Structural malformations in monochorionic twin pregnancy

• 1.
  

  Neural tube defects and facial clefts, holoprosencephaly, and cardiac and anterior abdominal wall defects

  
  
• 2.
  

  Encephalomalacic brain lesions, pulmonary stenosis, renal agenesis, limb reduction defects, aplasia cutis and intestinal atresia

  
  
• 3.
  

  Cardiac defects, including ventricular septal defect (VSD), lesions specific to TTTS: atrial septal defect, pulmonary stenosis

Congenital heart disease (CHD) is more prevalent in MC twins. There is some evidence to suggest CHD is more common in twins conceived through ART. A retrospective series of 381 MC twins reported a prevalence of CHD of 5%, which increased to 9% in the presence of TTTS. The most common anomalies identified were VSDs (2.1%) and anomalies of the outflow tracts (1.3%) in the general twin population followed by VSD (2.9%) and anomalies of the great arteries (2.9%) in the TTTS group. In contrast, DC twins may display more classic CHD such as hypoplastic heart syndrome and atrioventricular septal defects.

Chorionic villous sampling

Chorionic villus sampling in multiple pregnancies performed between 10 and 14 weeks’ gestation offers the advantage over amniocentesis in that it can be performed at an earlier gestational age, affording earlier and safer options for subsequent pregnancy management, including termination.

Amniocentesis

Before the procedure, an ultrasound examination is performed to determine the number of fetuses, the chorionicity, fetal position, fetal viability, identification of the fetus(s) when an anomaly is present, placental location and umbilical cord location, and results are carefully mapped out with samples being labelled according to the documented identifier information of each twin. Under ultrasound guidance, the usual scenario is that both sacs are sampled with separate needles; however, a single-needle technique can also be used. For the single-needle technique, the proximal sac is sampled first, the stylet is replaced and the needle is advanced into the second sac. The first 1 mL from the second sac should be discarded to avoid contamination. The advantage over the double-entry technique is that of fewer needle insertions, but tenting of the amniotic membrane may make it technically difficult to enter the second sac under direct visualisation, and a theoretical monoamniotic (MA) pregnancy can be created as a result. We recommend a two-needle entry technique, in which after the first needle is inserted in the first sac and a sample is obtained, the needle is held in place, and indigo carmine dye is injected into the same sac before the needle is withdrawn. The second sac is then carefully sampled, and clear amniotic fluid should be aspirated upon entry. Methylene blue dye is no longer recommended because it is associated with fetal risks such as fetal demise, intestinal atresia, methaemoglobinaemia in the infant and staining of the fetal skin.

A recent systematic review of procedure-related loss in twins after amniocentesis indicated the overall pregnancy loss rate was 3.07% (95% CI, 1.83–4.61; n = 4), with pooled data from four case-control studies showing a higher rate of pregnancy loss (2.59% vs 1.53%) at less than 24 weeks’ gestation. Losses before 28 weeks’ gestation could not be accurately determined because of the heterogeneity of the published data. The available data are limited by a lack of prospective trials and a lack of homogeneity regarding definitions of procedure-related loss, and few studies included a control group or reported on loss rates based on chorionicity. As a result, the exact loss rate after amniocentesis in multiple pregnancies remains undetermined but is likely in excess of 1% above the background risk.

Definition of discordant growth

Discordance in fetal growth can affect approximately 20% of twin pregnancies overall and approximately one third of all triplet pregnancies. In MC twins, unequal placental sharing, with severe growth discordance of 25% or greater complicates approximately 20% of all MC twins compared with only 7.6% of DC twins. For DC twins, it could be anticipated that a degree of discordance in fetal growth is likely on the basis of differing genetic potentials, placental architectures and implantation sites. Although a threshold of 10% has been suggested to represent an accepted normal physiological difference in growth potential, there has been a lack of agreement as to what constitutes pathological discordant growth, with varying definitions of a threshold ‘cutoff’ discordance (10%–30%) described. The inclusion in some studies of major congenital fetal anomalies and cases complicated by TTTS, in addition to a lack of clarification regarding analysis by chorionicity, have precluded the ability to define the exact cutoff of significant birth weight discordance associated with increased perinatal morbidity and mortality.

The prospective Evaluation of Sonographic Predictors of Restricted Growth in Twins (ESPRiT) study conducted in Ireland with complete perinatal outcome on 1001 twin pregnancies established that the threshold for significant birth weight discordance (i.e., that which is associated with an increase in composite perinatal morbidity) is 18% for both DC and MC twins in the absence of TTTS. Overall, the absolute risk for adverse perinatal outcome was found to be higher in MC versus DC twins at every level of discordance. Further studies did not find any increased risk for neonatal morbidity or mortality in groups of discordant but appropriate-for-gestational-age (AGA) twins. To address this, further analyses within the ESPRiT study determined that after adjusting for gestational age at delivery, within a subgroup of 819 twins deemed AGA, the threshold of 18% was maintained as a significant predictor of adverse outcome. In addition, a subgroup of twins with sIUGR was identified (in which IUGR was defined as less than the 5th centile: 11% (108 of 977), and a threshold of 18% for a difference between the IUGR and AGA twins conferred a fourfold increased risk for adverse perinatal outcome compared with concordant twins. Thus, although morbidity is increased in the setting of discordance when one twin has IUGR, the risk for adverse perinatal outcome is maintained even in the discordant AGA group when a threshold of 18% for intertwin growth discordance is applied.

On this basis, we recommend a threshold of 18% for significant intertwin discordance is applied to all types of twins regardless of chorionicity and whether or not IUGR is a feature:

• 1.
  

  Discordance of 18% or greater calculated as the difference in weights between the larger and smaller of the fetuses divided by the weight of the larger fetus:

This can occur in the following scenarios:

• a.
  

