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.

A prospective, double-blinded cohort study using quantitative fetal fibronectin testing in symptomatic women for the prediction of spontaneous preterm delivery.

BACKGROUND: Spontaneous preterm birth (PTB) affects 6.5% of deliveries in Hong Kong. Quantitative fetal fibronectin (fFN) is under-utilised as a test for PTB prediction in Hong Kong. Our objective was to evaluate the effectiveness of quantitative fFN in predicting spontaneous PTB in women with symptoms of threatened preterm labour (TPTL) in our population. METHODS: A prospective, double-blinded cohort study of women with a singleton gestation and TPTL symptoms presenting to a tertiary hospital in Hong Kong between 24 + 0 to 33 + 6 weeks was performed from 1st October 2020 and 31st October 2021. Women with vaginal bleeding, ruptured membranes, and cervical dilation > 3 cm were excluded. The primary outcome was to test the characteristics of quantitative fFN in predicting spontaneous PTB < 37 weeks. Secondary outcome was to investigate the relationship between fFN value and time to PTB. Test characteristics of quantitative fFN at different thresholds were evaluated. RESULTS: 48 women with TPTL were recruited. All had fFN testing at admission with the results being concealed from the obstetrician managing the patient. 10 mothers had PTB (< 37 weeks' gestation). 7/48 (15%) had a subsequent PTB within 14 days from testing and 5 (10%) delivered within 48 h. The negative predictive value (NPV) of predicting delivery within 14 days was 97.3% and 100% when using a cut-off of < 50ng/ml and < 10ng/ml respectively. Using > 200 ng/ml as cut-off can also reliably predict delivery within 48 h - 7 days with positive predictive value PPV of 100%; as well as PTB before 37 weeks. CONCLUSIONS: Quantitative fFN has predictive value for spontaneous PTB prediction in symptomatic women in a Hong Kong population. fFN concentration could help clinicians rule out PTB and avoid unnecessary interventions and hospitalisation.

Value of cervical electrical impedance spectroscopy to predict spontaneous preterm delivery in asymptomatic women: the ECCLIPPx prospective cohort study.

OBJECTIVES: Preterm birth (PTB) accounts for two-thirds of deaths of structurally normal babies and is associated with substantial lifetime healthcare costs. Prevention of PTB remains limited by the modest accuracy of prediction methods, namely transvaginal ultrasound (TVS) cervical length (CL) measurement and quantitative cervicovaginal fetal fibronectin (FFN) estimation. We report the first substantive study detailing the predictive performance of a cervical probe device based on electrical impedance spectroscopy (EIS) for PTB - the EleCtriCaL Impedance Prediction of Preterm birth by spectroscopy of the cervix (ECCLIPPx) study. We aimed to compare the accuracy of cervical EIS-based prediction of spontaneous PTB with that of prediction using TVS-CL and FFN in asymptomatic women in the mid-trimester. METHODS: We studied asymptomatic women with a singleton pregnancy at 20-22 weeks' and 26-28 weeks' gestation. EIS was performed using a Sheffield Mark 5.0 device that makes measurements in the frequency range 76 Hz to 625 kHz using a small probe housing tetrapolar electrodes. TVS-CL and FFN were also measured. The associations of cervical EIS, TVS-CL and FFN with spontaneous delivery before 37 weeks and before 32 weeks were determined by multivariate linear and non-linear logistic regression analysis. Areas under the receiver-operating-characteristics curves (AUC) plots of sensitivity against specificity were used to compare the predictive performance of all parameters, both in isolation and in combination. RESULTS: Of the 365 asymptomatic women studied at 20-22 weeks who were not receiving treatment, 29 had spontaneous PTB, 14 had indicated PTB and 322 had term birth. At the higher frequencies assessed, cervical EIS predicted spontaneous PTB before 37 weeks with an AUC of 0.76 (95% CI, 0.71-0.81), compared with AUCs of 0.72 (95% CI, 0.66-0.76) for TVS-CL and 0.62 (95% CI, 0.56-0.72) for FFN. Combining all three assessments improved the prediction of spontaneous PTB before 37 weeks (AUC, 0.79 (95% CI, 0.74-0.83)) compared with TVS-CL and FFN alone. Incorporating a history of spontaneous PTB (defined as previous mid-trimester miscarriage or spontaneous PTB (14 to < 37 weeks)) into the cervical EIS prediction model improved the accuracy of prediction of spontaneous PTB before 37 weeks (AUC, 0.83 (95% CI, 0.78-0.87)) and before 32 weeks (AUC, 0.86 (95% CI, 0.82-0.90)). CONCLUSIONS: Mid-trimester cervical EIS assessment predicts spontaneous PTB. Larger confirmatory studies investigating its potential clinical utility and to inform effective preventive interventions are required. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Self-reported pain scores as a predictor of preterm birth in symptomatic twin pregnancy: a retrospective study.

