Objective
To examine effects of fetoscopic laser occlusion of placental vascular anastomoses on umbilical venous volume flow in twin-to-twin transfusion syndrome.
Study Design
Absolute umbilical venous volume flow, measured preoperatively and 48 hours after fetoscopic laser occlusion was related to Doppler studies, bladder filling in donors, and anastomoses.
Results
Among 45 patients, recipients had decreased ductus venosus pulsatility index (ductus venosus-pulsatility index for veins, 1.16 vs 1.01; P < .001) and unchanged umbilical venous volume flow after fetoscopic laser occlusion (74.7 vs 74.5 mL; P = .407). Donors had decreased umbilical artery pulsatility (1.34 vs 1.11; P = .008), increased ductus venous-pulsatility index for veins (0.75 vs 0.91; P < .014), and significantly increased umbilical venous volume flow per kilogram by 52.3% (136.6 vs 208.0 mL/Kg/min; P < .001). Donor bladder filling occured at higher umbilical venous volume flow per kilogram (142.7 vs 221.4 mL/Kg/min; P < .012). Increase in umbilical venous volume flow per kilogram correlated with the net difference in arteriovenous anastomoses (Pearson r = 0.403, P = .006).
Conclusion
Fetoscopic laser occlusion in twin-to-twin transfusion syndrome corrects intertwin differences in umbilical venous volume flow by predominant effects in the donor. Reappearance of donor bladder filling correlates with correction of volume flow.
Twin-twin transfusion syndrome (TTTS) complicates approximately 10% of monochorionic twin pregnancies but contributes disproportionally to adverse outcome. One of the factors that contribute to these risks is the unbalanced transfer of blood volume across placental vascular anastomoses that can lead to TTTS with fetal manifestation that range from specific signs of volume imbalance to cardiac effects and demise of either twin. On the basis of the Quintero system for prenatal staging, fetoscopic laser occlusion (FLOC) has been demonstrated as an effective treatment in a randomized controlled trial.
The goal of FLOC is the selective occlusion of intertwin anastomoses that are responsible for the imbalance in blood volume between both twins. A corrective effect would therefore be expected to result in measurable changes in the amount of venous blood volume received by either twin. Although effects of FLOC on several peripheral Doppler parameters have been evaluated in multiple publications, there is relatively little information on the impact of FLOC on umbilical venous volume flow (UVF). It was therefore the aim of this study to investigate the immediate effects of FLOC of placental vascular anastomoses for TTTS on the UVF dynamics of both twins.
Patients and Methods
Patients referred for fetoscopic laser occlusion for TTTS were studied prospectively between July 2004 and February 2007. Inclusion criteria were as follows: (1) ultrasound diagnosis of a single monochorionic placenta; (2) diagnosis of TTTS established before 26 weeks’ gestation; (3) polyhydramnios in the recipient twin’s amniotic sac (maximum vertical pool >8 cm) and oligohydramnios in the donor (stuck) twin’s amniotic sac <2 cm; and (4) discordant bladder filling, with a distended bladder in the recipient, and a small or empty bladder in the donor. Exclusion criteria were (1) fetal death, (2) ruptured membranes, (3) leakage of amniotic fluid, and (4) if the patient was in labor. The study protocol was approved by the institutional review board at both participating centers.
All pregnancies underwent detailed ultrasound assessment for fetal anomaly, biometry, echocardiography, and signs of hydrops. Amniotic fluid index, maximum vertical amniotic fluid pocket, and placental location were noted. Umbilical artery (UA) and ductus venosus (DV) Doppler were performed, and UVF was determined from the intraabdominal portion of the umbilical vein to provide a constant point of measurement. The technique was previously described in a study that reported preoperative cardiovascular relationships in 45 TTTS patients also included in this study. To provide quality flow-velocity waveforms with high signal-to-noise ratio, the angle of insonation was kept below 45 degrees. Once the waveforms were obtained, measurements for absolute blood flow velocities from the frozen image were taken with angle correction. For the measurement of the umbilical vein diameter from a maximally magnified image, the calipers were placed on the echogenic border of the opposing vessel walls. Severity staging was based on criteria published by Quintero et al. All patients had complete measurement of all Doppler parameters before surgery and at 48 hours after the procedure. This interval was chosen to allow cardiovascular equilibration.
Several expressions of UVF were determined, including absolute UVF, UVF corrected for the sonographically estimated fetal weight (UVF/Kg), recipient-to-donor UVF ratio (R/D-UVF), and recipient-to-donor difference in weight-corrected UVF (Δ-UVF/Kg). R/D-UVF/Kg eliminates the potential contribution of gestational age. A negative Δ-UVF/Kg indicates net flow toward the donor, whereas positive values indicate net flow toward the recipient. To calculate UVF/kg, estimated fetal weight obtained at the first examination was used for each fetus. R/D-UVF and Δ-UVF/Kg parameters were calculated from recipient to donor for each pair of twins. For each of these UVF parameters the differences pre- and postprocedure were calculated.
