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Objectives: To determine whether first-trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB), and to develop prediction models using maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risk for sPTB., Methods: This was a retrospective secondary analysis of data derived from a prospective cohort study on first-trimester screening for pre-eclampsia in singleton pregnancies attending for routine Down syndrome screening at 11 + 0 to 13 + 6 weeks' gestation at a tertiary obstetric unit between December 2016 and September 2019. A split-sample internal validation method was used to explore and develop prediction models for all sPTB at < 37 weeks and for PTB at < 37 weeks after preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG). Screening performance was assessed using receiver-operating-characteristics (ROC)-curve analysis, with calculation of the areas under the ROC curves (AUCs)., Results: A total of 9298 singleton pregnancies were included in this study. sPTB at < 37 weeks occurred in 362 (3.89%) cases, including 231 (2.48%) cases of PPROM. sPTB at < 34 weeks occurred in 87 (0.94%) cases, including 39 (0.42%) cases of PPROM. Identified maternal risk factors for sPTB at < 37 weeks included chronic hypertension, conception using in-vitro fertilization and history of PTB. Maternal risk factors for PPROM at < 37 weeks included conception using in-vitro fertilization and history of PTB. Median PlGF multiples of the median (MoM) and PAPP-A MoM were significantly reduced in women with sPTB at < 37 weeks, as well as in those who had PPROM, compared to those who delivered at term. Screening by a combination of maternal risk factors, PAPP-A and PlGF achieved better performance in predicting sPTB at < 37 weeks (AUC, 0.630 vs 0.555; detection rate (DR), 24.8% vs 16.6% at a false-positive rate (FPR) of 10%; P ≤ 0.0001) and PPROM at < 37 weeks (AUC, 0.643 vs 0.558; DR, 28.1% vs 17.0% at a FPR of 10%; P ≤ 0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUCs of 0.628 and 0.650, respectively., Conclusions: We demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM at < 37 weeks. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model that includes maternal risk factors, PAPP-A and PlGF before clinical application. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To estimate the cost-effectiveness of strategies to prevent spontaneous preterm delivery (PTD) in asymptomatic singleton pregnancies, using prevalence and healthcare cost data from the Swedish healthcare context., Methods: We designed a decision analytic model based on the Swedish CERVIX study to estimate the cost-effectiveness of strategies to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy. The model was constructed as a combined decision-tree model and Markov model with a time horizon of 100 years. Four preventive strategies, namely 'Universal screening', 'High-risk-based screening' (i.e. screening of high-risk women only), 'Low-risk-based screening' (i.e. treatment of high-risk population and screening of remaining women) and 'Nullipara screening' (i.e. treatment of high-risk population and screening of nulliparous women only), included second-trimester cervical length (CL) screening by transvaginal ultrasound followed by vaginal progesterone treatment in the case of a short cervix. A fifth preventive strategy involved vaginal progesterone treatment of women with previous spontaneous PTD or late miscarriage but no CL screening ('No screening, treat high-risk group'). For comparison, we used a sixth strategy implying no specific intervention to prevent spontaneous PTD, reflecting the current situation in Sweden ('No screening'). Probabilities for a short cervix (CL ≤ 25 mm; base-case) and for spontaneous PTD at < 33 + 0 weeks and at 33 + 0 to 36 + 6 weeks were derived from the CERVIX study, and probabilities for stillbirth, neonatal mortality and long-term morbidity (cerebral palsy) from Swedish health data registers. Costs were based on Swedish data, except costs for cerebral palsy, which were based on Danish data. We assumed that vaginal progesterone reduces spontaneous PTD before 33 weeks by 30% and spontaneous PTD at 33-36 weeks by 10% (based on the literature). All analyses were from a societal perspective. We expressed the effectiveness of each strategy as gained quality-adjusted life years (QALYs) and presented cost-effectiveness as average (ACER; average cost per gained QALY compared with 'No screening') and incremental (ICER; difference in costs divided by the difference in QALYs for each of two strategies being compared) cost-effectiveness ratios. We performed deterministic and probabilistic sensitivity analysis. The results of the latter are shown as cost-effectiveness acceptability curves. Willingness-to-pay was set at a maximum of 500 000 Swedish krona (56 000 US dollars (USD)), as suggested by the Swedish National Board of Health and Welfare., Results: All interventions had better health outcomes than did 'No screening', with fewer screening-year deaths and more lifetime QALYs. The best strategy in terms of improved health outcomes was 'Low-risk-based screening', irrespective of whether screening was performed at 18 + 0 to 20 + 6 weeks (Cx1) or at 21 + 0 to 23 + 6 weeks (Cx2). 