BACKGROUND: To evaluate the self-reported pain scores as a predictor of preterm birth (PTB) in symptomatic twin pregnancy and to develop a nomogram for the prediction model. METHODS: We conducted a retrospective study of 148 cases of symptomatic twin pregnancies before 34 weeks of gestation visited at Seoul national university hospital from 2013 to 2018. With other clinical factors, self-reported pain score was evaluated by the numerical rating scale (NRS) pain scores for pain intensity. By multivariate analyses and logistic regression, we developed a prediction model for PTB within 7 days. Using the Cox proportional hazards model, the curves were plotted to show the predictability of the PTB according to NRS pain score, while adjusting the other covariates. RESULTS: Twenty-three patients (15.5 %) delivered preterm within 7 days. By a logistic regression analysis, higher NRS pain score (OR 1.558, 95 % CI 1.093-2.221, P < 0.05), shorter cervical length (OR 3.164, 95 % CI 1.262-7.936, P < 0.05) and positive fibronectin results (OR 8.799, 95 % CI 1.101-70.330, P < 0.05) affect PTB within 7 days. Using the variables, the area under the receiver operating characteristic curve (AUROC) of the prediction model was 0.917. In addition, we developed a nomogram for the prediction of PTB within 7 days. CONCLUSIONS: Self-reported pain scores combined with cervical length and fetal fibronectin are useful in predicting impending PTB in symptomatic twin pregnancy.

Compliance with Fetal Fibronectin Testing at a Canadian Tertiary Care Perinatal Centre.

OBJECTIVE: The purpose of this study was to assess compliance with fetal fibronectin (fFN) testing recommendations at a single tertiary care perinatal centre. The secondary objective was to identify factors associated with compliance with these recommendations. METHODS: A retrospective cohort study was conducted from January 1, 2016 to December 31, 2016 of all patients who presented to the IWK Health Centre with suspected preterm labour. Inclusion criteria included symptoms of preterm labour prior to 370 weeks gestation, singleton or multiple pregnancy, and established fetal wellbeing. Exclusion criteria included severe fetal anomaly, contraindications to tocolysis, transfer from community hospital, or inadequate documentation. Provider compliance was evaluated to determine: 1) whether the test was performed for appropriate indications according to provincial fFN guidelines; 2) whether fFN results were appropriately being used to inform patient care. Logistic regression was used to determine factors associated with compliance. RESULTS: A total of 528 patients presented with symptoms of preterm labour. The overall compliance with testing recommendations was 76.1%. Compliance for patients who met criteria for fFN testing was 73%, and compliance for those not meeting criteria was 76.4%. Of patients with a negative fFN result, 85.3% were appropriately discharged home without intervention. Gestational age, time of day, and non-obstetrician provider type were found to be associated with compliance. CONCLUSION: Despite regional and national guidelines, this study demonstrates a compliance rate of 76% in our centre, indicating a gap in provider knowledge regarding proper use and interpretation of fFN. Non-obstetrician provider type was associated with decreased compliance.

Using quantitative fetal fibronectin to predict term labour onset in Australian rural women: A pilot study.

