Prediction Of Spontaneous Preterm Birth Research Articles

Noninvasive factors predicting the maintenance of pregnancy for more than 4 weeks after rescue cerclage in singleton pregnancies with cervical dilatation and prolapsed membrane.

Studies on noninvasive factors and predicting the maintenance of pregnancy, and those comparing the usefulness of these factors with invasive amniotic fluid markers in predicting the maintenance of pregnancy following rescue cerclage, are lacking. Therefore, this study aimed to determine whether C-reactive protein (CRP) levels, White blood cell (WBC) count, absolute neutrophil count (ANC), and platelet-to-lymphocyte ratio (PLR) in maternal blood, which are noninvasive and readily available clinical markers, can predict the maintenance of pregnancy following rescue cerclage in patients with cervical insufficiency (CI). A total of 142 singleton pregnant women (15-28 wk) who underwent rescue cerclage for CI were retrospectively evaluated. The interleukin (IL)-6 concentration in the amniotic fluid; CRP levels, WBC count, ANC, and PLR in the maternal peripheral blood; and degree of cervical dilatation were evaluated before cerclage. The primary outcome was whether the pregnancy was maintained for >4 weeks after rescue cerclage. Among the 142 patients, prolonged pregnancy for >4 weeks following emergent cerclage was observed in 107 (75.35%), while 35 (24.65%) gave birth within 4 weeks. This study demonstrated that the degree of cervical dilatation at diagnosis; WBC count, ANC, and CRP levels in the maternal peripheral blood; and IL-6 concentration in the amniotic fluid significantly differed between the successful and failure groups (all P < .05). The area under the curve (AUC) of the amniotic fluid IL-6 concentration was .795 for the prediction of spontaneous preterm birth within 4 weeks after rescue cerclage. Additionally, the AUC of the CRP level, cervical dilatation, WBC count, ANC, and PLR were .795, .703, .695, .682, and .625, respectively. These findings suggest that the preoperative CRP levels can be considered a useful noninvasive marker comparable to amniotic fluid IL-6 concentration for identifying pregnant women with CI at high risk of spontaneous preterm birth following rescue cerclage.

Changes of uterocervical angle and cervical length in early and mid-pregnancy and their value in predicting spontaneous preterm birth.

Objective: To explore the feasibility of transvaginal ultrasound measurement of uterocervical angle (UCA) and cervical length (CL) in early and mid-pregnancy and evaluate their combined prediction of spontaneous preterm birth (sPTB) in singleton pregnancies. Patients and Methods: This retrospective study comprised 274 pregnant women who underwent transvaginal ultrasound measurement of CL in mid-pregnancy (15-23+6weeks); in 75 among them, CL also had been measured in early-pregnancy (<14 weeks). These 274 pregnant women were further divided into a preterm group (n = 149, <37weeks gestation) and a control group (n = 125, >37weeks gestation) according to delivery before or after 37weeks, respectively. In the preterm group, 35 patients delivered before 34weeks and the remaining 114 delivered between 34 and 37weeks. Results: The optimal threshold of CL to predict preterm birth risk in women with <37weeks gestation was 3.38cm, and the optimal threshold of the UCA to predict preterm birth risk in the same group of women was 96°. The optimal threshold of CL to predict preterm birth risk in women with <34weeks gestation was 2.54cm, while that of the UCA in the same group of patients was 106°. The area under the curve for predicting preterm birth by combining the UCA and CL measurements was greater than that by using the UCA or CL alone (p < 0.01). The sensitivity and specificity for predicting preterm birth at <34 weeks gestation was 71.7% and 86.4%, respectively; and the sensitivity and specificity for predicting preterm birth at <37weeks gestation was 87.6% and 80.6%, respectively. The difference between the two groups in CL and UCA were not significant in early pregnancy (p > 0.01), but only in mid-pregnancy (p < 0.01). There was a negative correlation between UCA and gestational week at delivery (r = -0.361, p < 0.001) and a positive correlation between CL and gestational week at delivery (r = 0.346, p < 0.001) in mid-pregnancy. The proportion of deliveries at <34 weeks was highest when the UCA was >105°, and the proportion of deliveries between 35 and 37weeks was highest when the UCA was between 95° and 105°. The proportion of deliveries at <34weeks was highest when the CL was <2.5cm. Conclusion: The combination of UCA and CL has a better ability to predict preterm birth than either measurement alone. A more obtuse UCA or a shorter CL is associated with an earlier spontaneous preterm birth. The UCA increases from early to mid-pregnancy, while the CL decreases from early to mid-pregnancy.

