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Predictive Value of Cervical Length Measurement and Fibronectin Testing in Threatened Preterm Labor
... The authors were contacted but did not provide us with data. Seven articles on fFN were included [16][17][18][19][20][21][22] and four on phIGFBP-1 [6,8,23,24]. One article compared phIGFBP-1 with fFN, with and without CL measurement [25]. ...
... The characteristics of the included studies are summarized in Appendix C. Of the eight articles on fFN, four were prospective cohort studies [16,20,21,25], of which two double blinded [18,19], and two were retrospective cohort studies [17,22]. In total, five articles studied qualitative fFN [17,19,21,22,25] and three quantitative fFN [16,18,20]. ...
... The characteristics of the included studies are summarized in Appendix C. Of the eight articles on fFN, four were prospective cohort studies [16,20,21,25], of which two double blinded [18,19], and two were retrospective cohort studies [17,22]. In total, five articles studied qualitative fFN [17,19,21,22,25] and three quantitative fFN [16,18,20]. Three studies were based on the same biological samples, investigating qualitative fFN, quantitative fFN, and qualitative fFN versus phIGFBP-1, respectively [16,21,25]. ...
An accurate prognostic method for preterm birth (PTB) could avoid unnecessary treatment(s) with potentially negative effects. The objective was to explore the prognostic accuracy of commercially available bedside cervicovaginal biomarker tests in combination with cervical length (CL) compared to CL measurement alone and/or a biomarker test alone, for PTB within 7 days after testing symptomatic women at 22–34 weeks. The MEDLINE, Cochrane, Embase and Web of Science databases were searched from inception to August 28th, 2019. Seven hundred and eight articles were identified and screened using Rayyan. Studies reporting on the predictive accuracy of combined tests compared to CL or biomarker alone for the prediction of PTB within 7 days of testing in symptomatic women with intact membranes were included. A piloted data extraction form was used. Direct comparisons of the prognostic accuracy of the combination test with CL measurement or a biomarker alone were done, as well as comparisons of prognostic accuracy of the included combination tests (indirect comparisons). Twelve articles were included (seven on fetal fibronectin, four on phosphorylated insulin-like growth factor binding protein-1, one comparing both). A variety of CL cut-offs was reported. The results could not demonstrate superiority of a combination method compared to single methods. Due to data scarcity and quality, the superiority of either predictive test for PTB, either combination or single, cannot be demonstrated with this systematic review. We recommend further research to compare available biomarkers.
... 2 Women with threatened preterm labor (PTL) between 24 and 34 weeks present at a rate approximately 2-3 times higher than those that go on to deliver. 3 The treatment course for women admitted with a presumed diagnosis of PTL includes interventions with limited efficacy. 4 Tocolytics are used to prolong pregnancy for 2 days to achieve proper action of corticosteroids and for in utero transfer to a high risk facility equipped with a NICU; however, no tocolytic drug is associated with a reduction in prenatal or neonatal morbidity, and the use of tocolytics does not lengthen gestation beyond 1 week. 5 Antenatal corticosteroids are the only therapy to show promise in women at risk of preterm delivery between 24 and 34 weeks for the primary purpose of advancing fetal lung development, but there is insufficient evidence to demonstrate any benefit beyond a single course. ...
... While it aids in categorizing women with a long cervix (>30 mm) as low risk and women with a short cervix (<15 mm) as very high risk, it fails to properly establish the risk when CL is equivocal. 4,8,9 Several biomarkers have been investigated for this purpose. Most notably, fetal fibronectin (fFN) was determined to be useful for its high negative predictive value (NPV), but significantly lacks the positive predictive value (PPV) to accurately identify women at risk of imminent delivery. ...
... Using CL in combination with quantitative fFN shows a slightly improved performance; yet, the best PPV achieved was 28%. 4 The most recent biomarker introduced into this space is placental alpha macroglobulin-1 (PAMG-1; PartoSure, Parsagen Diagnostics, Inc.). Several trials have already shown the effectiveness of PAMG-1 for assessing the risk of preterm birth, showing PPV as high as 76% and 78%. ...
Aim:
We aimed to evaluate the combined value of placental alpha microglobulin-1 (PAMG-1) and cervical length (CL) via transvaginal ultrasound for assessing risk of imminent spontaneous preterm delivery in patients presenting with threatened preterm labor (PTL).
Methods:
Clinical exam, PAMG-1 test, cardiotocography, and CL measurement via transvaginal ultrasound were performed on all patients meeting inclusion criteria. Ninety-nine patients at 22(+0) -36(+6) gestational weeks with the symptoms of PTL were included. The interval between sample collection and delivery was measured for each method.
Results:
Performance metrics were calculated for PAMG-1 test, CL < 25 mm, and contractions ≥ 8/h. The sensitivity, specificity, positive predictive value, and negative predictive value for the PAMG-1 test were 100%, 95%, 75%, 100% and 100%, 98%, 88%, 100% for 7 and 14 days, respectively; the respective values for CL < 25 mm were 83%, 59%, 22%, 96% and 79%, 59%, 24%, 94% for 7 and 14 days; and those for contractions ≥ 8/h were 42%, 38%, 8%, 83% and 43%, 38%, 10%, 80% for 7 and 14 days. Specificity for the PAMG-1 test was statistically significant (P < 0.001) in pairwise comparisons for all other methods. Patients were divided into four groups for analysis of PAMG-1 test performance as follows: CL < 15 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively); CL < 25 mm (100%, 94%, 83%, 100% and 100%, 97%, 92%, 100% for 7 and 14 days, respectively); CL of 15-30 mm (100%, 95%, 64%, 100% and 100%, 97%, 82%, 100% for 7 and 14 days, respectively); and CL ≥ 30 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively).
Conclusion:
The use of the PAMG-1 test in patients with a CL of 15-30 mm is highly predictive of imminent spontaneous preterm delivery in women presenting with threatened PTL and could save hospital resources.
... Nine percent of pregnancies are complicated by an episode of threatened preterm labor (PTL) requiring hospital referral (1). Actual labor will occur within the first 7 days of presentation in 5-10% of these women (1,2). The overall majority of women with threatened PTL, however, remain pregnant after the first 7 days and 50% will eventually deliver at term (3)(4)(5). ...
... In women with threatened PTL both tests can be applied to identify those women who are unlikely to deliver (3,5,8,9). Recently, we found in our APO-STEL-I study that combining CL and fFN could improve the selection of women who were unlikely to deliver within 7 days compared to using either test alone (2). ...
... We used data of the APOSTEL-I study (2). This nationwide prospective cohort study enrolled 714 women with threatened PTL and intact membranes between 24 and 34 weeks' GA in all 10 (2,13). ...
To stratify the risk of spontaneous preterm delivery using cervical length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor who remained pregnant after seven days.
Prospective observational study.
Nationwide cohort of women with threatened preterm labor from the Netherlands.
Women with threatened preterm labor between 24 and 34 weeks with a valid CL and fFN measurement and remaining pregnant 7 days after admission.
Kaplan Meier and Cox proportional hazards models were used to estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery.
Spontaneous delivery between seven and 14 days after initial presentation and spontaneous preterm delivery before 34 weeks.
The risk of delivery between seven and 14 days was significantly increased for women with a CL <15 mm or a CL ≥15 - <30 mm and a positive fFN, compared to women with a CL ≥30 mm (HR 22.3 (95%CI 2.6 - 191) and 14 (95%CI 1.8 - 118), respectively. For spontaneous preterm delivery before 34 weeks the risk was increased for women with a CL <15 mm (HR 6.3 (95%CI 2.6-15)) or with a CL ≥15 - <30 mm with either positive fFN (HR 3.6 (95%CI 1.5-8.7)) or negative fFN (HR 3.0 (95%CI 1.2-7.1)) compared to women with a CL ≥ 30mm.
In women remaining pregnant seven days after threatened preterm labor, CL and fetal fibronection results can be used in risk stratification for spontaneous delivery. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
... References: [34,35] Consensus-based recommendation 6.E35 ...
... A prospective randomized study showed that emergency cerclage in women with twin pregnancy and cervical opening reduced the rate of preterm births before 34 Internationally, the term Triple I has replaced the term chorioamnionitis to differentiate maternal fever from infection or inflammation or both (▶ Table 8). ...
Aim The revision of this guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of the guideline is to improve the prediction, prevention and management of preterm birth based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations.
Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote).
Recommendations Part 2 of this short version of the guideline presents statements and recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.
... A short cervical length can also contribute to preterm birth and has been observed in preterm births in about 30% of asymptomatic pregnant 10 . Although, not all pregnant women have the opportunity to assess their cervical length 11 . Obstetricians and gynecologists rarely measure cervical length unless there are symptoms or risk factors for preterm labor, such as abdominal pain or increased vaginal discharge. ...
... Despite inconsistent recommendations regarding the routine assessment of cervical length during pregnancy (9,10,11), this study does recommend the targeted use of cervical length sonography. However, based on the ndings of this study, there may not be a need for global cervical length evaluation but rather a regional and country-speci c approach to allowing early interventions to reduce preterm birth rates. ...
Introduction: Infant mortality is highest in preterm births. Cervical length may indicate early preterm delivery, according to studies. We assessed cervical length, gestational age, birth weight, and delivery Apgar scores.
Methods: This research included 100 women bearing 100 live foetuses (mean maternal age: 29.42±6.26 years, mean gestational range 18-20 weeks). Transvaginal ultrasound measured cervical length in all women. Birth weight, gestational age, and Apgar scores were recorded.
Results: 0% had cervical length less than 15 mm, 9% 15-25 mm, 75% 25-35 mm, and 16% >35 mm. ANOVA showed a significant relationship between cervical length classification and gestational age (p=0.031) and birth weight (p=0.001), but not Apgar scores (p=0.35) or gestational age at birth (p=0.29). Birth weight correlated significantly (p=0.04).
