Preterm Birth In Asymptomatic Women Research Articles

EG-VEGF maternal levels predict spontaneous preterm birth in the second and third trimesters in pregnant women with risk factors for placenta-mediated complications

Prediction of spontaneous preterm birth in asymptomatic women remains a great challenge for the public health system. The aim of the study was to determine the informational value of EG-VEGF circulating levels for prediction of spontaneous preterm birth in the second and third trimesters in pregnant women at high risk for placenta-mediated complications. A prospective multicenter cohort study including 200 pregnant patients with five-serum sampling per patient. Women with spontaneous preterm birth have higher concentrations of serum EG-VEGF than uncomplicated patients at 24 weeks, 28 weeks and 32 weeks (p = 0.03, 0.02 and < 0.001). The areas under the curve reached 0.9 with 100% sensitivity at 32 weeks for the prediction of spontaneous preterm birth. Serum EG-VEGF concentrations could be considered as a reliable biomarker of spontaneous preterm birth in high-risk for placenta-mediated complications pregnant women.

How to screen the cervix and reduce the risk of spontaneous preterm birth in asymptomatic women without a prior preterm birth.

Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality globally. PTB rates have increased in South Korea despite reduction in birth rates. A history of PTB is a strong predictor of subsequent PTB and screening of cervical length between 16 0/7 weeks and 24 0/7 weeks of gestation is recommended in women with a singleton pregnancy and a prior spontaneous PTB. However, the prediction and prevention of spontaneous PTBs in women without a prior PTB remain a matter of debate. The scope of this review article comprises cervical screening and prevention strategies for PTB in asymptomatic women without a prior PTB, based on recent evidence and guidelines.

Progesterone, cerclage, pessary, or acetylsalicylic acid for prevention of preterm birth in singleton and multifetal pregnancies - A systematic review and meta-analyses.

Preterm birth is the leading cause of childhood mortality and morbidity. We aimed to provide a comprehensive systematic review on randomized controlled trials (RCTs) on progesterone, cerclage, pessary, and acetylsalicylic acid (ASA) to prevent preterm birth in asymptomatic women with singleton pregnancies defined as risk of preterm birth and multifetal pregnancies. Six databases (including PubMed, Embase, Medline, the Cochrane Library) were searched up to February 2022. RCTs published in English or Scandinavian languages were included through a consensus process. Abstracts and duplicates were excluded. The trials were critically appraised by pairs of reviewers. The Cochrane risk-of-bias tool was used for risk of bias assessment. Predefined outcomes including preterm birth, perinatal/neonatal/maternal mortality and morbidity, were pooled in meta-analyses using RevMan 5.4, stratified for high and low risk of bias trials. The certainty of evidence was assessed using the GRADE approach. The systematic review followed the PRISMA guideline. The search identified 2,309 articles, of which 87 were included in the assessment: 71 original RCTs and 16 secondary publications with 23,886 women and 32,893 offspring. Conclusions were based solely on trials with low risk of bias (n = 50).Singleton pregnancies: Progesterone compared with placebo, reduced the risk of preterm birth <37 gestational weeks: 26.8% vs. 30.2% (Risk Ratio [RR] 0.82 [95% Confidence Interval [CI] 0.71 to 0.95]) (high certainty of evidence, 14 trials) thereby reducing neonatal mortality and respiratory distress syndrome. Cerclage probably reduced the risk of preterm birth <37 gestational weeks: 29.0% vs. 37.6% (RR 0.78 [95% CI 0.69 to 0.88]) (moderate certainty of evidence, four open trials). In addition, perinatal mortality may be reduced by cerclage. Pessary did not demonstrate any overall effect. ASA did not affect any outcome, but evidence was based on one underpowered study.Multifetal pregnancies: The effect of progesterone, cerclage, or pessary was minimal, if any. No study supported improved long-term outcome of the children. Progesterone and probably also cerclage have a protective effect against preterm birth in asymptomatic women with a singleton pregnancy at risk of preterm birth. Further trials of ASA are needed. Prevention of preterm birth requires screening programs to identify women at risk of preterm birth. [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021234946].

