1

Why is it important to diagnose chorionicity

and how do we do it?

Geoffrey A. Machin* MD, PhD, FRCPath (UK), FRCP (C)

Emeritus Professor of Pediatric Pathology, University of Alberta, Canada 3931 Cherrilec Cresent, Victoria,

British Columbia, Canada, V8N 1R7

Because the monochorionic (MC) placenta is designed for a singleton fetus, and might notprovide adequate physiological support for twins, obstetric problems are more frequent in MCthan dichorionic (DC) twins. Problems arise because asymmetric cord insertions cause growthdiscordance as a result of unequal sharing of placental tissue. Approximately 95% of MC twinplacentas contain interfetal vascular connections of some kind, sometimes in severalcombinations. Such connections can cause twin–twin transfusion syndrome and twin reversedarterial perfusion. The survivor can also suffer damage if the co-twin dies spontaneously or frominappropriate methods of selective termination. These complications are progressive and oftenadvanced by 18 weeks gestation. Monoamniotic twins carry greater risks than diamniotic twins,especially entangled cords. MC twins are often discordant for congenital anomalies. Diagnosis ofMC twinning is optimal in the first trimester. Optimal management of these MC twin disorders isnot yet established; long-term follow-up studies are unsatisfactory. In clinical practice,chorionicity is not always determined in the first trimester.

Key words: twin; twinning; monochorionic; monoamniotic; dichorionic; diamniotic; umbilicalcord; velamentous; marginal; demise; termination; ultrasound; twin transfusion; growthdiscordance; termination of pregnancy.

WHY IS TWIN CHORIONICITY IMPORTANT?

Two-thirds of monozygotic (MZ) twins split more than 2 days post-conception,resulting in twin fetuses who rely on a truly single (monochorionic, MC) placenta.Although such a placenta is optimal for a singleton fetus, the majority of MC twinsnevertheless thrive in these unusual conditions. However, certain MC twins suffer froma group of inter-related disorders that are mainly caused by the vascular anatomy that ischaracteristic of MC twin placentas; these vascular disorders occur only very rarely indichorionic (DC) twins.1 Each MC twin placenta is unique in its vascular composition,hence each MC twin pair has a unique clinical status. MC twin vascular disorders areprogressive, difficult to manage, vary in severity and timing, and may be fully developed

1521-6934/$ - see front matter Q 2004 Published by Elsevier Ltd.

Best Practice & Research Clinical Obstetrics and GynaecologyVol. 18, No. 4, pp. 515–530, 2004doi:10.1016/j.bpobgyn.2004.04.013

available online at http://www.sciencedirect.com

* Tel./Fax: þ250-477-7116.E-mail address: geoffmachin@shaw.ca (G.A. Machin).

by 18 weeks of gestation, at the time of dating ultrasound. MC twins and theircomplications are uncommon in the practice of any individual obstetrician and requirespecialized care over and above that needed for DC twins. MC twins occur in naturallyand in artificially conceived multifetal pregnancies, and are frequent components ofnaturally conceived higher-order multifetal pregnancies (HOMPs).

When congenital anomalies occur in MZ twins (including MC twins), the twins areusually discordant. Such twins can mistakenly be assumed to be DZ (and DC). Unlessspecial methods are used for selective termination of anomalous MC twin fetuses, bothfetuses might be lost.

With some rare exceptions2, MC twinning is the gold standard in the diagnosis ofmonozygosity (MZ), which could be important in postnatal life. However, few parentsof MC twins are given this information postnatally. Unfortunately, many parents of like-sexed DC twins are told that their twins are DZ, despite the well-known fact that one-third of MZ twins are DC.

For improved outcomes from vascular complications of MC twinning, thediagnosis of monochorionicity should be made as early as possible, so that treatmentcan be planned before end-stage disease is reached, commonly at 20–24 weeksgestation. The distinction between MC and DC twins is by identification of theso-called ‘twin peak’ (or ‘lambda’) sign by first-trimester ultrasound. Detailedassessment of septal membrane thickness and the number of membrane layers isalso possible in the second trimester, although vascular diseases are often advancedby this time.

