Preterm Birth In Symptomatic Women Research Articles

Clinical application of amino-terminal pro-brain natriuretic peptide concentration in amniotic fluid for the prediction of preterm birth in symptomatic women

BackgroundPreterm birth accounts for 60-80% of neonatal mortality. Approximately one-third of preterm births are caused by the spontaneous onset of preterm labor. Nevertheless, 70%-90% of women diagnosed with preterm labor will not deliver within seven days. Thus, many women will be unnecessarily treated by preterm labor with risk medications. Better tools are needed to categorize women in preterm labor into high or low risk of preterm delivery. ObjectiveTo evaluate the amino-terminal pro-brain natriuretic peptide concentration in the amniotic fluid as a prognostic test to predict the risk of delivery within 48 h or 7 days and before 34+0 or 37+0 weeks in women in preterm labor. Study Design102 pregnant women presenting signs and symptoms of spontaneous preterm birth (22+0 to 34+0 weeks of gestation) were included. Amniotic fluid was obtained by amniocentesis, and amino-terminal pro-brain natriuretic peptide concentration was measured. Below normal concentration was defined as < 0.5 multiples of the median of the standard curve according to gestational age. We estimated the risk of preterm delivery risk according to normal or lower-than-normal concentrations of amino-terminal pro-brain natriuretic peptide. The predictive capacity of the test (below normal concentration of amino-terminal pro-brain natriuretic peptide) was evaluated to identify spontaneous preterm birth at 48 h or 7 days from amniocentesis, and less than 34+0 or 37+0 weeks at delivery. ResultsFor the outcome delivery within 48 h, lower than normal amino-terminal pro-brain natriuretic peptide concentration had 94.6% sensitivity, 73.8% specificity, 96% negative predictive value, and positive and negative likelihood ratios 3.6 and 0.07, respectively. For the outcome delivery within 7 days, the test had 93.9% sensitivity, 88.7% specificity, 94% negative predictive value, and positive and negative likelihood ratios 8.3 and 0.07, respectively. For the outcome of spontaneous preterm birth before 34+0 and 37+0 weeks, below normal amino-terminal pro-brain natriuretic peptide had 80% sensitivity, 83% specificity, 78% negative predictive value, positive and negative likelihood ratio 4.7 and 0.24 and 64.1% sensitivity, 91.7% specificity, 44% negative predictive value, positive and negative likelihood ratio 7.7 and 0.39 respectively. ConclusionAmong patients in spontaneous preterm labor, the detection of lower-than-normal concentrations of amino-terminal pro-brain natriuretic peptide (< 0.5 multiples of the median) in amniotic fluid has an excellent predictive capacity to identify those patients at low risk of preterm delivery within 48 h or 7 days.

EP19.29: Identification of spontaneous preterm birth in symptomatic women by using cervicovaginal fluid biomarker and cervical length

EP19.29: Identification of spontaneous preterm birth in symptomatic women by using cervicovaginal fluid biomarker and cervical length

An analysis of cervicovaginal β-HCG and prolactin levels as a predictive biomarker of preterm birth in symptomatic women

An analysis of cervicovaginal β-HCG and prolactin levels as a predictive biomarker of preterm birth in symptomatic women

Screening and prevention of preterm birth in twin pregnancies.

Preterm birth (PTB) is commonest cause of perinatal mortality and morbidity in multiple pregnancies with significant long-term sequelae. The etiology of PTB is multifactorial. Universal screening by a transvaginal assessment of cervical length (CL) at midtrimester scan is recommended for all women with twin pregnancies. Women with CL≤25mm should be offered prophylactic vaginal progesterone to mitigate the risk of PTB. Other modalities like home uterine activity monitoring, digital cervical examination, fetal fibronectin (FFN) assessment, and screening for infections are not recommended. History-indicated cerclage is not advised in unselected twin pregnancies, but a combination of physical examination-indicated cerclage, tocolytics, and antibiotics may be considered in twin pregnancies with a dilated cervix prior to 24 weeks' gestation. Routine use of cervical pessary is not advised and should be limited to research settings. Neither transvaginal CL nor FFN assessment is supported by evidence to predict the risk of PTB in symptomatic women with multiple pregnancies. More research is warranted to develop and validate algorithms to predict PTB to provide individualized care to these high-risk pregnancies.

