Elsevier

Clinics in Perinatology

Volume 47, Issue 4, December 2020, Pages 719-731
Clinics in Perinatology

Neurologic Outcomes After Prenatal Treatment of Twin-Twin Transfusion Syndrome

https://doi.org/10.1016/j.clp.2020.08.002Get rights and content

Section snippets

Key points

  • Fetoscopic laser surgery seems to have perinatal survival and neurologic morbidity benefits when compared with amnioreduction for the treatment of early onset, advanced-stage twin-twin transfusion syndrome (TTTS).

  • Earlier gestational age at birth, low birthweight, and higher stage of twin-twin transfusion at diagnosis may be associated with poorer neurologic outcomes after laser therapy.

  • Although neuroimaging can increase antenatal detection of those pediatric survivors at risk for subsequent

Twin-twin transfusion syndrome

TTTS is caused by pathologic intertwin anastomoses allowing for unbalanced shunting of blood and vasoactive mediators between twins. It occurs most commonly in MCDA gestations, although all monochorionic multiple gestations are at risk.7, 8, 9 Ultrasound is the mainstay of TTTS diagnosis and evaluation, with a sonographic diagnosis requiring the identification of oligohydramnios in the donor twin and polyhydramnios in the recipient twin. A staging system exists for disease severity that

Amnioreduction for twin-twin transfusion syndrome treatment

Amnioreduction involves ultrasound-guided drainage of excess amniotic fluid from the recipient twin’s amniotic sac for therapeutic benefit. Before the development of fetoscopic laser surgery, amnioreduction represented first-line treatment of TTTS. The goal of amnioreduction is to reduce uterine distention and thereby lower the risk of preterm labor and PPROM. It can also reduce maternal discomfort. It has additionally been theorized to increase donor twin placental perfusion, although this

Fetoscopic laser surgery for twin-twin transfusion syndrome treatment

Laser therapy was first described by De Lia and colleagues13 in 1990 and involved introduction of a fetoscope with laser fiber into the recipient sac after maternal laparotomy to visualize and photocoagulate placental surface vessels. It has since evolved into a percutaneous fetoscopic technique involving a selective approach for preferentially targeting intertwin anastomoses. Following early single-center experiences suggesting benefit to laser as a treatment of TTTS, the Eurofetus randomized

Neurologic outcomes after amnioreduction for twin-twin transfusion syndrome

Neurologic impairment is a key pediatric outcome measure among survivors, and for some parents it can be more important than overall survival. Compared with singleton pregnancies, unselected twin gestations are at higher risk of neurologic morbidity. Scher and colleagues16,17 reported on 25,772 twin births in 5 populations in the United States and Australia and found that twins had a 4-fold increase in risk when compared with singletons. Undoubtedly, a significant proportion of this difference

Neurologic outcomes after laser surgery for twin-twin transfusion syndrome

There is a range of neurologic outcomes reported in the literature among survivors of laser surgery for TTTS (Table 1). A review of more than 1300 pregnancies examined neurodevelopmental outcomes after laser surgery at a median pediatric age of 21 to 26 months and found rates of minor impairment of 7% to 11% and severe impairment (defined as the presence of at least one of the following: CP, severe motor skills delay or cognitive developmental delay, bilateral blindness, or deafness) that

Neurologic morbidity compared between donor and recipient twins

In TTTS, donor and recipient twins are each at risk, but face different hemodynamic challenges. Given the different pathophysiological conditions that each twin faces, it is hypothesized that donor twins are at risk for ischemic injuries due to cerebral malperfusion, whereas the recipient twins are at risk for ischemia due to polycythemia-associated vascular sludging as well as hemorrhagic events due to hypertensive, hypervolemic overload.26 The literature seems to indicate that donors and

Neurologic morbidity based on Quintero stage at diagnosis

Initial TTTS stating has been shown to be a predictor of outcomes after laser therapy. Advancing Quintero staging and worsening outcomes have been found to be positively correlated not only for immediate outcomes such as perinatal mortality and morbidity but also for long-term neuromorbidity. In the Eurofetus trial, the investigators found that in fetuses undergoing laser and amnioreduction for TTTS, advancing Quintero stage was associated with lower rates of single survival.28 The same has

Neurologic morbidity after single twin demise

Stage V TTTS can occur after expectant management or attempts at therapy. In a systematic review that included 160 monochorionic twin pregnancies, Ong and colleagues31 found that death of one twin was associated with increased risk of preterm delivery, with 68% delivering preterm, and neurologic abnormality at 4 weeks of life, which was observed in 18% of survivors. But even with PTB notwithstanding, whenever a single monochorionic twin fetal demise occurs there is potential for surviving

Neurologic morbidity of pregnancies with persistent anastomosis after laser

The aim of fetoscopic laser surgery is to functionally separate, or “dichorionize,” monochorionic twin fetal circulations, ideally eliminating all intertwin residual anastomoses. In reality, complete photocoagulation of all intertwin anastomoses is often not achieved. Investigators have hypothesized that residual patent anastomosis may actually play more of a role in neurologic outcomes by precipitating recurrent TTTS, acute intertwin exsanguination, and twin anemia polycythemia sequence (TAPS).

