uog journal club: intrafetal laser treatment for twin reversed arterial perfusion sequence

UOG Journal Club: July 2013Intrafetal 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. ThilaganathanVolume 42, Issue 1, Date: July 2013, pages 6–14

Journal Club slides prepared by Dr. Katherine Goetzinger(UOG Editor for Trainees)

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

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



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



Retrospective Cohort Study

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



Methodology

Expectantmanagement

(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



Results

Data presented as n (%) or median.

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



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 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%)




• 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%)




Bias assessment plot

0.2 0.5 0.8 1.1 1.40.26

0.22

0.18

0.14

0.10

Proportion

Standard error

Bias assessment plot

-0.20 0.05 0.30 0.55 0.80 1.050.25

0.22

0.19

0.16

0.13

Proportion

Standard error

No evidence of significant publication bias

Neonatal survivalP = 0.19

PTB <37 weeksP = 0.10




• 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



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

• 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





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?

uog journal club: intrafetal laser treatment for twin reversed arterial perfusion sequence

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