CONTRASTING OBSTETRIC OUTCOMES IN DIZYGOTIC ANDMONOCHORIONIC TWINS

Table 1 contrasts outcomes in DC and MC twins pregnancies from recent reports inthe literature.3–7

Another recent study in a health maintenance organization in Colorado, USA,showed that MC twins had higher frequency of adverse perinatal outcomes. MC twinswere at significant risk for a very low birth weight (OR ¼ 3.0) similar to that forpreterm birth (OR ¼ 3.8).8

Additionally, a recent population-based study from Besancon, France, showed thatMC twinning (OR ¼ 6.0) and premature ruptured membranes (OR ¼ 4.3) weresignificant risk factors for neurologic disability in infants born at ,33 weeks.9

With one exception, these studies3–9 show marked differences in outcomes of MCand DC twin pregnancies. The excess of adverse outcomes (perinatal death, neurologicmorbidity) in MC twins is largely explained by vasculogenic events in MC twin placentas.

VASCULOGENIC COMPLICATIONS OF MONOCHORIONICTWINNING

The principal disorders in MC twinning have overlapping causes and effects:

† severe growth discordance (SGD)† twin–twin transfusion (TTT)† twin reversed arterial perfusion (TRAP)

516 G. A. Machin

† vascular instability in the absence of any of the above, resulting in congenital heartdisease of ‘flow’ type (usually in one twin) and brain lesions (in both twins)

† impending fetal demise of a compromised fetus and selective reduction of acompromised/anomalous fetus, with effects on the co-twin

† long-term neonatal and pediatric morbidity from all of the above, affecting brain,heart and kidneys

† monoamniotic (MA) twins have additional risks because of cord complications† special types of ‘blood-borne concordance’ in MC twins who are actually discordant

for congenital abnormalities.

THE VASCULAR STRUCTURES OF MONOCHORIONICTWIN PLACENTAS

There are two vascular determinants of clinical behavior in MC twins: (i) combinationsof cord insertions; and (ii) types, combinations and flow directions in inter-twin vascularconnections on and in the placenta.

Cord insertions

In singleton placentas, velamentous (1%) and marginal (9%) cord insertions are rare10;they are far more common in twins. They are thought to arise from a process oftrophotropism, i.e. only that part of the original trophoblastic sphere that is fullyimplanted in the endometrium survives as the placenta proper. The remaining chorionictissue regresses to form the chorionic membrane. It is not known why a small numberof singleton cord insertion sites do not face the endometrium but velamentous andmargin insertions (VMI) presumably result when the cord insertion is ‘marooned’ from

Table 1. Obstetric/neonatal outcomes measured in MC and DC twins.

Reference Location Study type Outcome measures MC DC

3 Nova Scotia, Population PND 35/588 (5.9%) 25/1468 (1.7%)

Canada Mean BWD 11.7% 11.0%

BWD . 25% 8.6% 6.5%

4 Mumbai, India ?Population PND 18% 9%

BWD 35% 14%

5 Tochigi, Japan Referral NND to 1 year 4/88 (4.5%) 6/328 (1.8%)

Neurologic disability 5.7% 1.8%

6 Birmingham, UK Referral PND 3/48 (6.2%) 14/190 (6.2%)

7 Toronto, Canada Referral Infants of 24–30-weeks

gestation surviving

18–24 months; death

and neurologic disability

39% 25%

In ref. 3 there were more double fetal deaths in MC (2.8%) than DC (0.5%) pregnancies. In ref. 6 TTT

was present in 14/44 (32%) MC pregnancies and was responsible for 7/9 adverse outcomes. All MC infants

with adverse outcomes had birth weight discordance $25% and this was true of 4/12 (33%) DC infants.

The basis for the anomalous result in ref. 7 is not clear. In ref. 8 adverse outcomes were found in 42% of

twins with TTT. BWD, birth weight discordance; DC, dichorionic; MC, monochorionic; NND, neonatal

death; PND, perinatal death; TTT, twin–twin transfusion.

