Diagnosis of twin-to-twin transfusion syndrome, selective fetal growth restriction,

twin anaemia-polycythaemia sequence, and twin reversed arterial perfusion

sequence
Monochorionic twin pregnancies are well known to be at risk for a variety of severe complications, a true challenge for the maternal–fetal medicine
specialist. With current standards of care, monochorionicity should be established in the first trimester. Subsequently, frequent monitoring using the appropriate
diagnostic tools, and in-depth knowledge about the pathophysiology of all possible clinical presentations of monochorionic twin abnormalities, should lead to
timely recognition, and appropriate management. Virtually all unique diseases found in monochorionic twins are directly related to placental angio-architecture.
This, however, cannot be established reliably before birth. The clinician needs to be aware of the definitions and symptoms of twin-to twin transfusion syndrome,
selective fetal growth restriction, twin anaemia–polycythaemia sequence, and twin reversed arterial perfusion sequence, to be able to recognise each disease and
take the required action.
In this chapter, we address current standards on correct and timely diagnoses of severe complications of monochorionic twin pregnancies.

Introduction

Monochorionic twin pregnancies are associated with a variety of serious complications, unique to this group. The underlying
pathophysiology of most of these complications seems to be related, directly or indirectly, to the unique angio-architecture of the
monochorionic placenta [1]. Imbalanced blood flow, with net transfer of blood and likely of numerous regulating factors, is the accepted
cause of twintwin transfusion syndrome (TTTS) and twin anaemia–polycythemia sequence (TAPS). Although the accepted cause of
selective fetal growth restriction (sFGR) is an unequally shared placenta, and the reversed blood flow in the cord and the body of the
acardiac twin explains its features, the underlying pathophysiology may start with imbalanced blood flow through particular types of
vascular anastomoses. With current imaging technology, we cannot reliably visualise these anastomoses. Ultrasound and Doppler
examinations enable us to detect early signs and symptoms of the various pathologic conditions in monochorionic twins. As for some,
treatment options exist, timely diagnosis and referral is of vital importance. In this chapter, we aim to discuss the clinically relevant
diagnostic tools that can and should apply in the management of monochorionic twin pregnancies.

Twin-to-twin transfusion syndrome

Monochorionic twins share a single placenta with vascular anastomoses that connect the fetal circulations, allowing inter-twin
blood transfusion. This is a physiological phenomenon as long as blood flow between the fetuses is balanced. Unbalanced net inter-twin blood
transfusion, however, may lead to various forms of serious pathology. The best-known clinical syndrome is TTTS, which is a chronic form of
feto–fetal transfusion and affects about 9% of monochorionic twins [2].
In the past, TTTS was diagnosed at the time of birth based on neonatal criteria that included a growth discordance of 15–20%
associated with discordant cord or neonatal haemoglobin concentration of >5 g/dl [3]. A subsequent study byWenstrom et al. [4] showed that
any combination of weight and haemoglobin discordance could be seen with equal frequency. The investigators concluded that the historical
paediatric parameters should be abandoned for the diagnosis of TTTS.
Nowadays, TTTS is diagnosed prenatally by ultrasound examination. It typically presents in the second trimester of pregnancy,
and the diagnosis is based on the presence of a twin oligo–polyhydramnios sequence (TOPS). The following ultrasound criteria are required
to diagnose TTTS: (1) the twin gestation is diagnosed as monochorionic (ideally with a scan carried out in the first trimester showing a T sign);
and (2) a combination of oligohydramnios exists in one twin’s amniotic cavity, with polyhydramnios in the other twin’s amniotic cavity.
Oligohydramnios is defined as a maximum vertical pocket (MVP) of <2 cm. This twin is commonly called the donor twin. Polyhydramnios
was originally defined as a MVP of >8 cm[5]. Subsequent studies in Europe have proposed to increase the threshold to 10 cm or more for the
MVP after 20 weeks’ gestation [6]. This twin is described as the recipient twin. A twin gestation that meets the above criteria is classified as
TTTS. Quintero et al. [5], in 1999, described a classification of TTTS (Table 1), which has been widely adopted and used throughout the
world.
Table 1
Staging of twin-to-twin transfusion syndrome.

a Oligohydramnios: maximum vertical pocket of 2 cm or less; polyhydramnios: maximum vertical pocket of 8 cm or over (or >10 cm at >20 weeks’ gestation).
b Absent or reversed diastolic velocity in the umbilical artery or ductus venosus or pulsatile umbilical venous velocity.