Prediction of spontaneous preterm birth in women with previous full dilatation cesarean delivery

A previous term (≥37 weeks' gestation), full-dilatation cesarean delivery is associated with an increased risk for a subsequent spontaneous preterm birth. The mechanism is unknown. We hypothesized that the cesarean delivery scar characteristics and scar position relative to the internal cervical os may compromise cervical function, thereby leading to shortening of the cervical length and spontaneous preterm birth. This study aimed to determine the relationship of cesarean delivery scar characteristics and position, assessed by transvaginal ultrasound, in pregnant women with previous full-dilatation cesarean delivery with the risk of shortening cervical length and spontaneous preterm birth. This was a single-center, prospective cohort study of singleton pregnant women (14 to 24 weeks' gestation) with a previous term full-dilatation cesarean delivery who attended a high-risk preterm birth surveillance clinic (2017-2021). Women underwent transvaginal ultrasound assessment of cervical length, cesarean delivery scar distance relative to the internal cervical os, and scar niche parameters using a reproducible transvaginal ultrasound technique. Spontaneous preterm birth prophylactic interventions (vaginal cervical cerclage or vaginal progesterone) were offered for short cervical length (≤25 mm) and to women with a history of spontaneous preterm birth or late miscarriage after full-dilatation cesarean delivery. The primary outcome was spontaneous preterm birth; secondary outcomes included short cervical length and a need for prophylactic interventions. A multivariable logistic regression analysis was used to develop multiparameter models that combined cesarean delivery scar parameters, cervical length, history of full-dilatation cesarean delivery, and maternal characteristics. The predictive performance of models was examined using the area under the receiver operating characteristics curve and the detection rate at various fixed false positive rates. The optimal cutoff for cesarean delivery scar distance to best predict a short cervical length and spontaneous preterm birth was analyzed. Cesarean delivery scars were visualized in 90.5% (220/243) of the included women. The spontaneous preterm birth rate was 4.1% (10/243), and 12.8% (31/243) of women developed a short cervical length. A history- (n=4) or ultrasound-indicated (n=19) cervical cerclage was performed in 23 of 243 (9.5%) women; among those, 2 (8.7%) spontaneously delivered prematurely. A multiparameter model based on absolute scar distance from the internal os best predicted spontaneous preterm birth (area under the receiver operating characteristics curve, 0.73; 95% confidence interval, 0.57-0.89; detection rate of 60% for a fixed 25% false positive rate). Models based on the relative anatomic position of the cesarean delivery scar to the internal os and the cesarean delivery scar position with niche parameters (length, depth, and width) best predicted the development of a short cervical length (area under the receiver operating characteristics curve, 0.79 [95% confidence interval, 0.71-0.87]; and 0.81 [95% confidence interval, 0.73-0.89], respectively; detection rate of 73% at a fixed 25% false positive rate). Spontaneous preterm birth was significantly more likely when the cesarean delivery scar was <5.0 mm above or below the internal os (adjusted odds ratio, 6.87; 95% confidence interval, 1.34-58; P =.035). In pregnancies following a full-dilatation cesarean delivery, cesarean delivery scar characteristics and distance from the internal os identified women who were at risk for spontaneous preterm birth and developing short cervical length. Overall, the spontaneous preterm birth rate was low, but it was significantly increased among women with a scar located <5.0 mm above or below the internal cervical os. Shortening of cervical length was strongly associated with a low scar position. Our novel findings indicate that a low cesarean delivery scar can compromise the functional integrity of the internal cervical os, leading to cervical shortening and/or spontaneous preterm birth. Assessment of the cesarean delivery scar characteristics and position seem to have use in preterm birth clinical surveillance among women with a previous, full-dilatation cesarean delivery and could better identify women who would benefit from prophylactic interventions.

Cervical elastography in predicting spontaneous preterm birth in singleton pregnancy with a short cervix receiving progesterone treatment at 18 to 24 weeks’ gestation

Background A short cervix in the second trimester is known to increase the risk of preterm birth, which can be reduced with the administration of vaginal progesterone. However, some studies have suggested that a significant number of cases still experience preterm birth despite progesterone treatment. Objective This study was aimed to investigate the potential value of transvaginal cervical elasticity measured by E-Cervix as a predictor for spontaneous preterm birth (sPTB) in singleton pregnancies receiving progesterone treatment for a short cervix (CL ≤ 2.5 cm) diagnosed at 18 to 24 weeks’ gestation. Study design This prospective study was conducted at a single center premature high-risk clinic from January 2020 to July 2022. Singleton pregnancies with a short cervix at 18 to 24 weeks’ gestation were enrolled. Cervical elastography using E-Cervix was performed, and maternal and neonatal demographic characteristics, cervical length (CL), elasticity contrast index (ECI), cervical hardness ratio, mean internal os strain (IOS), and mean external os strain (EOS) were compared before and after progesterone treatment in sPTB and term birth groups. Multivariate logistic regression was used to analyze the association between elasticity parameters and spontaneous preterm birth. The screening performance of CL and optimal cervical elasticity parameters in predicting sPTB was evaluated using receiver-operating characteristic (ROC) curve analysis. Results A total of 228 singleton pregnant women were included in the study, among which 26 (11.4%) had sPTB. There were no significant differences in maternal characteristics and gestational age at enrollment between women with and without sPTB. At the start of progesterone treatment, there were no significant differences in cervical elasticity parameters between the two groups. After two weeks of progesterone treatment, women who had sPTB showed significantly higher levels of ECI, IOS, EOS (p = 0.0108, 0.0001, 0.016), and lower hardness ratio (p = 0.011) compared to those who had a full-term birth. Cervical length did not show significant differences between the two groups, regardless of whether progesterone treatment was administered before or after. Among the post-treatment cervical elasticity parameters, IOS and EOS were associated with a 3.38-fold and 2.29-fold increase in the risk of sPTB before 37 weeks (p = 0.032, 0.047, respectively). The AUROC of the combined model including CL, IOS, and EOS (0.761, 95% CI0.589–0.833) was significantly higher than the AUROC of CL alone (0.618, 95% CI 0.359–0.876). At a fixed false-positive of 13%, the addition of IOS and EOS in the CL model increased sensitivity from 34.6% to 57.6%, PPV from 25.7% to 36.5%, and NPV from 91.1% to 94.1%. Conclusion When assessing the risk of sPTB in singleton pregnancies with a short cervix receiving progesterone therapy, relying solely on cervical length is insufficient. It is crucial to also evaluate cervical stiffness, particularly the strain of the internal and external os, using cervical elastography.

