Risk factors of early spontaneous preterm birth despite carrying a cervical pessary in singleton pregnancies with a short cervix: Development of a risk prediction model.

Introduction: We aimed to identify the incidence and risk factors of spontaneous preterm birth in pessary carriers with singleton pregnancies and a short cervix in the mid-trimester of pregnancy. Material and Methods: Patient data were obtained from the PECEP Trial. We analyzed singleton pregnancies in pessary carriers with a short cervix (≤25 mm) between 18 and 22 gestational weeks. Demographics and obstetric history were compared to identify risk factors for spontaneous preterm birth < 34 gestational weeks. Each demographic and obstetric variable was compared between spontaneous preterm birth < 34 and ≥ 34 weeks of gestation.Regression analysis was used to identify risk factors. A risk score model was generated using the odds ratio for significant factors. The risk score model and spontaneous preterm birth risk were assessed using the receiver operating characteristic curve. Perinatal outcomes were compared by risk score. Results: Among 190 pregnant individuals, 12 (6.3%) had spontaneous preterm birth < 34 gestational weeks. In the bivariate analysis, statistically significant differences between those with and without spontaneous preterm birth were only observed for mean cervical length at diagnosis and mean cervical length after pessary placement. By multiple logistic regression analysis, maternal age (OR 0.818; 95% CI 0.69-0.97; P 0.020), cervical length at diagnosis (OR 0.560; 95% CI 0.43-0.73; P < 0.001) and smoking status (OR 7.276; 95% CI 1.02-51.80; P 0.048) remained significantly associated with spontaneous preterm birth.The ROC curve from the multiple logistic regression analysis, including cervical length, maternal age and smoking status, had an area under the curve (AUC) of 0.952 (P < 0.001). The ROC curve for the risk score model incorporating all three variables had an AUC of 0.864 (95% CI 0.77-0.96; P < 0.001). A high-risk score was predictive of spontaneous preterm birth with a sensitivity of 75%, specificity of 84%, positive predictive value of 24%, and negative predictive value of 98%.Women with a high-risk score had a significantly reduced latency to delivery and poorer neonatal outcomes than those with a low-risk score. Conclusions: Patients at a high risk for spontaneous preterm birth despite pessary therapy may be identified using cervical length at diagnosis added to maternal age and smoking status.

Reference values for interleukin-6 in the amniotic fluid of asymptomatic pregnant women.

INTRODUCTION: Nowadays, proinflammatory factors are considered to play an important role in the pathophysiology of threatened preterm labor or chorioamnionitis. The aim of this study was to establish the normal reference range for interleukin-6 (IL-6) levels in the amniotic fluid and to identify factors which may alter this value. MATERIAL AND METHODS: Prospective study in a tertiary-level center including asymptomatic pregnant women undergoing amniocentesis for genetic studies from October 2016 to September 2019. IL-6 measurements in amniotic fluid were performed using a fluorescence immunoassay with microfluidic technology (ELLA Proteinsimple, Bio Techne). Maternal history and pregnancy data were also recorded. RESULTS: This study included 140 pregnant women. Of those, women who underwent termination of pregnancy were excluded. Therefore, a total of 98 pregnancies were included in the final statistical analysis. The mean gestational age was 21.86 weeks (range: 15-38.7) at the time of amniocentesis, and 38.6 weeks (range: 30.9-41.4) at delivery. No cases of chorioamnionitis were reported. The log10 IL-6 values follow a normal distribution (W = 0.990, p = 0.692). The median, and the 5th, 10th, 90th, and 95th percentiles for IL-6 levels were 573, 105, 130, 1645, and 2260 pg/mL, respectively. The log10 IL-6 values were not affected by gestational age (p = 0.395), maternal age (p = 0.376), body mass index (p = 0.551), ethnicity (p = 0.467), smoking status (p = 0.933), parity (p = 0.557), method of conception (p = 0.322), or diabetes mellitus (p = 0.381). CONCLUSIONS: The log10 IL-6 values follow a normal distribution. IL-6 values are independent of gestational age, maternal age, body mass index, ethnicity, smoking status, parity and method of conception. Our study provides a normal reference range for IL-6 levels in the amniotic fluid that can be used in future studies. We also observed that normal IL-6 values were higher in the amniotic fluid than in serum.