Conclusions: Cervical length screening during the second trimester should be regular in selected nations or areas to decrease premature labour.
... However, a woman with a cervical length <25 mm has a 6-fold increased risk of preterm delivery [27]. Combining cervical length of 15-30 mm with fetal fibronectin testing to predict delivery by women with symptoms of preterm labor improved identification of women with a low risk to deliver spontaneously within 7 days [28]. A high negative predictive value (NPV), but low PPV, make fetal fibronectin a good test to exclude premature delivery, but not a good test to predict it [29]. ...
... A high negative predictive value (NPV), but low PPV, make fetal fibronectin a good test to exclude premature delivery, but not a good test to predict it [29]. For a subgroup of symptomatic patients with a cervical length 15-30 mm, the PPV of fetal fibronectin remains poor [28]. ...
Background
Presence of placental α microglobulin-1 (PAMG-1) in cervicovaginal fluid is a bedside test to predict preterm delivery.
Objective
To determine whether the accuracy of a positive PAMG-1 test result to predict preterm birth within 7 days and 14 days in our hospital setting can be improved by adding cervical length.
Methods
We recruited 180 pregnant women who attended the labor ward of Siriraj Hospital, Thailand, from 2016 to 2018 for this prospective observational study of diagnostic accuracy. We used data from 161 women who met inclusion criteria including symptoms of preterm labor between 20 0/7 and 36 6/7 weeks’ gestation without ruptured membranes and with cervical dilatation <3 cm and effacement <80%. Presence of PAMG-1 in cervicovaginal fluid was tested using a PartoSure kit, cervical length was measured by transvaginal ultrasound, and the time to spontaneous delivery was calculated.
Results
Pregnant women with labor pain who had cervical length <30 mm (45/161; 28%) went into delivery within 7 days, and women with a cervical length <15 mm (11/14; 79%) went into delivery within 7 days. When the PAMG-1 test result was positive and cervical length was ≤15 mm, the positive predictive value (PPV) was 83%; and when cervical length was ≤30 mm the PPV was 69%. The optimal cut off from receiver operating characteristic curve analysis showed that a cervical length <25 mm and PAMG-1 positive result has a PPV of 80% to predict preterm birth within 7 days and 90% within 14 days. The area under the curve (95% confidence interval) for a positive PAMG-1 result and cervical length ≤25 mm to predict preterm birth <7 days was 0.61 (0.50, 0.73) and <14 days was 0.60 (0.49, 0.70).
Conclusions
Cervical length ranging 15–30 mm combined with a positive PAMG-1 test result has a high accuracy to predict imminent spontaneous delivery within 7 days by women with preterm labor and cervical dilatation <3 cm in clinical practice.
... Cervical length has an inverse relationship with the risk of preterm birth in symptomatic women, and dynamic shortening of cervical length is also associated with preterm birth [6][7][8] . Similarly, elevated fetal fibronectin levels have been linked to an increased risk of preterm birth in women with threatened preterm labor [9][10][11] . ...
... It remains a clinical challenge to differentiate between high and low risk of preterm birth in women presenting with threatened preterm labor, as over half of these women eventually deliver at term 12 . This is especially the case for women who are defined as being at high risk of preterm birth based on cervical length and fetal fibronectin status at admission, but who have arrested preterm labor after 48 h of tocolysis 10,13 . To date, little is known about the value of an additional transvaginal cervical-length measurement following an episode of threatened preterm labor after contractions have ceased. ...
Objectives:
To assess the association between preterm birth and cervical length after arrested preterm labour in high-risk women.
Methods:
In this post-hoc analysis of a randomised clinical trial, transvaginal cervical length was measured in women in whom contractions had ceased 48h after admission for threatened preterm labour. At admission, women were defined as high risk of preterm birth based on cervical length <15 mm or cervical length 15-30 mm with a positive foetal fibronectin test. Using logistic regression analysis, the association of cervical length after 48h (C2) and change in cervical length between admission (C1) and 48h later (Δc = C2-C1) was investigated with preterm birth before 34 weeks and delivery within 7 days of admission.
Results:
A total of 164 women were included in the analysis. Women whose cervical length (Δc) increased between admission for threatened preterm labour and 48 hours later (N=32%) were found to have a lower risk of preterm birth <34 weeks, compared to women whose cervical length did not change (odds ratio (OR) 0.24, 95% CI 0.09 to 0.69). The risk of women with a decrease in cervical length was not different (OR 1.45 95% CI 0.62 to 3.41) compared to no change in cervical length. Moreover, a longer absolute cervical length (C2) after 48 hours resulted in a lower risk of preterm birth <34 weeks and a lower risk of delivery <7 days (OR 0.90, 95% CI 0.84 to 0.96 and OR 0.91, 95% CI 0.82 to 1.02, respectively). Sensitivity analysis in women randomised to no intervention showed comparable results.
Conclusions:
Our study suggests that the risk of preterm birth before 34 weeks is lower when cervical length increased between admission for threatened preterm labour and 48 hours later when contractions have ceased, compared to when cervical length did not change or decreased. This article is protected by copyright. All rights reserved.
... [13][14][15][16] The APOSTEL-I study showed that women with a cervical length ≤ 15 mm or a cervical length between 15 and 30 mm and a positive fFN test result are at increased risk for preterm delivery within 7 days. 17 Therefore, in our local protocol women with a cervical length ≤ 15 mm or a cervical length between 15 and 30 mm and a positive fFN test result are admitted and treated. Women with a cervical length between 15 and 30 mm and a negative fFN test result or a cervical length ≥ 30 mm are not treated. ...
... Previous literature found that the combination of cervical length between 15 and 30 mm and fFN could reduce the number of referrals and admissions to perinatal centers with 10% (compared with cervical length as the sole predictor). 17 While earlier studies showed fFN testing has a high negative predictive value, the validity of the fFN test with blood on the sample is still controversial. In the present study we found that the negative predictive value of fFN testing remained 100% and that blood on the fFN sample does not affect the validity of the fFN test. ...
Aim:
To evaluate the clinical management to withhold treatment for preterm labor in symptomatic women with an intermediate cervical length and negative fetal fibronectin (fFN) testing.
Methods:
A retrospective cohort study was performed in a tertiary care teaching hospital in the Netherlands. Pregnant women with a gestational age between 23+5 to 34+0 weeks, with the presence of regular uterine contractions accompanied by a cervical length between 15 and 30 mm and intact membranes, who underwent fFN testing were included to obtain the diagnostic value of fFN testing for preterm delivery within 7 days.
Results:
Fetal fibronectin testing has an extremely high negative predictive value (100%) and sensitivity (100%) for delivery within 7 days, in singleton and multiple pregnancies. However, specificity (64%) and positive predictive value (10%) of fFN testing in singleton pregnancies are low. Blood present on the fFN sample does not affect the reliability of the fFN test; the negative predictive value remains 100%.
Conclusion:
Women with symptoms of early preterm labor, intact membranes, a cervical length between 15 and 30 mm and negative fFN testing do not deliver within 7 days. Administration of corticosteroids and tocolytics can safely be withhold. Furthermore, blood on the fFN sample does not change the reliability of the fFN test.
... The combination of cervical length measurement on ultrasound and biomarker testing in the cervicovaginal secretions should enable a differentiation to be made in pregnant women at low risk (< 2-5 %) for a preterm delivery within 7 days who do not need tocolysis and pregnant women at high risk for whom an inpatient admission and tocolysis as well as induction of foetal lung maturation is recommended. Indicative for this recommendation were a meta-analysis by De Franco et al. [9] as well as the results of a prospective cohort study (n = 665, 24th-34th weeks of pregnancy) from the Netherlands, with disproportionate inclusion of later weeks of the time period mentioned and thus a significant bias [10]. Pregnant women with preterm contractions and a cervical length > 30 mm or a cervical length of 15-30 mm and negative fibronectin have a preterm delivery rate < 5 % within a week. ...
... Pregnant women with regular preterm contractions, a cervical length < 15 mm or a cervical length of 15-30 mm and a positive fibronectin test had a risk of preterm delivery within 7 days of 52 and 11-17 % respectively and thus an indication for tocolysis [10]. In a subgroup analysis of the APOSTEL-I study, the combination of cervical length measurement on ultrasound and the determination of foetal fibronectin proved to be cost-effective through the reduction in inpatient admissions, tocolysis and induction of foetal lung maturation [12]. ...
Tocolysis is among the most common obstetric measures. The objective is to prolong the pregnancy by at least 48 hours to complete foetal lung maturation and for the in-utero transfer of the pregnant woman to a perinatal centre. The indication for tocolysis is regular, premature contractions (≥ 4/20 min) and a dynamic shortening of the cervical length/cervical opening between 22 + 0 to 33 + 6 weeks of pregnancy. In this connection, the cervical length measured on ultrasound and the determination of biomarkers in the cervicovaginal secretions can be important decision-making aids. Beta sympathomimetics should no longer be used due to the high rate of severe maternal adverse effects. Given controversial data, magnesium sulphate is no longer recommended for tocolysis in current guidelines. Atosiban is as effective for prolonging pregnancy as beta sympathomimetics and nifedipine, has the lowest rate of maternal adverse effects, but also the highest drug costs. Nifedipine and indomethacin are recommended in international guidelines for acute tocolysis, however there are indications of increased neonatal morbidity following indomethacin. Current problems are, above all, the lack of randomised, controlled comparative and placebo-controlled studies, the data which are controversial to some extent, and the insufficient evidence of tocolytics to significantly improve the neonatal outcome.
