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Seminars in Fetal & Neonatal Medicine 15 (2010) 15–20

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Seminars in Fetal & Neonatal Medicine


journal homepage: www.elsevier.com/locate/siny

Twin-to-twin transfusion syndrome: current understanding of pathophysiology,


in-utero therapy and impact for future development
Michael Bebbington a, b, *
a
Center for Fetal Diagnosis and Treatment, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
b
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

s u m m a r y

Keywords: Whereas monochorionic twins account for only 30% of twin gestations, they contribute to a dispropor-
Fetal cardiology tionate extent to the overall twin perinatal morbidity and mortality. Twin-to-twin transfusion syndrome
Fetal therapy can occur at any point in a monochorionic gestation but is associated with significant increases in both
Laser therapy
morbidity and mortality when it develops before 26 weeks of gestation. It is still not possible to predict
Monochorionic twins
accurately those pregnancies that will be affected. This has resulted in the practice of routine ultrasound
Twin-to-twin transfusion syndrome
surveillance beginning at the end of the first trimester. Our understanding of the physiology still has
many gaps but there is an increased recognition of the heterogeneity that exists especially in the early
stages of the disease. The role of the cardiovascular response of the recipient twin offers the potential for
further refining the application of our current treatment modalities and may offer insight into future
therapies. The optimal therapy at this point in time resides clearly with selective laser photocoagulation,
and further refinements of techniques and patient selection may continue to improve outcomes. Finally,
the in-utero responses generated by the fetuses to the physiologic stress of twin-to-twin transfusion may
influence their response or ability to respond to cardiovascular stress in later life. If there is in-utero
programming, then the detection and timely treatment of conditions such as twin–twin transfusion
syndrome may have lifelong implications for both members of the twin pair.
Ó 2009 Elsevier Ltd. All rights reserved.

1. Introduction postimplantation blastocyst phase then monochorionic mono-


amniotic (MCMA) twins occur. Only 1–2% of MZ twins are MCMA. It
Monozygotic (MZ) twin pregnancies account for about 30% of is the monochorionic twins that are susceptible to additional
spontaneously conceived twins. It is estimated that the occurrence complications because of their unique placental architecture. Both
of MZ twins is 0.4–0.45% of non-stimulated in-vivo conceptions.1 fetuses share the placental mass and virtually all monochorionic
The incidence of monochorionic twins is rising, owing to the twin pregnancies have vascular anastomoses that allow the flow of
increase in the use of assisted reproductive technology (ART) blood between the fetuses. Normally this flow is balanced with
to achieve pregnancy. The use of ART has been associated with equal amounts exchanged between the two fetuses. In about 15% of
a 2–12-fold increase in the conception of MZ twins.2 This is cases, the flow becomes unbalanced and this creates the environ-
important because of the increased perinatal risk in twin gestations ment for the development of twin-to-twin transfusion syndrome
in general but in MZ twins in particular. (TTTS). Left untreated, the perinatal mortality rate is about 90%.3
In all, 25–30% of MZ twins are dichorionic, diamniotic (DCDA)
meaning that the embryo splits before embryonic cell differentia- 2. Pathophysiology
tion. The perinatal outcome of dizygotic (DZ) twins and dichorionic
MZ twins does not differ: 70–75% are monochorionic diamniotic TTTS is not a homogeneous clinical entity and encompasses
(MCDA) where the inner cell mass divides during the preimplan- a spectrum of severities. It can develop at different gestational ages
tation blastocyst stage. If the division takes place in the and with different degrees of clinical findings. There can be
a dynamic nature to the findings from one evaluation to the next.
Some cases demonstrate rapid progression whereas others follow
a more indolent course. It is difficult to completely understand the
* Center for Fetal Diagnosis and Treatment, Children’s Hospital of Philadelphia,
34th Street & Civic Center Blvd, Philadelphia, PA 19104, USA. Tel.: þ1 267 426 7187;
reasons for the degree of clinical variations that are observed and at
fax: þ1 215 590 2447. present it is not possible to predict whether a patient will display
E-mail address: bebbington@email.chop.edu a stable type of TTTS or show rapid clinical progression.

