Progestogen maintenance therapy for prolongation of pregnancy after an episode of preterm labour: A systematic review and meta-analysis.

BACKGROUND: Evidence for progestogen maintenance therapy after an episode of preterm labour (PTL) is contradictory. OBJECTIVES: To assess effectiveness of progestogen maintenance therapy after an episode of PTL. SEARCH STRATEGY: An electronic search in Central Cochrane, Ovid Embase, Ovid Medline and clinical trial databases was performed. SELECTION CRITERIA: Randomised controlled trials (RCT) investigating women between 16+0 and 37+0 weeks of gestation with an episode of PTL who were treated with progestogen maintenance therapy compared with a control group. DATA COLLECTION AND ANALYSIS: Systematic review and meta-analysis were conducted. The primary outcome was latency time in days. Secondary neonatal and maternal outcomes are consistent with the core outcome set for preterm birth studies. Studies were extensively assessed for data trustworthiness (integrity) and risk of bias. MAIN RESULTS: Thirteen RCT (1722 women) were included. Progestogen maintenance therapy demonstrated a longer latency time of 4.32 days compared with controls (mean difference [MD] 4.32, 95% CI 0.40-8.24) and neonates were born with a higher birthweight (MD 124.25 g, 95% CI 8.99-239.51). No differences were found for other perinatal outcomes. However, when analysing studies with low risk of bias only (five RCT, 591 women), a significantly longer latency time could not be shown (MD 2.44 days; 95% CI -4.55 to 9.42). CONCLUSIONS: Progestogen maintenance therapy after PTL might have a modest effect on prolongation of latency time. When analysing low risk of bias studies only, this effect was not demonstrated. Validation through further research, preferably by an individual patient data meta-analysis is highly recommended.

Implications of training for pessary placement and accuracy of cervical length measurements after pessary placement: A prospective, double-blind, randomized clinical trial.

BACKGROUND: Cervical pessary placement as an intervention for preterm birth prevention in women with a short cervix is a simple, painless procedure with few complications and a reasonable cost. Its efficacy depends on the expertise of the obstetrician performing the procedure. Therefore, it is reasonable to assume that untrained obstetricians with no expertise in pessary placement are more likely to insert the pessary incorrectly, thereby reducing its efficacy. Nevertheless, the impact of pessary placement expertise and training, as well as the accuracy of cervival length measurements, has never been evaluated. OBJECTIVE: To evaluate the impact of providing training for pessary placement to obstetricians with no expertise in this intervention. To this end, the percentage of correct pessary placements and accuracy of cervical length measurements after pessary placement achieved by obstetricians who received such training was compared with the results achieved by obstetricians who did not receive any training. METHODS: This prospective, double-blind, randomized clinical trial included 91 pregnant women requiring a cervical pessary due to a short cervix. Patients were assigned at random to a group treated by untrained obstetricians with no expertise in pessary placement (untrained group, n = 45) or to a group treated by trained obstetricians with no expertise in pessary placement (trained group, n = 46). The primary outcomes were the quality of pessary placement and the accuracy of cervical length measurements after pessary placement. RESULTS: Obstetricians in the trained group achieved a significantly higher percentage of correct pessary placements than obstetricians in the untrained group (97.8 % and 65.2 %, respectively; p < 0.001). No significant differences were observed between groups in terms of the accuracy of cervical length measurements after pessary placement (p = 0.661), and both groups showed moderate to good agreement with the expert's measurements (intraclass correlation coefficient 0.840 and 0.749, respectively). No differences in pregnancy outcomes were observed between groups. CONCLUSION: This study showed that providing training in pessary placement to obstetricians with no expertise in this procedure increases the quality of pessary placement. Furthermore, the inconsistent results found in pessary studies may be explained, in part, by a lack of training in pessary placement.

The evaluation of maternal systemic thiol/disulphide homeostasis for the short-term prediction of preterm birth in women with threatened preterm labour: a pilot study.

