Search

© 2016 El Ayadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credite

Objectives To compare the predictive value of the shock index ( SI) with conventional vital signs in postpartum haemorrhage ( PPH), and to establish 'alert' thresholds for use in low-resource settings. Design Retrospective cohort study. Setting UK tertiary centre. Population Women with PPH ≥1500 ml ( n = 233). Methods Systolic blood pressure ( BP), diastolic BP, mean arterial pressure, pulse pressure, heart rate ( HR) and SI ( HR/systolic BP) were measured within the first hour following PPH. Values measured at the time of highest SI were selected for analysis. The area under the receiver operating characteristic curve ( AUROC) for each parameter, used to predict admission to an intensive care unit and other adverse outcomes, was calculated. Sensitivity, specificity and negative/positive predictive values determined thresholds of the best predictor. Main outcome measures Intensive care unit (ICU) admission, blood transfusion ≥4 iu, haemoglobin level <7 g/dl, and invasive surgical procedures. Results Shock index has the highest AUROC to predict ICU admissions (0.75 for SI [95% CI 0.63-0.87] compared with 0.64 [95% CI 0.44-0.83] for systolic BP). SI compared favourably for other outcomes: SI ≥0.9 had 100% sensitivity (95% CI 73.5-100) and 43.4% specificity (95% CI 36.8-50.3), and SI ≥1.7 had 25.0% sensitivity (95% CI 5.5-57.2) and 97.7% specificity ( CI 94.8-99.3), for predicting ICU admission. Conclusions Shock index compared favourably with conventional vital signs in predicting ICU admission and other outcomes in PPH, even after adjusting for confounding; SI <0.9 provides reassurance, whereas SI ≥1.7 indicates a need for urgent attention. In low-resource settings this simple parameter could improve outcomes. It was not possible to adjust for resuscitative measures administered following vital sign measurement that may have influenced the outcome. [ABSTRACT FROM AUTHOR]

Preterm birth remains an important global problem, and an important contributor to under-5 mortality. Reducing spontaneous preterm birth rates at the global level will require the early identification of patients at risk of preterm delivery in order to allow the initiation of appropriate prophylactic management strategies. Ideally these strategies target the underlying pathophysiologic causes of preterm labor. Prevention, however, becomes problematic as the causes of preterm birth are multifactorial and vary by gestational age, ethnicity, and social context. Unfortunately, current screening and diagnostic tests are non-specific, with only moderate clinical risk prediction, relying on the detection of downstream markers of the common end-stage pathway rather than identifying upstream pathway-specific pathophysiology that would help the provider initiate targeted interventions. As a result, the available management options (including cervical cerclage and vaginal progesterone) are used empirically with, at best, ambiguous results in clinical trials. Furthermore, the available screening tests have only modest clinical risk prediction, and fail to identify most patients who will have a preterm birth. Clearly defining preterm birth phenotypes and the biologic pathways leading to preterm birth is key to providing targeted, biomolecular pathway-specific interventions, ideally initiated in early pregnancy Pathway specific biomarker discovery, together with management strategies based on early, mid-, and-late trimester specific markers is integral to this process, which must be addressed in a systematic way through rigorously planned biomarker trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gravett, Menon, Tribe, Hezelgrave, Kacerovsky, Soma-Pillay, Jacobsson and McElrath.)