1744-165X/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.siny.2009.05.001
16 M. Bebbington / Seminars in Fetal & Neonatal Medicine 15 (2010) 15–20

Commonly MC placentas have anastomoses between pairs of that includes the presence of a single placenta, a thin inter-twin
arteries (AA) from the different circulations and less commonly membrane usually measuring a thickness of <2 mm, and the
between pairs of veins (VV). These AA and VV anastomoses lie on absence of a twin peak sign. In any twin gestation, the establish-
the surface of the placenta and mediate bidirectional flow with the ment of chorionicity is paramount at the time of the earliest
net direction and volume of flow varying according to the pressure ultrasound evaluation. TTTS is defined sonographically by
dynamics between the circulations of the two fetuses. The unbal- discrepancy in the amount of amniotic fluid. There must be poly-
anced transfusion of blood is mediated at least in part by arterio- hydramnios with a deepest vertical pocket of >8 cm in the sac of
venous (AV) anastomoses within the placenta. The number and size the recipient twin, and oligohydramnios with a deepest vertical
vary within each placenta but each only allows for unidirectional pocket of <2 cm in the sac of the donor twin. In some European
flow. The presence of AV anastomoses without a compensating AA centers the gestational age is taken into consideration with poly-
anastomosis is associated with a higher risk for the development of hydramnios consisting of a deepest vertical pocket of >8 cm before
TTTS.4 This underlying angio-architecture is likely further influ- 20 weeks of gestation and >10 cm after 20 weeks. Other sono-
enced by the diameter of the vessels involved and the intrinsic graphic features include a discordance in sizes between the co-
placental resistance. twins of >20%, concordant fetal gender, Doppler changes within
If the shift of blood flow becomes significant, the donor twin the fetal vasculature, frank hydrops or demise of one or both
becomes hypovolemic and oliguric while the recipient twin fetuses. Current clinical staging follows that proposed by Quintero
becomes hypervolemic and polyuric. In the donor twin, the renal (Table 1).11 This staging system has been a very useful construct to
system, in response to the decreased circulating volume, activates allow for comparison of treatment results and for choosing
the renin–angiotensin system (RAS). The effect is to increase tubular between various management strategies as it incorporates the
reabsorption and the production of angiotensin 2, mediating vaso- severity of the underlying disease. It does, however, create the
constriction to maintain circulating volume. This produces hyper- impression that the natural history of TTTS follows an orderly
tension within the donor. This may also have the paradoxical effect progression over time. Clinical experience has shown that this is
of decreasing renal and placental perfusion, further worsening oli- not the case. The natural history of TTTS is variable and unpre-
guria and resulting in growth restriction. The observation of dictable. This staging system also does not incorporate elements
decreased or absent diastolic flow in the umbilical artery of the describing the fundamental cardiovascular perturbations that are
donor would implicate the effect of these endocrine products on the central to understanding of the disease and that are present in
vascular tone of the placental bed. In the recipient twin, a variety of subtle form even at the earliest stage of the disease process. Rychik
mediators may be involved in response to increased blood volume. et al. have proposed the addition of a cardiovascular scoring system
The increased atrial pressure mediates an increase in cardiac atrial from the Children’s Hospital of Philadelphia (CHOP) to quantify the
natriuretic peptide synthesis. This increases glomerular filtration magnitude of cardiovascular derangement (Table 2).12 A more
rate and decreases tubular reabsorption in the kidney.5 Suppression precise gradation of severity based in the physiologic underpin-
of antidiuretic hormone also increases the recipient’s production of nings of the disease should augment and refine the clinical diag-
urine. Renal downregulation of the RAS is the expected response to nosis and assist in the measuring of the effectiveness of various
the recipient hypervolemia, and study of the recipient kidneys has treatment modalities or possibly assist in the selection of patients
revealed changes consistent with a hypertensive microangiopathy for specific treatments. Significant degrees of cardiovascular
due to high levels of circulating RAS effectors.6 It has been abnormalities are seen even in the early Quintero staging such that
hypothesized that these effectors are transferred from the donor to a substantial number of twin pairs had a higher grade of disease
the recipient through the placental anastomoses. A recent study has severity based on the cardiovascular assessment than that desig-
shown that the recipient placenta may play a role in the source for nated by the Quintero stage.
RAS activation in the recipient twin.7 Cardiovascular findings in the Various attempts have been made to identify sonographic
recipient twin such as ventricular hypertrophy, atrioventricular features that may predict or increase the likelihood of developing
(AV) valve regurgitation and increased pulmonary outflow and TTTS. The first has been the use of nuchal translucency (NT)
aortic outflow velocities can be attributed to volume overload. Other measurements done between 11 and 13þ6 weeks of gestation.
findings, however, are inconsistent with this simple perspective. If Increased NT is a marker for chromosomal anomalies, cardiac
the changes within the recipient only occur in response to volume defects and a range of genetic syndromes. It has also been postu-
loading then there should be an increase in the combined cardiac lated that the underlying hemodynamic changes in TTTS may be
output. This has not been observed. The observed cardiomegaly present much earlier than is apparent from our current sono-
appears to result primarily from myocardial hypertrophy rather graphic criteria and may manifest as increased NT in the recipient
than cardiac dilation.8 The development of pulmonic stenosis and fetus. One study evaluated the presence of an NT measurement
obstruction of the right ventricular outflow tract would not be >95th percentile for gestational age in MCDA twins that were
expected strictly on the basis of volume loading. These findings structurally and chromosomally normal. The definition of severe
suggest an increase in cardiac afterload secondary to the develop- TTTS included cases with an ultrasound diagnosis consistent with
ment of systemic hypertension.9 Endothelin-1, a potent vasocon-
strictor, has been implicated in the production of systemic
hypertension in the recipient twin.10 Table 1
Staging of twin-to-twin transfusion syndrome.
Thus the imbalance of blood volume brought about by the
presence of vascular anastomoses initiates a cascade of events in Stage Findings
both fetuses that would be somewhat adaptive were they not 1 Polyhydramnios in recipient sac (MVP >8 cm) and oligohydramnios in the
confined to an intrauterine environment but instead lead to signif- donor sac (MVP <2 cm)
2 No visible bladder in the donor twin
icant morbidity and mortality that is associated with untreated TTTS.
3 Doppler abnormality consisting of absent or reverse flow in the umbilical
artery, reverse flow in the ductus venosus or pulsatile flow in the umbilical
3. Clinical diagnosis vein
4 Ascites or hydrops in either fetus
There is a spectrum of sonographic features that may suggest 5 Demise of either fetus

