Value of Combined Bone Morphogenetic Protein-2/7 Testing in the Assessment of Infected Preterm Labor.

Objective: To analyze the clinical significance of bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-7 (BMP-7), members of the bone morphogenetic protein family, in infectious preterm birth, to provide references for future prevention and management of IPB. Methods: The study participants were 20 pregnant women with IPB admitted to between January 2022 and January 2023 (research group) and 20 concurrent normal pregnancies (control group). Serum BMP2, BMP-7 inflammatory factors were quantified. Differences in BMP2 and BMP-7 were identified. The Receiver Operating Characteristic curve analyzed the evaluation value of BMP2 and BMP-7 on infectious preterm birth and adverse pregnancy outcomes in pregnant women, and Pearson correlation coefficient determined the correlation of the two with inflammatory factors levels. Results: The research group was higher in serum BMP2 and BMP-7 levels than control group (P < .05). The joint detection by BMP2 and BMP-7 had a sensitivity of 80.00% and a specificity of 90.00% in diagnosing infectious preterm birth (P < .05), and its sensitivity and specificity in predicting adverse pregnancy outcomes in infectious preterm birth pregnant women were 100.0% and 66.67%, respectively (P < .05). According to Pearson correlation coefficient analysis, there was an obvious positive relationship between BMP-2 and BMP-7 and inflammatory factors in research group (P < .05). Conclusions: BMP-2 and BMP-7 are elevated in IPB and are linked to inflammatory factor levels. Joint detection of BMP2 and BMP-7 shows promising potential for evaluating infectious preterm birth.

Assessment of uterine contractions in labor and delivery.

Normal labor and delivery are dependent on the presence of regular and effective contractions of the uterine myometrium. The mechanisms responsible for the initiation and maintenance of adequate and synchronized uterine activity that are necessary for labor and delivery result from a complex interplay of hormonal, mechanical, and electrical factors that have not yet been fully elucidated. Monitoring uterine activity during term labor and in suspected preterm labor is an important component of obstetrical care because cases of inadequate and excessive uterine activity can be associated with substantial maternal and neonatal morbidity and mortality. Inadequate labor progress is a common challenge encountered in intrapartum care, with labor dystocia being the most common indication for cesarean deliveries performed during labor. Hereafter, an accurate assessment of uterine activity during labor can assist in the management of protracted labor by diagnosing inadequate uterine activity and facilitating the titration of uterotonic medications before a trial of labor is prematurely terminated. Conversely, the ability to diagnose unwanted or excessive uterine activity is also critical in cases of threatened preterm labor, tachysystole, or patients undergoing a trial of labor after cesarean delivery. Knowledge of uterine activity in these cases may guide the use of tocolytic medications or raise suspicion of uterine rupture. Current diagnostic capabilities are less than optimal, hindering the medical management of term and preterm labor. Currently, different methods exist for evaluating uterine activity during labor, including manual palpation, external tocodynamometry, intrauterine pressure monitoring, and electrical uterine myometrial activity tracing. Legacy uterine monitoring techniques have advantages and limitations. External tocodynamometry is the most widespread tool in clinical use owing to its noninvasive nature and its ability to time contractions against the fetal heart rate monitor. However, it does not provide information regarding the strength of uterine contractions and is limited by signal loss with maternal movements. Conversely, the intrauterine pressure catheter quantifies the strength of uterine contractions; however, its use is limited by its invasiveness, risk for complications, and limited additive value in all but few clinical scenarios. New monitoring methods are being used, such as electrical uterine monitoring, which is noninvasive and does not require ruptured membranes. Electrical uterine monitoring has yet to be incorporated into common clinical practice because of lack of access to this technology, its high cost, and the need for appropriate training of clinical staff. Further work needs to be done to increase the accessibility and implementation of this technique by experts, and further research is needed to implement new practical and useful methods. This review describes current clinical tools for uterine activity assessment during labor and discusses their advantages and shortcomings. The review also summarizes current knowledge regarding novel technologies for monitoring uterine contractions that are not yet in widespread use, but are promising and could help improve our understanding of the physiology of labor, delivery, and preterm labor, and ultimately enhance patient care.

Reproducibility and usability assessment of the novel Fine Birth device for threatened preterm labor diagnosis.