FLOC was performed using a technique that was previously described by Quintero et al, where all vessels were followed to their terminal end. Number and type of anastomoses were recorded intraoperatively. Only patients in whom the entire placenta, dividing membrane, and all anastomoses were fully visualized were included in the analysis. There is no mathematical way to estimate the net difference in blood flow by visual inspection of the number and directionality of the anastomoses. To provide a basis for statistical analysis, the overall net difference of arteriovenous (AV) anastomoses was calculated by subtracting the number of donor-to-recipient from recipient-to-donor AV anastomoses.
Statistical analysis
The main outcome of this study was the difference in the UVF/Kg before and after FLOC for pregnancies with 2 survivors. All variables and measurements were tested for normality using the Kolmogorov-Smirnoff test. The appropriate statistical method for comparison of the continuous variables is the 2-way repeated measures analysis of variance (ANOVA). As Doppler measurements and blood flow values were not normally distributed, several techniques to achieve appropriate normalization of data applied. Because these were unsuccessful, pre- and postprocedure parameters were compared using the Wilcoxon signed rank test. Pearson or Spearman-Rho correlation were used to evaluate the relationships between intertwin difference in UVF/Kg pre- and postoperatively and their relationship with peripheral Doppler parameters. To compare paired categorical variables, McNemar’s χ 2 test was used. UVF changes were also related to postoperative bladder filling of the donor. Data were analyzed with the SPSS statistical package 15.0 (SPSS Inc, Chicago, IL). A probability value of < .05 was considered statistically significant.
Results
Fifty-one patients met inclusion criteria and underwent FLOC at a median gestational age of 21.4 weeks (range, 17.3–24.6 weeks). Of these, 45 patients had 2 surviving fetuses 48 hours after FLOC. Among these survivors, 3 (6.7%), 22 (48.8%), 17 (37.8%), and 3 (6.7%) cases presented as Quintero stages 1, 2, 3, and 4, respectively. Perioperative clinical data of the study group are presented in Table 1 .
| Data | Median (min-max) |
|---|---|
| Gestational age at procedure, wk | 21.4 (17.3-24.6) |
| Estimated fetal weight at procedure, g | |
| Recipients | 411 (180-840) |
| Donors | 342 (132-635) |
| Number of Anastomoses | |
| AV-recipient to donor | 4 (0-15) |
| AV-donor to recipient | 6 (2-16) |
| Arterioarterial | 2 (0-4) |
| Venovenous | 2 (0-4) |
| Unknown | 1 (0-2) |
| Deepest amniotic fluid pocket, cm | |
| Recipients, preoperative | 12 (9-21) |
| Recipients, postoperative | 5 (2-9) |
| Donors, preoperative | 0 (0-2) |
| Donors, postoperative | 1 (0-4) |
| Operation time, min | 32 (13-68) |
FLOC resulted in a decrease in the UA pulsatility index (PI) in both twins. Absent or reversed end-diastolic flow in the UA, observed in 1 (2.2%) recipient and 5 (11.1%) donors preoperatively, resolved in all but 3 of the donors. The DV-PI for veins (DV-PIV) decreased in recipients but increased in donors ( Table 2 ). Before FLOC, absent or reversed flow during atrial contraction in the DV was observed in 17 recipients (37.8%) and 2 (4.5%) donors. After surgery this resolved in 7 of 17 recipients (41.2%; P = .034), whereas it was seen in 5 donors (11.1%; P = .434). Hydropic changes (pleural effusion, ascites, or skin edema) appeared in 5 (11.1%) donors after surgery.
| Parameter | Preoperative Median (min-max) | Postoperative Median (min-max) | P |
|---|---|---|---|
| Recipient UA-PI | 1.31 (0.77-2.83) | 1.28 (0.79-1.81) | .035 |
| Donor UA-PI | 1.34 (0.80-2.75) | 1.11 (0.75-2.39) | .008 |
| Recipient DV-PIV | 1.16 (0.49-4.00) | 1.01 (0.47-3.43) | < .001 |
| Donor DV-PIV | 0.75 (0.20-1.86) | 0.91 (0.20-3.46) | .014 |
| Recipient UVF, mL/min | 74.7 (24.9-390.1) | 74.5 (33.8-191.9) | .407 |
| Donor UVF, mL/min | 45.6 (12.3-113.5) | 65.7 (24.9-243.5) | < .001 |
| Recipient UVF/Kg, mL/Kg/min | 171.7 (55.2-565.4) | 170.1 (109.6-356.6) | .509 |
| Donor UVF/Kg, mL/Kg/min | 136.6 (55.9-301.8) | 208.0 (55.3-656.3) | < .001 |
| (Recipient-donor)-UVF/Kg, mL/Kg/min | 28.1 (−103.7-266.7) | −35.9 (−540.4-66.3) | < .001 |
| (Recipient/donor)-UVF | 1.50 (0.4-4.9) | 1.13 (0.2-2.7) | .001 |
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