Diagnosing chorionicity: how and why 517

the placenta proper as trophoblast regresses elsewhere for lack of endometrialsupport. It is easier to see why VMI is more common in DC twins, where there isthe likelihood that implanting placentas will collide or interfere with each other’simplantation process, with aberrant trophoblastic regression. In MC twinning, however,VMI can be explained by the fact that the intercord distance is already determinedbefore implantation and the single placenta is unable to ‘spin’ or ‘adjust’ once it hasimplanted. If cords are inserted far apart on the early disc, one cord insertion might beexposed by trophotropism. VMI cords are found in 43% of MC twins (Table 2).

The combination of cord insertion sites within MC twin pairs affects clinicaloutcomes. In SGD, the cord of the larger twin is usually paracentrally inserted (PCI),whereas the smaller twin has a VMI (Figure 1). In TTT, the donor often has VMI and therecipient has PCI, but this not always so and SGD is not a component in the diagnosis of

Table 2. Relative frequencies of cord insertion types in twins, by chorionicity.10

Marginal or

velamentous

Central or

eccentric

Chorionicity n % n % Total ðnÞ

MC 226 43 298 57 524

DC 199 23 659 77 858

Total 425 31 957 69 1382

Figure 1. Postpartum MC/DA placental perfusion, showing unequal sharing secondary to asymmetric cordinsertions. Twin A (on the left) has a marginal cord insertion, whereas the cord of twin B is centrally inserted.The vascular equator runs vertically between the cord insertions and is defined by the vascular connections.There is markedly unequal placental sharing in favour of twin B. Placental parenchyma to the left of the equatorreturns to the twin A.

518 G. A. Machin

TTT. TRAP twins usually have closely adjacent cord insertions, allowing the presence oflarge direct vascular connections between the roots of the cords. Many MA twins alsohave adjacent cord insertions, and their cords are always entwined. This causesdifficulty in rare cases requiring treatment for TTTor in which selective termination isconsidered.11 The relative frequency of types of cord insertion in clinical conditionsfound in MC twins are shown in Table 3.12

In a comparison of SGD (.20%) in DC and MC twins13, velamentous cord insertionwas associated with a 13-fold risk of growth discordance in MC twins. A total of 46% ofsuch cases had growth discordance. In MC twins this can be severe enough to causeoligohydramnios in the restricted twin. However, it should not be confused with TTT, inwhich both oligohydramnios and polyhydramnios are present.

Interfetal vascular connections

The primitive villous circulation develops independently of the fetal cardiovascularsystem. As fetal veins and arteries grow out from the umbilical cord on to thesurface of the placenta, they capture cotyledons and connect with the underlyingprimitive villous sinusoids via scattered foramina in the chorionic plate, one foreach cotyledon. Thus, in the course of each artery/vein pair on the chorionic plate,there are only two fixed points: cord insertion and the cotyledonary foramen.Elsewhere, arteries and veins run independently on the chorionic plate, but alwaysconverge in artery/vein pairs on the foramina, where they enter and leave theunderlying parenchyma via the stem villi. In MC twin placentas, the two sets of fetalarteries and veins emerge from the cord insertions and run across the chorionicplate, seeking to ‘colonize’ or ‘imperialize’ cotyledons. For most zones of MC twinplacentas, appropriate artery/vein pairs are connected to each cotyledon. However,the MC twin placenta has a vascular equator, which is a band of tissue runningacross the placenta at right angles to the intercord insertion line and roughlyequidistant between the cord insertions. At the vascular equator, both twinscompete to acquire cotyledons—any given foramen can be captured by anartery/vein pair from one twin or by an artery from one twin and a vein from theother twin. This latter arrangement gives rise to the arterio-venous connection

Table 3. Cord insertions in clinical subtypes of 58 monochorionic twin pairs.12

VMI PCI

Clinical Status n % n %

Severe TTT Recipient 11 69 5 31

Severe TTT Donor 12 75 4 25

Mild TTT Recipient 8 50 8 50

Mild TTT Donor 9 56 7 44

SGD Larger 5 50 5 50

SGD Smaller 8 80 2 20

Control Twin A 8 50 8 50

Control Twin B 7 44 9 56

Total 68 59 48 41

SGD, severe growth discordance; TTT, twin–twin transfusion.

