Fetal Fibronectin Research Articles

Prediction of recurrent preterm delivery in asymptomatic women- an anxiety reducing measure?

ObjectivesThe QUiPP application is used to predict the risk of recurrent preterm birth (PTB) in asymptomatic high risk women with a previous PTB. Our study aims to evaluate the impact of the use of the QUiPP app on maternal anxiety levels.Study designA retrospective cohort study on asymptomatic pregnant women attending the Prevention of Preterm Birth Clinic in a busy tertiary unit. Women included in the study had a history of previous PTB. The study assessment occurred at approximately 4 weeks prior to the gestation of the earliest previous PTB and included measurement of cervical length and vaginal fetal fibronectin. Data was inputted into the QUiPP application, which in turn estimated risk of preterm delivery at specific intervals. Measured outcomes were gestation at delivery, time from risk assessment to delivery, infant birth weight, NICU admission and length of stay. In addition, maternal anxiety levels were retrospectively assessed using a questionnaire with a Likert scale.ResultsSeventy six women were included in the study. All women were asymptomatic for preterm labour at assessment. The mean gestation at the time of risk assessment was 27 weeks, the mean time from risk assessment to delivery was 72 days. Average gestation at time of delivery was 37 weeks (range 22–42 weeks). The preterm birth rate was 29% (n = 22).Seventy seven percent of women who delivered <37 weeks, and 80% who delivered <34 weeks were given QUiPP scores predicting a ≥5% chance of PTB within four weeks of their actual delivery date. Sixteen percent of infants were admitted to NICU (n = 12) with a mean length of stay of 21 days. All infants went home well with their parents.Eighty four percent of respondents to our questionnaire reported feeling anxious about their pregnancy prior to attending the clinic. After receiving a QUIPP score 90% said they felt reassured and 79% reported that the felt less anxious.ConclusionIn asymptomatic women, the use of the QUiPP app helps to predict, prevent, and optimise PTB. This surveillance has a beneficial role for maternal mental well-being in that it reduces anxiety at a key time during a pregnancy.

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

Congenital uterine anomalies are associated with late miscarriage and spontaneous preterm birth. 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. 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. 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 asfollows: 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. 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.

Comparison Between Fetal Fibronectin vs Cervical Length in Patient With Unfavourable Cervix in Prediction of Successful Induction of Labor

Comparison Between Fetal Fibronectin vs Cervical Length in Patient With Unfavourable Cervix in Prediction of Successful Induction of Labor

Utility of cervical length and quantitative fetal fibronectin for predicting spontaneous preterm delivery among symptomatic nulliparous women.

To validate the utility of fetal fibronectin (fFN) and cervical length (CL) in predicting preterm delivery among symptomatic nulliparous women. A retrospective cohort study of nulliparous women who presented with uterine contractions, abdominal pain, or cervical change at 21-34 gestational weeks at Fukushima Medical University Hospital, Japan, between 2008 and 2017. fFN (categorized as <50ng/dL, 50-199ng/dL, >200ng/dL) and CL (≥15mm or <15mm) were evaluated simultaneously. Adjusted odds ratios (aORs) and confidence intervals (CIs) for preterm delivery before 37 or 34weeks, and delivery within 28 or 14days were calculated (references: fFN, <50ng/dL; CL, ≥15mm). Among 285 women who met the study criteria, CL less than 15mm was a risk factor for preterm delivery before 37 (aOR, 4.1; 95% CI, 1.1-6.7) and 34 (aOR, 6.8; 95% CI, 2.3-20.2) weeks. fFN of 200ng/dL or higher was a risk factor for delivery within 28 (aOR, 19.8; 95% CI, 4.3-90.2) and 14 (aOR, 10.8; 95% CI, 1.7-67.6) days. Among symptomatic nulliparous women, short CL was found to be a risk factor for preterm delivery and higher fFN levels were related to short gestational latency.