The aim of this study was to investigate maternal systemic thiol/disulphide homeostasis (TDH) for the short-term prediction of preterm birth in women with threatened preterm labour (TPL). This prospective study included 75 pregnant women whose pregnancies were complicated by TPL. Thirty-seven of them delivered within 7 days and 38 of them delivered beyond 7 days. Maternal serum samples were collected at the day of diagnosis and the TDH was measured. The maternal disulphide level was significantly higher in pregnant women who delivered within 7 days (25.0 ± 9.8 µmol/L vs 19.4 ± 9.8 µmol/L, p: .015). The threshold value of 22.1 µmol/L for maternal disulphide level predicted delivery within 7 days with 62.2% sensitivity and 60.5% specificity (area under curve 0.651, confidence interval 0.53-0.78). The likelihood ratios for short cervix (≤25 mm) and maternal disulphide level (≥22 µmol/L) to predict delivery within 7 days was found to be 8.7 and 7.3, respectively. The likelihood ratio of combining two tests to predict delivery within 7 days was found to be 11.4. The maternal TDH, which is an indicator of oxidative stress status in maternal compartment, is disturbed in TPL cases who delivered within 7 days. Elevated maternal disulphide level along with cervical length screening predicts a short latency period in pregnancies with TPL. IMPACT STATEMENTWhat is already known on this subject? Spontaneous preterm delivery is one of the major complication of pregnancy and the common cause of neonatal morbidity and mortality. Threatened preterm labour (TPL) is also a frequent complaint in obstetric emergency care units in all around the world. Triaging women with TPL is mandatory for planning further management therapies, since the most of them will eventually deliver at term. Only the measurement of cervical length in symptomatic women has moderate accuracy in predicting preterm delivery. Short cervix is described as an independent predictor of preterm delivery in women with TPL, its predictive accuracy as a single measurement is relatively limited. On this account, several potential markers like foetal fibronectin in the cervicovaginal fluid, salivary oestriol, prolactin in vaginal discharge, maternal serum calponin and interleukin-6 in the amniotic fluid were examined to predict preterm delivery in previous studies. However, none of them represented an excessive predictive accuracy like high sensitivity, PPV or NPV.What do the results of this study add? We report a method which has higher diagnostic and predictive performance to identifying TPL women with high risk of preterm delivery. According to the current literature, there are accumulated data about the correlation between oxidative stress (OS) and preterm delivery regardless of the amniotic membrane status. However, it is still debated whether OS is a trigger or a consequence of preterm delivery. Our study provides evidence for the first time that maternal serum thiol/disulphide homeostasis, which is an indicator of OS in maternal compartment, is disturbed in TPL cases who delivered within 7 days. The high disulphide level in maternal serum, along with cervical length measurement (short cervix) accurately predicts a short latency period in TPL cases.What are the implications of these findings for clinical practice and/or further research? This novel test combination (maternal serum disulphide level and cervical length measurement) could be used clinically to triage pregnant women presenting with TPL, avoiding overtreatment, unnecessary hospitalisations and increased medical costs. The future research would be addressed on reducing maternal OS by using new antioxidant treatment strategies to improve perinatal and long-term childhood outcomes.

Prediction of preterm delivery in threatened preterm labour with short cervical length.

In this study, we evaluated the value of the uterocervical angle (UCA), myometrial thickness (MT), sICAM-1, sVCAM-1, soluble E-selectin (sE-selectin) and pentraxin 3 (PTX3) levels in women with threatened preterm labour (TPL) in predicting spontaneous preterm birth (sPTB) within 14 days in symptomatic women with cervical length (CL) measurements between 10 and 25 mm. Forty-six patients diagnosed with TPL, 47 healthy pregnant women were evaluated in a case-control study. sE-selectin (AUC = 0.744, p = .007) and PTX3 (AUC = 0.711, p = .019) were found to be effective in predicting preterm delivery within 14 days. In conclusion, maternal sE-selectin and PTX3 levels may be helpful in identifying pregnancies that will deliver within 14 days in symptomatic women with CL measurements between 10 and 25 mm. However, maternal sICAM-1 and sVCAM-1 levels, MT and UCA are not effective in the prediction of sPTB in TPL pregnancies. Impact StatementWhat is already known on this subject? Aetiology of spontaneous preterm birth (sPTB) is unclear and believed to be multifactorial, infection, inflammation, vascular endothelial dysfunction and uteroplacental ischaemia are all considered to be related to preterm delivery syndrome. Transvaginal cervical length (CL) measurement is a good indicator of increased risk of sPTB. Inflammation is accepted to have a central role in the process of labour.What do the results of this study add? soluble E-selectin (sE-selectin) and pentraxin 3 (PTX3) levels may be helpful in identifying pregnancies that will deliver within 14 days in symptomatic women with CL measurements between 10 and 25 mm.What are the implications of these findings for clinical practice and/or further research? This study will help understand the important role of the inflammatory process in predicting spontaneous preterm birth.

