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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Clinicians' experiences of using and implementing a medical mobile phone app (QUiPP V2) designed to predict the risk of preterm birth and aid clinical decision making.

BACKGROUND: As the vast majority of women who present in threatened preterm labour (TPTL) will not deliver early, clinicians need to balance the risks of over-medicalising the majority of women, against the potential risk of preterm delivery for those discharged home. The QUiPP app is a free, validated app which can support clinical decision-making as it produces individualised risks of delivery within relevant timeframes. Recent evidence has highlighted that clinicians would welcome a decision-support tool that accurately predicts preterm birth. METHODS: Qualitative interviews were undertaken as part of the EQUIPTT study (The Evaluation of the QUiPP app for Triage and Transfer) (REC: 17/LO/1802) which aimed to evaluate the impact of the QUiPP app on management of TPTL. Individual semi-structured telephone interviews were used to explore clinicians' (obstetricians' and midwives') experiences of using the QUiPP app and how it was implemented at their hospital sites. Thematic analysis was chosen to explore the meaning of the data, through a framework approach. RESULTS: Nineteen participants from 10 hospital sites in England took part. Data analysis revealed three overarching themes which were: 'experience of using the app', 'how QUiPP risk changes practice' and 'successfully adopting QUiPP: context is everything'. With these final themes we appeared to have achieved our aim of exploring the clinicians' experiences of using and implementing the QUiPP app. CONCLUSION: This study explored different clinician's experiences of implementing the app. The organizational and cultural context at different sites appeared to have a large impact on how well the QUiPP app was implemented. Future work needs to be undertaken to understand how best to embed the intervention within different settings. This will inform scale up of QUiPP app use across the UK and ensure that clinicians have access to this free, easy-to-use tool which can positively aid clinical decision making when caring for women in TPTL. CLINICAL TRIAL REGISTRY AND REGISTRATION NUMBER: ISRCTN 17846337, registered 08th January 2018, https://doi.org/10.1186/ISRCTN17846337 .

Placental growth factor in suspected preterm pre-eclampsia: a review of the evidence and practicalities of implementation.

Despite extensive research, the pathophysiology and prevention of pre-eclampsia remain elusive, diagnosis is challenging, and pre-eclampsia remains associated with adverse maternal and perinatal outcomes. Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), have been identified as valuable biomarkers for preterm pre-eclampsia, accelerating diagnosis and reducing maternal adverse outcomes by risk stratification, with enhanced surveillance for high-risk women. PlGF-based testing is increasingly being implemented in clinical practice in several countries. This review provides healthcare providers with an understanding of the evidence for PlGF-based testing and describes the practicalities and challenges to implementation. TWEETABLE ABSTRACT: Placental growth factor in pre-eclampsia: evidence and implementation of testing.

Incidence and characteristics of pregnancy-related death across ten low- and middle-income geographical regions: secondary analysis of a cluster randomised controlled trial.

OBJECTIVE: The aim of this article is to describe the incidence and characteristics of pregnancy-related death in low- and middle-resource settings, in relation to the availability of key obstetric resources. DESIGN: This is a secondary analysis of a stepped-wedge cluster randomised controlled trial. SETTING: This trial was undertaken at ten sites across eight low- and middle-income countries in sub-Saharan Africa, India and Haiti. POPULATION: Institutional-level consent was obtained and all women presenting for maternity care were eligible for inclusion. METHODS: Pregnancy-related deaths were collected prospectively from routine data sources and active case searching. MAIN OUTCOME MEASURES: Pregnancy-related death, place, timing and age of maternal death, and neonatal outcomes in women with this outcome. RESULTS: Over 20 months, in 536 233 deliveries there were 998 maternal deaths (18.6/10 000, range 28/10 000-630/10 000). The leading causes of death were obstetric haemorrhage (36.0%, n = 359), hypertensive disorders of pregnancy (20.6%, n = 206), sepsis (14.1%, n = 141) and other (26.5%, n = 264). Approximately a quarter of deaths occurred prior to delivery (28.4%, n = 283), 35.7% (n = 356) occurred on the day of delivery and 35.9% (n = 359) occurred after delivery. Half of maternal deaths (50.6%; n = 505) occurred in women aged 20-29 years, 10.3% (n = 103) occurred in women aged under 20 years, 34.5% (n = 344) occurred in women aged 30-39 years and 4.6% (n = 46) occurred in women aged ≥40 years. There was no measured association between the availability of key obstetric resources and the rate of pregnancy-related death. CONCLUSIONS: The large variation in the rate of pregnancy-related death, irrespective of resource availability, emphasises that inequality and inequity in health care persists. TWEETABLE ABSTRACT: Inequality and inequity in pregnancy-related death persists globally, irrespective of resource availability.