Quantitative fetal fibronectin to predict spontaneous preterm delivery after laser surgery for twin-twin transfusion syndrome

Our goal was to assess whether quantitative fetal fibronectin (qfFN) is associated with spontaneous preterm birth (sPTB) after laser surgery for twin-twin transfusion syndrome (TTTS). qfFN was collected within 24 hours before and after laser surgery. Aims were: (1) To determine if qfFN changed with operative fetoscopy; and (2) To estimate the number of patients needed to study the predictive value of qfFN for sPTB <28 and <32 weeks. Results are reported as median (range). Among 49 patients, there was no net difference in qfFN levels after laser surgery [0.0 ng/mL (−37 to +400), p = 0.6041]. However, patients with a qfFN increase >10 ng/mL were 19 times more likely to undergo sPTB at <28 weeks (OR = 19.5). We determined that 383 and 160 patients would be needed to achieve adequate statistical power for qfFN to be predictive of sPTB at a GA <28 weeks and <32 weeks, respectively. In conclusion, laser surgery did not alter the qfFN level within the entire cohort, but qfFN may be useful in identifying a subset of patients at increased risk of preterm delivery.

Serum multiple cytokines for the prediction of spontaneous preterm birth in asymptomatic women: A nested case-control study

BackgroundCurrent biomarkers such as fetal fibronectin and cervical length are accurate predictors of spontaneous preterm birth (sPTB) in women with clinically suspected preterm risk; however, these are not effective for predicting the risk of sPTB in asymptomatic women. Therefore, we performed this study with the objective of determining whether the combinations of specific serum cytokines could accurately predict the sPTB risk in asymptomatic women. MethodsWe conducted a nested case-control study with 129 incident sPTB cases and 258 individually matched controls who participated in an ongoing birth cohort study. The maternal serum levels of the selected 35 cytokines were measured. We evaluated the relationship between the multiple cytokines and sPTB risk using conditional logistic regression and elastic net model. ResultsA panel of cytokines was significantly associated with an increased risk of sPTB. The odds ratio (OR) of sPTB per standard deviation (SD) increase of the predictive model score was 1.57 (95% CI 1.25–1.97) for the cytokines model. The combination of the selected serum cytokines was substantially more effective in predicting the risk for sPTB, as the receiver–operator characteristic curve (AUC) values were 0.546 and 0.559 in the single cytokine model and it improved to 0.642 in the multiple cytokines model (PAUC difference = 0.02 for TNF-α vs. multiple cytokines; PAUC difference = 0.05 for TRAIL vs. multiple cytokines). Moreover, the prediction was more accurate in overweight pregnant women, with an AUC = 0.879. ConclusionsThe current study suggested that the combination of selected serum cytokines can more effectively predict the risk of sPTB in asymptomatic women compared with the use of single cytokine.

Three biomarker tests to help diagnose preterm labour: a systematic review and economic evaluation.