Clinicians' experiences of using and implementing a medical mobile phone app (QUiPP V2) designed to predict the risk of preterm birth and aid clinical decision making.

BACKGROUND: As the vast majority of women who present in threatened preterm labour (TPTL) will not deliver early, clinicians need to balance the risks of over-medicalising the majority of women, against the potential risk of preterm delivery for those discharged home. The QUiPP app is a free, validated app which can support clinical decision-making as it produces individualised risks of delivery within relevant timeframes. Recent evidence has highlighted that clinicians would welcome a decision-support tool that accurately predicts preterm birth. METHODS: Qualitative interviews were undertaken as part of the EQUIPTT study (The Evaluation of the QUiPP app for Triage and Transfer) (REC: 17/LO/1802) which aimed to evaluate the impact of the QUiPP app on management of TPTL. Individual semi-structured telephone interviews were used to explore clinicians' (obstetricians' and midwives') experiences of using the QUiPP app and how it was implemented at their hospital sites. Thematic analysis was chosen to explore the meaning of the data, through a framework approach. RESULTS: Nineteen participants from 10 hospital sites in England took part. Data analysis revealed three overarching themes which were: 'experience of using the app', 'how QUiPP risk changes practice' and 'successfully adopting QUiPP: context is everything'. With these final themes we appeared to have achieved our aim of exploring the clinicians' experiences of using and implementing the QUiPP app. CONCLUSION: This study explored different clinician's experiences of implementing the app. The organizational and cultural context at different sites appeared to have a large impact on how well the QUiPP app was implemented. Future work needs to be undertaken to understand how best to embed the intervention within different settings. This will inform scale up of QUiPP app use across the UK and ensure that clinicians have access to this free, easy-to-use tool which can positively aid clinical decision making when caring for women in TPTL. CLINICAL TRIAL REGISTRY AND REGISTRATION NUMBER: ISRCTN 17846337, registered 08th January 2018, https://doi.org/10.1186/ISRCTN17846337 .

Prediction of labour onset in women who present with symptoms of preterm labour using cervical length.

BACKGROUND: Diagnosis of preterm labour is difficult because initial symptoms and signs are often mild and may occur in continuing pregnancies. This study aims to investigate the utility of measuring cervical length, using transvaginal ultrasound, in women presenting to the delivery suite with symptoms of preterm labour. METHODS: This was a prospective cohort study performed in KK Women's and Children's Hospital, Singapore from September 2017 to July 2018. Women with singleton pregnancies, presenting with symptoms of contraction pain, between 24+ 0 to 36+ 6 weeks gestation, were included. Transvaginal ultrasound cervical length measurements were done at presentation to the labour ward, after four hours and in the following morning. The primary outcome of the study was delivery within 1 week. All statistical analyses were conducted with Microsoft Excel and Statistical Package for the Social Sciences. RESULTS: A total of 95 subjects were included. A one-millimeter increase in the 1st cervical length increases scan-to-delivery time by 0.802 days (p-value 0.003, CI 0.280-1.323). Receiver Operator Characteristic (ROC) curve analysis for prediction of delivery within 1 week showed an Area Under Curve (AUC) of 0.667, optimal cut-off value of 27.5mm (sensitivity 77.8 %, specificity 61.6 %). A one-millimetre increase in the 3rd cervical length increases scan-to-delivery time by 0.770 days (p-value 0.023, CI 0.108-1.432). ROC curve analysis for prediction of delivery within 1 week showed an AUC of 0.915, optimal cut-off value of 25.5mm (sensitivity 100 %, specificity 73.6 %). However, the change in cervical length over a period of 1 day was not significant in predicting delivery within 1 week. CONCLUSIONS: Our results indicate that by using a cervical length cut off of 27.5mm at presentation, we would have predicted 77.8 % of deliveries within 1 week. If we were to repeat the cervical length scan the next day, with the same cut-off of 27.5mm, we would have predicted 100 % of deliveries within 1 week. In our study, measuring the transvaginal ultrasound cervical length is a reliable diagnostic test for delivery within 1 week. However, the results are limited by the small sample size. Further studies should be conducted with a larger sample size.

Ten women's decision-making experiences in threatened preterm labour: Qualitative findings from the EQUIPTT trial.