Implications of training for pessary placement and accuracy of cervical length measurements after pessary placement: A prospective, double-blind, randomized clinical trial.

BACKGROUND: Cervical pessary placement as an intervention for preterm birth prevention in women with a short cervix is a simple, painless procedure with few complications and a reasonable cost. Its efficacy depends on the expertise of the obstetrician performing the procedure. Therefore, it is reasonable to assume that untrained obstetricians with no expertise in pessary placement are more likely to insert the pessary incorrectly, thereby reducing its efficacy. Nevertheless, the impact of pessary placement expertise and training, as well as the accuracy of cervival length measurements, has never been evaluated. OBJECTIVE: To evaluate the impact of providing training for pessary placement to obstetricians with no expertise in this intervention. To this end, the percentage of correct pessary placements and accuracy of cervical length measurements after pessary placement achieved by obstetricians who received such training was compared with the results achieved by obstetricians who did not receive any training. METHODS: This prospective, double-blind, randomized clinical trial included 91 pregnant women requiring a cervical pessary due to a short cervix. Patients were assigned at random to a group treated by untrained obstetricians with no expertise in pessary placement (untrained group, n = 45) or to a group treated by trained obstetricians with no expertise in pessary placement (trained group, n = 46). The primary outcomes were the quality of pessary placement and the accuracy of cervical length measurements after pessary placement. RESULTS: Obstetricians in the trained group achieved a significantly higher percentage of correct pessary placements than obstetricians in the untrained group (97.8 % and 65.2 %, respectively; p < 0.001). No significant differences were observed between groups in terms of the accuracy of cervical length measurements after pessary placement (p = 0.661), and both groups showed moderate to good agreement with the expert's measurements (intraclass correlation coefficient 0.840 and 0.749, respectively). No differences in pregnancy outcomes were observed between groups. CONCLUSION: This study showed that providing training in pessary placement to obstetricians with no expertise in this procedure increases the quality of pessary placement. Furthermore, the inconsistent results found in pessary studies may be explained, in part, by a lack of training in pessary placement.

Cervical pessary and cerclage placement for preterm birth prevention and cervicovaginal microbiome changes.

INTRODUCTION: Our objective was to compare the vaginal microbiome in low-risk and high-risk pregnant women and to explore a potential association between vaginal microbiome and preterm birth. MATERIAL AND METHODS: A pilot, consecutive, longitudinal, multicenter study was conducted in pregnant women at 18-22 weeks of gestation. Participants were assigned to one of three groups: control (normal cervix), pessary (cervical length ≤25 mm) and cerclage (cervical length ≤25 mm or history of preterm birth). Analysis and comparison of vaginal microbiota as a primary outcome was performed at inclusion and at 30 weeks of gestation, along with a follow-up of pregnancy and perinatal outcomes. We assessed the vaginal microbiome of pregnant women presenting a short cervix with that of pregnant women having a normal cervix, and compared the vaginal microbiome of women with a short cervix before and after placement of a cervical pessary or a cervical cerclage. RESULTS: The microbiome of our control cohort was dominated by Lactobacillus crispatus and inners. Five community state types were identified and microbiome diversity did not change significantly over 10 weeks in controls. On the other hand, a short cervix was associated with a lower microbial load and higher microbial richness, and was not correlated with Lactobacillus relative abundance. After intervention, the cerclage group (n = 19) had a significant increase in microbial richness and a shift towards community state types driven by various bacterial species, including Lactobacillus mulieris, unidentified Bifidobacterium or Enterococcus. These changes were not significantly observed in the pessary (n = 26) and control (n = 35) groups. The cerclage group had more threatened preterm labor episodes and poorer outcomes than the control and pessary groups. CONCLUSIONS: These findings indicate that a short cervix is associated with an altered vaginal microbiome community structure. The use of a cerclage for preterm birth prevention, as compared with a pessary, was associated with a microbial community harboring a relatively low abundance of Lactobacillus, with more threatened preterm labor episodes, and with poorer clinical outcomes.

Retro cervical tunneling to ensure correct placement for robotic-assisted transabdominal cerclage.