Diagnosing chorionicity: how and why 519

(AVC), which is the key element in the development of TTT (Figure 2). In an AVC,the artery and vein do not communicate on the surface. Rather, they pass into thecotyledon in the usual way. Net transfusion always occurs in an AVC down thearterio-venous pressure gradient. An AVC can be recognized at fetoscopy orpostpartum by the fact that the feeder artery and draining vein traverse a commonforamen. The number of AVCs varies in MC twins, and they are often bidirectional(Figure 2).

Figure 2. Vascular connections at the equator (close-up of Figure 1). There are several bidirectional arterio-venous connections (ringed, directions of flow shown), as well as a single, direct arterio-arterial anastomosis(lower edge, box).

520 G. A. Machin

As arteries grow out across the fetal surface, they might encounter arteries from theother twin and form direct, end-to-end arterio-arterial anastomoses (AAAs). A similarprocess results in veno-venous anastomoses (VVAs). (Note: veins never form direct,end-to-end connections with arteries on the surface. An AVC consists of an artery andvein from different twins that traverse the same cotyledonary foramen but connect atthe capillary level in the villi.) The majority of MC twin placentas contain one AAA,seldom more. In contrast, VVAs are much less common but, when present, there maybe several per placenta. The relative rarity of VVAs might result from low flow rates andpressures in chorionic plate veins and VVAs, with spontaneous thrombosis/sclerosis.The structure and function of fetal vascular connections are contrasted in Table 4.

CLINICAL CORRELATIONS WITH INTERFETALVASCULAR CONNECTIONS

Interfetal vascular connections are present in 95–98% of MC twin placentas. Clinicaloutcomes depend on diameters and directions of flow in these various connections.Table 5 shows the mean number and type of vascular connections seen in MC twinplacentas of several clinical subtypes.12

Table 4. Structure and function of interfetal vascular connections in MC twin placentas.

Type AVC AAA VVA

Frequency Majority of placentas, Up

to 2–5 per placenta

Majority of placentas, One

per placenta

15–20% of placentas, Up

to 2–3 per placenta

Flow/pressure Always present, low

pressure

High pressure. No net

flow if twin cardiac

outputs are equal

Low pressure. Not net

flow if twin cardiac out-

puts are equal. Potential

for rapid transfusion of

large volumes

Flow direction Unidirectional in each

AVC but different AVCs

can flow in opposite

directions

Bidirectional, minimal,

pulsatile

Bidirectional, minimal,

non-pulsatile

AAA, arterio-arterial anastomoses; AVC, arterio-venous connection; VVA, veno-venous

anastomoses.

Table 5. Mean numbers of vascular connections in MC twin pairs with subtypes of clinical disease.12

Clinical status All connections AAA VVA AVC, both directions

Severe TTT 1 0 0 1

Mild TTT 2 1 0 1

SGD 3 0 0 3

Controls 5 2 1 2

AAA, arterio-arterial anastomoses; AVC, arterio-venous connection; SGD, severe growth

discordance; TTT, twin–twin transfusion; VVA, veno-venous anastomoses.

Diagnosing chorionicity: how and why 521

Severe growth discordance

Whereas differential cord insertions are be the main factor in SGD, these pregnancieshave fewer superficial connections than control MC placentas (Table 5).

Antenatal chronic twin–twin transfusion

This occurs when there is steady, unidirectional flow in a dominant (causative) AVC thatis compensated inadequately or not at all by any contradirectional flow in coexistingconnections elsewhere on the vascular equator. The severity of TTT is variable and isprobably determined by the combination and direction of interfetal vascularananstomoses. A single AVC in the absence of any other effective connectionsdooms the twins to early, severe TTT (Table 5).

There are two routes by which flow in the causative AVC can be compensated: (i) byan AVC in the opposite direction; and (ii) by surface AAAs or VVAs that allow therecipient to download to the donor across a newly established pressure gradient,thereby establishing a dynamic equilibrium. Fortunately, the majority of MC twinplacentas contain combinations of these connections. Although transfusion is alwaystaking place across AVCs, the complexity of different connections does not permitimbalance and development of TTT. The presence of an AAA largely protects againstthe development of TTT14; TTT that occurs in the presence of an AAA or bidirectionalAVCs is usually mild. At fetoscopy for laser vascular coagulation, the characteristicanatomy of the AVC is easily seen.