Preterm birth may result in short- and long-term health problems for the child. Accurate diagnoses of preterm births could prevent unnecessary (or ensure appropriate) admissions into hospitals or transfers to specialist units. The purpose of this report is to assess the test accuracy, clinical effectiveness and cost-effectiveness of the diagnostic tests PartoSure™ (Parsagen Diagnostics Inc., Boston, MA, USA), Actim® Partus (Medix Biochemica, Espoo, Finland) and the Rapid Fetal Fibronectin (fFN)® 10Q Cassette Kit (Hologic, Inc., Marlborough, MA, USA) at thresholds ≠50 ng/ml [quantitative fFN (qfFN)] for women presenting with signs and symptoms of preterm labour relative to fFN at 50 ng/ml. Systematic reviews of the published literature were conducted for diagnostic test accuracy (DTA) studies of PartoSure, Actim Partus and qfFN for predicting preterm birth, the clinical effectiveness following treatment decisions informed by test results and economic evaluations of the tests. A model-based economic evaluation was also conducted to extrapolate long-term outcomes from the results of the diagnostic tests. The model followed the structure of the model that informed the 2015 National Institute for Health and Care Excellence guidelines on preterm labour diagnosis and treatment, but with antenatal steroids use, as opposed to tocolysis, driving health outcomes. Twenty studies were identified evaluating DTA against the reference standard of delivery within 7 days and seven studies were identified evaluating DTA against the reference standard of delivery within 48 hours. Two studies assessed two of the index tests within the same population. One study demonstrated that depending on the threshold used, qfFN was more or less accurate than Actim Partus, whereas the other indicated little difference between PartoSure and Actim Partus. No study assessing qfFN and PartoSure in the same population was identified. The test accuracy results from the other included studies revealed a high level of uncertainty, primarily attributable to substantial methodological, clinical and statistical heterogeneity between studies. No study compared all three tests simultaneously. No clinical effectiveness studies evaluating any of the three biomarker tests were identified. One partial economic evaluation was identified for predicting preterm birth. It assessed the number needed to treat to prevent a respiratory distress syndrome case with a 'treat-all' strategy, relative to testing with qualitative fFN. Because of the lack of data, our de novo model involved the assumption that management of pregnant women fully adhered to the results of the tests. In the base-case analysis for a woman at 30 weeks' gestation, Actim Partus had lower health-care costs and fewer quality-adjusted life-years (QALYs) than qfFN at 50 ng/ml, reducing costs at a rate of £56,030 per QALY lost compared with qfFN at 50 ng/ml. PartoSure is less costly than Actim Partus while being equally effective, but this is based on diagnostic accuracy data from a small study. Treatment with qfFN at 200 ng/ml and 500 ng/ml resulted in lower cost savings per QALY lost relative to fFN at 50 ng/ml than treatment with Actim Partus. In contrast, qfFN at 10 ng/ml increased QALYs, by 0.002, and had a cost per QALY gained of £140,267 relative to fFN at 50 ng/ml. Similar qualitative results were obtained for women presenting at different gestational ages. There is a high degree of uncertainty surrounding the test accuracy and cost-effectiveness results. We are aware of four ongoing UK trials, two of which plan to enrol > 1000 participants. The results of these trials may significantly alter the findings presented here. The study is registered as PROSPERO CRD42017072696. The National Institute for Health Research Health Technology Assessment programme.

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.

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

BackgroundAccurate 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.MethodsA 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.DiscussionWe 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 registrationThe EQUIPTT trial was prospectively registered on 16th January 2018 with the ISRCTN registry (no. 17846337).

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

Recent data suggest that quantitative measurements of fetal fibronectin can be used accurately to predict increased risk of preterm birth. 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. 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 48h, 14days and <34weeks gestation at qfFN thresholds of 10, 50 and 200ng/mL was assessed. The overall rate of sPTB <34weeks was 4.1% (n=373). For deliveries within 48h, within 14days and <34weeks, a qfFN threshold of 200ng/mL had positive predictive values of 26.7%, 42.9% and 46.7%, respectively, when compared to patients with qfFN values of 0-9ng/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 200ng/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.

The utility of fetal fibronectin in asymptomatic singleton and twin pregnancies with a cervical length ≤ 10 mm

Objective: To examine the utility of fetal fibronectin (fFN) for predicting spontaneous preterm birth (PTB) in asymptomatic women with a cervical length (CL) ≤10 mm compared to those with a CL 11–25 mm.Methods: Data was collected on all women with nonanomalous singleton and twin gestations who underwent transvaginal CL at a single institution between 2009 and 2012. Women with an incidental short cervix (CL ≤ 25 mm) between 22 and 32 weeks who had an fFN result within 7 days thereafter were included. Indicated preterm deliveries at <14 days of fFN, women who underwent cerclage placement, and terminations of pregnancy were excluded. The primary outcome was spontaneous PTB within 7 and 14 days of the fFN. Sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) of fFN for a CL ≤ 10 mm was calculated for singletons and twins and compared to those with a CL 11–25 mm.Results: Of the 213 women included, 117 (54.9%) were singletons and 96 (45%) were twins. Baseline characteristics were similar between those with a CL ≤ 10 mm and with a CL 11–25 mm in both singletons and twins. The NPV of fFN for delivery within 7 days in singletons and twins with a CL ≤ 10 mm was 100%, similar to those with a CL 11–25 mm (93–100%). The NPV of fFN for delivery within 14 days in singletons and twins with a CL ≤ 10 mm remained high (87.5–100%) when compared to those with a CL 11–25 mm (93–100%). The PPV of fFN for delivery within 7 and 14 days in both singletons and twins with a CL ≤ 10 mm was low (10–25%) and similar to those with a CL 11–25 mm (7.1–24.4%).Conclusions: The NPV of fFN in asymptomatic singleton and twin pregnancies with a CL ≤ 10 mm is high and comparable to the NPV of fFN in women with a longer CL. Routine fFN collection in this select population should be considered as it may avoid unnecessary and costly admissions, as well as assist with timing of antenatal corticosteroids.