  Both twins AGA but discordant in weight of 18% or greater.

  
  
• b.
  

  Both twins IUGR and discordant in weight of 18% or greater; however, in this scenario, usually both twins are concordant in weight.

  
  
• 2.
  

  sIUGR in which one twin is AGA and one twin has IUGR when the EFW is less than the 10th centile (<5th centile has been defined as sIUGR in some studies )

Ultrasound surveillance and screening for discordant growth in twins

Doppler surveillance

Multivessel Doppler assessments follow the same recommendations in twins as in singletons. However, the relative contribution that Doppler assessments can make in the identification of twin growth discordance is undetermined. Abnormal Doppler waveforms may follow a different pattern of progression in MC twins compared with that of DC twins, and this is likely a factor of the intertwin vasculature in addition to placental insufficiency. Latency of absent end diastolic flow (AEDF) (defined as the difference between gestational age at diagnosis of AEDF and gestational age at delivery or intrauterine death) has been shown to be longer (54 days) in non-TTTS MC twins compared with DC twins (30 days; P = .04) and singletons (11 days, P = .0001). This may be a factor of the earlier gestation of presentation of AEDF in MC fetuses compared with both singleton and DC fetuses and the presence of placental anastomoses, particularly arterio-arterial anastomoses (AAA) that likely maintain growth, although on a lower centile.

In MC twins, a pattern of cyclical or intermittent absent or reversed end-diastolic flow (AREDF) has been demonstrated in 20% of growth-restricted twins. This pattern is felt to occur because of retrograde transmission of cyclical pressure changes from a large AA anastomosis to the umbilical artery (UA) waveform in the smaller MC twin, in which it manifests as fluctuating end-diastolic flow (EDF).

A classification system for Doppler patterns in cases of sIUGR in MC twins was proposed by Gratacos et al in 2008, and this system has since been applied to a number of studies in which fetal intervention in sIUGR has been undertaken. The Gratacos classification system for Doppler changes in the smaller twin of a MC pair with sIUGR includes type I, positive EDF; type II, persistent AREDF; and type III, intermittent or cyclical AREDF. Research groups that have applied the Gratacos system to their series of twins with sIUGR have reported varying rates of unexpected fetal demise within groups II and III. The surprisingly high rate of unexpected demise in one study within group III suggest sIUGR with intermittent AREDF may be associated with an unpredictable natural history, and such cases warrant close surveillance and timely delivery. It may be that differing patterns of Doppler waveforms exist in the setting of generalised discordance in fetal weight, as opposed to when one twin is IUGR, and further larger studies are required.

Perinatal outcome with selective intrauterine growth restriction

Severely growth discordant MC twins (≥25%) are more likely to be delivered before 30 weeks’ gestation and have a longer neonatal intensive care stay (>10 days) than their DC counterparts. Overall, the reported incidence of IUFD in the growth-restricted twin is reported to be between 14% and 40%.

Although an intertwin growth discordance of at least 18% adversely affects perinatal outcome at any gestational age, longer term neurodevelopmental outcome appears to be largely driven by gestational age at delivery. Within the ESPRiT study, 119 twins (including 24 MC pairs) with a birth weight discordance of 20% or greater have been analysed to date at 24 and 42 months of age. Compared with the larger twin, the smaller twin of a discordant pair significantly underperformed in assessments of cognition language and motor skills (mean composite cognitive score difference, −1.7; 95% CI, 0.3–3.1; P = .01) and language and motor skills. However, before 33 weeks’ gestation, gestational age at birth had a far greater impact on cognitive outcomes than degree of birth weight discordance (mean composite cognitive score difference, −5.8; 95% CI, 1.2–10.5; P = .008). Neuromorbidity (determined radiologically up to 28 days of life) has also been identified in the larger twin of a discordant pair; the incidence of neurologic damage was reported to be as high as 37% in the AGA-co-twin of a pair when the smaller one had evidence of intermittent AREDF and when the risk persisted even if both survived. As with cases of larger co-twin demise, neuromorbidity is also thought to be attributed to antenatal ischemic events driven by large AAA.

Management of discordant growth

The frequency of surveillance for uncomplicated MC twins should include sonographic assessments including biometry, documentation of the deepest vertical pocket (DVP) of amniotic fluid, visibility and appearance of the fetal bladders, and UA Doppler assessment at least every 2 weeks from 16 weeks’ gestation. For complicated MC pregnancies, surveillance should extend to include umbilical artery and middle cerebral artery PI and peak systolic velocities, in addition to ductus venosus (DV) waveforms in the setting of an abnormal UA Doppler waveform. The basis of this scheduling of visits is to screen for sonographic stigmata of TTTS in MC twins and fetal growth discordance in all twins.

For uncomplicated DC twins, surveillance has been recommended at every 3 to 4 weeks from the time of the anatomical sonogram at 18 to 22 weeks’ gestation. More frequent sonography for uncomplicated DC twins has also been suggested. Data from the prospective ESPRiT study supports this concept: of 789 DC twin pregnancies, the detection of fetal growth restriction and abnormal UA Doppler was increased from 69% to 88% and 62% to 82%, respectively, with a 2-weekly rather than a 4-weekly ultrasonography schedule for DC twins, suggesting that sonographic surveillance every 4 weeks in DC twins is under-performing sonography every 2 weeks.