The Endocannabinoid System - The Prediction of Spontaneous Preterm Birth in High-Risk Women: Protocol of a Study.

Spontaneous preterm birth (sPTB) is a major cause of perinatal morbidity and mortality, even in developed countries. Prediction of sPTB is therefore a valuable tool to reduce the associated risks. The current standard for the prediction of sPTB consists, in addition to anamnestic data, of previous sPTB and previous second trimester miscarriage, measurement of cervical length by transvaginal ultrasound (TVU CL) together with assessment of fetal fibronectin levels in cervicovaginal fluid. Other evaluation parameters, such as the level of endocannabinoids in the pregnant woman's blood, could increase the sensitivity of this management. Endocannabinoids (eCBs) are a part of the endocannabinoid system (ECS); out of them anandamide (arachidonoyl-ethanolamide, AEA), in particular, plays an important role in the regulation of pregnancy and childbirth. We present the protocol for an open, non-randomized study to evaluate concentrations of AEA and other endocannabinoids: 2 linoleoylglycerol (2-AG), 2 linoleoylglycerol (2-LG), 2 oleoylglycerol (2-OG), and 2 arachidonoyldopamine (2-ADOPA or also NADA) in the blood of pregnant women as potential predictors of sPTB. In a total of 230 women with a history of sPTB or miscarriage, eCBs levels between 22 and 28 weeks of gestation will be assessed from maternal blood, in addition to the standard procedure. The aim of the study is to determine the relationship between blood concentrations of the endocannabinoids tested and the risk of sPTB. The results of this study will describe the prognostic significance of maternal blood eCBs levels for sPTB, and could subsequently enable improved screening programs for early identification of sPTB.

Prediction of spontaneous preterm birth using supervised machine learning on metabolomic data: A case-cohort study.

To identify and internally validate metabolites predictive of spontaneous preterm birth (sPTB) using multiple machine learning methods and sequential maternal serum samples, and to predict spontaneous early term birth (sETB) using these metabolites. Case-cohort design within a prospective cohort study. Cambridge, UK. A total of 399 Pregnancy Outcome Prediction study participants, including 98 cases of sPTB. An untargeted metabolomic analysis of maternal serum samples at 12, 20, 28 and 36 weeks of gestation was performed. We applied six supervised machine learning methods and a weighted Cox model to measurements at 28 weeks of gestation and sPTB, followed by feature selection. We used logistic regression with elastic net penalty, followed by best subset selection, to reduce the number of predictive metabolites further. We applied coefficients from the chosen models to measurements from different gestational ages to predict sPTB and sETB. sPTB and sETB. We identified 47 metabolites, mostly lipids, as important predictors of sPTB by two or more methods and 22 were identified by three or more methods. The best 4-predictor model had an optimism-corrected area under the receiver operating characteristics curve (AUC) of 0.703 at 28 weeks of gestation. The model also predicted sPTB in 12-week samples (0.606, 95% CI 0.544-0.667) and 20-week samples (0.657, 95% CI 0.597-0.717) and it predicted sETB in 36-week samples (0.727, 95% CI 0.606-0.849). A lysolipid, 1-palmitoleoyl-GPE (16:1)*, was the strongest predictor of sPTB at 12 weeks of gestation (0.609, 95% CI 0.548-0.670), 20 weeks (0.630, 95% CI 0.569-0.690) and 28 weeks (0.660, 95% CI 0.599-0.722), and of sETB at 36 weeks (0.739, 95% CI 0.618-0.860). We identified and internally validated maternal serum metabolites predictive of sPTB. A lysolipid, 1-palmitoleoyl-GPE (16:1)*, is a novel predictor of sPTB and sETB. Further validation in external populations is required.

EG-VEGF maternal levels predict spontaneous preterm birth in the second and third trimesters in pregnant women with risk factors for placenta-mediated complications

Prediction of spontaneous preterm birth in asymptomatic women remains a great challenge for the public health system. The aim of the study was to determine the informational value of EG-VEGF circulating levels for prediction of spontaneous preterm birth in the second and third trimesters in pregnant women at high risk for placenta-mediated complications. A prospective multicenter cohort study including 200 pregnant patients with five-serum sampling per patient. Women with spontaneous preterm birth have higher concentrations of serum EG-VEGF than uncomplicated patients at 24 weeks, 28 weeks and 32 weeks (p = 0.03, 0.02 and < 0.001). The areas under the curve reached 0.9 with 100% sensitivity at 32 weeks for the prediction of spontaneous preterm birth. Serum EG-VEGF concentrations could be considered as a reliable biomarker of spontaneous preterm birth in high-risk for placenta-mediated complications pregnant women.