Background: Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT "Stitch, Pessary, or Progesterone Randomised Trial" was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy., Methods and Findings: SuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14+0 and 23+6 weeks' gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage (n = 128), cervical pessary (n = 126), or vaginal progesterone (n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks' gestation. Secondary outcomes included PTB <34 weeks', <30 weeks', and adverse perinatal outcome. Analysis was by intention to treat. A total of 386 pregnant women between 14+0 and 23+6 weeks' gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) -0.7% [-12.1 to 10.7], cerclage versus progesterone RD 6.2% [-5.0 to 17.0], and progesterone versus pessary RD -6.9% [-17.9 to 4.1]). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain. A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic., Conclusions: In this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapies would be reasonable clinical management. These results can be used as a counselling tool for clinicians when managing women with a short cervix., Trial Registration: EU Clinical Trials register. EudraCT Number: 2015-000456-15, clinicaltrialsregister.eu., ISRCTN Registry: ISRCTN13364447, isrctn.com., Competing Interests: AS is a member of PLOS Medicine’s editorial board. The authors have declared that no other competing interests exist., (Copyright: © 2024 Hezelgrave et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To determine the performance of the predictive markers of spontaneous preterm birth, cervicovaginal quantitative fetal fibronectin (fFN) and cervical length, in asymptomatic high-risk women with transabdominal, history-indicated or ultrasound-indicated cervical cerclage., Methods: This was a secondary analysis of a prospective cohort of asymptomatic high-risk women with cervical cerclage and no other prophylactic intervention (including progesterone), who attended the preterm birth clinic at a central London teaching hospital between October 2010 and September 2016. Women had either transabdominal cerclage, placed prior to conception, history-indicated cerclage, placed before 14 weeks' gestation, or ultrasound-indicated cerclage for a short cervix (< 25 mm), placed before 24 weeks. All women underwent serial cervical length assessment on transvaginal ultrasound in the second trimester (16-28 weeks), and quantitative fFN testing from 18 weeks onward. Test performance was analyzed for the prediction of spontaneous preterm birth before 30 weeks (cerclage failure), 34 weeks and 37 weeks, using receiver-operating-characteristics (ROC)-curve analysis., Results: Overall, 181 women were included in the analysis. Cervical length and fFN were strong predictors of spontaneous preterm birth before 30 weeks in women with cerclage, with areas under the ROC curve (AUC) of 0.86 (95% CI, 0.79-0.94) and 0.84 (95% CI, 0.75-0.92), respectively. Cervical length was a better predictor of preterm birth before 30 weeks in women with history-indicated compared to those with ultrasound-indicated cerclage, although both showed clinical utility (AUC, 0.96 (95% CI, 0.91-1.00) vs 0.79 (95% CI, 0.66-0.91); P = 0.01). Quantitative fFN was a strong predictor of spontaneous preterm birth before 30 weeks in women with history-indicated cerclage (AUC, 0.91 (95% CI, 0.75-1.00)) and retained clinical utility in those with ultrasound-indicated cerclage (AUC, 0.76 (95% CI, 0.64-0.89)). There were no spontaneous deliveries before 34 weeks in women with a transabdominal cerclage, so AUC was not calculated. Delivery was delayed significantly in this group (P < 0.01)., Conclusions: Cervical length and quantitative fFN retain clinical utility for the prediction of spontaneous preterm birth in women with cervical cerclage, and prediction is best in women with a history-indicated stitch. These tests can be relied upon to discriminate risk and have utility when planning clinical management with regard to treatment failure. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Spontaneous preterm birth remains the main driver of childhood morbidity and mortality. Because of an incomplete understanding of the molecular pathways that result in spontaneous preterm birth, accurate predictive markers and target therapeutics remain elusive., Objective: This study sought to determine if a cell-free RNA profile could reveal a molecular signature in maternal blood months before the onset of spontaneous preterm birth., Study Design: Maternal samples (n=242) were obtained from a prospective cohort of individuals with a singleton pregnancy across 4 clinical sites at 12-24 weeks (nested case-control; n=46 spontaneous preterm birth <35 weeks and n=194 term controls). Plasma was processed via a next-generation sequencing pipeline for cell-free RNA using the Mirvie RNA platform. Transcripts that were differentially expressed in next-generation sequencing cases and controls were identified. Enriched pathways were identified in the Reactome database using overrepresentation analysis., Results: Twenty five transcripts associated with an increased risk of spontaneous preterm birth were identified. A logistic regression model was developed using these transcripts to predict spontaneous preterm birth with an area under the curve =0.80 (95% confidence interval, 0.72-0.87) (sensitivity=0.76, specificity=0.72). The gene discovery and model were validated through leave-one-out cross-validation. A unique set of 39 genes was identified from cases of very early spontaneous preterm birth (<25 weeks, n=14 cases with time to delivery of 2.5±1.8 weeks); a logistic regression classifier on the basis of these genes yielded an area under the curve=0.76 (95% confidence interval, 0.63-0.87) in leave-one-out cross validation. Pathway analysis for the transcripts associated with spontaneous preterm birth revealed enrichment of genes related to collagen or the extracellular matrix in those who ultimately had a spontaneous preterm birth at <35 weeks. Enrichment for genes in insulin-like growth factor transport and amino acid metabolism pathways were associated with spontaneous preterm birth at <25 weeks., Conclusion: Second trimester cell-free RNA profiles in maternal blood provide a noninvasive window to future occurrence of spontaneous preterm birth. The systemic finding of changes in collagen and extracellular matrix pathways may serve to identify individuals at risk for premature cervical remodeling, with growth factor and metabolic pathways implicated more often in very early spontaneous preterm birth. The use of cell-free RNA profiles has the potential to accurately identify those at risk for spontaneous preterm birth by revealing the underlying pathophysiology, creating an opportunity for more targeted therapeutics and effective interventions., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The syndrome of spontaneous preterm birth (sPTB) presents a challenge to mechanistic understanding, effective risk stratification, and clinical management. Individual associations between sPTB, self-reported ethnic ancestry, vaginal microbiota, metabolome, and innate immune response are known but not fully understood, and knowledge has yet to impact clinical practice. Here, we used multi-data type integration and composite statistical models to gain insight into sPTB risk by exploring the cervicovaginal environment of an ethnically heterogenous pregnant population (n = 346 women; n = 60 sPTB < 37 weeks' gestation, including n = 27 sPTB < 34 weeks). Analysis of cervicovaginal samples (10-15+6 weeks) identified potentially novel interactions between risk of sPTB and microbiota, metabolite, and maternal host defense molecules. Statistical modeling identified a composite of metabolites (leucine, tyrosine, aspartate, lactate, betaine, acetate, and Ca2+) associated with risk of sPTB < 37 weeks (AUC 0.752). A combination of glucose, aspartate, Ca2+, Lactobacillus crispatus, and L. acidophilus relative abundance identified risk of early sPTB < 34 weeks (AUC 0.758), improved by stratification by ethnicity (AUC 0.835). Increased relative abundance of L. acidophilus appeared protective against sPTB < 34 weeks. By using cervicovaginal fluid samples, we demonstrate the potential of multi-data type integration for developing composite models toward understanding the contribution of the vaginal environment to risk of sPTB.

There is much interest in the role of innate immune system proteins (antimicrobial peptides) in the inflammatory process associated with spontaneous preterm birth (sPTB). After promising pilot work, we aimed to validate the association between the antimicrobial peptides/proteins elafin and cathelicidin and sPTB. An observational cohort study of 405 women at high-risk, and 214 women at low-risk of sPTB. Protein concentrations of elafin and cathelicidin, and the enzyme human neutrophil elastase (HNE) were measured in over 1,000 cervicovaginal fluid (CVF) samples (10 to 24 weeks' gestation). Adjusted CVF cathelicidin and HNE concentrations (but not elafin) were raised in high-risk women who developed cervical shortening and who delivered prematurely and were predictive of sPTB < 37 weeks, with an area under the curve (AUC) of 0.75 (95% CI 0.68 to 0.81) for cathelicidin concentration at 14 to 15 +6  weeks. Elafin concentrations were affected by gestation, body mass index and smoking. CVF elafin in early pregnancy was modestly predictive of sPTB < 34 weeks (AUC 0.63, 0.56-0.70). Alterations in innate immune response proteins in early pregnancy are predictive of sPTB. Further investigation is warranted to understand the drivers for this, and their potential to contribute towards clinically useful prediction techniques.