Intervention for selective intrauterine growth restriction

Selective reduction may be an option to maximise the intact survival of the larger twin if demise of the smaller twin is anticipated. Survival rates of 80% to 90% can be expected in the larger twin after cord occlusion of the smaller twin. Alternatively, selective fetoscopic laser ablation with the aim of salvaging the larger twin and sometimes both is a potential option. A number of centres have now described initial outcomes after fetal intervention using selective fetoscopic laser ablative techniques with reports of survival rates for the larger twin between 68% and 100% but also with survival rates for the smaller twin between 25% and 39% ( Table 44.2 ). The limitation with the use of this technique for sIUGR in the absence of TTTS is that the lack of polyhydramnios in the larger twin may render this option technically difficult, and inadvertent prelabour premature rupture of membranes is a possible adverse outcome. Additional technicalities to consider include the setting of an anterior placenta with large AA vessels or close proximity of cord insertion sites. Although there is a lack of data from large prospective series, both options of cord occlusion and selective fetoscopic laser ablation are feasible. It is likely going to continue to be challenging to establish criteria for fetal therapy in the case of sIUGR in MC pregnancies given this largely remains a contentious issue amongst experts. Counselling should focus on the wishes of the parents, technical concerns of individual cases and local expertise.

Gestational age at selective intrauterine growth restriction

Second trimester

In the second and third trimesters, the incidence of sIUFD is reported to be between 0.5% and 2% in DC twins, 26% in MC twins and up to 17% of triplets. The risk for adverse outcome in the surviving twin is higher in MC compared with DC pregnancies owing to the organisation of the placental and intertwin vasculature in MC pregnancies that can be compromised after sIUFD. It is still unclear exactly which gestational age at which sIUFD in a MC pregnancy confers the greatest risk for adverse sequelae in the surviving twin. Experts generally agree that the increasing size of the vascular anastomoses would confer a greater degree of acute circulatory compromise in the event of the death of one MC twin later in gestation. In a recent systematic review and meta-analysis, MC twins were eight times more likely to have neuromorbidity than DC twins when sIUFD occurred between 28 and 33 weeks’ gestation.

In general, for MC twins, when one twin dies, the surviving fetus is affected by increased risk for (i) demise, (ii) neurodisability and multiorgan failure and (iii) increased risk for premature delivery before 34 weeks’ gestation (iatrogenic and spontaneous).

Although rates of preterm delivery are comparable for MC and DC pregnancies, after sIUFD, MC pregnancies have approximately five times higher risk for co-twin death (odds ratio (OR), 5.24; 95% CI, 1.75–15.7; P = .05) ( Fig. 44.1 ).

Co-twin death after single intrauterine fetal death. Cochrane Q = 0.6, I 0% (odds ratio [OR] 4.81; 95% CI, 1.39–16.6; p <0.05).

Reproduced from Shek NW, Hillman SC, Kilby MD. Single-twin demise: pregnancy outcome. Best Pract Res Clin Obstet Gynaecol 28 (2):249–263, 2014.

Complications

Neuromorbidity and neuroimaging

Although, remarkably, most survivors do not have evidence of neurodisability, neurologic injury is by far the most pertinent concern of parents. Cerebral palsy has been reported in between 6% and 10% of survivors after a single IUFD compared with survival of both twins. The systematic review of Hillman and coworkers reported that rate of neurodevelopmental impairment for MC compared with DC twins after single IUFD was 26% compared with 2%, or an OR of 4.81 (95% CI, 1.39–16.6; P < .05) ( Fig. 44.2 ).

Neuromorbidity after single intrauterine fetal death. Cochrane Q = 0.99, I ² 0% (odds ratio [OR] 4.81; 95% CI, 1.39–16.6; p <0.05). CA, Cerebral atrophy; CP, cerebral palsy; MD, motor development; MR, mental retardation; QP, quadriplegia; TP, tetraplegia.

Reproduced from Shek NW, Hillman SC, Kilby MD. Single-twin demise: pregnancy outcome. Best Pract Res Clin Obstet Gynaecol 28 (2):249–263, 2014.

Severe cerebral injury has been identified prenatally in 8% to 26% and postnatally in up to 34% of cases of MC twins complicated by sIUFD. Predictors of severe cerebral injury were found to be advanced gestational age at single IUFD (OR, 1.14; 95% CI, 1.01–1.29) for each week of gestation; P = .03), TTTS detected before single IUFD (OR, 5.0; 95% CI, 1.30–19.13); P =.02) and an earlier gestation at delivery (OR, 0.83; 95% CI, 0.69–0.99 for each gestational week; P = .04).

Patterns of cerebral injury are well described in survivors of sIUFD, including (i) hypoxic ischaemic lesions in the white matter may lead to multicystic encephalomalacia, porencephaly, microcephaly and hydrencephaly; (ii) haemorrhagic lesions and (iii) vascular aberrations leading to neural tube defects, limb reduction anomalies and optic nerve hypoplasia. When the IUFD occurs before 28 weeks’ gestation, it is more likely to result in multicystic encephalomalacia which affects cerebral white matter, and is associated with profound neurologic impairment. Periventricular leukomalacia and germinal matrix haemorrhage can also occur in the second trimesters. The grey matter can be affected when the insult happens nearer term, and in the late third trimester, subcortical leukomalacia, basal ganglia damage or lenticulostriate vasculopathy may develop.

Although some secondary sequelae, including ventriculomegaly, porencephalic cysts, cerebral atrophy or cerebral infarcts, may be visible on prenatal fetal ultrasound some 1 to 4 weeks after the event, the initial fetal ultrasonogram often underestimates the degree of cerebral injury. Diffusion-weighted magnetic resonance imaging (MRI) appears to be the most sensitive modality for examining recent ischaemic changes, followed by conventional T2-weighted MR and fetal neurosonography.

Some caution should be given to interpreting findings on imaging because not all lesions translate into clinically relevant morbidity. Nonetheless, MR is a useful adjunct to ultrasonography. Ideally, a multicentre registry of such select cases in addition to large prospective neuroimaging data linked with long-term school age neurodevelopmental outcome in all twins would permit more accurate assessment of the actual prevalence and significance of such lesions.

