Background
Endoscopic laser coagulation of placental anastomoses is the first-line treatment for severe twin-to-twin transfusion syndrome. A recent randomized controlled trial reported that laser coagulation along the entire vascular equator was associated with a similar dual survival and survival of at least 1 twin compared with the group that was treated with the selective technique. In addition, there was a significantly lower incidence of postoperative recurrence of twin-to-twin transfusion syndrome and the development of twin anemia-polycythemia sequence in the equatorial group.
Objective
The purpose of this study was to report on neonatal survival in twin-to-twin transfusion syndrome pregnancies that were treated with endoscopic laser therapy with the use of the equatorial technique and to examine the relationship between preoperative factors and twin loss.
Study Design
Endoscopic equatorial laser therapy was carried out as the primary treatment for twin-to-twin transfusion syndrome in all consecutive monochorionic diamniotic twin pregnancies that were referred at a single fetal surgery Center over a 4-year period. All visible placental anastomoses were coagulated; additional laser ablation of the placental tissue between the coagulated vessels was carried out. Pre-laser ultrasound data, periprocedural complications, pregnancy outcome, and postnatal survival at hospital discharge were recorded and analyzed.
Results
A total of 106 pregnancies were treated during the study period. Median gestational age at laser therapy was 19.7 weeks (range, 15.1-27.6 weeks). There was postoperative recurrence of twin-to-twin transfusion syndrome or the development of twin anemia-polycythemia sequence in 2 (1.9%) and 2 (1.9%) cases, respectively. The survival rates of both and at least 1 twin were 56.6% and 83.0%, respectively. Donor survival was significantly lower compared with the recipient co-twin (64.2% vs 75.5%, respectively; P < .05). The rate of fetal death, which was the most common cause of twin loss, was significantly higher in donors compared with recipient fetuses (23.6% vs 10.4%, respectively; P < .05). In cases with absent or reversed end-diastolic velocity in the donor umbilical artery, dual and donor survival rates were significantly lower compared with the remaining twin-to-twin transfusion syndrome pregnancies (40.0% vs 64.8% and 40.0% vs 76.1%, respectively; P < .05). There were no significant differences between the 2 groups in the survival of at least 1 twin and in the recipient survival.
Conclusions
Endoscopic equatorial laser therapy was associated with a survival of both and at least 1 twin of approximately 55% and 83%, respectively, with a low rate of recurrent twin-to-twin transfusion syndrome and twin anemia-polycythemia sequence. In addition, the preoperative finding of abnormal donor umbilical artery Doppler on ultrasound identified a subgroup of twin-to-twin transfusion syndrome pregnancies with a lower dual survival rate caused by increased intrauterine deaths of donor twins.
Endoscopic laser coagulation of placental anastomoses is the first-line treatment for severe twin-to-twin transfusion syndrome (TTTS), which affects 10-15% of monochorionic diamniotic twin pregnancies. Most of the studies that have examined the effects of laser therapy on postnatal survival have used the selective technique, by which only visible anastomoses are coagulated. Additional laser ablation of the placental tissue between the anastomoses along the vascular equator has been proposed to achieve a complete coagulation of all nonvisible vascular connections between the 2 placental territories.
Only few studies have examined pregnancy and neonatal outcomes with the use of equatorial laser therapy for the treatment of TTTS. A recent randomized controlled trial has shown that this approach, also called the “Solomon” technique, was associated with a similar dual survival and survival of at least 1 twin compared with the group treated with the selective technique. In addition, there was a significantly lower incidence of postoperative recurrence of TTTS and development of twin anemia-polycythemia sequence (TAPS) in the equatorial group.
The aim of this study is to report on neonatal survival in TTTS pregnancies that were treated with endoscopic equatorial laser therapy and to examine the relationship between preoperative factors and twin loss.
Methods
Endoscopic equatorial laser therapy was carried out as the primary treatment for TTTS in all consecutive monochorionic diamniotic twin pregnancies that were referred at a single fetal surgery center in Italy over a 4-year period (2011-2014).
In all cases, a detailed ultrasound (RAB 4-8 transducer, Voluson E8; GE Medical Systems, Milwaukee, WI) examination was performed within 48 hours before laser treatment. The minimum required criteria for the diagnosis of TTTS were oligohydramnios in the sac of the donor, defined as a maximum vertical pocket of amniotic fluid of ≤2 cm, and polyhydramnios in the sac of the recipient twin, defined as a maximum vertical pocket of ≥8 cm at <20 weeks gestation and ≥10 cm thereafter. The estimated fetal weight was derived from the appropriate reference ranges for gestation, and the intertwin discordance in estimated fetal weight was calculated as the weight difference divided by the weight of the large twin. Doppler assessments of the umbilical arteries and the ductus venosus of both twins were carried out in all cases.
