The legacy of maternal SARS-CoV-2 infection on the immunology of the neonate.

Despite extensive studies into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the effect of maternal infection on the neonate is unclear. To investigate this, we characterized the immunology of neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy. Here we show that maternal SARS-CoV-2 infection affects the neonatal immune system. Despite similar proportions of B cells, CD4+ T cells and CD8+ T cells, increased percentages of natural killer cells, Vδ2+ γδ T cells and regulatory T cells were detected in neonates born to mothers with recent or ongoing infection compared with those born to recovered or uninfected mothers. Increased plasma cytokine levels were also evident in neonates and mothers within the recent or ongoing infection group. Cytokine functionality was enhanced in neonates born to SARS-CoV-2-exposed mothers, compared to those born to uninfected mothers. In most neonates, this immune imprinting was nonspecific, suggesting vertical transmission of SARS-CoV-2 is limited, a finding supported by a lack of SARS-CoV-2-specific IgM in neonates despite maternal IgG transfer.

"I had given up on being a mother": a survey of 183 women's experience of transabdominal cerclage (TAC).

BACKGROUND: Transabdominal cerclage (TAC) is a relatively uncommon intervention for preventing preterm birth. This study aimed to investigate the experience of women who had undergone this procedure. METHODS: The survey was designed in collaboration with a preterm birth studies public and patient involvement (PPI) group and ethical approval was granted by KCL BDM Research Ethics Panel (LRS-19/20-13205). Members of closed Facebook group, UK TAC Support, were invited to complete an online questionnaire about their experience of TAC, and pregnancies before and after having it placed. The survey was open between December 2019 and May 2020. Open and closed questions provided both qualitative and quantitative data for analysis, which was carried out using NVivo Pro 2020 v.1.4.1 qualitative data management software and SPSS Statistics 27 (IBM). RESULTS: One hundred eighty-three participants completed the survey, having had TAC procedures carried out in 36 hospitals. Altogether, participants had experienced 287 preterm births (PTB) and late miscarriages (LM), equating to an average of 1.6 each (range 0-5), including 18 stillbirths. TAC was indicated in 123 (67%) for previous PTB and/or LM, 29 (16%) for cervical surgery and 31 (17%) for both. 151 (83%) TAC procedures were open, 32 (17%) laparoscopic. 86% (n = 157) were placed outside pregnancy. Of those placed in pregnancy, gestation at TAC ranged from 7 to 16 weeks. When comparing earliest pre- and post-TAC pregnancy gestation (excluding first trimester losses), median gestational weeks gained following TAC was 15.5 weeks (SD 6.89). Qualitative themes included: the struggle to get treatment; lack of TAC knowledge amongst clinicians; gratitude, hope and feeling protected; possible detrimental effects of TAC. CONCLUSIONS: This very high-risk group found having a TAC gave great reassurance and hope, and were very grateful to have found the care they needed. However, they often struggled to get this support, frequently due to lack of clinician awareness. This may improve following roll-out of NHS England's Saving Babies Live Care Bundle and NHS commissioning guidelines for care of women at risk of PTB.

Development and validation of a risk prediction model of preterm birth for women with preterm labour symptoms (the QUIDS study): A prospective cohort study and individual participant data meta-analysis.