'Low-risk-based screening' at Cx1 was cost-effective, while 'Low-risk-based screening' at Cx2 entailed high costs compared with other alternatives. The ACERs were 2200 USD for 'Low-risk-based screening' at Cx1 and 36 800 USD for 'Low-risk-based screening' at Cx2. Cost-effectiveness was particularly sensitive to progesterone effectiveness and to productivity loss due to sick leave during pregnancy. The probability that 'Low-risk-based screening' at Cx1 is cost-effective compared with 'No screening' was 71%., Conclusion: Interventions to prevent spontaneous PTD in asymptomatic women with a singleton pregnancy, including CL screening with progesterone treatment of cases with a short cervix, may be cost-effective in Sweden. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: Pre-eclampsia (PE) causes substantial maternal and neonatal mortality and morbidity. In addition to the personal impact on women, children and their families, PE has a significant economic impact on our society. Recent research suggests that a first-trimester multivariate model is highly predictive of preterm (< 37 weeks' gestation) PE and can be combined successfully with targeted prophylaxis (low-dose aspirin), resulting in an 80% reduction in prevalence of disease. The aim of this study was to examine the potential health outcomes and cost implications following introduction of first-trimester prediction and prevention of preterm PE within a public healthcare setting, compared with usual care, and to conduct a cost-effectiveness analysis to inform health-service decisions regarding implementation of such a program., Methods: A decision-analytic model was used to compare usual care with the proposed first-trimester screening intervention within the obstetric population (n = 6822) attending two public hospitals within a metropolitan district health service in New South Wales, Australia, between January 2015 and December 2016. The model, applied from early pregnancy, included exposure to a variety of healthcare professionals and addressed type of risk assessment (usual care or first-trimester screening) and use of (compliance with) low-dose aspirin prescribed prophylactically for prevention of PE. All pathways culminated in six possible health outcomes, ranging from no PE to maternal death. Results were presented as the number of cases of PE gained/avoided and the incremental increase/decrease in economic costs arising from the intervention compared with usual care. Significant assumptions were tested in sensitivity/uncertainty analyses., Results: The intervention produced, across all gestational ages, 31 fewer cases of PE and reduced aggregate economic health-service costs by 1 431 186 Australian dollars over the 2-year period. None of the tested iterations of uncertainty analyses reported additional cases of PE or higher economic costs. The new intervention based on first-trimester screening dominated usual care., Conclusion: This cost-effectiveness analysis demonstrated a reduction in prevalence of preterm PE and substantial cost savings associated with a population-based program of first-trimester prediction and prevention of PE, and supports implementation of such a policy. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: The aim of this national study was to examine the incidence of preterm pre-eclampsia (PE) and the proportion of women with risk factors for PE, according to the criteria suggested by the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG), during a 10-year period in Denmark., Methods: Data from The Danish National Patient Registry and the Danish Medical Birth Registry were used to obtain the incidence of preterm PE with delivery < 37 weeks' gestation and risk factors for PE for all deliveries in Denmark from 1 January 2008 to 31 December 2017. The proportion of women with at least one high-risk factor and/or at least two moderate-risk factors for PE, according to the NICE and ACOG criteria, and the detection rate for preterm PE were examined. Race, socioeconomic status and the woman's weight at birth were not available from the registries used, and information on Type-2 