Validation of a Nomogram for Predicting Preterm Birth in Women With Threatened Preterm Labor: A Prospective Cohort Study in Iranian Tertiary Referral Hospitals.

In this prospective cohort study, we aimed to investigate external validity of the Allouche's nomogram to predict preterm birth in symptomatic women in Iran. We employed six variables of cervical length, uterine contractions, rupture of membranes, vaginal bleeding, gestational age, and multiple pregnancy to draw the nomograms. These variables were examined in the first day of women's hospitalization and participants followed up until giving birth. The concordance index of area under the curve (AUC) was used for validation of the nomograms. Of the participants 10% gave birth within 48 hours and 29% before 34 weeks. The nomogram had sufficient accuracy in predicting birth within 48 hours (AUC 0.89 [95% CI 0.82-0.96]) and birth before 34 weeks (AUC 0.89 [95% CI 0.84-0.94]). The optimal risk threshold for nomogram predicting birth within 48 hours was 0.16. Use of these two nomograms, can improve the health of women and their neonates.

Cumulative life stressors and stress response to threatened preterm labour as birth date predictors.

Preterm birth represents one of the main causes of neonatal morbimortality and a risk factor for neurodevelopmental disorders. Appropriate predictive methods for preterm birth outcome, which consequently would facilitate prevention programs, are needed. We aim to predict birth date in women with a threatened preterm labour (TPL) based on stress response to TPL diagnosis, cumulative life stressors, and relevant obstetric variables. A prospective cohort of 157 pregnant women with TPL diagnosis between 24 and 31weeks gestation formed the study sample. To estimate the stress response to TPL, maternal salivary cortisol, α-amylase levels, along with anxiety and depression symptoms were measured. To determine cumulative life stressors, previous traumas, social support, and family functioning were registered. Then, linear regression models were used to examine the effect of potential predictors of birth date. Lower family adaptation, higher Body Mass Index (BMI), higher cortisol levels and TPL diagnosis week were the main predictors of birth date. Gestational week at TPL diagnosis showed a non-linear interaction with cortisol levels: TPL women with middle- and high-cortisol levels before 29weeks of gestation went into imminent labour. A combination of stress response to TPL diagnosis (salivary cortisol) and cumulative life stressors (family adaptation) together with obstetric factors (TPL gestational week and BMI) was the best birth date predictor. Therefore, a psychosocial therapeutic intervention program aimed to increase family adaptation and decrease cortisol levels at TPL diagnosis as well as losing weight, may prevent preterm birth in symptomatic women.

Can stress predict delivery date?: Role of chronic and acute stress to the threatened preterm labor as predictors of delivery date

IntroductionThreatened preterm labor (TPL) is a traumatic event during pregnancy that involves a threat to the physical integrity of the upcoming baby. Despite biomarkers would be the strongest delivery date predictors, an assessment of chronic and acute stress response to TPL diagnosis may improve this prediction.ObjectivesThe objective is to predict delivery date in women with TPL based on their response to this diagnosis and chronic stressors, along with relevant obstetric variables.MethodsA prospective cohort study was conducted with a sample was formed by 157 pregnant women with TPL diagnosis between 24 and 31 weeks. Determination of salivary cortisol, α-amylase levels, along with anxiety and depression symptoms were measured to estimate stress response to TPL. Cumulative life stressors as traumas, social and familiar functioning were also registered. To examine the effect of the possible predictor variables of delivery date, linear regression models were used.ResultsA correlation was found between the variables of response to chronic stress and between the variables of psychological response to stress. The main predictors of preterm delivery were low family adaptation, higher BMI, higher cortisol levels, and the week of diagnosis of TPL (&lt;29 weeks of gestation).ConclusionsThe best predictor of delivery date was the combination of the stress response to the diagnosis of TPL measured by cortisol in saliva, cumulative life stressors (mainly family adaptation) and obstetric factors (week TPL and BMI). Through psychosocial therapeutic intervention programs, it is possible to influence this modifiable predictive factors of preterm birth in symptomatic women.