Quintero Stage I is defined as an oligo–polyhydramnios sequence with MVP of amniotic fluid of the donor and recipient twin of 2
or less and 8 cm or more (or >10 cm at >20 weeks’ gestation), respectively.
Stage II is a more progressive stage, including no visualisation of bladder filling in the donor twin. Some investigators have argued
that the presence of a small bladder that fails to fill during prolonged ultrasound examination should also qualify as stage II disease [7]. Stage
III disease is diagnosed when the Doppler results are critically abnormal, including absent (Fig. 1) or reversed (Fig. 2) diastolic velocity in the
umbilical artery or in the ductus venosus (Fig. 3), or pulsatile umbilical venous velocity (Fig. 4) in either the donor, recipient twin, or both.
Therefore, many combinations of Doppler abnormalities are possible. Typically, umbilical artery flow abnormalities are seen in donor twins,
whereas recipients more often show abnormal ductus venous or pulsatile umbilical venous Doppler studies, indicative of imminent cardiac
failure. Subdividing stage III into stage III-D, III-R, or III-DR, to indicate which twin experiences Doppler abnormalities, is advocated by
several centres.
 Stage IV disease is present when fetal hydrops (e.g. ascites, pericardial effusion, or both, pleural effusions, or scalp oedema) is
diagnosed in either twin. Typically this is first seen in the recipient twin. Fetal demise of either fetus is named stage V disease.
Several studies have shown that disease severity defined by Quintero stage at presentation is one the determinants of fetal outcome
[6,8,9]. Progression to a higher stage is associated with a poorer prognosis [10]. Therefore, early diagnosis of TTTS is important. Essential
for optimal outcome is timely diagnosis and timely referral. Despite all the publications and even complete textbooks onTTTS, late referrals
with women already in labour, or hydropic fetuses, do still occur. Essential, therefore, is to adhere to, at least, fortnightly ultrasound
examination, and in particular combined with patient instruction to report onset of symptoms [11]. It is advised that these fortnightly scans are
carried out during the whole pregnancy, starting from 14 weeks gestation. As TTTS usually occurs between 16 and 24 weeks [12], it is of
great importance that the fortnightly scans that are carried out at this time period should specifically focus on (early) signs to detect TTTS, as
stated in the National Institute of Health and Clinical Excellence guidelines [13]. Although less common, TTTS can occur up to 30 weeks or
beyond, and some centres have shown feasibility of fetoscopic laser surgery beyond the common 26-week limit [14,15]. Continuation of the
fortnightly scans throughout the pregnancy, therefore, seems to be logical advice.
Fetal biometry should not be used to diagnose TTTS. Although estimated fetal weight differences have long been abandoned in
diagnosing TTTS, a general belief still exists that donor twins should be smaller than recipients. Typically, a growth discordance of 20% or
more or 25% has been used as a diagnostic criterion for selective growth restriction in one of the twin fetuses. Such a birth weight difference,
however, is as frequently seen in monochorionic as in dichorionic twins [16]. In a study of 270 patients with TTTS, only 20% met the criteria
for selective growth restriction in the donor twin [17]. Consequently, a difference in estimated fetal weight is not considered a mandatory
feature of TTTS.
It may, however, be a challenge to distinguish monochorionic twins with single growth restriction from TTTS. The growth
restricted twin may mimic the donor twin presenting with oligohydramnios, a small bladder, and abnormal flow in the umbilical artery. The
lack of polyhydramnios in the other amniotic cavity, however, rules out the diagnosis of TTTS. The finding of polyhydramnios without
visualisation of an inter-twin membrane may lead to the false diagnosis of a monoamniotic twin pregnancy. Although TTTS may occur in
monoamniotic pregnancies, it is more likely that the donor twin has anhydramnios, with its amniotic membrane tightly wrapped around its
body. This is called the ‘stuck’ twin phenomenon (Fig. 5). In most cases, the donor twin is fixed to the uterine wall. A variant of this classic
stuck twin occurs when dividing membranes envelops the donor twin with severe oligohydramnios and connected to the uterine wall by a
laminar stalk of these membranes, the so-called ‘cocoon-sign’ [18] or intrauterine sling [19]. It may seem ‘unstuck’ and free floating in the
recipient’s amniotic cavity with polyhydramnios, and can therefore be misdiagnosed as being surrounded by a normal amount of amniotic
fluid. Other causes of stuck twins, not associated with TTTS that have been identified are viral infections, renal disease, and agenesis of the
ductus venosus [20].
In conclusion, the diagnosis and evaluation of stage and severity requires careful history taking, complete detailed evaluation of
both twins, their anatomy and functional assessment, placenta and amniotic fluid, with an open mind to rare but important alternative diagnoses.
Once the diagnosis is confirmed or at least extremely likely, determining the optimal time and method for intervention becomes the next
challenge, which will be discussed elsewhere in this issue of Best Practice and Research Clinical Obstetrics and Gynaecology.

