1. UOG Journal Club: July 2013
Intrafetal laser treatment for twin reversed arterial perfusion sequence:
cohort study and meta-analysis
G. Pagani, F. D’Antonio, A. Khalil, A. Papageorghiou, A. Bhide and B. Thilaganathan
Volume 42, Issue 1, Date: July 2013, pages 6–14
Journal Club slides prepared by
Dr. Katherine Goetzinger
(UOG Editor for Trainees)

2. Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
• Twin reversed arterial perfusion (TRAP) sequence is a unique
complication of monochorionic twins
• TRAP sequence is characterized by retrograde perfusion of an
acardiac mass by a normal (pump) twin through placental
arterioarterial anastomoses
• TRAP sequence results in a hyperdynamic circulation and high
output cardiac failure of the pump twin
• The goal of antenatal management has been to prevent demise of
the pump twin by intrauterine therapy when cardiac strain of the
pump twin or increased growth of the acardiac twin occurs

3. 1. To ascertain the outcome of TRAP cases managed either
expectantly or with intrafetal laser therapy in a single center
2. To systematically review the literature to assess outcomes of
TRAP cases treated with intrafetal laser therapy
Objectives
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013

4. Inclusion Criteria: All TRAP cases identified from 2000-2012
Exposure: Expectant management vs fetal laser when indicated
• Fetal laser indicated by rapid growth of the TRAP mass, development of a
hyperdynamic circulation, or cardiac strain in the pump twin
Outcomes: Fetal loss, gestational age at demise, GA at live birth, birth weight,
gestational age interval from treatment to delivery
Methodology
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
Retrospective Cohort Study

5. Inclusion Criteria: Studies reporting the outcome of TRAP cases treated by laser
therapy
Outcomes: Overall survival and preterm birth
Analysis:
•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-Analysis
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
Methodology

6. Expectant
management
(n = 6)
Intrafetal laser
treatment
(n = 17)
GA at presentation (weeks) 13 + 3 13 + 3
GA at treatment (weeks) --- 18 + 4
Fetal loss 6 (100%) 3 (18%)
GA at demise (weeks) 14 + 4 22 + 1
Fetal survival 0 (0%) 14 (82%)
GA at live birth (weeks) --- 37 + 1
Birth weight (g) --- 2530 g
Retrospective Cohort
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
Results
Data presented as n (%) or median.

7. Potentially appropriate studies identified from search
(n = 81)
Citations retrieved for detailed evaluation of
manuscript
(n = 23)
Studies included in systematic review
(n = 10)
Citations excluded based on
title or abstract
(n = 58)
Studies excluded
(n = 13)
These 10 studies included 34 pregnancies complicated by TRAP sequence which
were treated by intrafetal laser
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
Results: Systematic Review

8. 0.0 0.2 0.4 0.6 0.8 1.0
Combined 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)
O'Donoghue 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)
42/51
14/17
1/1
6/7
5/6
2/2
1/1
6/10
2/2
1/1
2/2
2/2
I2 = 0% (95% CI = 0% to
51.2%)
Study n/N
The overall neonatal
survival after intrafetal
laser treatment was
80% (95% CI, 69–89%)
There was no
significant
heterogeneity between
studies
(I2
= 0%)
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
Results: Systematic Review

9. • The overall risk of PTB <37 weeks was 40% (95% CI, 27– 59%) with
no 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 <16
weeks (19%) compared ≥16 weeks (66%)
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
Results: Systematic Review

10. Bias assessment plot
0.2 0.5 0.8 1.1 1.4
0.26
0.22
0.18
0.14
0.10
Proportion
Standard error
Bias assessment plot
-0.20 0.05 0.30 0.55 0.80 1.05
0.25
0.22
0.19
0.16
0.13
Proportion
Standard error
No evidence of significant publication bias
Neonatal survival
P = 0.19
PTB <37 weeks
P = 0.10
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
Results: Systematic Review

11. • Expectant management of TRAP sequence has a high fetal loss rate
• Serial ultrasound and Doppler monitoring is ineffective at identifying TRAP
cases at high risk of fetal demise
• Early intervention with intrafetal laser treatment may improve pregnancy
outcomes in cases of TRAP, especially if performed prior to 16 weeks
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
Conclusions
• Routine intrafetal laser therapy prior to 16 weeks’ gestation should be
considered in pregnancies affected by TRAP sequence in order to reduce
associated adverse pregnancy outcomes
Implications for practice

12. • Large series of cases
• Meta-analysis to overcome sample
size issues
• Stratified analysis performed based
on gestational age
• No significant heterogeneity
between studies
Strengths
• No randomized comparison group
• Use of composite outcome in
stratified analysis
• Potential for publication bias
• Variable quality of studies included
with none reporting efforts to reduce
bias
• Range of laser technique and
experience between studies is likely
Limitations
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013

13. Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and
meta-analysis
Pagani et al., UOG 2013
Discussion points
• What is the optimal surveillance strategy in pregnancies diagnosed with TRAP
sequence?
• Should elective intrafetal therapy routinely be performed in all cases of TRAP
sequence 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 following
intrafetal therapy for TRAP?