the diagnosis of TTTS. There must be evidence of monochorionicity MVP, maximum vertical pocket of amniotic fluid.
M. Bebbington / Seminars in Fetal & Neonatal Medicine 15 (2010) 15–20 17

Table 2
Children’s Hospital of Philadelphia (CHOP) Cardiovascular Score.

Recipient twin 0 1 2 3
Ventricular characteristics Dilatation None Mild >Mild
Hypertrophy None Mild >Mild
Systolic dysfunction None Mild >Mild
Valve function Tricuspid regurgitation None Mild >Mild
Mitral regurgitation None Mild >Mild
Venous Doppler characteristics Tricuspid inflow 2 peaks 1 peak
Mitral inflow 2 peaks 1 peak
Ductus venosus flow Forward Notching Reversal
Umbilical vein flow No pulsation Pulsation
Great vessel analysis PA vs Ao size PA > Ao PA ¼ Ao PA < Ao
Donor twin UA Doppler Normal Decrease AEDF REDF

PA, pulmonary artery; Ao, aorta; AEDF, absent end diastolic flow; REDF, reverse end diastolic flow; UA, umbilical artery.

Quintero stage 2 that resulted in pregnancy loss, intrauterine fetal specificity measured 0.85 and 0.97 respectively. The odds ratio of
demise (IUFD), intrauterine treatment or postmortem evidence developing TTTS if an AA anastomosis was not detected was 8.6.
that the cause of death was TTTS. The presence of an increased NT This demonstrates feasibility of detection; nevertheless, if they are
in at least one of the fetuses predicted the development of severe not detected, is it that they are truly not present or does detection
TTTS with a sensitivity of 0.32, a specificity of 0.88 and a positive require a certain level of special skill or patience during the eval-
likelihood ratio of 1.45.13 Kagan et al. evaluated the ability of uation? Factors relying on a special level of skill or persistence will
discordance in the measurement of NT between 11 to 13þ6 weeks to never perform as well in general use as they do with those that
predict the subsequent need for endoscopic treatment of TTTS.14 A originate them.
discordance of more than 20% was associated with a sensitivity of Again as a screening tool, it is unclear whether any of these
0.57, a specificity of 0.77 and a positive likelihood ratio of 1.73. As provides additional benefit over the observation of a discrepancy in
a screening tool, the use of discordant NT measurements does not the amniotic fluid volumes. A study of multifactorial screening
provide sufficient discrimination to be recommended for routine confirms this impression.18 Evaluating a group of 202 MCDA
use. Combining increased NT thickness with abnormal flow in the pregnancies with multivariate regression, the only factors that
ductus venosus (DV) has also been proposed as a screening tool for significantly predicted an adverse outcome, including TTTS, were
early TTTS. An abnormal NT thickness was defined as >95th differences in the crown–rump length and discordance in the
percentile for gestational age with a discrepancy between the amniotic fluid volume in the first trimester. Screening strategies
co-twins of 0.5 mm considered significant. An abnormal DV may be able to identify a subgroup of patients at higher risk, but it is
waveform was defined as reversal of the A-wave during atrial unclear whether those cases identified at a lower risk will be
contraction. In a prospective series of 50 cases, four cases developed subjected to different clinical care following their risk stratification.
TTTS.15 An abnormal DV Doppler was seen in all four cases. An The fact that none of the above sonographic screening tools
additional two cases with abnormal DV Doppler developed another functions well individually or collectively underscores that the best
