Zonulin: can it be used as a marker for preterm labor?

OBJECTIVE: Inflammation has been reported to increase zonulin levels, a protein that regulates intestinal permeability. The aim of this study was to investigate the association of serum zonulin levels with preterm labor in pregnant women. PATIENTS AND METHODS: A total of 180 pregnant women between 32-42 weeks of gestation were included in the study. Among those whose gestational week is less than 37, preterm labor (group 1), normal course pregnant (group 2), and gestational weeks between 37-42 pregnant women with normal course (group 3), term labor (group 4) groups were formed. RESULTS: Zonulin levels were not statistically different between groups. Among the inflammation markers, only C-reactive protein levels were significantly higher in group 1 compared to groups 2 and 3. There were a total of 18/90 (20%) pregnant women with premature rupture of membranes (PROM) in the delivery groups. The mean zonulin level was higher in those with PROM (155.3±50.2 ng/ml) than those without PROM (128.8±59 ng/ml). However, there was no statistically significant difference between them. CONCLUSIONS: In conclusion, serum zonulin levels were not useful as a marker for predicting preterm labor. However, examining large-scale studies about the relationship between PROM and zonulin is still needed.

Anaphylaxis-induced premature uterine contractions: a case report and literature review.

BACKGROUND: Preterm labor is caused by multiple etiologies, including intra-amniotic infection and/or intra-amniotic inflammation, vascular disorders, cervical disease, decidual senescence, and breakdown of maternal-fetal tolerance. Accumulating evidence in vivo and in vitro has shown that an allergic reaction, including anaphylaxis, can induce preterm uterine contractions. This report describes a case of a pregnant woman who developed anaphylaxis and regular uterine contractions after the ingestion of a strawberry-coated biscuit. We also review the mechanism of allergic reaction (hypersensitivity)-induced preterm labor. Case presentation A 31-year-old woman (gravida 1, para 0) at 30+2 weeks of gestation was admitted to the labor and delivery unit with regular uterine contractions and anaphylactic symptoms after she ingested a strawberry-coated biscuit as a snack. The uterine contractions resolved after the treatment of anaphylaxis by administering antihistamines and epinephrine. The patient subsequently delivered at 39+3 weeks of gestation. The amniotic fluid profile showed no infection or inflammation. A postpartum skin-prick test confirmed a positive type 1 hypersensitivity reaction to the strawberry-coated biscuit. CONCLUSIONS: We report a case of anaphylaxis-induced uterine contractility in which uterine contractions subsided after the treatment of anaphylaxis. The absence of intra-amniotic infection and/or intra-amniotic inflammation and the cause of the anaphylaxis were confirmed. Our findings indicate that maternal allergic reactions may be one of the mechanisms of preterm labor.

Understanding the course of attention deficit hyperactivity disorder in children born after a threatened preterm labor: a 6-year cohort study.

BACKGROUND: Recent research suggests that children born after suspected preterm labor may observe a potential cluster with different attention deficit hyperactivity disorder features, depending on the time of birth. However, the evolution of symptoms and their predictors remain unknown in this population. OBJECTIVE: This study aimed to examine the trajectories of attention deficit hyperactivity disorder symptoms of children born after suspected preterm labor, between ages 2 and 6 years, considering prematurity condition and comparing with controls. In addition, this study aimed to find potential modifiable predictors of evolution to enhance prognosis. STUDY DESIGN: In this prospective cohort study, 119 mother-child pairs who experienced suspected preterm labor and 60 controls were included. Patients were divided according to prematurity condition in full term (n=27), late preterm (n=55), and very preterm (n=37). Attention deficit hyperactivity disorder symptoms were assessed at ages 2 and 6 years. The association between potential modifying factors (group, time of assessment, sex, birthweight percentile, maternal history of trauma, maternal anxiety at diagnosis, and maternal anxiety during the children's assessments) and disorder trajectories was assessed by adjusting the Bayesian mixed linear models. All analyses were performed in R (version 4.3.0; R Foundation for Statistical Computing, Vienna, Austria). RESULTS: An interaction emerged between time and group, with late-preterm neonates born after suspected preterm labor being the only group to improve from ages 2 to 6 years (-2.26 points in Conners scale per percentile decrease and 0.98 probability of effect). Another interaction between time and maternal anxiety at postnatal time assessments intensified over time (0.07 and 0.84). Predictors of symptom severity included lower weight percentile at birth (-0.2 and 0.96), male sex (-2.99 and <0.99), higher maternal anxiety at diagnosis (+0.08 and 0.99), and maternal history of trauma (+0.23 and 0.98). CONCLUSION: Unlike very-preterm and full-term children, those born late preterm showed an improvement over time, probably because late-preterm children do not carry the sequelae derived from severe prematurity but benefit from close monitoring. As maternal psychopathology emerged as a determinant modifier of course and severity, it is crucial to develop targeted psychological interventions for pregnant individuals and reevaluate monitoring programs for their offspring, regardless of prematurity.