Fig. 1. Absent end-diastolic flow in the umbilical artery.

Fig. 2. Reversed end-diastolic flow in the umbilical artery.

Fig. 3. Negative a-wave in ductus venosus

Fig. 4. Pulsations in the umbilical vein.

Selective fetal growth restriction

Abnormal fetal growth by definition means that at least two biometric measurements have been carried out, with an interval of at
least 1 and preferably 2 weeks, showing a deviation from the normal growth rate. A single measurement can only depict fetal size at the
moment of assessment. Still, most investigators of fetal growth restriction define their group of interest as a single estimation of, most
commonly, estimated fetal weight or sometimes of fetal abdominal circumference alone, falling below a certain cut-off level in a growth chart
or reference range. Others argue that any significant discordance in growth or size in monochorionic twins, which genetically have the same
growth potential, should be regarded as pathologic [2]. Thus, a significant discordance, even if the smaller twin is above the 10th centile,
should alert the clinician. An increasing body of literature is showing an association between a significant difference in twin birth weight and
perinatal mortality or neonatal outcome [12,21]. A recent retrospective cohort study [12] showed that both birth weight and estimated fetal
weight discordance were associated with adverse outcome, unrelated to the individual fetal size percentile [12]. The cut-off that best separated
poor from good outcome was 25% discordance. A prospective evaluation of a large Irish cohort of twin pregnancies (both monochorionic and
dichorionic twins) revealed that a discordant abdominal circumference of more than 10%, detected between 14 and 22 weeks, best predicted
adverse outcome [22]. A still unresolved issue, however, is how to translate this important knowledge into guidelines for management during
pregnancy. Birth weight obviously can be measured with accuracy within grams. Ultrasound estimation of fetal weight is well known to be
quite unreliable, with deviations often into the 10–15% range, particularly in earlier gestation [23]. Therefore, to use a certain percentage
discordance in estimated fetal weight may lead to incorrect diagnoses, with both a risk for over- and underestimating pathology. Obviously,
such a cut-off determined by receiver operator characteristic curve analysis does not mean that an EFW discordance less than 25% can be
ignored.
A recent attempt to reach consensus among world experts for a universal definition of sFGR in monochorionic twins lead to heated
debates, underlining the fact that we currently lack well-designed, adequately powered prospective studies providing evidence for the use of
one particular definition over another one.We agree with the authors of a recent review on twin growth that ‘although there are multiple
publications on the increased morbidity and mortality rates with discordant growth, there is a paucity of reports on how to manage them
optimally and deliver them in a timely manner’ [24].
For current clinical practice, we suggest that detection of discordant growth in monochorionic twins should lead to more close
evaluation of the condition of the smaller twin, including Doppler studies. Any concern on the condition of the smaller twin (decreased
amniotic fluid, abnormal Doppler results) should alert the clinician to consider further management in a centre specialised in monochorionic
twin pathology. Serial and frequent evaluations will lead to individualised management plans, in which gestational age plays a major role.
Currently, the place of several management options, including inhospital surveillance, planned preterm delivery, fetoscopic laser surgery, or
selective feticide, is still unclear, warranting further prospective studies. To optimise generalisability of such studies, it would be of great value
to have a uniform, generally accepted definition and classification system.
Until such time, we suggest that a discordantly growing set of monochorionic twins, with one having an estimated fetal weight less
than the 10th centile, or discordant abdominal circumference greater than10%, or an estimated fetal weight greater than 20–25%, represents a
high-risk situation, and should be diagnosed as sFGR, warranting specialist care.
This particular group invariably has a unique placental angio-architecture, and poses special dilemmas for the clinician owing to
the so-called feto–fetal conflict; for one fetus, frequent monitoring and iatrogenic preterm birth iswarranted, whereas the other may not benefit
from early birth, often on the contrary.
Discussions on which growth charts to use have been ongoing for decades. It is still widely accepted that growth charts for
singletons should be used when evaluating the growth of twins. Many ultrasound machines and electronic databases have specific growth
charts programmed into them. Every couple of years, new and often-improved reference ranges for the general or a specific population are
published, of which the authors often state that their use will improve care. Given the variation in measurement and the biological variation
between pregnancies and fetuses, the use of one chart or another is unlikely to have a major effect in managing sFGR. Using the same
equipment, algorithm and chart throughout pregnancy makes sense but should not be vitally important.