The acceptability of cervical electrical impedance spectroscopy within a multi-modal preterm birth screening package: a mixed methods study

BackgroundReducing the rate of preterm birth is a cornerstone of global efforts to address child mortality, however existing screening tests offer imperfect prediction. Cervical electrical impedance spectroscopy (EIS) is a novel technique to quantify the ripening changes which precede labour. Mid-trimester EIS measurements have been shown to accurately predict preterm birth in asymptomatic women. This study aimed to comprehensively evaluate the acceptability of cervical EIS to low and high-risk women as part of a package of screening tests performed during a larger prospective trial.MethodsIn this parallel convergent mixed methods study, 40 women completed questionnaires before and after screening tests (EIS, cervical length measurement and fetal fibronectin quantification). Quantitative outcomes were anxiety levels before and after screening (Spielberger State Trait Anxiety Inventory, STAI-6), pain (Short Form McGill Pain Questionnaire) and ratings of EIS device appearance and test acceptability (visual analogue scales). Twenty-one women (11 high-risk, 10 low-risk) also attended a semi-structured qualitative interview. Interviews were recorded and transcribed, then thematic analysis was performed. A convergence coding matrix was constructed to enable triangulation of quantitative and qualitative results.ResultsHigh risk women demonstrated a significant reduction in anxiety following screening (mean STAI-6 score 34.5 vs. 29.0, p = 0.002). A similar trend was observed among low-risk participants. Ratings of pain, EIS device appearance and procedural acceptability did not differ between groups. Mean pain ratings were low (visual analogue scale 0.97 and 1.01), comparing favourably to published evaluations of conventional screening tests. Qualitative analysis provided insight into both the physical consequences and emotional experiences of screening. Additional determinants of the screening experience included device design, pre-existing perspectives on intimate examination, attitudes to knowledge in pregnancy and interaction with clinical staff. Finally, a range of practical considerations regarding wider use of EIS were identified, with valuable complementary detail regarding acceptability for use in antenatal care.ConclusionsCervical EIS is well tolerated and acceptable to both low and high-risk women when performed as part of a multi-modal screening package. These results provide useful insights to inform the design of future study and screening protocols.

Can early pregnancy decorin levels be a potential predictor for preterm birth?

This study investigates the role of maternal decorin levels measured in the early second trimester of pregnancy in detecting the potential for preterm birth in late pregnancy. The prospective, case-control study was carried out in tertiary university hospital from June to December 2021.Maternal serum samples were collected from 350 women aged 18-40 years with a singleton pregnancy during early second-trimester screening for aneuploidy, and stored at -80°C. All participants were followed up until delivery and 25 patients diagnosed with preterm birth group and 40 full-term healthy women were included in the study. The median maternal serum decorin level was 3.82 (1.15-12.37) ng/ml in the preterm birth (PTB) group and 4.63 (1.20-10.02) ng/ml in the control group, there was no statistically difference between the groups (p = 0.111). The mean gestational age was statistically significantly lower in the preterm birth group (33.1±2.7 weeks) than in the control (39±1.16 weeks) (p <0.001). The mean fetal weight was statistically significantly lower in the preterm birth group (2023.8±477 g) than in the control group (3309.7±353 g) (p <0.001). Early second-trimester serum levels of decorin alone may not be a sufficiently accurate biomarker as a biochemical model for the prediction of preterm birth in asymptomatic women.

A Nested Case-Control Study of the Relationship between Salivary Inflammatory Mediators, Periodontal Parameters, and Preterm Birth in a Chinese Population.

Background To explore whether salivary inflammatory mediators and periodontal indices at different gestational stages can be taken as indicators of preterm birth (PTB). Methods This nested case-control study enrolled systemically healthy pregnant women at 9 to 36 weeks of gestation. Periodontal indices were measured at the enrollment date, and interleukin-1β (IL-1β), IL-6, tumor necrosis factor (TNF-α), prostaglandin E2 (PGE2), and 8-hydroxy-deoxyguanosine (8-OHdG) in the saliva were determined by enzyme-linked immunosorbent assay (ELISA). The birth outcome was recorded. Results PTB occurred in 26 women. A total of 104 matched women with full-term birth (FTB) were used as controls. The PTB women enrolled at 24-28 gestational weeks displayed a significantly greater bleeding index (BI), probing pocket depth (PD), PD ≥ 4 mm sites (%), saliva-TNF-α, and saliva-PGE2 (P < 0.05). BI and PGE2 in the saliva were found to be positively associated with PTB (OR = 4.79, P = 0.048, 95%CI = 1.014 to 22.628; OR = 1.07, P = 0.04, 95%CI = 1.004 to 1.135, respectively). The areas under the receiver operating characteristic curve (ROC) of BI and saliva-PGE2 were 0.82 and 0.78, respectively, and that of the combined detection was 0.91, which was larger than either marker alone, although the differences were not significant (P > 0.05). Conclusions The combination of BI and PGE2 in saliva at 24-28 gestational weeks could be a predictor of PTB in asymptomatic women. However, the results should be further explored with larger sample size.