BACKGROUND: Many women living in rural and remote Australia are required to travel large distances to birth in a hospital with maternity facilities, incurring considerable financial, social and emotional burden for them and their families. No studies to date have investigated the use of quantitative fetal fibronectin (qfFN) to predict term labour in asymptomatic pregnant women. A tool which is able to more accurately predict term labour has the potential to guide informed travel decision-making for women and healthcare professionals in rural and remote Australia. AIM: The aim of this study is to determine if qfFN can reliably predict term labour in asymptomatic women from rural and remote areas. MATERIALS AND METHODS: Thirty-nine women from rural Australia provided 71 fFN samples between June 2016 and October 2018, from 37 weeks' gestation, with at least one week between samples for those providing multiple samples. Days from fFN sampling until spontaneous onset of labour were recorded. Using generalised estimating equation modelling we examined the utility of fFN as a predictor for onset of labour at term after adjusting for confounders. RESULTS: There was a small-to-moderate negative correlation (rs -0.27, P < 0.05) between time until labour and fFN. Quantitative fFN was observed to be a significant predictor of time until labour after adjusting for confounding variables (P < 0.001). CONCLUSION: fFN levels may play a role in predicting term labour in rural women; however, future studies with a larger sample size are required to validate the findings of our pilot study.

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.

Quantitative fetal fibronectin for prediction of preterm birth in asymptomatic twin pregnancy.

INTRODUCTION: To evaluate cervicovaginal fluid quantitative fetal fibronectin, measured by a bedside analyzer, to predict spontaneous preterm birth in twin pregnancy before 30 weeks of gestation. MATERIAL AND METHODS: In a prospective cohort study, we studied the accuracy of quantitative fetal fibronectin measured between 18 and 27+6 weeks of gestation in high-risk asymptomatic women with twin pregnancies, to predict spontaneous preterm birth before 30 weeks of gestation. Predefined fetal fibronectin thresholds were ≥10, ≥50 and ≥200 ng/mL. Predictive statistics were also calculated to evaluate accuracy of "early" tests, performed between 18 and 21+6 weeks and "standard" tests performed between 22+0 and 27+6 weeks of gestation in the same cohort. Subgroup analysis was performed according to cervical length measurement. In addition, we compared accuracy of prediction with quantitative fetal fibronectin measured during the standard test period in asymptomatic twin pregnancy with no additional risk factors, to twin pregnancies with one or more additional risk factors for spontaneous preterm birth. RESULTS: Of 130 eligible women identified with quantitative fetal fibronectin tests undertaken during the standard testing period, 9% delivered before 30 weeks of gestation. Quantitative fetal fibronectin was significantly related to outcome before 30/40 (ROC curves of 0.8 [95% CI 0.7-1]). Early tests were not significantly predictive; ROC area 0.53 (95% CI 0.29-0.81). There was a trend towards better predictive accuracy when one or more additional risk factors for spontaneous preterm birth or cervical length were considered. CONCLUSIONS: Quantitative fetal fibronectin measured from 22 to 27+6 weeks of gestation accurately predicts spontaneous preterm birth at <30 weeks of gestation. Tests undertaken earlier are of limited value. Consideration of cervical length or prior history in addition to quantitative fetal fibronectin strengthens prediction.

The Biomarkers for Preterm Birth Study-A prospective observational study comparing the impact of vaginal biomarkers on clinical practice when used in women with symptoms of preterm labor.

INTRODUCTION: This study aims to compare the use of qualitative fetal fibronectin, quantitative fetal fibronectin, and placental α-microglobulin-1 in women with symptoms of preterm labor, to evaluate which vaginal biomarker performs the best in clinical practice. MATERIAL AND METHODS: This prospective observational study included women who presented with symptoms of preterm labor at 24+0 to 34+0  weeks of gestation at a large tertiary maternity hospital in Auckland, New Zealand. Women were managed according to hospital guidelines using qualitative fetal fibronectin. Quantitative fetal fibronectin and placental α-microglobulin-1 tests were also taken, with clinicians blinded to the results. Management and delivery outcomes were collected from clinical records. The primary outcome was the rate of antenatal hospital admission. Analysis was performed according to predefined management protocols for each of the tests. RESULTS: A total of 128 women had all three biomarkers tests taken. Spontaneous preterm birth rates were 7/128 (5.5%) ≤34+0  weeks and 20/128 (15.6%) <37+0  weeks of gestation; 5/128 (3.9%) delivered within 7 days of testing. Positive results were recorded in 28 qualitative fetal fibronectin tests, 25 quantitative fetal fibronectin tests with 11 ≥200 ng/mL, and 16 placental α-microglobulin-1 tests. The use of quantitative fetal fibronectin or placental α-microglobulin-1 would have lowered antenatal admission rates: 27/128 (21.1%) for qualitative fetal fibronectin, 11/128 (8.6%) for quantitative fetal fibronectin (admission threshold ≥200 ng/mL), and 15/128 (11.7%) for placental α-microglobulin-1. No additional women with quantitative fetal fibronectin <200 ng/mL delivered within 7 days or missed corticosteroids compared with standard care (qualitative fetal fibronectin); however, an additional 3 cases had a false-negative placental α-microglobulin-1 and clinical care may have been compromised (no antenatal corticosteroids or admission). CONCLUSIONS: The use of quantitative fetal fibronectin (admission threshold ≥200 ng/mL) has the potential to reduce the rate of antenatal admissions for women with symptoms of preterm labor without compromising use of antenatal interventions that improve outcomes for babies born preterm.