BACKGROUND: Timely interventions in women presenting with preterm labour can substantially improve health outcomes for preterm babies. However, establishing such a diagnosis is very challenging, as signs and symptoms of preterm labour are common and can be nonspecific. We aimed to develop and externally validate a risk prediction model using concentration of vaginal fluid fetal fibronectin (quantitative fFN), in combination with clinical risk factors, for the prediction of spontaneous preterm birth and assessed its cost-effectiveness. METHODS AND FINDINGS: Pregnant women included in the analyses were 22+0 to 34+6 weeks gestation with signs and symptoms of preterm labour. The primary outcome was spontaneous preterm birth within 7 days of quantitative fFN test. The risk prediction model was developed and internally validated in an individual participant data (IPD) meta-analysis of 5 European prospective cohort studies (2009 to 2016; 1,783 women; mean age 29.7 years; median BMI 24.8 kg/m2; 67.6% White; 11.7% smokers; 51.8% nulliparous; 10.4% with multiple pregnancy; 139 [7.8%] with spontaneous preterm birth within 7 days). The model was then externally validated in a prospective cohort study in 26 United Kingdom centres (2016 to 2018; 2,924 women; mean age 28.2 years; median BMI 25.4 kg/m2; 88.2% White; 21% smokers; 35.2% nulliparous; 3.5% with multiple pregnancy; 85 [2.9%] with spontaneous preterm birth within 7 days). The developed risk prediction model for spontaneous preterm birth within 7 days included quantitative fFN, current smoking, not White ethnicity, nulliparity, and multiple pregnancy. After internal validation, the optimism adjusted area under the curve was 0.89 (95% CI 0.86 to 0.92), and the optimism adjusted Nagelkerke R2 was 35% (95% CI 33% to 37%). On external validation in the prospective UK cohort population, the area under the curve was 0.89 (95% CI 0.84 to 0.94), and Nagelkerke R2 of 36% (95% CI: 34% to 38%). Recalibration of the model's intercept was required to ensure overall calibration-in-the-large. A calibration curve suggested close agreement between predicted and observed risks in the range of predictions 0% to 10%, but some miscalibration (underprediction) at higher risks (slope 1.24 (95% CI 1.23 to 1.26)). Despite any miscalibration, the net benefit of the model was higher than "treat all" or "treat none" strategies for thresholds up to about 15% risk. The economic analysis found the prognostic model was cost effective, compared to using qualitative fFN, at a threshold for hospital admission and treatment of ≥2% risk of preterm birth within 7 days. Study limitations include the limited number of participants who are not White and levels of missing data for certain variables in the development dataset. CONCLUSIONS: In this study, we found that a risk prediction model including vaginal fFN concentration and clinical risk factors showed promising performance in the prediction of spontaneous preterm birth within 7 days of test and has potential to inform management decisions for women with threatened preterm labour. Further evaluation of the risk prediction model in clinical practice is required to determine whether the risk prediction model improves clinical outcomes if used in practice. TRIAL REGISTRATION: The study was approved by the West of Scotland Research Ethics Committee (16/WS/0068). The study was registered with ISRCTN Registry (ISRCTN 41598423) and NIHR Portfolio (CPMS: 31277).

MAVRIC: a multicenter randomized controlled trial of transabdominal vs transvaginal cervical cerclage.

BACKGROUND: Vaginal cerclage (a suture around the cervix) commonly is placed in women with recurrent pregnancy loss. These women may experience late miscarriage or extreme preterm delivery, despite being treated with cerclage. Transabdominal cerclage has been advocated after failed cerclage, although its efficacy is unproved by randomized controlled trial. OBJECTIVE: The objective of this study was to compare transabdominal cerclage or high vaginal cerclage with low vaginal cerclage in women with a history of failed cerclage. Our primary outcome was delivery at <32 completed weeks of pregnancy. STUDY DESIGN: This was a multicenter randomized controlled trial. Women were assigned randomly (1:1:1) to receive transabdominal cerclage, high vaginal cerclage, or low vaginal cerclage either before conception or at <14 weeks of gestation. RESULTS: The data for 111 of 139 women who were recruited and who conceived were analyzed: 39 had transabdominal cerclage; 39 had high vaginal cerclage, and 33 had low vaginal cerclage. Rates of preterm birth at <32 weeks of gestation were significantly lower in women who received transabdominal cerclage compared with low vaginal cerclage (8% [3/39] vs 33% [11/33]; relative risk, 0.23; 95% confidence interval, 0.07-0.76; P=.0157). The number needed to treat to prevent 1 preterm birth was 3.9 (95% confidence interval, 2.32-12.1). There was no difference in preterm birth rates between high and low vaginal cerclage (38% [15/39] vs 33% [11/33]; relative risk, 1.15; 95% confidence interval, 0.62-2.16; P=.81). No neonatal deaths occurred. In an exploratory analysis, women with transabdominal cerclage had fewer fetal losses compared with low vaginal cerclage (3% [1/39] vs 21% [7/33]; relative risk, 0.12; 95% confidence interval, 0.016-0.93; P=.02). The number needed to treat to prevent 1 fetal loss was 5.3 (95% confidence interval, 2.9-26). CONCLUSION: Transabdominal cerclage is the treatment of choice for women with failed vaginal cerclage. It is superior to low vaginal cerclage in the reduction of risk of early preterm birth and fetal loss in women with previous failed vaginal cerclage. High vaginal cerclage does not confer this benefit. The numbers needed to treat are sufficiently low to justify transabdominal surgery and cesarean delivery required in this select cohort.