Objectives: Accurate mid-pregnancy prediction of spontaneous preterm birth (sPTB) is essential to ensure appropriate surveillance of high-risk women. Advancing the QUiPP App prototype, QUiPP App v.2 aimed to provide individualized risk of delivery based on cervical length (CL), quantitative fetal fibronectin (qfFN) or both tests combined, taking into account further risk factors, such as multiple pregnancy. Here we report development of the QUiPP App v.2 predictive models for use in asymptomatic high-risk women, and validation using a distinct dataset in order to confirm the accuracy and transportability of the QUiPP App, overall and within specific clinically relevant time frames., Methods: This was a prospective secondary analysis of data of asymptomatic women at high risk of sPTB recruited in 13 UK preterm birth clinics. Women were offered longitudinal qfFN testing every 2-4 weeks and/or transvaginal ultrasound CL measurement between 18 + 0 and 36 + 6 weeks' gestation. A total of 1803 women (3878 visits) were included in the training set and 904 women (1400 visits) in the validation set. Prediction models were created based on the training set for use in three groups: patients with risk factors for sPTB and CL measurement alone, with risk factors for sPTB and qfFN measurement alone, and those with risk factors for sPTB and both CL and qfFN measurements. Survival analysis was used to identify the significant predictors of sPTB, and parametric structures for survival models were compared and the best selected. The estimated overall probability of delivery before six clinically important time points (< 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks after testing) was calculated for each woman and analyzed as a predictive test for the actual occurrence of each event. This allowed receiver-operating-characteristics curves to be plotted, and areas under the curve (AUC) to be calculated. Calibration was performed to measure the agreement between expected and observed outcomes., Results: All three algorithms demonstrated high accuracy for the prediction of sPTB at < 30, < 34 and < 37 weeks' gestation and within 1, 2 and 4 weeks of testing, with AUCs between 0.75 and 0.90 for the use of qfFN and CL combined, between 0.68 and 0.90 for qfFN alone, and between 0.71 and 0.87 for CL alone. The differences between the three algorithms were not statistically significant. Calibration confirmed no significant differences between expected and observed rates of sPTB within 4 weeks and a slight overestimation of risk with the use of CL measurement between 22 + 0 and 25 + 6 weeks' gestation., Conclusions: The QUiPP App v.2 is a highly accurate prediction tool for sPTB that is based on a unique combination of biomarkers, symptoms and statistical algorithms. It can be used reliably in the context of communicating to patients the risk of sPTB. Whilst further work is required to determine its role in identifying women requiring prophylactic interventions, it is a reliable and convenient screening tool for planning follow-up or hospitalization for high-risk women. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Introduction: Shock index (SI) is a predictor of hemodynamic compromise in obstetric patients. The SI threshold for action is not well understood. We aimed to evaluate SI thresholds as predictors of outcomes in obstetric patients., Material and Methods: We undertook a prospective cohort study at three South African hospitals of women with postpartum hemorrhage (n = 283) or maternal sepsis (n = 126). The "first" and "worst" SI following diagnosis were recorded. SI was compared with conventional vital signs as predictors of outcomes. The performance of SI <.9, SI .9-1.69 and SI ≥1.7 to predict outcomes (maternal death; Critical Care Unit admission; major procedure; hysterectomy) and hemorrhage-specific outcomes (lowest hemoglobin <70 g/l; blood transfusion ≥4 IU) were evaluated., Results: "First" SI was one of two best performing vital signs for every outcome in postpartum hemorrhage and sepsis. In hemorrhage, risk of all outcomes increased with increasing "first" SI; for blood transfusion ≥4 IU odds ratio was 4.24 (95% confidence interval 1.25-14.36) for SI ≥1.7 vs SI .9-1.69. In sepsis, risk of all outcomes increased with increasing "worst" SI. Sensitivity, specificity, positive and negative predictive values of "first" SI <.9 vs SI ≥.9 for maternal death were 100.0%, 55.2%, 4.6% and 100.0%, respectively, in hemorrhage and 80.0%, 50.4%, 12.3% and 96.7%, respectively, in sepsis., Conclusions: The shock index was a consistent predictor of outcomes compared with conventional vital signs in postpartum hemorrhage and sepsis. SI <.9 performed well as a rule-out test and SI .9-1.69 and SI ≥1.7 indicated increased risk of all outcomes in both cohorts. These thresholds may alert to the need for urgent intervention and prevent maternal deaths., (© 2019 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology(NFOG).)

Objectives: Haemorrhage, hypertension, sepsis and abortion complications (often from haemorrhage or sepsis) contribute to 60% of all maternal deaths. Each is associated with vital signs (blood pressure (BP) and pulse) abnormalities, and the majority of deaths are preventable through simple and timely intervention. This paper presents the development and evaluation of the CRADLE Vital Signs Alert (VSA), an accurate, low-cost and easy-to-use device measuring BP and pulse with an integrated traffic light early warning system. The VSA was designed to be used by all cadres of healthcare providers for pregnant women in low-resource settings with the aim to prevent avoidable maternal mortality and morbidity., Methods: The development and the mixed-methods clinical evaluation of the VSA are described., Results: Preliminary fieldwork identified that introduction of BP devices to rural clinics improved antenatal surveillance of BP in pregnant women. The aesthetics of the integrated traffic light system were developed through iterative qualitative evaluation. The traffic lights trigger according to evidence-based vital sign thresholds in hypertension and haemodynamic compromise from haemorrhage and sepsis. The VSA can be reliably used as an auscultatory device, as well as its primary semiautomated function, and is suitable as a self-monitor used by pregnant women., Conclusion: The VSA is an accurate device incorporating an evidence-based traffic light early warning system. It is designed to ensure suitability for healthcare providers with limited training and may improve care for women in pregnancy, childbirth and in the postnatal period., Competing Interests: Competing interests: None declared.

