MULTIPLE PREGNANCY

INTRODUCTION

Background

• 3% of all livebirths
• Increase in all types of multiple pregnancies due to
  • Increase use of ART / Sociodemographic factors / Advanced maternal age
• Monozygous twinning rates are relatively constant (3-5/1000 births)
• Dizygous pregnancy rates vary (from 1.3 to 49/1000) with
  • ART
  • Maternal age
  • Race
  • Nutrition
  • Geography
• Multiple pregnancies -1 in 5 IVF pregnancies, 1 in 80 for women who conceive naturally
• ART increases the prevalence of both DC and MC twinning
• Day 5 blastocyst transfers seems to have a significantly higher rate of MZ twinning
• To reduce incidence as a result of ART
  • Elective single embryo transfer (eSET)
  • Single blastocyst transfer
  • Selective fetal reduction

Zygosity

• Chromosomal abnormality in the twin pregnancy related to zygosity
• dizygotic / non-identical twin (70%) – Fertilization of more than one oocyte à develop their own placentae
• Monozygotic twin / genetically identical twins (30%) – Two Splitting of a single fertilized oocyte à may share a placenta according to the time of separation
• Dichorionicity occurs in 80% of twins, and genotyping is required to confirm zygosity

Chorionicity

• Early establishment of chorionicity is crucial to mx of twins
• Complications –  MC  >  DC twins
• 20% of twins are MC – associated with 26 % risk of perinatal mortality
• Dizygous twins are always DCDA.
• Chorionicity of MZ twins depends on the timing of embryo splitting

DIAGNOSIS OF TWIN PREGNANCY & DETERMINATION OF CHORIONICITY

• All women with a twin pregnancy should be offered an US btn 11+0 – 13+6wks (CRL 45-84 mm) to assess
  • No. of amniotic sacs – amnionicity difficult to establish accurately before 7-8 wks in MC
  • No. of fetal poles
  • Fetal viability
  • Gestational age
    • In IVF – knows the time of fertilization
    • In spontaneously conception à CRL of the larger fetus (to avoid the risk of estimating it from a baby with early growth pathology)
  • Chorionicity –
    • more sensitive & specific in T1 (nearly 100% accuracy)
    • Composite method (Presence of lambda or delta or twin peak sign / T-sign, no. of placental masses & ect) using USS in T1à sensitivity & specificity > 95%.
    • In mid-trimester – only 80–90 % accuracy

• Appearance of the membrane attachment to placenta (lambda/T-sign)
  • Number of placental masses
    • 3% of MC placentas have two placental masses (bilobed placenta)
  • Membrane thickness in 2D USS
    • < 1.8 mm for MC twins
    • 1.5–2.0 mm can be inconclusive for MC twins
    • But when used with other factors, chorionicity can usually be defined in 99% of cases
  • The number of membrane layers (subjectively noted)
  • Concordant fetal sex [in MC twins]
  • In difficult cases, zygosity studies may need to be performed
  • Exclude major congenital malformations
    • anencephaly
    • large cystic hygroma
    • Exclude ‘acardiac twinning’
  • Screening for Down syndrome – NT
  • Accurate labelling (nomenclature)
    • Lateral / vertical orientation was a reliable method of twin labelling (i.e. upper and lower, or left and right)
    • Approximately 90% were oriented laterally & 10% vertically
    • Serial growth scan measurements can be consistently applied to the same twin throughout pregnancy and that any intrauterine or neonatal management can be directed towards the correct twin.
• A photographic record should be placed in the patient’s notes document
• If uncertainty about the diagnosis (a photographic record of the ultrasound appearance of the membrane attachment to the placenta) à second opinion should be sought.
• If still doubt à referred to a specialist without delay (chorionicity is best determined before 14 wks of gestation)
• If doubt, even after referral (Eg: late booking) à pregnancy should be managed as MC until proved otherwise.

All twin pregnancies should be offered an ultrasound scan btn 11 – 13+6 weeks to assess viability, determine chorionicity and to screen for Down’s syndrome

ANTENATAL MANAGEMENT

• Same advice about diet, lifestyle and nutritional supplements as in routine standard care.
• Higher incidence of anaemia à  FBC should be performed at 20-24 weeks to identify women who need supplementation of iron / folic acid, repeated at 28 weeks as routine.
• Manage by a nominated MDT consisting specialist obstetricians, specialist midwives and ultrasonographers, all have experience and knowledge of managing twin pregnancies.
• Access to a perinatal mental health specialist, women’s health physiotherapist, an infant feeding specialist and a dietician.
• A dedicated clinic for birth preparation and psychological support.
• Counselling on complication.

OPTIMUM ULTRASOUND REGIMEN FOR MC TWIN

• USS every 2 weeks in uncomplicated MC twins from 16+0wks onwards until delivery (although first presentation of TTTS is rare after 26+0weeks of gestation, it can occur)
• Between 16 – 26 wks focus primarily on the detection of TTTS.
• From 20 wks, screening for sGR should be included, UAPI should be performed even in the absence of signs of TTTS or growth discordance and plotted on standard charts
• After 26 wks, the main purpose is to detect sGR or concordant growth restriction, and more rarely TAPS or late-onset TTTS
• At every US examination
  • Fetal biometry (head, abdominal & femur measurements) à EFW, Growth discordant
  • Liquor volume in each of the amniotic sacs should be assessed – DVP of both sac
  • Umbilical artery pulsatility index (UAPI)
  • Fetal bladders – size and visibility
• At any point à If there is evidence of significant growth discordance or a suspicion of TTTS
  • UAPI
  • MCA PSV & PI
  • Ductus venosus Doppler should be performed

COMPLICATION

• Twins are more at risk of pregnancy complications

Maternal complications

maternal mortality associated with multiple births is 2.5 times higher than singleton births.