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

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

Longitudinal change in cervical length following vaginal or abdominal cervical cerclage: a randomized comparison.

BACKGROUND: Cervical cerclage has been shown to reduce the risk of recurrent spontaneous preterm birth in a high-risk patient population; however, the mechanism is not well understood. Transabdominal cerclage is superior to low and high vaginal cerclage in reducing early spontaneous preterm birth and fetal loss in women with previous failed vaginal cerclage. Cervical length measurements are commonly used to monitor high-risk women and may explain the mechanism of success. OBJECTIVE: This study aimed to evaluate the rate of change in longitudinal cervical length after randomized placement of low transvaginal, high transvaginal, or transabdominal cerclage in women with a previous failed vaginal cerclage. STUDY DESIGN: This was a planned analysis of longitudinal transvaginal ultrasound cervical length measurements from patients enrolled in the Vaginal Randomised Intervention of Cerclage trial, a randomized controlled trial comparing transabdominal cerclage or high transvaginal cerclage with low transvaginal cerclage. Cervical length measurements at specific gestational ages were compared over time and between groups, using generalized estimating equations fitted using the maximum-likelihood random-effects estimator. In addition, cervical length measurements were compared in women with transabdominal cerclage placed before and during pregnancy. The diagnostic accuracy of cervical length as a predictor of spontaneous preterm birth at <32 weeks of gestation was explored. RESULTS: This study included 78 women who underwent longitudinal cervical length assessment (70% of the analyzed cohort) with a history of failed cerclage, of whom 25 (32%) were randomized to low transvaginal cerclage, 26 (33%) to high transvaginal cerclage, and 27 (35%) to transabdominal cerclage. Abdominal cerclage was superior to low (P=.008) and high (P=.001) vaginal cerclage at maintaining cervical length over the surveillance period (14 to 26 weeks of gestation) (+0.08 mm/week, 95% confidence interval, -0.40 to 0.22; P=.580). On average, the cervical length was 1.8 mm longer by the end of the 12-week surveillance period in women with transabdominal cerclage (+1.8 mm; 95% confidence interval, -7.89 to 4.30; P=.564). High vaginal cerclage was no better than low cervical cerclage in the prevention of cervical shortening; the cervix shortened by 13.2 mm over 12 weeks in those with low vaginal cerclage (95% confidence interval, -21.7 to -4.7; P=.002) and by 20 mm over 12 weeks in those with high vaginal cerclage (95% confidence interval, -33.1 to -7.4; P=.002). Preconception transabdominal cerclage resulted in a longer cervix than those performed during pregnancy; this difference was significant after 22 weeks of gestation (48.5 mm vs 39.6 mm; P=.039). Overall, cervical length was an excellent predictor of spontaneous preterm birth at <32 weeks of gestation (receiver operating characteristic curve, 0.92; 95% confidence interval, 0.82-1.00). CONCLUSION: In women with a previous failed cervical cerclage, in the next pregnancy, the cervical length in women treated with vaginal cerclage funneled and shortened over time, whereas there was preservation of cervical length in women who receive transabdominal cerclage. Cervical length remained longer in transabdominal procedures performed before pregnancy than in transabdominal procedures performed during pregnancy. Overall, cervical length was an excellent predictor of spontaneous preterm birth in our cohort. Our findings may explain the mechanism of benefit for transabdominal cerclage, with its high placement better maintaining the structural integrity of the cervix at the level of the internal os.

