Objective
To evaluate pre- and postoperative predictors of preterm birth in twin-to-twin transfusion syndrome treated with fetoscopic placental laser coagulation.
Study Design
Prospective cohort study (n = 166) assessing cervical length (pre and postoperatively), amniotic fluid interleukin-6, serum C-reactive protein and duration of surgery. Logistic regression was used to investigate associations with preterm delivery.
Results
Preterm delivery within 7 days, before 28.0 and 32.0 weeks occurred in 4.8%, 16.8%, and 28.9%, respectively. The only significant predictor of delivery within 7 days was postoperative cervical length (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3–0.9). Concerning delivery before 32.0 weeks, preoperative cervical length (OR, 0.9; 95% CI, 0.8–1.0), and gestational age (OR, 0.8; 95% CI, 0.4–0.9) were independent risk factors but the association was weak. The presence of a single survivor after surgery was associated with a clear reduction of risk (OR, 0.3; 95% CI, 0.1–0.6). Inflammatory biomarkers and duration of surgery did not discriminate risk of prematurity.
Conclusion
No strong preoperative predictive factor of preterm birth could be identified. A single survivor was a strong protective factor of very preterm birth.
Fetoscopic laser coagulation of placental anastomosis has become the firstline option for the treatment of twin-to-twin transfusion syndrome (TTTS). One of the main risks of fetoscopy is the increased incidence of preterm birth with respect to uncomplicated twin pregnancy, which explains a substantial proportion of the perinatal loss associated with this procedure. Laser is associated with rates of 13-17%, 22-29%, and 49-54% of preterm delivery before 24 weeks, 28 and 34 weeks, respectively. Thus, in a relevant proportion of cases, fetoscopic laser is associated with perinatal loss because of delivery within the weeks following the procedure. The ability to identify which factors are associated with the risk of very preterm delivery may be of help both for parent counsel and in the planning of clinical surveillance after therapy.
The risk of preterm delivery after fetoscopic therapy has been assessed only in relation to cervical length. In a large collaborative study, a cervical length less than 30 mm increased the risk for preterm delivery less than 28 weeks, 32 and 34 weeks of gestation by about 41.1%, 52.9% and 73.5% the presence of a single survivor after surgery seemed to modulate this effect. In line with these authors, in a later study, a cervical length of less than 15 mm was associated with a 50% risk of delivery before 28 weeks. In contrast, Chavira et al recently reported no effect of preoperative cervical length on the gestational age at delivery and latency from surgery to delivery.
The effect of other clinical parameters such as gestational age at procedure or cervical length after fetoscopy has not been evaluated. Likewise, the value of inflammatory biomarkers of preterm delivery has not been investigated. We hypothesized that maternal serum C-reactive protein (CRP) or intraamniotic interleukin-6 (IL-6), which have been suggested to be early markers of preterm labor, could also be of value in cases undergoing fetoscopy.
In this study, we aimed to confirm previous results reported for cervical length and to evaluate the diagnostic value of other clinical parameters and of intraamniotic inflammatory markers to predict preterm delivery in TTTS treated by fetoscopy.
Materials and Methods
A prospective cohort study was performed from January 2006 to December 2008. The patients enrolled in this study were all consecutive monochorionic diamniotic twin pregnancies complicated by TTTS who were treated with fetoscopic laser treatment at a single institution during the study period. Written informed consent was obtained from all subjects to perform the fetoscopic procedure and to donate amniotic fluid and maternal blood for research purposes. The Institutional Review Board of Hospital Clinic approved the collection and use of these samples and information for research purposes.
TTTS was diagnosed according to the Eurofoetus criteria. Briefly, TTTS was defined by polyuric polyhydramnios in the recipient twin, with a deepest vertical pool of amniotic fluid of at least 8 cm before 20 weeks of gestation (or at least 10 cm after 20 weeks) together with a markedly distended bladder during most of the examination, and with oliguric oligohydramnios in the donor twin with a deepest vertical pool less than 2 cm and a markedly small or nonvisible bladder during most of the examination.
Maternal serum was obtained from routine preoperative blood tests collected on admission. Transvaginal cervical length was measured before and 24 hours after surgery. All procedures were performed percutaneously under local or regional anesthesia. Prophylactic antibiotics (cefazoline 2 g intravenously) were administered perioperatively in all cases. Fetoscopic placental laser coagulation was performed after the previously published surgical protocol. After surgery, amniotic fluid was drained from the amniotic cavity of the recipient and part of it was collected for later assessment of IL-6.
A complete course of antenatal steroids, betamethasone 12 mg intramuscular injection with 2 doses given 24 hours apart, was administered beyond 24.0 weeks. Perioperative tocolysis was considered in all cases if cervical length before surgery was less than 15 mm and in all cases of gestational age at surgery was ≥24.0 weeks. The tocolytic treatment of choice was nifedipine. Atosiban was administered only if preoperative cervical length was less than 15 mm in patients beyond 24 weeks. The cutoff of 24 weeks was arbitrarily established as part of the internal protocol of the center. Cervical length and maternal and fetal status were closely monitored for signs of chorioamnionitis, labor and/or fetal compromise during admission. Maternal and neonatal medical records were reviewed in all cases.
Preterm delivery was defined as delivery after spontaneous labor. Preterm premature rupture of membranes (PPROM) was defined by the presence of clinical amniotic fluid leakage before the onset of labor, after sterile speculum inspection confirmed by alkaline pH in the absence of vaginal infection. Postoperative occurrence of a single fetal death within 4 weeks from surgery was recorded to assess the impact of a reduction from 2 to 1 fetus in the length of gestation. The limit of 4 weeks was established arbitrarily to include cases where fetal reduction, and consequently the theoretical benefit of the reduction in the number of fetuses, occurred relatively early in pregnancy.
Laboratory methods
CRP was measured immediately after collection from maternal serum. A volume of 10 mL of amniotic fluid was centrifuged at 4000 rpm for 10 minutes at 4°C and stored at −70°C until assayed for IL-6. IL-6 levels were measured by enzyme-linked immunoassay (ELISA) (Invitrogen Biosource, San Diego, CA). The minimum detectable level of IL-6 was 0.2 ng/mL.
Statistical analysis
Data were collected in an Access Database made for this purpose. Statistical analyses were performed with the Statistical calculations using the Statistical Package for the Social Sciences (SPSS 14.0; SPSS Inc, Chicago, IL) software. Univariate analysis was performed with results reported as mean, range, and standard deviation (SD). Two-by-two contingency tables were constructed and the χ 2 test was used to identify significant differences among cervical length before and after the procedure and the risk of preterm delivery. Logistic regression was performed to investigate the relationship between cervical length, maternal serum CRP, amniotic fluid IL-6, duration of surgery, amniotic fluid volume drained, intrauterine death of 1 of the twins within 4 weeks after surgery, presence of cerclage, and the risk for preterm delivery within the 7 days after surgery as well as the risk for preterm delivery before 28.0 and 32.0 weeks of gestation. The results are expressed as adjusted odds ratio (OR) and 95% confidential interval (CI). A P value of < .05 was used to indicate significance.
Results
From January 2006 to December 2008, 166 consecutive monochorionic diamniotic twin pregnancies complicated by TTTS were included in our study. These complicated twins were treated by laser coagulation of intertwin vascular anastomosis.
Table 1 summarizes characteristics of the study population. None of the pregnant women included had a previous history of late miscarriage before 24.0 weeks and 3 (2.2%) patients had a history of preterm delivery before 34.0 weeks.