Twin reversed arterial perfusion

Cord insertions are usually as close as 2–3 cm and there is one large AAA and onelarge VVA between the roots of the cords. The pump twin perfuses the whole of theplacenta with normal artery/vein pairs to all cotyledons. The acardiac twin is effectivelya side branch from the umbilical vessels of the pump twin. ‘Twice-used’ blood flowsback in the VVA from acardiac to pump twin. Simply stated, this blood has perfusedboth twins without a replenishing cycle through the placenta. Toxic products from theregressing body of the acardiac twin are transferred directly to the brain of the pumptwin. Flow in the VVA is also sluggish, with a tendency to thrombosis and the risk ofcerebral thromboembolism in the pump twin.

Vascular instability

In the absence of TTT or demise of one twin, MC twin pairs can be discordant forspecific types of congenital heart disease thought to result from transient reduced flowthrough ventricles and great vessels during cardiogenesies, i.e. as early as 4–6 weeks ofgestation. These ‘flow’ lesions include left heart hypoplasia and pulmonary atresia.15

Impending fetal demise—selective reduction

When there is impending fetal demise or an indication for selective termination (e.g.TTT, SGD, discordant anomaly), standard technical methods used for singletons andDC twins cannot be applied because the intracardiac toxic agents rapidly reach theintended survivor twin via interfetal vascular anastomoses, resulting in the loss of both

522 G. A. Machin

twins. This ‘problem’ becomes an advantage when selective reduction is used inHOMPs containing MC twins, because the high-risk MC twin pair can be selectivelyreduced by one procedure.16 However, during spontaneous fetal demise of one MCtwin, the other twin might develop cystic encephalomalacia.17 Fetal rescue shouldtherefore be planned and implemented before fetal demise: the types and directions ofinterfetal connections should be considered in management options. Selectivetermination in TRAP is straightforward because placental vascular distribution to andfrom the placenta by the pump twin is not disturbed when the circulation to theacardiac twin is interrupted. This is because the pump twin is already perfusing thewhole placenta. However, in all other MC twin pairs—in which both twins have cardiacactivity and have been perfusing their respective placental zones—the death of one twinopens up the body and placental territory of that twin as potential sumps in whichblood from the intended survivor could pool.18 Thus the prognosis for the survivor inTTT is better when the donor dies first than when the recipient dies first (Table 6).19

Two factors account for this: (i) the causative AVC does not permit retrograde flowback from recipient to donor; and (ii) the placental territory of the donor is frequentlysmall, limiting blood loss from the surviving recipient. The converse applies when therecipient dies first—the surviving donor might bleed across the causative AVC into therecipient and/or its placental zone, with consequent hypotension and bradycardia. Itmight be necessary to consider ablation of any connecting vessels before cord ablation.When terminating a small fetus with SGD, the small placental zone probably does notpose a threat of significant blood loss by the larger twin.

Long-term neonatal and pediatric morbidity in survivingmonochorionic twins

Survival rates and neurologic outcomes

Despite their high risks, there are few large, population-based studies investigating thelong-term health of MC twins.9 In a comparison between 164 DC and 44 MC twinpairs6, the relative rates of death and major neurologic handicap were 3.6% and 10.2%,respectively. The single best predictor of adverse outcome in 59 MC twin pairs wasamniotic fluid volume discordance20, although hemoglobin discordance also correlateswell with adverse outcomes.21 Vascular instability in the absence of TTT might havecaused a concordant Pena-Shokeir phenotype in an MC twin pair of a tripletpregnancy.22 These studies probably contain MC twins with several vasculogenicdisorders, predominantly TTT and SGD.