Ultrasonographic cervical length screening at 20-24 weeks of gestation in twin pregnancies for prediction of spontaneous preterm birth: A 10-year Taiwanese cohort.

Shortened cervical length is one of the primary predictors for spontaneous preterm deliveries in twin pregnancies. However, there is lack of consensus regarding cut-off values. Recent evidence highlights that established cut-offs for cervical length screening might not always apply across different populations. This study aims to present the distribution of cervical length in Taiwanese twin pregnancies and to assess its predictive value for spontaneous preterm birth during mid-trimester screening. This retrospective analysis of cervical length screening in Taiwan evaluated 469 twin pregnancies between 20-24 weeks of gestation. Outcome data were obtained directly from the medical records of the delivery hospital. The study explored the predictive value of cervical length screening for spontaneous preterm birth and the characteristics of cervical length distribution in Taiwanese twin pregnancies. The average gestational age at screening was 22.7 weeks. Cervical length values displayed a non-normal distribution (p-value <0.001). The median, 5th and 95th centiles were 37.5 mm 25.1 mm, and 47.9 mm, respectively. Various cut-off values were assessed using different methods, yielding positive [negative] likelihood ratios for spontaneous preterm births between 32-37 weeks of gestational age (GA) (1.3-30.1 and [0.51-0.92]) and for very preterm births between 28-32 weeks GA (5.6-51.1 and [0.45-0.64]). The findings from our analysis of Taiwanese twin pregnancies uphold the moderate predictive potential of cervical length screening, consistent with prior investigations. The presented likelihood ratios for predicting preterm birth at different gestational ages equip clinicians with valuable tools to enhance their diagnostic rationale and resource utilization. By fine-tuning screening parameters according to the spontaneous preterm birth prevalence and clinical priorities of the particular population, healthcare providers can enhance patient care. Our data implies that a cervical length below 20 mm might provide an optimal balance between minimizing false negatives and managing false positives when predicting spontaneous preterm birth.

EP19.22: Prediction of spontaneous preterm birth using maternal history, PAPP‐A and cervical length at 11–13 weeks in a South Asian Population

EP19.22: Prediction of spontaneous preterm birth using maternal history, PAPP‐A and cervical length at 11–13 weeks in a South Asian Population

Prediction of spontaneous preterm birth using CCL2 and CXCL10 in maternal serum of symptomatic high-risk pregnant women: a prospective cohort study

IntroductionCCL2 and CXCL10 are putative biomarkers for the prediction of spontaneous preterm birth. This study evaluates these markers in a cohort of pregnant high-risk women.Material and methodsIn our prospective study, we included 109 women with signs of preterm labor between 20 + 0 and 31 + 6 weeks of gestation. Inclusion criteria were regular (< 3/30 min) or painful contractions, cervical length < 25 mm or a history of previous preterm birth (PTB). Blood samples were obtained upon first admission to our clinic. Biomarker concentrations were measured using pre-coated sandwich immunoassays (ELISA). Primary study outcome was spontaneous preterm birth < 34 weeks, secondary outcome was delivery < 37 weeks or within seven days after study inclusion.ResultsSixteen women (14.7%) delivered < 34 weeks and twenty women between 34 + 0 and 36 + 6 weeks (18.4%). Six patients (5.5%) gave birth within seven days after study admission. CXCL10 showed higher medium serum levels in women with PTB < 34 weeks (115 pg/ml compared to 61 pg/ml ≥ 34 weeks; p < 0.001) and < 37 weeks (103 pg/ml vs. 53 pg/ml; p < 0.001). In contrary, lower CCL2 serum levels were associated with PTB < 34 weeks (46 pg/ml vs. 73 pg/ml; p = 0.032) and birth within 7 days (25 pg/ml vs. 73 pg/ml; p = 0.008). The CXCL10/CCL2-ratio further improved the predictive model with a ROC-AUC of 0.83 (95% CI 0.73–0.93, p < 0.001) for delivery < 34 weeks. These corresponds to a sensitivity, specificity and positive predictive value of 0.67, 0.86 and 0.43 at a cut-off of 2.2.ConclusionLow maternal serum CCL2 levels are associated with a higher risk of preterm delivery within seven days. High CXCL10 serum levels are more associated with a high risk for preterm birth < 34 weeks. Elevated CXCL10/CCL2-ratio is showing the best predictive performance.Trial registration number (DRKS-ID)DRKS00010763, Registration date: September 02, 2016.

