth M, Bricker L, Neilson JP, et al. Ultrasound for fetal assessment in early pregnancy. Cochrane Database Syst Rev
2010;(4):CD007058.
[20] Taipale P, Hiilesmaa V. Predicting delivery date by ultrasound and last menstrual period in early gestation. Obstet Gynecol
2001;97:189–94.
[21] Selbing A, Fjällbrant B. Accuracy of conceptual age estimation from fetal crown-rump length. J Clin Ultrasound 1984;12:
343–6.
[22] Rossavik IK, Torjusen GO, Gibbons WE. Conceptual age and ultrasound measurements of gestational sac and crown-rump
length in in vitro fertilization pregnancies. Fertil Steril 1988;49:1012–7.
[23] Robinson HP, Fleming JE. A critical evaluation of sonar “crown-rump length” measurements. Br J Obstet Gynaecol 1975;
82:702–10.
[24] Hadlock FP, Shah YP, Kanon DJ, et al. Fetal crown-rump length: reevaluation of relation to menstrual age (5–18 weeks)
with high resolution real-time US. Radiology 1992;182:501–5.
[25] Drumm JE, Clinch J, MacKenzie G. The ultrasonic measurement of fetal crown-rump length as a method of assessing
gestational age. Br J Obstet Gynaecol 1976;83:417–21.
[26] Wisser J, Dirschedl P, Krone S. Estimation of gestational age by transvaginal sonographic measurement of greatest em-
bryonic length in dated human embryos. Ultrasound Obstet Gynecol 1994;4:457–62.
[27] Martins WP, Nastri CO, Barra DA, et al. Fetal volume and crown-rump length from 7 to 10 weeks of gestational age in
singletons and twins. Eur J Obstet Gynecol Reprod Biol 2009;145:32–5.
[28] Salomon LJ, Cavicchioni O, Bernard JP, et al. Growth discrepancy in twins in the first trimester of pregnancy. Ultrasound
Obstet Gynecol 2005;26:512–6.
 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214 213

[29] Chaudhuri K, Su LL, Wong PC, et al. Determination of gestational age in twin pregnancy: which fetal crown-rump length
should be used? J Obstet Gynaecol Res 2013;39:761–5.
*[30] Dias T, Mahsud-Dornan S, Thilaganathan B, et al. First-trimester ultrasound dating of twin pregnancy: are singleton
charts reliable? BJOG 2010;117:979–84.
*[31] D’Antonio F, Khalil A, Dias T, et al., on behalf of the Southwest Thames Obstetric Research Collaborative (STORK). Crown-
rump length discordance and adverse perinatal outcome in twins: analysis of the Southwest Thames Obstetric Research
Collaborative (STORK) multiple pregnancy cohort. Ultrasound Obstet Gynecol 2013;41:621–6.
*[32] Dias T, Ladd S, Mahsud-Dornan S, et al. Systematic labeling of twin pregnancies on ultrasound. Ultrasound Obstet Gynecol
2011;38:130–3.
[33] D’Antonio F, Dias T, Thilaganathan B on behalf of the Southwest Thames Obstetric Research Collaborative (STORK). Does
antenatal ultrasound labeling predict birth order in twin pregnancies? Ultrasound Obstet Gynecol 2013;41:274–7.
[34] Miller J, Chauhan SP, Abuhamad AZ. Discordant twins: diagnosis, evaluation and management. Am J Obstet Gynecol 2012;
206:10–20.
[35] Sonntag J, Waltz S, Schollmeyer T, et al. Morbidity and mortality of discordant twins up to 34 weeks of gestational age.
Eur J Pediatr 1996;155:224–9.
[36] Hollier LM, McIntire DD, Leveno KJ. Outcome of twin pregnancies according to intrapair birth weight differences. Obstet
Gynecol 1999;94:1006–10.
[37] Victoria A, Mora G, Arias F. Perinatal outcome, placental pathology, and severity of discordance in monochorionic and
dichorionic twins. Obstet Gynecol 2001;97:310–5.