complication. None of the remaining 44 cases with a normal DV method for early diagnosis is likely the regular ultrasound evalua-
Doppler developed TTTS. This results in a sensitivity of 0.66 and tion of ‘at risk’ monochorionic pregnancies. This strategy too is not
a specificity of 1.0. presently supported by strong research findings. A small case series
Folding of the inter-twin membrane is an ultrasound marker evaluated the ability to make a timely diagnosis of TTTS with
that demonstrates a decrease in the amount of amniotic fluid in one a program of biweekly ultrasound combined with patient reporting
sac compared to the other and has also been proposed as of symptoms suggestive of TTTS.19 Although only four of 23 patients
a screening test for MCDA twin gestations that will develop TTTS. developed TTTS, the authors concluded that sonography combined
Sebire et al. prospectively evaluated 83 MCDA pregnancies that with maternal symptom monitoring allowed the diagnosis and
presented for routine NT screening.16 Serial ultrasound evaluations management of all cases before the onset of severe complications.
were performed at 10–14, 15–17 and 19–21 weeks. Membrane
folding was seen in 23 cases, 12 of which developed severe TTTS. 4. Treatment
The remaining 11 had a more ‘moderate’ syndrome with a subjec-
tive major discrepancy in the amniotic fluid volume between the Since the publication of the Eurofetus randomized trial
two sacs. Thus 52% of those observed to have membrane folding comparing amnioreduction with selective laser photocoagulation,
developed severe TTTS. Only one of these was detected at the time there has been no question that laser therapy is currently the
of the initial ultrasound done at 10–14 weeks. Although this optimal therapy for TTTS that develops before 26 weeks of gesta-
appears to be a useful marker, what is unclear is whether this tion.20 Of all the available therapies, it is the one that seeks to
provides additional information over the simple observation of interrupt the vascular connections on the chorionic plate that are
discordance in the amniotic fluid volume during a routine ultra- responsible for the development of the syndrome. The group that
sound. A subsequent evaluation done by the same group showed underwent laser therapy had a significantly higher mean gesta-
a sensitivity of 0.43, a specificity of 0.98 and a positive likelihood tional age at delivery (33 vs 29 weeks) along with higher survival of
ratio of 21.5.13 at least one fetus to 28 days of age (76% vs 56%). Postnatal follow-up
The presence of AA anastomoses is considered protective for the was only to 6 months’ duration but demonstrated improved
development of TTTS. Placental mapping for the presence of AA neurologic outcomes with decreased risk of periventricular leuko-
anastomoses by color flow and spectral Doppler has technical malacia in the laser group (6% vs 14%) and a higher likelihood of
limitations, the majority of anastomoses being detectable only after being free of neurologic complications at 6 months of age (52% vs
18 weeks of gestation.17 Increasing gestational age, the presence of 31%). The Eurofetus trial confirmed the many prior studies of lesser
an anterior placenta and larger diameter vessels enhanced the epidemiologic rigor. A recent meta-analysis of ten of these studies
ability to detect an AA anastomosis. The overall sensitivity and supported the superiority of laser therapy over amnioreduction.21
18 M. Bebbington / Seminars in Fetal & Neonatal Medicine 15 (2010) 15–20