OBJECTIVE: To demonstrate the step-by-step surgical technique of robotic-assisted transabdominal cerclage, highlighting a new posterior compartment approach. DESIGN: Stepwise explanation of a surgical technique using surgical video. SETTING: The procedure was performed at the Obstetrics and Gynecology Department, Hospital Vall d'Hebron in Barcelona, Spain, a tertiary medical center. The local institutional review board considers that case reports are exempt from research approval. PATIENT(S): A 26-year-old non-pregnant patient, with a history of cervical incompetence, three second-trimester losses, and vaginal cerclage failure during her previous pregnancy. INTERVENTION(S): Robotic-assisted transabdominal cerclage placement was performed. An 8-mm, 30° scope; monopolar scissors; and Maryland bipolar graspers were used. A uterine manipulator was used for better exposure. First, a bladder flap was created, and the uterine vessels were identified and skeletonized. Next, a window between the uterine vessels and the uterine cervix at the level of the cervical-isthmic junction was created bilaterally. At the posterior compartment, the dissection of the root of the uterosacral ligaments was carefully performed. A retrocervical pocket was created with monopolar scissors and sharp dissection. The procedure was finished with the Mersilene tape placement. First, the tape was passed through the window created in the right broad ligament, with a posterior-to-anterior direction, the retro cervical pocket, and finally through the left broad ligament. The knot was placed anteriorly and reperitonization was performed. In addition to this operation, robotic-assisted transabdominal cerclage was successfully performed in another six patients with good surgical and obstetrics outcomes. MAIN OUTCOME MEASURE(S): Intraoperative technique to ensure successful robot-assisted abdominal cerclage placement. RESULT(S): The patient became pregnant six months following the robotic-assisted transabdominal cerclage. Her pregnancy was closely followed up at the High-Risk Obstetric Unit, and she had no complications during pregnancy. An elective cesarean section was performed at 36 weeks with a healthy newborn baby that was discharged with the mother three days after delivery. CONCLUSION(S): The development of a retro cervical pocket during robotic-assisted transabdominal cerclage can be performed safely and effectively. It may help prevent displacement of the Mersilene tape during endoscopic knotting.

Prediction of preterm birth and adverse perinatal outcomes after cervical pessary placement in singleton pregnancies with short cervical length.

OBJECTIVES: To identify ultrasound-assessed cervical characteristics, modified after pessary placement, which could be predictive of spontaneous preterm birth (sPTB) at < 34 weeks of gestation (WG) or severe adverse perinatal outcomes (APO). STUDY DESIGN: This prospective observational study conducted at Vall d'Hebron Universitary Hospital assessed multiple cervical characteristics in women with short cervical length (CL). All participants were examined by transvaginal ultrasound before and immediately after a cervical pessary was placed. Cervical assessment included CL, uterocervical angles (UCA), and cervical consistency indexes (cervical consistency index (CCI) and cervical length consistency index (CLCI)). Pregnancy outcomes were recorded to determine the capacity of these variables for predicting sPTB at < 34 WG and severe APO. RESULTS: Thirty-one women with short CL, 17 (54.8%) with asymptomatic midtrimester short CL, and 14 (45.2%) after arrested threatened preterm labor were enrolled. After pessary placement, transvaginal ultrasound detected four participants in whom the pessary was not correctly placed around the cervix (12.9%); additionally, significant changes were observed in most cervical baseline characteristics, with CL, anterior UCA (A-UCA), CLCI, and intersegmentary angle (ISA) being predictive of sPTB at <34 WG and severe APO. Receiver operator curves were calculated to compare the predictive capacity of these variables, with CL and A-UCA after pessary placement being the best predictive parameters with an area under the curve of 0.88 and 0.87, respectively. CONCLUSIONS: Transvaginal ultrasound after pessary placement detects incorrect pessary placement after pessary insertion and during follow-up. APO and sPTB can be predicted by measuring CL, A-UCA, CLCI, and ISA immediately after pessary placement, being CL and A-UCA more accurate and easier to be measured. Our results help to better identify women in whom the pessary is more likely to fail. Further research is required to assess the effectiveness of applying alternative, sequential or additional treatments to reduce prematurity and our results could be considered when designing such studies.