Endoscopic laser surgery was performed with a semi-rigid 2.0-mm diameter fetoscope (Karl Storz GmbH, Tuttlingen, Germany) through a 3.3-mm diameter cannula (Cook Medical, Bloomington, IN), which was introduced transabdominally into the sac of the recipient twin after the administration of prophylactic antibiotics and local anesthesia. A 400-μm diameter diode laser fiber (Dornier Med Tech, Wessling, Germany) with a power output of 20-30 W was used for coagulation of the placental surface. All visible intertwin vascular anastomoses were coagulated with additional laser ablation of the placental tissue between the coagulated vessels, as previously described. Subsequently, amnioreduction of the polyhydramnios was undertaken through the cannula over a period of 10-15 minutes to obtain subjective normalization of the amniotic fluid volume on ultrasonographic examination. All patients underwent a period of observation in the hospital of approximately 48 hours. Weekly follow-up evaluation was undertaken at our Centre for the first 4 weeks postoperatively and at the referring hospitals thereafter.
Maternal demographic characteristics, ultrasound findings, and details of intrauterine intervention were recorded in a database. Pregnancy outcome and neonatal survival at hospital discharge were collected when they became available from the referring hospitals or from the patients.
The study did not require formal ethical approval because data collection did not alter clinical management or standard of care; information on postnatal outcome routinely is recorded for each case that undergoes intrauterine treatment at our Centre. Informed consent for the use of confidential information according to the Hospital privacy policy was obtained for each patient.
Statistical analysis
Comparisons in the examined parameters between different groups were performed with the use of the chi-square test or Fisher’s exact test for categoric variables and the Mann-Whitney U test for continuous variables. The tests were considered significant at a probability value of <.05 with the use of 2-tailed tests.
Logistic regression analysis was used to determine the variables that provided a significant contribution in the prediction of postnatal twin survival. Univariate analysis was carried out to examine the individual variables that contributed to survival by assessment of their odds ratios and 95% confidence intervals. Subsequently, multivariate logistic regression analysis with backward stepwise elimination was performed to determine which of these variables provide a significant independent contribution in the logistic model.
The data were analyzed with the statistical software package IBM SPSS (version 19.0; (IBM Corporation, Armonk, NY) and Excel for Windows 2010 (Microsoft Corporation, Redmond, WA).
Results
Endoscopic equatorial laser therapy was carried out at our Centre in 106 cases of TTTS during the study period. Table 1 shows the main obstetric and fetal characteristics of the study population. Complications within 14 days after surgery included preterm premature rupture of membranes in 4 cases (3.8%), preterm labor in 5 cases (4.7%), and maternal bleeding in 3 cases (2.8%). In 1 patient (0.9%), bleeding at the site of trocar entry required maternal blood transfusion, with no further complications. In 2 cases (1.9%), there was recurrence of TTTS that was treated with repeat laser therapy. In additional 2 (1.9%) pregnancies, there was the development of TAPS that was treated with fetal blood transfusion of the anemic twin.
Characteristics | Measure |
---|---|
Obstetric | |
Median gestational age at laser therapy, wk (range) | 19.7 (15.1–27.6) |
Median cervical length, mm (range) | 34.5 (12–45) |
Placenta location, n (%) | |
Anterior | 51 (48.1) |
Posterior | 55 (51.9) |
Fetal | |
Median estimated fetal weight, g (range) | |
Donor | 232 (112–992) |
Recipient | 316 (145–1176) |
Estimated fetal weight discordance ≥25%, n (%) | 45 (42.5) |
Donor smaller than recipient, n (%) | 105 (99.1) |
Umbilical artery absent or reversed end-diastolic velocity, n (%) | |
Donor | 35 (33.0) |
Recipient | 2 (1.9) |
Ductus venosus absent or reversed a-wave, n (%) | |
Donor | 9 (8.5) |
Recipient | 20 (18.9) |
Quintero stage, n (%) | |
I | 27 (25.5) |
II | 27 (25.5) |
III | 51 (48.1) |
IV | 1 (0.9) |
Details on pregnancy outcome and neonatal survival are shown in Table 2 . The survival rates of both and at least 1 twin at neonatal hospital discharge were 56.6% and 83.0%, respectively. Donor survival was significantly lower compared with the recipient co-twin (64.2% vs 75.5%, respectively; P < .05). The prevalence of fetal death, which was the most common cause of twin loss, was significantly higher in donor fetuses compared with recipient fetuses (23.6% vs 10.4%, respectively; P < .05).
