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

4. Retrospective Cohort Study
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and meta-analysis
Pagani et al., UOG 2013
Methodology
Retrospective Cohort Study
Inclusion Criteria: All TRAP cases identified from
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

5. Systematic Review & Meta-Analysis
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and meta-analysis
Pagani et al., UOG 2013
Methodology
Systematic Review & Meta-Analysis
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)

6. Results Retrospective Cohort
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and meta-analysis
Pagani et al., UOG 2013
Results
Retrospective Cohort
Expectant
management
(n = 6)
Intrafetal laser
treatment
(n = 17)
GA at presentation (weeks)
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
Data presented as n (%) or median.

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

8. Results: Systematic Review
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and meta-analysis
Pagani et al., UOG 2013
Results: Systematic Review
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
O'Donoghue 2008
0.60 (0.26, 0.88)
Weisz 2004
Sepulveda 2004
Soothill 2002
Jolly 2001
Proportion (95% confidence interval)
42/51
14/17
1/1
6/7
5/6
2/2
6/10
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%)

9. Results: Systematic Review
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and meta-analysis
Pagani et al., UOG 2013
Results: Systematic Review
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%)

10. Results: Systematic Review
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and meta-analysis
Pagani et al., UOG 2013
Results: Systematic Review
Neonatal survival
P = 0.19
PTB <37 weeks
P = 0.10
No evidence of significant publication bias

11. Implications for practice
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and meta-analysis
Pagani et al., UOG 2013
Conclusions
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
Implications for practice
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

12. Strengths Limitations
Intrafetal laser treatment for twin reversed arterial perfusion sequence: cohort study and meta-analysis
Pagani et al., UOG 2013
Strengths
Limitations
Large series of cases
Meta-analysis to overcome sample size issues
Stratified analysis performed based on gestational age
No significant heterogeneity between studies
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

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 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?