Management of pregnancy after fertility-sparing surgery for cervical cancer.

Cervical cancer is increasingly diagnosed in women who have not yet completed their reproductive plans. For women with early-stage disease (FIGO stage IA1-IB1), fertility-sparing procedures, such as conization, trachelectomy or radical trachelectomy, represent the treatments of choice. However, women who undergo repeated conization or trachelectomy represent a challenge for obstetricians because they are at increased risk of infertility, mid-trimester miscarriage, preterm premature rupture of membranes and preterm delivery. So far, the evidence-based guidance on the management of these pregnancies is limited. This article reviews the literature discussing pregnancy management in women after fertility-sparing surgery for early cervical cancer. Although the evidence is limited, certain measures are desirable, including screening and treatment of asymptomatic bacteriuria, screening for cervical incompetence and progressive cervical shortening by transvaginal ultrasonography, and fetal fibronectin testing. Vaginal progesterone supplementation should be primary prevention for all women after trachelectomy. Women with a history of preterm delivery or late miscarriage may benefit from cervical cerclage. Elective delivery by cesarean section in the early-term period is desirable.

The diagnostic value of fetal fibronectin testing in clinical practice.

AIM: To evaluate the clinical management to withhold treatment for preterm labor in symptomatic women with an intermediate cervical length and negative fetal fibronectin (fFN) testing. METHODS: A retrospective cohort study was performed in a tertiary care teaching hospital in the Netherlands. Pregnant women with a gestational age between 23+5 to 34+0 weeks, with the presence of regular uterine contractions accompanied by a cervical length between 15 and 30 mm and intact membranes, who underwent fFN testing were included to obtain the diagnostic value of fFN testing for preterm delivery within 7 days. RESULTS: Fetal fibronectin testing has an extremely high negative predictive value (100%) and sensitivity (100%) for delivery within 7 days, in singleton and multiple pregnancies. However, specificity (64%) and positive predictive value (10%) of fFN testing in singleton pregnancies are low. Blood present on the fFN sample does not affect the reliability of the fFN test; the negative predictive value remains 100%. CONCLUSION: Women with symptoms of early preterm labor, intact membranes, a cervical length between 15 and 30 mm and negative fFN testing do not deliver within 7 days. Administration of corticosteroids and tocolytics can safely be withhold. Furthermore, blood on the fFN sample does not change the reliability of the fFN test.

Prenatal care for woman after fertility-sparing surgery for cervical cancer.

AIM: To summarize the current knowledge about the care of pregnant women after fertility-preserving operations for cervical cancer. STUDY TYPE: Review article. SETTING: Department of Gynecology and Obstetrics, 1st Faculty of Medicine, Charles University and General University Hospital, Prague. METHODOLOGY: Search of published literature on a given topic using the PubMed database. RESULTS: Pregnant women after fertility-sparing surgery for cervical cancer can benefit from screening and treatment for asymptomatic bacteriuria, cervical incompetence screening, and progressive cervical shortening by transvaginal ultrasonography. Tests to determine the presence of biomarkers of preterm birth in cervicovaginal fluid improve the prediction of preterm birth. Vaginal progesterone supplementation should be the primary prevention of preterm birth in all women after trachelectomy. Women with a history of preterm birth or late abortion may benefit from cerclage. The preferred mode of delivery is the cesarean section after 37 weeks of gestation. CONCLUSION: Due to the lack of data, pregnancy management in women who have undergone fertility-sparing surgery for early cervical cancer is inconsistent. An increasing number of pregnancies after fertility-sparing surgery will likely prompt clinical research in this field.