Follow-up in specific subgroups, such as TTT, is reported in a few small series. In aseries of 47 TTT twin pairs, 49 (52%) survived. Of these survivors, 40 were followed;13 (32%) had specific delayed language development and/or minor neurologicdysfunction whereas nine (22%) had severe psychomotor retardation with cerebral

Table 6. Vascular anatomy and results of single fetal demise in 16 pairs of MC twins with TTT.19

Fate of co-twin Recipient died first ðn ¼ 16Þ Donor died first ðn ¼ 10Þ

Co-twin fetal demise 9/16 0/10

Severe anemia of survivor 7/7 1/10

Brain lesions of survivor 6/7 2/10

Diagnosing chorionicity: how and why 523

palsy.23 Of eleven TTT pairs with fetal death of one twin, three survivors died in theneonatal period, two had severe neurologic deficits and two had cerebral echodensitiesby ultrasound.24 In a study comparing the incidence of echogenic white-matter lesionsin twins, 12 (30%) of 40 MC twins and 2 (3.3%) of 62 DC twins were affected.25 Detailedplacental examination showed that superficial vascular connections were present inthese cases and that VVA were strongly associated with white-matter necrosis.

The main discussion point in the treatments available for TTT concerns theneurologic status of survivors.26 A cohort of 89 TTT survivors was tested forneurologic outcome at a median of 21 months. Of these, 69 (78%) were intact, 10 (11%)had minor deficiencies and 10 (11%) had major neurological handicaps. It is certainlyclinically valid to consider TTT as displaying a spectrum of severity. ‘Milder’ casesrespond to amnioreduction because they have several vascular connections that arere-established by removing amniotic fluid volume and pressure. However, ‘severe’ casesoften have a single causative arterio-venous anastomosis and early laser therapy mightbe the only route to intact survival. However, large series with detailed placental studyare required before the role of vascular connections can be fully clarified in terms ofoutcome.

Cardiac disease

MC twins might have structural congenital heart disease of the ‘flow’ type. Such lesionsare not necessarily the result of the abnormal MZ twinning itself, nor do they indicategenetic discordance in MZ twin pairs. Rather, they are thought to rise throughabnormal transcardiac flow, either in early cardiogenesis15 or as the result of chronicantenatal TTT. In a series of 73 TTT pairs, seven (9.6%) of recipients developed rightventricular outflow tract (RVOT) obstruction. Four recipients died with RVOTatresia.27 In a similar study28 of 17 TTT pairs, all recipients showed varying degrees ofright heart failure in utero and 45% of the surviving recipients had residual rightventricular hypertrophy and/or dilatation that resolved in the ensuing 6 months afterbirth. A large study of 136 MC twin pairs showed a prevalence of structural congenitalheart disease in 6/87 (6.9%) of TTT survivors and 4/177 (2.2%) of MC twins withoutTTT, whereas the incidence in TTT recipients was 5/42 (12%). One of the non-TTTtwins had aortic coarctation but the majority of the other lesions were right-sidedobstructions.29 Assuming that right ventricular obstruction represents a response todecreased forward flow, increased blood viscosity and a combination of these factors,left-sided lesions might have a similar pathogenesis in early disturbed aortic flow duringcardiogenesis without overt TTT.15

Renal disease

Transient or permanent postnatal oliguria is described in TTT donor survivors,usually on the basis of renal tubular dysgenesis.30,31 Abnormal proximal convolutedtubular structure and function is probably caused by renal hypoperfusion. Thesepermanent injuries must already be present in fetal life and might account forparadoxical cases of TTT in which the donor fetus does not appear to respond toadequate treatment.

Whereas neurologic disorders in surviving MC twins can be caused partly byprematurity and partly by placental vascular considerations, cardiac as well as renalstructural changes are attributable entirely to the vascular structures of MC placentas,with the added factors of specific clinical conditions such as SGD, TTTand fetal demise.

524 G. A. Machin

Monoamniotic twins

In addition to the vasculogenic risks of monochorionicity, monoamniotic (MA) twins(5% of MC twins) incur other potential complications that increase their risks abovethose of MC, diamniotic (DA) twins. It has been suggested that MA twins do notdevelop TTT because their close cord insertions ensure that large AAAs and VVAs runbetween the roots of the cords.32 In general, it is hard to make the diagnosis of TTT inMC/MA twins when oligohydramnios and polyhydramnios cannot be present bydefinition. However, one potential case of TTT with polyhydramnios and hydrops hasbeen reported in MA twins.33 (In my personal practice, I have seen two such cases, bothwith atypically remote cord insertions.)