Variable | Measure |
---|---|
Pregnancy outcome | |
Median gestational age at delivery, wk (range) | 30.6 (16.3–40.3) |
Delivery, n (%) | |
<24 Wk | 16 (15.1) |
24-28 Wk | 17 (16.0) |
29-32 Wk | 40 (37.8) |
>32 Wk | 33 (31.1) |
Neonatal outcome | |
Dual survival, n (%) | 60 (56.6) |
At least 1 survivor, n (%) | 88 (83.0) |
Individual twin survival, n (%) | |
Donor | 68 (64.2) |
Recipient | 80 (75.5) a |
Median birthweight of live births, g (range) | |
Donor | 1399 (490–2460) |
Recipient | 1600 (530–3320) a |
Causes of twin loss | |
Intrauterine death, n (%) | |
Donor | 25 (23.6) |
Recipient | 11 (10.4) a |
Premature rupture of membranes at <24 wk–miscarriage, n (%) | 9 (8.5) |
Selective fetocide, n (%) | 5 (4.7) |
Neonatal death, n (%) | 4 (3.8) |
Preoperative findings in survivors, compared with cases with fetal or neonatal death, are shown in Table 3 . In donor fetuses who died, there was a significantly higher prevalence of estimated fetal weight discordance with the co-twin ≥25% and abnormal umbilical artery Doppler findings. No difference in the examined parameters was observed in recipient twins according to postnatal survival.
Variable | Donor fetus | Recipient fetus | ||||
---|---|---|---|---|---|---|
Alive (n = 68) | Dead (n = 38) | P value | Alive (n = 80) | Dead (n = 26) | P value | |
Obstetric factors | ||||||
Gestational age at laser therapy, wk (range) | 20.2 (16.3–27.6) | 18.9 (15.1–26.3) | .140 | 19.4 (15.0–26.9) | 20.1 (15.7–27.6) | .665 |
Cervical length, mm (range) | 35.0 (18–45) | 33.0 (12–41) | .263 | 35.0 (12–45) | 33.0 (16–40) | .268 |
Anterior placenta, n (%) | 34 (50.0) | 21 (55.3) | .687 | 45 (56.3) | 10 (38.5) | .175 |
Fetal factors, n (%) | ||||||
Estimated fetal weight discordance ≥25% | 23 (33.8) | 22 (57.9) | .024 | 31 (38.8) | 14 (53.8) | .253 |
Donor umbilical artery absent or reversed end-diastolic velocity | 14 (20.6) | 21 (55.3) | < .01 | 25 (31.3) | 10 (38.5) | .632 |
Donor ductus venosus absent or reversed a-wave | 3 (4.4) | 6 (15.8) | .067 | 5 (6.3) | 4 (15.4) | .218 |
Donor visible bladder | 31 (45.6) | 16 (42.1) | .839 | 43 (53.8) | 16 (61.5) | .507 |
Recipient umbilical artery absent or reversed end-diastolic velocity | 1 (1.5) | 1 (2.6) | 1 | 1 (1.3) | 1 (3.8) | .432 |
Recipient ductus venosus absent or reversed a-wave | 12 (17.6) | 8 (21.1) | .796 | 12 (15.0) | 8 (30.8) | .088 |
Donor survival was significantly lower in Quintero stage III cases compared with stage I and II (47.1% vs 85.2% and 47.1% vs 74.1%, respectively; P < .05), with no difference between stage I and II pregnancies ( P = .501). No significant difference in recipient survival was observed according to Quintero stages.
Logistic regression analysis demonstrated that significant predictors of donor survival were estimated fetal weight discordance ≥25% and absent or reversed end-diastolic velocity in the umbilical artery. In the multivariate analysis, the only independent contribution to donor survival was provided by abnormal umbilical artery Doppler examination ( Table 4 ).
Variable | Univariate analysis | Multivariate analysis | ||||
---|---|---|---|---|---|---|
Odds ratio | 95% Confidence interval | P value | Odds ratio | 95% Confidence interval | P value | |
Gestational age at laser therapy, wk | 1.151 | 0.994–1.334 | .061 | — | — | — |
Cervical length, mm | 1.033 | 0.963–1.108 | .369 | — | — | — |
Anterior placenta | 0.810 | 0.365–1.796 | .603 | — | — | — |
Estimated fetal weight discordance ≥25% | 0.372 | 0.164–0.841 | 0.018 | — | — | — |
Visible bladder | 0.868 | 0.389–1.935 | .729 | — | — | — |
Donor umbilical artery absent or reversed end-diastolic velocity | 0.210 | 0.088–0.500 | < .001 | 0.249 | 0.101–0.610 | .002 |
Donor ductus venosus absent or reversed a-wave | 0.246 | 0.058–1.048 | .058 | — | — | — |