A multivariable prediction model for intra-amniotic infection in patients with preterm labor and intact membranes including a point of care system that measures amniotic fluid MMP-8.

OBJECTIVES: Among patients with preterm labor and intact membranes (PTL), those with intra-amniotic infection (IAI) present the highest risk of adverse perinatal outcomes. Current identification of IAI, based on microbiological cultures and/or polymerase chain reaction amplification of the 16S ribosomal RNA gene, delay diagnosis and, consequently, antenatal management. The aim to of the study was to assess the performance of a multivariable prediction model for diagnosing IAI in patients with PTL below 34.0 weeks using clinical, sonographic and biochemical biomarkers. METHODS: From 2019 to 2022, we prospectively included pregnant patients admitted below 34.0 weeks with diagnosis of PTL and had undergone amniocentesis to rule in/out IAI. The main outcome was IAI, defined by a positive culture and/or 16S ribosomal RNA gene in amniotic fluid. Based on the date of admission, the sample (n=98) was divided into a derivation (2019-2020, n=49) and validation cohort (2021-2022, n=49). Logistic regression models were developed for the outcomes evaluated. As predictive variables we explored ultrasound cervical length measurement at admission, maternal C-reactive protein, gestational age, and amniotic fluid glucose and matrix metalloproteinase-8 (MMP-8) levels. The model was developed in the derivation cohort and applied to the validation cohort and diagnostic performance was evaluated. Clinical management was blinded to the model results. RESULTS: During the study period, we included 98 patients admitted with a diagnosis of PTL. Of these, 10 % had IAI. The final model included MMP-8 and amniotic fluid glucose levels and showed an area under the receiver operating characteristic curve to predict the risk of IAI of 0.961 (95 % confidence interval: 0.860-0.995) with a sensitivity of 75 %, specificity of 93.3 %, positive likelihood ratio (LR) of 11.3 and negative LR of 0.27 in the validation cohort. CONCLUSIONS: In patients with PTL, a multivariable prediction model including amniotic fluid MMP-8 and glucose levels might help in the clinical management of patients undergoing amniocentesis to rule in/out IAI, providing results within a few minutes.

Management of preterm labor: Clinical practice guideline and recommendation by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine Foundation.

This practice guideline follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the management of preterm labor. In fact, this document provides further guidance for healthcare practitioners on the appropriate use of examinations with the aim to improve the accuracy in diagnosing preterm labor and allow timely and appropriate administration of tocolytics, antenatal corticosteroids and magnesium sulphate and avoid unnecessary or excessive interventions. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world in the light of scientific literature and serves as a guideline for use in clinical practice.

FIGO good practice recommendations for preterm labor and preterm prelabor rupture of membranes: Prep-for-Labor triage to minimize risks and maximize favorable outcomes.

Preterm labor occurs in around 10% of pregnancies worldwide. Once diagnosed, significant efforts must be made to reduce the likelihood of morbidity and mortality associated with preterm birth. In high-resource settings, access to hospitals with a neonatal intensive care unit (NICU) is readily available, whereas access to NICU care is limited in low- and middle-income countries (LMICs) and many rural settings. Use of FIGO's Prep-for-Labor triage method rapidly identifies low- and high-risk patients with preterm labor to enable clinicians to decide whether the patient can be managed on site or if transfer to a level II-IV facility is needed. The management steps described in this paper aim to minimize the morbidity and mortality associated with preterm labor and in the setting of preterm labor with preterm premature rupture of membranes (PPROM). The methods for accurate diagnosis of PPROM and chorioamnionitis are described. When the risk of preterm birth is high, antenatal corticosteroids should be administered for lung maturation combined with limited tocolysis for 48 hours to permit the corticosteroid course to be completed. Magnesium sulfate is also administered for fetal neuroprotection. Implementation of FIGO's Prep-for-Labor triage method in an LMIC setting will help improve maternal and neonatal outcomes.

Prediction of spontaneous preterm birth using CCL2 and CXCL10 in maternal serum of symptomatic high-risk pregnant women: a prospective cohort study.

