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UOG Journal Club: Intrafetal laser treatment for twin reversed arterial perfusion sequence

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  • Both expectant management and IFL treatment group were effectively exactly the same (ie both recieved nil treatment) until 18 weeks. Yet all in EM group (n=6) died before 18 weeks and all IFL group (n=17) survived!!! eventhough neither received any treament!!
    In effect you could say that 6/23 (26%) died by 18 weeks without treatment, not the 100% as described in the paper!!
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  • 1. UOG Journal Club: July 2013Intrafetal laser treatment for twin reversed arterial perfusion sequence:cohort study and meta-analysisG. Pagani, F. D’Antonio, A. Khalil, A. Papageorghiou, A. Bhide and B. ThilaganathanVolume 42, Issue 1, Date: July 2013, pages 6–14Journal Club slides prepared byDr. Katherine Goetzinger(UOG Editor for Trainees)
  • 2. Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013• Twin reversed arterial perfusion (TRAP) sequence is a uniquecomplication of monochorionic twins• TRAP sequence is characterized by retrograde perfusion of anacardiac mass by a normal (pump) twin through placentalarterioarterial anastomoses• TRAP sequence results in a hyperdynamic circulation and highoutput cardiac failure of the pump twin• The goal of antenatal management has been to prevent demise ofthe pump twin by intrauterine therapy when cardiac strain of thepump twin or increased growth of the acardiac twin occurs
  • 3. 1. To ascertain the outcome of TRAP cases managed eitherexpectantly or with intrafetal laser therapy in a single center2. To systematically review the literature to assess outcomes ofTRAP cases treated with intrafetal laser therapyObjectivesIntrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013
  • 4. Inclusion Criteria: All TRAP cases identified from 2000-2012Exposure: Expectant management vs fetal laser when indicated• Fetal laser indicated by rapid growth of the TRAP mass, development of ahyperdynamic circulation, or cardiac strain in the pump twinOutcomes: Fetal loss, gestational age at demise, GA at live birth, birth weight,gestational age interval from treatment to deliveryMethodologyIntrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013Retrospective Cohort Study
  • 5. Inclusion Criteria: Studies reporting the outcome of TRAP cases treated by lasertherapyOutcomes: Overall survival and preterm birthAnalysis:•Forest plots: fixed and random effects models•Between-study heterogeneity: Higgin’s I2•Publication bias: Funnel plots and Begg and Mazumdar’s rank correlation test•Cases stratified by gestational age at therapy (<16 vs ≥16 weeks)Systematic Review & Meta-AnalysisIntrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013Methodology
  • 6. Expectantmanagement(n = 6)Intrafetal lasertreatment(n = 17)GA at presentation (weeks) 13 + 3 13 + 3GA at treatment (weeks) --- 18 + 4Fetal loss 6 (100%) 3 (18%)GA at demise (weeks) 14 + 4 22 + 1Fetal survival 0 (0%) 14 (82%)GA at live birth (weeks) --- 37 + 1Birth weight (g) --- 2530 gRetrospective CohortIntrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013ResultsData presented as n (%) or median.
  • 7. Potentially appropriate studies identified from search(n = 81)Citations retrieved for detailed evaluation ofmanuscript(n = 23)Studies included in systematic review(n = 10)Citations excluded based ontitle or abstract(n = 58)Studies excluded(n = 13)These 10 studies included 34 pregnancies complicated by TRAP sequence whichwere treated by intrafetal laserIntrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013Results: Systematic Review
  • 8. 0.0 0.2 0.4 0.6 0.8 1.0Combined 0.80 (0.69, 0.89)This study 0.82 (0.57, 0.96)Wegrzyn 2012 1.00 (0.03, 1.00)Scheier 2011 0.86 (0.42, 1.00)Lewi 2010 0.83 (0.36, 1.00)Sepulveda 2009 1.00 (0.16, 1.00)Cavoretto 2009 1.00 (0.03, 1.00)ODonoghue 2008 0.60 (0.26, 0.88)Weisz 2004 1.00 (0.16, 1.00)Sepulveda 2004 1.00 (0.03, 1.00)Soothill 2002 1.00 (0.16, 1.00)Jolly 2001 1.00 (0.16, 1.00)Proportion (95% confidence interval)42/5114/171/16/75/62/21/16/102/21/12/22/2I2 = 0% (95% CI = 0% to51.2%)Study n/NThe overall neonatalsurvival after intrafetallaser treatment was80% (95% CI, 69–89%)There was nosignificantheterogeneity betweenstudies(I2= 0%)Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013Results: Systematic Review
  • 9. • The overall risk of PTB <37 weeks was 40% (95% CI, 27– 59%) withno evidence of statistically significant heterogeneity (I2= 24.8%)• The overall risk of PTB <32 weeks was 7% (95% CI, 4–21%)• Adverse pregnancy outcome (fetal demise and PTB <37 weeks)was significantly lower (p=0.0025) when treatment occurred <16weeks (19%) compared ≥16 weeks (66%)Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013Results: Systematic Review
  • 10. Bias assessment plot0.2 0.5 0.8 1.1 1.40.260.220.180.140.10ProportionStandard errorBias assessment plot-0.20 0.05 0.30 0.55 0.80 1.050.250.220.190.160.13ProportionStandard errorNo evidence of significant publication biasNeonatal survivalP = 0.19PTB <37 weeksP = 0.10Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013Results: Systematic Review
  • 11. • Expectant management of TRAP sequence has a high fetal loss rate• Serial ultrasound and Doppler monitoring is ineffective at identifying TRAPcases at high risk of fetal demise• Early intervention with intrafetal laser treatment may improve pregnancyoutcomes in cases of TRAP, especially if performed prior to 16 weeksIntrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013Conclusions• Routine intrafetal laser therapy prior to 16 weeks’ gestation should beconsidered in pregnancies affected by TRAP sequence in order to reduceassociated adverse pregnancy outcomesImplications for practice
  • 12. • Large series of cases• Meta-analysis to overcome samplesize issues• Stratified analysis performed basedon gestational age• No significant heterogeneitybetween studiesStrengths• No randomized comparison group• Use of composite outcome instratified analysis• Potential for publication bias• Variable quality of studies includedwith none reporting efforts to reducebias• Range of laser technique andexperience between studies is likelyLimitationsIntrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013
  • 13. Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study andmeta-analysisPagani et al., UOG 2013Discussion points• What is the optimal surveillance strategy in pregnancies diagnosed with TRAPsequence?• Should elective intrafetal therapy routinely be performed in all cases of TRAPsequence regardless of ultrasound findings?• If so, what is the optimal gestational age for treatment?• Would restricting the window of intrafetal laser treatment to 13-16 weeks’gestation increase the risk of chorion-amnion separation?• What is the optimal surveillance strategy post-procedure?• Should care for TRAP pregnancies be centralized?• What is the long-term neurologic outcome for the surviving co-twin followingintrafetal therapy for TRAP?