A recent large cohort study on twins from Ireland (ESPRiT study) [25] showed that the Hadlock formula and curves [25], at least
up to 30–32 weeks, can be used to evaluate twin growth. After this gestational age, twin growth deviates from this curve, and progressively
slows down (Professor S. Daly, personal communication). As this is most likely caused by reduced placental function, with a genetic growth
potential of each twin being not dissimilar to singletons, the use of a specific twin chart would only lead to a risk of missing signs of growth
restriction, and is therefore not recommended.
The next two steps in the diagnostic pathway are to identify the most likely cause for the sFGR, and to evaluate fetal condition.
Obviously, as in any pathologic pregnancy, a full, detailed anatomy scan, including evaluation of cardiac structure and function, is essential.
Viral infections may, quite surprisingly, cause discordant pathology in monochorionic twins, and should be excluded in any case of growth
restriction. Discordancy for genetic syndromes and chromosomal aberrations does occur, and may need amniocentesis to rule out.
Most often, however, the picture can be fully explained by the presence of an unequally shared placenta. An additional role is likely
for the type and size of the vascular anastomoses, and their influence on the amount of nutrients and oxygen transferred to each fetus [26]. The
placental and vascular anatomy may not become clear until after birth. Looking for the cord insertion site may give a clue, with the smaller
twin often having a marginal insertion [27]. On the other hand, many monochorionic twins have a different insertion of the cord, with one
being more marginal than the other, without showing signs of sFGR. Although it is customary, and recommended, to look for the insertion
sites, perhaps even in the first trimester [2], the clinical value of such a screening is yet unknown.
More useful is assessment of blood flow waveforms in the umbilical arteries. Growth-restricted fetuses are known to often show
abnormal Doppler waveforms in the umbilical artery. In singletons, this attributed to an increased placental resistance. The most common
parameters used to evaluate these waveforms are the Pulsatility Index, and presence, absence or reversed end-diastolic flow [28]. Clinical
severity of fetal growth restriction is correlated to the Pulsatility Index and to the end-diastolic flow velocity. Reversed end-diastolic flow is
thought to occur mainly when, in addition to an increased downstream resistance, the fetal heart starts to decompensate with a decreased
ability to generate adequate systolic output. In singletons, this is regarded as a sign of impending demise.
In monochorionic twins with sFGR, however, the blood flow in the umbilical arteries of the smaller twin is influenced by the types
and diameters of the vascular anastomoses. They almost always present arterio-arterial anastomoses, and certainly influence Doppler
waveforms in the umbilical arteries. A unique pattern for this type of twin is the so-called intermittent absent end-diastolic flow, most likely
caused by changes in synchronicity of the two fetal heart rates. This pattern is often associated with a larger size arterio-arterial anastomoses
[28]. Just as in singletons, absent end diastolic flow seems to carry a worse prognosis compared with fetuses with positive end-diastolic flow
in the umbilical artery [29]. A now universally adopted staging, based on umbilical artery Doppler waveforms in the cord of the small twin,
was proposed by Gratacos et al. [30] They divided sIUGR twins in Stage I, with constantly present end-diastolic flow, stage II with continuous
absent end diastolic flow, and stage III with intermittent absent end diastolic flow. Most of the recent publications on sIUGR report these
stages, and often confirm that a higher stage signifies a worse prognosis. Stage III in particular, with the likely presence of a large arterio-
arterial anastomoses, seems to have a high risk for sudden fetal demise or brain damage in survivors. Outcomes, however, vary widely, and
the predictive value of the Doppler measurements and Gratacos classification urgently requires more appropriate, detailed studies. For optimal
interpretation of the umbilical artery Doppler waveforms, strict adherence to careful measurement protocols is important. In Table 2, we
outline the preferred method for this measurement.
In addition to assessing the umbilical artery Doppler waveforms, other functional parameters need to be evaluated to obtain a
complete picture of the fetal condition. These, however, are similar to parameters used in singletons with growth restriction, and include
middle cerebral artery Pulsatility index, peak systolic velocity, ductus venosus waveforms, and pulsatility in the intrahepatic umbilical vein
using Doppler, amniotic fluid volume, fetal movements, and fetal heart rate tracing.
Once the diagnosis of sFGR is clear, and its severity established, then the highly individualised, strongly gestational age-dependent
options for further management need to be considered. In general, the options consist of expectant management, fetoscopic laser coagulation,
selective feticide, and delivery or termination of the whole pregnancy. Interventions in monochorionic twins will be discussed in another
chapter in this issue.