BACKGROUND: Preterm delivery is considered the leading cause of mortality worldwide in children under 5 years old. Approximately 45 million pregnant women are hospitalized yearly for threatened preterm labor. However, only 50% of pregnancies complicated by threatened preterm labor end in delivery before the estimated date, classifying the rest as false threatened preterm labor. The ability of current diagnostic methods to predict threatened preterm labor is low (low positive predictive value), ranging between 8% and 30%. This highlights the need for a solution that accurately detects and differentiates between false and real threatened preterm labors in women who attend obstetrical clinics and hospital emergency departments with delivery symptoms. OBJECTIVE: Primarily, this aimed to assess the reproducibility and usability of a novel medical device, the Fine Birth, aimed at accurately diagnosing threatened preterm labor through the objective quantification of pregnant women's cervical consistency. Secondarily, this study aimed to evaluate the effect of training and the incorporation of a lateral microcamera on the device's reliability and usability outcomes. STUDY DESIGN: A total of 77 singleton pregnant women were recruited during their follow-up visits to the obstetrical and gynecologic departments at 5 Spanish hospitals. The eligibility criteria included pregnant women aged ≥18 years; women with a normal fetus and uncomplicated pregnancy; women without prolapse of membranes, uterine anomalies, previous cervical surgery, or latex allergy; and women signing the informed written consent. Cervical tissue stiffness was assessed using the Fine Birth device, whose technology is based on the propagation of torsional waves through the studied tissue. Cervical consistency measurements were taken for each woman until obtaining 2 valid measurements by 2 different operators. The intraobserver and interobserver reproducibilities of the Fine Birth measurements were assessed using the intraclass correlation coefficients with a 95% confidence interval and the Fisher test P value. The usability was evaluated on the basis of the clinicians' and participants' feedback. RESULTS: There was good intraobserver reproducibility (intraclass correlation coefficient, 0.88; 95% confidence interval, 0.84-0.95; Fisher test P value<.05). As the results obtained for the interobserver reproducibility did not reach the desired acceptable values (intraclass correlation coefficient of <0.75), a lateral microcamera was added to the Fine Birth intravaginal probe, and the operators involved in the clinical investigation received the corresponding training with the modified device. The analysis of 16 additional subjects demonstrated excellent interobserver reproducibility (intraclass correlation coefficient, 0.93; 95% confidence interval, 0.78-0.97) and an improvement after the intervention (P<.0001). CONCLUSION: The robust reproducibility and usability results obtained after the insertion of a lateral microcamera and the corresponding training make the Fine Birth a promising novel device to objectively quantify the patient's cervical consistency, diagnose threatened preterm labor, and, thus, predict the risk of spontaneous preterm birth. Further research is needed to demonstrate the clinical utility of the device.

Assessment of Features between Multichannel Electrohysterogram for Differentiation of Labors.

Electrohysterogram (EHG) is a promising method for noninvasive monitoring of uterine electrical activity. The main purpose of this study was to characterize the multichannel EHG signals to distinguish between term delivery and preterm birth, as well as deliveries within and beyond 24 h. A total of 219 pregnant women were grouped in two ways: (1) term delivery (TD), threatened preterm labor (TPL) with the outcome of preterm birth (TPL_PB), and TPL with the outcome of term delivery (TPL_TD); (2) EHG recording time to delivery (TTD) ≤ 24 h and TTD > 24 h. Three bipolar EHG signals were analyzed for the 30 min recording. Six EHG features between multiple channels, including multivariate sample entropy, mutual information, correlation coefficient, coherence, direct partial Granger causality, and direct transfer entropy, were extracted to characterize the coupling and information flow between channels. Significant differences were found for these six features between TPL and TD, and between TTD ≤ 24 h and TTD > 24 h. No significant difference was found between TPL_PB and TPL_TD. The results indicated that EHG signals of TD were more regular and synchronized than TPL, and stronger coupling between multichannel EHG signals was exhibited as delivery approaches. In addition, EHG signals propagate downward for the majority of pregnant women regardless of different labors. In conclusion, the coupling and propagation features extracted from multichannel EHG signals could be used to differentiate term delivery and preterm birth and may predict delivery within and beyond 24 h.

A prognostic model, including quantitative fetal fibronectin, to predict preterm labour: the QUIDS meta-analysis and prospective cohort study.

BACKGROUND: The diagnosis of preterm labour is challenging. False-positive diagnoses are common and result in unnecessary, potentially harmful treatments (e.g. tocolytics, antenatal corticosteroids and magnesium sulphate) and costly hospital admissions. Measurement of fetal fibronectin in vaginal fluid is a biochemical test that can indicate impending preterm birth. OBJECTIVES: To develop an externally validated prognostic model using quantitative fetal fibronectin concentration, in combination with clinical risk factors, for the prediction of spontaneous preterm birth and to assess its cost-effectiveness. DESIGN: The study comprised (1) a qualitative study to establish the decisional needs of pregnant women and their caregivers, (2) an individual participant data meta-analysis of existing studies to develop a prognostic model for spontaneous preterm birth within 7 days in women with symptoms of preterm labour based on quantitative fetal fibronectin and clinical risk factors, (3) external validation of the prognostic model in a prospective cohort study across 26 UK centres, (4) a model-based economic evaluation comparing the prognostic model with qualitative fetal fibronectin, and quantitative fetal fibronectin with cervical length measurement, in terms of cost per QALY gained and (5) a qualitative assessment of the acceptability of quantitative fetal fibronectin. DATA SOURCES/SETTING: The model was developed using data from five European prospective cohort studies of quantitative fetal fibronectin. The UK prospective cohort study was carried out across 26 UK centres. PARTICIPANTS: Pregnant women at 22+0-34+6 weeks' gestation with signs and symptoms of preterm labour. HEALTH TECHNOLOGY BEING ASSESSED: Quantitative fetal fibronectin. MAIN OUTCOME MEASURES: Spontaneous preterm birth within 7 days. RESULTS: The individual participant data meta-analysis included 1783 women and 139 events of spontaneous preterm birth within 7 days (event rate 7.8%). The prognostic model that was developed included quantitative fetal fibronectin, smoking, ethnicity, nulliparity and multiple pregnancy. The model was externally validated in a cohort of 2837 women, with 83 events of spontaneous preterm birth within 7 days (event rate 2.93%), an area under the curve of 0.89 (95% confidence interval 0.84 to 0.93), a calibration slope of 1.22 and a Nagelkerke R2 of 0.34. The economic analysis found that the prognostic model was cost-effective compared with using qualitative fetal fibronectin at a threshold for hospital admission and treatment of ≥ 2% risk of preterm birth within 7 days. LIMITATIONS: The outcome proportion (spontaneous preterm birth within 7 days of test) was 2.9% in the validation study. This is in line with other studies, but having slightly fewer than 100 events is a limitation in model validation. CONCLUSIONS: A prognostic model that included quantitative fetal fibronectin and clinical risk factors showed excellent performance in the prediction of spontaneous preterm birth within 7 days of test, was cost-effective and can be used to inform a decision support tool to help guide management decisions for women with threatened preterm labour. FUTURE WORK: The prognostic model will be embedded in electronic maternity records and a mobile telephone application, enabling ongoing data collection for further refinement and validation of the model. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015027590 and Current Controlled Trials ISRCTN41598423. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 52. See the NIHR Journals Library website for further project information.