Development and validation of predictive models for QUiPP App v.2: tool for predicting preterm birth in asymptomatic high-risk women.

OBJECTIVES: Accurate mid-pregnancy prediction of spontaneous preterm birth (sPTB) is essential to ensure appropriate surveillance of high-risk women. Advancing the QUiPP App prototype, QUiPP App v.2 aimed to provide individualized risk of delivery based on cervical length (CL), quantitative fetal fibronectin (qfFN) or both tests combined, taking into account further risk factors, such as multiple pregnancy. Here we report development of the QUiPP App v.2 predictive models for use in asymptomatic high-risk women, and validation using a distinct dataset in order to confirm the accuracy and transportability of the QUiPP App, overall and within specific clinically relevant time frames. METHODS: This was a prospective secondary analysis of data of asymptomatic women at high risk of sPTB recruited in 13 UK preterm birth clinics. Women were offered longitudinal qfFN testing every 2-4 weeks and/or transvaginal ultrasound CL measurement between 18 + 0 and 36 + 6 weeks' gestation. A total of 1803 women (3878 visits) were included in the training set and 904 women (1400 visits) in the validation set. Prediction models were created based on the training set for use in three groups: patients with risk factors for sPTB and CL measurement alone, with risk factors for sPTB and qfFN measurement alone, and those with risk factors for sPTB and both CL and qfFN measurements. Survival analysis was used to identify the significant predictors of sPTB, and parametric structures for survival models were compared and the best selected. The estimated overall probability of delivery before six clinically important time points (< 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks after testing) was calculated for each woman and analyzed as a predictive test for the actual occurrence of each event. This allowed receiver-operating-characteristics curves to be plotted, and areas under the curve (AUC) to be calculated. Calibration was performed to measure the agreement between expected and observed outcomes. RESULTS: All three algorithms demonstrated high accuracy for the prediction of sPTB at < 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks of testing, with AUCs between 0.75 and 0.90 for the use of qfFN and CL combined, between 0.68 and 0.90 for qfFN alone, and between 0.71 and 0.87 for CL alone. The differences between the three algorithms were not statistically significant. Calibration confirmed no significant differences between expected and observed rates of sPTB within 4 weeks and a slight overestimation of risk with the use of CL measurement between 22 + 0 and 25 + 6 weeks' gestation. CONCLUSIONS: The QUiPP App v.2 is a highly accurate prediction tool for sPTB that is based on a unique combination of biomarkers, symptoms and statistical algorithms. It can be used reliably in the context of communicating to patients the risk of sPTB. Whilst further work is required to determine its role in identifying women requiring prophylactic interventions, it is a reliable and convenient screening tool for planning follow-up or hospitalization for high-risk women. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Development and validation of predictive models for QUiPP App v.2: tool for predicting preterm birth in women with symptoms of threatened preterm labor.