Optimal timing of cervical cerclage removal following preterm premature rupture of membranes; a retrospective analysis.

OBJECTIVE: Preterm prelabour rupture of membranes occurs in over one third of pregnant women with a cervical cerclage in situ. In the setting of preterm prelabour rupture of membranes, clinicians are faced with the difficult decision of the optimal timing for removing the cerclage. We compared the maternal and neonatal outcomes following immediate removal or retention of the cervical cerclage. STUDY DESIGN: Women were retrospectively identified from St Thomas's Hospital Preterm Surveillance clinic database. Asymptomatic women with preterm prelabour rupture of membranes were identified and separated into those that had the cerclage removed and those that had the cerclage retained within 24 h of presentation. Women who were symptomatic at presentation and who delivered within 24 h of presentation were excluded from the analysis. Maternal outcomes measured were latency between preterm prelabour rupture of membranes and delivery, gestation at delivery and maternal chorioamnionitis and infection markers. Neonatal outcomes including birthweight and Apgar scores were also measured. RESULTS: 43 women with cerclage retained for over 24 h following preterm prelabour rupture of membranes were compared to 25 women in whom the cerclage was removed. The latency between preterm prelabour rupture of membranes and delivery was on average 70.4 h longer in women who had their cerclage retained compared to the removed group (p = 0.009). Rates of chorioamnionitis, maternal blood results, neonatal birthweight and Apgar scores did not differ significantly between the two groups, however a trend towards higher rates of chorioamnionitis (60 % vs 45 %) were seen in the retained group. CONCLUSION: Cervical cerclage retention in women following preterm prelabour rupture of membranes was associated with a longer latency period to delivery and was not significantly associated with any adverse obstetric, maternal or neonatal outcomes. Therefore, in women at risk of spontaneous preterm birth, cerclage retention may be beneficial, however these women and their babies should be monitored closely for any signs of infection. Further prospective randomised controlled studies assessing these outcomes as well as longer-term outcomes in these women and their children are needed.

A prognostic model, including quantitative fetal fibronectin, to predict preterm labour: the QUIDS meta-analysis and prospective cohort study.