VP46.13: Prediction of spontaneous preterm birth in asymptomatic women with prior preterm delivery by cervical elastography

VP46.13: Prediction of spontaneous preterm birth in asymptomatic women with prior preterm delivery by cervical elastography

Cervical pessary in singleton gestations with arrested preterm labor: a randomized clinical trial

Cervical pessary been proven to be effective in asymptomatic women with singleton gestations and with short midtrimester cervical length, while efficacy of this device in women with arrested preterm labor is still a subject of debate. To test the hypothesis that in women with singleton pregnancy, and with arrested preterm labor, use of cervical pessary would reduce the rate of preterm birth at less than 37 weeks of gestation. Parallel group, non-blinded, randomized trial. Eligible women were those with a diagnosis of arrested preterm labor between 24 0/7 - 33 6/7 weeks of gestations. Participants were randomized in a 1:1 ratio to either cervical pessary or no pessary. The primary endpoint was preterm birth at less than 37 weeks of gestation. A sample size of 120 participants was planned, but the trial was stopped before complete enrollment. 61 women with singleton pregnancies and arrested preterm labor at 24 0/7 - 33 6/7 weeks were enrolled in the trial. 32 women were randomized into the cervical pessary group, and 29 into the control group. Preterm birth at less than 37 weeks of gestation occurred in 14 women (43.8%) in the pessary group, and 6 women (20.7%) in the control group (relative risk 2.98, 95% confidence interval 0.96 to 9.30). In this underpowered trial, among women with singleton pregnancies and arrested preterm labor, use of a cervical pessary, compared with no pessary use, does not result in a lower rate of preterm birth at less than 37 weeks of gestation.

Controversies in the prevention of spontaneous preterm birth in asymptomatic women: an evidence summary and expert opinion.

Preterm birth prevention is multifaceted and produces many nuanced questions. This review addresses six important clinical questions about preterm birth prevention as voted for by members of the UK Preterm Clinical Network. The questions cover the following areas: preterm birth prevention in 'low-risk' populations; screening for asymptomatic genital tract infection in women at high risk of preterm birth; cervical length screening with cerclage or vaginal pessary insitu; cervical shortening whilst using progesterone; use of vaginal progesterone in combination with cervical cerclage; and optimal advice about intercourse for women at high risk of preterm birth.

Guideline No. 401: Sonographic Cervical Length in Singleton Pregnancies: Techniques and Clinical Applications.

• To assess the association between sonography-derived cervical length measurement and preterm birth. • To describe the various techniques to measure cervical length using sonography. • To review the natural history of the short cervix. • To review the clinical uses, predictive ability, and utility of sonography-measured short cervix. Reduction in rates of prematurity and/or better identification of those at risk, as well as possible prevention of unnecessary interventions. Clinicians involved in the obstetrical management or cervical imaging of patients at increased risk of a short cervix. Women at increased risk of a short cervix or at risk of preterm birth. Literature published up to June 2019 was retrieved through searches of PubMed and the Cochrane Library using appropriate controlled vocabulary and key words (preterm labour, ultrasound, cervix, cervical insufficiency, transvaginal, transperineal, cervical length, fibronectin). Results were restricted to general and systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies. There were no date or language restrictions. Grey (unpublished) literature was identified through searching the websites of health technology assessment agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence and this guideline were reviewed by the Diagnostic Imaging Committee of the Society of Obstetricians and Gynaecologists of Canada, and the recommendations were made and graded according to the rankings of the Canadian Task Force on Preventive Health Care (Online Appendix Table A1). Preterm birth is a leading cause of perinatal morbidity and mortality. Use of the sonographic technique reviewed in this guideline may help identify women at risk of preterm birth and, in some circumstances, lead to interventions that may reduce the rate of preterm birth. SUMMARY STATEMENTS (CANADIAN TASK FORCE ON PREVENTIVE HEALTH CARE GRADING IN PARENTHESES): RECOMMENDATIONS (CANADIAN TASK FORCE ON PREVENTIVE HEALTH CARE GRADING IN PARENTHESES).