• EARLY PREGNANCY ISSUES
  • Miscarriage
  • Hyperemesis gravidarum
  • Increased mechanical symptoms of pregnancy
  • Gastro-esophageal reflux
  • ANTENATAL
    • Polyhydramnios
    • Preterm labour and delivery
      • Twins – 5 times compared with singletons
      • Twin delivery <37 weeks – up to 50%
      • Delivery <32 weeks is approximately twice as common in MC compared with DC
      • (5% for DC and 10% for MC twins compared with 1% for singleton)
      • Triplets – 17% by 29 weeks, 27 % by 32 weeks & 75% by 35 week
      • Prediction in twin pregnancies is as difficult as in singleton pregnancies
      • Cervical assessment – frequency of monitoring/assessment of the cervix is unclear
      • In singleton – cervical length of 15 mm is predictive of preterm labour.
      • In twin, the mean cervical length is similar to that of singletons (38 mm), but a cervical length of 25 mm at 23 weeks predicts about 80% of women <30 weeks (FP-11%)
      • Management
        • Progesterone supplementation does not prevent early preterm labour in twin
        • No reduction in the incidence of preterm labour in twin
          • Home uterine monitoring
          • Fetal fibronectin estimation
          • Prophylactic cervical cerclage
          • Tocolysis
        • Routine hospitalisation for bed rest in multiple pregnancies – not enough evidence (No reduction in preterm birth or perinatal death, although there is a suggestion that fetal growth is improved.
        • Uncomplicated twin – bed rest may be harmful (risk of very preterm birth is increased)

• APH
  • Anaemia
  • HT disorders (Pre-eclampsia)
    • Women with twin pregnancies may be at higher risk of hypertension.
    • NICE suggest that women with multiple pregnancies should take 75 mg of aspirin daily from 12 weeks until the birth of their babies if they have one or more of the following risk factors for hypertension:
      • First pregnancy
      • Age 40 years or older
      • Pregnancy interval of more than 10 years
      • BMI of 35 kg/m2or more at first visit
      • Family history of pre-eclampsia
  • GDM
  • INTRAPARTUM
    • Operative delivery
  • POSTPARTUM
    • PPH
    • Problems with breastfeeding
    • Postnatal depression
    • Increased stay in hospital

Fetal complications

• Increase in fetal and neonatal mortality compared with singleton .
• Perinatal morbidity & mortality increase with increasing order of multiple pregnancy.
• Majority of perinatal deaths are associated with preterm birth and IUGR
• Loss rate (mainly before 24 weeks)
  • MC twins -14.2 %
  • DC twins – 2.6 %
  • Differential loss rate is mainly due to TTTS (accounts for 20 % of SB)
• Stillbirth rate compared with singleton
  • Twin – 2.5 times
  • Triplet & higher-order births – 3.1 times
• Neonatal deathrate compared with singleton
  • Twin – 6.7 times
  • Triplet & higher-order births – 14.8 times
• Complication of MC  arise from shared placenta and vascular placental anastomoses
• Specific complications associated with inter-twin vascular anastomoses
  • TTTS
  • sGR
  • twin anaemia-polycythaemia sequence (TAPS)
  • twin reversed arterial perfusion (TRAP) sequence
  • single IUD – not exclusive to MC twin – more common & effects on the co-twin
  • Discordant fetal anomalies (structural and chromosomal anomalies)

OUTCOME – MC vs DC

• MC are associated with even higher perinatal risk

	MC	DC
FETAL LOSS RATE	14.2	2.6
PERINATAL MORTALITY	11.6	5.0
NEUROLOGICAL MORBIDITY	7 Fold high
MEAN BIRTH WEIGHT (both)		Higher
MEAN GESTATIONAL AGE AT DELIVERY		Higher
CHROMOSOMAL ABNORMALITIES	Same

Vanishing twin & fetus papyraceous – in all types

• Up to 21% of twin are complicated by either miscarriage or loss of one twin in the early stages.
• ‘vanishing twin’ phenomenon (fetal resorption) detected by high resolution US.
• Miscarriage rate is 5 times higher than normal twins.
• No increased monitoring needed if the baby appears structurally normal.
• Pregnancy is most likely to progress as expected for a singleton.
• Loss of a co-twin in T2 or T3 carries a risk of preterm delivery, neurological sequelae or death to the remaining fetus. It may result in the phenomenon known as fetus papyraceous, where the anatomically-preserved demised fetus can be identified at the later delivery of the surviving twin.