INTRODUCTION: CCL2 and CXCL10 are putative biomarkers for the prediction of spontaneous preterm birth. This study evaluates these markers in a cohort of pregnant high-risk women. MATERIAL AND METHODS: In our prospective study, we included 109 women with signs of preterm labor between 20 + 0 and 31 + 6 weeks of gestation. Inclusion criteria were regular (< 3/30 min) or painful contractions, cervical length < 25 mm or a history of previous preterm birth (PTB). Blood samples were obtained upon first admission to our clinic. Biomarker concentrations were measured using pre-coated sandwich immunoassays (ELISA). Primary study outcome was spontaneous preterm birth < 34 weeks, secondary outcome was delivery < 37 weeks or within seven days after study inclusion. RESULTS: Sixteen women (14.7%) delivered < 34 weeks and twenty women between 34 + 0 and 36 + 6 weeks (18.4%). Six patients (5.5%) gave birth within seven days after study admission. CXCL10 showed higher medium serum levels in women with PTB < 34 weeks (115 pg/ml compared to 61 pg/ml ≥ 34 weeks; p < 0.001) and < 37 weeks (103 pg/ml vs. 53 pg/ml; p < 0.001). In contrary, lower CCL2 serum levels were associated with PTB < 34 weeks (46 pg/ml vs. 73 pg/ml; p = 0.032) and birth within 7 days (25 pg/ml vs. 73 pg/ml; p = 0.008). The CXCL10/CCL2-ratio further improved the predictive model with a ROC-AUC of 0.83 (95% CI 0.73-0.93, p < 0.001) for delivery < 34 weeks. These corresponds to a sensitivity, specificity and positive predictive value of 0.67, 0.86 and 0.43 at a cut-off of 2.2. CONCLUSION: Low maternal serum CCL2 levels are associated with a higher risk of preterm delivery within seven days. High CXCL10 serum levels are more associated with a high risk for preterm birth < 34 weeks. Elevated CXCL10/CCL2-ratio is showing the best predictive performance. TRIAL REGISTRATION NUMBER (DRKS-ID): DRKS00010763, Registration date: September 02, 2016.

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.

Prediction of Preterm Labor from the Electrohysterogram Signals Based on Different Gestational Weeks.

Timely preterm labor prediction plays an important role for increasing the chance of neonate survival, the mother's mental health, and reducing financial burdens imposed on the family. The objective of this study is to propose a method for the reliable prediction of preterm labor from the electrohysterogram (EHG) signals based on different pregnancy weeks. In this paper, EHG signals recorded from 300 subjects were split into 2 groups: (I) those with preterm and term labor EHG data that were recorded prior to the 26th week of pregnancy (referred to as the PE-TE group), and (II) those with preterm and term labor EHG data that were recorded after the 26th week of pregnancy (referred to as the PL-TL group). After decomposing each EHG signal into four intrinsic mode functions (IMFs) by empirical mode decomposition (EMD), several linear and nonlinear features were extracted. Then, a self-adaptive synthetic over-sampling method was used to balance the feature vector for each group. Finally, a feature selection method was performed and the prominent ones were fed to different classifiers for discriminating between term and preterm labor. For both groups, the AdaBoost classifier achieved the best results with a mean accuracy, sensitivity, specificity, and area under the curve (AUC) of 95%, 92%, 97%, and 0.99 for the PE-TE group and a mean accuracy, sensitivity, specificity, and AUC of 93%, 90%, 94%, and 0.98 for the PL-TL group. The similarity between the obtained results indicates the feasibility of the proposed method for the prediction of preterm labor based on different pregnancy weeks.

The increased cfRNA of TNFSF4 in peripheral blood at late gestation and preterm labor: its implication as a noninvasive biomarker for premature delivery.