diabetes was found to be invalid., Results: Of the 597 492 deliveries during the study period, any PE was registered in 3.2%, preterm PE < 37 weeks in 0.7% and early-onset PE < 34 weeks' gestation in 0.3%. These proportions remained largely unchanged from 2008 to 2017. Overall, the NICE criteria were fulfilled in 7.5% of deliveries and the ACOG criteria in 17.3%. In the total population, the NICE criteria identified 47.6% of those with preterm PE and the ACOG criteria identified 60.5%. The current criteria for offering aspirin treatment in Denmark largely correspond to having at least one NICE high-risk factor. In 2017, a total of 3.5% of deliveries had at least one NICE high-risk factor, which identified 28.4% of cases that later developed preterm PE., Conclusions: The incidence of preterm PE remained largely unchanged in Denmark from 2008 to 2017. Prediction of PE according to high-risk maternal factors could be improved by addition of moderate-risk factors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal-Perinatal Medicine (SONPM) National Perinatal COVID-19 Registry., Methods: This was an analysis of data from the PAN-COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP-SONPM National Perinatal COVID-19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection., Results: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP-SONPM). For obstetric outcomes, in PAN-COVID overall and in those with confirmed infection in PAN-COVID and AAP-SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (< 37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.1% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP-SONPM. Extreme preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP-SONPM. Neonatal SARS-CoV-2 infection was reported in 0.9% of all deliveries in PAN-COVID overall, in 2.0% in those with confirmed infection in PAN-COVID and in 1.8% in AAP-SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a small-for-gestational-age (SGA) neonate were 8.2% in PAN-COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP-SONPM. Mean gestational-age-adjusted birth-weight Z-scores were -0.03 in PAN-COVID and -0.18 in AAP-SONPM., Conclusions: The findings from the UK and USA registries of pregnancies with SARS-CoV-2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN-COVID study, although not in the AAP-SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS-CoV-2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess the accuracy of placental alpha microglobulin-1 (PAMG-1), fetal fibronectin (fFN) and phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1) tests in predicting spontaneous preterm birth (sPTB) within 7 days of testing in women with symptoms of preterm labor, through a systematic review and meta-analysis of the literature. The test performance of each biomarker was also assessed according to pretest probability of sPTB ≤ 7 days., Methods: The Cochrane, MEDLINE, PubMed and ResearchGate bibliographic databases were searched from inception until October 2017. Cohort studies that reported on the predictive accuracy of PAMG-1, fFN and phIGFBP-1 for the prediction of sPTB within 7 days of testing in women with symptoms of preterm labor were included. Summary receiver-operating characteristics (ROC) curves and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive (LR+) and negative (LR-) likelihood ratios were generated using indirect methods for the calculation of pooled effect sizes with a bivariate linear mixed model for the logit of sensitivity and specificity, with each diagnostic test as a covariate, as described by the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy., Results: Bivariate mixed model pooled sensitivity of PAMG-1, fFN and phIGFBP-1 for the prediction of sPTB ≤ 7 days was 76% (95% CI, 57-89%), 58% (95% CI, 47-68%) and 93% (95% CI, 88-96%), respectively; pooled specificity was 97% (95% CI, 95-98%), 84% (95% CI, 81-87%) and 76% (95% CI, 70-80%) respectively; pooled PPV was 76.3% (95% CI, 69-84%) (P < 0.05), 34.1% (95% CI, 29-39%) and 35.2% (95% CI, 31-40%), respectively; pooled NPV was 96.6% (95% CI, 94-99%), 93.3% (95% CI, 92-95%) and 98.7% (95% CI, 98-99%), respectively; pooled LR+ was 22.51 (95% CI, 15.09-33.60) (P < 0.05), 3.63 (95% CI, 2.93-4.50) and 3.80 (95% CI, 3.11-4.66), respectively; and pooled LR- was 0.24 (95% CI, 0.12-0.48) (P < 0.05), 0.50 (95% CI, 0.39-0.64) and 0.09 (95% CI, 0.05-0.16), respectively. The areas under the ROC curves for PAMG-1, fFN and phIGFBP-1 for sPTB ≤ 7 days were 0.961, 0.874 and 0.801, respectively., Conclusions: In the prediction of sPTB within 7 days of testing in women with signs and symptoms of preterm labor, the PPV of PAMG-1 was significantly higher than that of phIGFBP-1 or fFN. Other diagnostic accuracy measures did not differ between the three biomarker tests. As prevalence affects the predictive performance of a diagnostic test, use of a highly specific assay for a lower-prevalence syndrome such as sPTB may optimize management. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: New tools are required to improve the identification of women who are at increased risk for spontaneous preterm birth (sPTB). Quantitative analysis of tissue texture on ultrasound has been used to extract robust features from the ultrasound image to detect subtle changes in its microstructure. This may be applied to the cervix. The aim of this study was to determine if there is an association between quantitative analysis of cervical texture (CTx) on mid-trimester ultrasound and sPTB < 37 + 0 weeks' gestation., Methods: This was a single-center nested case-control study of a prospective cohort of 677 consecutive women with singleton pregnancy assessed between 19 + 0 and 24 + 6 weeks' gestation. Women at increased risk for sPTB were included unless they received treatment to prevent sPTB. Women who delivered < 37 + 0 weeks (sPTB) were considered as cases and were matched in a 1: 10 ratio with randomly selected contemporary controls who delivered at term. For each woman, one ultrasound image of the cervix was obtained for which quality was assessed, cervical length (CL) measured offline and a region of interest in the midportion of the anterior cervical lip delineated for use in local binary patterns analysis of CTx. A learning algorithm was developed to obtain the combination of CTx features best associated with sPTB based on feature transformation and discriminant analysis regression. The ability of the learning algorithm to predict sPTB was evaluated using a leave-one-out cross-validation technique, which produced a CTx-based score for each participant. Receiver-operating characteristics (ROC) curves were produced and sensitivity, specificity, and positive and negative likelihood ratios were calculated for the optimal cut-off based on the ROC curve. The results were compared with those obtained for CL. Investigators studying the images were blinded to pregnancy outcome at all times., Results: Images from 310 women (27 cases and 283 controls) were of sufficient quality and included in the study. Median CTx-based score was significantly lower in cases compared with controls (-1.01 vs -0.07, P ≤ 0.0001). CTx-based score maintained its significant association with sPTB after adjusting for possible confounders (history of sPTB, conization or Müllerian malformation, and CL < 25 mm). CTx-based score was a better predictor of sPTB (AUC, 0.77; 95% CI, 0.66-0.87) than was CL (AUC, 0.60; 95% CI, 0.47-0.72) (P = 0.03). Median CL was similar for cases and controls (37.7 vs 38.6 mm, P = 0.26), although cases were more likely to have CL < 25 mm (18.5% vs 0.4%, P < 0.001)., Conclusion: Quantitative analysis of CTx enables the extraction of information relevant to sPTB from ultrasound images to generate a CTx-based score that is associated independently with sPTB. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To assess cervical length (CL) longitudinally between the first and second trimesters and to determine the proportion of women with short CL. The study also aimed to assess if women with short CL at 19-24 weeks' gestation could be identified at the time of combined first-trimester screening (cFTS) at 11-14 weeks' gestation, in order to determine the potential value of implementation of CL screening for prediction of preterm delivery in a Danish population., Methods: This was a prospective longitudinal study of women with singleton pregnancy attending three University Hospitals in Denmark for combined first-trimester screening from 1 November 2013 to 1 December 2014. Exclusion criteria were multiple pregnancy, uterine anomaly, cerclage or progesterone treatment at inclusion. CL was measured on transvaginal sonography at 11-14 weeks (Cx1), 19-21 weeks (Cx2) and 23-24 weeks (Cx3), by trained operators as a straight line from external to internal os. Women with CL ≤ 25 mm were referred to a maternal-fetal medicine specialist for treatment according to a standardized management protocol., Results: Of the 4904 eligible women, 3477 (71%) participated and had Cx1 recorded. Of those, 3232 (93.0%) had CL measured on all three scans. Median Cx1 was 37 mm, and median Cx2 and Cx3 were 40 mm. The proportion of women with CL ≤ 25 mm increased with gestational age, from 0.41% (95% CI, 0.19-0.62%) at Cx1 to 1.79% (95% CI, 1.34-2.24%) at Cx3. In total, the proportion of women with second-trimester CL (Cx2 or Cx3) ≤ 25 mm was 2.0% (n = 67), of