Fig. 5. ‘Stuck’ twin.

Table 2
Guideline for measuring umbilical artery Doppler waveforms in monochorionic twins.
Use colour Doppler to visualise the umbilical arteries.
Put the Doppler cursor in a free loop of the umbilical artery, close to the insertion into the placenta.
Ensure an angle of insonation of as near as zero as possible.
Only measure the waveforms in the absence of fetal and maternal breathing movements.
Assess a minimum of 12 waveforms in each umbilical artery.
In case of persistent positive end diastolic flow, measure the Pulsatility Index.
In case of absent end diastolic flow or reversed end-diastolic flow, determine whether this alternates with several
waveforms with positive end diastolic flow to define intermittent absent end diastolic flow.

Twin anaemia-polycythaemia sequence

In 2007, a separate form of chronic feto–fetal transfusion was first named twin-anaemia–polycythaemia- sequence (TAPS) [31]. It
is characterised by the presence of large inter-twin haemoglobin differences without amniotic fluid discordances that are needed to diagnose
TTTS. It may occur spontaneously or iatrogenically after laser surgery for TTTS. The spontaneous form occurs in 3–5% of monochorionic
twin pregnancies, whereas the post-laser form complicates about 2–13% of TTTS cases [2,32,33].
The typical angioarchitecture in TAPS placentas are the minuscule size (<1 mm), and the small number of mostly unidirectional
arterio-venous anastomoses. The volume of blood passage is reduced owing to the lower vascular resistance in small-calibre vessels compared
with the vascular resistance in larger vessels (Poiseuille’s law). It is, therefore, hypothesised that inter-twin blood transfusion occurs very
slowly, which allows haemodynamic compensatory mechanisms to take place. The hypovolaemic donor and hypervolaemic recipient may
remain euvolemic by activation or inactivation of the reninangiotensin system, which can explain the absence of TOPS. It was described
recently that arteriovenous anastomoses are usually evenly distributed along the vascular equator, except in TAPS placentas, where most
anastomoses are localised near the placental margin [34]. Arterio-arterial anastomoses are rare, and venovenous anastomoses are absent in
TAPS placentas [34,35].
Twin anaemia–polycythaemia sequence may be diagnosed prenatally as well as postnatally. Absence of antenatal ultrasound signs
of TOPS is an essential prerequisite for the diagnosis of TAPS [36]. Antenatal diagnosis is based on a combination of Doppler ultrasound
abnormalities showing an increased peak systolic velocity in the middle cerebral artery (MCA-PSV) in the donor twin, suggestive of fetal
anaemia and a decreased MCA-PSV in the recipient twin (suggestive of polycythaemia). Proposed
cut-off levels for the donor and recipient twin are greater than 1.5 multiples of the median (MoM) and less than 1.0 MoM, respectively, and
are summarised in Table 2 [27]. These levels are based on best practice; however, they still need to be validated and compared with postnatal
haemoglobin levels. For timely detection of TAPS (and eventually treatment of the disease), it is prudent to measure MCA-PSV with Doppler
ultrasound at least fortnightly in all monochorionic twins, particularly after laser treatment.
Postnatal diagnosis uses haematological criteria (e.g. chronic anaemia with increased reticulocyte count in the donor and
polycythaemia in the recipient) combined with placental injection studies (Table 3).
Table 3
Antenatal and postnatal diagnostic criteria for twin anaemia polycythaemia sequence.
Antenatal criteria Postnatal criteria
MCA-PSV over 1.5 MoM in the donor and MCA-PSV less than 1.0 MoM in the Inter-twin haemoglobin difference over 8.0 g/dl and at least one of the following:
recipien reticulocyte count ratio over 1.7; placenta with only small (diameter <1 mm); and