Uterocervical angle versus cervical length in the prediction of spontaneous preterm birth in women with history of spontaneous preterm birth: a prospective observational study

BackgroundPreterm delivery is a leading cause of neonatal mortality and morbidity. History of spontaneous preterm birth is the greatest risk factor for another preterm delivery. So, every effort should be made to prevent the recurrence of preterm delivery in this vulnerable group. This study aimed to evaluate the predictive ability of the anterior uterocervical angle and cervical length in preterm birth.Patients and MethodsThis was a prospective cohort study that included 70 patients with a history of spontaneous preterm birth. Ultrasound measurements of cervical length and anterior uterocervical angle were set to be measured for each patient at three visits; first between 16 0/7 and 24 0/7 weeks, second between 24 1/7 and 32 0/7 weeks, and the third was between 32 1/7 and 36 6/7 weeks. The correlation between both measures and the prediction of preterm birth among study participants was the primary outcome of the study. Neonatal outcome among the study patients was a secondary measure of outcome.ResultsThe incidence of preterm birth among study participants was 31.41%. Cervical length and uterocervical angle showed progressive decrease and increase respectively throughout pregnancy. At the 2nd visit, the two measures were significantly different between those who delivered at term and those with preterm delivery with the cervical length being significantly shorter in the preterm arm (3.0 ± 0.49 versus 3.38 ± 0.36, p < 0.001) and uterocervical angle being significantly bigger among the same arm (110.1 ± 18.48 versus 84.42 ± 12.24, p < 0.001). A uterocervical angle > 89.8° at the second visit predicted preterm birth with 81.8% sensitivity and 70.8% specificity while cervical length ≤ 3.22 cm at the second visit predicted preterm birth with 68.1% sensitivity and 62.5% specificity. Multivariant logistic regression analysis showed that uterocervical angle > 89.8° at the second visit increased the odds ratio for preterm birth by 9.ConclusionUterocervical angle can be a useful ultrasound marker for the prediction of preterm birth among high risk patients. A cutoff value of 89.8° can be used as a threshold above which prophylactic measures such as cervical cerclage or progesterone therapy can be provided.Trial registrationNCT05632003 (First posted date: 30/11/2022).

A systematic review of prediction models for spontaneous preterm birth in singleton asymptomatic pregnant women with risk factors

BackgroundsSpontaneous preterm birth (SPB) is a global problem. Early screening, identification, and prevention in asymptomatic pregnant women with risk factors for preterm birth can help reduce the incidence and mortality of preterm births. Therefore, this study systematically reviewed prediction models for spontaneous preterm birth, summarised the model characteristics, and appraised their quality to identify the best-performing prediction model for clinical decision-making. MethodsPubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, VIP Database, and Wanfang Data were searched up to September 27, 2021. Prediction models for spontaneous preterm births in singleton asymptomatic pregnant women with risk factors were eligible for inclusion. Six independent reviewers selected the eligible studies and extracted data from the prediction models. The findings were summarised using descriptive statistics and visual plots. ResultsTwelve studies with twelve developmental models were included. Discriminative performance was reported in 11 studies, with an Area Under the Curve (AUC) ranging from 0.75 to 0.95. The AUCs of the seven models were greater than 0.85. Cervical length (CL) is the most commonly used predictor of spontaneous preterm birth. A total of 91.7% of the studies had a high risk of bias in the analysis domain, mainly because of the small sample size and lack of adjustment for overfitting. ConclusionThe accuracy of the models for spontaneous preterm births in singleton asymptomatic women with risk factors was good. However, these models are not widely used in clinical practice because they lack replicability and transparency. Future studies should transparently report methodological details and consider more meaningful predictors with new progress in research on preterm birth.

Cervical elastography: finding a novel predictor for improving the prediction of preterm birth in uncomplicated twin pregnancies.

This study set out to investigate a novel ultrasound parameter using cervical elastosonography for improving the prediction of spontaneous preterm birth (sPTB) in twin pregnancies. The study was comprised of 106 twin pregnancies from October 2020 to January 2022 in Beijing Obstetrics and GynecologyHospital. They were divided into two groups according to gestational age (GA) at delivery (delivery < 35weeks and delivery ≥ 35weeks). There were five elastographic parameters: Elasticity Contrast Index (ECI), Cervical Hardness Ratio (CHR), Closed Internal cervical ostium Strain rate (CIS); External cervical ostium strain rate (ES), CIS/ES ratio and Cervical Length (CL). All of the clinical and ultrasonic indicators with P < 0.1 were considered candidate indicators via univariate logistic regression. Based on the extracted unified combination of clinical indicators, the combinations of permutation with the candidate ultrasound indicators were performed step by step in multivariable logistic regression. The best ultrasound indicator with the lowest Akaike Information Criterion (AIC) and the highest Areas Under the receiver operating characteristic Curve (AUC) was chosen for establishing the prediction score. Over 30% (36/106) of those who delivered before 35weeks gestation. There were distinct differences in the clinical characteristics and cervical elastography parameters between the two groups. Seven major clinical variables were identified as a unified clinical indicator. CISmin as the best ultrasound elastography predictor indicated the lowest AIC and the highest AUC and outperformed alternative indicators significantly in the prediction of delivery before 35weeks of gestation. Unfortunately, CLmin which was commonly used in clinical practice ranked far from all of the cervical elastography parameters and presented the highest AIC and the lowest AUC. A preliminary scoring rule was established and the ability to predict the risk of sPTB in twin pregnancies was improved (Accuracy: 0.896 vs 0.877; AIC: 81.494 vs 91.698; AUC: 0.923 vs 0.906). The cervical elastosonography predictor such as CISmin might be a more useful indicator applied for enhancing the ability in predicting twin pregnancies preterm birth than CL. Furthermore, there would be more benefits for advancing clinical decision-making in actual clinical practice by using cervical elastosonography in the near future.