Introduction: Given the important roles of immune tolerance and inflammation in both preterm and term labor, some inflammation-related genes could be related to the initiation of labor, even preterm labor. Inspection of cell-free RNA (cfRNA) engaged in inflammation in maternal blood may represent the varied gestational age and may have significant implications for the development of noninvasive diagnostics for preterm birth. Methods: To identify potential biomarkers of preterm birth, we investigated the cfRNA and exosomal miRNA in the peripheral blood of pregnant women at different gestational ages that undergo term labor or preterm labor. 17 inflammatory initiation-related cfRNAs were screened by overlapping with the targets of decreasing miRNAs during gestation and highly expressed cfRNAs at late gestation in maternal blood. To reveal the origins and mechanisms of these screened cfRNAs, the datasets of single-cell RNA sequencing from peripheral blood mononuclear cells of pregnant women, the fetal lung, and the placenta across different gestational ages were analyzed. Results: During late gestation, TNFSF4 expression increased exclusively in pro-inflammatory macrophages of maternal blood, whereas its receptor, TNFRSF4, increased expression in T cells from the decidua, which suggested the potential cell-cell communication of maternally-originated pro-inflammatory macrophages with the decidual T cells and contributed to the initiation of labor. Additionally, the cfRNA of TNFSF4 was also increased in preterm labor compared to term labor in the validation cohorts. The EIF2AK2 and TLR4 transcripts were increased in pro-inflammatory macrophages from both fetal lung and placenta but not in those from maternal mononuclear cells at late gestation, suggesting these cfRNAs are possibly derived from fetal tissues exclusively. Moreover, EIF2AK2 and TLR4 transcripts were found highly expressed in the pro-inflammatory macrophages from decidua as well, which suggested these specific fetal-origin macrophages may function at the maternal-fetal interface to stimulate uterine contractions, which have been implicated as the trigger of parturition and preterm labor. Discussion: Taken together, our findings not only revealed the potential of peripheral TNFSF4 as a novel cfRNA biomarker for noninvasive testing of preterm labor but further illustrated how maternal and fetal signals coordinately modulate the inflammatory process at the maternal-fetal interface, causing the initiation of term or preterm labor.

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.

A nomogram to optimize the timing of antenatal corticosteroids in threatened preterm delivery.

BACKGROUND: Recent observational studies reported a high rate of suboptimal use of antenatal corticosteroids (too anticipated or retrospectively not indicated) for women at risk of preterm delivery despite a recommended use within 7 days before delivery. OBJECTIVE: This study aimed to elaborate a nomogram aiming at optimizing the timing of administration of antenatal corticosteroids in case of threatened preterm labor, asymptomatic short cervix, or uterine contractions. STUDY DESIGN: This was an observational retrospective study conducted in a tertiary hospital. All women between 24 and 34 weeks of gestation who received corticosteroids during hospitalization for threatened preterm delivery, asymptomatic short cervix, or uterine contractions requiring tocolysis between 2015 and 2019 were included. Clinical, biological, and sonographic data of women were used to construct logistic regression models for predicting delivery within 7 days. The model was validated on an independent series of women hospitalized in 2020. RESULTS: Among the 1343 women included in this study, the risk factors independently associated with a delivery within 7 days in multivariate analysis were vaginal bleeding (odds ratio, 14.47; 95% confidence interval, 7.81-26.81; P<.001); need for a second-line tocolysis, such as atosiban (odds ratio, 5.66; 95% confidence interval, 3.39-9.45; P<.001); C-reactive protein level (per 1 mg/L increase; odds ratio, 1.03; 95% confidence interval, 1.02-1.04; P<.001); cervical length (per 1 mm increase; odds ratio, 0.84; 95% confidence interval, 0.82-0.87; P<.001); uterine scar (odds ratio, 2.98; 95% confidence interval, 1.33-6.65; P=.008), and gestational age at admission (per week of amenorrhea increase; odds ratio, 1.10; 95% confidence interval, 1.00-1.20; P=.041). Based on these results, a nomogram was developed that, in retrospect, would have allowed physicians to avoid or delay antenatal corticosteroids in 57% of cases in our population. The discrimination of the predictive model was good when applied to the validation set of 232 women hospitalized in 2020. It would have enabled physicians to avoid or delay antenatal corticosteroids in 52% of cases. CONCLUSION: This study developed a simple use, accurate prognostic score to identify women at risk of delivery within 7 days in cases of threatened preterm delivery, asymptomatic short cervix, or uterine contractions and thereby optimized the use of antenatal corticosteroids.

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.

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.

Activity restriction for women with arrested preterm labor: a randomized controlled trial.