BACKGROUND: Clinical triage of women in threatened preterm labour (TPTL) could be improved through utilising the QUiPP App, as symptoms alone are poor predictors of early delivery. As most women in TPTL ultimately deliver at term, they must weigh this likelihood with their own personal considerations, and responsibilities. The importance of personal considerations was highlighted by the 2015 Montgomery ruling, and the significance of shared decision-making. AIMS: Through qualitative interviews, the primary aim was to explore women's decision-making experiences in TPTL through onset of symptoms, triage, clinical assessment, and discharge. METHODS: Qualitative interviews were undertaken as part of the EQUIPTT study (REC: 17/LO/1802) using a semi-structured interview schedule. Descriptive labels of the coding scheme were applied to the raw transcript data. This coding scheme was then increasingly refined into key themes and allowed parallels to be made within and between cases. RESULTS: Ten ethnically diverse women who presented at six different London hospitals sites in TPTL were interviewed. Three final themes emerged from the data incorporating 10 sub-themes, 'Seeking help', 'Being "assessed" vs making clinical decisions together', and 'End result.' CONCLUSION: Women described their busy lives and the need to juggle their commitments. Participants drew comparisons between their TPTL symptoms and 'period pain,' contrasting to typical medical terminology. Shared decision-making and the clinician-patient relationship could be improved through clinicians utilizing terminology women understand and relate to. Women used language that highlighted the clinician-patient power balance. While not fully involved in shared decision-making, women were overall satisfied with their care.

Prevention of preterm birth: Proactive and reactive clinical practice-are we on the right track?

Preterm birth remains the major cause of death and disability among children under the age of five. In developing countries antenatal preterm birth prevention clinics are set up to provide cervical length surveillance and/or treatment modalities such as cerclage or progesterone for those women with identified risk factors such as previous cervical treatment or preterm birth. However, 85% of women have no risk factors for PTB and currently there is no biomarker to screen women early in pregnancy. Women will present unexpectedly in threatened preterm labour and we have no choice but to adopt a re-active approach to their care by using predication and preparation strategies such as fetal fibronectin, tocolytic therapy and steroids. Despite these strategies approximately 15-20% of these women will give birth preterm before 34 weeks. There is a urgent need to re-design primary, secondary and tertiary prevention strategies for spontaneous preterm labour (sPTL) in singleton pregnancies aimed at identifying and addressing key gaps in clinical practice and research.

Early detection of mental illness for women suffering high-risk pregnancies: an explorative study on self-perceived burden during pregnancy and early postpartum depressive symptoms among Chinese women hospitalized with threatened preterm labour.

BACKGROUND: The mental health of pregnant women, particularly those with elevated risks, has been an issue of global concern. Thus far, few studies have addressed the mental health of pregnant women with threatened preterm labour (TPL). This study investigated the prevalence of self-perceived burden (SPB) among Chinese women hospitalized due to TPL during pregnancy and early postpartum depressive disorders, exploring the effect of SPB and other potential risk factors on the early signs of postpartum depressive disorders. METHODS: A self-reported survey was conducted in the obstetrics department of Anhui Provincial Hospital, China. Women hospitalized with TPL were approached 1 week after delivery. One hundred fifty women were recruited from January 2017 to December 2017. The Self-Perceived Burden Scale (SPBS) and Edinburgh Postnatal Depression Scale (EPDS) were the main measures. Descriptive statistics, Spearman correlations, and a multiple logistic regression were employed for data analysis. RESULTS: SPB and early postpartum depressive disorders were commonly experienced by Chinese women hospitalized with TPL, and SPB was positively and significantly correlated with depressive symptoms. A multiple logistic regression analysis revealed that for the women hospitalized with TPL during pregnancy, the emotional aspect of SPB (OR = 1.42, 95% CI = 1.11-1.83, p = 0.006), age (OR = 1.14, 95% CI = 1.02-1.27, p = 0.023), occupation (OR = 3.48, 95% CI = 1.18-10.20, p = 0.023), the history of scarred uterus (OR = 7.96, 95% CI = 1.49-42.48, p = 0.015), the delivery mode of the present birth (OR = 6.19, 95% CI = 1.72-22.30, p = 0.005), and family support during pregnancy (OR = 0.60, 95% CI = 0.45-0.82, p = 0.001) were significant factors predicting early postpartum depressive symptoms. CONCLUSION: This study indicates that SPB and early postpartum depressive disorders are prevalent mental issues among Chinese women hospitalized with TPL, and that SPB, especially perceived emotional burden, is a strong predictor of early postpartum depressive disorders. Our study suggests the necessity of paying attention to mental health issues, e.g. SPB and postpartum depressive symptoms among hospitalized women with TPL, and providing appropriate interventions at the prenatal stage to prevent adverse consequences.