Preterm Delivery Prediction Using Phosphorylated Insulin-Like Growth Factor in Rural Kenya [OP01-1A

INTRODUCTION: To evaluate the feasibility and accuracy of a test analyzing for the presence of phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1), in predicting preterm delivery in asymptomatic women in the rural Kenya. METHODS: This was a prospective cohort study conducted by Saving Mothers from 2013-2019. Asymptomatic women presenting for routine prenatal care in West Pokot, Kenya were enrolled. Pregnant women were recruited prior to 24 weeks and offered the opportunity to return at 28-32 weeks gestation to obtain the phosphorylated insulin-like growth factor binding protein-1 (pIGFBP-1) assay. Dating was established by last menstrual period and confirmed by ultrasound. Patients who tested positive received betamethasone, and were referred to the maternity waiting home. Outcome data was collected after delivery and sensitivity, specificity, positive and negative predictive values were reported for the test. RESULTS: 669 women were recruited. 469 returned for the second visit to receive the test, and presently 370 have complete data for analysis. 180 tested positive for preterm birth risk, 143 of whom delivered prior to 37 weeks gestation (Positive Predictive Value = 79.4%). 190 tested negative, 176 of whom delivered after 37 weeks (Negative Predictive Value = 92.6%). Sensitivity for the test was 91.0%. Specificity was 82.6%. CONCLUSION: The pIGFBP-1 point of care test is effective in predicting risk for preterm birth in asymptomatic women in rural Kenya. This allows for risk-stratification in low resource settings. Proper intervention may optimize utilization of scarce resources and improve maternal and child health.

Cervical Assessment by Transvaginal Ultrasound for Predicting Preterm Birth in Asymptomatic Women

Abstract Preterm birth (PTB) is defined as delivery before completing 37 weeks of gestation. It is the main cause of neonatal morbidity and mortality in the most countries. The inherent cervical length and strength are two main features of the cervix that determine whether or not a pregnant woman is at risk for PTB. Routine transvaginal cervical length screening was recommended for women with singleton pregnancy and history of prior spontaneous PTB, while the issue of universal cervical length screening and the screening in multiple gestations remain an object of debate. Strain sonoelastography and shear-wave sonoelastography have been used to evaluate the cervical stiffness in pregnant women, but the predictive value for PTB still requires further investigations. In this review, we will discuss the measurement methods of cervical length and cervical stiffness, and compare the value of cervical assessment by transvaginal ultrasound for predicting PTB in asymptomatic women.

Current Approaches to Risk Assessment and Prevention of Preterm Birth-A Continuing Public Health Crisis.

Background: Preterm birth remains a major cause of neonatal morbidity and mortality. Several potential pathways and pathophysiologic processes can lead to preterm birth, complicating efforts to screen for the risk of preterm birth and making implementation of prevention strategies difficult.Methods: Based on a review of the literature, this article addresses screening strategies for preterm birth risk stratification and interventions for preterm birth prevention.Results: In women with a history of a prior spontaneous preterm birth, cervical cerclage placement in the setting of short cervix reduces the rate of recurrent spontaneous preterm birth. Weekly injections of 17-hydroxyprogesterone caproate (17-P) have been used as standard treatment for the prevention of recurrent preterm birth since 2011. However, results of a replication study of 17-P published in 2020 have raised questions regarding the effectiveness of this drug, and it is under review by the US Food and Drug Administration. Among women with no history of preterm birth, cervical length appears to be the best predictor of risk for preterm birth in asymptomatic women. In women with a cervical length <25 mm, vaginal progesterone has been demonstrated to reduce the risk of preterm birth.Conclusion: Strategies including cervical length screening, vaginal progesterone administration, cervical cerclage placement, and, potentially, 17-P administration may help reduce rates of preterm birth when used in the appropriate patient populations. Development of protocols for patient evaluation and risk stratification will help identify patients at highest risk for preterm birth and allow use of the best available therapeutic interventions.