OBJECTIVE: To develop enhanced prediction models to update the QUiPP App prototype, a tool providing individualized risk of spontaneous preterm birth (sPTB), for use in women with symptoms of threatened preterm labor (TPTL), incorporating risk factors, transvaginal ultrasound assessment of cervical length (CL) and cervicovaginal fluid quantitative fetal fibronectin (qfFN) test results. METHODS: Participants were pregnant women between 23 + 0 and 34 + 6 weeks' gestation with symptoms of TPTL, recruited as part of four prospective cohort studies carried out at 16 UK hospitals between October 2010 and October 2017. The training set comprised all women whose outcomes were known in May 2017 (n = 1032). The validation set comprised women whose outcomes were gathered between June 2017 and March 2018 (n = 506). Parametric survival models were developed for three combinations of predictors: risk factors plus qfFN test results alone, risk factors plus CL alone, and risk factors plus both qfFN and CL. The best models were selected using the Akaike and Bayesian information criteria. The estimated probability of sPTB < 30, < 34 or < 37 weeks' gestation and within 1 or 2 weeks of testing was calculated and receiver-operating-characteristics (ROC) curves were created to demonstrate the diagnostic ability of the prediction models. RESULTS: Predictive statistics were similar between the training and the validation sets at most outcome time points and for each combination of predictors. Areas under the ROC curves (AUC) demonstrated that all three algorithms had good accuracy for the prediction of sPTB at < 30, < 34 and < 37 weeks' gestation and within 1 and 2 weeks' post-testing in the validation set, particularly the model combining risk factors plus qfFN alone (AUC: 0.96 at < 30 weeks; 0.85 at < 34 weeks; 0.77 at < 37 weeks; 0.91 at < 1 week from testing; and 0.92 at < 2 weeks from testing). CONCLUSIONS: Validation of the new prediction models suggests that the QUiPP App v.2 can reliably calculate risk of sPTB in women with TPTL. Use of the QUiPP App in practice could lead to better targeting of intervention, while providing reassurance and avoiding unnecessary intervention in women at low risk. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Desarrollo y validación de modelos predictivos para la Aplicación QUiPP v.2: herramienta para predecir el parto pretérmino en mujeres con síntomas de amenaza de parto prematuro OBJETIVO: Desarrollar modelos de predicción mejorados para actualizar el prototipo de la Aplicación QUiPP, una herramienta que proporciona el riesgo individualizado de parto pretérmino espontáneo (PPTE), para su uso en mujeres con síntomas de amenaza de parto pretérmino (APPT), mediante la incorporación de los factores de riesgo, la evaluación de la longitud cervical (LC) mediante ecografía transvaginal y los resultados de la prueba de fibronectina fetal cuantitativa (qfFN, por sus siglas en inglés) del líquido cérvico-vaginal. MÉTODOS: Las participantes fueron mujeres embarazadas entre 23 + 0 y 34 + 6 semanas de gestación con síntomas de APPT, reclutadas como parte de cuatro estudios de cohorte prospectivos llevados a cabo en 16 hospitales del Reino Unido entre octubre de 2010 y octubre de 2017. El grupo de entrenamiento comprendía a todas las mujeres cuyos resultados se conocían en mayo de 2017 (n = 1032). El grupo de validación estaba compuesto por mujeres cuyos resultados se recogieron entre junio de 2017 y marzo de 2018 (n = 506). Se desarrollaron modelos paramétricos de supervivencia para tres combinaciones de predictores: factores de riesgo más resultados de pruebas de qfFN solamente, factores de riesgo más LC solamente, y factores de riesgo más tanto qfFN como LC. Los mejores modelos fueron seleccionados utilizando los criterios de información de Akaike y Bayesiano. Se calculó la probabilidad estimada de PPTE a <30, <34 o <37 semanas de gestación y dentro de 1 o 2 semanas de la prueba y se crearon curvas de la característica operativa del receptor (ROC, por sus siglas en inglés) para demostrar la capacidad de diagnóstico de los modelos de predicción. RESULTADOS: Las estadísticas de predicción fueron similares entre los grupos de entrenamiento y de validación en la mayoría de los puntos de tiempo de los resultados y para cada combinación de predictores. Las áreas bajo las curvas (ABC) ROC demostraron que los tres algoritmos tuvieron una buena precisión para la predicción del PPTE a <30, <34 y <37 semanas de gestación y dentro de 1 a 2 semanas después de la prueba en el grupo de validación, en particular el modelo que combina los factores de riesgo más qfFN por si solo (ABC: 0,96 a <30 semanas; 0,85 at <34 semanas; 0,77 at <37 semanas; 0,91 at <1 semana de la prueba; y 0,92 a <2 semanas de la prueba CONCLUSIONES: La validación de los nuevos modelos de predicción sugiere que la Aplicación QUiPP v.2 puede calcular de manera fiable el riesgo de PPTE en mujeres con APPT. El uso de la Aplicación QUiPP en la práctica podría llevar a un mejor cribado para la intervención, a la vez que daría seguridad y evitaría intervenciones innecesarias en mujeres con bajo riesgo.