BACKGROUND: The diagnosis of preterm labour is challenging. False-positive diagnoses are common and result in unnecessary, potentially harmful treatments (e.g. tocolytics, antenatal corticosteroids and magnesium sulphate) and costly hospital admissions. Measurement of fetal fibronectin in vaginal fluid is a biochemical test that can indicate impending preterm birth. OBJECTIVES: To develop an externally validated prognostic model using quantitative fetal fibronectin concentration, in combination with clinical risk factors, for the prediction of spontaneous preterm birth and to assess its cost-effectiveness. DESIGN: The study comprised (1) a qualitative study to establish the decisional needs of pregnant women and their caregivers, (2) an individual participant data meta-analysis of existing studies to develop a prognostic model for spontaneous preterm birth within 7 days in women with symptoms of preterm labour based on quantitative fetal fibronectin and clinical risk factors, (3) external validation of the prognostic model in a prospective cohort study across 26 UK centres, (4) a model-based economic evaluation comparing the prognostic model with qualitative fetal fibronectin, and quantitative fetal fibronectin with cervical length measurement, in terms of cost per QALY gained and (5) a qualitative assessment of the acceptability of quantitative fetal fibronectin. DATA SOURCES/SETTING: The model was developed using data from five European prospective cohort studies of quantitative fetal fibronectin. The UK prospective cohort study was carried out across 26 UK centres. PARTICIPANTS: Pregnant women at 22+0-34+6 weeks' gestation with signs and symptoms of preterm labour. HEALTH TECHNOLOGY BEING ASSESSED: Quantitative fetal fibronectin. MAIN OUTCOME MEASURES: Spontaneous preterm birth within 7 days. RESULTS: The individual participant data meta-analysis included 1783 women and 139 events of spontaneous preterm birth within 7 days (event rate 7.8%). The prognostic model that was developed included quantitative fetal fibronectin, smoking, ethnicity, nulliparity and multiple pregnancy. The model was externally validated in a cohort of 2837 women, with 83 events of spontaneous preterm birth within 7 days (event rate 2.93%), an area under the curve of 0.89 (95% confidence interval 0.84 to 0.93), a calibration slope of 1.22 and a Nagelkerke R2 of 0.34. The economic analysis found that the prognostic model was cost-effective compared with using qualitative fetal fibronectin at a threshold for hospital admission and treatment of ≥ 2% risk of preterm birth within 7 days. LIMITATIONS: The outcome proportion (spontaneous preterm birth within 7 days of test) was 2.9% in the validation study. This is in line with other studies, but having slightly fewer than 100 events is a limitation in model validation. CONCLUSIONS: A prognostic model that included quantitative fetal fibronectin and clinical risk factors showed excellent performance in the prediction of spontaneous preterm birth within 7 days of test, was cost-effective and can be used to inform a decision support tool to help guide management decisions for women with threatened preterm labour. FUTURE WORK: The prognostic model will be embedded in electronic maternity records and a mobile telephone application, enabling ongoing data collection for further refinement and validation of the model. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015027590 and Current Controlled Trials ISRCTN41598423. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 52. See the NIHR Journals Library website for further project information.

Identifying which women with symptoms of labour will give birth early is challenging, so many women unnecessarily receive therapies aimed at preventing complications in preterm birth. A test called quantitative fetal fibronectin, which uses vaginal swab samples, may help to improve the diagnosis of preterm labour. Fetal fibronectin is a protein that is released from the fetal membranes that surround the developing baby in the womb. The lower the concentration of fetal fibronectin, the less likely the occurrence of preterm birth. Our aim was to see if quantitative fetal fibronectin, in combination with some features of pregnancy (e.g. previous pregnancy history and twin pregnancy), can accurately predict preterm birth in women who have symptoms of preterm labour. We asked women, their partners, doctors and midwives what information would be most useful to them, and how this should be presented. We then analysed previous research data; we used quantitative fetal fibronectin and clinical risk factors together to predict the chance of preterm birth. We explored which features could predict preterm birth most effectively while still being good value to the NHS. To ensure that this risk predictor worked in UK populations, we undertook a research study across 26 UK hospitals. Women who had symptoms of preterm labour were invited to participate. We collected information from these women (approximately 3000 women), including quantitative fetal fibronectin results. We found that a risk predictor comprising quantitative fetal fibronectin and four other features performed best at predicting whether or not preterm birth will occur within the next week for women with symptoms of preterm labour, and that this had potential to be clinically useful and cost-effective. The quantitative fetal fibronectin testing process was acceptable to women, and clinicians found the risk predictor useful. We used our findings to develop a risk calculator to help women and clinicians assess how likely preterm birth is, and decide whether or not to start treatment.

The use of quantitative fetal fibronectin for the prediction of preterm birth in women with exposed fetal membranes undergoing emergency cervical cerclage.