Identifying which women with symptoms of labour will give birth early is challenging, so many women unnecessarily receive therapies aimed at preventing complications in preterm birth. A test called quantitative fetal fibronectin, which uses vaginal swab samples, may help to improve the diagnosis of preterm labour. Fetal fibronectin is a protein that is released from the fetal membranes that surround the developing baby in the womb. The lower the concentration of fetal fibronectin, the less likely the occurrence of preterm birth. Our aim was to see if quantitative fetal fibronectin, in combination with some features of pregnancy (e.g. previous pregnancy history and twin pregnancy), can accurately predict preterm birth in women who have symptoms of preterm labour. We asked women, their partners, doctors and midwives what information would be most useful to them, and how this should be presented. We then analysed previous research data; we used quantitative fetal fibronectin and clinical risk factors together to predict the chance of preterm birth. We explored which features could predict preterm birth most effectively while still being good value to the NHS. To ensure that this risk predictor worked in UK populations, we undertook a research study across 26 UK hospitals. Women who had symptoms of preterm labour were invited to participate. We collected information from these women (approximately 3000 women), including quantitative fetal fibronectin results. We found that a risk predictor comprising quantitative fetal fibronectin and four other features performed best at predicting whether or not preterm birth will occur within the next week for women with symptoms of preterm labour, and that this had potential to be clinically useful and cost-effective. The quantitative fetal fibronectin testing process was acceptable to women, and clinicians found the risk predictor useful. We used our findings to develop a risk calculator to help women and clinicians assess how likely preterm birth is, and decide whether or not to start treatment.

AACC Guidance Document on Laboratory Testing for the Assessment of Preterm Delivery.

Identifying women with preterm labor who will go on to deliver prematurely is crucial to improving outcomes for mother and baby and for saving healthcare resources. Even among those with symptoms, the number of women who deliver preterm is low, and thus the low positive predictive value (PPV) and high negative predictive value (NPV) associated with available biomarkers does not substantially reduce the uncertainty of the clinical diagnosis. While there is some promise in the use of fetal fibronectin (fFN), interleukin 6 (IL-6), or placental alpha microglobulin 1 (PAMG-1) for predicting preterm birth (PTB), their use is unlikely to provide considerable clinical value in populations with a low prevalence. To provide real clinical benefit, a biomarker must demonstrate a high PPV to allow identification of the minority of symptomatic women who will deliver prematurely. As none of the currently available biomarkers exhibit this performance characteristic, we do not recommend their routine clinical use in populations with a pre-test probability of PTB of <5%. Limiting biomarker testing to only high-risk women identified on the basis of cervical length or other characteristics will increase the pre-testprobability in the tested population, thereby improving PPV. PAMG-1 is associated with a higher PPV than fFN and may show clinical utility in populations with a higher pre-test probability, but further work is required to conclusively demonstrate improved outcomes in this patient group.

A Rapid Amniotic Fluid Interleukin-6 Assessment for the Identification of Intra-Amniotic Inflammation in Women with Preterm Labor and Intact Membranes.

OBJECTIVES: A multivariable predictive model has recently been developed with good accuracy to predict spontaneous preterm delivery within 7 days in women with preterm labor (PTL) and intact membranes. However, this model measures amniotic fluid (AF) interleukin (IL)-6 concentrations using the ELISA method, thereby limiting clinical implementation. The main objectives of this study were to validate the automated immunoassay as a quantitative method to measure AF IL-6 in women with PTL and to evaluate the diagnostic performance of AF IL-6 alone and as part of a multivariable predictive model to predict spontaneous delivery in 7 days with this automated method. STUDY DESIGN: This is a retrospective observational study in women with PTL below 34 weeks who underwent amniocentesis to rule out microbial invasion of the amniotic cavity. Women with clinical signs of chorioamnionitis, cervical length measurement at admission >5th centile, maternal age <18 years, and no consent to perform amniocentesis for this indication were excluded. The local Institutional Review Boards approved the study (HCB/2019/0940). Analysis of AF IL-6 Concentrations: AF IL-6 concentrations were measured using an automated Cobas e602 electrochemiluminescence immunoanalyzer and Human IL-6 Quantikine ELISA kit. RESULTS: Of the entire study group (n = 100), 38 women spontaneously delivered within 7 days after admission. Both laboratory methods showed good agreement (intraclass correlation coefficient: 0.937 (95% confidence interval [CI] 0.908-0.957); p < 0.001). Diagnostic performance of AF IL-6 to predict spontaneous delivery within 7 days when it was included in the multivariable predictive model showed an area under the receiver operating characteristic curve of 0.894 (95% CI 0.799-0.955), sensitivity of 97%, specificity of 74%, positive predictive value of 73%, negative predictive value of 97%, positive likelihood ratio (LR) of 3.7, and negative LR of 0.045. CONCLUSION: While both analytical methods were comparable for measuring AF IL-6 concentrations in women with PTL, the Cobas immunoanalyzer provided rapid diagnosis of intra-amniotic inflammation within minutes. The predictive model showed a good diagnostic performance to target women at high risk of spontaneous delivery within 7 days.