Placental growth factor testing for suspected pre-eclampsia: a cost-effectiveness analysis.

OBJECTIVE: To calculate the cost-effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care. DESIGN: Cost-effectiveness analysis. SETTING: Eleven maternity units participating in the PARROT stepped-wedge cluster-randomised controlled trial. POPULATION: Women presenting with suspected pre-eclampsia between 20+0 and 36+6  weeks' gestation. METHODS: Monte Carlo simulation utilising resource use data and maternal adverse outcomes. MAIN OUTCOME MEASURES: Cost per maternal adverse outcome prevented. RESULTS: Clinical care with PlGF testing costs less than current standard practice and resulted in fewer maternal adverse outcomes. There is a total cost-saving of UK£149 per patient tested, when including the cost of the test. This represents a potential cost-saving of UK£2,891,196 each year across the NHS in England. CONCLUSIONS: Clinical care with PlGF testing is associated with the potential for cost-savings per participant tested when compared with current practice via a reduction in outpatient attendances, and improves maternal outcomes. This economic analysis supports a role for implementation of PlGF testing in antenatal services for the assessment of women with suspected pre-eclampsia. TWEETABLE ABSTRACT: Placental growth factor testing for suspected pre-eclampsia is cost-saving and improves maternal outcomes.

Comparison of three commercially available placental growth factor-based tests in women with suspected preterm pre-eclampsia: the COMPARE study.

OBJECTIVE: To compare the performance of three placental growth factor (PlGF)-based tests in predicting delivery within 14 days from testing in women with suspected preterm pre-eclampsia before 35 weeks' gestation. METHODS: This was a retrospective analysis of samples collected from three prospective pregnancy cohort studies. Participants were pregnant women with suspected preterm pre-eclampsia recruited in tertiary maternity units in the UK and Ireland. Samples were analyzed simultaneously according to the manufacturers' directions. The tests compared were the DELFIA Xpress PlGF 1-2-3 test, the Triage PlGF test and the Elecsys immunoassay soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio. Areas under receiver-operating characteristics curves (AUCs) were compared. The main outcome measure was detection of a difference of 0.05 in AUC between tests for delivery within 14 days of testing. RESULTS: Plasma samples from 396 women and serum samples from 244 women were assayed. In predicting delivery within 14 days secondary to suspected pre-eclampsia prior to 35 weeks' gestation, no significant differences were observed in AUCs (P = 0.795), sensitivities (P = 0.249), positive predictive values (P = 0.765) or negative predictive values (P = 0.920) between the three tests. The specificity of the Elecsys sFlt-1/PlGF ratio test was higher than that of the other two tests (P < 0.001). CONCLUSIONS: The tests perform similarly in their prediction of need for delivery within 14 days in women with suspected pre-eclampsia. The high negative predictive values support the role of PlGF-based tests as 'rule-out' tests for pre-eclampsia. © 2018 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Predicting delivery of a small-for-gestational-age infant and adverse perinatal outcome in women with suspected pre-eclampsia.

OBJECTIVE: To evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small-for-gestational-age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre-eclampsia. METHODS: This was a prospective, multicenter observational study in which 47 biomarkers and ultrasound parameters were measured in 397 women with a singleton pregnancy presenting with suspected preterm pre-eclampsia between 20 + 0 and 36 + 6 weeks' gestation, with the objective of evaluating them as predictors of subsequent delivery of a SGA infant and adverse perinatal outcome. Women with confirmed pre-eclampsia at enrollment were excluded. Factor analysis and stepwise logistic regression were performed in two prespecified groups stratified according to gestational age at enrollment. The primary outcome was delivery of a SGA infant with a birth weight < 3rd customized centile (SGA-3), and secondary outcomes were a SGA infant with a birth weight < 10th customized centile and adverse perinatal outcome. RESULTS: In 274 women presenting at 20 + 0 to 34 + 6 weeks' gestation, 96 (35%) delivered a SGA-3 infant. For prediction of SGA-3, low maternal placental growth factor (PlGF) concentration had a sensitivity of 93% (95% CI, 84-98%) and negative predictive value (NPV) of 90% (95% CI, 76-97%) compared with a sensitivity of 71% (95% CI, 58-82%) and a NPV of 79% (95% CI, 68-87%) for ultrasound parameters (estimated fetal weight or abdominal circumference < 10th centile). No individual biomarker evaluated had a better performance than did PlGF, and marker combinations made only small improvements to the test performance. Similar results were found in 123 women presenting between 35 + 0 and 36 + 6 weeks' gestation. CONCLUSION: In women presenting with suspected preterm pre-eclampsia, measurement of PlGF offers a useful adjunct for identifying those at high risk of delivering a SGA infant, allowing appropriate surveillance and timely intervention. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