Host defense peptides (HDPs) in the pregnant female reproductive tract provide protection against infection. The relationship between HDPs and infection/inflammation is poorly understood. Therefore, we investigated the regulation of HDPs by 1α, 25-dihydroxyvitamin D3 (1,25-(OH)2) in the presence/absence of infectious/inflammatory agents. Endocervical epithelial cells (END1/E6E7, n = 6) were exposed to 1,25-(OH)2, calcipotriol, interleukin 1β (IL-1β), granulate-macrophage colony-stimulating factor (GM-GSF), and lipopolysaccharide (LPS). Elafin, human beta defensin (hBD2), cathelicidin, secretory leucocyte protease inhibitor, interleukin 8, 1,25-(OH)2 receptor, and toll-like receptor 4 (TLR4) expression was determined using quantitative polymerase chain reaction and/or enzyme-linked immunosorbent assay. Host defense peptide gene and protein expression was assessed in cervicovaginal cells/fluid, respectively, from first trimester pregnant women (n = 8-12). Interleukin 1β induced elafin and hBD2. The 1,25-(OH)2 induced cathelicidin expression in the presence of IL-1β and LPS. The 1,25-(OH)2 also attenuated IL-1β-induced IL-8 expression and LPS enhancement of TLR4. Host defense peptides and TLR4 profiles in cervicovaginal cells and fluid samples from pregnant women were similar to END1/E6E7 cells. In conclusion, HDPs are differentially regulated in END1/E6E7 cells. The 1,25-(OH)2 induction of cathelicidin and suppression of IL-8 highlights a mechanism by which 1,25-(OH)2 supplementation could enhance the pregnant innate immune defenses.

Background: Increasingly, women of reproductive age participate in recreational running, but its impact on pregnancy outcome is unknown. We investigated whether running affects gestational age at delivery and birth weight as indicators of cervical integrity and placental function, respectively., Methods: 1293 female participants were recruited from parkrun, which organises weekly runs involving 1.25 million runners across 450 parks worldwide. Those under 16 or unable to provide outcome data were excluded. Women were categorised according to whether they continued to run during pregnancy or not. Those who continued were further stratified dependent on average weekly kilometres, and which trimester they ran until. Retrospectively collected primary outcomes were gestational age at delivery and birthweight centile. Other outcomes included assisted vaginal delivery rate and prematurity at clinically important gestations., Results: There was no significant difference in gestational age at delivery: 279.0 vs 279.6 days (mean difference 0.6 days, CI -1.3 to 2.4 days; P=0.55) or birthweight centile: 46.9%vs 44.9% (mean difference 2.0%, CI -1.3% to -5.3%; P=0.22) in women who stopped running and those who continued, respectively. Assisted vaginal delivery rate was increased in women who ran: 195/714 (27%) vs 128/579 (22%) (OR 1.32; CI 1.02 to 1.71; P=0.03)., Conclusion: Continuing to run during pregnancy does not appear to affect gestational age or birthweight centile, regardless of mean weekly distance or stage of pregnancy. Assisted vaginal delivery rates were higher in women who ran, possibly due to increased pelvic floor muscle tone. Randomised prospective analysis is necessary to further explore these findings., Competing Interests: Competing interests: None declared.

Objectives: To evaluate the association between blood pressure (BP) measurements and adverse outcomes in women with pre-eclampsia., Study Design: A prospective cohort study of women with pre-eclampsia admitted to three South African tertiary facilities. BP was measured using the CRADLE Vital Signs Alert (VSA), incorporated with a traffic light early warning system; green: systolic BP <140 mmHg and diastolic BP <90 mmHg, yellow: systolic BP 140-159 and/or diastolic BP 90-109 mmHg (but neither is above the upper threshold), red: systolic BP ≥160 mmHg and/or diastolic BP ≥110 mmHg., Main Outcome Measures: Maternal: death, eclampsia, stroke, kidney injury; process measures: magnesium sulfate use, Critical Care Unit (CCU) admission; perinatal: stillbirth, neonatal death, preterm delivery., Results: Of 1547 women with pre-eclampsia (including 42 twin pregnancies), 33.0% of women triggered a red light on admission and 78.6% at their highest BP. Severe hypertension and adverse outcomes were common across yellow and red categories. Comparing admission red to yellow lights, there was a significant increase in kidney injury (OR 1.74, CI 1.31-2.33, trend test p = .003), magnesium sulfate use (OR 3.40, CI 2.24-5.18, p < .001) and CCU admission (OR 1.50, CI 1.18-1.91, p < .001), but not for maternal death, eclampsia, extended perinatal death or preterm delivery., Conclusion: The CRADLE VSA, with integrated traffic light early warning system, can identify women who are hypertensive, at increased risk of severe pre-eclampsia complications and in need of escalation of care. Women who triggered a red light were at increased risk of kidney injury, magnesium sulfate use and CCU admission., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To determine the effect of a low-lying placenta on the concentration of quantitative fetal fibronectin (qfFN) in the cervicovaginal fluid (CVF), and predictive accuracy for spontaneous preterm birth in asymptomatic high-risk women (18  +   0 -24  +   0 weeks gestation)., Methods: Median concentrations of qfFN were compared in women who had a low-lying placenta, covering the cervical os (n = 61) to matched controls (n= 61) without a low-lying placenta. Proportions of women with raised qfFN concentrations (>10 ng/ml), and false positive and negative rates (FPR and FNR) for spontaneous preterm delivery were also compared., Results: The median concentration of qfFN in women with low-lying placenta was 5.0 ng/mL, compared with 6.0 ng/mL in controls. Proportion of women with raised levels (>10 ng/mL), positive levels (>50 ng/mL) and very high levels (>200 ng/mL) were similar in both groups (62.3% versus 59.0%, 16.3% versus 22.0% and 6.5% versus 4.9%, p > 0.05 for all thresholds). The FPR and FNR rate for delivery before 34 and 37 weeks were also comparable (FPR 90.0% versus 85.7% and 80.0% versus 78.6%; FNR 5.8% versus 4.3% and 9.8% versus 8.5%)., Conclusions: CVF qfFN concentrations in asymptomatic high-risk women are not affected by the presence of a low-lying placenta.