vascular anastomoses.
MCA-PSV, middle cerebral artery peak systolic velocity.
We advise the use of inter-twin haemoglobin differences instead of specific cut-off levels for anaemia and polycythaemia. A
case-control study showed that all TAPS cases had an intertwin haemoglobin difference of more than 8.0 g/dl [37]. Uncomplicated
monochorionic twins, however, also sporadically have large inter-twin haemoglobin differences, owing to either acute peripartum TTTS or
acute placentofetal transfusion after delivery of the first twin [38]. An additional criterion to differentiate between TAPS and an acute form
of inter-twin transfusion is therefore required: determination of the reticulocyte count. As blood loss in the acute situation (e.g. peripartum
TTTS or placentofetal transfusion) occurs rapidly, the reticulocyte count in the anaemic donor-twin is not increased. On the contrary, in
TAPS cases, the reticulocyte count in the anaemic twin is always increased, reflecting chronic blood loss, and is always significantly raised
compared with the recipient co-twin. An increased inter-twin reticulocyte count ratio of over 1.7 was found to be pathognomonic for TAPS
[39].
A third postnatal criterion for TAPS is based on placental findings, meaning a small number of (residual) minuscule (diameter of
<1 mm) arterio-venous anastomoses.
Twin anaemia–polycythaemia sequence may present in various forms, ranging from only mildly elevated MCA-PSV Doppler
studies to fetal death. A staging system has been developed to distinguish between these different levels of severity. In addition, this staging
system will help to compare and analyse future TAPS cases, including the evaluation of effect of treatment [36] (Table 4).
Monochorionic twins are classified into different stages according to their Doppler ultrasound findings at first detection. The aim
of this staging system is to reflect the increasing severity of anaemia and polycythaemia in twin pairs with TAPS, including ultrasound signs
of clinical deterioration related to increased fetal anaemia. Stage 1 is defined as MCA-PSV donor greater than 1.5 MoM and MCA-PSV
recipient less than 1.0 MoM. Stage 2 is defined as MCA-PSV donor greater than 1.7 MoM and MCA-PSV recipient less than 0.8 MoM. In
stage 3, abnormal Doppler finding as described in stage 1 and 2 are found and, additionally, signs of cardiac compromise of the donor are
seen (absent or reversed enddiastolic flow in umbilical artery, pulsatile flow in the umbilical vein, increased pulsatility index or reversed flow
in ductus venosus). In stage 4, fetal hydrops caused by severe fetal anaemia is present. Stage 5 is diagnosed when intrauterine fetal death
after TAPS occurs in one or both fetuses.
It is known that TAPS is not always diagnosed antenatally. Doppler ultrasound measurements are not carried out in all cases, and
MCA PSV values may be falsely negative. For these cases, a postnatal staging system using only the intertwin haemoglobin difference on
day 1 is available (Table 5).
Table 4
Antenatal twin anaemia–polycythaemia sequence classification.
Antenatal stage Findings at Doppler ultrasound examination.
Stage 1 MCA-PSV donor over 1.5 MoM and MCA-PSV recipient less than 1.0 MoM,
without other signs of fetal compromise.
Stage 2 MCA-PSV donor over 1.7 MoM and MCA-PSV recipient less than 0.8 MoM,
without other signs of fetal compromise.
Stage 3 As stage 1 or 2, with cardiac compromise of donor, defines as critically abnormal
flow.a
Stage 4 Hydrops of donor.

Stage 5 Intrauterine demise of one or both fetuses preceded by twin anaemia

polycythaemia sequence.
MCA-PSV, middle cerebral artery peak systolic velocity.
a Critically abnormal Doppler is defined as absent or reversed end-diastolic flow in umbilical artery, pulsatile flow in the umbilical vein, increased pulsatility index or
reversed flow in ductus venosus.