The QUiPP App: a safe alternative to a treat-all strategy for threatened preterm labor.

OBJECTIVE: To evaluate the impact of triaging women at risk of spontaneous preterm birth (sPTB) using the QUiPP App, which incorporates a predictive model combining history of sPTB, gestational age and quantitative measurements of fetal fibronectin, compared with a treat-all policy (advocated by the UK National Institute for Health and Care Excellence) among women with threatened preterm labor before 30 weeks' gestation. METHODS: Prospectively collected data of pregnant women presenting with symptoms of preterm labor (abdominal pain or tightening) at 24-34 weeks' gestation were retrieved from the research databases of the EQUIPP and PETRA studies for subanalysis. Each episode of threatened preterm labor was retrospectively assigned a risk for sPTB within 7 days using the QUiPP App. A primary outcome of delivery within 7 days was used to model the performance accuracy of the QUiPP App compared with a treat-all policy. RESULTS: Using a 5% risk of delivery within 7 days according to the QUiPP App as the threshold for intervention, 9/9 women who presented with threatened preterm labor < 34 weeks would have been treated correctly, giving a sensitivity of 100% (one-sided 97.5% CI, 66.4%) and a negative predictive value of 100% (97.5% CI, 98.9-100%). The positive predictive value for delivery within 7 days was 30.0% (95% CI, 11.9-54.3%) for women presenting before 30 weeks and 20.0% (95% CI, 12.7-30.1%) for women presenting between 30 + 0 and 34 + 0 weeks. If this 5% threshold had been used to triage women presenting between 24 + 0 and 29 + 6 weeks, 89.4% (n = 168) of admissions could have been safely avoided, compared with 0% for a treat-all strategy. No true case of preterm labor would have been missed, as no woman who was assigned a risk of < 10% delivered within 7 days. CONCLUSION: For women with threatened preterm labor, the QUiPP App can accurately guide management at risk thresholds for sPTB of 1%, 5% and 10%, allowing outpatient management in the vast majority of cases. A treat-all approach would not have avoided admission for any woman, and would have exposed 188 mothers and their babies to unnecessary hospitalization and steroid administration and increased the burden on network and transport services owing to unnecessary in-utero transfers. Prediction of sPTB should be performed before 30 weeks to determine management until there is evidence that such a high level of unnecessary intervention, as suggested by the treat-all strategy, does less harm than the occurrence of rare false negatives. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Development and validation of a tool incorporating quantitative fetal fibronectin to predict spontaneous preterm birth in symptomatic women.

OBJECTIVE: To develop a reliable and validated tool for prediction of spontaneous preterm birth (sPTB) in symptomatic women that incorporates quantitative measurements of fetal fibronectin (qfFN) and other relevant risk factors. METHODS: Data were analyzed that had been collected prospectively from 382 women who presented at an emergency assessment unit between 22 + 0 and 35 + 6 weeks' gestation with symptoms of preterm labor. Clinicians were blinded to qfFN although they were aware of qualitative fFN results. Parametric survival models for sPTB, with time-updated covariates, were developed for combinations of predictors and the best was selected using the Akaike and Bayesian information criteria. The model was developed on the first 190 consecutive women and validated on the subsequent 192. The estimated probability of delivery before 30, 34 or 37 weeks' gestation and within 2 or 4 weeks of testing was calculated for each patient and was compared to actual event rates. Predictive statistics were calculated to compare training and validation sets. RESULTS: The final model that was selected used qfFN and previous sPTB/preterm prelabor rupture of membranes (PPROM) as predictors. Predictive statistics were similar for training and validation sets and there was good agreement between expected and observed sPTB for all outcomes. Areas under the receiver-operating characteristics curves ranged from 0.77 to 0.88, indicating accurate prediction across all five delivery outcomes. CONCLUSIONS: sPTB in symptomatic women can be predicted accurately using a model combining qfFN and previous sPTB/PPROM. Clinicians can use this model, which has been incorporated into an App (QUiPP), to determine accurately a woman's risk of sPTB and potentially tailor management decisions appropriately.