Objective: Spontaneous preterm birth is the leading cause of neonatal morbidity and mortality. Cervicovaginal fetal fibronectin (fFN) has enhanced prediction of preterm birth and, more recently, quantified results have become available so that management can planned more effectively and targeted to individual women. Manufacture guidelines stipulate that fetal fibronectin (fFN) samples should be discarded in the presence of moderate to heavy vaginal bleeding but there hasn't yet been any formal investigation into the effect of blood staining on fetal fibronectin concentration and subsequent preterm birth prediction. The objective for this study was to determine the impact of blood stained swabs on quantitative fetal fibronectin (qfFN) concentration and prediction of spontaneous preterm birth (sPTB) in asymptomatic high-risk women., Study Design: Predefined blinded sub-analysis of a larger prospective study of qfFN in asymptomatic women at high-risk of preterm labour. Women with and without blood stained swabs were matched for gestational age at testing and delivery, risk factors and cervical length measurement., Results: Median fFN concentration in blood stained swabs (n=58) was 66ng/ml vs. 7.5ng/ml in the controls (n=58) (p<0.0001). At ≥50ng/ml threshold the false positive ratio (FPR) in blood stained was 25/33 (75.8%) vs. 8/15 (53%) in controls, (risk difference 22.4; -6.8 to 51.6, p=0.18). At ≥50ng/ml threshold the false-negative ratio (FNR) in blood stained was 2/25 (8.0%) vs. 1/43 (2.3%) in controls (risk difference -5.7; -17.2 to 5.9, p=0.55). At each threshold 10, 50 and 200ng/ml blood stained swabs had higher sensitivity but lower specificity for predicting preterm birth. Receiver Operating Characteristic (ROC) curve, the strongest global measure of test performance, for prediction of delivery at <34 weeks gestation was similar in blood stained vs. control groups. (0.78 vs. 0.84) in blood stained vs. control groups respectively., Conclusion: Blood stained swabs have elevated qfFN concentrations but may still have predictive value, and clinical utility. Very low fFN values (<10ng/ml) are especially reassuring and indicate lower risk of delivery than non-blood stained swabs. The higher false positive rate must be noted and explained to the patient., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Objective: To determine the normal ranges of vital signs, including blood pressure (BP), mean arterial pressure (MAP), heart rate (HR) and shock index (SI) (HR/systolic BP), in the immediate postpartum period to inform the development of robust obstetric early warning scores., Study Design: We conducted a secondary analysis of a prospective observational cohort study evaluating vital signs collected within one hour following delivery in women with estimated blood loss (EBL) <500ml (316 women) delivering at a UK tertiary centre over a one-year period. Simple and multiple linear regression were used to explore associations of demographic and obstetric factors with SI., Results: Median (90% reference range) was 120 (100-145) for systolic BP, 75 (58-90) for diastolic BP, 90 (73-108) for MAP, 81 (61-102) for HR, and 0.66 (0.52-0.89) for SI. Third stage Syntometrine® administration was associated with a 0.03 decrease in SI (p = 0.035) and epidural use with a 0.05 increase (p = 0.003). No other demographic or obstetric factors were associated with a change in shock index in this cohort., Conclusion: This is the first study to determine normal ranges of maternal BP, MAP, HR and SI within one hour of birth, a time of considerable haemodynamic adjustment, with minimal effect of demographic and obstetric factors demonstrated. The lower 90% reference point for systolic BP and upper 90% reference point for HR correspond to triggers used to recognise shock in obstetric practice, as do the upper 90% reference points for systolic and diastolic BP for obstetric hypertensive triggers. The SI upper limit of 0.89 in well postpartum women supports current literature suggesting a threshold of 0.9 as indicating increased risk of adverse outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Clinically, once a woman has been identified as being at risk of spontaneous preterm birth (sPTB) due to a short cervical length, a decision regarding prophylactic treatment must be made. Three interventions have the potential to improve outcomes: cervical cerclage (stitch), vaginal progesterone and cervical pessary. Each has been shown to have similar benefit in reduction of sPTB, but there have been no randomised control trials (RCTs) to compare them., Methods: This open label multi-centre UK RCT trial, will evaluate whether the three interventions are equally efficacious to prevent premature birth in women who develop a short cervix (<25 mm on transvaginal ultrasound). Participants will be asymptomatic and between 14 +0 and 23 +6 weeks' gestation in singleton pregnancies. Eligible women will be randomised to cervical cerclage, Arabin pessary or vaginal progesterone (200 mg once daily) (n = 170 women per group). The obstetric endpoints are premature birth rate <37 weeks' of gestation (primary), 34 weeks and 30 weeks (secondary outcomes) and short-term neonatal outcomes (a composite of death and major morbidity). It will also explore whether intervention success can be predicted by pre-intervention biomarker status., Discussion: Preterm birth is the leading cause of perinatal morbidity and mortality and a short cervix is a useful way of identifying those most at risk. However, best management of these women has presented a clinical conundrum for decades. Given the promise offered by cerclage, Arabin pessary and vaginal progesterone for prevention of preterm birth in individual trials, direct comparison of these prophylactic interventions is now essential to establish whether one treatment is superior. If, as we hypothesise, the three interventions are equally efficacious, this study will empower women to make a choice of treatments based on personal preference and quality of life issues also explored by the study. Our exploratory analysis into whether the response to intervention is related to the pre-intervention biomarker status further our understanding of the pathophysiology of spontaneous preterm birth and help focus future research questions., Trial Registration: EudraCT Number: 2015-000456-15 . Registered 11th March 2015.