Cervical length and quantitative fetal fibronectin in the prediction of spontaneous preterm birth in asymptomatic women with congenital uterine anomaly.

BACKGROUND: Congenital uterine anomalies are associated with late miscarriage and spontaneous preterm birth. OBJECTIVE: Our aim was 1) to determine the rate of spontaneous preterm birth in each type of congenital uterine anomaly, and 2) to assess the performance of quantitative fetal fibronectin and cervical length measurement by transvaginal ultrasound in asymptomatic women with congenital uterine anomalies for the prediction of spontaneous preterm birth at <34 and <37 weeks of gestation. MATERIALS AND METHODS: This was a retrospective cohort of women with congenital uterine anomalies asymptomatic for spontaneous preterm birth, from 4 tertiary referral centers in the United Kingdom (2001-2016). Congenital uterine anomalies were categorized into fusion (unicornuate, didelphic, and bicornuate uteri) or resorption defects (septate, with or without resection, and arcuate uteri), based on prepregnancy diagnosis. All women underwent serial transvaginal ultrasound cervical length assessment in the second trimester (16 to 24 weeks' gestation); a subgroup underwent quantitative fetal fibronectin testing from 18 weeks' gestation. We investigated the relationship between congenital uterine anomalies and predictive test performance for spontaneous preterm birth at <34 and <37 weeks' gestation. RESULTS: A total of 319 women were identified as having congenital uterine anomalies in our high-risk population. Of the women, 7% (23/319) delivered spontaneously at <34 weeks' gestation and 18% (56/319) at <37 weeks' gestation. Rates of spontaneous preterm birth by type were as follows: 26% (7/27) for unicornuate, 21% (7/34) for didelphic, 16% (31/189) for bicornuate, 13% (7/56) for septate, and 31% (4/13) for arcuate. In all, 80% (45/56) of women who had spontaneous preterm birth at <37 weeks did not develop a short cervical length (<25 mm) during the surveillance period (16-24 weeks). The diagnostic accuracy of short cervical length had a low sensitivity (20.3) for predicting spontaneous preterm birth at <34 weeks. Cervical length had an area under the receiver operating curve of 0.56 (95% confidence interval, 0.48-0.64) and 0.59 (95% confidence interval, 0.55-0.64) for prediction of spontaneous preterm birth at <34 and <37 weeks, respectively. The area under the curve for cervical length to predict spontaneous preterm birth at <34 weeks was 0.48 for fusion defects (95% confidence interval, 0.39-0.57) but 0.78 (95% confidence interval, 0.66-0.91) for women with resorption defects. Overall quantitative fetal fibronectin had an area under the curve of 0.63 (95% confidence interval, 0.49-0.77) and 0.58 (95% confidence interval, 0.49- 0.68) for prediction of spontaneous preterm birth at <34 and <37 weeks, respectively. The area under the curve for prediction of spontaneous preterm birth at <37 weeks with quantitative fetal fibronectin for fusion defects was 0.52 (95% confidence interval, 0.41-0.63) but 0.79 (95% confidence interval, 0.63-0.95) for women with resorption defects. Results were similar when women with intervention were excluded. CONCLUSION: The commonly used markers cervical length and quantitative fetal fibronectin have utility in prediction of spontaneous preterm birth in resorption congenital uterine defects but not in fusion defects. This is contrary to findings in other high-risk populations. These findings need to be accounted for when planning antenatal care, and have potential implications for predictive tests used in spontaneous preterm birth surveillance and intervention.

Effect of QUiPP prediction algorithm on treatment decisions in women with a previous preterm birth: a prospective cohort study.