Neuroimaging after Selective Laser Photocoagulation

Because of the angioarchitecture of the shared placenta and sudden hemodynamic shifts in TTTS, twins are at risk of cerebral ischemia, infarction, and possible reperfusion injury. In TTTS, antenatal detection of these lesions is possible even before any intervention.40 Several types of cerebral lesions have been described: cystic periventricular leukomalacia, IVH, posthemorrhagic ventricular dilation, cerebral atrophy, and ischemic stroke.41 Cerebral lesions can be detected on ultrasound or

Summary

Pediatric neurologic outcomes overall seem superior after fetoscopic laser photocoagulation when compared with amnioreduction or expectant management for the management of TTTS. Major neurologic morbidity rates after laser surgery have been reported in several series, with results ranging from as low as 4% to as high as 18%, with most of the reviews revealing rates less than 10%. Earlier gestational age at birth, low birthweight, and higher stage of twin-twin transfusion at diagnosis may be

Clinics Care Points

  • Although there is currently clinical equipoise regarding the optimal management of stage I disease, it is widely accepted that intervention is recommended for stage II to IV TTTS due to a substantial risk of perinatal morbidity and mortality with untreated early onset advanced-stage TTTS.

  • Fetoscopic laser therapy is considered superior treatment to amnioreduction as it has been associated with improved survival and lower rates of neurological morbidity; as the procedure has aged, overall

Disclosure

R.S. Miller disclosed receiving honorarium for writing a article on TRAP sequence for UpToDate. D. Sutton has no disclosures.

First page preview

First page preview
Click to open first page preview

References (58)

  • B.R. Vohr et al.

    Are outcomes of extremely preterm infants improving? Impact of Bayley assessment on outcomes

    J Pediatr

    (2012)
  • V. Miller

    Neonatal cerebral infarction

    Semin Pediatr Neurol

    (2000)
  • F. Slaghekke et al.

    Fetoscopic laser coagulation of the vascular equator versus selective coagulation for twin-to-twin transfusion syndrome: an open-label randomised controlled trial

    Lancet

    (2014)
  • R. Bejar et al.

    Antenatal origin of neurologic damage in newborn infants. II. Multiple gestations

    Am J Obstet Gynecol

    (1990)
  • A.R. Hart et al.

    Accuracy of in-utero MRI to detect fetal brain abnormalities and prognosticate developmental outcome: postnatal follow-up of the MERIDIAN cohort

    Lancet Child Adolesc Health

    (2020)
  • M. Mailath-Pokorny et al.

    Magnetic resonance methods in fetal neurology

    Semin Fetal Neonatal Med

    (2012)
  • A.G. Sutcliffe et al.

    Outcome for children born after in utero laser ablation therapy for severe twin-to-twin transfusion syndrome

    BJOG

    (2001)
  • C.S. Banek et al.

    Long-term neurodevelopmental outcome after intrauterine laser treatment for severe twin-twin transfusion syndrome

    Am J Obstet Gynecol

    (2003)
  • J. McIntosh et al.

    Long term developmental outcomes of pre-school age children following laser surgery for twin-to-twin transfusion syndrome

    Early Hum Dev

    (2014)
  • B.E. Hamilton et al.

    Births: final data for 2014

    Natl Vital Stat Rep

    (2015)
  • Y.M. Lee et al.

    Twin chorionicity and the risk of stillbirth

    Obstet Gynecol

    (2008)
  • D. Roberts et al.

    Interventions for the treatment of twin-twin transfusion syndrome

    Cochrane Database Syst Rev

    (2014)
  • Society for Maternal-Fetal Medicine et al.

    Twin-twin transfusion syndrome

    Am J Obstet Gynecol

    (2013)
  • R.A. Quintero et al.

    Staging of twin-twin transfusion syndrome

    J Perinatol

    (1999)
  • J.E. De Lia et al.

    Fetoscopic neodymium:YAG laser occlusion of placental vessels in severe twin-twin transfusion syndrome

    Obstet Gynecol

    (1990)
  • T.M. Crombleholme et al.

    A prospective, randomized, multicenter trial of amnioreduction vs selective fetoscopic laser photocoagulation for the treatment of severe twin-twin transfusion syndrome

    Am J Obstet Gynecol

    (2007)
  • J. Akkermans et al.

    Twenty-five years of fetoscopic laser coagulation in twin-twin transfusion syndrome: a systematic review

    Fetal Diagn Ther

    (2015)
  • A.I. Scher et al.

    The risk of mortality or cerebral palsy in twins: a collaborative population-based study

    Pediatr Res

    (2002)
  • X. Li et al.

    Prognosis and long-term neurodevelopmental outcome in conservatively treated twin-to-twin transfusion syndrome

    BMC Pregnancy Childbirth

    (2011)
  • Cited by (0)

    Funding source: R.S. Miller disclosed receiving honorarium for writing a article on TRAP sequence for UpToDate. D. Sutton has no disclosures.

    View full text