Fetal fibronectin test for threatened preterm delivery 48h after admission: Cost-effectiveness study

ObjectiveThe aim of this work was to assess the cost-effectiveness of the fetal fibronectin (fFN) test at 48 h after admission for threatened preterm delivery to promote early discharge. Study designBefore-and-after study to calculate the incremental cost-effectiveness ratio (ICER). Patients were enrolled 48 h after admission in a tertiary care centre for threatened preterm delivery between 24+0 and 34+6 weeks. fFN testing was performed. During the first period, physician was blinded to fFN test and discharge occurred after apparent reduced symptomatology at physician’s discretion. During the second period, fFN test was revealed to physician and discharge was immediately proposed to negative test patients. The costs considered in this analysis were the direct medical costs from the hospital perspective: costs of hospitalisation, treatment, and imaging procedures. The efficacy criterion selected was the number of deliveries at 7 and at 14 days after admission for threatened preterm delivery. ResultsThe study included 178 pregnant patient, 99 during the first period (July 2008-October 2009) and 79 during the second (March 2010-February 2012). The lengths of hospital stays were shorter during the second period, with more than 50% of women discharged home between 48 and 72 h (p < 0.0001) resulting in a cost-saving of 76 051 euros. The number of deliveries at 7 and at 14 days was similar between the two periods. ConclusionThe fFN test at 48 h after admission supported early discharge and was safe and cost-effective.

Evaluation of additive effect of quantitative fetal fibronectin to cervical length for prediction of spontaneous preterm birth among asymptomatic high-risk women

Objective: To determine if quantitative fetal fibronectin (qFFN) in addition to transvaginal ultrasound (TVU) cervical length (CL) measurement between 180/7 and 236/7 weeks would be predictive of spontaneous preterm birth (sPTB) at <350/7 weeks among asymptomatic high-risk women as defined by those with prior sPTB > 200/7 weeks.Material and methods: A prospective observational study of asymptomatic women with singleton gestations between 180/7 and 236/7weeks and one or more prior SPTB was performed. Women at their anatomy scan who opted into universal CL screening were enrolled. At enrollment, a vaginal speculum exam was performed to collect cervico-vaginal fluid from the posterior fornix using fetal fibronectin (FFN) swab. These women were then followed until delivery. Women with multiple gestations, rupture of membranes, vaginal bleeding, intercourse, or vaginal exam within 48 h of enrollment were excluded. Physicians were blinded to the qFFN levels, but the CL measurements were made available. The primary outcome was sPTB < 350/7 weeks.Results: Of the 105 asymptomatic women with prior sPTB who were prospectively enrolled, 19 (18.1%) had recurrent sPTB < 370/7 weeks. None of the sPTB were iatrogenic. Using receiver-operating characteristic curves, qFFN ≥ 10 ng/mL had the highest sensitivity with subsequent lowest false negative rate, while FFN ≥ 50 ng/mL was identified as being the best balance of sensitivity and false positive rate for predicting sPTB < 350/7 weeks. As compared with CL ≤ 25 mm alone, with the use of CL ≤ 25 mm or qFFN ≥ 50 ng/mL as screening criteria for prediction of SPTB < 350/7 weeks, sensitivity improved from 18.2 to 63.6%, specificity decreased from 96.8 to 82.1%, positive predictive value (PPV) decreased from 40.0 to 29.2%, negative predictive value (NPV) marginally improved from 91.1 to 95.1%.Conclusion: In women with singleton gestations with prior SPTB, qFFN can be used as an adjunct to triage patients who are found to have a shortened cervix. Sensitivity and NPVs improved with the addition of qFFN to TVU CL screening alone in women with singleton gestations with prior SPTB. However, specificity and PPVs decreased.