692: Physical exam indicated cerclage in twin pregnancy, randomized clinical trial

Twin pregnancies with dilated cervix in the second trimester are at increased risk of pregnancy loss and preterm birth (PTB); there is no proven therapy to prevent PTB in this group of women. We aimed to evaluate if physical exam indicated cerclage reduces the incidence of PTB in asymptomatic women with twin gestations and cervical dilation < 24 weeks Multicenter open label randomized clinical trial of women with twin pregnancy and asymptomatic cervical dilation from 1-4 cm between 16 0/7 to 23 6/7 weeks were enrolled from 5/2015 to 7/2019 in 8 centers. They were randomized to cerclage or no cerclage. Exclusion criteria: monoamniotic pregnancy, fetal growth restriction, twin-twin transfusion syndrome, major fetal malformations, known genetic anomaly, signs of labor or clinical chorioamnionitis. Primary outcome: incidence of PTB < 34 weeks. Secondary outcomes: PTB < 32, < 28 and < 24 weeks, interval from diagnosis to delivery and perinatal mortality. Data was analyzed as intention to treat 30 women were enrolled. 17 women were randomized to cerclage and 13 women to no cerclage. 4 women in the cerclage group did not receive the surgical procedure. Maternal demographics were not significantly different, more women in the cerclage group received indomethacin and antibiotics (Table 1). When comparing cerclage group vs no cerclage group, the incidence of PTB < 34 weeks was significantly reduced in the cerclage group: 12/17 (70%) vs 13/13 (100%) RR: 0.7 [95% CI 0.5-0.96], PTB < 32, < 28, and < 24 weeks were all significantly reduced in the cerclage group by 36%, 52% and 65% respectively. Interval from diagnosis to delivery: 8.3±5.8 vs 2.9±3.0 weeks (p=0.02). Perinatal death was significantly reduced in the cerclage group by 77% (Table 2) In this randomized trial, physical exam indicated cerclage, indomethacin and antibiotics in asymptomatic twin pregnancies with dilated cervix < 24 weeks significantly decreased PTB at all evaluated gestational ages, most importantly cerclage decreased very early PTB < 28 weeks by 52% and perinatal mortality by 77%, compared with no cerclageView Large Image Figure ViewerDownload Hi-res image Download (PPT)

The risk of spontaneous preterm birth in asymptomatic women with a short cervix (≤25 mm) at 23−28 weeks’ gestation

Asymptomatic short cervical length is an independent risk factor for spontaneous preterm birth. However, most studies have focusedon the associated risk of a short cervical length when encountered between 16and 23 weeks' gestation. The relationship between cervical length and riskof spontaneous preterm birth after 23 weeks is not well known. To evaluate the risk of spontaneous preterm birth in asymptomatic women with a short cervix (≤25 mm) at 23-28 weeks' gestation. A retrospective cohort study of women with asymptomatic short cervix (cervical length ≤25 mm) at extreme prematurity, defined as 23-28 weeks' gestation, was performed at a single center from January 2015 to March 2018. Women with symptoms of preterm labor, multiple gestations, fetal or uterine anomalies, cervical cerclage, or those with incomplete data were excluded from the study. Demographic information as well as data on risk factors for spontaneous preterm birth were collected. Patients were divided into 4 groups based on the cervical length measurement (≤10 mm, 11-15 mm, 16-20 mm, and 21-25 mm). The primary outcome was time interval from enrollment to delivery. Secondary outcomes included delivery within 1 and 2 weeks of enrollment, gestational age at delivery, and delivery prior to 32, 34, and 37 weeks, respectively. Continuous variables were compared using Kruskal-Wallis test, whereas categorical variables were compared using the χ2 or Fisher exact test as appropriate. The Wilcoxon test for difference in survival time was used to compare gestational age at delivery among the 4 cervical length groups, with data stratified based on gestational age at enrollment. Of the 126 pregnancies that met inclusion criteria, 22 (17.4%) had a cervical length of ≤10 mm, 23 (18.3%) had a cervical length of 11-15 mm, 37 (29.4%) had a cervical length of 16-20 mm, and 44 (34.9%) had a cervical length of 21-25 mm. Baseline characteristics were similar among all 4 groups. The shorter cervical length group was associated with a shorter time interval from enrollment to delivery (cervical length ≤10 mm, 10 weeks; cervical length 11-15 mm, 12.7 weeks; cervical length of 16-20 mm, 13 weeks; cervical length of 21-25 mm, 13.2 weeks; P= .006). Regardless of the cervical length measurement, delivery within 2 weeks was extremely uncommon (1 patient; 0.8%). The prevalence of spontaneous preterm birth at <32 weeks or <34 weeks was higher in women with a cervical length of ≤10 mm compared to those with a longer cervical length (P < .001). The risk of spontaneous preterm birth in asymptomatic women with a sonographic short cervix increases as cervical length decreases. The risk is substantially higher in women with a cervical length of ≤10 mm. Women with a cervical length of ≤10 mm also had the shortest time interval to delivery. Nevertheless, delivery within 1 or 2 weeks is highly unlikely, regardless of the cervical length at the time of enrollment. Therefore, based on our data, we suggest that management decisions such as timing of administration of antenatal corticosteroids in asymptomatic patients with a cervical length of ≤25 mm at 23-28 weeks' gestation may be delayed until additional indications are present.