Evolución y costes de la prematuridad por indicación médica en un hospital de tercer nivel / Evolution and costs of the medically indicated preterm birth in a tertiary care university hospital

INTRODUCCIÓN Y OBJETIVO: Analizar la evolución y los costes de los partos prematuros iatrogénicos en un hospital universitario de tercer nivel. MÉTODOS: Estudio de cohortes retrospectivo de los partos con edad gestacional comprendida entre 24 y 36+6 semanas en dos periodos temporales: 2001-2005 y 2011-2016. Se identificaron los partos prematuros por indicación médica o iatrogénicos (PPI). Se analizaron variables demográficas y de resultado. Los costes se calcularon mediante el grupo relacionado con el diagnóstico (GRD) de cada ingreso. RESULTADOS: Se obtuvo una muestra de 620 partos prematuros iatrogénicos. La tasa de prematuridad global se mantuvo estable en 9%. La tasa de prematuridad iatrogénica experimentó un incremento relativo del 9,7%. Entre las pacientes con un PPI se apreció un incremento en la edad materna de 27,7 a 32,9 años, de la obesidad (32,2% a 55,5%) y del uso de técnicas de reproducción asistida (6% a 11,1%). Preeclampsia y retraso del crecimiento (CIR) fueron las principales causas de PPI, en los que se incrementó la tasa de cesáreas de 66,9% a 78%, la estancia media de 7,8 días a 9,6 y el coste por paciente de 3.068,6 a 7.331,9 euros. CONCLUSIONES: Se observa un aumento de PPI en el segundo periodo, manteniéndose la prematuridad global. Los cambios demográficos podrían explicar este incremento. Estos cambios están implicados en la fisiopatología de la preeclampsia y el CIR y en el aumento de su incidencia. La prevención primaria y secundaria de esas complicaciones podría reducir la incidencia y los costes de la prematuridad iatrogénica.

INTRODUCTION AND OBJECTIVES: To evaluate the incidence, evolution, causes and costs of premature births (PB) due to medical indication (iatrogenic) in a tertiary care university hospital METHODS: Retrospective cohort study of all deliveries with gestational age between 24 and 36+6 weeks, in two periods 2001-2005 and 2011-2016. Iatrogenic births were identified. Clinical, epidemiological, diagnostic and economic variables were analysed. RESULTS: A sample size of 620 iatrogenic deliveries was obtained. We found a 9.7% relative increase in iatrogenic prematurity rate in the second period as well as an increase in maternal age from 27.7 to 32.9, obesity from 32.2% to 55.5% and the use of assisted reproductive techniques from 6% to 11.1%. Preeclampsia and intrauterine growth restriction were found to be the main causes of iatrogenic premature delivery. In these cases the rates of cesarean section increased from 66.9% to 78%. The average stay per patient and the cost calculated by diagnosis related group (DRG) also showed a statistically significant increase from 7.8 days and 3,068.6 euros to 9.6 days and 7,331.9 euros. CONCLUSIONS: We observed an increase in iatrogenic prematurity in the second period despite the unchanged rate of spontaneous PB. Demographic changes in the population, as well as an increase in obstetric related conditions, seem to be responsible for this increase. Primary and secondary prevention of clinical characteristics may reduce the incidence and costs derived from this type of prematurity.

Does Assessment of Cervical Phosphorylated Insulin-like Growth Factor Binding Protein-1 by Bedside Vaginal Swab Test Really Predict Preterm Birth?

Preterm birth is the first cause of neonatal mortality and is associated with elevated risks of long-term complications such as neurodevelopmental impairment. Prediction of spontaneous preterm birth, one of the biggest challenges in obstetrics, aims at delaying birth in order to allow corticosteroid therapy and, if necessary, transfer of patient to a higher-level maternity care unit. We aimed to assess the predictive role of phIGFBP-1 (Actim® Partus) diagnostic test on patients at risk of preterm labor, routinely used in our institution. We conducted a retrospective cohort study on 99 patients admitted in the high-risk pregnancy unit of our institution from June 2012 to November 2014. The primary outcome measures were delivery before 34+0 and 37+0 weeks. Data analysis allowed measure of Actim® Partus test sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV and NPV), diagnostic efficiency as well as positive and negative likelihood ratios. Actim® Partus test features (Se, Sp, PPV and NPV) were 53.3, 67.9, 23.5 and 88.7% respectively for deliveries occurring ≤ 34+0 weeks and 54.2, 75.4, 55.8, and 74.2%, respectively, for deliveries occurring ≤ 37+0 weeks. Diagnostic efficiency of the test was 65.7% (≤ 34+0 weeks) and 67.7% (≤ 37+0 weeks). Positive likelihood ratios were 1.6 (≤ 34+0 weeks) and 2.2 (≤ 37+0 weeks). Negative likelihood ratios were 0.7 (≤ 34+0 weeks) and 0.6 (≤ 37+0 weeks). Results of our study show that phIGFBP-1 diagnostic test is not accurate enough in predicting preterm birth before 34+0 or 37+0 weeks, and therefore, there is little clinical interest in its everyday use.

Personalized assessment of cervical length improves prediction of spontaneous preterm birth: a standard and a percentile calculator.