... 3 De fibronectinetest is van toegevoegde waarde als 'rule-out test' om vrouwen te identificeren die niet op korte termijn zullen bevallen. [4][5][6] Hierdoor kunnen overbehandeling en onnodige opnames en overplaatsingen voorkomen worden. 7,8 Een kosteneffectiviteitsanalyse laat zien dat deze strategie een kostenbesparing van 480-1512 euro per patiënt kan opleveren. ...
... Hoewel deze resultaten al in 2009 zijn gepubliceerd en in 2014 een grootschalige studie verscheen die de klinische waarde van deze test bevestigde, 4,5 wordt het gebruik van de fibronectinetest niet vermeld in de landelijke richtlijn 'Dreigende vroeggeboorte' van de Nederlandse Vereniging voor Obstetrie en Gynaecologie (NVOG) uit 2011. 3 Wij onderzochten in hoeverre de fibronectinetest inmiddels bij de diagnostiek van dreigende vroeggeboorte in Nederland wordt gebruikt. ...
Objective:
Analysis of national implementation of the foetal fibronectin test in the diagnostics of threatened preterm labour in the Netherlands, and indication of the possible obstacles and consequences of implementation or no implementation.
Design:
National questionnaire, retrospective cohort study and cost-effectiveness calculation.
Methods:
We approached all hospitals in the Netherlands (n = 86) with a questionnaire on use of the fibronectin test. We also collected data on women who were referred to the Academic Medical Center (AMC), a tertiary care centre in Amsterdam, with symptoms of threatened preterm labour. We investigated whether the referred patients gave birth within 7 days, and whether unnecessary transfer to a centre with a neonatal intensive care unit (NICU) could have been avoided by implementation of the fibronectin test in the referring hospital.
Results:
The fibronectin test was used in 34% of the hospitals and an additional 17% were in the process of implementation. The most important reasons not to use the fibronectin test were of a financial nature (50%). The cohort study included 96 women who were referred from secondary care. In our cohort, 36% of all transfers could have been avoided by implementation of the fibronectin test in secondary care.
Conclusion:
The fibronectin test can greatly reduce overtreatment and unnecessary transfer in threatened preterm labour, but implementation remains limited. Costs of the test are an obstacle for the referring hospitals, while implementation prevents unnecessary transport, admission and treatment of pregnant women, giving a potential saving of at least EUR 1,027,930 per year. Inclusion in the Netherlands Society for Obstetrics and Gynaecology (Nederlandse Vereniging voor Obstetrie en Gynaecologie, NVOG) guidelines would be a first step towards wider implementation. Slow implementation exemplifies a more widespread problem: the current reimbursement system does not stimulate such cost-saving innovations.
... When preterm labour occurs, the management includes the administration of antenatal corticosteroids to promote foetal lung maturity and tocolytic therapy to inhibit uterine contraction (ACOG 2012;Theplib and Phupong 2016). However, 75-95% of these women will not deliver within seven days after their presentation of preterm labour (van Baaren et al. 2014). If we can identify women who will not deliver within seven days, unnecessary admission and tocolytic therapy can be avoided. ...
... A meta-analysis reported that biomarkers, such as foetal fibronectin, are of a limited accuracy in the prediction of imminent spontaneous delivery in symptomatic patients because of poor positive predictive values. A combined use of foetal fibronectin and the cervical length for predicting timing of delivery within seven days have been found to have a low sensitivity and specificity (Sotiriadis et al. 2010;van Baaren et al. 2014). ...
The aim of this study was to predict the timing of delivery within seven days in singleton pregnant women with threatened preterm labour and preterm labour by using a three-dimensional (3D) ultrasound measurement of foetal adrenal gland volume enlargement, a foetal zone enlargement and cervicovaginal placental alpha microglobulin-1 (PAMG-1) test. This prospective cohort study included singleton pregnant women at 22–36⁺⁶ weeks of gestation who presented with threatened preterm labour and with preterm labour. Transabdominal 3D ultrasound measurement of the whole foetal adrenal gland and of the foetal adrenal zone were performed. Qualitative cervicovaginal PAMG-1 detection was performed at the same time. One hundred and fifty-four pregnant women were included into the study. Eighty-four pregnant women had threatened preterm labour and seventy pregnant women had preterm labour. Twenty-nine pregnant women (18%) delivered within seven days. Use of foetal adrenal gland volume enlargement, foetal zone enlargement and the PAMG-1 test in combination increased sensitivity; if one parameter was positive, the sensitivity, specificity, positive predictive value and negative predictive value were 82.8%, 27.2%, 20.9% and 87.2%, respectively, in the prediction of the timing of delivery within seven days. The combination of foetal adrenal gland enlargement and PAMG-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour.
• Impact Statement
• What is already known on this subject? An increased foetal adrenal gland volume is significantly correlated with the risk of preterm birth.
• What do the results of this study add? The combination of a foetal adrenal gland enlargement and a placental alpha microglobulin-1 increased sensitivity for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and preterm labour.
• What are the implications of these findings for clinical practice and/or further research? The combination of a foetal adrenal gland enlargement and placental alpha microglobulin-1 may be used for the prediction of the timing of delivery within seven days in pregnant women presenting with threatened preterm labour and with preterm labour.
... [51][52][53] Several observational studies have noted that the combination of CL and fetal fibronectin (FFN) assessment may improve prediction of PTB among women with symptoms of acute preterm labor. [54][55][56] In triage units that combine CL screening and FFN testing in "symptomatic" patients, FFN does not add to PTB prediction in women with a very short (<20 mm) or long (>30 mm) CL. In these situations FFN may be discarded because the NPV of CL 30 mm alone is high (96-100%) and women with CL <20 mm are at high enough risk that PTL treatment should be initiated based on CL alone. ...
... 54 When used in combination with CL screening, FFN may be most useful in women with CL of 20-29 mm (e.g. the "grey zone"); in this situation a "negative test" (z80% of cases) may allow for no treatment while a positive test would suggest the need for intervention (antenatal corticosteroids, transfer to tertiary center, etc). [54][55][56] There remains some controversy with the routine use of FFN with or without CL screening to detect true PTL in symptomatic women. To date, only one interventional trial has shown that knowledge of CL and FFN improves outcomes. ...
... Spontaneous PTB is by preceded by threatened preterm labor (PTL), defined as preterm contractions leading to cervical effacement or dilation [5][6][7]. However, not all women with threatened PTL deliver preterm. ...
... Women who have experienced an episode of threatened PTL but who do not deliver remain at an increased risk for PTB in the following weeks of pregnancy [5,6]. An effective treatment is currently not available for these women. ...
Objective:
Threatened preterm labor (tPTL) is a complication of pregnancy. Identification of women and clinical definition differs between countries. This study investigated differences in tPTL and effectiveness of vaginal progesterone to prevent preterm birth (PTB) between two countries.
Methods:
Secondary analysis of a randomized controlled trial (RCT) from Argentina and Switzerland comparing vaginal progesterone to placebo in women with tPTL (n = 379). Cox proportional hazards analysis was performed to compare placebo groups of both countries and to compare progesterone to placebo within each country. We adjusted for baseline differences. Iatrogenic onset of labor or pregnancy beyond gestational age of interest was censored.
Results:
Swiss and Argentinian women were different on baseline. Risks for delivery <14 days and PTB < 34 and < 37 weeks were increased in Argentina compared to Switzerland, HR 3.3 (95% CI 0.62-18), 54 (95% CI 5.1-569) and 3.1 (95% CI 1.1-8.4). In Switzerland, progesterone increased the risk for delivery <14 days [HR 4.4 (95% CI 1.3-15.7)] and PTB <37 weeks [HR 2.5 (95% CI 1.4-4.8)], in Argentina there was no such effect.
Conclusion:
In women with tPTL, the effect of progesterone may vary due to population differences. Differences in populations should be considered in multicenter RCTs.
... Optimal timing of the first course of ACS can prevent the rise of the question whether or not to repeat a course. In women with symptoms of PTL, measurement of the cervical length (CL) by vaginal ultrasound in combination with fetal fibronectin (fFN) testing might improve the recognition of women at low risk of PTD within the next seven days [28][29][30][31][32]. ...
... Clinicians could prescribe nifedipine, indomethacin, atosiban and/or ritodrine. Corticosteroids were given to women at the discretion of the clinician on call [32]. ...
... 60 The screening of women with symptomatic PTL should mostly be done using TVU CL and fetal fibronectin (FFN) testing. [61][62][63][64] With these screening tests, clinicians can identify women at high risk for PTB who might need corticosteroids, tocolytics, and transfer ...
... Due to the limitation of FFN alone, it is suggested that the women with preterm contractions be screened with TVU CL screening first and, if the cervix is borderline (20-29 mm), FFN testing is suggested to improve screening of women who are at risk for PTB within 1 to 2 weeks of presentation. [62][63][64] Women with preterm contractions but TVU CL greater than 30 mm represent about 50% of women presenting with threatened PTL. These women have a less than 2% chance of delivering within 1 week and a greater than 95% chance of delivering equal to or greater than 35 weeks without therapy. ...
Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. With research efforts, the rate of PTB decreased to 11.4% in 2013. Transvaginal ultrasound (TVU) cervical length (CL) screening predicts PTB. In asymptomatic singletons without prior spontaneous PTB (sPTB), TVU CL screening should be done. If the cervix is 20 mm or less, vaginal progesterone is indicated. In asymptomatic singletons with prior sPTB, serial CL screening is indicated. In multiple gestations, routine cervical screening is not indicated. In symptomatic women with preterm labor, TVU CL screening and fetal fibronectin testing is recommended.
Copyright © 2015 Elsevier Inc. All rights reserved.