OBJECTIVE: Emergency cervical cerclage is often considered a controversial salvage measure for those pregnancies at high risk of mid-trimester loss or early preterm birth. To determine the efficacy and benefit of emergency cerclage insertion, we assessed the predictive value of quantitative fetal fibronectin (fFN) concentration in cervicovaginal fluid for spontaneous preterm birth in women with exposed fetal membranes prior to cerclage insertion. STUDY DESIGN: This was a retrospective observational study from St Thomas' Hospital, London of a cohort of women with singleton pregnancy and exposed fetal membranes presenting between 18 and 23+6 weeks of gestation (n = 35), in the period 2015-2018. fFN concentrations in cervicovaginal fluid were measured quantitatively at presentation in all women within 24 h prior to cerclage insertion. RESULTS: 35 eligible women with exposed fetal membranes who underwent an emergency cervical cerclage were identified. The median gestational age was 20 + 0 weeks (18 + 6-21 + 2) at presentation and 29 + 3 weeks (23 + 3-38 + 2) at delivery, with a median time from emergency cerclage to delivery of 65.5 days (17-126.5). In total, 12 women (34 %) delivered within 28 days of emergency cerclage insertion. 60 % of women with an fFN level above 500 ng/mL delivered within 28 days of cerclage insertion, and they all delivered before 37 weeks gestation. No women with fFN levels below 10 ng/mL delivered within 28 days and 75 % of these women delivered at term. Concentration of quantitative fFN at presentation correlated negatively with time to delivery (Spearman's rs = -0.52, p = 0.0016). Mann-Whitney U analysis demonstrated a significant difference in the distribution of qfFN concentrations in women who delivered preterm compared to those who did not, both within 28 days from testing (p = 0.0048) and <37 weeks (p = 0.006). CONCLUSION: Quantitative fFN has a role in predicting spontaneous preterm birth even in women with exposed fetal membranes undergoing emergency cervical cerclage. Given the serious risks associated with cervical cerclage surgery, qfFN could be used to counsel these patients at high risk of preterm delivery, as well as assisting in the decision to insert a cerclage.

Development of a video to teach clinicians how to perform a transabdominal cerclage.

BACKGROUND: A transabdominal cerclage has been shown in a recent randomized controlled trial to be superior to a low vaginal cerclage in reducing the risk of early preterm birth (8% [3/39] vs 33% [11/33]; relative risk, 0.23; 95% confidence interval, 0.07-0.76; P=.01570) and fetal loss (3% [1/39] vs 21% [7/33]; relative risk, 0.12; 95% confidence interval, 0.016-0.930) in women with a previous failed vaginal cerclage.1 OBJECTIVE: We sought to create a video illustrating a transabdominal cerclage procedure for use as a teaching resource and describing this uncommon but important procedure for dissemination among clinicians. STUDY DESIGN: Transabdominal cerclage insertion in a non-gravid and gravid uterus (less than 14 weeks' gestation) via laparotomy and laparoscopy was filmed with patients' and clinicians' consent in main theatres at St Thomas' Hospital and University College London Hospital. The film footage was edited, and an audio narration by the surgeon was included to provide a description of the procedures. RESULTS: We developed an 8-minute video with an audio narration describing the insertion and management issues of an abdominal cerclage for free dissemination among clinicians who wish to learn how to perform this procedure. CONCLUSION: An abdominal cerclage has been shown to significantly reduce early preterm birth and fetal loss more effectively than a low vaginal cerclage in women with a previous failed cerclage. More obstetricians and gynecologists need to be trained on how to perform the transabdominal cerclage procedure to increase its availability to suitable women. This procedure is technically straightforward and can be taught via video, which can easily be shared among clinicians at a low cost.

Quantitative fetal fibronectin screening in asymptomatic high-risk patients and the spectrum of risk for recurrent preterm delivery.