Predicting Preterm Birth with Strain Ratio Analysis of the Internal Cervical Os: A Prospective Study.

(1) Background: Cervical elastography is a new concept that could allow clinicians to assess cervical consistency in various clinical scenarios. We aimed to evaluate the predictive performance of the strain ratio (SR) at the level of the internal os, either individually or in combination with other parameters, in the prediction of spontaneous preterm birth (PTB) at various gestational ages. (2) Methods: This prospective study included 114 pregnant patients with a high-risk profile for PTB who underwent cervical elastography during the second trimester. Clinical and paraclinical data were assessed using univariate analysis, logistic regression, and sensitivity analysis. (3) Results: The SR achieved an area under the receiver operating curve (AUROC) value of 0.850, a sensitivity of 85.71%, and a specificity of 84.31% in the prediction of PTB before 37 weeks of gestation. The combined model showed superior results in terms of accuracy (AUROC = 0.938), sensitivity (92.31%), and specificity (95.16%). When considering PTB subtypes, the highest AUROC value (0.80) and accuracy (95.61%) of this marker were achieved in the prediction of extremely preterm birth, before 28 weeks of gestation. (4) Conclusions: The SR achieved an overall good predictive performance in the prediction of PTB and could be further evaluated in various cohorts of patients.

Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) Can Predict Spontaneous Preterm Birth?

To investigate the role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in the prediction of spontaneous preterm birth. Data was retrospectively collected from hospital record between February 2018 and November 2022. Pregnant women (n = 78) with a single pregnancy between 24 and 34 weeks of gestation, presented with labor pain, and had regular uterine contractions (threatened preterm labor - TPL) were included. Patients delivered within the first week after TPL were included in group 1 (n = 40) and who delivered after in group 2 (n = 38). Two groups were investigated for NLR and PLR values. The median cervical length among women who gave birth within a week was significantly lower (24.5 versus 30.0 p < 0.001). The median neutrophil-to-lymphocyte ratio among women who gave birth within a week was significantly higher (6.4 versus 4.5 p < 0.001). The median platelet-to-lymphocyte ratio among women who gave birth within a week was significantly higher (151 versus 131 p < 0.001). The cut-off values to predict preterm birth were >5 for NLR (sensitivity: 90%, specificity: 92.1%), >139 for PLR (sensitivity: 97.5%, specificity: 100%). NLR and PLR values predict spontaneous preterm birth with high sensitivity and specificity. By predicting preterm birth, the pregnancy process can be managed sensitively and smoothly.

Longitudinal change in cervical length following vaginal or abdominal cervical cerclage: a randomized comparison

Cervical cerclage has been shown to reduce the risk of recurrent spontaneous preterm birth in a high-risk patient population; however, the mechanism is not well understood. Transabdominal cerclage is superior to low and high vaginal cerclage in reducing early spontaneous preterm birth and fetal loss in women with previous failed vaginal cerclage. Cervical length measurements are commonly used to monitor high-risk women and may explain the mechanism of success. This study aimed to evaluate the rate of change in longitudinal cervical length after randomized placement of low transvaginal, high transvaginal, or transabdominal cerclage in women with a previous failed vaginal cerclage. This was a planned analysis of longitudinal transvaginal ultrasound cervical length measurements from patients enrolled in the Vaginal Randomised Intervention of Cerclage trial, a randomized controlled trial comparing transabdominal cerclage or high transvaginal cerclage with low transvaginal cerclage. Cervical length measurements at specific gestational ages were compared over time and between groups, using generalized estimating equations fitted using the maximum-likelihood random-effects estimator. In addition, cervical length measurements were compared in women with transabdominal cerclage placed before and during pregnancy. The diagnostic accuracy of cervical length as a predictor of spontaneous preterm birth at <32 weeks of gestation was explored. This study included 78 women who underwent longitudinal cervical length assessment (70% of the analyzed cohort) with a history of failed cerclage, of whom 25 (32%) were randomized to low transvaginal cerclage, 26 (33%) to high transvaginal cerclage, and 27 (35%) to transabdominal cerclage. Abdominal cerclage was superior to low (P=.008) and high (P=.001) vaginal cerclage at maintaining cervical length over the surveillance period (14 to 26 weeks of gestation) (+0.08 mm/week, 95% confidence interval, -0.40 to 0.22; P=.580). On average, the cervical length was 1.8 mm longer by the end of the 12-week surveillance period in women with transabdominal cerclage (+1.8 mm; 95% confidence interval, -7.89 to 4.30; P=.564). High vaginal cerclage was no better than low cervical cerclage in the prevention of cervical shortening; the cervix shortened by 13.2 mm over 12 weeks in those with low vaginal cerclage (95% confidence interval, -21.7 to -4.7; P=.002) and by 20 mm over 12 weeks in those with high vaginal cerclage (95% confidence interval, -33.1 to -7.4; P=.002). Preconception transabdominal cerclage resulted in a longer cervix than those performed during pregnancy; this difference was significant after 22 weeks of gestation (48.5 mm vs 39.6 mm; P=.039). Overall, cervical length was an excellent predictor of spontaneous preterm birth at <32 weeks of gestation (receiver operating characteristic curve, 0.92; 95% confidence interval, 0.82-1.00). In women with a previous failed cervical cerclage, in the next pregnancy, the cervical length in women treated with vaginal cerclage funneled and shortened over time, whereas there was preservation of cervical length in women who receive transabdominal cerclage. Cervical length remained longer in transabdominal procedures performed before pregnancy than in transabdominal procedures performed during pregnancy. Overall, cervical length was an excellent predictor of spontaneous preterm birth in our cohort. Our findings may explain the mechanism of benefit for transabdominal cerclage, with its high placement better maintaining the structural integrity of the cervix at the level of the internal os.