BACKGROUND: A sonographic short cervix (length <25 mm during midgestation) is the most powerful predictor of preterm birth. Current clinical practice assumes that the same cervical length cutoff value should apply to all women when screening for spontaneous preterm birth, yet this approach may be suboptimal. OBJECTIVE: This study aimed to (1) create a customized cervical length standard that considers relevant maternal characteristics and gestational age at sonographic examination and (2) assess whether the customization of cervical length evaluation improves the prediction of spontaneous preterm birth. STUDY DESIGN: This retrospective analysis comprises a cohort of 7826 pregnant women enrolled in a longitudinal protocol between January 2006 and April 2017 at the Detroit Medical Center. Study participants met the following inclusion criteria: singleton pregnancy, ≥1 transvaginal sonographic measurements of the cervix, delivery after 20 weeks of gestation, and available relevant demographics and obstetrical history information. Data from women without a history of preterm birth or cervical surgery who delivered at term without progesterone treatment (N=5188) were used to create a customized standard of cervical length. The prediction of the primary outcome, spontaneous preterm birth at <37 weeks of gestation, was assessed in a subset of pregnancies (N=7336) that excluded cases with induced labor before 37 weeks of gestation. Area under the receiver operating characteristic curve and sensitivity at a fixed false-positive rate were calculated for screening at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation in asymptomatic patients. Survival analysis was used to determine which method is better at predicting imminent delivery among symptomatic women. RESULTS: The median cervical length remained fundamentally unchanged until 20 weeks of gestation and subsequently decreased nonlinearly with advancing gestational age among women who delivered at term. The effects of parity and maternal weight and height on the cervical length were dependent on the gestational age at ultrasound examination (interaction, P<.05 for all). Parous women had a longer cervix than nulliparous women, and the difference increased with advancing gestation after adjusting for maternal weight and height. Similarly, maternal weight was nonlinearly associated with a longer cervix, and the effect was greater later in gestation. The sensitivity at a 10% false-positive rate for prediction of spontaneous preterm birth at <37 weeks of gestation by a short cervix ranged from 29% to 40% throughout pregnancy, yet it increased to 50%, 50%, 53%, and 54% at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation, respectively, for a low, customized percentile (McNemar test, P<.001 for all). When a cervical length <25 mm was compared to the customized screening at 20 to 23 6/7 weeks of gestation by using a customized percentile cutoff value that ensured the same negative likelihood ratio for both screening methods, the customized approach had a significantly higher (about double) positive likelihood ratio in predicting spontaneous preterm birth at <33, <34, <35, <36, and <37 weeks of gestation. Among symptomatic women, the difference in survival between women with a customized cervical length percentile of ≥10th and those with a customized cervical length percentile of <10th was greater than the difference in survival between women with a cervical length ≥25 mm and those with a cervical length <25 mm. CONCLUSION: Compared to the use of a cervical length <25 mm, a customized cervical length assessment (1) identifies more women at risk of spontaneous preterm birth and (2) improves the distinction between patients at risk for impending preterm birth in those who have an episode of preterm labor.

Comparison of transabdominal and transvaginal ultrasonography for the assessment of cervical length in the third trimester of pregnancy.

OBJECTIVE: This study aimed to compare TA and transvaginal (TV) ultrasound assessment of cervical length (CL), as well as to assess the feasibility of the TA approach in the third trimester of pregnancy. MATERIALS AND METHODS: This was prospective study of low-risk women at 31-34 gestational weeks who underwent TA and TV CL measurements during a routine 3rd trimester scan. All examinations were performed by one operator who was blind to the measurements. Differences between the two methods were evaluated. RESULTS: 240 women were initially enrolled in the study. Paired TA and TV measurements were obtained in 123 (51.3%) women. The mean TV CL was 35.2 ± 6.8 mm and the mean TA CL was 34.7 ± 6.5 mm. There was a significant correlation between the CL measured by the two different methods (r = 0.816). No significant differences were identified between the mean CL measurements of the two techniques (t = -1.360; p = 0.176). Moreover, regarding the feasibility of TA technique, it was less likely to obtain TA CL images in cases with a cephalic fetal presentation (p = 0.028). CONCLUSION: At 31-34 gestational weeks, with an empty bladder, the cervix can be visualized by the TA approach in only about half of the cases (51.3%). The TA CL measurements show a significant correlation with the TV ones. More research is needed to determine the potential predictive value of the TA ultrasound for preterm labor.

Comparison of the effectiveness of a PAMG-1 test and standard clinical assessment in the prediction of preterm birth and reduction of unnecessary hospital admissions.

PURPOSE: The purpose of this study is to first compare the performance of the PAMG-1 biomarker test to that of standard clinical assessment (SCA) for the risk assessment of spontaneous preterm delivery (sPTD) among women with symptoms of preterm labor (PTL) and then calculate the potential impact on unnecessary admission reduction. MATERIALS AND METHODS: Patients of gestational age 240/7-366/7 with PTL symptoms, cervical dilatation ≤3 cm, no intercourse within 24 h, and clinically intact membranes were recruited consecutively into this prospective observational study. Specificity (SP), sensitivity (SN), positive-predictive value (PPV), and negative-predictive value (NPV) for the PAMG-1 test and SCA, for which a positive result was defined as patient admission, for predicting spontaneous delivery ≤7 and ≤14 d of presentation were calculated. RESULTS: One hundred and forty-eight patients were included in the analysis, 132 of which had both SCA and PAMG-1 results available. For the prediction of sPTD ≤7 d for SCA and PAMG-1, the PPV and NPV were 10% and 100%, and 71% and 98%, respectively. For prediction of sPTD ≤14 d for SCA and PAMG-1, the PPV and NPV were 14% and 100%, and 86% and 96%, respectively. Sixty-one per cent (81/132) of patients were admitted for treatment and/or observation. CONCLUSION: Our study reinforces the critical role of the PAMG-1 biomarker test to aid in risk assessment of imminent spontaneous preterm delivery in patients with symptoms of PTL. The PAMG-1 test was found to be statistically superior to standard clinical assessment alone, with respect to specificity. Based on our data, the introduction of a PAMG-1 test result into clinical decision making could reduce up to 91% of unnecessary admissions for women presenting with threatened preterm labor.