... For our study we used data from one prospective cohort study and three multicentre randomised controlled trials (RCTs) on preterm birth performed in the Dutch consortium for women's health research between 2006 and 2012. The prospective cohort study was the APOSTEL I (NTR 1857), which evaluated the use of fetal fibronectin testing and cervical length in 714 women with threatened preterm labour [12]. The APOSTEL II-trial (NTR 1336) compared maintenance tocolysis with nifedipine to placebo in 406 women with threatened preterm labour [13]. ...
... The PROTWINtrial (NTR 1858) compared a cervical pessary to expectant management in 813 multiple pregnancies [9]. The full design and results of these studies have been described elsewhere [9,[12][13][14]. ...
... PTL was diagnosed as the presence of regular uterine contractions (at least two contractions every 10 min), along with cervical length (measured using transvaginal ultrasound) shorter than 15 mm or within 15-30 mm with a positive PartoSure test (Parsagen Diagnostics Inc., Boston, MA) [43]. ...
Objective
The aim of this study was to evaluate CD36 concentrations in amniotic fluid in pregnancies complicated by spontaneous delivery with intact fetal membranes (preterm labor, PTL) and preterm prelabor rupture of membranes (PPROM) with respect to the presence of the intra-amniotic infection.
Methods
A total of 80 women with PPROM and 71 with PTL were included in the study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid CD36 concentrations were assessed by enzyme-linked immunosorbent assay. Microbial colonization of the amniotic cavity (MIAC) was determined by the cultivation and non-cultivation approach. Intra-amniotic inflammation (IAI) was defined as an amniotic fluid bedside interleukin-6 concentration ≥3000 pg/mL. Intra-amniotic infection was characterized by the presence of both MIAC and IAI.
Results
Women with PPROM with intra-amniotic infection had higher amniotic fluid CD36 concentrations than women without infection (with infection: median 346 pg/mL, IQR 262–384 vs. without infection: median 242 pg/mL, IQR 199–304; p = .006) A positive correlation between amniotic fluid CD36 concentrations and interleukin-6 concentrations was found (rho = 0.48; p < .0001). In PTL pregnancies, no statistically significant difference was found in the amniotic fluid level of CD36 between intra-amniotic infection, sterile IAI, and negative amniotic fluid.
Conclusions
The presence of intra-amniotic infection is characterized by higher amniotic fluid CD36 concentrations in pregnancies complicated by PPROM. An amniotic fluid CD36 cutoff value of 252.5 pg/mL was found to be optimal for the prediction of intra-amniotic infection. In PTL pregnancies, no statistically significant change in CD36 concentration was found with respect to the presence of intra-amniotic infection.
... Therefore, determining the high-risk group for preterm labor and preventing preterm labor and its complications have been the most important issues of obstetrics. The currently used methods for predicting preterm labor with high negative predictive value are cervical length measurement and cervicovaginal fetal fibronectin [10]. In the present study, we evaluated some of the oxidative stress parameters such as biochemical markers that can be used for the prediction of preterm labor. ...
Purpose
The purpose of this study was the evaluation of total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI) and superoxide dismutase (SOD) levels in women with threatened preterm labor (TPL) and also to compare the levels of these oxidative stress biomarkers of TPL pregnancies that had preterm and term deliveries.
Methods
This case–control study was conducted on 46 patients diagnosed with TPL and 47 healthy pregnant women matched for gestational age. Patients with threatened preterm labor were divided into two groups: true preterm birth (TPB) group (n = 16) and false preterm birth (FPB) group (n = 30) groups. Maternal serum SOD, TOS and TAS levels were measured by a spectrophotometric method using a commertial kit. OSI level for each patient was calculated by using the formula: (TOS (μmol·H2O2·equiv/L) × 100)/(TAS (μmol·Trolox·equiv/L)).
Results
The mean TAS levels of the TPB and FPB groups were significantly lower than those of the control group (0.96 ± 0.3 vs 1.36 ± 0.34, p1 < 0.001; 0.97 ± 0.22 vs 1.36 ± 0.34, p2 < 0.001, respectively). The mean SOD, TOS and OSI levels of the TPB and FPB groups were significantly higher than those of the control group (p < 0.001). There was no significant difference between the TPB and FPB groups for any oxidative stress biomarkers.
Conclusion
The maternal serum oxidative stress biomarkers are increased in pregnancies with TPL. However, these are not effective in predicting preterm birth in pregnancies with TPL.
... If not medically induced, approximately 25% of cases are caused by preterm rupture of membranes (pPROM); 30% of cases are caused by inflammation and infection, while 45% of cases are considered spontaneous with intact membranes 5 . Recently, cervical length (CL) shortening 6 has become a clinical marker of PTB risk 7,8 . Although still controversial, the National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Network uses a cutoff of 25 mm to define a short cervix at 22 to 24 weeks of gestation in both low-and high-risk pregnancies 9 . ...
Objective:
Recently, the PTB risk has been related to the objective measurement of cervical length (CL), since a CL of less than 25 mm is an accurate predictor of increased risk of PTB. Primary prevention of preterm labor is based on the early identification of symptoms and on pharmacological treatments with tocolytic drugs for inhibition of uterine contractions that are associated with a shortening of the cervix. Unfortunately, most of these drugs have important side effects.
Patients and methods:
This study aimed to evaluate whether the administration of a combination of oral α-lipoic acid (ALA), magnesium, vitamin B6 and vitamin D to pregnant women presenting risk factors for PTB could reduce the rate of cervical shortening at 19-22 weeks of gestational age.
Results:
A total of 122 women attending the first-trimester aneuploidy screening at 11-14 weeks of pregnancy and presenting risk factors for PTB were included in the study. Cervical length significantly decreased in the control group compared with the treatment group (-3.86 ± 1.97 vs. 1.50 ± 1.26; p=0.02). Although the rate of preterm birth did not significantly decrease (9.5% vs. 5.1%), admission for threatened PTB was statistically reduced in the treatment group compared with the control group (3.4% vs. 14.3%).
Conclusions:
Oral supplementation of ALA, magnesium, vitamin B6 and vitamin D significantly counteracted cervix shortening in pregnant women presenting risk factors for PTB.
... Current literature suggests a window of optimal efficacy between 48 hours and seven days after administration of the first dose of ACS [5, 10 -12]. Administration of a full course of ACS in PTB is recommended by worldwide guidelines [13 -16], being used as a quality marker for delivery room practice despite the unpredictable nature of PTB, which leads to a liberal application of ACS to all PTB [17,18]. Currently, only 23 to 40 % of ACS are administered in the window of optimal efficacy, which puts a large number of infants at risk for detrimental outcomes [10,19,20]. ...
Introduction A common problem in the treatment of threatened preterm birth is the timing and the unrestricted use of antenatal corticosteroids (ACS). This study was performed to evaluate the independent effects of the distinct timing of antenatal corticosteroids on neonatal outcome parameters in a cohort of very low (VLBW; 1000 – 1500 g) and extreme low birth weight infants (ELBW; < 1000 g). We hypothesize that a prolonged ACS-to-delivery interval leads to an increase in respiratory complications.
Materials and Methods Main data source was the prospectively collected single center data for the German nosocomial infection surveillance system (KISS) between 2015 and 2018. Multivariate regression analysis was performed to determine independent effects of the ACS-to-delivery interval on the need for ventilation, surfactant or the occurrence of bronchopulmonary dysplasia, neonatal sepsis or necrotizing enterocolitis. Subgroup analysis was performed for ELBW and VLBW neonates.
Results A total of 239 neonates were included. We demonstrate a significantly increased risk of respiratory distress characterized by the need for ventilation (OR 1.045; CI 1.011 – 1.080) and surfactant administration (OR 1.050, CI 1.018 – 1.083) depending on the ACS-to-delivery interval irrespective of other confounders. Every additional day between ACS and delivery increased the risk for ventilation by 4.5% and for surfactant administration by 5%. Subgroup analysis revealed significant differences of respiratory complications in VLBW infants.
Conclusions Our data strongly support the deliberate use and timing of antenatal corticosteroids in pregnancies with threatened preterm birth versus a liberal strategy. When given more than 7 days before birth, each day between application and delivery increases is relevant concerning major effects on the infant. Especially VLBW preterm neonates benefit from optimal timing.
... p = 0.001). These results are in line with the research conducted by DeFranco et al. 10 and Van Baaren et al. 11 which stated the role of cervical length in predicting preterm labor. Berghella et al. 4 stated that cervical length could be used as a predictor and prevent preterm labor. ...
Objective: To determine and compare either change in length, anterior angle, and consistency of cervix can be used as the predictors of preterm labor or not.Methods: This case-control study involved 54 pregnant women with gestational age 20 - 37 weeks, which the case group is women in preterm labor and the control group were not in labor at Sanglah General Hospital, Bali, Indonesia from November 2018 to October 2019. The samples were examined using Transvaginal Sonography (TVS) to collect Cervical Length (CL), Anterior Cervical Angle (ACA), and Cervical Consistency Index (CCI) data.Results: Short CL could increase the risk of preterm labor by 9 times (OR = 8.80, 95% CI = 2.50-30.97, p-value 0.001). Wide ACA could increase the risk by 10 times (OR = 10.45, CI 95% = 2.92-37.39, p = 0.001). Low CCI could increase the risk by 7 times (OR = 7.43, 95% CI = 1.80-30.67, p = 0.003). Anterior cervical angle has the greatest role in the occurrence of preterm labor, followed by CL and CCI, although statistically insignificant (p=0.138; p=0.212= p:0.203).Conclusion: Performing cervical examination using TVS as the antenatal care routine can help predict and prevent preterm delivery.