Ability of a preterm surveillance clinic to triage risk of preterm birth: a prospective cohort study.

OBJECTIVE: To identify whether preterm surveillance clinics (PSCs) risk-stratify high-risk women accurately by comparing outcomes of those admitted to hospital on the basis of asymptomatic testing with those not admitted. METHODS: We performed a subanalysis from a larger prospective cohort study on sonographic cervical length, quantitative fetal fibronectin (qfFN) and risk of spontaneous preterm birth. We identified 1130 asymptomatic singleton pregnancies at high risk of preterm birth, screened between 23 and 28 weeks of gestation at a PSC in a tertiary hospital in London, UK. Gestational age at delivery, the proportion of preterm births that delivered < 30 weeks and neonatal outcomes were compared between women admitted electively when asymptomatic as a consequence of screening-test results and those who were not routinely admitted. RESULTS: In total, 66 (6%) women attending the PSC were admitted to hospital following asymptomatic screening (inpatient group). The mean gestational age at delivery for those not admitted electively (outpatient group) was at term and was significantly higher than that of those admitted from PSC (38.4 vs 31.2 weeks; P < 0.0001). Preterm birth < 30 weeks' gestation was rare in the outpatient group relative to those admitted (1.32% vs 36.4%; P < 0.0001). Neonatal mortality was 0.188% in the outpatient group compared with 4.55% in those admitted electively (P < 0.0001). The incidence of other complications such as neonatal death, 5-min Apgar score < 7, special care baby unit/neonatal intensive care unit admission, respiratory distress syndrome, intraventricular hemorrhage and low birth weight were significantly lower in those managed as outpatients than in those admitted electively. CONCLUSION: PSCs measuring cervical length and qfFN accurately triage asymptomatic high-risk pregnant women, enabling those at highest risk of adverse outcome to be identified for elective admission to hospital and appropriate management. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Development and validation of a tool incorporating cervical length and quantitative fetal fibronectin to predict spontaneous preterm birth in asymptomatic high-risk women.

OBJECTIVE: To develop a predictive tool for spontaneous preterm birth (sPTB) in asymptomatic high-risk women that includes quantification of fetal fibronectin (fFN) along with cervical length (CL) measurement and other clinical factors. METHODS: Data were analyzed that had been collected prospectively from 1249 women at high risk for sPTB attending preterm surveillance clinics. Clinicians were blinded to quantitative measurements of fFN (qfFN), although they were aware of qualitative fFN results. Parametric survival models for sPTB, with time-updated covariates, were developed and the best was selected using the Akaike and Bayesian information criteria. The model was developed on the first 624 consecutive women and validated on the subsequent 625. Fractional polynomials were used to accommodate possible non-linear effects of qfFN and CL. The estimated probability of delivery before 30, 34 or 37 weeks' gestation and within 2 or 4 weeks of testing was calculated for each patient and analyzed as a predictive test for the actual occurrence of each event. Predictive statistics were calculated to compare training and validation sets. RESULTS: The final model that was selected used a log-normal survival curve with CL, √qfFN and previous sPTB/preterm prelabor rupture of membranes as predictors. Predictive statistics were similar for training and validation sets. Areas under the receiver-operating characteristics curves ranged from 0.77 to 0.99, indicating accurate prediction across all five delivery outcomes. CONCLUSIONS: sPTB in high-risk asymptomatic women can be predicted accurately using a model combining qfFN and CL, which supersedes the single-threshold fFN test, demographic information and obstetric history. This algorithm has been incorporated into an App (QUiPP) for widespread use.