[38] Hartley RS, Hitti J, Emanuel I. Size-discordant twin pairs have higher perinatal mortality rates than non discordant pairs.
Am J Obstet Gynecol 2002;187:1173–8.
[39] Demissie K, Ananth CV, Martin J, et al. Fetal and neonatal mortality among twin gestations in the United States: the role
of intrapair birth weight discordance. Obstet Gynecol 2002;100:474–80.
[40] Redman ME, Blackwell SC, Refuerzo JS, et al. The ninety-fifth percentile for growth discordance predicts complications of
twin pregnancy. Am J Obstet Gynecol 2002;187:667–71.
[41] Branum AM, Schoendorf KC. The effect of birth weight discordance on twin neonatal mortality. Obstet Gynecol 2003;101:
570–4.
*[42] Amaru RC, Bush MC, Berkowitz RL, et al. Is discordant growth in twins an independent risk factor for adverse neonatal
outcome? Obstet Gynecol 2004;103:71–6.
[43] Blickstein I, Mincha S, D Goldman R, et al. The Northwestern twin chorionicity study: testing the ‘placental crowding’
hypothesis. J Perinat Med 2006;34:158–61.
[44] Breathnach FM, McAuliffe FM, Geary M, et al., Perinatal Ireland Research Consortium. Definition of inter-twin birth
weight discordance. Obstet Gynecol 2011;118:94–103.
*[45] Sebire NJ, D’Ercole C, Soares W, et al. Inter-twin disparity in fetal size in monochorionic and dichorionic pregnancies.
Obstet Gynecol 1998;91:82–5.
[46] Kalish RB, Chasen ST, Gupta M, et al. First trimester prediction of growth discordance in twin gestations. Am J Obstet
Gynecol 2003;189:706–9.
[47] Kalish RB, Gupta M, Perni SC, et al. Clinical significance of first trimester crown-rump length disparity in dichorionic twin
gestations. Am J Obstet Gynecol 2004;191:1437–40.
[48] Bartha JL, Ling Y, Kyle P, et al. Clinical consequences of first-trimester growth discordance in twins. Eur J Obstet Gynecol
Reprod Biol 2005;119:56–9.
[49] Tai J, Grobman WA. The association of crown-rump length discordance in twin gestations with adverse perinatal out-
comes. Am J Obstet Gynecol 2007;197:369.e1–4.
[50] Banks CL, Nelson SM, Owen P. First and third trimester ultrasound in the prediction of birthweight discordance in
dichorionic twins. Eur J Obstet Gynecol Reprod Biol 2008;138:34–8.
[51] Bhide A, Sankaran S, Sairam S, et al. Relationship of inter-twin crown-rump length discrepancy to chorionicity, fetal
demise and birth-weight discordance. Ultrasound Obstet Gynecol 2009;34:131–5.
[52] Bora SA, Bourne T, Bottomley C, et al. Twin growth discrepancy in early pregnancy. Ultrasound Obstet Gynecol 2009;34:
38–42.
[53] Fareeduddin R, Williams 3rd J, Solt I, et al. Discordance of first-trimester crown-rump length is a predictor of adverse
outcomes in structurally normal euploid dichorionic twins. J Ultrasound Med 2010;29:1439–43.
[54] Shahshahan Z, Hashemi M. Crown-rump length discordance in twins in the first trimester and its correlation with
perinatal complications. J Res Med Sci 2011;16:1224–7.
[55] Memmo A, Dias T, Mahsud-Dornan S, et al. Prediction of selective fetal growth restriction and twin-to-twin transfusion
syndrome in monochorionic twins. BJOG 2012;119:417–21.
[56] Palmer K, Delpachitra P, Onwude J, et al. Can discordance in CRL at the first trimester predict birth weight discordance in
twin pregnancies? J Perinat Med 2012;13(40):489–93.
[57] Harper LM, Roehl KA, Odibo AO, et al. First trimester growth discordance and adverse pregnancy outcomes in dichorionic
twins. Ultrasound Obstet Gynecol 2013;2013(41):627–31.