Maternal risks

Reports of the risk for maternal coagulopathy or maternal infection caused by the retention of a deceased twin remain unsubstantiated. There also does not appear to be an increased risk for maternal infection in an ongoing pregnancy and in the presence of a retained deceased twin. There is a dearth of information regarding the psychological trauma of the loss of one twin in a multiple pregnancy, which is likely to be underestimated, and probably attributable to the focus on the subsequent management of the surviving twin.

Management

After the diagnosis of sIUFD, subsequent management should involve referral to a fetal medicine specialist. Management should depend on the chorionicity and whether or not the sIUFD occurred before or after viability. If chorionicity has not previously been performed, the pregnancy should be assigned as MC.

Staging

Twin–twin transfusion syndrome is staged according to the system developed by Quintero and coworkers in 1999, which remains the gold standard method for assessing severity of TTTS. The Eurofoetus criteria are an adaptation using a cutoff of 10 cm instead of 8 cm after 20 weeks’ gestation. There are five stages in the Quintero system broadly based on the range of presentations of fetal disease ( Fig. 44.3 ). The classification is useful for describing the condition in a consistent manner, but it does not always denote a logical order of disease progression, although early TTTS is usually associated with a better prognosis than later disease (stages III–V) ( Box 44.1 ).

Twin–twin transfusion syndrome (TTTS) showing the donor twin with oligohydramnios (deepest vertical pocket, 8 mm) and the notable polyhydramnios in the sac of the recipient. In this case, the donor (bbb) appeared to be ‘stuck’, with an absent bladder in addition to absent end-diastolic flow in the umbilical artery; therefore, this was a case of stage 3 TTTS.

Early prediction of twin–twin transfusion Syndrome

Although not necessary to secure a diagnosis of TTTS, additional first and second trimester sonographic features have been associated with the development of the condition.

A systematic review and meta-analysis that included more than 2000 pregnancies of which 323 developed TTTS concluded modest sensitivities of NT discrepancy (53%; 95% CI, 43.8%–62.7%) and abnormal DV flow (50%, 95% CI, 33.4%–66.6%) for the subsequent development of the condition.

Discordant amniotic fluid in both sacs, although not meeting the criteria for stage I, has been shown to progress to TTTS in fewer than 15% of cases. A further study found that cases of isolated oligohydramnios in the donor progressed to TTTS and cases of isolated polyhydramnios in the recipient progressed in in 49% (26 of 53) and 20% (6 of 20) of cases, respectively. Persistent amniotic fluid discordance in association with AREDF in the umbilical artery has also been associated with progression to TTTS. Although not based on large prospective series, findings of discordant amniotic fluid volume or isolated amniotic fluid volume differences in either sac in the absence of TTTS, in addition to the markers mentioned already discussed, probably warrant more heightened sonographic surveillance for the possibility of the development of TTTS ( Table 44.3 ).

Causes

Cardiovascular changes and echocardiographic features

Twin–twin transfusion syndrome confers an increased risk for both structural and functional cardiac disease, in particular for the recipient. The abnormal placental architecture may predispose to abnormal cardiac formation in MC twins. The cardiac functional changes secondary to volume overload featuring in the recipient include cardiomegaly, biventricular hypertrophy, and in severe cases, cardiac failure. Atrioventricular regurgitation involving the tricuspid valve and to a lesser degree the mitral value can complicate up to 71% of cases of severe TTTS. Overall two thirds of recipient fetuses have evidence of diastolic dysfunction, indicated by prolonged ventricular isovolumetric relaxation time. Right ventricular outflow tract obstruction can complicate up to 10% of recipients and is associated with significant mortality and the requirement for neonatal balloon valvuloplasty. The pathogenesis appears to be primarily related to hypertrophy and altered diastolic filling pressures or diastolic dysfunction across the right ventricle, where decreased flow through the right ventricle leads to diminished growth of the right ventricular outflow tract and resultant varying degrees of pulmonary stenosis or atresia.

Cardiac dysfunction has also been reported in 10% to 55% of cases of early-stage disease through more sensitive assessments of cardiac function using myocardial performance indices. After intervention, cardiac function can normalise in recipients some 4 weeks after laser therapy. Studies have also indicated that at approximately 10 years after a pregnancy complicated by TTTS, both donors and recipients demonstrated cardiac function within the normal range.

Given the associated cardiac functional changes in the recipient, an alternative cardiovascular scoring system has been proposed ( Table 44.4 ). Although the scoring system has not been proven to enhance prediction of outcome, proponents of the addition of fetal echocardiographic findings in early TTTS staging classification recognise the potential for this to become a more refined preoperative discriminatory strategy ( Fig. 44.4 ). Most tertiary referral centres perform serial echocardiography before and after treatment of TTTS. Further prospective research into novel, more specialised fetal cardiac functional assessments to more accurately define myocardial deformation as an index of ventricular function may improve outcome by predicting progression of early disease to help determine appropriate timing of delivery.

TABLE 44.4

CHOP Cardiovascular Scoring System for Twin–Twin Transfusion Syndrome

Reproduced from Rychik J, Tian Z, Bebbington M, et al. The twin-twin transfusion syndrome: spectrum of cardiovascular abnormality and development of a cardiovascular score to assess severity of disease. Am J Obstet Gynecol 197 (4):392.e1–e8, 2007.