Accuracy of qualitative maternal cervicovaginal fetal fibronectin test in predicting spontaneous preterm birth in symptomatic pregnant women

Background: The incidence of preterm birth is increasing worldwide. Preterm birth is a common cause of neonatal morbidity and mortality commonly associated with low-birth weight and deficiency of lung surfactants in the newborn. Children who were born preterm have higher rates of cerebral palsy, neurodevelopmental anomalies, learning disabilities, and respiratory illnesses compared with children born at term with attendant psychosocial and financial burden on the parents or carers. These problems may be minimized via the use of a preterm birth prediction test such as the maternal cervicovaginal fetal fibronectin test (FFT) to determine those women in genuine preterm labor and at a higher risk for preterm birth. Effective treatment can then be focused on this group of women to reduce the incidence of preterm birth. However, the FFT in preterm birth prediction is underutilized in Nigeria. Aim: To determine the role of cervicovaginal fetal fibronectin testing as a predictor of spontaneous preterm birth in symptomatic pregnant women in a local setting. Setting: This study was conducted at the obstetrics unit of the Department of Obstetrics and Gynaecology at the Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Osun state, Nigeria. The OAUTHC comprises two obstetrics units – Ife Hospital Unit (IHU) and Wesley Guild Hospital Unit at Ilesha (WGH). Design: Cross-sectional, descriptive study. Methods: In this study, 182 booked and unbooked singleton antenatal mothers between 28 weeks and 36 weeks 6 days gestation who had symptoms suggestive of preterm labor were recruited. An interviewer administered questionnaire was filled for each subject and a sterile speculum vaginal examination was then performed to obtain a specimen of the subject's cervicovaginal secretion using a sterile cotton swab. A qualitative FFT was done on each sample collected, then recruited mothers were monitored till delivery and further data obtained. Outcome Measures: The main outcome measures were the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of FFT in predicting spontaneous preterm birth in symptomatic pregnant women. Results: A total of 182 women presenting with symptoms suggestive of preterm labor were recruited: 171 (93.96%) women delivered at term, whereas 11 (6.04%) women had preterm birth with a calculated preterm birth rate of 7.33 per 1000 deliveries during the study period. Also, 7 (3.85%) women had a positive FFT, while 175 (96.15%) women had a negative test. FFT had a sensitivity, specificity, PPV, and NPV of 9.09%, 96.49%, 14.29%, and 94.29%, respectively; a LR+ and LR- of 2.59 (95% confidence interval, CI, 0.34–19.68) and 0.94 (95% CI, 0.78–1.14) respectively; a relative risk of 2.59 (95% CI, 0.341–19.675); a calculated accuracy of 91.21% (95% CI, 86.12%–94.89%); and an area under the receiver operating characteristic curve of 0.60. Conclusion: The high NPV of fetal fibronectin sampling in a population of pregnant women with symptoms supports less intervention for patients with negative results.

561: A high cervical fetal fibronectin concentration increases the risk of intra-amniotic infection/inflammation in preterm labor

561: A high cervical fetal fibronectin concentration increases the risk of intra-amniotic infection/inflammation in preterm labor

Rationale & design of the PROMISES study: a prospective assessment and validation study of salivary progesterone as a test for preterm birth in pregnant women from rural India

BackgroundIn India, 3.6 million pregnancies are affected by preterm birth annually, with many infants dying or surviving with disability. Currently, there is no simple test available for screening all women at risk of spontaneous PTB in low income setting, although high resource settings routinely use cervical length measurement and cervico-vaginal fluid fetal fibronectin for identification and care of women at risk due to clinical history. In rural India, where the public health system has limited infrastructure, trained staff and equipment, there is a greater need to develop a low-cost screening approach for providing early referral, treatment and remedial support for pregnant women at risk of preterm birth. There is interest in the use of a salivary progesterone test as a screening tool preliminary evidence from India, Egypt and UK has shown promise for this type of test. The test requires further validation in a low resource community setting.MethodsThe Promises study aims to validate and test the feasibility of introducing a low-cost salivary progesterone preterm birth prediction test in two rural districts in India with high rates of prematurity. It is a prospective study of 2000 pregnant women recruited from Panna and Satna in Madhya Pradesh over approximately 24 months. Demographic and pregnancy outcome data will be collected, and pregnancies will be dated by ultrasound sonography. Saliva progesterone will be measured by ELISA in samples obtained between 24–28 weeks of gestation. The association between salivary progesterone and preterm birth will be determined and the utility of salivary progesterone to predict preterm birth < 34, as well as < 30 and < 37 weeks assessed. Additional qualitative data will be obtained in terms of acceptability and feasibility of saliva progesterone testing and knowledge of PTB.DiscussionA validated cost-effective saliva test, which has potential for further adaptation to a ‘point of care’ setting will allow early identification of pregnant women at risk of preterm birth, who can be linked to an effective pathway of care and support to reduce preterm birth and associated adverse consequences. This will reduce both economic and emotional burden on the affected women and their families.