[58] Fajardo-Expósito MA, Hervías B, González FB, et al. First trimester fetal head and trunk volume predict growth distur-
bance in twin pregnancy. Prenat Diagn 2011;31:543–7.
[59] El Kateb A, Nasr B, Nassar M, et al. First-trimester ultrasound examination and the outcome of monochorionic twin
pregnancies. Prenat Diagn 2007;27:922–5.
[60] Kagan KO, Gazzoni A, Sepulveda-Gonzalez G, et al. Discordance in nuchal translucency thickness in the prediction of
severe twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 2007;29:527–32.
[61] Fratelli N, Prefumo F, Fichera A, et al. Nuchal translucency thickness and crown rump length discordance for the pre-
diction of outcome in monochorionic diamniotic pregnancies. Early Hum Dev 2011;87:27–30.
[62] Matias A, Maiz N, Montenegro N, et al. Ductus venosus flow at 11–13 weeks in the prediction of birth weight discordance
in monochorionic twins. J Perinat Med 2011;39:467–70.
[63] Blickstein I. Is it normal for multiples to be smaller than singletons? Best Pract Res Clin Obstet Gynaecol 2004;18:613–23.
214 F. D’Antonio, A. Bhide / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 201–214

[64] Papaioannou GI, Syngelaki A, Maiz N, et al. Prediction of outcome in dichorionic twin pregnancies at 6-10 weeks’
gestation. Am J Obstet Gynecol 2011;205:348.e1–348.e15.
[65] Frates MC, Benson CB, Doubilet PM. Pregnancy outcome after a first trimester sonogram demonstrating fetal cardiac
activity. J Ultrasound Med 1993;12:383–6.
[66] Mukri F, Bourne T, Bottomley C, et al. Evidence of early first-trimester growth restriction in pregnancies that subsequently
end in miscarriage. BJOG 2008;115:1273–8.
[67] Wapner RJ, Johnson A, Davis G, et al. Prenatal diagnosis in twin gestations: a comparison between second-trimester
amniocentesis and first-trimester chorionic villus sampling. Obstet Gynecol 1993;82:49–56.
[68] Schinzel AA, Smith DW, Miller JR. Monozygotic twinning and structural defects. J Pediatr 1979;95:921–30.
[69] Syngelaki A, Chelemen T, Dagklis T, et al. Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11–13
weeks. Prenat Diagn 2011;31:90–102.
[70] Carvalho MH, Brizot ML, Lopes LM, et al. Detection of fetal structural abnormalities at the 11–14 week ultrasound scan.
Prenat Diagn 2002;22:1–4.
[71] Dane B, Dane C, Sivri D, et al. Ultrasound screening for fetal major abnormalities at 11–14 weeks. Acta Obstet Gynecol
Scand 2007;86:666–70.
[72] Allen SR, Gray LJ, Frentzen BH, et al. Ultrasonographic diagnosis of congenital anomalies in twins. Am J Obstet Gynecol
1991;165:1056–60.
[73] Edwards MS, Ellings JM, Newman RB, et al. Predictive value of antepartum ultrasound examination for anomalies in twin
gestations. Ultrasound Obstet Gynecol 1995;6:43–9.
[74] Sperling L, Kiil C, Larsen LU, et al. Detection of chromosomal abnormalities, congenital abnormalities and transfusion
syndrome in twins. Ultrasound Obstet Gynecol 2007;29:517–26.
[75] Sueters M, Middeldorp JM, Lopriore E, et al. Timely diagnosis of twin-to-twin transfusion syndrome in monochorionic
twin pregnancies by biweekly sonography combined with patient instruction to report onset of symptoms. Ultrasound
Obstet Gynecol 2006;28:659–64.
*[76] Quintero RA, Morales WJ, Allen MH, et al. Staging of twin-twin transfusion syndrome. J Perinatol 1999;19:550–5.
[77] Matias A, Ramalho C, Montenegro N. Search for hemodynamic compromise at 11–14 weeks in monochorionic twin
pregnancy: is abnormal flow in the ductus venosus predictive of twin-twin transfusion syndrome? J Matern Fetal
Neonatal Med 2005;18:79–86.