The technique for laser therapy has undergone some changes is the recommendation for serial weekly surveillance of middle
since it was first proposed by De Lia.22 A laparotomy is no longer cerebral artery Doppler velocities after laser therapy to detect
performed with the procedure now performed percutaneously. The developing anemia (TAPS) that is amenable to treatment with
use of general anaethesia has given way to the use of conscious intrauterine transfusion or to detect signs of persistence of TTTS or
sedation or local anaesthetic. The method for ablation of the vessels reversal of TTTS.
crossing the inter-twin membrane has changed from a non- Amnioreduction is no longer the mainstay of therapy for TTTS. It
selective approach, in which all vessels crossing the inter-twin may, however, still have a role to play in the management of TTTS
membrane were photocoagulated,23 to a selective approach under certain conditions. It may be a useful procedure to allow
involving precise identification of the anastomotic vessels.24 This a patient to be transported to a center where more definitive
change resulted in an improved survival of at least one fetus from therapy may be offered. It may be useful to decompress the uterus
61% in the non-selective group to 83.1% in the selected group in cases where there is evidence of cervical shortening or proximal
largely as a result of less dual intrauterine demise in the selected funneling to allow a cervical cerclage to be placed before laser
laser group. therapy. It can be used in managing symptomatic polyhydramnios
Further refinements in laser technique have been explored. when TTTS develops outside of the gestational age where laser
Quintero et al. have proposed a sequential selective laser photo- therapy can be performed or where laser therapy is technically not
coagulation of the communicating vessels.25 The rationale for possible. Finally it may be a useful therapy in the management of
photocoagulation of the AV anastomoses from the donor to the stage 1 TTTS.
recipient first is that this could improve the hemodynamic status of Since the initial clinical staging was proposed by Quintero, it has
the donor and result in less demise of the donor twin. Although been realized that a number of early stage TTTS cases do not
they do report a lower rate of IUFD among donors in the sequential progress and remain at stage 1 or may even regress. Several studies
technique (21.4% vs 7.3%), this was a non-randomized study and the have evaluated this. Taylor et al. reported a progression rate of 31%
groups were severely unbalanced in terms of size. Also, there was in a cohort of 22 stage 1 patients.31 Dickinson and Evans found
no difference between the groups in overall stage – the sequential a progression rate of 45.5% in their cohort of 22 patients.32 Finally in
group had twice as many stage 1 patients as did the selective group. a cohort of 46 patients with stage 1 disease, O’Donoghue et al.
Adoption of this technique awaits further evaluation. found a 30.4% rate of progression.33 Our own study of 42 patients
The finding of residual anastomoses following laser surgery is of with stage 1 TTTS revealed a progression rate of only 10%.34 Though
great clinical concern. Depending on the number, size, direction studies have found that amnioreduction did not alter the rate of
and vessels involved they can result in persistent TTTS, reversal of progression or regression, it can still be useful for symptomatic
TTTS, twin anemia polycythemia sequence (TAPS), intrauterine relief from polyhydramnios. In a similar way, selective termination
demise of both twins, or hypotensive sequelae in a surviving twin. of one fetus by bipolar cord coagulation or radiofrequency ablation
These residual connections can represent anastomoses that were is only selectively used in the management of TTTS. Cases where
missed at the time of laser ablation or revascularization of previ- there are discordant anomalies, pre-existing injury or imminent
ously ablated vessels. In one study that evaluated 50 placentas demise of one twin would be considered situations where selective