BACKGROUND: In the past, some pregnant women have been recommended to be in activity restriction because of the presumed increased risk of preterm birth due to the increased release of catecholamines, which might stimulate myometrial activity, during exercise and aerobic activity. OBJECTIVE: This study aimed to test the hypothesis that in women with singleton pregnancy and arrested preterm labor, activity restriction would reduce the rate of preterm birth at <37 weeks of gestation. STUDY DESIGN: This was a parallel-group nonblinded randomized trial conducted at a single center in Italy. Eligible patients were those with a diagnosis of arrested preterm labor, defined as not delivering after 48 hours of hospitalization for threatened preterm labor, with transvaginal ultrasound cervical length ≤25 mm, no other symptoms of possible uterine contractions, and cervical dilatation <3 cm at pelvic examination. Inclusion criteria were singleton pregnancies between 24 0/7 and 33 6/7 weeks of gestation. Participants were randomized in a 1:1 ratio to either activity restriction at the time of discharge or no activity restriction. Women in the intervention group were recommended activity restriction, defined as the following: pelvic rest, prohibition of sexual activity, and reduction of work and/or nonwork activity. The primary endpoint was preterm birth at <37 weeks of gestation. RESULTS: A total of 120 participants were included in the trial; 60 patients were enrolled in the activity restriction group and 60 in the control group. Preterm birth at <37 weeks of gestation occurred in 15 of 60 women (25.0%) in the activity restriction group and 23 of 60 women (38.3%) in the control group (relative risk, 0.65; 95% confidence interval, 0.38-1.12). There was no significant between-group difference in the incidence of preterm birth at <32 weeks and in neonatal outcomes, but the trial was not powered for these outcomes. CONCLUSION: In singleton gestations with arrested preterm labor, activity restriction, including pelvic rest, prohibition of sexual activity, and reduction of work and/or nonwork activity, does not result in a lower rate of preterm birth at <37 weeks. Given the evidence on the lack of benefits, use of activity restriction in this population should be discouraged.

Noninvasive prediction models of intra-amniotic infection in women with preterm labor.

BACKGROUND: Among women with preterm labor, those with intra-amniotic infection present the highest risk of early delivery and the most adverse outcomes. The identification of intra-amniotic infection requires amniocentesis, perceived as too invasive by women and physicians. Noninvasive methods for identifying intra-amniotic infection and/or early delivery are crucial to focus early efforts on high-risk preterm labor women while avoiding unnecessary interventions in low-risk preterm labor women. OBJECTIVE: This study modeled the best performing models, integrating biochemical data with clinical and ultrasound information to predict a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days. STUDY DESIGN: From 2015 to 2020, data from a cohort of women, who underwent amniocentesis to rule in or rule out intra-amniotic infection or inflammation, admitted with a diagnosis of preterm labor at <34 weeks of gestation at the Hospital Clinic and Hospital Sant Joan de Déu, Barcelona, Spain, were used. At admission, transvaginal ultrasound was performed, and maternal blood and vaginal samples were collected. Using high-dimensional biology, vaginal proteins (using multiplex immunoassay), amino acids (using high-performance liquid chromatography), and bacteria (using 16S ribosomal RNA gene amplicon sequencing) were explored to predict the composite outcome. We selected ultrasound, maternal blood, and vaginal predictors that could be tested with rapid diagnostic techniques and developed prediction models employing machine learning that was applied in a validation cohort. RESULTS: A cohort of 288 women with preterm labor at <34 weeks of gestation, of which 103 (35%) had a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days, were included in this study. The sample was divided into derivation (n=116) and validation (n=172) cohorts. Of note, 4 prediction models were proposed, including ultrasound transvaginal cervical length, maternal C-reactive protein, vaginal interleukin 6 (using an automated immunoanalyzer), vaginal pH (using a pH meter), vaginal lactic acid (using a reflectometer), and vaginal Lactobacillus genus (using quantitative polymerase chain reaction), with areas under the receiving operating characteristic curve ranging from 82.2% (95% confidence interval, ±3.1%) to 85.2% (95% confidence interval, ±3.1%), sensitivities ranging from 76.1% to 85.9%, and specificities ranging from 75.2% to 85.1%. CONCLUSION: The study results have provided proof of principle of how noninvasive methods suitable for point-of-care systems can select high-risk cases among women with preterm labor and might substantially aid in clinical management and outcomes while improving the use of resources and patient experience.

Cervicovaginal Cytokines to Predict the Onset of Normal and Preterm Labor: a Pseudo-longitudinal Study.