Use of fetal fibronectin testing in women transferred for threatened preterm labour in remote far north Queensland.

BACKGROUND: Threatened preterm labour is a common reason for medical transfer from remote communities; however, many transferred women do not deliver preterm. A tool for prediction of preterm birth such as fetal fibronectin may reduce transfers and related social and economic costs. AIM: To review the use of fetal fibronectin testing in women transferred for threatened preterm labour from Cape York to Cairns Hospital between 2011 and 2015 and determine the role testing could play in reducing transfers and associated costs. MATERIALS/METHODS: Records from the Royal Flying Doctor Service and Cairns Hospital were accessed. Women transferred solely for threatened preterm labour were included in the study. Fetal fibronectin testing, hospital admission, outpatient stays and birth outcome data were collated and analysed. Costs were assigned using the National Hospital Cost Data Collection, round 19. RESULTS: Forty-seven women were included in the study; however, only 20 underwent fetal fibronectin testing. Transfer of 30 women who had either a negative test or were not tested but delivered at term resulted in 41 inpatient nights and 443 excess outpatient nights, costing an estimated AU$57 408. Aeromedical transfers were estimated to cost a further $151 500. CONCLUSION: Adherence to clinical guidelines and greater availability and use of fetal fibronectin testing in Cape York have the potential to reduce aeromedical transfers for threatened preterm labour. Substantial inpatient and excess outpatient stays could be avoided with associated reduction in health system and social costs. Strategies to improve adherence to guidelines and increase access to testing are required.

Study protocol: quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 2, UK Prospective Cohort Study.

INTRODUCTION: The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (fFN) concentration, in combination with clinical risk factors. METHODS AND ANALYSIS: The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts, USA) which quantifies fFN in a vaginal swab. In QUIDS part 2, we will perform a prospective cohort study in at least eight UK consultant-led maternity units, in women with symptoms of preterm labour at 22+0 to 34+6 weeks gestation to externally validate a prognostic model developed in QUIDS part 1. The effects of quantitative fFN on anxiety will be assessed, and acceptability of the test and prognostic model will be evaluated in a subgroup of women and clinicians (n=30). The sample size is 1600 women (with estimated 96-192 events of preterm delivery within 7 days of testing). Clinicians will be informed of the qualitative fFN result (positive/negative) but be blinded to quantitative fFN result. Research midwives will collect outcome data from the maternal and neonatal clinical records. The final validated prognostic model will be presented as a mobile or web-based application. ETHICS AND DISSEMINATION: The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). VERSION: Protocol V.2, Date 1 November 2016. TRIAL REGISTRATION NUMBER: ISRCTN 41598423andCPMS: 31277.

[Fibronectin test in threatened preterm labour: cost-saving but not yet widely implemented in the Netherlands]. / Fibronectinetest bij dreigende vroeggeboorte.

OBJECTIVE: Analysis of national implementation of the foetal fibronectin test in the diagnostics of threatened preterm labour in the Netherlands, and indication of the possible obstacles and consequences of implementation or no implementation. DESIGN: National questionnaire, retrospective cohort study and cost-effectiveness calculation. METHODS: We approached all hospitals in the Netherlands (n = 86) with a questionnaire on use of the fibronectin test. We also collected data on women who were referred to the Academic Medical Center (AMC), a tertiary care centre in Amsterdam, with symptoms of threatened preterm labour. We investigated whether the referred patients gave birth within 7 days, and whether unnecessary transfer to a centre with a neonatal intensive care unit (NICU) could have been avoided by implementation of the fibronectin test in the referring hospital. RESULTS: The fibronectin test was used in 34% of the hospitals and an additional 17% were in the process of implementation. The most important reasons not to use the fibronectin test were of a financial nature (50%). The cohort study included 96 women who were referred from secondary care. In our cohort, 36% of all transfers could have been avoided by implementation of the fibronectin test in secondary care. CONCLUSION: The fibronectin test can greatly reduce overtreatment and unnecessary transfer in threatened preterm labour, but implementation remains limited. Costs of the test are an obstacle for the referring hospitals, while implementation prevents unnecessary transport, admission and treatment of pregnant women, giving a potential saving of at least EUR 1,027,930 per year. Inclusion in the Netherlands Society for Obstetrics and Gynaecology (Nederlandse Vereniging voor Obstetrie en Gynaecologie, NVOG) guidelines would be a first step towards wider implementation. Slow implementation exemplifies a more widespread problem: the current reimbursement system does not stimulate such cost-saving innovations.

Economic consequences of over-diagnosis of threatened preterm labor.