Variable	Parameter	Finding	Numeric score	Fetuses with this finding ( n )
Donor	Umbilical artery	Normal	0	96 (64%)
		Decreased diastolic blood flow	1	34 (23%)
		Absent or reversed diastolic blood flow	2	20 (13%)
Recipient	Ventricular hypertrophy	None	0	77 (51%)
		Present	1	73 (49%)
	Cardiac dilation	None	0	78 (52%)
		Mild	1	47 (31%)
		>Mild	2	25 (17%)
	Ventricular dysfunction	None	0	117 (78%)
		Mild	1	12 (8%)
		>Mild	2	21 (14%)
	Tricuspid valve regurgitation	None	0	97 (65%)
		Mild	1	31 (21%)
		>Mild	2	22 (15%)
	Mitral valve regurgitation	None	0	131 (87%)
		Mild	1	6 (4%)
		>Mild	2	13 (9%)
	Tricuspid valve inflow	Double peak	0	113 (75%)
		Single peak	1	37 (25%)
	Mitral valve inflow	Double peak	0	135 (90%)
		Single peak	1	15 (10%)
	Ductus venosus	All antegrade	0	114 (76%)
		Absent diastolic blood flow	1	13 (9%)
		Reverse diastolic blood flow	2	23 (15%)
	Umbilical vein	No pulsations	0	136 (91%)
		Pulsations	1	14 (9%)
	Right-sided outflow tract	Pulmonary artery > aorta	0	126 (84%)
		Pulmonary artery = aorta	1	13 (9%)
		Pulmonary artery < aorta	2	8 (5%)
		Right ventricle outflow obstruction	3	3 (2%)
	Pulmonary regurgitation	None	0	145 (97%)
		Present	1	5 (3%)

 

CHOP, Children’s Hospital of Philadelphia.

Children’s Hospital of Philadelphia (CHOP) Cardiovascular Scoring system of twin–twin transfusion syndrome according to the Quintero stage. The bar graph shows the percentage of twin pairs with a particular cardiovascular grade for each Quintero stage. Note the presence of significant discrepancy in categorisation of severity in particular for Quintero stages II and III, in which a wide variety of cardiovascular (CV) grades are found.

Reproduced from Rychik J, Tian Z, Bebbington M, et al. The twin-twin transfusion syndrome: spectrum of cardiovascular abnormality and development of a cardiovascular score to assess severity of disease. Am J Obstet Gynecol 197 (4):392.e1–e8, 2007.

Treatment

The past 2 decades have witnessed considerable modifications in the treatment of TTTS. Before the introduction of fetoscopic laser ablation for TTTS in 1990, treatment options were limited to either serial amnioreduction as a temporary solution to minimise the risk for premature rupture of the membranes (PPROM) and the maternal symptoms secondary to uterine overdistention caused by recipient polyhydramnios or microseptostomy aimed at equilibrating the amniotic fluid volume. These treatments were palliative and did not address the underlying cause. Furthermore, the landmark Eurofoetus randomised controlled trial reported higher survival rates with at least one survivor and less short-term neurodisability after fetoscopic laser ablation versus serial amnioreduction (76% compared with 56% and 6% compared with 14%, respectively). Regarding serial amnioreduction, a subsequent meta-analysis and Cochrane review reported mortality rates of up to 60% and rate of neurodisability as high as 50%. The current recommended treatment of choice for TTTS is fetoscopic laser coagulation of the vascular anastomoses, with dual survival rates reported as ranging between 35% and 78%, and neuromorbidity rates between 13% and 17%.

Fetoscopic laser surgery

The goal of fetosopic laser surgery for TTTS is to coagulate the intertwin placental vascular anastomoses so as to effectively create a dichorionisation of an MC placenta. The procedure can be done under local anaesthetic, avoiding the need for regional anaesthesia for routine cases. Prophylactic antibiotics and calcium channel blockers are administered perioperatively. All fetal interventions should be undertaken by experienced operators. Under continuous ultrasound guidance, a trochar (with a size 7- to 12-Fr cannula) is inserted into the recipient sac. The Seldinger technique using a cannula and guidewire has also been described. Depending on the gestational age at the time of the laser procedure, a 1.3- or 2.0-mm fetoscope is used with a straight scope and 0-degree angle in cases of a posterior placenta and a 30-degree curved scope to aid optimum visualisation of an anterior placenta. Some operators recommend the use of a purely diagnostic larger fetoscope for the mapping process first, switching to a smaller one with a separate channel for the laser fibre thereafter. The vascular equator, having been mapped out ultrasonographically before the procedure, is then directly visualised in its entirety, and all visible anastomoses crossing the intertwin membrane are identified and coagulated using a neodymium (Nd):YAG laser with a 400- or 600-μm laser fibre ( Fig. 44.5 ). After confirmation that all anastomoses are coagulated, the recipient sac is then drained under direct ultrasound guidance to a vertical pocket of approximately 6 cm. A fetal karyotype is routinely sent after patient consent. Fetal survival is typically confirmed within 24 hours, and pregnancies are followed up according to local protocols.

Laser ablation of an arteriovenous anastomosis during a fetoscopic procedure for treatment of twin–twin transfusion syndrome. Arteries have a darker colour because of deoxygenated blood.

Fetoscopic laser ablation has undergone some modifications over the years. The first procedure described consisted of coagulation of all vessels crossing the membrane, but after initial reports of high associated procedure-related loss, the procedure was subsequently modified by Quintero in 1998 as the ‘selective’ laser approach. The selective approach involves carefully mapping out the vascular equator and coagulating only the vessels believed truly to be intertwin anastomoses. This was further modified again as the sequential selective approach, in which the vessels are coagulated in a specific order aimed at minimising disruption in intertwin blood flow during coagulation. In brief, for the sequential selective laser approach, donor AV anastomoses are first targeted followed by recipient AV to donor, then AA anastomoses if present (rare) and last VV anastomoses to allow for some interprocedure blood flow back from the recipient to the donor. Limited evidence from three nonrandomised cohort studies of 344 MC pregnancies comparing the sequential technique ( n = 224) with the standard selective technique ( n = 120) indicated improved dual survival (75% vs 52%; P = .002, respectively) and decreased donor and recipient demise (10% vs 34%; P = .02 and 7% vs 16%; P = .02, respectively). However, this approach has not been universally accepted.