postpartum from MCDA twins that had undergone laser ablation, termination could be offered as a means of protecting the co-twin
residual surface anastomoses that should have been treated with from the risks of a spontaneous intrauterine demise.
laser ablation were found in 32%.26 The pregnancies with residual The treatment of stage 1 TTTS is controversial; whether the best
anastomoses were more frequently associated with adverse therapy is simple observation, amnioreduction or laser photoco-
outcome such as double fetal demise or evidence of anemia in one agulation has not yet been determined. Other therapies such as
twin requiring intrauterine transfusion. Case reports have been selective termination via bipolar cord coagulation or radio-
published that use treatment of fetal anemia through intrauterine frequency ablation or termination of the pregnancy are not usually
transfusion to determine the rate of blood flow through the residual considered at this early stage. There are few studies that report
AV anastomosis.27 Advanced mathematical modeling of twin-to-twin outcomes for laser treatment specifically for stage 1 disease. Mid-
transfusion has led to the development of equations that can be used in deldorp et al. reported on the outcomes of 100 pregnancies
similar situations.28 A more recent study found a similar frequency managed by laser surgery.35 From that series there were 10 cases of
of residual surface anastomoses but noted that most measure <1 mm stage 1 TTTS treated with laser with a 95% survival at birth. They do
in diameter and are more commonly located near the placental not breakdown their postnatal mortality events by stage and so it is
margins.29 The presence of deeper anastomoses within the placenta impossible to determine the survival to discharge from hospital for
that cannot be photocoagulated by laser therapy have also been the subgroup of stage 1 cases. The Eurofetus trial20 included 11
identified.26 Their contribution to the post-laser complication rate pregnancies with stage 1 TTTS, six in the laser group and five in the
from ongoing exchange of blood would appear to be unimportant amnioreduction group. They reported that the survival rate was
in producing hematological or hemodynamic changes of clinical higher in the laser group compared to the amnioreduction group
significance.30 for all stages, but they only reported a comparison between the
The occurrence of demonstrated residual anastomoses has led therapies for stages 1 and 2 combined, showing 86% survival at 6
to several procedural changes. It is incumbent on those who months for the laser group and 58% survival for the amnioreduction
perform laser therapy to be exceedingly vigilant when mapping the group. As such, the results for the 11 stage 1 patients are grouped
placenta. This may involve multiple runs over the vascular equator with the results from the much larger stage 2 group of 62 patients,
to look for residual small anastomoses that may have been missed so it is difficult to draw definite conclusions on outcomes in this
initially and to ensure that all laser sites are adequately photo- smaller group. If the rate of progression in stage 1 TTTS is low and
coagulated. A modification of the selective technique has been outcomes are good for those that do not progress, then is it
proposed that involves performing an initial selective laser ablation appropriate to expose these pregnancies to the risks of laser
and then using the laser to connect the ablation sites. This essen- therapy? In the absence of an ability to predict those cases that are
tially photocoagulates the vascular equator in what is known as the likely to progress, it is difficult to select those cases of stage 1
‘Solomon’ technique. There is currently a randomized trial disease that may benefit from treatment before they progress.
underway to determine whether application of this technique is There are discussions currently underway to develop a randomized
able to reduce the frequency of TAPS or recurrent TTTS. The second trial for the management of stage 1 TTTS.
M. Bebbington / Seminars in Fetal & Neonatal Medicine 15 (2010) 15–20 19