Unlike TTT, TRAP is found quite frequently in MA twins, probably because the closecord insertions are favorable to this condition. Indeed, a recent review of 25 MA twinsfound 2 cases of TRAP.34 Regardless, virtually all MA twins have entwined cords fromearly gestation.35 These often quite complex entanglements can cause single or doublefetal demise simply through umbilical venous compression. A notched arterial velocitywaveform36 and color flow Doppler detection of extremely high umbilical venousflow37 are clues to cord entanglement. One reason to favor cesarean section for MAtwins is the fact that the nuchal cord of the presenting twin might actually belong to thesecond twin.38 In a series of twelve MA twins pairs diagnosed in the first trimester, theoutcomes were poor because four pairs were conjoined, four were discordant formajor regional anomalies and four structurally normal pairs had cord entanglement;only two pairs survived.39

Discordance for anuria caused by urinary tract malformation can be particularlyconfusing because normal urinary production by one twin into the common amnioticcavity masks the effects of anuria on the part of the other twin, including Potter’soligohydramnios syndrome, especially lethal pulmonary hypoplasia.40

Blood-borne concordance in monochorionic twins

Neonatal hypothyroidism is frequently (85%) caused by defective differentiationand/or migration of the thyroid gland (thyroid dysgenesis). In two large databases ofcongenital hypothyroidism screening programs, five MZ twin pairs were found to bediscordant for thyroid dysgenesis.41 All pairs were MC/DA and had potentiallymisleading results for thyroid screening, with less elevated thyroid stimulatinghormone (TSH) levels than would be expected in the twins with hypothyroidism. Atdefinitive diagnosis, there was a 7-fold increase in TSH levels over those found atscreening. This was taken as evidence of a protective effect during fetal life, in whichthe normal co-twin transfused euthyroid blood to the thyroid-deficient co-twin.Under such circumstances, the diagnosis of neonatal hypothyroidism might be delayedin discordant MC/MZ twins.

Retrospective analysis of newborn blood spots in some leukemic children hasidentified infrequent monoclonal cells with gene fusion sequences identical inbreakpoint with cells from the overt leukemia that subsequently developed.42 Uniqueand identical breakpoints in fusion genes have now been found in MC/MZ twins whoboth developed common acute lymphoblastic leukemia at 3 years 6 months and 4 years10 months of age.43 Transplacental transfusion of mutated cells probably occurred infetal life.

Diagnosing chorionicity: how and why 525

General comments on vascular structures

In all of these considerations, one must remember that the interfetal vascularconnections established in early pregnancy do not remain constant thereafter. Cases ofTTT with atypical late onset can be caused by thrombosis in the venous arm of acompensatory AVC, disturbing a previous dynamic equilibrium.44 It seems likely thatthere are more AVCs and VVAs in early gestation than later. VVAs are particularlydangerous because they permit large and rapid flows at low resistance.25 The higherfetal loss rate before 24 weeks gestation in MC/DA versus MC/DC twins (12% versus 2%)could in large part be caused by vascular complications, including TTT.45 It is crucialto recall that each MC placenta has its own pattern of cord insertions and vascularconnections, and that these connections are the cause for the unique and dangerousconditions that largely determine clinical outcomes in MC twins. Further progress isneeded to apply available postpartum knowledge to the in vivo MC twin pregnancy.Unfortunately, none of this will be relevant unless MC placentation is diagnosed in earlypregnancy.

DIAGNOSIS OF MONOCHORIONIC TWIN PREGNANCY,AND ITS COMPLICATIONS

The prime objective of obstetric ultrasound in multifetal pregnancy is the unequivocaldetermination of chorionicity and the ascertainment of MC twins. It is generallyrecommended that a sequence of factors be considered: fetal external genital sex,placental masses and septal thickness.46 However, MC twins can be unlike-sexed, eitherbecause of anomalous development after in vitro fertilization (IVF) with blastocysttransfer2 or because of postzygotic chromosome abnormality (heterokaryotypia).47

Counting placental masses can be unreliable, as evidenced by two reports of bilobedMC twin placentas.48,49 (In my own practice, I have seen eight such cases inapproximately 600 consecutive MC twin pregnancies. The ultrasound examination in alleight cases concluded that placentation was DC on the basis of two distinct placentalmasses, despite failure to see a lambda sign. There were no adverse outcomes.)