Multi fetal pregnancy reduction (MFPR)

• multifetal pregnancy reduction at approximately 12 wks should be offered to women with higher multiples to lower the incumbent risks.
• Post-procedure miscarriage rates – <10%
• Reductions from higher multiples to twins carry outcomes as good as those of unreduced twin and the chance of taking home a live baby increases from 80 % to 90%

SCREENING FOR CHROMOSOMAL ABNORMALITIES IN MC

• MC are not increased risk of chromosomal abnormalities over DC,
• prevalence of aneuploidy is slightly increased overall in multiple pregnancies as an indirect association with increased maternal age

Aneuploidy screening

• Risk of Down’s syndrome is 1 in 700 pregnancies
• Risk for MZ twins is the same as for singletons, but DZ twins has doubled as each twin has its own individual risk
• Serum screening in multiple pregnancies is not as reliable as in singletons
• T1 – Combined screening test
  • NT with serum markers (PAPP-A & b-hCG) at 11+0 – 13+6weeks of gestation (CRL 45–84 mm) à sensitivity – 90% & false positive rate -10% (singletons – 2.5% and DC twin – 5%)
  • Detection rate depending on the chorionicity:
    • MC twins – 75-80% with a 3% false positive rate (same as for singletons)
    • DC twins (If one baby is affected) – 40 – 50% with a 3% false positive rate
  • NT + T1 serum markers + maternal age
    • Pregnancy specific risk is calculated in MC twins
    • Fetus specific risk is calculated in DC  twins
• Detection rates can be improved by
• Presence of additional USS markers
• Nasal bone
• Ductus venosus Doppler waveform analyses
• Tricuspid Doppler waveform analyses (TR)
  • Additional biochemical markers – increase up to 87%
• AFP
• uE3
• Presentation beyond 14 weeks – quadruple test may be offered up to 20 weeks
• T2 – quadriple screen test (serum screening)
  • 80% detection rate
  • False positive rate – 3%
  • In MC twins provides a pregnancy specific risk
• Non-invasive prenatal testing (NIPT)
  • detection rates btn 98-99% & FP rates of <0.4%
  • Singleton pregnancies – Detection rate  99% & FP  rate – 0.8%
  • Twin pregnancies – Detection rate 94.4% & FP  rate – 0%.

• If increased NT, the option of invasive testing should be discussed
• Before invasive procedure (for karyotyping) careful ultrasound mapping is important
• Both amniocentesis and CVS are possible in twin pregnancy
• Risks of miscarriage & other procedure related complications are – 1 in 50 twins
• Loss rates for amniocentesis in twins similar to singletons, in higher-order multiples – No data
• double amniocentesis has a lower risk of sampling the same fetus.
• CVS carries a higher loss rate & less reliable than amniocentesis as up to 4 % of CVS samples show evidence of co-twin contamination.

SCREENING FOR  STRUCTURAL ABNORMALITIES IN MC

• Common abnormalities in twin (MZ > DZ) & higher order is cardiac (than singleton)
  • In DZ  – comparable to that of singleton (2-3%)
  • In MZ  – up to 10% (2-3 times of dizygotic)
• Higher incidence in MZ owing to the unusual nature of the cleavage of the conceptus
• Abnormalities specific to MZ twins are often midline
• During the process of development – often midline structural anomalies
  • NTDs
  • Cleft lip
  • VATER association
• Disorders of laterality occur when embryonic migration has begun prior to zygotic splitting and may explain the increased incidence of some anomalies in MZ twin pregnancies,
  • Cardiac anomalies – fetal 2Decho is ideally offered at 22-24 weeks
• Disruption in a previously normal formed fetus – predominantly abnormal vascular connections in MZ twin predispose to
  • Limb reduction defects
  • Bowel atresia
  • Hydrancephaly
  • Porencephaly
• Constraint of sharing the uterine cavity
  • Talipes
  • Congenital dislocation of the hip
• An extreme example is the development of conjoined twins.
• MZ offspring may be genetically& phenotypically dissimilar. Mechanisms may include
  • Unequal allocation of blastomeres btn the two embryos
  • Disrupted embryonic migration
  • Somatic mosaicism or chimerism
  • Variations in penetrance
• Discordant for chromosomal, genetic and structural anomalies reported in MZ twins.
  • Discordant single gene disorders
  • Imprinting defects
  • Aneuploidy
• Discordant structural anomalies found in MZ twin pairs, from neural tube defects and holoprosencephaly to lateral and ventral body wall defects, and anomalies related to the VATER association

• Recommended same T2 USS screening regimen for MC & DC – cannot determine MZ using US
• For all MC twins – routine detailed US btn 18 – 20+6 weeks of gestation which includes extended views of the fetal heart anatomy

Discordant structural anomaly

• Accurate diagnosis & determination of chorionicity is critical
• 1–2% of twin face the dilemma of expectant Mx VS selective termination
• Higher rateof structural anomaly is observed in twins compared to singletons
• Structural anomalies in MC  are twice than expected in DC.
• In a structurally / size discordant MC pair, discordant aneuploidy is exceedingly rare, although, not impossible.
• Depending on the anomaly detected, parents may be faced with a choice of
  • Continuing the pregnancy
  • Delivering both a normal and an affected baby
  • Terminating the affected fetus and risking the viability of the healthy co-twin.
• If not performed in the T1, is usually delayed until the T3 when viability of the normal twin is more certain. This must be balanced against the risk of spontaneous premature labour, especially in cases complicated by polyhydramnios such as anencephaly