Solomon technique

The most recent modification is known as the ‘Solomon’ technique, whereby after the vessels are coagulated, in essence, a ‘line’ is drawn with the laser fibre along the placental vascular equator connecting the ‘dots’ to completely separate the placenta, at least at the chorionic surface level ( Fig. 44.6 ). This procedure evolved to target even the smallest and sometimes ‘invisible’ connecting vessels because of the high percentage of residual vascular anastomoses reported after laser therapy, in addition to the complication of twin anaemia–polycythemia sequence and recurrent TTTS rates reported as 33%, 13% and 14%, respectively.

Colour-dye staining of placentas after standard treatment with selective fetoscopic laser ablation ( A ) and using the Solomon technique ( B ). In A , the arrows point to the individual laser spots, but in B , the complete vascular equator has been coagulated from one margin of the placenta to the other.

Reproduced from Slaghekke F, Lopriore E, Lewi L, et al. Fetoscopic laser coagulation of the vascular equator versus selective coagulation for twin-twin transfusion syndrome: an open-label randomised controlled trial. Lancet 383 (9935):2144–2151, 2014.

Twin anaemia–polycythemia sequence (TAPS) has been described in MC pregnancies and includes the presence of anaemia in the donor (defined as middle cerebral artery peak systolic velocity (MCA-PSV) >1.5 MoMs) and polycythemia in the recipient (MCA-PSV <0.8 or 1.0 MoMs) but without amniotic fluid abnormalities. A staging system has been proposed ( Table 44.5 ). It is a rare condition, and although it can occur spontaneously (3%–5%), the available evidence suggests it is can complicate up to 13% of cases of TTTS after fetoscopic laser ablation and is believed to be a consequence of chronic intertwin transfusion through very small placental anastomoses. The goal of the Solomon technique is to thus target these small vessels and prevent the development of TAPS. The available evidence of this novel technique suggests that TAPS and recurrent TTTS are reduced with the Solomon technique compared with the standard laser technique.

TABLE 44.5

Proposed Staging System for Twin Anaemia–Polycythemia Sequence

Reproduced from Slaghekke F, Kist WJ, Oepkes D, et al. Twin anaemia-polycythemia sequence: diagnostic criteria, classification, perinatal management and outcome. Fetal Diagn Ther 27 :181–90, 2010.

Antenatal stage	Findings at Doppler ultrasound examination
1	MCA-PSV donor >1.5 MoM and MCA-PSV recipient <1.0 MoM without other signs of fetal compromise
2	MCA-PSV donor >1.7 MoM and MCA-PSV recipient <0.8 MoM without other signs of fetal compromise
3	As stage 1 or 2, with cardiac compromise of donor, defined as critically abnormal flow a
4	Hydrops of donor
5	Intrauterine demise of one or both fetuses preceded by TAPS

 

MCA-PSV, Middle cerebral artery peak systolic velocity; MoM, multiples of the median; TAPS, twin anaemia–polycythaemia sequence.

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.

Regarding the Solomon technique, a randomised trial and two retrospective studies have been described to date. For the two retrospective studies, a total of 97 MC pregnancies were treated with the Solomon technique compared with 152 treated with the standard laser surgery. In these studies, dual survival was significantly higher in the Solomon versus the standard laser treated group (84.6% and 68.4% vs 46.1% and 50.5%, respectively). In one of the studies, Ruano and coworkers reported no cases of TAPS or recurrent TTTS with the Solomon technique compared with 5.3% and 7.9% of cases treated with laser, respectively. In the study by Baschat and coworkers, significantly less TAPS (2.6% vs 4.2%; P < .05) and recurrent TTTS were reported (3.9% vs 8.5%). In the multicentre randomised controlled trial (RCT), 274 women were randomised to either the Solomon technique ( n = 139) or the standard laser group ( n = 135), and no significant differences were found for overall perinatal survival (74% vs 73%, 1.04; 95% CI, 0.66–1.63), dual survival (64% vs 60%, 1.16; 95% CI, 0.71–1.89) or at least one survivor (85% vs 87%, 0.85; 95% CI, 0.71–1.89). However, there was a significant reduction in TAPS in the Solomon group (3% vs 16% for the standard group; OR, 0.16; 95% CI, 0.05–0.49) and recurrent TTTS (1% vs 7%, 0.21; 95% CI, 0.04–0.98).

Complications

Single or dual fetal demise may occur immediately and up to several weeks after laser treatment. Single deaths within 24 hours of the procedure were reported in 60% of cases and within 1 week in 75% of cases. Donors are more susceptible to IUFD, possibly partly because of underlying unequal placental sharing. Postoperative IUGR and AREDF in the UA increases risk for donor IUFD, and this can occur even some time after intervention. Recipient twin demise can occur with more advanced disease in the setting of reversed DV A-wave and hydrops and with recipient IUGR.

Premature rupture of the membranes and preterm delivery are inherent risks with the invasive nature of the procedure. Postprocedural PPROM complicates approximately 10% to 30% of all cases, although it is variably defined within studies. In general, perioperative factors, including instrument choice, have not been found to be associated with PPROM. Laser ablation performed at an earlier gestational age (<17 weeks’ gestation) may increase the risk for PPROM occurring shortly after surgery. In terms of risk factors for preterm delivery, in addition to iatrogenic PPROM, cervical length was found to be significantly associated with preterm delivery. Placement of a cervical cerclage after laser treatment may be offered, but data are controversial, and randomised controlled trials are lacking.