The relationship between the anti-Porphyromonas gingivalis immunoglobulin G subclass antibody and small for gestational age delivery: a longitudinal study in pregnant Japanese women.

BACKGROUND: Maternal serum IgG antibody against Porphyromonas gingivalis is an indicator of both periodontitis and adverse pregnancy outcomes. This study aims to evaluate the anti-P. gingivalis IgG and IgG subclasses1-4 in threatened preterm labour (TPL) patients and their association with small for gestational age (SGA). METHODS: Serum, saliva and subgingival plaque samples were collected from 47 TPL patients compared with 48 healthy pregnant women. The amount of P. gingivalis was measured in saliva and plaque using real-time polymerase chain reaction. The serum anti-P. gingivalis IgG titre and anti-P. gingivalis subclasses IgG 1-4 concentration were measured using enzyme-linked immunosorbent assay. RESULTS: The amount of anti-P. gingivalis IgG-1 was significantly lower in the TPL group than in the healthy group. Fourteen subjects delivered SGA infants in the TPL group. The pocket probing depth (PPD), clinical attachment loss, PPD ≥ 5 mm%, amount of P. gingivalis in plaque, anti-P. gingivalis IgG and anti-P. gingivalis IgG-4 were significantly higher in the TPL-SGA group than in the TPL-normal weight group. Moreover, logistic regression analysis revealed the detection frequency of P. gingivalis in plaque and placenta weight were significantly correlated with SGA in TPL. In the receiver operating characteristic curve analysis, an amount of P. gingivalis in plaque ≥ 86.45 copies showed a sensitivity of 0.786 and a specificity of 0.727 (AUC 0.792) for predicting SGA in TPL. CONCLUSION: Lower anti-P. gingivalis IgG-1 amounts are related to TPL, while higher anti-P. gingivalis IgG and IgG-4 are related with SGA in TPL. Further, greater colonisation of P. gingivalis in plaque might increase the risk of SGA and can be useful in prediction of SGA in TPL.

Predictive value of the quantitative fetal fibronectin levels for the management of women presenting with threatened preterm labour - A revised cut off level: A retrospective cohort study.

OBJECTIVE: To evaluate a new a cut off level of fetal fibronectin as a predictor of birth in women with threatened preterm labour. DESIGN: A retrospective cohort study performed at Ipswich hospital, Ipswich, Queensland, Australia, in women with threatened preterm labour with intact membranes between 23 weeks to 34 + 6 week gestation. STUDY DESIGN: A quantitative fetal fibronectin (fFN) was performed. Maternal demographics and birth outcome data were extracted from the routinely collected perinatal data held by the hospital. The odds of preterm birth were estimated for each cut off value of fFN (10, 50 and 200 ng ml-1) using logistic regression and accounting for multiple presentations by the same woman. RESULTS: Among the 447 presentations and 376 pregnancies, rates of preterm birth <34 weeks were 2.9%, 9.2%, 3.3%, 19.6%, 4.2% and 35.3% for each category of values respectively (fFN <10, ≥10, <50, ≥50, <200 and ≥200 ng ml-1). Birth rates within 7 d of testing were 1.1%, 7.5%, 1.8%, 16.1%, 2.1% and 41.2% respectively. Comparing fFN level of <10 to a level of 10-199 ng ml-1 there was no significant increase in odds of preterm birth < 34 weeks or birth within the next 7 d (OR 2.28, 95% CI 0.84-6.17 and OR 3.61, 95% CI 0.89-14.7 respectively. CONCLUSION: In women presenting with TPL, those with levels of <200 ng ml-1 have a low risk of birthing within 7 d or before 34 weeks gestation. This allows a personalised decision making and probable discharge home without need for steroid loading.

Women with threatened preterm labour followed by term delivery have an increased risk of spontaneous preterm birth in subsequent pregnancies: a population-based cohort study.