MC twin

• Management is complex – shared circulations within the placenta
• Fetal surveillance depending on the anomaly
• MDT Input (e.g. Genetics team, paediatric cardiologist, paediatric surgeons) – appropriate birth planning (place, timing and mode), including access to intrauterine mx where it is possible
• Referred promptly for assessment & counselling in a fetal medicine centre
• Detailed US assessment, fetal karyotyping and a discussion of prognosis is required with reference both to the abnormal and normal twin.
• Meticulous mapping of the position of the twins should be performed both at the time of prenatal diagnostic tests and invasive treatments.
• During amniocentesis, both amniotic sacs should be sampled
• Prior to invasive testing, appropriate counselling & selective reduction should be discussed
• Monitoring for DIC is not indicated in MC twin undergoing selective reduction.
• Selective feticide by intravascular injection of an abortifacient is not an option in MC pregnancies because of the presence of placental anastomoses.
• The potential risks of intrafetal (radiofrequency ablation)/ umbilical cord ablative procedures should be discussed prospectively, including the risk of co-twin loss and neurological morbidity – More invasive & higher risk procedures
  • Overall, up to 82% of co-twins survived
  • Fetal loss rates – 15 – 18%
  • PROM – 10-15%
  • Transfusional neurological sequelae – up to 15%
  • Chorioamnionitis remain significant complications
• Documentation and discussion of heterokaryotypic monozygotic karyotypic abnormalities should take place

DC twin

• Selective feticide is an option (separate inter-twin circulations)

TWIN TO TWIN TRANSFUSION SYNDROME (TTTS)

• acute or chronic
• Complicates up to 15% of MC
• Very rarely, TTTS complicates MCMA twin, as well as both DC & MC triplet pregnancies.

Acute TTTS

• Present as sudden onset of maternal discomfort and increasing girth, following rapid development of polyhydramnios.
• Mortality is extremely high usually as a consequence of premature delivery, either spontaneous or iatrogenic.

Definition

Pathogenesis

• Almost all monochorionic placentas contain vascular anastomoses running btn two fetal umbilical cords within (deep placental vascular connections) and on the surface (superficial placental vascular connections) of the placenta, which connect the fetal circulations.
• Deep anastomoses occur btn arteries and veins. These arteriovenous(AV) connections are unidirectional, and require the presence of ‘balancing’ superficial anastomoses to prevent TTTS
• Superficial anastomoses are bi-directional and are commonly found between arteries (arterio-arterial anastomoses) and veins (veno-venous anastomoses)
• Bidirectional flow allows compensatory activity in the event of pressure differences within the placenta, and if reduced or absent this predisposes to TTTS.
• In 80% of cases, due to haemodynamic imbalances caused by unidirectional deep arterio-venous anastomotic vessels and a relative lack of superficial vascular anastomoses leads to net flow of blood from one twin (the ‘donor’) to the other (the ‘recipient’) causing haemodynamic imbalance between the fetal circulations à adversely affecting fetal cardiac function, renal function by discordant activation of the renin–angiotensin axis and fetoplacental perfusion.
• hypervolaemia & polyhydramnios in the recipient and hypovolaemia & oligohydramnios in the donor twin, with the separating membrane completely covering this fetus & compressed against the uterine wall, (stuck twin)
• Progression of the syndrome in the donor leads to severe growth restriction and in severe cases, absent or reversed end-diastolic frequencies in the umbilical artery. If untreated, the perinatal mortality rate of TTTS is extremely high (>90 %).
• The recipient usually appropriately grown for gestational age, has a large distended bladder and may develop organomegaly, with abnormal DV doppler frequencies related to polycythaemia and hydrops. Tricuspid regurgitation is an ominous sign of cardiac dysfunction in the recipient and is associated with significant postnatal cardiac dysfunction. Recipient fetuses may also develop neonatal hypertension.
• accounts for  20% of stillbirths in multiple pregnancies
• usually a gradual process, it can happen suddenly with the death of one twin, usually the recipient.
• reverse in 5 % of cases (TAPS) with the donor becoming the recipient and vice versa à occur after treatment with amnioreduction or laser.
• Postnatal perfusion studies have noted unequal placental ‘territory’ shared by the fetuses with associated marginal or ‘velamentous’ cord insertions. Such findings are common both in TTTS and sGR (which is often associated with TTTS).

Presentations

• US finding
• Sudden increases in abdominal size or breathlessness

Screening

• T1 NT measurements should not be offered
• USS from 16+0weeks onwards, at 2-weekly intervals (fetal biometry & liquor volumes-  DVP) Fetal bladders should also be visualised.

Ultrasound diagnosis

• A discrepancy in NT  in T1 – an early marker for TTTS
• Most commonly, diagnosis of TTTS is made in T2 with discordant growth or discrepant liquor volumes
• Significant amniotic fluid discordance (key to the diagnosis)
  • Oligohydramnios with DVP <2 cm in one sac (the donor) & polyhydramnios in the other sac (DVP >8 cm before 20 weeks & >10 cm after 20 weeks) (the recipient)
• Discordant bladder appearances
  • No urine in the ‘donor’ fetal bladder in severe TTTS (presenting <26 weeks)
• Doppler abnormalities
  • Haemodynamic & cardiac compromise – both in ‘recipient’ and/or ‘donor’ twins

Staging

• At diagnosis, TTTS should be staged using the Quintero system
• has some prognostic value
  • Course of the condition is unpredictable
    • Improvement – 1/3
    • Rapid deterioration within a short time span – 1/3
    • Remaining same throughout the pregnancy – 1/3
  • Progress from stage I to stage III without obviously passing through stage II
• A relationship btn Quintero stage at dx and mean gestational age at delivery and perinatal survival