[78] Casasbuenas A, Wong AE, Sepulveda W. Nuchal translucency thickness in monochorionic multiple pregnancies: value in
predicting pregnancy outcome. J Ultrasound Med 2008;27:363–9.
[79] Linskens IH, de Mooij YM, Twisk JW, et al. Discordance in nuchal translucency measurements in monochorionic dia-
mniotic twins as predictor of twin-to-twin transfusion syndrome. Twin Res Hum Genet 2009;12:605–10.
*[80] Lewi L, Lewi P, Diemert A, et al. The role of ultrasound examination in the first trimester and at 16 weeks’ gestation to
predict fetal complications in monochorionic diamniotic twin pregnancies. Am J Obstet Gynecol 2008;199:493.e1–7.
[81] Sebire NJ, D’Ercole C, Hughes K, et al. Increased nuchal translucency thickness at 10–14 weeks of gestation as a predictor
of severe twin-to-twin transfusion syndrome. Ultrasound Obstet Gynecol 1997;10:86–9.
[82] Matias A, Montenegro N, Loureiro T, et al. Screening for twin-twin transfusion syndrome at 11–14 weeks of pregnancy:
the key role of ductus venosus blood flow assessment. Ultrasound Obstet Gynecol 2010;35:142–8.
[83] Maiz N, Staboulidou I, Leal AM, et al. Ductus venosus Doppler at 11 to 13 weeks of gestation in the prediction of outcome
in twin pregnancies. Obstet Gynecol 2009;113:860–5.
[84] Heyborne KD, Porreco RP, Garite TJ, et al. Improved perinatal survival of monoamniotic twins with intensive inpatient
monitoring. Am J Obstet Gynecol 2005;192:96–101.
[85] Cordero L, Franco A, Joy SD. Monochorionic monoamniotic twins: neonatal outcome. J Perinatol 2006;26:170–5.
[86] Bromley B, Benacerraf B. Using the number of yolk sacs to determine amnionicity in early first trimester monochorionic
twins. J Ultrasound Med 1995;14:415–9.
[87] Corbett SL, Shmorgun D. Yolk sac number does not predict reliably amnionicity in monochorionic twin pregnancies: a
case of a monochorionic monoamniotic twin pregnancy with two distinct yolk sacs on early first-trimester ultrasound.
Ultrasound Obstet Gynecol 2012;39:607–8.
*[88] Rossi AC, Prefumo F. Impact of cord entanglement on perinatal outcome of monoamniotic twins: a systematic review of
the literature. Ultrasound Obstet Gynecol 2013;41:131–5.
[89] Moore TR, Gale S, Benirschke K. Perinatal outcome of forty-nine pregnancies complicated by acardiac twinning. Am J
Obstet Gynecol 1990;163:907–12.
[90] Wong AE, Sepulveda W. Acardiac anomaly: current issues in prenatal assessment and treatment. Prenat Diagn 2005;25:
796–806.
[91] Lewi L, Valencia C, Gonzalez E, et al. The outcome of twin reversed arterial perfusion sequence diagnosed in the first
trimester. Am J Obstet Gynecol 2010;203:213.e1–4.
[92] Pagani G, D’Antonio F, Khalil A, et al. Intrafetal laser treatment for twin reversed arterial perfusion sequence: a cohort
study and meta-analysis. Ultrasound Obstet Gynecol 2013;42:6–14.
[93] Fitzgerald EJ, Toi A, Cochlin DL. Conjoined twins. Antenatal ultrasound diagnosis and a review of the literature. Br J Radiol
1985;58:1053–6.
[94] Schmidt W, Heberling D, Kubli F. Antepartum ultrasonographic diagnosis of conjoined twins in early pregnancy. Am J
Obstet Gynecol 1981;139:961–3.
[95] Pajkrt E, Jauniaux E. First-trimester diagnosis of conjoined twins. Prenat Diagn 2005;25:820–6.