Shock index: an effective predictor of outcome in postpartum haemorrhage?

OBJECTIVES: To compare the predictive value of the shock index (SI) with conventional vital signs in postpartum haemorrhage (PPH), and to establish 'alert' thresholds for use in low-resource settings. DESIGN: Retrospective cohort study. SETTING: UK tertiary centre. POPULATION: Women with PPH ≥ 1500 ml (n = 233). METHODS: Systolic blood pressure (BP), diastolic BP, mean arterial pressure, pulse pressure, heart rate (HR) and SI (HR/systolic BP) were measured within the first hour following PPH. Values measured at the time of highest SI were selected for analysis. The area under the receiver operating characteristic curve (AUROC) for each parameter, used to predict admission to an intensive care unit and other adverse outcomes, was calculated. Sensitivity, specificity and negative/positive predictive values determined thresholds of the best predictor. MAIN OUTCOME MEASURES: Intensive care unit (ICU) admission, blood transfusion ≥ 4 iu, haemoglobin level <7 g/dl, and invasive surgical procedures. RESULTS: Shock index has the highest AUROC to predict ICU admissions (0.75 for SI [95% CI 0.63-0.87] compared with 0.64 [95% CI 0.44-0.83] for systolic BP). SI compared favourably for other outcomes: SI ≥ 0.9 had 100% sensitivity (95% CI 73.5-100) and 43.4% specificity (95% CI 36.8-50.3), and SI ≥ 1.7 had 25.0% sensitivity (95% CI 5.5-57.2) and 97.7% specificity (CI 94.8-99.3), for predicting ICU admission. CONCLUSIONS: Shock index compared favourably with conventional vital signs in predicting ICU admission and other outcomes in PPH, even after adjusting for confounding; SI <0.9 provides reassurance, whereas SI ≥ 1.7 indicates a need for urgent attention. In low-resource settings this simple parameter could improve outcomes. It was not possible to adjust for resuscitative measures administered following vital sign measurement that may have influenced the outcome.

Diagnostic accuracy of placental growth factor and ultrasound parameters to predict the small-for-gestational-age infant in women presenting with reduced symphysis-fundus height.

OBJECTIVES: To assess the diagnostic accuracy of placental growth factor (PlGF) and ultrasound parameters to predict delivery of a small-for-gestational-age (SGA) infant in women presenting with reduced symphysis-fundus height (SFH). METHODS: This was a multicenter prospective observational study recruiting 601 women with a singleton pregnancy and reduced SFH between 24 and 37 weeks' gestation across 11 sites in the UK and Canada. Plasma PlGF concentration < 5(th) centile, estimated fetal weight (EFW) < 10(th) centile, umbilical artery Doppler pulsatility index > 95(th) centile and oligohydramnios (amniotic fluid index < 5 cm) were compared as predictors for a SGA infant < 3(rd) customized birth-weight centile and adverse perinatal outcome. Test performance statistics were calculated for all parameters in isolation and in combination. RESULTS: Of the 601 women recruited, 592 were analyzed. For predicting delivery of SGA < 3(rd) centile (n = 78), EFW < 10(th) centile had 58% sensitivity (95% CI, 46-69%) and 93% negative predictive value (NPV) (95% CI, 90-95%), PlGF had 37% sensitivity (95% CI, 27-49%) and 90% NPV (95% CI, 87-93%); in combination, PlGF and EFW < 10(th) centile had 69% sensitivity (95% CI, 55-81%) and 93% NPV (95% CI, 89-96%). The equivalent receiver-operating characteristics (ROC) curve areas were 0.79 (95% CI, 0.74-0.84) for EFW < 10(th) centile, 0.70 (95% CI, 0.63-0.77) for low PlGF and 0.82 (95% CI, 0.77-0.86) in combination. CONCLUSIONS: For women presenting with reduced SFH, ultrasound parameters had modest test performance for predicting delivery of SGA < 3(rd) centile. PlGF performed no better than EFW < 10(th) centile in determining delivery of a SGA infant.