Treatment

• not start until 16 weeks of gestation
• an individual basis
• Treatment options
  • Laser ablation of the communicating anastomoses – selective ablation
  • Serial amnioreduction
  • Septostomy
  • Selective feticide (occlusive feticide)

Laser treatment

• Coagulate the vascular anastomoses contributing to TTTS
• May be selective or non-selective
• Non-selective
  • Destroys all vessels crossing the inter twin membrane
  • Including the healthy circulation
  • May increase mortality in the donor twin
• Selective ablation
  • Ablates only specific connections
  • Amnioreduction is performed following laser ablation in most cases.
• Before 26 wks should be treated by fetoscopic laser ablation rather than amnioreduction or septostomy – should be Solomon technique.
  • Indication for laser
    • Quintero stage II or more
    • Quintero stage I with significant polyhydramnios (≥8cm)
    • Quintero stage I with cervical shortening (<25mm)
  • Complications
    • IUD – 13-33%
    • Ruptured membranes – 10%.
    • Late complications
      • Recurrent TTTS – up to 14% (missed anastomoses)
      • Post laser TAPS due to reversal of flow – 13% à Follow-up with MCA PSV
      • Secondary structural heart disease (primarily right-sided cardiac Lesions, predominantly pulmonary stenosis) – 11%
• Fetoscopic laser coagulation of anastomoses is a more effective 1st-line Rx than serial amnioreduction for severe TTTS diagnosed before 26 weeks of gestation
• Eurofetus consortium trial – laser ablation Vs amnioreduction
  • survival of one or both twins following laser (76%) compared with serial amnioreduction (56%).
  • Median gestational age at delivery was increased in the laser group (33 weeks vs 29 weeks)
  • laser was associated with a reduced incidence of periventricular leukomalacia.
  • As live birth rates were similar in both groups, this survival advantage may reflect the differences in gestation rather than a consequence of the therapy.
  • In addition, early stage disease was not well-represented in this study, leaving persistent doubt about the benefit of laser in early disease – .
• Laser ablation remains the treatment of choice due to the significant reduction in long-term neurological morbidity, even though it does not appear to improve survival (stillbirth, neonatal and post-neonatal) significantly compared with amnioreduction – Cochrane Review 2014, compared with amnioreduction with laser coagulation.
• TTTS before 26 weeks should be treated by laser ablation – RCOG

Serial amnioreduction

• Aims to reduce liquor volume in the recipient twin & to prevent premature delivery
• require repeated procedures
• Not treat the underlying cause of feto-fetal transfusion.
• Associated risks include
• Premature labour
• Ruptured membranes
• Chorioamnionitis
• Placental abruption
• Indication
  • Laser coagulation is not available
  • Diagnosed after 26 weeks of pregnancy
  • stage I disease where the evidence for laser ablation is less robust
• Disadvantage
  • May complicate future Rx if associated with inadvertent septostomy (Chorioamniotic separation may hinder subsequent laser ablation)

Septostomy:

• Aims to disrupt the inter-twin membrane allowing normalisation of liquor volume btn the two sacs, and may be followed by amniodrainage as an adjunctive treatment.
• A randomised controlled trial comparing amnioreduction with septostomy in TTTS before 24 wks of gestation
  • rate of survival of at least one twin was similar in both groups (78% vs 80%),
  • no significant advantage of septostomy with amnioreduction over amnioreduction alone.

Selective feticide

• Selective termination of pregnancy using bipolar diathermy of one of the umbilical cords or using radiofrequency ablation, with inevitable sacrifice of that baby – 85% success rate
  • In advanced TTTS (one of the twin pair is in extrems)
  • If there is evidence of cerebral damage in either twin
• Singleton survival rates would appear to be similar to survival rates achievable by laser ablation

Uncertainty exists regarding the optimum management of early (stage I) disease, where there is some evidence that aggressive treatment may confer little benefit

Current management of TTTS

• Stage 1 – expectant management or amnioreduction
• Stages 2–4 – laser ablation
• If imminent fetal demise of one twin threatens the co-twin – selective reduction

Termination of pregnancy

• Some women request termination of pregnancy when severe TTTS is diagnosed and this should be discussed as an option

Post treatment follow-up

• In treated TTTS pregnancies à USS of the fetal heart by the fetal medicine specialist to exclude functional heart anomalies
• Weekly US assessment (including examination of the fetal brain, heart and limbs) and serial measurements of UAPI, MCA PSV and DV  Doppler velocities should be performed.
• After 2 wks post Rx, US interval can be increased to every 2 weeks (noting UAPI, MCA PSV and DVP) with documentation of adequate fetal growth (by calculating EFW)

TOD / MOD

• Previously complicated by TTTS and treated à Delivery of the surviving twin(s) btn 34+0 and 36+6weeks or earlier if there are concerns
• Prophylactic maternal steroids should be given if possible prior to delivery.
• MOD can be individualised, but often CS.

TWIN ANAEMIA POLYCYTHEMIA SEQUENCE (TAPS)

• Form of TTTS
• Occur spontaneously in up to 2% of MC twins
• Occurring in up to 13% of cases post laser ablation
• Severe sequelae may result – hydrops fetalis and fetal death
• Optimal treatment is unclear

Definition

• Significant discordance in Hb level btn twins without significant AF discordance.