OBJECTIVE: To investigate whether adherence to a cervical length-based protocol can reduce both unnecessary admissions and the socioeconomic costs associated with inappropriately admitted patients. METHODS: The present retrospective observational study included women admitted for threatened preterm labor (TPL) at 24-34 weeks of pregnancy to a tertiary hospital in the Canary Islands, 2009-2014. Data were reviewed from all patients admitted for TPL. Those with a long cervix (>25 mm) were classified as "inappropriate admissions", and both the economic burden based on diagnosis-related group (DRG) and the social costs associated with sick leave for these women were calculated. RESULTS: During the 6-year study period, 430 women were admitted for TPL. The rate of inappropriate hospital admissions was 45% in the first year, but was reduced to 23% in the final year (P<0.001); the premature delivery rates in these years did not differ (P=0.224). The mean DRG-based cost of the admission per patient with a long cervix was EU euros €2099. The total annual costs from inappropriate admission (both social security sick leave costs and hospital costs) were estimated to be up to €571 047.37 during the 6-year study period, and reduced from €60 420.76 in 2009 to €29 998.04 in 2014. CONCLUSION: Reductions in inappropriate admissions from applying cervical length-based management protocol could reduce healthcare costs without increasing the incidence of premature delivery.

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.

False Labor at Term in Singleton Pregnancies: Discharge After a Standardized Assessment and Perinatal Outcomes.

OBJECTIVE: To evaluate perinatal outcomes in women sent home with a diagnosis of false labor at term and assess the time interval to return for delivery. METHODS: This was a prospective observational cohort study of women at 37 0/7 to 41 6/7 weeks of gestation without pre-existing medical complications who presented to our hospital-based triage unit with symptoms of labor and underwent a standardized evaluation. Women diagnosed as having false labor with a live singleton fetus in cephalic presentation without a prior cesarean delivery and sent home were compared with a group of similar women diagnosed to be in spontaneous labor. Women with hypertension, diabetes, and known fetal malformations were excluded. Using a perinatal composite outcome of respiratory insufficiency, intraventricular hemorrhage, culture-proven sepsis, Apgar score 3 or less at 5 minutes, phototherapy, and perinatal death, we tested the noninferiority of being sent home compared with being admitted for labor. The relationship of cervical dilatation to the time interval from discharge home to delivery was also analyzed. RESULTS: Between October 2012 and March 2016, a total of 3,949 women met inclusion criteria and were diagnosed with false labor, discharged, and returned to deliver, whereas 2,592 similar women were admitted in early labor. The mean interval from discharge to return was 4.9 days. Cesarean delivery rates were not different between the study groups-11% for both (P=.69), and the perinatal composite outcome rates were not significantly different between those sent home and those admitted-3.2% compared with 3.1% (P=.79). Women with more advanced cervical dilatation at discharge returned and delivered significantly earlier than those with less dilatation regardless of parity. CONCLUSION: Discharge with false labor at term after a standardized assessment in a triage unit was not associated with increased rates of adverse perinatal composite outcomes or cesarean delivery. The time interval to return for delivery was significantly associated with the cervical dilatation at discharge.

Teste qualitativo para a detecção de fibronectina fetal para diagnóstico trabalho de parto prematuro / Qualitative test for the detection of fetal fibronectin for the diagnosis of preterm labor