Immediate procedural complications include perioperative haemorrhage, for which an amnioinfusion of saline may improve visibility. Intermediate complications include chorioamnionitis, abruption, sepsis and rarely (also occurring without fetoscopic laser ablation) limb necrosis. Maternal mirror syndrome and a case of spontaneous posterior uterine rupture have been described. We recently had a case of TTTS associated with gross maternal obesity, in which the patient went into cardiac arrest shortly after regional anaesthesia and before the fetoscopic procedure commenced, ultimately requiring an emergency hysterotomy. Overall maternal complications are estimated at approximately 5%. These complications underpin the invasive nature of the procedure, and future studies should consistently report on all outcomes, not just perinatal survival.

Prognosis

Antenatal surveillance and timing of delivery

There are no data regarding optimal antenatal monitoring for pregnancies complicated by TTTS. Weekly monitoring of UA Doppler, MCA-PSV and DV Doppler velocities should initially be undertaken, extending this to 2-weekly assessments after 2 weeks with documentation of adequate fetal growth. A targeted fetal echocardiogram is recommended by a fetal medicine specialist. The average gestational age at delivery for cases treated by fetoscopic laser surgery remains constant at 32 weeks’ gestation and does not appear to be affected by technique of fetoscopic laser treatment used. Although with the advent of the Solomon technique and projected reduced incidence of recurrent TTTS and TAPS, more cases may well be delivered at a later gestational age. With the currently available data, in the absence of PPROM, a course of corticosteroids and elective delivery between 34 and 36 weeks’ gestation may be reasonable.

Cause

The majority of cases occur with an MC placenta, although DC cases have been described. The presence of large AA between the two twins’ umbilical arteries during embryogenesis results in low pressure deoxygenated blood from the ‘‘pump twin’s’ umbilical artery to flow retrogradely into the perfused twin’s umbilical arteries (or artery because there is often only one) to the iliac vessels, thus perfusing the lower part of the body to a far greater extent than the upper part. The result is a spectrum of malformations, reduction anomalies of previously existing tissues and incomplete morphogenesis of tissues primarily in the upper body. The pump twin may become compromised and is at risk for congestive cardiac failure because of continued growth of the perfused twin and the overall volume of parasitic tissue needing to be perfused by the normal heart.

Sonographic assessment

The acardiac twin typically appears as an amorphous mass with tissue oedema, deformed lower limbs and rudimentary or absent upper limbs and head, with a two-vessel cord. There may be polyhydramnios in the acardiac twin’s sac, indicating the presence of functional renal tissue. The pump twin may have cardiomegaly, polyhydramnios, hydrops and pleural and pericardial effusions.

The TRAP sequence can be diagnosed as early as 9 weeks’ gestation but may be mistaken for a demised twin or an anencephalic fetus. In the second trimester, a history of continued growth or ‘twitching’ of a ‘presumed dead’ twin on subsequent scans should alert one to the diagnosis. Although cardiac pulsations are as a rule absent, rare cases of monoventricular heart with pulsations have been reported. Definitive diagnosis can be established by demonstrating the TRAP sequence using colour flow to demonstrate reverse flow through the perfused twin’s aorta, and pulsed Doppler to show the paradoxical direction of arterial flow towards the acardiac twin.

Perinatal complications

Polyhydramnios resulting in preterm delivery is reported in up to 50% of these cases. The normal pump twin is also at risk for fetal hydrops (28%) and intrauterine demise (25%). Healy and coworkers (1994) reviewed 189 case reports in the literature spanning approximately 30 years (1960–1991) and reported the overall perinatal mortality rate for the pump twin to be 35% in twins and 45% in triplets. Premature delivery before 32 weeks’ gestation and the presence of arms, ears, larynx, trachea, pancreas, kidney and small intestine in the perfused fetus have been significantly associated with perinatal death. Poor prognostic features such as acardiac twin: pump twin weight or AC ratio greater than 0.7, elevated combined ventricular output, elevated cardiothoracic ratio and congestive cardiac failure, polyhydramnios, abnormal venous Dopplers or fetal anaemia have been proposed as predictors of outcome.

Antenatal management

Aneuploidy has been reported in 33% of perfused twins and 9% of pump twins, and a karyotype should be offered on this basis. Serial measurements of both twins should be undertaken because of the association between increased acardiac pump twin weight or AC ratio or rapid growth in the acardiac twin and adverse outcome. Given the poor prognosis associated with cardiac failure and polyhydramnios, the occasional unanticipated demise of pump twins and the technical difficulties in treatment at later gestations, prophylactic intervention is increasingly advocated and at an early gestation age.

Intervention

Selective delivery or termination of the acardiac twin with the goal of optimising the outcome for the pump twin have been described. There are a few case reports of successful selective delivery of the acardiac twin by hysterotomy and subsequent delivery of the pump twin between 27 and 35 weeks’ gestation. A number of less invasive techniques have since been described, including interstitial laser, fetoscopic-guided occlusion of the acardiac twin’s cord and radiofrequency ablation (RFA). Technical difficulties occasionally arise during external cord procedures in the presence of short, thin or hydropic cords. Similarly, intrafetal ablative techniques may fail when there is significant flow or large intraabdominal vessels within the acardiac structure. Treatment is rarely indicated after 25 weeks’ gestation when a temporising approach with amnioreduction, and early delivery may be preferable.