5. Long-term outcomes the optimal treatment for stage 1 disease and this will require the
cooperation and participation of multiple centers. If programming
Survival of one or both fetuses is only one aspect of the takes place within the intrauterine environment, then ongoing
outcomes in TTTS. The mean gestational age at delivery even in long-term follow-up studies that will evaluate the children into
successfully treated cases is still less than that seen in MCDA twin their school years and beyond are needed to understand the impact
gestations without TTTS. Thus complications of prematurity still of TTTS on the development of diseases in later life.
factor into the long-term outcomes. The Eurofetus trial provided
information on neurologic outcomes at 6 months of age, with 52%
of surviving infants from the laser group being free of major
neurologic sequelae compared to 31% of surviving infants in the Practice points
amnioreduction group.20 Reliable assessment of neurologic
abnormalities requires a longer follow-up period than 6 months  Monochorionic twins are associated with a dispropor-
although the occurrence of periventricular leukomalacia is a strong tionately high perinatal morbidity and mortality. The
predictor of the subsequent development of cerebral palsy. The determination of chorionicity is an essential component
of any ultrasound evaluation of a twin pregnancy.
frequency of longer-term neurologic sequelae has been docu-
 There is no reliable way to screen MCDA twins for the
mented in many case series of varying size and duration of follow- development of TTTS. Routine surveillance with ultra-
up. The largest involves 145 infants from pregnancies undergoing sound on a biweekly basis appears to be the most effi-
laser therapy before 26 weeks of gestation.36 These infants were cient tool at present.
followed to a mean age of just over 3 years. Children were cate-  Clinical diagnosis of even early stage TTTS should
gorized as having normal physical and neurologic development, prompt a referral to a center experienced in the evalu-
minor neurologic deficiency with the prospect to normalization or ation and management of complex MC pregnancies
severe neurologic abnormality leading to permanent disability including the ability to perform laser therapy.
based on standardized testing. This showed 86.8% of children with
normal development, 7.2% with minor neurologic abnormality and
6% with major neurologic abnormality.
With the dramatic effects on cardiac physiology that are seen in
the recipient twin in TTTS, the long-term outcome of the cardio-
vascular system has also come into question. The CHOP Cardio- Research directions
vascular Score, which is a broad, multifactor representation of
 Further development in the understanding of the
cardiac function primarily in the recipient, shows a significant
prenatal pathophysiology of TTTS.
reduction post laser therapy.37,38 It has also been demonstrated that
 Further elucidate the long-term impact of in-utero
there is improvement in both the right and left ventricular intervention.
myocardial performance index post laser when compared to  A randomized controlled trial is needed to determine the
preoperative assessment.39 Serial postoperative evaluations show optimal treatment for early stage TTTS.
continued improvement over time. The development of right
ventricular tract outflow obstruction in some recipient twins is
seen to improve following laser therapy but may not resolve
completely, resulting in acquired congenital heart disease that Conflict of interest statement
requires evaluation postnatally. Postnatal studies with long-term
cardiac follow-up are few. One study of 89 survivors of MCDA None declared.
pregnancies treated for TTTS with laser showed that in 87% of Funding sources
survivors, postnatal echocardiography was normal at a median age
of 21.5 months.40 The prevalence of congenital heart disease and None.
particularly pulmonary stenosis in the recipient twin was increased
compared to the general population (11.2% vs 0.3%). References
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