Measurement of the uterocervical angle for the prediction of preterm birth in symptomatic women

PurposeTo examine if the uterocervical angle (UCA) can be used to predict preterm delivery in women with painful and regular uterine contractions and a cervical length of 25 mm or less.MethodsRetrospective study at the perinatal unit of the University Hospital of Tuebingen, Germany. Women with singleton gestation and preterm contractions between 24 + 0 and 33 + 6 weeks’ gestation were included. For the UCA measurement, a line is placed from the internal os to the external os irrespective of whether the cervix is straight or curved. A second line is drawn to delineate the lower uterine segment. The angle between the two lines is the UCA measurement. The measurements were taken on stored images from our database.ResultsThe study consisted of 213 singleton pregnancies. At the time of UCA measurement, median maternal and gestational age was 31.4 years and 29.7 weeks’ gestation. Median gestational age at delivery was 35.3 weeks and the corresponding birth weight 2480 g, respectively. The UCA measurement in women who delivered within 2 days, between 3–7 days and after 7 days was not helpful to distinguish between these three groups [median UCA measurements: 108.5°, 108.0° and 107.3° (Kruskal–Wallis test p = 0.576)]. Uni- and multivariate logistic multiple regression analysis demonstrated that the delivery within 2 days was only dependent on the gestational age and the cervical length at the time of presentation.ConclusionThe measurement of UCA is not useful in predicting preterm birth in the subsequent 7 days after an episode of preterm contractions.

Cervicovaginal fluid cytokines as predictive markers of preterm birth in symptomatic women.

ObjectiveHere, we investigated whether cytokines in the cervicovaginal fluid (CVF) can be predictive markers of preterm birth (PTB).MethodsA multi-center prospective cohort study was conducted on 59 singleton pregnant women hospitalized for preterm labor (PTL) and/or preterm premature rupture of membranes (pPROM) between 22 weeks and 36 weeks 6 days of gestation from 2014 to 2015. The levels of 13 inflammatory cytokines (macrophage inflammatory protein [MIP]-1α, MIP-1β, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, IL-8, IL-17α, granulocyte colony stimulating factor [G-CSF], IL-7, IL-4, IL-5, IL-10, and IL-13) were measured using a multiplex bead-based immunoassay and that of fetal fibronectin (fFN) was measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using Student’s t-test, Mann-Whitney U test, Pearson’s correlation, and receiver operating characteristic (ROC) curve analysis in SPSS version 20.0.ResultsAmong the 13 cytokines assessed, the levels of 3 cytokines (MIP-1α, IL-6, and IL-7) were negatively correlated with gestational age at delivery (P=0.028, P=0.002, and P=0.018, respectively). Sensitivities of MIP-1α, IL-6, and IL-17α were 70%, 80%, and 75%, respectively, and their specificities were 57%, 65%, and 69%, respectively. The sensitivity and specificity of fFN were 33% and 95%, respectively.ConclusionIn symptomatic women diagnosed with PTL and/or pPROM, cytokines from cervicovaginal fluid, especially IL-6 and IL-17α, could be better predictive markers of PTB than fFN.

Use of complete blood count for predicting preterm birth in asymptomatic pregnant women: A propensity score-matched analysis.

BackgroundAccurate prediction of preterm birth (PTB) is still difficult, mostly because of the multifactorial etiology of PTB. Previous studies have been mostly focused on the prediction of PTB in symptomatic women or those presenting with threatened preterm labor. We aimed to study whether complete blood count (CBC) parameters at 20‐30 weeks of pregnancy can predict asymptomatic PTB.MethodsIn this retrospective case‐control study, the preterm and term delivery groups were matched by propensity score‐matched (PSM) analysis. Baseline data and the CBC parameters examined at 20‐30 weeks of gestation were recorded.ResultsThe combined marker of neutrophil‐to‐lymphocyte ratio (NLR), hemoglobin (HGB), and platelet distribution width (PDW) accurately predicts PTB at a cutoff value of 0.25, with sensitivity and specificity of 88.6% and 40.5% and negative and positive predictive value of 97.9% and 10.2%, respectively.ConclusionThe combined marker of CBC parameters can supplement other markers to predict PTB about 10 weeks in advance. This combined marker had a very high negative predictive value for PTB. Therefore, in subjects with normal combined marker value, further screening tests for PTB may be eliminated unless clinical suspicion is high.

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

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

Serum relaxin and cervical length for prediction of spontaneous preterm birth in second-trimester symptomatic women.