OBJECTIVE: We sought to determine whether a single quantitative vaginal fetal fibronectin (fFN) test at 24 weeks' gestational age (GA) can delineate the spectrum of risk of spontaneous preterm delivery (sPTD) in an asymptomatic high-risk population comprised of patients with a prior preterm birth. STUDY DESIGN: We performed a secondary analysis of a prospectively collected dataset in asymptomatic patients at high risk with singleton gestations who underwent quantitative fFN screening at 24 weeks. Data from 563 women with a history of preterm delivery (PTD) were available. The association between quantitative fFN concentrations collected at 24 weeks and subsequent GA at delivery was analyzed. RESULTS: The overall PTD rate < 34 weeks and < 37 weeks was 6.7% and 19.7%, respectively. In all, 497 of 563 patients (88%) at 24 weeks had an fFN level of 0 ng/mL. As the fFN concentrations increased, sPTD rates progressively increased. Compared with the fFN 0 ng/mL group, the relative risk for sPTD < 34 weeks was sequentially increased in each group, respectively: 2.42 (fFN 1-49 ng/mL; 95% confidence interval [CI], 0.76-5.66), 4.68 (fFN 50-199 ng/mL; 95% CI, 1.28-10.95), and 9.94 (fFN > 200 ng/mL; 95% CI, 2.90-19.67). Similar trends were seen between groups at different GAs from 32-37 weeks. CONCLUSION: In asymptomatic women with a prior PTD, quantitative fFN assessment at 24 weeks effectively delineates the risk of recurrent sPTD. Quantification of fFN may provide additional information regarding the spectrum of risk of subsequent sPTD than would be derived from the standard qualitative screen currently used.

How Do Home and Clinic Blood Pressure Readings Compare in Pregnancy?

Hypertensive disorders during pregnancy result in substantial maternal morbidity and are a leading cause of maternal deaths worldwide. Self-monitoring of blood pressure (BP) might improve the detection and management of hypertensive disorders of pregnancy, but few data are available, including regarding appropriate thresholds. This systematic review and individual patient data analysis aimed to assess the current evidence on differences between clinic and self-monitored BP through pregnancy. MEDLINE and 10 other electronic databases were searched for articles published up to and including July 2016 using a strategy designed to capture all the literature on self-monitoring of BP during pregnancy. Investigators of included studies were contacted requesting individual patient data: self-monitored and clinic BP and demographic data. Twenty-one studies that utilized self-monitoring of BP during pregnancy were identified. Individual patient data from self-monitored and clinic readings were available from 7 plus 1 unpublished articles (8 studies; n=758) and 2 further studies published summary data. Analysis revealed a mean self-monitoring clinic difference of ≤1.2 mm Hg systolic BP throughout pregnancy although there was significant heterogeneity (difference in means, I2 >80% throughout pregnancy). Although the overall population difference was small, levels of white coat hypertension were high, particularly toward the end of pregnancy. The available literature includes no evidence of a systematic difference between self and clinic readings, suggesting that appropriate treatment and diagnostic thresholds for self-monitoring during pregnancy would be equivalent to standard clinic thresholds.

Quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 1: Individual participant data meta-analysis and health economic analysis.

INTRODUCTION: The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (qfFN) concentration, in combination with clinical risk factors. METHODS AND ANALYSIS: The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts) which quantifies fFN in a vaginal swab. In part 1 of the study, we will develop and internally validate a prognostic model using an individual participant data (IPD) meta-analysis of existing studies containing women with symptoms of preterm labour alongside fFN measurements and pregnancy outcome. An economic analysis will be undertaken to assess potential cost-effectiveness of the qfFN prognostic model. The primary endpoint will be the ability of the prognostic model to rule out spontaneous preterm birth within 7 days. Six eligible studies were identified by systematic review of the literature and five agreed to provide their IPD (n=5 studies, 1783 women and 139 events of preterm delivery within 7 days of testing). ETHICS AND DISSEMINATION: The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). PROSPERO REGISTRATION NUMBER: CRD42015027590. VERSION: Protocol version 2, date 1 November 2016.

Study protocol: quantitative fibronectin to help decision-making in women with symptoms of preterm labour (QUIDS) part 2, UK Prospective Cohort Study.