Pathogenesis

• ‘Miniscule’ artery–vein anastomoses (<1 mm) allowing the slow transfusion of blood from donor to the recipient
• Associated with highly discordant Hb levels at birth ( ≥8 g/dl)
• The absence of severe amniotic fluid discordances may be related to very slow inter-twin blood transfusion, allowing more time for haemodynamic compensatory mechanisms to take place

Screening

• Routine screening of MC twins using serial MCA PSV measurements is not recommended
• Confined to complicated MC twin pregnancy where the risk of TAPS is high (TTTS or sGR)
• So, should be screened for following laser ablation for TTTS and in other complicated MC

Diagnosis

• Presence of increased MCA PSV in the donor, suggestive of fetal anaemia (> 1.5 multiples of the normal median), and a decreased MCA PSV in the recipient twin, suggestive of polycythaemia (< 1.0 multiples of the normal median), with the absence of significant oligohydramnios /polyhydramnios sequence.
• Postnatal diagnosis – presence of (chronic) anaemia in the donor (including reticulocytosis) and polycythaemia in the recipient. Postnatal haematological criteria include an inter-twin haemoglobin difference > 8 g/dl and a reticulocyte count ratio > 1.7
• Can do Ferritin level to differentiate from acute loss

Treatment

• Solomon technique for TTTS significantly reduces the risk of recurrent disease and TAPS.
• Little evidence relating to the outcome and optimal management
• Possible options
  • Expectant management
  • Delivery
  • Intrauterine blood transfusion (intravenous and/or intraperitoneal, with or without partial exchange transfusion)
  • Selective feticide
  • Fetoscopic laser surgery – only Rx for the cause of this disease
• Outcome may range from double intrauterine fetal demise to the birth of two healthy neonates with significant inter-twin Hb discordance.
• Neonatal morbidities
  • Haematological problems at birth
  • Donor twins may be severely anaemic – require blood transfusions
  • Recipient twins may be severely polycythaemic –  require partial exchange transfusion
  • May cause severe cerebral injury

SELECTIVE GROWTH RESTRICTION (sGR)

• Occurs in up to 15% of MC twins in the absence of TTTS and in over 50% of MC twins complicated by TTTS
• Specific MC twin pathological entity associated with a significant differing placental territory between each fetus, inter-fetal placental anastomoses and abnormal fetoplacental blood flow
• Discordant growth is recognised as an independent risk factor for adverse perinatal outcome
• Associated with a substantial increase in perinatal mortality and morbidity for both twins
• Mx of discordant growth is more complex in MC pregnancies due to the associated placental anastomoses conjoining the fetal circulations.
• There may be diagnostic ‘overlap’ between mild TTTS and sGR
• TTTS represents a distinct entity of which discordant growth is a common feature.
• In isolated sGR this will differ as there is commonly oligohydramnios in one of the amniotic sacs and normal liquor in the other amniotic sac.

Definition

• Significant intrauterine fetal size discordance (difference in EFW of > 20%), termed ‘selective growth restriction’

Pathogenesis

• Discordant fetal growth (usually one fetus is usually normal size and the other small for gestational age) may be due to,
  • Unequal placental sharing
  • Marginal or velamentous cord insertions (common in MC twins)
  • Differences in genetic potential between co-twins
  • Placental dysfunction confined to one placenta only or one placental territory within a shared placenta
• However, even if both fetuses have an EFW > 10th centile there may be significant size discordance. This is termed sGR.

Screening

• From 20 wks (2-weekly), calculate EFW discordance using two or more biometric parameters
• % of EFW discordance = ([larger twin EFW – smaller twin EFW]/larger twin EFW) x 100.
• DVP should be measured and recorded (to differentiate from TTTS).
• EFW discordance of >20% is associated with an increase in perinatal risk à referred for assessment and mx in fetal medicine units
• UAPI measurements from 20 weeks of gestation and plotted on gestational nomogram charts

Types

• Type 1 – positive diastolic velocities
• Type 2 – AREDV
• Type 3 – cyclical diastolic waveforms (iAREDV)
  • More common in MCDA sGR (45%) than, – Uncomplicated (5%) pregnancies

       – Those complicated by severe TTTS (2%)

Prognosis

• Type 1 – a relatively good outcome (more than 90% perinatal survival)
• Type 2 – high risk (up to 29%) of IUD of the growth-restricted twin and/or preterm delivery.
• Type 3 – 10–20% risk of unexpected fetal demise of the smaller twin (even if stable ultrasound features and/or normal CTG hours or days before) and 10–20% risk of neurological injury in the larger twin

Follow-up

• UA Doppler evaluation in MC twins with sGR allows definition of prognosis and potential morbidity.
• AREDV and ‘cyclical’ umbilical artery Doppler waveforms (intermittent AREDV [iAREDV]) are at increased risk of perinatal mortality and morbidity

