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

Abstract

Objective: The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin transfusion syndrome (TTTS).

Study design: This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients.

Results: There was no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11 of 20) vs 55% (11 of 20) (P = 1.0, odds ratio [OR] 1, 95% confidence interval [CI] 0.242 to 4.14) or recipients at 30% (6 of 20) vs 45% (9 of 20) (P = .51, OR 1.88, 95% CI 0.44 to 8.64). There was no difference in 30 day survival of 1 or both twins on a per-pregnancy basis between AR at 75% (15 of 20) and SFLP at 65% (13 of 20) (P = .73, OR 1.62, 95% CI 0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) was not statistically significant for AR at 60% (24 of 40) vs SFLP 45% (18 of 40) (P = .18, OR 2.01, 95% CI 0.76 to 5.44). There was a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14 of 20) vs the AR arm at 35% (7 of 20) (P = .25, OR 5.31, 95% CI 1.19 to 27.6). This was offset by increased recipient neonatal mortality of 30% (6 of 20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality (P = .055, OR 3.025/point) by logistic regression analysis.

Conclusion: The outcome of the trial did not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS.

Figure 1

196 subjects were screened a total of 251 times with 138 subjects not found to be eligible. Of the 58 found to be eligible for the trial, 15 declined randomization. Of the 58 eligible, 43 consented to randomization but 1 withdrew. 21 subjects were randomized to each arm of the study and a single subject dropped out of each arm.

Figure 2

The distribution by stage using the Quintero staging system is equally distributed among stages II, III, and IV in both the amnioreduction (AR) and selective fetoscopic laser photocoagulation (SFLP) groups. There were no stage I patients in the trial. There is no statistically significant difference in stage distribution between amnioreduction (AR) and selective fetoscopic laser photocoagulation (SFLP).

Figure 3

The survival to 30 days of age when broken down by recipient and donor shows no significant difference in survival between AR) or SFLP groups for either recipients or donors.

Figure 4

There is no statistically significant difference in survival of 1 or both twins to 30 days of life.

Figure 5

Despite the differences observed in recipient fetal mortality, there were no statistically significant differences in overall survival to 30 days of age. The reason was that while there were more fetal recipient deaths in the SFLP arm than in the AR arm of the study, more recipients were declared treatment failures in the AR arm (7 of 20), versus the SFLP arm (0 of 20). Neonatal death occurred in 6 of the 7 cases declared treatment failures.

Figure 6

There is a statistically significantly increased fetal mortality in recipients treated by SFLP (70%) versus those treated by AR (35%, p < 0.025, OR=5.31, 95% CI= 1.19 to 27.6)

Figure 7

The difference in fetal recipient survival is more pronounced among recipients in stages III and IV that were treated by AR (63%) versus SFLP (12.5%, p < 0.03). Despite these differences in fetal recipient survival, there is no difference in survival at 30 days because 7/20 recipients in the AR arm met criteria for treatment failure (in which 6 of the 7 were neonatal deaths) while 0/20 in the SFLP arm did so.