Radiofrequency ablation of intraabdominal vessels is emerging as the procedure of choice for TRAP sequence. It is relatively simple compared with other cord occlusive methods and probably safer than interstitial laser. Tines extending from the tip of the needle anchor the ablative device in the region of the intraumbilical vessels. One sizeable series of 29 cases reported a survival rate with RFA between 18 and 24 weeks’ gestation in TRAP of 86% with a mean gestational age at delivery of 34.6 weeks gestation. In a recent systematic review of 26 studies spanning 20 years, survival rates for pump twins were better with intervention (ablation or cord coagulation) compared with expectant management (OR, 2.22; 95% CI, 1.23–4.01, P = .008). Furthermore ablation was favoured over cord occlusion (pump twin survival (OR, 9.84; 95% CI, 1.56–62.00; P = .01), with the difference being greater in the presence of one or more poor prognostic features (OR, 8.58; 95% CI, 1.47–49.96; P = .02). However, there were insufficient data to determine which features should guide management. A multicentre randomised trial comparing early versus late intervention is ongoing (TRAP Intervention STudy: Early Versus Late Intervention for Twin Reversed Arterial Perfusion Sequence [TRAPIST]).

Regarding long-term neurodevelopmental outcome in MC twins after fetal therapy, of 17 cases of TRAP sequence treated by selective reduction in one centre, of 11 pump twins who survived, all were reported to have had a normal neurodevelopmental outcome (range of follow-up, 1 month–5 years). In a further study of follow-up of 10 survivors after cord coagulation for TRAP, three had evidence of neurodevelopmental delay, including 1 with severe mental delay and 2 with minor delays; 2 cases were complicated by PPROM and delivered at 28 and 29 weeks’ gestation, and the other case was delivered at 29 weeks’ gestation for nonreassuring fetal testing. The authors favoured prophylactic intervention in cases of TRAP rather than delayed intervention on the basis of cardiac compromise of the pump twin. Long-term larger follow-up series on neurologic outcome in surviving pump twins is deficient. Selective termination procedures used for TRAP sequence are described in more detail later in this chapter.

Sonographic assessment

In the first trimester, the typical picture is that of an monoamniotic (MA) twin pregnancy with a single yolk sac alongside two embryonic poles. The diagnosis should be made with caution in the first trimester, and follow-up is recommended. From 8 weeks’ gestation, fetal activity helps differentiate normal MA from conjoined twins. Increased NT and subcutaneous oedema may be noted in thoracopagus twins, the most common form of conjoined twins. The fetal pole is typically bifid in appearance.

In the second trimester, the sonographic features comprise of lack of a separating membrane and an inability to demonstrate completely separate fetal bodies, with both heads persistently at the same level with no change in their relative positions. In the case of omphalopagus, the conjoined twins’ fetal presentations may be discordant because of backward flexion of the upper spine. There may be more than three vessels when the umbilical cord is single. Doppler waveforms of the UA show a characteristic ‘double-layer’ spectral pattern reflecting two separate arterial supplies within the same umbilical cord, which is considered diagnostic of conjoined twins. Prenatal MRI, particularly in the third trimester, can provide additional information in planning for delivery and postnatal surgery. Fetal MRI recently identified significantly reduced cerebral and placental perfusion in omphalopagus conjoined twins compared with a singleton pregnancy. MRI can be superior to ultrasonography in cases of maternal obesity or oligohydramnios and produces three-dimensional reconstructed images in any plane. Postnatal MRI is important, particularly in craniopagus, to assess cortical fusion and in thoracopagus to evaluate intracardiac anatomy, blood flow and ventricular wall motion.

Management

Aneuploidy is rare, and invasive testing is usually not recommended. The option of termination of pregnancy should be discussed. The prognosis for the twins depends upon the extent of fusion and the presence of separate organs. Twins with cerebral or cardiac fusion have poor prognosis. Antenatal paediatric surgical consultation with a national centre with expertise in conjoined twins is valued, and although the majority of parents decide on termination, those who continue may do so with the understanding of the need for major surgical separation and reconstruction and its associated short- and long-term morbidity.

After defining the extent of fusion and associated anomalies, serial scans are required to monitor fetal growth and amniotic fluid volume. In the third trimester, polyhydramnios complicates 50% of cases, and amnioreduction may occasionally be indicated. In terms of mode of delivery, vaginal delivery may be possible in preterm cases and when neonatal survival is not anticipated, but near-term caesarean section is necessary and might need to be classical to maximise survival and minimise trauma to viable twins. Uterine rupture has been reported with vaginal delivery.

Postnatally, detailed MRI and computed tomography imaging with a multidisciplinary team approach involving paediatric surgeons specialised in separation procedures is warranted. In addition, psychiatric, social services, physiotherapy, rehabilitation and nursing support are necessary.

Conjoined twins fall into three management categories: (i) inoperable cases, (ii) operable but warrant emergency separation because of cardiac instability and (iii) planned elective separation.

Emergency separation carries a high mortality rate of 71%. In contrast, elective separation, usually planned between 2 to 4 months of age, is safer and has a survival rate of up to 80% in some centres. In a recent review of 36 sets of conjoined twins spanning over 12 years, the majority were thoracopagus, and of 5 sets of twins who underwent surgery, 6 children survived.

Sonographic assessment

The diagnosis can be made in the first trimester by visualisation of two separate fetuses with no clear dividing membrane and a single yolk sac. Visualisation of two yolk sacs does not necessarily exclude an MA pregnancy because the number of yolk sacs depends on the time of splitting of the germinal disk. When there are two yolk sacs and no dividing membrane before 9 weeks’ gestation, a repeat scan must be performed at a later stage because the intertwin membrane in an MCDA twin pregnancy may not easily be seen in early pregnancy.

The presence of a single placenta; absent intertwin membrane; same-sex, freely moving nonstuck twins in normal amniotic fluid volume supports the diagnosis from the second trimester. A pathognomonic feature of MA twins is the presence of cord entanglement, which can be demonstrated from 10 weeks’ gestation onwards by insonating a common mass of cord vessels between the two fetuses with colour-flow Doppler ( Fig. 44.7 ). Two distinct arterial waveform patterns with different heart rates can be discerned in the same direction within the same-pulsed wave sampling gate.

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