The review of results of foetal fibronectin at the Royal Cornwall Hospital Treliske

The manufacturer of a popular qualitative fFN assay, changed to using a quantitative assay following results from EQUIPPE study. The objective of our study was to compare our hospital data collated from our qualitative fFN assay with EQUIPPE’s data, with a view to establish its validity in our hospital. We undertook a retrospective study over a 22-month period to review the data of 432 preterm pregnant women at less than 34 weeks of gestation, who presented to the labour ward with symptoms of threatened preterm labour warranting a fFN test. None of the patient with results between 11 and 199 ng/mL delivered within 7 days. However, there was a rise in percentage of delivery at higher levels. For example, 73% of patients with levels greater or equal to 500 ng/mL delivered within 7 days. Our results are comparable with those of the EQUIPPE study. This has led to changes that could potentially save our hospital money. Impact statement What is already known on this subject? The fFN test is a well validated test used to diagnose a preterm delivery. Most units are changing from the qualitative assays that just show positive or negative results to quantitative assays that give specific numeric values. Manufacturers give a numeric range for positive and negative results. What do the results of this study add? Although our study is local to our population, our findings show that potentially more money could be saved and fewer women separated from their families, if the negative level of the fFN test is increased (following a review of their local practice). What are the implications of these findings for clinical practice and/or further research? More units should review or audit their fFN results and choose what levels to use as a cut off for the test locally. More importantly, a multicentre research is needed to validate if the negative level needs increasing from 49 ng/mL.

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

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). 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 <10ng/mL, 10-49ng/mL, 50-199ng/mL and >200ng/mL to predict outcome was also examined. 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 >32weeks of gestation, between 23 and 346 weeks of gestation with TPTL and who had fFN tests were included in the study. Fetal fibronectin <50ng/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 <34weeks was 0% for fFN <10 and 2% for women with fFN levels <200ng/mL compared to nearly 30% for levels >200ng/mL. There is noncompliance with use of fFN to its full potential. This small study also provides support for the use of a 200ng/mL cut-off fFN level for birth <34weeks. This would avoid the need to transfer to a tertiary facility many women who present with TPTL.

Prediction of Preterm Birth: Maternal Characteristics, Ultrasound Markers, and Biomarkers: An Updated Overview.

There is not a single or combined screening method for preterm birth with high sensitivity which will truly identify the women at risk for preterm birth while also with high specificity to prevent unnecessary interventions and high treatment costs. Measurement of cervical length is the most cost-effective method that is used in clinical practice. Bedside tests have also been developed for detecting markers like fetal fibronectin, insulin-like growth factor binding protein-1 (IGFBP-1), interleukin-6, and placental alpha-macroglobulin-1. Taking the maternal history, health condition, and sociodemographical factors into consideration is recommended. Ultrasound markers apart from cervical length measurements as uterocervical angle and placental strain ratio are studied. Investigations on metabolomics, proteomics, and microRNA profiling have brought a new aspect on this subject. Maybe in the future, with clear identification of women at true risk for preterm birth, development of more effective preventive strategies will not be unfeasible.

Cost-effectiveness of Diagnostic Testing Strategies Including Cervical-Length Measurement and Fibronectin Testing in Women With Symptoms of Preterm Labor

(Abstracted from Ultrasound Obstet Gynecol 2018;51:596–603) In this study, the authors sought 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.