OBJECTIVE: The QUiPP algorithm combines cervical length, quantitative fetal fibronectin (qfFN) and medical history to quantify risk of preterm birth. We assessed the utility of QUiPP to inform preterm birth prevention treatment decisions. DESIGN: A prospective cohort study with a subsequent impact assessment using the QUiPP risk of birth before 34 weeks' gestation. SETTING: A UK tertiary referral hospital. SAMPLE: In all, 119 women with previous spontaneous preterm birth (sPTB) or preterm premature rupture of membranes (PPROM) before 34 weeks' gestation. METHODS: Cervical length and qfFN were measured at 19+0 to 23+0  weeks' gestation. Clinical management was based on history and cervical length. After birth, clinicians were unblinded to qfFN results and QUiPP analysis was undertaken. MAIN OUTCOME MEASURES: Predictive statistics of QUiPP algorithm using 10% risk of sPTB before 34+0  weeks as treatment threshold. RESULTS: Fifteen of 119 women (13%) had PPROM or sPTB before 34 weeks. Of these, 53% (8/15) had QUiPP risk of sPTB before 34+0  weeks above 10%. Applying this treatment threshold in practice would have doubled our treatment rate (20 versus 42%). QUIPP threshold of 10% had positive likelihood ratio (LR) of 1.3 (95% CI 0.76-2.18), and negative LR of 0.8 (95% CI 0.45-1.40) for predicting sPTB before 34+0  weeks. CONCLUSIONS: Use of the QUiPP algorithm in this population may lead to substantial increase in interventions without evidence that currently available treatment options are beneficial for this particular group. TWEETABLE ABSTRACT: Independent study finds that the QUiPP algorithm could lead to substantial increases in treatment without evidence of benefit.

EQUIPTT: The Evaluation of the QUiPP app for Triage and Transfer protocol for a cluster randomised trial to evaluate the impact of the QUiPP app on inappropriate management for threatened preterm labour.

BACKGROUND: Accurate diagnosis of preterm labour is needed to ensure correct management of those most at risk of preterm birth and to prevent the maternal and fetal risks incurred by unnecessary interventions given to the large majority of women, who do not deliver within a week of presentation. Intervention "just-in-case" results in many avoidable admissions, women being transferred out of their local hospital unnecessarily and most women receiving unwarranted drugs, such as steroids and tocolytics. It also precludes appropriate transfers for others as neonatal cots are blocked pre-emptively, resulting in more dangerous ex-utero transfers. We have developed the QUiPP App which is a clinical decision-making aid based on previous outcomes of women, quantitative fetal fibronectin (qfFN) values and cervical length. It is hypothesised that using the QUiPP app will reduce inappropriate admissions and transfers. METHODS: A multi-site cluster randomised trial will evaluate whether the QUiPP app reduces inappropriate management for threatened preterm labour. The 13 participating centres will be randomly allocated to receive either intervention or control. If the QUiPP app calculates risk of delivery within 7 days to be is less than 5%, clinicians are advised that interventions may be withheld. Women's experience of threatened preterm labour assessment will be explored using self-completed questionnaires, with a subset of participants being invited to semi-structured interview. A health economics analysis is also planned. DISCUSSION: We hypothesise that the QUiPP app will improve identification of the most appropriate women for admission and transfer and ensure that therapies known to reduce risk of preterm neonatal morbidities are offered to those who need them. We will determine which women do not require these therapies, thereby reducing over-medicalisation and the associated maternal and fetal risks for these women. The findings will inform future national guidelines on threatened preterm labour. Beyond obstetrics, evaluating the impact of an app in an emergency setting, and our emphasis on balancing harms of over-treatment as well as under-treatment, make EQUIPTT a valuable contribution to translational medicine. TRIAL REGISTRATION: The EQUIPTT trial was prospectively registered on 16th January 2018 with the ISRCTN registry (no. 17846337 ).

A high concentration of fetal fibronectin in cervical secretions increases the risk of intra-amniotic infection and inflammation in patients with preterm labor and intact membranes.

Objective To determine whether the risk of intra-amniotic infection/inflammation and spontaneous preterm delivery (SPTD) varies as a function of the concentration of cervical fetal fibronectin (fFN) in patients with preterm labor and intact membranes. Methods This prospective study included 180 patients with preterm labor and intact membranes who had a sample collected for quantitative fFN measurement and underwent amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Results (1) The prevalence of intra-amniotic infection/inflammation and SPTD within 7 days was 32.2% (58/180) and 33.9% (61/178), respectively; (2) The higher the fFN concentration, the greater the risk of intra-amniotic infection/inflammation and SPTD within 7 days (P<0.001, respectively); (3) An fFN concentration 150 ng/mL had a better diagnostic performance than an fFN 50 ng/mL in the identification of intra-amniotic infection/inflammation and SPTD within 7 days; (4) Among the patients with an fFN <50 ng/mL, intra-amniotic infection/inflammation was identified in 7.6% (6/79) of patients and 66.7% (4/6) delivered within 7 days. Conclusion The higher the concentration of fFN, the greater the risk of intra-amniotic infection/inflammation and SPTD in patients with preterm labor and intact membranes.