... Gestational age was established by first-trimester fetal biometry. PTL was diagnosed as the presence of regular uterine contractions (at least two every 10 min), along with cervical length, measured using transvaginal ultrasound, shorter than 15 mm or within the 15-30 mm range with a positive PartoSure test (Parsagen Diagnostics Inc., Boston, MA) (49). PPROM was diagnosed by examining the women, using a sterile speculum, for pooling of amniotic fluid in the posterior fornix of the vagina. ...
Spontaneous preterm birth is a serious medical condition responsible for substantial perinatal morbidity and mortality. Its phenotypic characteristics, preterm labor with intact membranes (PTL) and preterm premature rupture of the membranes (PPROM), are associated with significantly increased risks of neurological and behavioral alterations in childhood and later life. Recognizing the inflammatory milieu associated with PTL and PPROM, here we examined expression signatures of placental tryptophan metabolism, an important pathway in prenatal brain development and immunotolerance. The study was performed in a well-characterized clinical cohort of healthy term pregnancies (n = 39) and 167 preterm deliveries (PTL, n = 38 and PPROM, n = 129). Within the preterm group, we then investigated potential mechanistic links between differential placental tryptophan pathway expression, preterm birth and both intra-amniotic markers (such as amniotic fluid interleukin-6) and maternal inflammatory markers (such as maternal serum C-reactive protein and white blood cell count). We show that preterm birth is associated with significant changes in placental tryptophan metabolism. Multifactorial analysis revealed similarities in expression patterns associated with multiple phenotypes of preterm delivery. Subsequent correlation computations and mediation analyses identified links between intra-amniotic and maternal inflammatory markers and placental serotonin and kynurenine pathways of tryptophan catabolism. Collectively the findings suggest that a hostile inflammatory environment associated with preterm delivery underlies the mechanisms affecting placental endocrine/transport functions and may contribute to disruption of developmental programming of the fetal brain.
... Gestational age was determined based on firsttrimester fetal biometry. PTL was defined as the presence of regular uterine contractions (at least two every 10 min), along with the cervical length, measured using transvaginal ultrasound, shorter than 15 mm or within the 15-30 mm range with a positive PartoSure test (Parsagen Diagnostics Inc., Boston, MA) [34]. Transabdominal amniocentesis and cervical fluid sampling were performed at the time of admission, before administration of corticosteroids, antibiotics, or tocolytics. ...
Objective
To determine the concentration of interleukin-6 (IL-6) in the cervical fluid in women with spontaneous preterm labor with intact fetal membranes (PTL) complicated by intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation), or sterile intra-amniotic inflammation (the presence of intra-amniotic inflammation alone).
Methods
Eighty women with singleton pregnancies complicated by PTL between gestational ages 22 + 0 and 34 + 6 weeks were included in this retrospective cohort study. Samples of amniotic and cervical fluids were collected at the time of admission. Amniotic fluid samples were obtained via transabdominal amniocentesis, and cervical fluid was obtained using a Dacron polyester swab. Microbial invasion of the amniotic cavity was diagnosed based on the combination of culture and molecular biology methods. The concentration of IL-6 in the amniotic and cervical fluids were measured using an automated electrochemiluminescence immunoassay method. Intra-amniotic inflammation was defined as an amniotic fluid IL-6 concentration ≥3000 pg/mL.
Results
The presence of intra-amniotic infection and sterile inflammation was identified in 15% (12/80) and 26% (21/80) of the women, respectively. Women with intra-amniotic infection (median: 587 pg/mL; p = .01) and with sterile intra-amniotic inflammation (median: 590 pg/mL; p = .005) had higher concentrations of IL-6 in the cervical fluid than those without intra-amniotic inflammation (intra-amniotic infection: median 587 pg/mL vs. without inflammation, median: 136 pg/mL; p = .01; sterile intra-amniotic inflammation, median: 590 pg/mL vs. without inflammation, p = .005). No differences were found in the concentrations of IL-6 in the cervical fluid between women with intra-amniotic infection and sterile intra-amniotic inflammation (p = .81).
Conclusion
In pregnancies with PTL, both forms of intra-amniotic inflammation are associated with elevated concentrations of IL-6 in the cervical fluid.
... 5e8 However, a negative fFN result reliably reassures against delivery within 7 days, and therefore, the use of fFN is a standard practice as part of the evaluation of preterm labor at many institutions. 2,7 The manufacturers of the fFN test advise against its use in several clinical scenarios. For example, in the setting of vaginal bleeding or rupture of membranes, a false-positive result can occur owing to the presence of the protein in maternal serum and amniotic fluid, respectively. ...
Objective
To determine if recent cervical manipulation via transvaginal ultrasound (TVU), sterile vaginal examination (SVE), or coitus affects the accuracy of fetal fibronectin (fFN) results.
Data sources
An electronic search was performed in PubMed, SCOPUS, EMBASE, Ovid MEDLINE, ClinicalTrials.gov, The Cochrane Library, and CINAHL using a combination of pertinent keywords from inception until June 2019.
Study eligibility
We included all observational studies that provided individual level data on fFN results after recent TVU, SVE, and/or coitus.
Study appraisal and synthesis methods
Studies were appraised using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. Individual participant data from the included studies were pooled for each intervention. The primary outcome was agreement between pre- and post-manipulation swabs, estimated using proportion agreement and kappa (κ) statistics with 95% confidence intervals (CI). Secondary outcomes included frequency in which the fFN result changed after cervical manipulation and percentage of discordant pairs. Baseline fFN swabs were not obtained in studies examining coitus; therefore, the results of these articles were examined separately. Outcome data was combined to estimate relative risk of a positive qualitative fFN result after coitus and differences in concentration of quantitative fFN.
Results
Of 807 studies identified, six were included. Three studies assessed the effect of TVU (n=346 specimen pairs), two of SVE (n=122 specimen pairs), and two of coitus (n=262 specimen pairs) on fFN results, with one study assessing the effect of more than one intervention. The proportion agreement between specimen pairs before and after TVU and SVE was 93.4% (κ 0.69, 95% CI 0.57-0.81) and 88.5% (κ 0.69, 95% CI 0.54-0.84), respectively. For both TVU and SVE, discordance with a positive pre-intervention fFN and negative post-intervention fFN occurred more frequently than the converse. Patients reporting coitus within 24-48 hours were more likely to have a positive fFN result than controls (39.7% vs. 7.1%, RR 5.6; 95% CI, 3.0-10.6).
Conclusion
Cervical manipulation via TVU or SVE does not significantly affect fFN results; therefore, its use after these exposures is clinically acceptable. Conversely, the use of fFN in the setting of recent coitus should continue to be discouraged.
... Gebelik haftaları arasında CVS ve amniyosentez öncesi bakılan umbilikal arter Doppler'inde artmış pulsatilite endeksi (PI) ile trizomi 18 arasında bağlantı bulunmuştur (6). 12. gebelik haftasında yapılan servikal kanal uzunluğunun ölçümü ile preterm eylem riski olan gebelerin saptanabilmesini, literatüre göre daha erken haftaya çekmeyi hedefledik (7)(8)(9). Bu çalışmada; ultrasonografik parametrelerin, antenatal takipteki yeri ve hastaların daha gebeliğin erken dönemlerinde daha doğru bir şekilde bilgilendirilmeleri konusunda klinik yaklaşıma sağlayacağı katkılar araştırılacak ve tartışılacaktır. ...
... Measurement of cervical length using transvaginal ultrasound with a cut-off value of less than 25 mm in pregnancies between 16 and 34 weeks enables consideration of prophylactic interventions (16). Both cervical length and fetal fibronectin measurement are currently considered effective methods for assessing the risk of preterm birth in women with signs of preterm labour, particularly when used in combination (17). Such strategies are important as they enable practitioners to better deploy treatment and management strategies, for example, whether or not to administer antenatal corticosteroids and whether or not to initiate an in utero transfer. ...
The birth of a healthy baby is a cardinal pregnancy outcome, and one that is best brought about by midwifery, obstetric, and neonatal teams working in partnership with the expectant mother. The last decades have seen considerable improvement in the management of high-risk pregnancies and this has resulted in better condition of the infant at birth, thus optimizing chances for intact survival. Very often, decisions that need to be made are not black and white, such as the timing of preterm delivery when the health of the mother must be weighed against the risks for the infant. This chapter aims to provide an overview for obstetricians of the basic principles of newborn management, and wider aspects such as the organization of services, evaluating practice, and reducing uncertainties, that are also integral to high-quality care.
... These inclusion criteria are based on the results and conclusions of the APOSTEL 1 study 20 and current guidelines within the Netherlands and the UK. Moreover, our previous APOSTEL 3 study, with resembling inclusion criteria, showed that half of the women with these criteria deliver within 7 days, 10 validating this definition of women at high risk for preterm birth. ...
Introduction
Preterm birth complicates >15 million pregnancies annually worldwide. In many countries, women who present with signs of preterm labour are treated with tocolytics for 48 hours. Although this delays birth, it has never been shown to improve neonatal outcome. In 2015, the WHO stated that the use of tocolytics should be reconsidered and that large placebo-controlled studies to evaluate the effectiveness of tocolytics are urgently needed.
Methods and analysis
We designed an international, multicentre, randomised, double-blinded, placebo-controlled clinical trial. Women with threatened preterm birth (gestational age 30–34 weeks), defined as uterine contractions with (1) a cervical length of < 15 mm or (2) a cervical length of 15–30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or insulin-like growth factor binding protein-1 (Actim-Partus test) or (4) ruptured membranes, will be randomly allocated to treatment with atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Analysis will be by intention to treat. A sample size of 1514 participants (757 per group) will detect a reduction in adverse neonatal outcome from 10% to 6% (alpha 0.05, beta 0.2). A cost-effectiveness analysis will be performed from a societal perspective.