Background: Quantitative fetal fibronectin testing has demonstrated accuracy for prediction of spontaneous preterm birth in asymptomatic women with a history of preterm birth. Predictive accuracy in women with previous cervical surgery (a potentially different risk mechanism) is not known., Objective: We sought to compare the predictive accuracy of cervicovaginal fluid quantitative fetal fibronectin and cervical length testing in asymptomatic women with previous cervical surgery to that in women with 1 previous preterm birth., Study Design: We conducted a prospective blinded secondary analysis of a larger observational study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women measured with a Hologic 10Q system (Hologic, Marlborough, MA). Prediction of spontaneous preterm birth (<30, <34, and <37 weeks) with cervicovaginal fluid quantitative fetal fibronectin concentration in primiparous women who had undergone at least 1 invasive cervical procedure (n = 473) was compared with prediction in women who had previous spontaneous preterm birth, preterm prelabor rupture of membranes, or late miscarriage (n = 821). Relationship with cervical length was explored., Results: The rate of spontaneous preterm birth <34 weeks in the cervical surgery group was 3% compared with 9% in previous spontaneous preterm birth group. Receiver operating characteristic curves comparing quantitative fetal fibronectin for prediction at all 3 gestational end points were comparable between the cervical surgery and previous spontaneous preterm birth groups (34 weeks: area under the curve, 0.78 [95% confidence interval 0.64-0.93] vs 0.71 [95% confidence interval 0.64-0.78]; P = .39). Prediction of spontaneous preterm birth using cervical length compared with quantitative fetal fibronectin for prediction of preterm birth <34 weeks of gestation offered similar prediction (area under the curve, 0.88 [95% confidence interval 0.79-0.96] vs 0.77 [95% confidence interval 0.62-0.92], P = .12 in the cervical surgery group; and 0.77 [95% confidence interval 0.70-0.84] vs 0.74 [95% confidence interval 0.67-0.81], P = .32 in the previous spontaneous preterm birth group)., Conclusion: Prediction of spontaneous preterm birth using cervicovaginal fluid quantitative fetal fibronectin in asymptomatic women with cervical surgery is valid, and has comparative accuracy to that in women with a history of spontaneous preterm birth., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To assess the predictive value of quantitative fetal fibronectin (fFN) concentration in cervicovaginal fluid for spontaneous preterm birth in women with bulging fetal membranes., Study Design: This was a prospective observational study from five UK tertiary centres of a cohort of women with singleton pregnancy and bulging fetal membranes presenting between 18 and 32 weeks of gestation (n=62), in the period 2010-2014. fFN concentrations in cervicovaginal fluid were measured both quantitatively and qualitatively at presentation in all women. Predictive statistics and receiver operating characteristic (ROC) curves were calculated for both tests to predict spontaneous preterm birth within 14 days from testing and before 34 weeks of gestation., Results: 62 eligible women with bulging fetal membranes were recruited from screening of 2571 women at high risk of preterm birth. The median gestational age was 24(+0) (LQ-UQ, 21(+2)-25(+3)) at presentation and 34(+4) (25(+2)-39(+0)) at delivery, with a median time from testing to delivery of 58 days (17-110). Concentration of quantitative fFN at presentation correlated negatively with time to delivery (Spearman's rs=-0.615, p<0.001). The area under the ROC curve for quantitative fFN testing was 0.81 (95% CI 0.69-0.94) for prediction of spontaneous preterm birth within 14 days, and 0.84 (0.73-0.95) before 34 weeks of gestation., Conclusion: Quantitative fFN has a role in predicting spontaneous preterm birth even in women with bulging fetal membranes, suggesting that fFN leakage could potentially be an active process. This may aid the clinical management of this high-risk group in the future., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To identify whether preterm surveillance clinics (PSCs) risk-stratify high-risk women accurately by comparing outcomes of those admitted to hospital on the basis of asymptomatic testing with those not admitted., Methods: We performed a subanalysis from a larger prospective cohort study on sonographic cervical length, quantitative fetal fibronectin (qfFN) and risk of spontaneous preterm birth. We identified 1130 asymptomatic singleton pregnancies at high risk of preterm birth, screened between 23 and 28 weeks of gestation at a PSC in a tertiary hospital in London, UK. Gestational age at delivery, the proportion of preterm births that delivered < 30 weeks and neonatal outcomes were compared between women admitted electively when asymptomatic as a consequence of screening-test results and those who were not routinely admitted., Results: In total, 66 (6%) women attending the PSC were admitted to hospital following asymptomatic screening (inpatient group). The mean gestational age at delivery for those not admitted electively (outpatient group) was at term and was significantly higher than that of those admitted from PSC (38.4 vs 31.2 weeks; P < 0.0001). Preterm birth < 30 weeks' gestation was rare in the outpatient group relative to those admitted (1.32% vs 36.4%; P < 0.0001). Neonatal mortality was 0.188% in the outpatient group compared with 4.55% in those admitted electively (P < 0.0001). The incidence of other complications such as neonatal death, 5-min Apgar score < 7, special care baby unit/neonatal intensive care unit admission, respiratory distress syndrome, intraventricular hemorrhage and low birth weight were significantly lower in those managed as outpatients than in those admitted electively., Conclusion: PSCs measuring cervical length and qfFN accurately triage asymptomatic high-risk pregnant women, enabling those at highest risk of adverse outcome to be identified for elective admission to hospital and appropriate management. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To determine the optimal vital sign predictor of adverse maternal outcomes in women with hypovolemic shock secondary to obstetric hemorrhage and to develop thresholds for referral/intensive monitoring and need for urgent intervention to inform a vital sign alert device for low-resource settings., Study Design: We conducted secondary analyses of a dataset of pregnant/postpartum women with hypovolemic shock in low-resource settings (n = 958). Using receiver-operating curve analysis, we evaluated the predictive ability of pulse, systolic blood pressure, diastolic blood pressure, shock index, mean arterial pressure, and pulse pressure for three adverse maternal outcomes: (1) death, (2) severe maternal outcome (death or severe end organ dysfunction morbidity); and (3) a combined severe maternal and critical interventions outcome comprising death, severe end organ dysfunction morbidity, intensive care admission, blood transfusion ≥ 5 units, or emergency hysterectomy. Two threshold parameters with optimal rule-in and rule-out characteristics were selected based on sensitivities, specificities, and positive and negative predictive values., Results: Shock index was consistently among the top two predictors across adverse maternal outcomes. Its discriminatory ability was significantly better than pulse and pulse pressure for maternal death (p<0.05 and p<0.01, respectively), diastolic blood pressure and pulse pressure for severe maternal outcome (p<0.01), and systolic and diastolic blood pressure, mean arterial pressure and pulse pressure for severe maternal outcome and critical interventions (p<0.01). A shock index threshold of ≥ 0.9 maintained high sensitivity (100.0) with clinical practicality, ≥ 1.4 balanced specificity (range 70.0-74.8) with negative predictive value (range 93.2-99.2), and ≥ 1.7 further improved specificity (range 80.7-90.8) without compromising negative predictive value (range 88.8-98.5)., Conclusions: For women with hypovolemic shock from obstetric hemorrhage, shock index was consistently a strong predictor of all adverse outcomes. In lower-level facilities in low resource settings, we recommend a shock index threshold of ≥ 0.9 indicating need for referral, ≥ 1.4 indicating urgent need for intervention in tertiary facilities and ≥ 1.7 indicating high chance of adverse outcome. The vital sign alert device incorporated values 0.9 and 1.7; however, all thresholds will be prospectively validated and clinical pathways for action appropriate to setting established prior to clinical implementation.