Distribution of uterocervical angles of pregnant women at 16+ 0 to 23+ 6 weeks gestation with low risk for preterm birth: first vietnamese cohort of women with singleton pregnancies

BackgroundCervical length (CL) measured by ultrasound in the second trimester is a predictor of spontaneous preterm birth (sPTB). The uterocervical angle (UCA) has recently been suggested as a predictor to identify women at risk of sPTB. The aim of this study was to investigate the UCAs’ distribution in singleton pregnant women at 16+ 0 − 23+ 6 weeks of gestation with low risk for sPTB.MethodsThis was a prospective cohort study of 1,051 pregnant women with singleton pregnancies at low risk for preterm delivery. Pregnant women with a viable singleton fetus at 16+ 0 − 23+ 6 weeks of gestation were enrolled in the study conducted at the Haiphong Hospital of Obstetrics and Gynecology, Vietnam, from 09/2019 to 09/2020. CL and the UCA were assessed using transvaginal ultrasonography (TVS) by a single sonographer. Subjects were followed-up until the end of pregnancy, and maternal and neonatal outcomes were recorded. The UCAs’ range and their relationship with gestational age were evaluated using regression analysis. P < 0.05 was considered statistically significant.ResultsThe normal range of the UCA (5th − 95th percentiles) was 46.47° (95% CI, 40.27°-51.81°) to 127.06° (95% CI, 123.02° − 130.71°). The UCAs in the preterm birth (< 37 weeks) and full-term groups were 117.86° ± 20.25° and 83.80° ± 24.18°, respectively (p < 0.001). Linear regression analysis showed a significant change in the UCA range from 16+ 0 to 23+ 6 weeks of gestation (2.51 degrees per week, p < 0.001). The linear function yielded the highest correlation coefficient in the variation rule of the UCA values (r = 0.22). A total of 42/63 (66.7%) patients with preterm birth < 37 weeks had a UCA above the 75th percentile. The majority of women with preterm birth had a UCA ≥ 95° compared with those with full-term delivery (88.9% vs. 31.3%, p < 0.001).ConclusionsThe results of this study present background information about the normal range of UCA values in singleton pregnant women at 16+ 0 to 23+ 6 weeks at low risk for sPTB in this Vietnamese cohort. In this study population at low risk for sPTB, pregnant women with a UCA value ≥ 95o were also considered at risk for preterm birth.

Relationship between plasma concentration of 17-hydroxyprogesterone caproate and gestational age at preterm delivery

The effectiveness of 17-hydroxyprogesterone caproate is unclear as trials have provided conflicting results. With the absence of fundamental pharmacologic studies addressing dosing or the relationship between drug concentration and gestational age at delivery, the effectiveness of the medication cannot be evaluated. This study aimed to evaluate the relationship between plasma concentrations of 17-hydroxyprogesterone caproate and preterm birth rates and gestational age at preterm delivery and to assess the safety of the 500-mg dose. This study recruited 2 cohorts with previous spontaneous preterm birth; 1 cohort (n=143) was randomly assigned to either 250-mg or 500-mg 17-hydroxyprogesterone caproate, and the other cohort (n=16) was receiving the 250-mg dose for routine care. Steady-state trough plasma concentrations of 17-hydroxyprogesterone caproate obtained at 26 to 30 weeks of gestation were correlated to dose, spontaneous preterm birth rates, and measures of gestational length. Furthermore, maternal and neonatal safety outcomes were evaluated according to dose. There was a dose proportional increase in trough plasma concentrations with the 250-mg (median, 8.6 ng/m; n=66) and 500-mg (median, 16.2 ng/mL; n=55) doses. In 116 compliant participants with blood samples, drug concentration was not related to the spontaneous preterm birth rate (odds ratio, 1.00; 95% confidence interval, 0.93-1.08). However, there was a significant relationship between drug concentration and both the interval from the first administration to delivery (interval A: coefficient, 1.11; 95% confidence interval, 0.00-2.23; P=.05) and the interval from the 26- to 30-week blood draw to delivery (interval B: coefficient, 1.56; 95% confidence interval, 0.25-2.87; P=.02). The spontaneous preterm birth rate or measures of gestational length were not related to dose. Postenrollment cerclage adversely affected all pharmacodynamic assessments because it was a powerful predictor of spontaneous preterm birth (odds ratio, 4.03; 95% confidence interval, 1.24-13.19; P=.021) and both measures of gestational length (interval A [coefficient, -14.9; 95% confidence interval, -26.3 to -3.4; P=.011] and interval B [coefficient, -15.9; 95% confidence interval, -25.8 to -5.9; P=.002]). Initial cervical length was significantly related to the risk of postenrollment cerclage (odds ratio, 0.80; 95% confidence interval, 0.70-0.92; P=.001). Maternal and neonatal safety outcomes were similar in both dosing groups. In this pharmacodynamic study, trough plasma 17-hydroxyprogesterone caproate concentrations were significantly associated with gestational age at preterm birth but not with the preterm birth rate. Postenrollment cerclage was a powerful predictor of spontaneous preterm birth rate and gestational length. Initial cervical length predicted the risk of postenrollment cerclage. Adverse events were similar with the 500-mg and 250-mg doses of 17-hydroxyprogesterone caproate.