which 38.8% (n = 26) were detected at 19-21 weeks. The probability of short CL between 19 and 24 weeks was greater for those with shorter first-trimester CL. It was nearly nine-fold higher for women with Cx1 ≤ 25 mm compared with Cx1 ≥ 35 mm (17% vs 2%). The performance of Cx1 for prediction of short second-trimester CL was 50% at a 10% false-positive rate. It was found that more than 1500 women would need to be screened for short CL at 19-21 weeks to prevent one case of spontaneous preterm delivery before 34 weeks in a population such as the one in this study., Conclusions: There is an association between first-trimester CL and risk of short cervix in the second trimester. Once short CL was observed, risk of preterm delivery was greatly increased. However, whether universal CL screening should be implemented in this low-risk population depends on cost-benefit analysis taking into account the low proportions of women with short CL and at risk for preterm delivery. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To investigate the effectiveness of mid-trimester sonographic cervical consistency index (CCI) for the prediction of spontaneous preterm birth (sPTB) in low-risk pregnancies and to compare its performance with that of mid-trimester sonographic cervical-length (CL) measurement., Methods: This was a prospective cohort study of women with a singleton pregnancy examined by ultrasound at 19 + 0 to 24 + 6 weeks' gestation. All women underwent transvaginal ultrasound examination of the cervix, but CCI and CL were measured, offline, only in women without a risk factor for sPTB. Staff and participants were blinded to CL and CCI results. CCI was obtained by calculating the ratio between the anteroposterior diameter of the uterine cervix at maximum compression and at rest. The primary outcome was prediction of sPTB before 37 + 0 weeks. Receiver-operating characteristics (ROC) curves were produced and sensitivity and specificity were calculated for the optimal cut-off based on the ROC curve and for the 1 st , 5 th and 10 th centiles of CCI and CL. Intraclass correlation coefficients (ICC) and Bland-Altman plots were used to estimate intra- and interobserver agreement and reliability for measurement of CCI and CL., Results: Of the 749 women who underwent ultrasound examination of the cervix, 532 were included for analysis. The rates of sPTB before 37 + 0 and before 34 + 0 weeks were 4.1% (22/532) and 1.3% (7/532), respectively. The rates of short cervix < 25 mm and ≤ 20 mm were 0.9% (5/532) and 0.4% (2/532), respectively. The area under the ROC curve (AUC) with regard to predicting sPTB before 37 + 0 weeks was 0.84 (95% CI, 0.75-0.93) for CCI compared with 0.68 (95% CI, 0.56-0.81) for CL (P = 0.03). The optimal cut-off based on the ROC curve was 64.6% for CCI (sensitivity, 77.3%; specificity, 82.7%) and that for CL was 37.9 mm (sensitivity, 72.7%; specificity, 61.2%). The AUC with regard to predicting sPTB before 34 + 0 weeks was 0.87 (95% CI, 0.71-1.0) for CCI compared with 0.71 (95% CI, 0.47-0.94) for CL (P = 0.25). The optimal cut-off based on the ROC curve was 63.6% for CCI (sensitivity, 85.7%; specificity, 84.0%) and that for CL was 37.9 mm (sensitivity, 85.7%; specificity, 61.3%). Intraobserver ICC was > 0.90 both for CCI and CL, while interobserver ICC was 0.89 for CCI and 0.90 for CL., Conclusions: Second-trimester CCI is a better predictor of sPTB < 37 weeks in low-risk pregnancies than is CL. External validation is needed as well as studies assessing the value of CCI as a screening tool in unselected and high-risk populations. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To assess the predictive value of sonographic cervical-length (CL) measurement in mid-gestation for spontaneous preterm birth (PTB) in asymptomatic triplet pregnancy., Methods: This was a retrospective study of asymptomatic triplet pregnancies followed at five Italian tertiary referral centers, between 2002 and 2015. CL was measured transvaginally between 18 and 24 weeks' gestation. Pregnancies with medically indicated PTB were excluded. Demographic and pregnancy characteristics of pregnancies complicated by PTB were analyzed and the distributions of CL measurements in these patients were calculated. Logistic regression analysis was performed to assess the association between CL and PTB, adjusted for confounders. Performance of CL measurement in prediction of PTB < 28, < 30 and < 32 weeks of gestation was assessed., Results: A total of 120 triplet pregnancies were included in the final analysis. Median CL was 35 (interquartile range (IQR), 29-40) mm measured at a median gestational age of 20 + 2 (IQR, 20 + 0 to 23 + 4) weeks. Overall, 23 (19.2%), 17 (14.2%) and