Under these circumstances, diagnosis should principally rest on assessing themembranous septum. Terms such as ‘thick’ and ‘thin’ are best used without absolutequantitative measurements. The two amniotic layers of the MC twin placenta are ‘wispyor faintly seen and visualized in short segments’ (Figure 3a). In contrast, the DC septumis ‘well-defined and imaged over a long segment’ (Figure 3b). The ‘lambda’ or ‘twin peak’sign for DC, and the ‘T’ sign for MC, are identifiable in the majority of cases.50 In thisseries of 150 twin pregnancies diagnosed at 10–14 weeks and with histologicconfirmation of chorionicity in like-sexed twin pairs, one DC pair was incorrectlydiagnosed as MC on the basis of septal membrane thickness and a ‘T’ sign. No MC pairswere misdiagnosed as DC. Septal thickness was 2.2 mm (range 0.7–4.1) and 0.9 mm(range 0.6–1.2) in DC and MC placentas, respectively.50

Whereas it is acceptable to err on the side of caution and to suspectmonochorionicity because of thin septal membranes, it is best to avoid the use ofimprecise terms such as ‘sacs’, which could imply either chorionic layers or amnioticlayers. There might be an undue tendency to concentrate on the number of amnionsrather than the number of chorions, such that chorionicity is never actually stated in thereport. Considering the rarity of MC/MA twins, it is not justified to look very carefullyfor amnions at the expense of delineating the number of chorions. MC/DA twins have

526 G. A. Machin

Figure 3. First-trimester ultrasound diagnosis of chorionicity. (a) Thin, wispy septal membranes of MC DAtwins; (b) ‘lambda’ or ‘twin peak’ sign in DC twins.

Diagnosing chorionicity: how and why 527

two yolk sacs whereas MC/MA twins have only one.51 Because cord entwining is almostuniversal in MC/MA twins, this aids in the diagnosis, making amniography unnecessary.37

SUMMARY

Management of MC twin pregnancy is challenging. Several related disorders occurin 10–15% of cases. These are caused by the special vascular structure of MCplacentation, which is unique for each MC placenta. Improved prognosis will bestbe achieved by first-trimester diagnosis, careful prenatal monitoring, randomizedtrials for TTT and long-term follow-up studies of MC twin survivors.

REFERENCES

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2. Souter VL, Kapur RP, Nyholt DR, et al. A report of dizygous monochorionic twins. New England Journal ofMedicine 2003; 349: 154–158.

*3. Dube J, Dodds L & Armson BA. Does chorionicity or zygosity predict adverse perinatal outcomes intwins? American Journal of Obstetrics and Gynecology 2002; 186: 579–583.

4. Hatkar PA & Bhide AG. Perinatal outcome of twins in relation to chorionicity. Journal of PostgraduateMedicine 1999; 45: 33–37.

5. Minakami H, Honma Y, Matsubara S, et al. Effects of placental chorionicity on outcome in twin pregnancy.Journal of Reproductive Medicine 1999; 44: 595–600.

6. Baghdadi S, Gee H, Whittle MJ & Khan KS. Twin pregnancy outcome and chorionicity. Acta Obstetrica etGynecologica Scandinavica 2003; 82: 18–21.

Practice points

† first-trimester ultrasound: (i) lambda sign or T-sign; (ii) assess septal membranethickness; (iii) number of yolk sacs; (iv) evidence for cord entwining

† second-trimester ultrasound: (i) cord insertions; (ii) differences in amnioticfluid volume; (iii) fetal growth discordance with asymmetric cord insertions; (iv)recognition of TRAP; (v) MZ/MC twins are usually discordant for congenitalanomalies; (vi) map AAC by Doppler in known MC twins

Research agenda

† is umbilical arterial Doppler flow measurement appropriate in MC twins?† the usefulness of seeking AAA by second/third trimester Doppler studies as a

diagnostic feature of MC twinning† the need for separate biometric tables for DC and MC twins† does early diagnosis of MC twins produce better outcomes through more

intensive surveillance?† what are long-term outcomes following selective terminations in non-TRAP

MC twins?† what are long-term outcomes for MC twin survivors in general?

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