Ethics and dissemination
This study has been approved by the Research Ethics Committee (REC) of the Amsterdam University Medical Centres, location AMC, as well as the REC’s in Dublin and the UK. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results.
Trial registration number
Nederlands Trial Register (Trial NL6469).
... The optimal cutoff value for CL was calculated as 31.1 mm with a high sensitivity. Consistent with the previous data, for women with arrested preterm labor with a CL above this limit, we can suggest to follow-up them in an outpatient setting [2,7,20,24,25]. ...
Objective
To investigate whether myometrial thickness (MT) to cervical length (CL) ratio could be used in the prediction of preterm birth (PTB) in singleton pregnancies presented with threatened preterm labor (TPL).
Methods
After 48 h of successful tocolysis, MT was measured transabdominally from the fundal, mid-anterior walls and the lower uterine segment (LUS) in 46 pregnancies presented with TPL. MT measurements were divided into CL, individually. The main outcome was PTB before 37 weeks of gestation.
Results
The patients were divided into two groups as women delivered ≥ 37 weeks (38.68 ± 1.01 weeks) (n = 25) and those delivered < 37 weeks (34.28 ± 2.53 weeks) (n = 21). The mean ± SD CL in the preterm delivery group was significantly shorter than the term delivery group (23.77 ± 9.23 vs 29.91 ± 7.03 mm, p < 0.05). Fundal, mid-anterior or LUS MT values were similar in both groups. However, in those who delivered preterm, the ratios of fundal MT-to-CL (p = 0.026) and mid-anterior MT-to-CL (p = 0.0085) were significantly different compared to those delivered at term. The optimal cutoff values for CL, fundal MT-to-CL and mid-anterior MT-to-CL ratios in predicting PTB were calculated as 31.1 mm, 0.19 and 0.20, respectively. Fundal MT-to-CL ratio predicted preterm delivery with 71% sensitivity, 72% specificity, 68% positive and 75% negative predictive values. For mid-anterior MT-to-CL ratio, respective values were 76, 76, 73 and 79%.
Conclusion
Measurement of MT along with CL may offer a promising method in the management of women presented with TPL.
... The previous observational studies showed that CL combined with fFN could improve the identification of women with a low risk of delivering spontaneously within 7 days [8,[32][33][34] and thus reduce costs and the number of hospitalizations [21]. The clinical trial conducted by Ness et al. also showed that CL combined with fFN was also associated with reduced evaluation time in triage for women with CL ≥ 30 mm [36]. ...
Background
Previous studies have showed that the early diagnosis of threatened preterm labor decreases neonatal morbidity and mortality, avoids maternal morbidity induced by antepartum bed rest and unnecessary treatment, and reduces costs. Although there are many diagnostic tests, none is clearly recommended by international guidelines. The aim of our study was to compare seven diagnostic methods in terms of effectiveness and cost using a decision analysis model in singleton pregnancy presenting threatened preterm labor, between 24 and 34 weeks of gestation.
Methods
Seven diagnostic strategies based on individual or combined use of the following tests: cervical length, cervical fibronectin test, cervical interleukin test and protein in maternal serum, were compared using a decision analysis model. Effectiveness was expressed in terms of serious adverse neonatal events avoided (neonatal morbidity and mortality) at the hospital discharge. The economic analysis was performed from the health care system perspective. Deterministic and probabilistic analyses were performed to test the robustness of the model.
Results
At 24–34 weeks of gestation, the association of cervical length and qualitative fibronectin was the most efficient strategy dominating all alternatives, reducing the perinatal death or severe neonatal morbidity rate up to 15% and the costs up to 31% according to the gestational age. This result was confirmed by the deterministic sensitivity analyses. The probabilistic analysis showed that the association of cervical length and qualitative fibronectin dominated cervical length < 15 mm in more than 90% of the simulations. The comparison with the other tests revealed more uncertainty.
Conclusions
A test using cervical length and qualitative fetal fibronectin appears to be the best diagnostic strategy. Decisions regarding its generalization and funding in France in this population of women should take into account the high, lifetime costs induced by prematurity.
Electronic supplementary material
The online version of this article (10.1186/s12962-018-0106-y) contains supplementary material, which is available to authorized users.
... Similar cervical diameters were also selected as inclusion criteria in the study by Van Baaren et al. They revealed that measurement of cervical length combined with foetal fibronectin testing in cases of a cervical length between 15 and 30 mm, improves the identification of women with a low risk for spontaneous delivery within 7 days [18]. ...
Background
To investigate the utility of vaginal placental alpha microglobulin-1 (PAMG-1) protein as a predictor of preterm delivery within 7 days in pregnancies at risk of premature birth.
Methods
This prospective study was performed in women at risk of premature birth. The levels of vaginal PAMG-1 and foetal fibronectin (fFN) and the transvaginal cervical length measurement (CLM) were investigated and compared.
Results
Seventy-two pregnant women were included in this study. The sensitivities of PAMG-1, fFN and CLM were 73.3, 73.6%, and 52.9%, respectively, while the specificities of PAMG-1, fFN and CLM were 92.9%, 94.3%, and 90.9%, respectively. The positive predictive values of PAMG-1, fFN and CLM were 73.3%, 82.3%, and 64.2%, respectively, and the negative predictive values of PAMG-1, fFN and CLM were 92.9%, 90.9%, and 86.2%, respectively.
Conclusion
The diagnostic accuracy of PAMG-1 is similar to that of fFN in terms of preterm labour detection within 7 days.
... The use of steroids should be reduced by adequate preterm birth risk assessment and by avoidance of early elective CS. Cervical length measurement, in combination with PAMG-1 testing can help to determine which women are at low risk of delivery within 7 days, and perhaps allow more judicious use of antenatal treatments [128]. In some cases when an early CS is needed establishment of fetal lung maturity may be better than giving steroids to all women [129]. ...
... On the other hand, CL is a marker of clinical value in the prediction of PTB, the shorter is the cervix, the higher is the risk of PTB [34,35]. However, a progressive shortening of the cervix has been reported throughout physiological pregnancy. ...
Introduction: Inflammation might be an important underlying cause of preterm birth. Our aim is to explore whether vaginal administration α-lipoic acid reduces cervical inflammation and shortening after primary tocolysis.
Matherials and Methods: Singleton pregnancies between 24-30 weeks remaining undelivered after hospitalization for preterm labor were randomly allocated to placebo (20 women, 15 analyzed) or vaginal ALA 400 mg daily (20 women, 17 analyzed) for 30 days. A cervical swab to quantify pro-inflammatory (IL1, IL2, IL6, IL8, TNFα) and anti-inflammatory (IL4, IL10) cytokines as well as transvaginal ultrasound cervical length measurement (CL) were performed before and after treatment.
Results: The % changes of pro-inflammatory cytokines do not differ between treatment groups, while IL4 significantly increases by vaginal ALA in comparison to placebo (118.0±364.3% vs. 29.9±103.5%, p = 0.012). Combined anti-inflammatory cytokines show same trend (292.5±208.5% vs. 64.5±107.4, p = 0.03). CL remains similar in vaginal ALA group (from 23.1±6.6 to 20.80±7.9 mm), while it significantly decreased in placebo group (from 20.4±6.5 to 13.8±7.5 mm, p < 0.001 vs. Baseline; p = 0.003 vs. vaginal ALA).
Conclusion: Vaginal ALA significantly stimulates anti-inflammatory ILs in the cervix of undelivered women after a preterm labor episode. This effect is associated with a stabilization of the CL.
... There is often warning of impending preterm delivery, and interventions can be considered that might prolong gestation or reduce the risk of an adverse outcome by 'preparing' the fetus, or enabling transfer to a centre with more experience of dealing with problems of prematurity. Cervical length measurement, in combination with fetal fibronectin testing, can help to determine which women are at low risk of delivery within 7 days, and perhaps allow a more judicious use of antenatal treatments [11] . Extremely preterm babies at risk of RDS should be born in centres where appropriate skills are available, as long-term health outcomes are better if they receive their initial neonatal care in tertiary units [12] . ...
Advances in the management of respiratory distress syndrome (RDS) ensure that clinicians must continue to revise current practice. We report the third update of the European Guidelines for the Management of RDS by a European panel of expert neonatologists including input from an expert perinatal obstetrician based on available literature up to the beginning of 2016. Optimizing the outcome for babies with RDS includes consideration of when to use antenatal steroids, and good obstetric practice includes methods of predicting the risk of preterm delivery and also consideration of whether transfer to a perinatal centre is necessary and safe. Methods for optimal delivery room management have become more evidence based, and protocols for lung protection, including initiation of continuous positive airway pressure and titration of oxygen, should be implemented from soon after birth. Surfactant replacement therapy is a crucial part of the management of RDS, and newer protocols for surfactant administration are aimed at avoiding exposure to mechanical ventilation, and there is more evidence of differences among various surfactants in clinical use. Newer methods of maintaining babies on non-invasive respiratory support have been developed and offer potential for greater comfort and less chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease although minimizing the time spent on mechanical ventilation using caffeine and if necessary postnatal steroids are also important considerations. Protocols for optimizing the general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.
... Fetal fibronectin (fFN) is the most evaluated biochemical marker used to predict preterm delivery. Women with a cervical length above 30 mm, or between 15 and 30 mm in combination with a negative fFN test, have been found to have a risk of less than 5 % for spontaneous preterm delivery within 7 days after testing [29]. In our study, the cervical length was found to be significantly shorter in women affected by preterm birth than in term deliveries (17.8 mm vs. 22.0 mm, respectively). ...
Purpose:
Worldwide, preterm birth annually affects more than 15 million infants. Despite increasing knowledge of the risk factors and mechanisms associated with preterm labor, the preterm birth rate has risen in most industrialized countries. The ability to identify women at high risk for spontaneous preterm birth is crucial yet remains difficult. The aim of the present study was to assess the value of cervical length measurements in combination with sonoelastography and interleukin 6 (IL-6) concentrations in cervicovaginal secretions to identify women at risk for preterm birth.