OBJECTIVES: To evaluate the association of a history of threatened preterm labour (TPL) followed by term delivery with the risk of spontaneous preterm delivery (PTD) in subsequent pregnancy. DESIGN: Population-based cohort study. SETTING: Data of the National Health Insurance Claims Database and a national health-screening programme for infants and children in South Korea. POPULATION: Women who had their first singleton delivery in 2010 and a subsequent second singleton delivery between 2011 and 2015. METHODS: Multivariable analysis adjusting for maternal age and interval between first and second deliveries was used to assess the risk of PTD based on PTD, TPL followed by term delivery, and term delivery in the first pregnancy. MAIN OUTCOME MEASURES: The risk of PTD during the second pregnancy. RESULTS: This study included 115 629 women with two consecutive deliveries during the study period. Spontaneous PTD rates in the second pregnancy were 7.71, 2.22 and 1.02% in women with PTD, TPL followed by term delivery, and term delivery in the first pregnancy, respectively. Threatened preterm labour followed by term delivery in the first pregnancy was associated with increased risk of PTD in the subsequent pregnancy after adjustment for potential confounding factors (adjusted odds ratio 2.21; 95% CI 1.76-2.78). CONCLUSION: Although women with a history of TPL followed by term delivery had a lower risk of PTD during a subsequent pregnancy compared with those with history of previous PTD, they still had a significantly increased risk of PTD compared with those who delivered at term without TPL. TWEETABLE ABSTRACT: The history of threatened preterm labour followed by term delivery is related to increased risk of subsequent spontaneous preterm delivery.

The review of results of foetal fibronectin at the Royal Cornwall Hospital Treliske.

The manufacturer of a popular qualitative fFN assay, changed to using a quantitative assay following results from EQUIPPE study. The objective of our study was to compare our hospital data collated from our qualitative fFN assay with EQUIPPE's data, with a view to establish its validity in our hospital. We undertook a retrospective study over a 22-month period to review the data of 432 preterm pregnant women at less than 34 weeks of gestation, who presented to the labour ward with symptoms of threatened preterm labour warranting a fFN test. None of the patient with results between 11 and 199 ng/mL delivered within 7 days. However, there was a rise in percentage of delivery at higher levels. For example, 73% of patients with levels greater or equal to 500 ng/mL delivered within 7 days. Our results are comparable with those of the EQUIPPE study. This has led to changes that could potentially save our hospital money. Impact statement What is already known on this subject? The fFN test is a well validated test used to diagnose a preterm delivery. Most units are changing from the qualitative assays that just show positive or negative results to quantitative assays that give specific numeric values. Manufacturers give a numeric range for positive and negative results. What do the results of this study add? Although our study is local to our population, our findings show that potentially more money could be saved and fewer women separated from their families, if the negative level of the fFN test is increased (following a review of their local practice). What are the implications of these findings for clinical practice and/or further research? More units should review or audit their fFN results and choose what levels to use as a cut off for the test locally. More importantly, a multicentre research is needed to validate if the negative level needs increasing from 49 ng/mL.

Nifedipine alone or combined with sildenafil citrate for management of threatened preterm labour: a randomised trial.

OBJECTIVE: To study the tocolytic action of nifedipine combined with sildenafil citrate (SC) and if the combination is superior to nifedipine alone in inhibiting threatened preterm labour (PTL). DESIGN: Prospective randomised study. SETTING: An Egyptian university hospital. POPULATION: Women with threatened PTL who received either nifedipine with SC or nifedipine alone. METHODS: Patients were randomly allocated to receive either (1) nifedipine 20 mg orally (stat dose), followed by 10 mg orally every 6-8 hours at the same time as vaginal administration of SC (25 mg at 8-hourly intervals) or (2) nifedipine alone. Medications were continued for 48-72 hours. MAIN OUTCOME MEASURES: The percentage of women who remained undelivered during hospitalisation. RESULTS: From January 2015 to November 2016, 239 women were randomised. The baseline characteristics of participants were similar. Nifedipine combined with SC was associated with more women remaining undelivered (81.8 versus 68.6%; P = 0.018) during hospitalisation. Regarding secondary outcomes, the addition of SC was also associated with fewer deliveries within 7 days of admission (9.1 versus 20.3%; P = 0.014), prolonged latency (29 versus 7 days; P = 0.002), fewer admissions to neonatal intensive care units (31.4 versus 44.1%; P = 0.043), fewer very preterm deliveries (from 28 to <32 weeks, 20.7 versus 38.1%; P = 0.043), and increased neonatal birthweight (1900 versus 1500 g; P = 0.018). CONCLUSIONS: Vaginal SC combined with nifedipine is an effective option for tocolytic therapy during threatened PTL. TWEETABLE ABSTRACT: Vaginal SC enhances the tocolytic effect of nifedipine.