To investigate whether serum relaxin level is associated with preterm birth in symptomatic women, either as a standalone test or in the context of a combined model of serum relaxin and cervical length (CL). This was a case-control study of women with a singleton pregnancy who presented between 24 + 0 and 26 + 6 weeks' gestation with threatened preterm labor and intact membranes. CL, full blood count, C-reactive protein level and maternal demographics were recorded at presentation, and blood samples were taken for relaxin measurement. Parameters were compared between women who delivered preterm (before 37 weeks) (n= 46) and those delivering at term (n= 66). Logistic regression with receiver-operating characteristics (ROC) curve analysis was used to assess significant predictors for birth before 37 and before 34 weeks. Women delivering before 37 weeks had higher mean serum relaxin levels and lower mean CL than those delivering at term (P< 0.0001). Relaxin alone had 63% (95% CI, 49-75%) sensitivity for birth before 37 weeks and 61% (95% CI, 47-74%) for birth before 34 weeks, at a 10% false-positive rate (FPR). Serum relaxin levels did not correlate with CL; a combined model of the two predictors had an area under the ROC curve of 0.895 (95%CI, 0.835-0.954) for the prediction of birth before 37 weeks and 0.869 (95% CI, 0.802-0.937) for birth before 34 weeks (n= 44). Serum relaxin > 1010 pg/mL had 58% sensitivity for prediction of preterm birth in women with a CL > 15 mm, at a 10% FPR. High serum relaxin level is associated with an increased risk of preterm birth in second-trimester symptomatic women with intact membranes. A combination of serum relaxin and CL increases predictive accuracy for preterm birth. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Clinical Application of Quantitative Foetal Fibronectin for the Prediction of Preterm Birth in Symptomatic Women

Aim: To evaluate the clinical application of the new Hologic quantitative foetal fibronectin (qfFN) bedside test for the prediction of spontaneous preterm birth (sPTB) in patients with symptoms suggestive of spontaneous threatened preterm labour (sPTL). Methods: A prospective observational study with 154 pregnant women presenting signs and symptoms of sPTL was conducted. These women were subjected to a qfFN test between 22 and 35 weeks of gestation For each cut-off threshold, the ability to predict sPTB at within 14 days of conducting the test and <37 weeks was assessed by calculating the positive predictive value (PPV), negative predictive value (NPV), likelihood ratios, odds ratios, sensitivity, and specificity. Results: For the outcome of delivery within 14 days of the test, qfFN <10 ng/mL had a 100% NPV and >200 ng/mL produced a 50.0% PPV; thus, qfFN added enhanced discrimination between high- and low-risk patients. The overall rate of sPTB (<37) was 13.3% (16/120), which increased progressively with increasing levels of fFN, with rates of 9.8% (8/81), 11.5% (3/26), 14.2% (1/7), 50% (3/6) within the 4 categories (fFN 0-9, 10-49, 50-200, 200+) respectively. Conclusions: The use of the qfFN testing in symptomatic patients allowed for more accurate identification of women at risk of sPTB and thus more directed management.

Performance of cervical phIGFBP-1 test alone or combined with short cervical length to predict spontaneous preterm birth in symptomatic women

We aimed to assess the accuracy of cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) test alone or in combination with cervical length (CL), to predict preterm birth (PTB) in symptomatic women. We performed a prospective cohort study from 2012 to 2015 including singleton pregnancies with symptoms of preterm labor, intact membranes and CL < 25 mm at 24–34 weeks of gestation. Studied outcome were spontaneous delivery within 7 and 14 days of testing and spontaneous PTB at <34 and <37 weeks of gestation. Among 180 women, 21 (11.7%) had a positive phIGFBP-1 test. Spontaneous PTB occurred within 7 days, 14 days of testing and before 34 weeks and 37 weeks in 7.8%, 10.6%, 12.9% and 28.8%, respectively. The phIGFBP-1 test had a low predictive performance for all studied outcomes varying for positive likelihood ratios (2.8 to 3.4) and negative likelihood ratios (0.8). Combining phIGFBP-1 and CL did not increase its predictive ability. After adjustment, positive phIGFBP-1 test was no more independently associated with a delivery within 7 days (p = 0.55), unlike CL < 15 mm (p = 0.04). In conclusion, phIGFBP-1 test alone or in combination with CL has a low predictive accuracy to predict PTB in symptomatic women.