Objective: To compare quantitative fetal fibronectin measurement from 18 to 21 weeks of gestation to measurement at 22-27 weeks of gestation for the prediction of spontaneous preterm birth., Methods: In a prospective cohort study, we studied the accuracy of cervicovaginal fluid quantitative fetal fibronectin concentrations measured between 18 0/7 weeks of gestation and 21 6/7 weeks of gestation in high-risk asymptomatic women to predict spontaneous preterm birth before 34 weeks of gestation. Predefined fibronectin thresholds were 10 or greater, 50 or greater, and 200 ng/mL or greater. Diagnostic accuracy of the early test (n=898) was compared with the standard test performed between 22 0/7 and 27 6/7 weeks of gestation (n=691) in the same cohort. Subgroup analysis was performed according to cervical length measurement., Results: Of 898 women, 8.7% delivered spontaneously before 34 weeks of gestation. Only 3.8% of the women with concentrations less than 10 ng/mL (65% of test results) delivered before 34 weeks of gestation. A concentration threshold of 10 ng/mL measured at 18 and 22 weeks of gestation had comparably high sensitivity (early 0.71, 95% confidence interval 0.60-0.81; standard 0.76, 0.63-0.87) and negative predictive value (early 0.96, 0.94-0.98; standard 0.97, 0.95-0.99) for delivery before 34 weeks of gestation. Specificity was also comparable (early 0.69, 0.65-0.72; standard 0.70, 0.66-0.74). A threshold of 200 ng/mL had high specificity (early 0.96, 0.94-0.98; standard 0.96, 0.94-0.97) with lower sensitivity (early 0.26, 0.17-0.37; standard 0.35, 0.22-0.49). Consideration of cervical length strengthened prediction., Conclusion: Quantitative cervicovaginal fetal fibronectin measured from 18 to 21 weeks of gestation has similar predictive value as measurement at 22-27 weeks of gestation for prediction of spontaneous preterm birth. Low fibronectin concentrations are associated with spontaneous preterm birthrates approaching population background levels.

Spontaneous preterm birth (sPTB) is the leading cause of neonatal morbidity and mortality globally. Accurate prediction of sPTB would enable targeting of interventions such as admission to hospital, antenatal corticosteroids, magnesium sulphate and in utero transfer as well as guiding prophylactic treatment (e.g., cerclage or progesterone). Measurement of fetal fibronectin concentration in the cervicovaginal fluid is a known predictor of sPTB. Traditionally a positive/negative test (defined by a threshold of 50 ng/ml), recent work has demonstrated improved prediction when used as a quantitative test, whereby the concentration of fetal fibronectin is measured by an automated bedside reader. This review examines the evidence surrounding the use of quantitative fetal fibronectin in asymptomatic women at high risk of sPTB, as well as those with symptoms of threatened sPTB.