Cervical modifications after pessary placement in singleton pregnancies with maternal short cervical length: 2D and 3D ultrasound evaluation.

The use of a pessary proved to prevent preterm birth in asymptomatic women with mid-trimester short cervical length (CL); however, the precise mechanisms by which the pessary confers its benefit remain unclear. The aim of this study was to evaluate multiple cervical characteristics assessed by 2-dimensional and 3-dimensional ultrasound before and after placement of a cervical pessary to ascertain its mechanism of action. In this prospective cohort study, we assessed the cervical characteristics in singleton pregnancies with maternal short CL and compared them with matched reference women with normal CL. The variables evaluated were: CL, uterocervical angles, cervical consistency indices (cervical consistency index and CL consistency index), cervical volume and vascular indices. All variables were re-assessed immediately after pessary placement and 4-6weeks later in all participants. Mann-Whitney U test was used to assess differences between groups and paired samples t test for comparisons in two different examinations in the same women. The aim of this study was to evaluate multiple cervical ultrasound variables before and after the placement of a cervical pessary and compare the evolution of these variables with a reference group with normal CL to better understand the device's mechanism of action. Thirty-three women with short CL and 24 reference women with normal CL were enrolled. At the time of enrollment, gestational age and maternal baseline characteristics did not differ between groups. Immediately after pessary placement, CL increased, uterocervical angles were narrower and cervical consistency increased significantly. When the magnitude of change in cervical variables was compared over time between the reference group and the study group, median CL had increased in the study group (1.47mm) but it had shortened in the reference group (-2.56mm). These inverse trends were statistically significant (P=0.006). Cervical pessary reduces both uterocervical angles and corrects cervical angulation by pushing the cervix up toward the uterus. Maintaining the cervix aligned to the uterine axis leads to reduced cervical tissue stretch, so avoiding further cervical shortening. All these changes were present after pessary placement; however, the clinical implications of these findings remain unknown.

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

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

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

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

Accuracy of fetal fibronectin for assessing preterm birth risk in asymptomatic pregnant women: a systematic review and meta‐analysis

Fetal fibronectin (fFN) is a validated test for assessing risk of preterm birth for women presenting with symptoms. Our aim was to evaluate the accuracy of fFN to detect the risk of preterm birth in asymptomatic women. Searches were conducted to identify studies where fFN was performed in asymptomatic women beyond 22weeks' gestation. EMBASE, MEDLINE, CINHAL, AMED and BNI were searched between 2005 and 2017. Studies before 2005 were identified from a published systematic review. Women were grouped as singleton pregnancies, with and without risk factors for preterm birth, and multiple pregnancy. Quality assessment was performed using QUADAS-2. When possible, data were pooled using a hierarchical, bivariate random effects model. Fifteen studies met the inclusion criteria: six studies of singleton pregnancies in women without risk factors (1236 women), four in women with risk factors for preterm birth (2628 women) and five studies were of multiple pregnancy (1427 women). The pooled sensitivity and specificity of fFN in "no risk factors singletons" were 0.48 (95% CI 0.20-0.77), and 0.96 (95% CI 0.86-0.99), respectively. The likelihood ratio of a positive test result was 12 (95% CI 4.70-30.68). The pooled sensitivity and specificity of fFN in "risk factors singletons" were 0.34 (95% CI 0.24-0.43), and 0.91 (95% CI 0.88-0.93). The accuracy of fFN in multiple pregnancies was inconclusive. Our findings suggest in asymptomatic singleton pregnancies without risk factors, a positive fFN result indicates a large shift from pre- to post-test probability, possibly identifying women at increased risk of preterm birth.

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: the Quadruple P randomised controlled trial

BackgroundPreterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments.Methods/designThe Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16–22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study.Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first.Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs.DiscussionThis trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples.Trial registrationTrial registration number: NTR 4414. Date of registration January 29th 2014.