Predicting spontaneous preterm birth in asymptomatic high-risk women with cervical cerclage.

To determine the performance of the predictive markers of spontaneous preterm birth, cervicovaginal quantitative fetal fibronectin (fFN) and cervical length, in asymptomatic high-risk women with transabdominal, history-indicated or ultrasound-indicated cervical cerclage. This was a secondary analysis of a prospective cohort of asymptomatic high-risk women with cervical cerclage and no other prophylactic intervention (including progesterone), who attended the preterm birth clinic at a central London teaching hospital between October 2010 and September 2016. Women had either transabdominal cerclage, placed prior to conception, history-indicated cerclage, placed before 14 weeks' gestation, or ultrasound-indicated cerclage for a short cervix (< 25 mm), placed before 24 weeks. All women underwent serial cervical length assessment on transvaginal ultrasound in the second trimester (16-28 weeks), and quantitative fFN testing from 18 weeks onward. Test performance was analyzed for the prediction of spontaneous preterm birth before 30 weeks (cerclage failure), 34 weeks and 37 weeks, using receiver-operating-characteristics (ROC)-curve analysis. Overall, 181 women were included in the analysis. Cervical length and fFN were strong predictors of spontaneous preterm birth before 30 weeks in women with cerclage, with areas under the ROC curve (AUC) of 0.86 (95% CI, 0.79-0.94) and 0.84 (95% CI, 0.75-0.92), respectively. Cervical length was a better predictor of preterm birth before 30 weeks in women with history-indicated compared to those with ultrasound-indicated cerclage, although both showed clinical utility (AUC, 0.96 (95% CI, 0.91-1.00) vs 0.79 (95% CI, 0.66-0.91); P = 0.01). Quantitative fFN was a strong predictor of spontaneous preterm birth before 30 weeks in women with history-indicated cerclage (AUC, 0.91 (95% CI, 0.75-1.00)) and retained clinical utility in those with ultrasound-indicated cerclage (AUC, 0.76 (95% CI, 0.64-0.89)). There were no spontaneous deliveries before 34 weeks in women with a transabdominal cerclage, so AUC was not calculated. Delivery was delayed significantly in this group (P < 0.01). Cervical length and quantitative fFN retain clinical utility for the prediction of spontaneous preterm birth in women with cervical cerclage, and prediction is best in women with a history-indicated stitch. These tests can be relied upon to discriminate risk and have utility when planning clinical management with regard to treatment failure. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Maternal Plasma RNA in First Trimester Nullipara for the Prediction of Spontaneous Preterm Birth ≤ 32 Weeks: Validation Study

The first-trimester prediction of spontaneous preterm birth (sPTB) has been elusive, and current screening is heavily dependent on obstetric history. However, nullipara lack a relevant history and are at higher risk for spontaneous (s)PTB ≤ 32 weeks compared to multipara. No available objective first-trimester screening test has proven a fair predictor of sPTB ≤ 32 weeks. We questioned whether a panel of maternal plasma cell-free (PCF) RNAs (PSME2, NAMPT, APOA1, APOA4, and Hsa-Let-7g) previously validated at 16-20 weeks for the prediction of sPTB ≤ 32 weeks might be useful in first-trimester nullipara. Sixty (60) nulliparous women (40 with sPTB ≤ 32 weeks) who were free of comorbidities were randomly selected from the King's College Fetal Medicine Research Institute biobank. Total PCF RNA was extracted and the expression of panel RNAs was quantitated by qRT-PCR. The analysis employed, primarily, multiple regression with the main outcome being the prediction of subsequent sPTB ≤ 32 weeks. The test performance was judged by the area under the curve (AUC) using a single threshold cut point with observed detection rates (DRs) at three fixed false positive rates (FPR). The mean gestation was 12.9 ± 0.5 weeks (range 12.0-14.1 weeks). Two RNAs were differentially expressed in women destined for sPTB ≤ 32 weeks: APOA1 (p < 0.001) and PSME2 (p = 0.05). APOA1 testing at 11-14 weeks predicted sPTB ≤ 32 weeks with fair to good accuracy. The best predictive model generated an AUC of 0.79 (95% CI 0.66-0.91) with observed DRs of 41%, 61%, and 79% for FPRs of 10%, 20%, and 30%, including crown-rump length, maternal weight, race, tobacco use, and age.