Evaluation of fetal fibronectin for threatened preterm labour in reducing inappropriate interventions.

BACKGROUND: Preterm birth is associated with significant perinatal morbidity and mortality. The fetal fibronectin test (fFN) is used to manage women presenting with threatened preterm labour (TPTL). AIM: To evaluate the use of fFN in women presenting with TPTL with regard to hospital admission, tertiary hospital transfer and use of tocolytics and steroids in our hospital, against recommended guidelines. The ability of fFN <10 ng/mL, 10-49 ng/mL, 50-199 ng/mL and >200 ng/mL to predict outcome was also examined. MATERIAL AND METHODS: This was a single-centre retrospective study from January 2015 to June 2017. All women who presented to Ipswich hospital, a level two facility for births at >32 weeks of gestation, between 23 and 346  weeks of gestation with TPTL and who had fFN tests were included in the study. RESULTS: Fetal fibronectin <50 ng/mL had a negative predictive value of 93.5% (95% CI 86.5-97.1). Despite this assurance, one in four presentations resulted in hospital admission and nearly one in ten in steroids and tocolysis administration. Birth <34 weeks was 0% for fFN <10 and 2% for women with fFN levels <200 ng/mL compared to nearly 30% for levels >200 ng/mL. CONCLUSION: There is noncompliance with use of fFN to its full potential. This small study also provides support for the use of a 200 ng/mL cut-off fFN level for birth <34 weeks. This would avoid the need to transfer to a tertiary facility many women who present with TPTL.

The efficacy of quantitative fetal fibronectin in predicting spontaneous preterm birth in symptomatic women: A retrospective cohort study.

BACKGROUND: Recent data suggest that quantitative measurements of fetal fibronectin can be used accurately to predict increased risk of preterm birth. AIM: The purpose of this study was to demonstrate that the quantification of fetal fibronectin improves diagnostic accuracy in women who present with symptoms suggestive of threatened preterm labour (TPL) using a quantitative fetal fibronectin (qfFN) bedside analyser. STUDY DESIGN: This was a retrospective cohort study of pregnant women who presented between 22+6 and 32+6  weeks gestation with symptoms of TPL who had qfFN measured using the Rapid fFN Q10 system. The ability to predict spontaneous preterm birth (sPTB) within 48 h, 14 days and <34 weeks gestation at qfFN thresholds of 10, 50 and 200 ng/mL was assessed. RESULTS: The overall rate of sPTB <34 weeks was 4.1% (n = 373). For deliveries within 48 h, within 14 days and <34 weeks, a qfFN threshold of 200 ng/mL had positive predictive values of 26.7%, 42.9% and 46.7%, respectively, when compared to patients with qfFN values of 0-9 ng/mL. The corresponding relative risks were 68.5, 53.8 and 38.0, respectively CONCLUSION: Quantitative fetal fibronectin testing with thresholds of 10, 50 and 200 ng/mL allows for more accurate prediction of preterm birth in symptomatic women. This higher degree of discrimination allows for more directed interventions for high-risk patients and reduces the cost and burden of unnecessary treatment for low-risk patients.

Current options of prediction of preterm labour.

OBJECTIVE: A summary of current possibilities to adequately determine spontaneous preterm labour. DESIGN: Review. SETTING: Department of Obstetrics and Gynecology, 1st Faculty of Medicine and General Teaching Hospital, Charles University in Prague. METHODS: Research of literature and current studies. CONCLUSION: Based on the combination of personal medical history, clinical signs, biomarkers and transvaginal ultrasonographic measurement of cervical length, it is possible to predict preterm labour. To avoid a major prediction miscalculation, it is necessary to understand and correctly evaluate certain clinical findings. This approach decreases redundant medical intervention and therefore leads to amelioration of perinatal outcome.

Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.