Twin-to-twin transfusion syndrome (TTTS)

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Twin-to-twin transfusion syndrome (TTTS)

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• gt 20 discordance in birthweight, and gt 5 g/dL
  discordance in cord haemoglobin levels
  insufficient
• ultrasound-based criteria, with particular
  attention to amniotic fluid discordance, bladder
  volumes, and fetal Doppler studies.

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Pathophysiology1. Placental architecture

• Almost all monochorionic twins have intertwin
  vascular anastomoses.
• Arterio-arterial (AA) anastomoses and veno-venous
  (VV) anastomoses are superficial anastomoses,
  travelling across the surface of the placenta
  without interruption between the two cord
  insertions.

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• Arterio-venous (AV) anastomoses are deep
  anastomoses, where an unpaired artery and vein
  pierce the chorionic plate in close adjacency to
  supply a shared placental cotyledon. --provide
  unidirectional flow of blood from the donor to
  the recipient.
• TTTS results from intertwin transfusion across
  shared placental vascular anastomoses
• TTTS occurred uncommonly (15) despite the high
  frequency of occurrence of cross-placental
  vascular communication.

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• TTTS is more likely to develop when there is a
  paucity of bi-directional AAs and VV anastomoses
  that can assist with regulation of intertwin
  circulatory imbalances.
• The larger the number and type of intertwin
  anastomoses, the less frequently clinical TTTS is
  observed.
• the antenatal detection of AA anastomoses
  predicts higher perinatal survival in pregnancies
  complicated by TTTS.

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Pathophysiology2. The fetal response

• Transfusion through the unidirectional AV
  anastomoses creates hydrostatic differences
  between the twins.
• Atrial natriuretic peptide (ANP) and vasopressin
  levels in the twins diverge the donor responds
  with oliguria, and the recipient with polyuria
  and polyhydramnios (Quintero stage 1).

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• The resultant haemoconcentration in the recipient
  creates an osmotic gradient from the maternal
  compartment, worsening the polyhydramnios
• As donor perfusion pressure continues to fall
  urine production finally ceases (Quintero stage
  2), resulting in a stuck twin.

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• The resultant inability to swallow aggravates the
  donor twin's hypotension, and vasoconstrictor
  peptides, such as the renin-angiotensin system
  (RAS) mediators, increase dramatically ?increased
  arterial resistance in the donor's placental
  territory? growth restriction.
• Absent or reversed end-diastolic flow (A/REDF) in
  the donor umbilical artery (UA) may be seen
  (Quintero stage 3 donor).

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• These RAS mediators are also transfused to the
  recipient via placental anastomoses( similar cord
  levels of renin and aldosterone despite
  discordant renal expression of renin between
  donors and recipients. )
• Systemic hypertension in the recipient fetus,
  initiated by the increase in cardiac output, now
  worsens.
• endothelin and fetal natriuretic peptides
  higher in recipient twins--these mediators likely
  work synergistically to induce pressure-overload
  cardiomyopathy.

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• Fetal echocardiography in recipient the presence
  of cardiomegaly secondary to biventricular
  hypertrophy, with the majority exhibiting right
  ventricular systolic and biventricular diastolic
  dysfunction.
• Right ventricular outflow tract obstruction may
  evolve (10 of recipient fetuses )
• Venous Dopplers ductus venosus (DV) and
  umbilical vein (UV) may now deteriorate
  (Quintero stage 3 recipient).

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• Continuing fetofetal transfusion in the face of
  such cardiac dysfunction ? progression to fetal
  hydrops (Quintero stage 4).
• Whether by terminal hypoperfusion in the donor,
  or by cardiac failure in the recipient, single
  fetal demise may ensue (Quintero stage 5).
• At or around the time of this death, acute
  fetofetal haemorrhage from the survivor into the
  placental and fetal vascular compartment of the
  dead twin can occur through the patent intertwin
  vascular anastomoses. ? profound hypotension ?
  high risk of death or severe neurological injury
  (approximately 30 for each) in the co-twin.

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Disease staging
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Screening for TTTS1. nuchal translucency

• Discordant crownrump length in the first
  trimester does not identify those pregnancies
  destined to develop TTTS, but increased nuchal
  translucency (NT) and/or NT discordance in
  monochorionic twins is associated with an
  increased risk for subsequent development of
  TTTS.
• Increased NT (gt 95th centile) at 1014 weeks a/w
  a likelihood ratio of 3.5 (95 CI, 1.96.2) for
  the development of severe TTTS. (Sebire et al.
  Hum Reprod 2000 )

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• This transient finding probably reflects impaired
  ventricular function of the immature fetal heart
  in the hypervolaemic recipient twin
• the improvement with advancing gestation is
  likely because of improved ventricular compliance
  and the establishment of diuresis.