Antenatal corticosteroids for fetal lung maturation have become mainstay treatment in women thought to be at high-risk of premature birth. To ensure treatment efficacy before delivery, the current practice is to administer steroids early to a woman considered at risk; however, neonatal benefit is lost after the seven-day treatment-to-delivery window. Over half of women who deliver before 34 weeks' gestation do not receive antenatal corticosteroids within this timeframe, but many still deliver prematurely; however, clinicians are reluctant to administer repeated courses of steroids due to concerns, among others, of impaired fetal growth. However, evidence is mounting regarding the optimal timing for steroids, including substantive benefits close to delivery, and the benefits of repeated courses if delivery has not occurred. Better targeted treatment is required to allow for maximum benefit; reducing unnecessary treatment in low-risk women, while targeting therapy in the high-risk cohort and offering repeat courses if the seven-day window is exceeded. Novel tools to aid prediction may help implement this strategy.

Objective: To assess the accuracy of the Microlife 3AS1-2 blood pressure (BP) device in pregnant women with low BP to investigate suitability for hypotensive detection in low-income and middle-income countries., Methods: A prospective observational study was carried out evaluating the Microlife 3AS1-2, a hand-held, upper-arm, semiautomated BP device, according to British Hypertension Society (BHS) protocol methods. Thirty (stable) pregnant women with a clinical systolic BP less than 100 mmHg and/or diastolic BP less than 60 mmHg were recruited from antenatal wards and clinics and their BP was measured by three trained observers at a district-level hospital in South Africa. Accuracy was assessed according to the BHS grading criteria (A/B=pass) and the ANSI/AAMI/ISO standard for mean difference and SD (≤5±8 mmHg)., Results: The device achieved an A/A grade according to the BHS grading criteria. The mean difference±SD between the observer and the test device was 0.5±6.2 and 1.3±5.4 mmHg for systolic and diastolic BP, respectively, fulfilling the standard required by the ANSI/AAMI/ISO protocol. All observer differences were within 4 mmHg., Conclusion: According to the BHS protocol, the Microlife 3AS1-2 BP device is accurate in pregnant women with low BP. The device has been validated previously in pregnancy and pre-eclampsia and also fulfils the criteria of the WHO for use in a low-resource setting. Although unstable women were not included in this validation (for safety and pragmatic reasons), this device could potentially improve the detection of shock secondary to obstetric haemorrhage or sepsis, as well as being used in pre-eclampsia, particularly in low-income and middle-income countries.

Objective: To evaluate the diagnostic accuracy of cervicovaginal fluid quantitative fetal fibronectin, measured by a bedside analyzer, to predict spontaneous preterm birth before 34 weeks of gestation., Methods: We conducted a prospective masked observational cohort study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women at high risk of spontaneous preterm birth (n=1,448; 22-27 6/7 weeks of gestation) measured using a rapid bedside analyzer. The routine qualitative result (positive-negative) was made available to clinicians at the time of testing, but the quantitative result remained blinded until after delivery., Results: Spontaneous preterm birth (less than 34 weeks of gestation) increased from 2.7%, 11.0%, 14.9%, 33.9%, and 47.6% with increasing concentration of fetal fibronectin (less than 10, 10-49, 50-199, 200-499, and 500 ng/mL or greater, respectively). A threshold of 200 ng/mL had a positive predictive value of 37.7 (95% confidence interval [CI] 26.9-49.4) with specificity 96% (95% CI 95.3-97.3). Women with a fetal fibronectin concentration of less than 10 ng/mL had a very low risk of spontaneous preterm birth at less than 34 weeks of gestation (2.7%), no higher than the background spontaneous preterm birth rate of the general hospital population (3.3%). The quantitative fetal fibronectin test predicted birth at less than 34 weeks of gestation with an area under the curve (AUC) of 0.78 (95% CI 0.73-0.84) compared with the qualitative test AUC 0.68 (95% CI 0.63-0.73). Quantitative fetal fibronectin discriminated risk of spontaneous preterm birth at less than 34 weeks of gestation among women with a short cervix (less than 25 mm); 9.5% delivered prematurely less than 10 ng/mL compared with 55.1% greater than 200 ng/mL (P<.001)., Discussion: Alternative risk thresholds (less than 10 ng/mL and greater than 200 ng/mL) improve accuracy when using quantitative fetal fibronectin measurements to define risk of spontaneous preterm birth. This is particularly relevant for asymptomatic women with a short cervix., Level of Evidence: II.

Objectives: To assess the accuracy of the Microlife 3AS1-2 blood pressure device in pregnancy and pre-eclampsia in a low-resource setting., Methods: Prospective validation according to the British Hypertension Society protocol. A total of 45 pregnant women were recruited from Kimberley Hospital (South Africa), of whom 15 had pre-eclampsia., Results: The Microlife 3AS1-2 device achieved an overall B/A grade in pregnancy (including pre-eclampsia), passing the British Hypertension Society protocol requirements and achieving the International Organization for Standardization standard with a mean difference and SD of -3.8 ± 7.3 and -1.5 ± 6.2 mmHg for systolic and diastolic pressures, respectively., Conclusion: The Microlife 3AS1-2 device can be recommended for use in pregnancy, including pre-eclampsia. In addition, it fulfils the requirements stipulated by the WHO for an automated blood pressure device suitable for use in a low-resource setting. This makes it the ideal device for antenatal clinics and primary healthcare facilities in low-income and middle-income countries.