Materials and Methods:
36 pregnant women with signs of threatened preterm birth were enrolled in our prospective cohort study. Cervical length measurement, sonoelastography, and IL-6 levels from cervicovaginal swab samples were measured.
Results:
The preterm birth rate was found to be 33.3% in our study cohort. Maternal age did not differ between the preterm and term birth groups. Measurement of the cervical length alone was found to have a sensitivity of 0.7 and a specificity of 0.8, whereas cervical sonoelastography had a sensitivity of 0.66 and a specificity of 0.82. By using a combination of both methods, the sensitivity and specificity were found to be 0.9 and 0.7, respectively. IL-6 levels were not found to differ between women with term deliveries and women with preterm births.
Conclusion:
Both, cervical sonoelastography and cervical length measurement are valuable tools in identifying women with threatened preterm birth. The highest correlation with the outcome preterm birth was achieved using a combination of both cervical length measurement and cervical sonoelastography.
... The APOSTEL-I study showed that women with a cervical length less than 15 mm or a cervical length between 15 and 30 mm and a positive fFN test result are at increased risk for preterm delivery within seven days. In addition, the risk of preterm birth in women who do not deliver within the first seven days continues to be increased (30 to 60 %) in the subsequent weeks of pregnancy [4,5,[7][8][9]. ...
Background
Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications.
The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor.
Methods/Design
This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery < 37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, α 0.05 and β 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat.
Discussion
The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened preterm labor and who remain at high risk for preterm birth.
Trial registration
Trial is registered at the Dutch Trial Register: http://www.trialregister.nl, NTR4210, date of registration: October 16th 2013.
... 27,29,30 In symptomatic patients, fFN and cervical length improved identification of women with a low risk to deliver spontaneously within 7 days. 31 In general, sensitivity and speci-ficity of these predictive factors are fairly low. We concentrated on women who did not deliver after initial therapy for threatened preterm labor because it may affect their management with regard to prolonged admission or discharge after initial medical treatment. ...
Objective The aim of this study was to assess which characteristics and results of vaginal examination are predictive for delivery within 7 days, in women with threatened preterm labor after initial treatment.
Study Design A secondary analysis of a randomized controlled trial on maintenance nifedipine includes women who remained undelivered after threatened preterm labor for 48 hours. We developed one model for women with premature prelabor rupture of membranes (PPROM) and one without PPROM. The predictors were identified by backward selection. We assessed calibration and discrimination and used bootstrapping techniques to correct for potential overfitting.
Results For women with PPROM (model 1), nulliparity, history of preterm birth, and vaginal bleeding were included in the multivariable analysis. For women without PPROM (model 2), maternal age, vaginal bleeding, cervical length, and fetal fibronectin (fFN) status were in the multivariable analysis. Discriminative capability was moderate to good (c-statistic 0.68; 95% confidence interval [CI] 0.60–0.77 for model 1 and 0.89; 95% CI, 0.84–0.93 for model 2).
Conclusion PPROM and vaginal bleeding in the current pregnancy are relevant predictive factors in all women, as are maternal age, cervical length, and fFN in women without PPROM and nulliparity, history of preterm birth in women with PPROM.
... 16 Neither fetal fibronectin nor transvaginal ultrasound cervical length measurement were in routine use at the Women's and Children's Hospital during the audit period, but are amongst the tools that continue to be studied for improving prediction and guiding the management of women presenting with symptoms of preterm labour, individually or in combination. [16][17][18] The decision to commence antenatal magnesium sulphate for fetal neuroprotection is further made difficult by limited evidence and consensus surrounding the safety and efficacy of repeat dosing, and the optimal dose and timing of administration, 19,20 which has in the past led to reluctance on the part of some clinicians at our institution to commence this therapy. 15 Clinicians need further guidance in assessing the risks of 'over-treatment' and under-recognition of imminent preterm birth. ...
Australian and New Zealand clinical practice guidelines, endorsed by the NHMRC in 2010, recommend administration of antenatal magnesium sulphate to women at risk of imminent preterm birth at less than 30 weeks' gestation to reduce the risk of their very preterm babies dying or having cerebral palsy. The purpose of the ongoing Working to Improve Survival and Health for babies born very preterm (WISH) implementation project is to monitor and improve the uptake of this neuroprotective therapy across Australia and New Zealand.
To quantify and explore reasons for nonreceipt of antenatal magnesium sulphate at the Women's and Children's Hospital, in Adelaide, South Australia.
Data from the case records of women who gave birth between 23(+0) and 29(+6) weeks' gestation from 2010 to mid-2013 were reviewed to determine the proportion of eligible mothers not receiving antenatal magnesium sulphate and to explore reason(s) for nonreceipt over this time period.
There was a reduction in the proportion of eligible mothers not receiving antenatal magnesium sulphate from 2010 (69.7%) to 2011 (26.9%), which was maintained in 2012 and 2013 (22.5%). In 2012-2013, nonreceipt was predominantly associated with immediately imminent (advanced labour, rapid progression of labour) or indicated emergent birth (actual or suspected maternal or fetal compromise).
Use of antenatal magnesium sulphate at the Women's and Children's Hospital is now predominantly in-line with the binational guideline recommendations. Ongoing education and enhanced familiarity with procedures may facilitate timely administration in the context of some precipitous or immediately imminent births.
© 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.
... Based on the fact that premature aging is a reason of preterm delivery [70], a deficiency of the membrane-negative form of RAGE (dominant-negative RAGE) should be considered as a potential factor of aging of premature fetal tissue [63,70,71]. Our finding of a correlation between sRANKL and sRAGE levels and the latency period from diagnosis until delivery was the reason why we decided to evaluate the Seven days is an accepted cut-off point for the duration of the latency period in group A [72][73][74]. The sensitivity for sRANKL reached 89.5 % and the specificity was 54.4 %, with a PPV of 63 % and NPV of 85.7 %, while those for sRAGE were 94.7 %, 59.1 %, 66.7 %, and 92.9 %, respectively. Prognostic values of so-called classic risk markers of preterm labor are usually measured in symptomatic patients (i.e., fetal fibronectin and cervical length) and range from 60 % to 100 % [74][75][76][77][78][79]. ...
This study aimed to determine the relationships between secretory and endogenous secretory receptors for advanced glycation end products (sRAGE, esRAGE), sRANKL, osteoprotegerin and the interval from diagnosis of threatened premature labor or premature rupture of the fetal membranes to delivery, and to evaluate the prognostic values of the assessed parameters for preterm birth.
Ninety women between 22 and 36 weeks' gestation were included and divided into two groups: group A comprised 41 women at 22 to 36 weeks' gestation who were suffering from threatened premature labor; and group B comprised 49 women at 22 to 36 weeks' gestation with preterm premature rupture of the membranes. Levels of sRAGE, esRAGE, sRANKL, and osteoprotegerin were measured. The Mann-Whitney test was used to assess differences in parameters between the groups. For statistical analysis of relationships, correlation coefficients were estimated using Spearman's test. Receiver operating characteristics were used to determine the cut-off point and predictive values.
In group A, sRAGE and sRANKL levels were correlated with the latent time from symptoms until delivery (r = 0.422; r = -0.341, respectively). The sensitivities of sRANKL and sRAGE levels for predicting preterm delivery were 0.895 and 0.929 with a negative predictive value (NPV) of 0.857 and 0.929, respectively. In group B, sRAGE and sRANKL levels were correlated with the latent time from pPROM until delivery (r = 0.381; r = -0.439). The sensitivity of sRANKL and sRAGE for predicting delivery within 24 h after pPROM was 0.682 and 0.318, with NPVs of 0.741 and 0.625, respectively. Levels of esRAGE and sRANKL were lower in group A than in group B (median = 490.2 vs 541.1 pg/mL; median = 6425.0 vs 11362.5 pg/mL, respectively).
Correlations between sRAGE, sRANKL, and pregnancy duration after the onset of symptoms suggest their role in preterm delivery. The high prognostic values of these biomarkers indicate their usefulness in diagnosis of pregnancies with threatened premature labor.
... (7) The best strategy to combine the two tests is additional fibronectin testing in women with a cervical length between 15 and 30 mm, reducing the number of unnecessary referrals and admissions to perinatal centres. (8) This approach would also be cost saving without compromising neonatal health outcomes. (9) A new bedside quantitative fetal fibronectin test showed added value over the conventional qualitative test with an increase of the positive predictive value for preterm delivery on short term by increasing the threshold from 50 ng/mL to 200 ng/mL or 500 ng/mL. ...
A cervical length (CL) assessment may predict preterm birth (PTB). This study aimed to analyze and compare the recommendations of guidelines on the role of CL in the prediction of PTB. There is no consensus regarding universal screening of asymptomatic women without a history of prior spontaneous PTB (sPTB), using CL. On the other hand, CL assessment is recommended in cases with a history of sPTB due to the high recurrence rate. Finally, there is discrepancy regarding CL assessment in asymptomatic women with multiple pregnancy. Although far from perfect, CL measurement remains the best available method to predict PTB.
Background: Many women living in rural and remote Australia are required to travel large distances to birth in a hospital with maternity capability, incurring considerable financial, social and emotional burden for women and their families. No studies to date have investigated the use of quantitative fetal fibronectin (qfFN) to predict term labour in asymptomatic pregnant women. A tool which is able to more accurately predict term labour has the potential to guide informed travel decision making for women and healthcare professionals in rural and remote Australia.
Aim: To determine if quantitative fetal fibronectin (qfFN) can reliably predict term labour in asymptomatic women from rural and remote areas.