Threatened preterm labour: Women's experiences of risk and care management: A qualitative study.

BACKGROUND: Preterm birth is a major cause of neonatal death and severe morbidity, so pregnant women experiencing symptoms of threatened preterm labour may be very anxious. The risk assessment and management that follows recognition of threatened preterm labour has the potential to either increase or decrease this anxiety. The aim of this study was to explore women's experience of threatened preterm labour, risk assessment and management in order to identify potential improvements in practice. DESIGN: One-to-one semi-structured interviews with 19 women who experienced assessment for threatened preterm labour took place between March 2015 and January 2017. A purposive sample approach was employed to ensure participants from different risk and demographic backgrounds were recruited at an inner city UK NHS hospital. Interviews were recorded and transcribed. Data was managed with NVivo software and analysed using the Framework Approach. A public and patient involvement panel contributed to the design, analysis and interpretation of the findings. FINDINGS: Data saturation was achieved after 19 interviews. 11 women were low risk and 8 were high risk for preterm birth. All high risk women had experience of being supported by a specialist preterm team. Four main themes emerged: (i) coping with uncertainty; (ii) dealing with conflicts; (iii) aspects of care and (iv) interactions with professionals. Both low and high risk women experiencing TPTL struggle to cope with the uncertainty of this unpredictable state. The healthcare management they receive can both help and hinder their ability to cope with this extremely stressful experience. High risk women were less likely to receive conflicting advice. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Clinicians should acknowledge uncertainty, minimize conflicting information and advice, and promote continuity of care models for all women, including those attending high risk clinics and in the ward environment.

Efficacy of serum procalcitonin to predict spontaneous preterm birth in women with threatened preterm labour: a prospective observational study.

BACKGROUND: A hypothesis of preterm parturition is that the pathogenesis of spontaneous preterm birth (sPTB) may be associated with an inflammatory process. Based on this theory, we have hypothesized that an inflammatory biomarker, procalcitonin (PCT), may be a good predictive marker of sPTB at the admission for threatened preterm labour (TPL). The present study was aimed to investigate the association between serum PCT and sPTB in women with TPL and to evaluate whether PCT levels may predict sPTB in women with TPL within 7 or 14 days. METHODS: In a prospective observational laboratory-based study, women with singleton pregnancies, TPL between 24 and 36 weeks and intact membranes, were enrolled between January 2014 and June 2016. Participants received routine medical management of TPL (tocolysis with atosiban, antenatal corticosteroids, and biological tests at admission (C-reactive protein, white blood cell count, and PCT measured on electrochemiluminescence immunoassay)). The primary endpoint was sPTB before 37 weeks of gestation. The value of serum PCT levels to predict sPTB within 7 or 14 days were evaluated using receiver-operating curves (ROC) analysis. RESULTS: A total of 124 women were included in our study. PCT levels did not statistically differ between women with sPTB (n = 30, 24.2%) and controls (n = 94) (median in ng/mL [interquartile range]: 0.043 [0.02-0.07] compared to 0.042 [0.02-0.13], respectively; P = 0.56). PCT levels did not also statistically differ between women with sPTB within 7 days (n = 7, 5.6%) or 14 days (n = 12, 9.7%) after testing and controls. Moreover, subgroup analysis revealed no difference among PCT levels at admission between 24 and 28 weeks, between 28 and 32 weeks and over 32 weeks, and controls. On the basis of the receiver-operating characteristic curve, the highest sensitivity and specificity corresponded to a PCT concentration of 0.038 ng/mL, with poor predictive values for sPTB within 7 or 14 days. CONCLUSION: Serum PCT was not relevant to predict sPTB within 7 or 14 days in women admitted with TPL between 24 and 36 weeks, and thus it is not a suitable biological marker to confirm the hypothesis of an inflammatory process associated with preterm parturition. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT01977079 ), Registered 24 October 2013.

Maternal serum cytokine levels in pregnancies complicated with threatened preterm labour.