Twin reversed arterial perfusion sequence

This unique complication of monochorionic twinning would seem easy to diagnose; however, confusion with single intrauterine
death or simply one anomalous twin is still common. Rapid and confident diagnosis of twin reversed arterial perfusion sequence (TRAP), also
known as acardiac twin, primarily depends on familiarity with the images and specific features. Commonly, one twin is anatomically
completely normal, although in advanced stages, cardiac overload may be causing cardiomegaly and hydrops. The other twin most often has
an underdeveloped head and upper body, and impressive oedema also mostly of the upper body. The classic feature is the absence of a beating
heart in the, at first often surprising, presence of fetal movements. In rare cases, a rudimentary pulsating cardiac structure and a relatively well-
developed upper body is seen. The confirmation of the diagnosis is by turning on the colour Doppler, and showing the inverse direction of
blood flow in the aorta.
Obviously, the best possible outcome in such a twin pregnancy is one healthy child. Apart from establishing the diagnosis, and
explaining to parents what this entails, our diagnostic tests are directed at assessing the risk of cardiac decompensation and demise of the so-
called ‘pump twin’. This information can then be used to consider an intervention, directed at stopping the blood flow to the acardiac twin. An
as yet unresolved issue is whether intervention should be offered to all patients with TRAP, as early as possible. Lewi et al. [40] reported that,
in a third of TRAP pregnancies, pump twin demise occurred before 18 weeks’ gestation, without reliable predictors of which pump twin would
die and when this would happen. Pagani et al. [41] also concluded that early intervention (in their view best by infra-fetal laser coagulation)
would result in the highest intact survival rate. Thus, serial monitoring would no longer be needed. For those that consider the evidence for
early intervention in all cases still insufficient, however, careful and frequent assessment of the parameters considered related to the risk of
pump twin death.
The first part of the diagnostic process, after establishing the diagnosis of TRAP, is evaluating the condition of the pump twin. A
full and detailed anatomy scan is indicated, as structural anomalies seem to be present more often than in other monochorionic twins. Secondly,
evaluation of cardiac function is a logical step, as cardiac failure caused by the need to provide the growing acardiac co-twin with blood.
Measuring cardio-thoracic circumference ratio and ventricular wall thickness plus ductus venosus waveforms can be carried out by any
obstetric sonographers. Whether more sophisticated echocardiography aids in management decisions is unclear, and likely depends on local
possibilities. Thirdly, the amount of blood flow in the acardiac twin, and its overall size and growth rate, could be related to the risk of pump
twin death. In addition, polyhydramnios may occur and add to the risk of adverse outcome.
The general idea behind serial monitoring is that the disease process is chronic and progressive, with early signs of deterioration
providing time to plan an intervention. In TRAP sequence, however, acute pump twin demise without any pathologic sign does occur, limiting
the value of serial monitoring. Although prospective, controlled studies comparing expectant management with early intervention are lacking,
available data in our view support the view that the best possible outcome, both in terms of survival as well as gestational age at birth, follows
early intervention aimed at stopping the blood flow to the acardiac twin.

Conclusion

Monochorionic twin pregnancies require frequent, detailed ultrasound and Doppler evaluation by specialists with knowledge and
experience in managing the various unique complications of such twins. Early referral in case of suspicion of abnormal or discordant amniotic
fluid, growth, or blood flow profiles is strongly advised. Most antenatal treatment modalities are still suboptimal, and require further research.
However, successful treatment relies on accurate and tinely diagnosis, of which the details are described in this chapter.

Practice points

 Every monochorionic twin should be evaluated at least once every 2 weeks for amniotic fluid volume and bladder filling of each
twin for tomel detection of TTTS.
 Women pregnant with monochorionic twin should be specifically instructed to seek medical attention when they experience a rapid
increase in uterine size or other signs possibly related to TTTS.
 Selective growth restriction, defined as one fetus in an monochorionic twin with an estimated fetal weight below the 10th centile,
ands appropriately measured umbilical artery blood flow patterns, help to evaluate severity and likelihood of complications.
 We recommend routine measurement of middle cerebral artery peak systolic velocities at least every 2 weeks in all monochorionic
twins, to enable diagnosis of TAPS.
 Suspected diagnosis of TTTS, sFGR, TAPS, and TRAPwarrants urgent contact with a specialised fetal medicine centre to guide
specific management