eight (6.7%) patients had a CL < 25, < 20 and < 15 mm, respectively. Spontaneous PTB < 32 weeks occurred in 41 (34.2%) cases, < 30 weeks in 23 (19.2%) and < 28 weeks in 12 (10%) cases. CL < 15 mm was significantly more frequent in the group of patients who delivered < 28 (P = 0.03) and < 30 (P = 0.01) weeks' gestation, compared with those who delivered after 28 and after 30 weeks, respectively, while CL < 20 mm was more common in triplet pregnancies with delivery < 32 weeks compared with those delivered ≥ 32 weeks (P = 0.03). Logistic regression analysis was possible only for PTB < 32 weeks due to the small number of cases that delivered < 30 and < 28 weeks. After adjustment for confounders, CL was not significantly associated with PTB < 32 weeks (adjusted odds ratio, 0.97; 95% CI, 0.94-1.01). CL measurement had an area under the receiver-operating characteristics curve of 0.41 (95% CI, 0.20-0.62), 0.41 (95% CI, 0.26-0.56) and 0.42 (95% CI, 0.31-0.54) for the prediction of spontaneous PTB < 28, < 30 and < 32 weeks, respectively., Conclusion: CL assessed in mid-gestation is a poor predictor of PTB < 28, < 30 and < 32 weeks' gestation in asymptomatic triplet pregnancy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To compare the performance of the placental alpha microglobulin-1 (PAMG-1) and fetal fibronectin (fFN) tests for the prediction of spontaneous preterm delivery in patients presenting to an emergency obstetric unit with threatened preterm labor, by conducting a retrospective audit of patient medical records from separate 1-year periods during which either fFN or PAMG-1 was used as the standard-of-care biochemical test., Methods: This was a retrospective cohort study based on chart review of electronic medical records of women with threatened preterm labor presenting at a level-III maternity hospital over two different periods: (1) the 'baseline' period (year 2012), during which the qualitative fFN test with a cut-off of 50 ng/mL was used as the standard-of-care biochemical test for the risk assessment of preterm delivery, and (2) the 'comparative' period (year 2016), during which the PAMG-1 test with a cut-off of 1 ng/mL was used as the standard-of-care biomarker test. Patients with a singleton pregnancy between 24 + 0 and 34 + 6 weeks' gestation with symptoms of early preterm labor, clinically intact membranes and cervical dilatation < 3 cm, who did not have a medically indicated preterm delivery within 14 days of testing, were selected for chart review and included in the analysis. Key parameters used for the analysis were biochemical test results, time of testing and time of delivery. Positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and positive and negative likelihood ratios (LR+ and LR-) for the prediction of spontaneous preterm delivery ≤ 7 and ≤ 14 days of presentation were calculated for the PAMG-1 and fFN tests., Results: Four hundred and twenty patients were identified as having presented with threatened preterm labor during the baseline period, of whom 378 (90.0%) met the eligibility criteria. Of these, 38 (10.1%) were fFN positive and 10 (2.6%) had spontaneous preterm delivery ≤ 7 days of presentation. PPV, NPV, LR+ and LR- of fFN were 7.9%, 97.9%, 3.2 and 0.8, respectively, for spontaneous preterm delivery ≤ 7 days. Four hundred and ten patients were identified as having presented with threatened preterm labor during the comparative period and 367 (89.5%) subjects met the eligibility criteria. Of these, 17 (4.6%) were PAMG-1 positive and 12 (3.3%) had spontaneous preterm delivery ≤ 7 days of presentation. PAMG-1 PPV and NPV were 35.3% and 98.3%, respectively, and LR+ and LR- were 16.1 and 0.5, respectively, for spontaneous preterm delivery ≤ 7 days., Conclusions: Before switching to PAMG-1, fFN was the standard-of-care test for the risk assessment of spontaneous preterm delivery. This retrospective audit of each test's performance over separate 1-year periods shows that we were more than twice as likely to get a positive fFN test than a positive PAMG-1 test, while the rate of discharging women who ultimately delivered spontaneously within 14 days of testing was not affected. Furthermore, a positive PAMG-1 test was more than four times more reliable than a positive fFN test in predicting imminent spontaneous preterm delivery. The use of a more reliable biomarker that is associated with fewer false-positive results could lead to a reduction in unnecessary admissions, interventions and use of hospital resources. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To investigate whether, in pregnancies complicated by spontaneous preterm delivery, fetal fraction of cell-free DNA (cfDNA) in maternal plasma at 11-13 weeks' gestation is altered and if this measurement could be useful in the prediction of preterm delivery., Methods: Fetal fraction of cfDNA was measured at 10 + 0 to 13 + 6 weeks' gestation in 3169 pregnancies, 3066 (96.7%) that delivered at ≥ 37 weeks and 103 (3.3%) with spontaneous delivery at < 37 weeks, including 21 that delivered at < 34 weeks and 82 that delivered at 34-37 weeks. The measured fetal fraction was converted to multiples of the median (MoM), corrected for maternal characteristics and gestational age, and the Mann-Whitney U-test was used to determine the significance of differences in the median values in the spontaneous preterm delivery groups from that in the term delivery group., Results: In the spontaneous preterm delivery groups (< 34 weeks' gestation, 34-37 weeks, < 37 weeks), compared to the term delivery group, there was no significant difference in the median fetal fraction MoM (1.004, 0.922 and 0.946, respectively, vs 1.015)., Conclusion: Measurement of fetal fraction in maternal plasma at 11-13 weeks' gestation is not predictive of spontaneous preterm delivery., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: The aim of this study was to evaluate the efficacy of the test for the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 (phIGFBP-1) in endocervical secretions in predicting preterm delivery in women with uterine contractions., Methods: The study included 210 women with a singleton pregnancy with documented uterine contractions and intact membranes at between 24 and 34 weeks' gestation who underwent the cervicovaginal phIGFBP-1 test and transvaginal sonographic measurement of cervical length. A receiver-operating characteristics (ROC) curve was used to determine the most useful cut-off point for cervical length. A multivariate logistic regression model was used in order to analyze the combination of significant predictive variables for preterm delivery following univariate analysis., Results: ROC curves indicated that 26 mm was the optimal cut-off value for cervical length in predicting preterm delivery. A cervical length of < 26 mm and the presence of phIGFBP-1 were statistically significant in univariate logistic regression analyses (P < 0.0001) with odds ratios of 16.18 and 9.29 for preterm delivery, respectively. Multivariate analysis of cervical length and phIGFBP-1 showed that they were independent and therefore useful in combination for predicting preterm delivery., Conclusions: Cervical length and the phIGFBP-1 test are independent variables that can be used together to predict preterm delivery in women with uterine contractions. A sonographically measured cervical length of > 26 mm with a negative phIGFBP-1 test in a patient with regular uterine contractions before 37 weeks' gestation seems to indicate a low risk of preterm delivery and may therefore allow avoidance of unnecessary therapies.

Objective: To evaluate whether measurement of the thickness of the fetal membranes by high-resolution ultrasound is a useful marker to predict preterm delivery., Methods: One hundred and fifty-eight women with singleton pregnancies at 18-35 gestational weeks were enrolled consecutively at our referral center for obstetric care and the thickness of their fetal membranes was measured using high-resolution ultrasound equipment. Data were analyzed to determine whether there were significant differences between those delivering at term and those delivering preterm. Receiver-operating characteristics (ROC) curves were used to determine the best cut-off point of membrane thickness for predicting preterm birth., Results: Women who delivered preterm had greater fetal membrane thickness than did those who delivered at term (1.67 +/- 0.27 mm vs. 1.14 +/- 0.30 mm, P < 0.0001). For the best cut-off indicated by ROC curve analysis (1.2 mm), the sensitivity and specificity for predicting preterm birth were 100% (95% CI, 80.3-100) and 69.5% (95% CI, 61.2-77.0), respectively, and positive and negative likelihood ratios were 3.3 and 0.0, respectively., Conclusion: Sonographic measurement of fetal membrane thickness could be helpful in the prediction of preterm delivery., ((c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.)