OBJECTIVE: To investigate serum inflammatory markers in singleton gestations complicated with threatened preterm labour (TPL). METHODS: Pregnant women complicated with TPL (n = 61) were recruited to measure maternal serum levels of a panel of cytokines and C-reactive protein and then compared to controls without TPL, matched for gestational age (n = 64) and term pregnancies in the prodromal phase of labour (PPL) (n = 31). In addition, baseline cytokine levels were compared among cases and controls according to the outcome. RESULTS: Women with TPL displayed higher CRP and white blood counts levels together with lower granulocyte macrophage colony-stimulating factor (GMC-SF) compared to both controls without TPL and to term gestations in the PPL. Also, interleukin 10 (IL-10), IL-6, IL-7, IL-8 and tumour necrosis alpha (TNF-α) levels were found significantly higher in TPL cases as compared to controls without TPL and term women in the PLL. Baseline cytokine levels (except IL-10) were higher among TPL cases who later delivered preterm. TPL cases delivering preterm displayed lower GMC-SF levels as compared to those delivering at term. Multivariate analysis found that gestational age at birth positively correlated with cervical length and inversely with CRP, IL-6 and TNF-α levels (p < 0.0001). CONCLUSIONS: TPL and preterm birth were related to inflammatory changes in the maternal side that correlate with cervical shortening and the initiation of uterine contractions.

Implementation of foetal fibronectin testing: Admissions, maternal interventions and costs at 1 year.

Foetal fibronectin testing (fFN) has a high negative predictive value for preterm delivery, but it has a cost implication. This two-stage prospective study evaluated the real patient costs and clinical impact of introducing the fFN test in women presenting acutely with threatened preterm labour in a tertiary UK obstetric hospital. Introduction of the fFN test for women with threatened preterm labour reduced antenatal admissions and in utero transfers, and reduced steroid treatment and tocolysis, even at 1 year after implementation. The total number of bed days for women with threatened preterm labour who did not deliver during admission fell from 132 (mean 8.8 days) to 25 days (mean 3.6 days). The mean cost of admission per woman before introduction of the fFN test was £1032 (95% CI £880 to £1184); after it was £339 (95% CI £261 to £417). In this small single centre study, the introduction of the test produced a cost saving of £693 per woman (95% CI, £464 to £922) which over 12 months potentially saves £74844 (95% CI £50,112 to £99,576). Further studies are needed to formally evaluate the cost-effectiveness of the fFN test and its impact on clinical decision-making in large populations.

Evaluation of risk factors can help to predict preterm delivery within 7 days in women hospitalized for threatened preterm labour.

OBJECTIVE: The ability to predict birth within 7 days of enrolment in women hospitalized for threatened preterm labour is essential for a proper decision to introduce corticosteroids for the treatment. METHOD: The study included 622 women hospitalized due threatened preterm labour. Eighteen risk factors were analysed. The predictive value for accumulation of studied risk factors was assessed using receiver operating characteristic (ROC) curve analysis and dimension-based models of assessment methods: (i) forward stepwise selection (conditional), (ii) forward stepwise selection (Wald) and (iii) backward stepwise elimination (conditional). RESULTS: The accumulation of five and above risk factors gives specificity and positive predictive value (PPV) of diagnosis preterm delivery within 7 days of enrolment approaching 100% (99 and 98, respectively). The predictive value for studied risk factors enabled establishing the following order for risk factors significance: (i) cigarette smoking before pregnancy; (ii) low socioeconomic status; (iii) frequent contractions during pregnancy; (iv) bleeding during pregnancy; (v) urinary tract infections. CONCLUSION: In women hospitalized for threatened preterm labour, the accumulation of five risk factors of preterm delivery predicts preterm delivery within 7 days of enrolment. That makes easier decision to introduce corticosteroids for the treatment.

[Prediction of spontaneous preterm birth in symptomatic patients: A review]. / Prédiction de la prématurité en cas de menace d'accouchement prématuré: revue de la littérature.

OBJECTIVE OF THE REVIEW: To identify predictors of preterm delivery in the context of threatened preterm labour. MAIN POINTS: Tobacco use and previous history of preterm delivery are the main anamnestic elements to predict preterm birth. High positive predictive value of vaginal examination is restricted to cases with strong cervical alterations like dilatation over 4 cm. In case of discrete cervical alterations, literature confirms the great interest for cervical length ultrasonographic measurement as it reduces false positive cases. Absence of fetal respiratory movements appears to be as sensitive as cervical length and could be more specific but its clinical use remains rare. Vaginal detection of fetal fibronectin is the most useful biomarker with high negative predictive value (>90%). Fibronectin quantitative test seems to enhance the positive predictive value. No other biomarker is currently used in clinical practice. Electromyography and elastography of the cervix appear to be promising approaches.