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Screening for TTTS2. First trimester ductus
venosus (DV)

• Among twin with discordant NT, discordant
  reversal of the a wave in the DV was useful in
  identifying those twins that went on to develop
  TTTS. (Matias et al. J Matern Fetal Med 2005 )

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Screening for TTTS3. Intertwin membrane folding

• an early ultrasound marker of amniotic fluid
  discordance
• the likelihood ratio of membrane folding on
  ultrasound at between 15 and 17 weeks gestation
  for the subsequent development of TTTS was 4.2
  (95 CI 3.06.0). (Sebire et al. Hum Reprod 2000
  )

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Surveillance for TTTS

• BIW after NT assessment for monochorionic twins
• amniotic fluid discordance, intertwin membrane
  folding, bladder volumes, and Doppler studies.

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Diagnosis and assessment of TTTS

• Minimum sonographic criteria
• (i) monochorionic twins, that is, single
  placenta, same sex twins, and absence of
  intervening chorion (twin peak sign)
• (ii) oligohydramnios (maximal vertical pocket
  (MVP)  2 cm) in the donor sac and
• (iii) polyhydramnios (MVP  8 cm) in the
  recipient sac.

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Differential diagnoses

• selective intrauterine growth restriction (IUGR),
  which also affects 15 of monochorionic twins,
  and may result in oligohydramnios, delayed growth
  and abnormal umbilical Dopplers in one twin.
• monochorionic twins discordant for anomaly
  (particularly renal agenesis) may result in
  anhydramnios around one twin.
• -- neither of these conditions is associated with
  polyhydramnios in the other twin

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Treatment options

• untreated perinatal mortality for severe
  midtrimester TTTS is up to 90.
• Selective laser photocoagulation (SLPC) of
  intertwin vascular anastomoses
• Amnioreduction and septostomy
• cord occlusion in TTTS

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TTTS in monochorionic monoamniotic (MCMA)

• much less common ?nearly all MCMA placentas have
  AA anastomoses, and a decreased number of AV
  anastomoses, when compared to MCDA placentas.
• may still occur --will lack the classic sign of
  discordant sac size.
• --The combination of polyhydramnios in the single
  amniotic cavity with discordant bladder size is
  usually sufficient to make the diagnosis,
  particularly where there are discordant cord
  diameters and abnormal Doppler waveforms.
• -- Stage 1 disease, however, may escape
  detection.

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TTTS in Dichorionic diamnion? Dizygotic twins?
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1. monochorionic dizygotic twins seems increase
after pregnancy by ART(?)

• Monochorionic (MC) dizygotic twins (DZT) are
  extremely rare in natural pregnancy
• Unusual monochorionic placentation with
  heterosexual twins. ( ObstetGynecol
  197036621-5. )
• sex-discordant monochorionic twins conceived by
  in vitro fertilization (The New England Journal
  of Medicine. 2003. 349(2) 154-159 )
• DZ monochorionic twins conceived by ART, of which
  one has both Klinefelter syndrome and
  Beckwith-Wiedemann syndrome (BWS). (Journal of
  Pediatrics.2005, 146(4)565-567)

--J Hum Genet. 200550(1)1-6.
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2. Twins with two separate placental masses can
still be monochorionic and therefore have
vascular anastomoses
pathogenesis of bipartite placentation in MC
twinning not clear
American Journal of Obstetrics and Gynecology 2006
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True DADC?

• The combination of the lambda sign or 2 separate
  placentas on sono in twin pregnancies predicts
  dichorionicity with a sensitivity of 97 and a
  specificity of 100 T sign -- the most useful
  sign in predicting monochorionicity with a
  sensitivity of 100 and a specificity of 98. (
  GA 10-14 wks)
• 2 separate placental masses are not per se DC
• Microscopic examination of the intertwin membrane
  after delivery -- the gold standard for
  chorionicity

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If true DADC

• Anastomotic communication was found almost
  universally in monochorionic placentation and
  very rarely with dichorionic placentas.
  (Placental injection studies in twin gestation.
  Robertson EG. Am J Obstet Gynecol 1983 147(2)
  170-174 )
• Vascular Anastomoses in Dichorionic
  Diamniotic-Fused Placentasside-to-side
  connections between small subchorionic vessels.
  (International Journal of Gynecological
  Pathology. 22(4)359-361, October 2003 )

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Non-immune hydrops fetalis

1. Cardiac failure
2. Anemia
3. Arteriovenous shunts
4. Mediastinal compression
5. Metabolic disorder
6. Fetal infection/tumor
7. Congenital renal/pulmonary/GI/skeletal defect
8. Chromosomal anomalies