Comparison of the Actim Partus test and the fetal fibronectin test in the prediction of spontaneous preterm birth in symptomatic women undergoing cervical length measurement

ObjectiveTo compare the accuracy of the Actim Partus test and fetal fibronectin (fFN) test in the prediction of spontaneous preterm delivery within seven days in symptomatic women undergoing cervical length measurement. Study designWe performed a post-hoc analysis on frozen samples of a nationwide cohort study in all 10 perinatal centres in the Netherlands. We selected samples from women with signs of preterm labour between 24 and 34 weeks of gestational age and a cervical length below 30mm. Delivery within seven days after initial assessment was the primary endpoint. We calculated sensitivity, specificity, and positive and negative predictive values for the combination of both the Actim Partus test and fFN test with cervical length. A test was considered positive in case of a cervical length between 15 and 30mm with a positive Actim Partus or fFN test, and a cervical length below 15mm regardless the test result. ResultsIn total, samples of 350 women were tested, of whom 69 (20%) delivered within seven days. Eighty-four women had a positive Actim Partus test and 162 women a positive fFN test, of whom 54 (64%) and 63 (39%) delivered within seven days, respectively. Ninety-seven women had a cervical length below 15mm, of whom 50 (52%) delivered within seven days. Sensitivity, specificity, positive and negative predictive values of combining cervical length with the Actim Partus test or the fFN test were 91%, 75%, 47% and 97%, and 96%, 58%, 36% and 98%, respectively. ConclusionAccording to this post-hoc study, in combination with cervical length, the Actim Partus test could be used as an alternative for the fFN test to identify women who will not deliver within seven days after presentation. Further evidence should be collected in a prospective comparative study.

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

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

847: A prospective blinded cohort study evaluating fetal fibronectin and cervical length in predicting preterm birth in symptomatic women

847: A prospective blinded cohort study evaluating fetal fibronectin and cervical length in predicting preterm birth in symptomatic women

PM.61 The Use of Quantitative Fetal Fibronectin to Predict Obstetric Outcome: A Comparison of a New and Established Quantitative Bedside Analyser in Asymptomatic High-Risk Women

Background Preterm birth (PTB) remains a significant cause of neonatal morbidity and mortality. The most accurate predictors of PTB are ultrasound determined cervical length (CL) and fetal fibronectin (fFN)1. Quantitative...

PL.23 Use of Quantitative Fetal Fibronectin May Improve Risk Assessment in Symptomatic Women at Risk of Preterm Birth

Background The presence of raised fetal fibronectin (fFN) levels in cervicovaginal secretions between 24–34 weeks gestation is associated with an increased risk of spontaneous preterm birth in symptomatic women. Recent...

Cervical Length Measurement for the Prediction of Preterm Birth in Symptomatic Women with a Twin Pregnancy: A Systematic Review and Meta-Analysis

Objective. The aim of this study was to assess whether cervical length measurement (CL) could predict preterm birth (PTB) in symptomatic women with a twin pregnancy. Methods. We searched MEDLINE and EMBASE to identify studies investigating the accuracy of CL measurement in predicting PTB in symptomatic women with a twin pregnancy. We extracted data to construct two-by-two tables and used bivariate meta-analysis to generate point estimates of sensitivity and specificity. Results. Five studies (N = 226) were included. Variation in definition of PTB and cut-off points for CL was strong. One study investigated delivery within seven days, demonstrating a sensitivity of 1.0 (95% CI: 0.83–1.0) and a specificity of 0.31 (95% CI 0.2–0.43) for a CL cutoff at 25 mm. Three studies reported on predicting PTB < 37 weeks at a CL cutoff of 30 mm, with sROC point estimates of 0.76 (95% CI: 0.66 to 0.84) and 0.37 (95% CI: 0.21 to 0.56) for sensitivity and specificity, respectively. For preterm birth <34 weeks, no pooled estimates could be estimated since only 2 studies with large heterogeneity were identified. Conclusions. There is limited evidence on the accuracy of cervical length measurement testing the prediction of preterm birth in symptomatic women with a twin pregnancy, especially on the most important outcome, that is, delivery within 7 days.