Inflammatory processes associated with human parturition are still not completely understood, not only because the gap between inflammation and the onset of labor has been difficult to study but also because of the limited knowledge about the role of cervicovaginal fluid (CVF) cytokines during the sequence of labor. We aimed to determine whether CVF cytokines could predict the onset of normal and preterm labor. Chemokines and proinflammatory and anti-inflammatory cytokines in CVF were measured in a pseudo-longitudinal manner in healthy women between 12 and 41 weeks gestation with intact fetal membranes before and during the first stage of labor. Women were grouped into five stages, from the absence of uterine activity and cervical changes to regular uterine contractions with cervix dilation > 3 cm (active phase of labor). Of 144 women with spontaneous labor, 96 gave birth at term, 48 gave birth preterm, and both groups displayed similar cytokine concentrations. We found positive correlations between proinflammatory cytokines and the initial sequence of labor, using individual cytokines and score-based data by principal component analysis (IFN-γ, TNF-α, IL-1ß, IL-6) as dependent variables. The risk of labor onset increased as the concentrations of IL-6 increased (hazard ratio = 202.09, 95% confidence interval = 24.57-1662.49, P < 0.001). The IL-6 concentration predicted the onset of labor within 12 days of sampling (area under the time-dependent ROC curve = 0.785, 95% confidence interval = 0.693-0.877). Here, we showed that regardless of gestational age, the onset of labor could be predicted by the IL-6 concentration in the CVF, since the initial sequence of spontaneous labor displayed an inflammatory response expressed by the increase in proinflammatory cytokines.

Preterm labor with intact membranes: a simple noninvasive method to identify patients at risk for intra-amniotic infection and/or inflammation.

OBJECTIVE: To develop a noninvasive scoring system to identify patients at high risk for intra-amniotic infection and/or inflammation, which would reduce the need for amniocentesis. METHODS: This prospective cohort study comprised patients admitted with preterm labor and intact membranes (20-34 weeks of gestation) who underwent a transabdominal amniocentesis and for whom concentrations of quantitative cervical fetal fibronectin and of maternal serum C-reactive protein (CRP) were determined. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Multivariate logistic regression analysis was performed to identify intra-amniotic infection/inflammtion with noninvasive parameters that had a significant relationship with univariate analysis. With four parameters identified by multivariate analysis, we generated a noninvasive risk scoring system. RESULTS: Of the study population consisting of 138 singleton pregnant women, (1) the overall rate of intra-amniotic infection/inflammation was 28.3% (39/138); (2) four parameters were used to develop a noninvasive risk scoring system [i.e. cervical fetal fibronectin concentration (score 0-2), maternal serum CRP concentration (score 0-2), cervical dilatation (score 0-2), and gestational age at presentation (score 0-1)]; the total score ranges from 0 to 7; 3) the area under the curve of the risk score was 0.96 (95% confidence interval (CI), 0.92-0.99), significantly higher than that of each predictor in the identification of intra-amniotic infection/inflammation (p < .001, for all); 4) the risk score with a cutoff of 4 had a sensitivity of 94.9% (37/39), a specificity of 90.9% (90/99), a positive predictive value of 80.4% (37/46), a negative predictive value of 97.8% (90/92), a positive likelihood ratio of 10.4 (95% CI, 5.6-19.5), and a negative likelihood ratio of 0.06 (95% CI, 0.15-0.22) in the identification of intra-amniotic infection/inflammation. CONCLUSIONS: (1) The combination of four parameters (concentrations of cervical fetal fibronectin and maternal serum CRP, cervical dilatation, and gestational age) was independently associated with intra-amniotic infection and/or inflammation; and (2) the risk scoring system comprised of the combination of 4 noninvasive parameters was sensitive and specific to identify the patients at risk for intra-amniotic infection and/or inflammation.

Fetal Fibronectin as a Predictor of Preterm Delivery: A Nigerian Cohort Study.

Background: Fetal fibronectin is a useful biomarker in the diagnosis and management of preterm labour. Objectives: To evaluate the relationship between cervical fetal fibronectin and preterm delivery and the association between cervical fetal fibronectin level and gestational age at delivery. Materials and Methods: A prospective cohort study was performed in a tertiary hospital in Nigeria, involving equal number of pregnant women with (96) and without (96) preterm labour. Fetal fibronectin assay was done using solid-phase immunogold assay. The data were analysed using IBM SPSS version 24. Descriptive and inferential statistical analyses were done. The level of significance was p-value <0.05. Results: Less than half (47.9%) of the women in the study group had preterm delivery while 13.09% of the women in the control group delivered preterm. Fetal fibronectin test had a sensitivity, specificity, positive predictive value and negative predictive value of 78%, 86.5%, 71.9%, and 89.0%, respectively, a positive likelihood ratio and negative likelihood ratio of 5.76(95% CI, 3.67 - 9.64) and 0.26(95% CI, 0.16 - 0.41), respectively. Conclusion: The findings in our study value of fetal fibronectin in predicting preterm delivery. Its use will support less intervention for patients with negative results.