Treatment

• Aim :
  • prolong pregnancy to at least viability and to achieve appropriate gestation for delivery (32–34 weeks)
  • avoid complication of single fetal death and the consequences for the surviving fetus
• Selective reduction – may be considered in early-onset sGR in association with poor fetal growth velocity and abnormal UA Doppler assessments (using vaso-occlusive techniques, such as bipolar cord occlusion or radiofrequency ablation)
• In type I sGR – Delivery by 34–36 weeks ( if there is satisfactory fetal growth velocity and normal umbilical artery Doppler waveforms)
• In type II and III sGR – Delivery by 32 weeks of gestation, unless fetal growth velocity is significantly abnormal or there is worsening of the fetal Doppler assessment.
• Timing of delivery (< 32 weeks of gestation) is dependent upon assessment by computerised CTG (short-term variation) and/or DV waveform velocimetry (abnormal)

SINGLE TWIN DEMISE

• Can occur in  uncomplicated MC twins, but more prevalent in MC twins complicated by sGR and TTTS (even treated)
•  After a single fetal demise

	DEATH	NEURO MORBIDITY	PRETERM BIRTH
MC	15	26	68
DC	3	2	54

Compilations (in Co-twin)

• Death
• Neurological morbidity
• Preterm birth
• Anaemia

Pathogenesis

• MC twins with intact placental vascular anastomoses à risk of acute ‘inter-twin’ transfusional events à  fetal death and neurological morbidity.
• Death of the co-twin à acute haemodynamic changes around the time of death àtransient or persistent hypotension and low perfusionà  risk of ischaemic organ damage, notably but not exclusively, to the watershed areas of the brain

Follow-up (Anaemia)

• Assessed by measurement of the fetal MCA PSV

Treatment (Anaemia)

• Presence of an increased MCA PSV suggest fetal anaemia (significant inter-twin transfusion)
• increase the risk of hypotensive neurological injury and thus, would be helpful information in the counselling of parents and timing of fetal brain MRI.
• Intrauterine transfusion is controversial, as this may improve fetal survival without reducing the long-term risks of neurological morbidity

Treatment

• Managed in a fetal medicine centre, with multidisciplinary expertise to manage these cases
• Rapid delivery is usually unwise, unless at term, as fetal brain injury of the surviving twin occurs at the time of demise of the co-twin (immediate delivery only adds prematurity to the possible hypotensive cerebral)
• A conservative mx policy is often appropriate, with serial fetal brain US and a fetal cranial MRI scan 4 weeks after co-twin demise to detect neurological morbidity
• In cases of single intrauterine demise with MRI or US findings of neurological morbidity, late termination of pregnancy would be an option

‘TRAP’ SEQUENCE

• Rarely, MZ twins can be heterokaryotypic.
• When anomalies are identified in the first or early T2  in one of a MC twin pair which may be markers of aneuploidy
• Risks of CVS Vs waiting for a double amniocentesis at 15–16 weeks have to discuss
• When both sacs are sampled à individual karyotype of each twin can be determined

Pathogenesis:

• Complicate 1% of MC pregnancies. Occurring in 1 in 35,000 cases
• Acardiac twin receives blood supply via a large AAA from normal co-twin (‘pump’ twin)
• Poorly oxygenated blood entering the circulation of the affected twin preferentially perfuses the caudal structures rather than the cephalad, resulting in abnormal development of all organ systems. absent or rudimentary development of the upper body structures
• head and the heart are commonly absent, with a preserved central trunk and rudimentary spine.
• Lower limbs may be more preserved due to the improved blood supply.
• Acardiac twins are frequently hydropic due to their abnormal lymphatic and vascular drainage.
• Perinatal mortality of the pump twin is considerable (death usually due to high-output cardiac failure leading to hydrops fetalis or polyhydramnios-induced preterm delivery)

Diagnosis

• Usually follows the detection of a grossly abnormal co-twin within a MC pair.
• The absence of cardiac pulsation in the acardiac twin is usually evident, although rudimentary cardiac tissue or transmitted pulsations may produce appearances of normal cardiac function.
• Paradoxical blood flow may be visualised by colour Doppler to confirm the diagnosis.

Treatment

• Acardiac twin / TRAP sequence do not always require invasive treatment
• Selection for treatment depends on
  • The relative size of the ‘acardiac’ twin to the ‘pump’ twin (the larger the acardiac twin, the greater the risk and need for therapy)
  • The presence of any cardiovascular impairment in the ‘pump’ twin
• If treatment is considered, should take place before 16 weeks of gestation (but evidence is not strong) in fetal medicine centres. Careful monitoring and ultrasound surveillance are required.
• Disruption of the acardiac twin’s cord or intra fetal vessel
  • Cord occlusion techniques
  • Ablation with laser
  • Ablation with diathermy
  • Radiofrequency interstitial thermal ablation (RITA)
•  Survival reported in >70 % of pump twins after treatment.