CONTEXTO: Parto prematuro é definido como nascimento antes das 37 semanas completas, ou seja, antes de 259 dias. Conforme o material publicado pela Organização Mundial de Saúde, o Relatório de Ação Global sobre o Nascimento Prematuro, cerca de 15 milhões de nascimentos prematuros ocorrem em todo o mundo, anualmente. O Brasil aparece em décimo lugar entre os dez países com os maiores números de partos prematuros, apresentando em 2010, 202.630 (7,08%) partos pré-termos (OMS, 2012). Assim, a prematuridade, ainda hoje, é um grande problema de saúde pública, constituindo-se em uma das causas de morbidade e mortalidade neonatal. No Brasil, o exame disponibilizado em serviços públicos de saúde para avaliação de gestante em risco de parto prematuro é a medida do colo uterino realizada por meio de ultrassonografia transvaginal (Febrasgo, 2012), onde o encurtamento do comprimento do colo do útero ou presença de dilatação observados por meio da ultrassonografia transvaginal pode predizer a possibilidade de parto prematuro espontâneo (Honest et al., 2003). No entanto, há grande variação entre os estudos com relação à idade gestacional para realização da ultrassonografia transvaginal, bem com a definição do ponto (medida em milímetros) de corte para avaliação da acurácia na previsão de parto prematuro espontâneo (Honest et al., 2003). TRATAMENTO RECOMENDADO: O fato de existir dificuldades relacionadas ao diagnóstico inicial do TPP faz com que até o momento não exista protocolo, baseado em evidências, sobre quais alterações de contratilidade uterina e do colo uterino justificam a realização do tratamento (Bittar, Zugaib, 2009). A maior parte dos tratamentos visa prevenir complicações neonatais por meio do uso de corticosteróides e antibióticos, além de evitar partos traumáticos. No entanto, existem práticas obstétricas para as quais ainda se tem pouca evidência de eficácia na prevenção ou tratamento de parto prematuro, como: repouso, hidratação, sedação, monitoramento de atividade uterina em casa e tocólise (Goldenberg, 2002). A TECNOLOGIA: A fibronectina fetal é uma glicoproteína adesiva complexa da matriz extracelular que ocupa o espaço entre trofoblasto e decídua materna, funcionando como material responsável pela adesão entre as membranas fetais e os tecidos uterinos (El-Messidi, Cameron, 2010; Renzo et al., 2011). Tal proteína pode ser detectada nas secreções cervico-vaginais das mulheres durante as primeiras 22 semanas de gravidez. Ainda, não se sabe o real significado da sua presença na vagina durante as primeiras 22 semanas de gravidez (El-Messidi, Cameron, 2010; Renzo et al., 2011), mas pode ser apenas um reflexo do crescimento normal de trofoblastos e da placenta. A detecção de fibronectina fetal nas secreções cervico-vaginais entre a 22ª e a 34ª semana de gestação completa está associada ao parto pré-termo nas mulheres grávidas sintomáticas e assintomáticas, pois, se relaciona com modificações bioquímicas, as quais levarão a alterações cervicais e contrações uterinas (Morrison, 1993, Goldenberg,1996). Para a detecção da fibronectina fetal, podem ser utilizados dois tipos de teste: o qualitativo e o quantitativo. No Brasil, está disponível o teste rápido (qualitativo), em que o resultado é obtido em dez minutos. EVIDÊNCIAS CIENTÍFICAS: O demandante realizou uma revisão sistemática cujo objetivo foi avaliar a acurácia de dois testes diagnósticos para detecção de partos prematuros em gestantes de risco, sintomáticas, entre a 20ª e 34ª semanas de gestação, o teste para detecção de fibronectina fetal e a medida do colo uterino por meio de ultrassonografia transvaginal, onde empregaram a seguinte estrutura para o acrônimo "PICO": População - Gestantes em trabalho de parto prematuro, sintomáticas, entre a vigésima quarta e a trigésima quarta semanas de gestação. Intervenção - Teste para detecção de fibronectina fetal. Comparador - Avaliação da medida do colo do útero por meio de Ultrassonografia Transvaginal. Outcome (Desfecho) - Acurácia de ambos os testes em diagnosticar a ocorrência ou não de partos antes da 34ª semana de gestação. Utilizando-se dos seguintes critérios de inclusão de artigos: Estudos que avaliem a acurácia de ambos os testes (sensibilidade, especificidade, valor preditivo negativo, valor preditivo positivo, likelihood + (LR+), likelihood- (LR-) na ocorrência de partos antes da 34ª semana de gestação, publicados no período de janeiro de 2000 a maio de 2013, que incluíram gestantes sintomáticas de risco para partos prematuros e que realizaram o teste da fibronectina fetal ou foram avaliadas quanto à medida do colo uterino entre a 20ª e 34ª semanas de gestação. Como fonte de busca foram utilizados o PUBMED, EMBASE e LILACS com os seguintes termos: fibronectina fetal, medida de colo uterino, acurácia do diagnóstico, parto prematuro, sensibilidade e especificidade e likelihoodratios. Sendo incluídos apenas estudos que apresentassem os dados de sensibilidade ou especificidade ou valor preditivo positivo ou valor preditivo negativo ou likelihoodratio de ambos os testes para detecção de partos prematuros antes da 34ª semana. Esses critérios foram aplicados pelo primeiro autor na leitura dos resumos e títulos dos artigos, e checada pelo segundo autor. Qualquer discrepância foi discutida e resolvida entre os autores. Se o título ou resumo atendesse à questão clínica delineada e aos tipos de publicação procurados, o texto integral do artigo foi recuperado para uma avaliação mais detalhada. CONSIDERAÇÕES FINAIS: A evidência atualmente disponível sobre a validade, eficácia e segurança da fibronectina fetal na predição de provável trabalho de parto prematuro, pela apresentação do proponente foi baseada em estudos observacionais de baixa qualidade pelo pouco rigor metodológico, além de revisão sistemática que inclui estudos apresentando grande heterogeneidade com nível de evidência baixa (GRADE [resultados inconsistentes, presença de indirectividade, imprecisão, ausência de cegamento, provável viés de seleção]) e grau de recomendação fraca a favor da tecnologia (GRADE ­ as vantagens provavelmente superam as desvantagens). A avaliação econômica apresentada (análise de custo-efetividade e de impacto orçamentário) apresenta limitações e incompletude em seus principais aspectos, não permitindo conclusões razoáveis e seguras. Neste sentido, os resultados apresentados pelos estudos mais recentes ( Baaren et al. 2013; Deshpande et al. 2013) sugerem que a fibronectina fetal em combinação com a medida do colo uterino através de ultrassonografia transvaginal pode predizer trabalho de parto prematuro com maior segurança e confiabilidade do que o uso do teste isolado da fibronectina fetal. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 04/02/2015 deliberaram, por unanimidade, por não recomendar a incorporação do teste qualitativo para detecção de fibronectina fetal para diagnóstico trabalho de parto prematuro. DECISÃO: PORTARIA Nº 15, de 9 de abril de 2015 - Torna pública a decisão de não incorporar o teste qualitativo para a detecção de fibronectina fetal para diagnóstico do trabalho de parto prematuro no âmbito do Sistema Único de Saúde - SUS.

Assessment of cervicovaginal vascular endothelial growth factor in predicting preterm delivery.

AIM: The aim of this study is to estimate the effectiveness of cervicovaginal vascular endothelial growth factor (VEGF) in predicting preterm delivery. METHODS: Cervicovaginal VEGF was measured in 30 women who presented symptoms or signs of threatened preterm labor and the control group of 30 healthy pregnant patients by enzyme-linked immunoassay. RESULTS: There was no statistically significant difference in cervicovaginal VEGF values between the threatened preterm labor group and the control group (P > 0.05). Similarly, no statistically significant difference was observed in terms of cervical length and cervicovaginal VEGF values between preterm and term-delivered groups (P > 0.05). Additionally, there was no correlation between cervicovaginal VEGF values and cervical length (P > 0.05) between the threatened preterm labor and the control groups. CONCLUSION: No correlation was found between cervicovaginal VEGF values and the preterm delivery. However, we believe that the role of VEGF in preterm delivery needs to be investigated further in well-designed studies with larger samples.