Materials and Methods: Thirty-nine women from rural Australia provided 71 fFN samples between June 2016 and October 2018, from 37 weeks gestation, with at least one week between samples for those providing multiple samples. Days from fFN sampling until spontaneous onset of labour were recorded. Using Generalised Estimating Equation modelling we examined the utility of fFN as a predictor for onset of labour at term, after adjusting for confounders.
Results: There was a small to moderate negative correlation (rs -0.27, p<0.05) between time until labour and fFN. Quantitative fFN was observed to be a significant predictor of time until labour after adjusting for confounding variables (p<0.001).
Conclusion: Fetal fibronectin (fFN) levels may have a role in predicting term labour in rural women; however, future studies with a larger sample size is required to validate the findings of our pilot study.
Background
Distinguishing between true and false preterm labor remains a challenge. The shortening in cervical length throughout a gestation has been theorized to be a possible predictor of spontaneous preterm birth. Though there are some studies evaluating cervical length shortening as a predictor of spontaneous preterm birth, it is not known whether the shortening in cervical length from an asymptomatic to symptomatic state, as when a patient presents with preterm labor symptoms, is predictive of spontaneous preterm birth.
Objective
To determine the utility of using cervical length (CL) shortening from an asymptomatic time point (anatomic ultrasound) to when a patient presents with preterm labor symptoms as a predictor of spontaneous preterm birth (sPTB).
Study Design
A prospective cohort study was performed that evaluated the use of transvaginal CL assessment in symptomatic women in predicting sPTB from January 2013- March 2015. Women with singleton gestations who presented to our institution between 22-33 6/7 weeks with preterm labor symptoms were included in the overall cohort. This was a planned secondary analysis to evaluate the shortening in CL from an asymptomatic state (anatomic ultrasound) to a symptomatic state as a predictor of preterm birth. For this analysis, inclusion criteria were: known delivery status, CL screening performed at anatomic ultrasound, and a valid CL measurement at time of preterm labor symptoms. Women with preterm rupture of membranes, cervical dilation >2cm, or moderate/severe bleeding were excluded. Cervical length shortening was defined as a decrease in CL of >10mm from anatomic ultrasound to the time of presentation with preterm labor symptoms. The outcome evaluated was sPTB < 37 weeks. Chi-square and receiver operating characteristic curves were used to evaluate the data. Multivariable logistic regression was used to calculate odds. Test characteristics of CL shortening >10mm were determined.
Results
549 women were included in the original cohort, and 277 women were included in this secondary analysis. The overall sPTB rate was 8.3%. There were 52 (19%) women with CL shortening >10mm. The rate of sPTB was significantly higher for those with CL shortening >10mm compared to those with CL shortening ≤10mm (21.2% vs. 5.3%, p=0.001). This higher risk of sPTB remained after adjusting for confounders including maternal age and prior spontaneous preterm birth (adjusted odds ratio 4.71 [1.84-12.09]). Using CL shortening of >10mm as a screening test had 47.8% sensitivity, 83.9% specificity, positive predictive value of 21.2%, and negative predictive value of 94.7%.
Conclusion
In women presenting with preterm labor symptoms, a CL that is >10mm shorter from anatomic ultrasound is associated with an increased risk of sPTB.
Premature birth makes a substantial contribution to the perinatal morbidity and mortality and is one of the main risk factors for disability-adjusted life years (DALYs). Since 2008 the incidence in Germany has been stable at slightly over 8 %. Germany therefore occupies one of the lowest places in Europe. The condition after premature birth is the weightiest individual risk factor for recurrence of a premature birth; however, the nulliparity and male sex of the fetus are of much greater importance for the total rate of premature births in a population. The reasons for the substantial differences in the premature birth rate between individual countries with the same level of development are mostly unclear. In individual cases the risk of premature birth can be reduced through the use of various preventive measures, e.g. progesterone, cervical cerclage and cervical pessaries.
Background We evaluated the necessity of urinary trypsin inhibitor for patients with threatened premature labor.
Methods We enrolled 146 women with singleton pregnancies who were treated for threatened premature labor as inpatients. The uterine cervical length of each patient was ≤ 25 mm at 22–35 weeks of gestation on transvaginal ultrasonography. The patients were divided into two groups: the urinary trypsin inhibitor group (91 patients treated with urinary trypsin inhibitor daily) or non-urinary trypsin inhibitor group (55 patients not treated with urinary trypsin inhibitor). The childbirth outcomes were retrospectively assessed.
Results The median cervical length measured on the day of admission was almost similar between the urinary trypsin inhibitor and non-urinary trypsin inhibitor groups. Depending on the symptoms of uterine contractions, we determined whether ritodrine hydrochloride and/or magnesium sulfate would be appropriate for treatment. The median gestational week at birth was 38 weeks in the urinary trypsin inhibitor group, and no obvious differences were observed when compared with the non-urinary trypsin inhibitor group. With regard to birth weight, no significant difference was found between the two groups (urinary trypsin inhibitor group, 2776 g; non-urinary trypsin inhibitor group, 2800 g).
Conclusion Our data showed no significant beneficial effects of urinary trypsin inhibitor in the maternal course and delivery outcomes.
Objective
The aim of this work was to assess the cost-effectiveness of the fetal fibronectin (fFN) test at 48 h after admission for threatened preterm delivery to promote early discharge.
Study design
Before-and-after study to calculate the incremental cost-effectiveness ratio (ICER). Patients were enrolled 48 h after admission in a tertiary care centre for threatened preterm delivery between 24⁺⁰ and 34⁺⁶ weeks. fFN testing was performed. During the first period, physician was blinded to fFN test and discharge occurred after apparent reduced symptomatology at physician’s discretion. During the second period, fFN test was revealed to physician and discharge was immediately proposed to negative test patients. The costs considered in this analysis were the direct medical costs from the hospital perspective: costs of hospitalisation, treatment, and imaging procedures. The efficacy criterion selected was the number of deliveries at 7 and at 14 days after admission for threatened preterm delivery.
Results
The study included 178 pregnant patient, 99 during the first period (July 2008-October 2009) and 79 during the second (March 2010-February 2012). The lengths of hospital stays were shorter during the second period, with more than 50% of women discharged home between 48 and 72 h (p < 0.0001) resulting in a cost-saving of 76 051 euros. The number of deliveries at 7 and at 14 days was similar between the two periods.
Conclusion
The fFN test at 48 h after admission supported early discharge and was safe and cost-effective.
If the first and second trimesters of pregnancy are defined by embryonic and fetal development, the third trimester is defined by consolidation of these processes through maturation, growth and preparation for delivery. Stillbirth continues to present a major problem in obstetric management and should, by necessity, be a focal point of third‐trimester fetal assessment. If congenital abnormalities are excluded, the leading causes of stillbirth are very early preterm birth, intrauterine growth restriction (IUGR), antepartum haemorrhage and infection. A number of tools can be used to assess risks for these complications and their application may help improve fetal outcomes. This chapter describes tools and approaches to third‐trimester fetal assessment. Ultrasound is often best applied as one component of multivariate risk assessment and this is the subject of much ongoing research, with applications as diverse as the prevention of stillbirth, shoulder dystocia or maternal perineal trauma.
Introduction:
The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (fFN) concentration, in combination with clinical risk factors.
Methods and analysis:
The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts, USA) which quantifies fFN in a vaginal swab. In QUIDS part 2, we will perform a prospective cohort study in at least eight UK consultant-led maternity units, in women with symptoms of preterm labour at 22+0 to 34+6 weeks gestation to externally validate a prognostic model developed in QUIDS part 1. The effects of quantitative fFN on anxiety will be assessed, and acceptability of the test and prognostic model will be evaluated in a subgroup of women and clinicians (n=30). The sample size is 1600 women (with estimated 96-192 events of preterm delivery within 7 days of testing). Clinicians will be informed of the qualitative fFN result (positive/negative) but be blinded to quantitative fFN result. Research midwives will collect outcome data from the maternal and neonatal clinical records. The final validated prognostic model will be presented as a mobile or web-based application.
Ethics and dissemination:
The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068).
Version:
Protocol V.2, Date 1 November 2016.
Trial registration number:
ISRCTN 41598423andCPMS: 31277.
Objective:
To evaluate the cost-effectiveness of combining cervical length (CL) measurement and fetal fibronectin (fFN) tests for women with symptoms of preterm labor between 24 and 34 weeks gestation.
Methods:
We performed a model-based cost-effectiveness analysis to evaluate seven test-treatment strategies based on CL and/or fFN in women with symptoms of preterm labor from a societal perspective, in which we weighted neonatal outcome and costs. Estimates of disease prevalence, test accuracy and costs, were based on two recently performed nationwide cohort studies in The Netherlands.
Results:
FFN testing and CL measurement as single tests to predict preterm delivery result in more costs and more adverse neonatal outcomes than strategies that combine both tests. Additional fFN testing in case of a CL between 15-30?mm was considered cost-effective; compared to a treat all strategy it led to a cost saving of ?3919 per woman with a small deterioration in neonatal health outcomes; 1 additional perinatal death and 21 adverse outcomes per 10,000 women with signs of preterm labor (ICERS respectively ?39 million and ?1.9 million). Implementing this strategy could in the Netherlands, a country with about 180,000 deliveries annually, leads to annual cost saving between ?2.4 and ?7.6 million, with only a small deterioration in neonatal health outcomes.
Conclusion:
Performing an additional fFN test in case of a CL between the 15 and 30?mm in women with symptoms of preterm labor between 24 and 34 weeks of gestation is a viable and cost saving strategy.
Objective We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days.
Methods We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome.
Results Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12–0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7–12).
Conclusion The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity.
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