MCMA PREGNANCIES

Management

• 1-2% of monochorionic gestations (1 in 3000-6000 pregnancies)
• Result of zygotic separation beyond eight days of conception
• Diagnosis – 1^st trimester USS à single placenta and two freely moving fetuses with no inter-twin membrane
• Low TTTS (5%)
• Congenital anomaly (20-25%)
• Associated with the highest perinatal loss rate of all twin forms – around 30-60%.
• Up to 60% of the antenatal fetal deaths occur prior to 32 weeks gestation
• Umbilical cord accidents and prematurity account for much of this loss rate, along with higher rates of congenital anomaly and growth restriction.
• Not preventable and cannot be predicted by CTG
• MCMA twins almost always have umbilical cord entanglement when visualised using colour flow Doppler. Such a finding has not consistently been demonstrated to contribute to overall morbidity and mortality.
• Surveillance & management should always be individualised (in fetal medicine centres)
• However, the majority of monoamniotic pregnancies undergo intensive surveillance with CTG monitoring and serial ultrasound in an attempt to detect impending cord occlusion.
• Management by using sulindac to reduce amniotic fluid volumes (evidence is scanty)
• Sulindac- NSAIDs- can cause steven jones Xn
• Medical amnioreduction with oral prostaglandin synthase inhibitors has been described with 100% survival of forty fetuses (20 pairs – in one study) {Reduce amniotic fluid levels à limit fetal movement à prevent tightening of the tangled cords}
• Risk of a non respiratory neonatal complication was significantly lower than the risk of fetal death after 32+4weeks à deliver MCMA twins at approximately 33 weeks (A retrospective multicentre cohort study of 193 MCMA twin)
• MCMA twins have a high risk of fetal death and should be delivered by CS between 32+0and 34+0weeks after steroid.
• Vaginal delivery is associated with risks of cord prolapse and fetal impaction in the maternal pelvis. usually reserved for the extremely premature or non-viable fetuses.
•  

CONJOINED TWINS

• Very rare (MCMA twin)
• Prevalence is one in 90 000 to 100 000 pregnancies
• The underlying pathogenic mechanism remains uncertain
• Incomplete division of the embryo may result in conjoined twins.
• Classification – largely descriptive and dependent on the anatomical areas joined.
  • Conjoined thorax (thoracopagus)
  • conjoined thorax and abdomen (thoracoomphalopagus) are the commonest subtypes
  • Conjoined pelvis and conjoined head (ischiopagus and craniopagus) being less common.

Diagnosis

• T1 US with detailed assessment of cardiovascular anatomy important for determining prognosis and planning management
• Require careful detailed expert US imaging (usually including MRI) and MDT discussion

Treatment

• Associated with significant mortality and morbidity à significant number of parents will opt for termination.
• Survival depends on the organs joined.
• 50% are stillborn
• Among the survivors up to 75% may have inoperable defects.
• Termination of pregnancy also an option
• Most cases are now prenatally diagnosed and delivered by EL LSCS
• Vaginal deliveries also reported à Risk of dystocia & uterine rupture also reported in undiagnosed cases prenatally

HIGHER ORDER MULTIPLE PREGNANCIES

• MC / DC triplet pregnancies have higher fetal loss rates than TC triplet pregnancies and may be complicated by feto–fetal transfusion syndrome, sGR and TAPS.
• Increased ultrasound surveillance is warranted

	MC TRIPLET	DC TRIPLET	TC TRIPLET
FETAL SURVIVAL	84%		92%
PERINATAL MORTALITY		5.5 fold increased risk

Treatment

	SELECTIVE REDUCTION	CONSERVATIVE MANAGEMENT
MISCARRIAGE (< 24 weeks)	8.1%	4.4%
EARLY PRETERM DELIVERY	10.4%	26.7%

• TTTS à laser ablation
• Selective reduction (intrafetal ablative therapy) should be discussed in all higher order pregnancies including triplets.

Antenatal steroids

• Use of corticosteroids in a targeted way (where preterm delivery is considered likely)
• Prophylactic steroids are not recommended
• Steroids should be offered in MC twin after 36 weeks and in triplet after 35 weeks as part of a planned delivery

Labour and delivery

• Delivery should be conducted in a unit where continuous electronic fetal monitoring is available and there is access to early recourse to CS.
• An experienced operator for expert management of the second twin, in particular with regard to vaginal breech delivery.
• Overall, there is a higher risk of a CS for twin pregnancies

TOD

Uncomplicated twin

• Continuing uncomplicated twin (MC/DC) beyond 38 weeks increases the risk of fetal death
• Additionally, intervention at 37 weeks does not appear to be associated with a significant difference in MOD or maternal complications when compared to expectant management.
• Continuing uncomplicated triplet beyond 36 weeks increases the risk of fetal death.
• MCMA twin – EL birth should be around 32 weeks after ANCS
• MCDA twin – elective birth from 36+0 weeks after ANCS (not associated with an increased risk of serious adverse outcomes)
• DC twin – elective birth from 37+0 weeks
• Triplet – elective birth from 35+0 weeks after a course of ANCS
• If elective birth is declined,
  • Weekly ultrasound assessment of wellbeing
  • Fortnightly fetal growth scans
• Complicated twin
  • TTTS or other complications – TOD must be individualised

MOD

• Twin pregnancy
• MCMA twin – CS
• Others based on the presentation of the first twin
• second twin is at higher risk of adverse perinatal outcomes but this was not reduced by a planned CS
• Current practice supports the policy of planned vaginal birth in uncomplicated pregnancies with a cephalic first twin. (Twin Birth Study  -planned Caesarean section did not reduce the risk of fetal or neonatal death or serious neonatal morbidity when compared with planned vaginal delivery)
• Vaginal delivery is preferred in vertex– vertex presentations. the optimal MOD for the 2^nd twin presenting as non-vertex is unknown
• For the very LBW infant (<1500 g),
• MOD – ??????
• Some advocate caesarean delivery in all cases
• There is little evidence that caesarean section improves perinatal outcome
• Triplets and higher-order multiples
  • May be safely delivered vaginally
  • But obvious difficulties in monitoring
  • So, CS is the more usual MOD

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