Objectives: To evaluate the ability of combinations of cervical length and maternal history to assess the risk of spontaneous preterm birth, and to provide a simple procedure for the optimal estimation of risk., Methods: This prospective observational study was carried out between January 1998 and May 2006. Transvaginal sonographic measurement of cervical length at 20 + 0 to 24 + 6 weeks of gestation was carried out in 58 807 singleton pregnancies as part of routine antenatal care. The outcome measure was spontaneous extreme (< 28 weeks), early (28-30 weeks), moderate (31-33 weeks) and mild (34-36 weeks) preterm birth. Logistic regression analysis was used to derive models for the prediction of spontaneous preterm birth from the maternal obstetric history, demographic characteristics and cervical length., Results: The rates of extreme, early, moderate and mild spontaneous preterm birth were 0.23%, 0.24%, 0.57% and 2.93%, respectively. The best prediction of spontaneous preterm birth was provided by cervical length (area under the receiver-operating characteristics curve (AUC), extreme 0.903, early 0.816, moderate 0.784 and mild 0.617) and this was improved by adding obstetric history (AUC, extreme 0.919, early 0.836, moderate 0.819 and mild 0.650). Addition of other parameters was without material effect. For a 10% screen-positive rate, models using cervical length and obstetric history had a sensitivity of 80.6%, 58.5%, 53.0% and 28.6% for extreme, early, moderate and mild spontaneous preterm birth, respectively. These models were expressed as tables of adjusted likelihood ratios to allow simple estimation of the risk of spontaneous preterm birth., Conclusions: A model combining cervical length and obstetric history provides a better prediction of spontaneous preterm birth than either factor alone, and the sensitivity of screening improves for increasing degrees of prematurity., (Copyright (c) 2008 ISUOG)

Objectives: To examine the clinical utility of the first-trimester markers of aneuploidy in their ability to predict preterm delivery., Methods: We examined 54 722 singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the median (MoM) of the expected normal median for a pregnancy of the same gestation and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown-rump length. The association between free beta-hCG, PAPP-A and delta NT and the incidence of preterm delivery before 37 weeks or early preterm delivery before 34 weeks was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratios (LR) for preterm delivery and early preterm delivery were also calculated after excluding other adverse pregnancy complications., Results: The risk of preterm delivery increased with decreasing maternal serum PAPP-A. In the 3132 cases delivering before 37 weeks the PAPP-A MoM was 0.91 and in the 1060 cases delivering before 34 weeks the PAPP-A MoM was 0.90. At the 5th centile of the normal outcome group for PAPP-A (0.415 MoM) the odds ratios for delivery before 37 weeks and before 34 weeks were 1.92 and 2.35, respectively. The respective values for the 5th centile of free beta-hCG (0.41 MoM) were 1.18 and 1.08 and for the 95th centile of delta NT they were 0.91 and 0.77, respectively., Conclusions: Low levels of maternal serum PAPP-A are associated, in the absence of an abnormal karyotype, with an increased risk of preterm or early preterm delivery. The LR profiles provided at various levels of PAPP-A may be of some help in counseling women with such results and may raise awareness among healthcare professionals for increased surveillance in such cases., (Copyright (c) 2007 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To evaluate the efficacy of cervical length measurement in combination with a bedside assessment of phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1) as a predictor of preterm delivery in asymptomatic pregnant women with a history of preterm birth., Methods: Cervical length was measured using transvaginal sonography at 22-24 weeks of gestation in 105 singleton pregnancies and a rapid strip test was performed to detect phIGFBP-1 in cervical secretions from 24 to 34 weeks. Receiver-operating characteristics (ROC) curves were constructed to compare the performance of phIGFBP-1 at different gestational ages, and cervical length at 22-24 weeks, in predicting preterm delivery., Results: The rate of spontaneous delivery before 37 and 34 weeks was 23.8% and 11.4%, respectively. Women with cervical lengths less than 20 mm had a risk of spontaneous preterm delivery before 34 and 37 weeks of 43.5% and 69.6%, respectively. The performance of phIGFBP-1 levels as a predictor of preterm delivery was significantly higher when the test was carried out at 30 weeks' gestation. Cervical assessment in combination with phIGFBP-1 at 30 weeks had the steepest ROC curve (area under the curve=0.93; 95% CI, 0.88-0.98, P<0.001)., Conclusion: Both cervical length and phIGFBP-1 measurement are useful in the prediction of preterm delivery in patients with a history of preterm birth and the combined method of measuring cervical length at 22-24 weeks and phIGFBP-1 at 30 weeks improves upon either method used alone., (Copyright (c) 2007 ISUOG.)