INTRODUCTION: The aim of the QUIDS study is to develop a decision support tool for the management of women with symptoms and signs of preterm labour, based on a validated prognostic model using quantitative fetal fibronectin (fFN) concentration, in combination with clinical risk factors. METHODS AND ANALYSIS: The study will evaluate the Rapid fFN 10Q System (Hologic, Marlborough, Massachusetts, USA) which quantifies fFN in a vaginal swab. In QUIDS part 2, we will perform a prospective cohort study in at least eight UK consultant-led maternity units, in women with symptoms of preterm labour at 22+0 to 34+6 weeks gestation to externally validate a prognostic model developed in QUIDS part 1. The effects of quantitative fFN on anxiety will be assessed, and acceptability of the test and prognostic model will be evaluated in a subgroup of women and clinicians (n=30). The sample size is 1600 women (with estimated 96-192 events of preterm delivery within 7 days of testing). Clinicians will be informed of the qualitative fFN result (positive/negative) but be blinded to quantitative fFN result. Research midwives will collect outcome data from the maternal and neonatal clinical records. The final validated prognostic model will be presented as a mobile or web-based application. ETHICS AND DISSEMINATION: The study is funded by the National Institute of Healthcare Research Health Technology Assessment (HTA 14/32/01). It has been approved by the West of Scotland Research Ethics Committee (16/WS/0068). VERSION: Protocol V.2, Date 1 November 2016. TRIAL REGISTRATION NUMBER: ISRCTN 41598423andCPMS: 31277.

Cerclage position, cervical length and preterm delivery in women undergoing ultrasound indicated cervical cerclage: A retrospective cohort study.

OBJECTIVE: The objectives were to assess whether anatomical location of ultrasound (USS) indicated cervical cerclage and/or the degree of cervical shortening (cervical length; CL) prior to and following cerclage affects the risk of preterm birth (PTB). METHOD: A retrospective cohort study of 179 women receiving cerclage for short cervix (≤25mm) was performed. Demographic data, CL before and after cerclage insertion, height of cerclage (distance from external os) and gestation at delivery were collected. Relative risk (RR) and odds ratio (OR) of preterm delivery were calculated according to the anatomical location of the cerclage within the cervix and the CL before and after cerclage as categorical and continuous variables. Partition tree analysis was used to identify the threshold cerclage height that best predicts PTB. RESULTS: 25% (n = 45) delivered <34 weeks and 36% (n = 65) delivered <37 weeks. Risk of PTB was greater with cerclage in the distal 10mm (RR2.37, 95% CI 1.45-3.87) or the distal half of a closed cervix (RR2.16, 95% CI 1.45-3.87). Increasing absolute cerclage height was associated with a reduction in PTB (OR 0.87, 95% CI 0.82-0.94). A cerclage height <14.5 mm best predicts PTB (70.8%). Increasing CL following cerclage was associated with a reduction in PTB (OR0.87, 95% CI 0.82-0.94). Conversely, the risk of PTB was increased where CL remained static or shortened further following cerclage (RR2.34, 95% CI 1.04-5.25). CONCLUSION: The higher a cerclage was placed within a shortened cervix, the lower the subsequent odds of PTB. Women whose cerclage is placed in the distal 10mm of closed cervix or whose cervix fails to elongate subsequently, should remain under close surveillance as they have the highest risk of PTB.

The vaginal microbiome during pregnancy and the postpartum period in a European population.

The composition and structure of the pregnancy vaginal microbiome may influence susceptibility to adverse pregnancy outcomes. Studies on the pregnant vaginal microbiome have largely been limited to Northern American populations. Using MiSeq sequencing of 16S rRNA gene amplicons, we characterised the vaginal microbiota of a mixed British cohort of women (n = 42) who experienced uncomplicated term delivery and who were sampled longitudinally throughout pregnancy (8-12, 20-22, 28-30 and 34-36 weeks gestation) and 6 weeks postpartum. We show that vaginal microbiome composition dramatically changes postpartum to become less Lactobacillus spp. dominant with increased alpha-diversity irrespective of the community structure during pregnancy and independent of ethnicity. While the pregnancy vaginal microbiome was characteristically dominated by Lactobacillus spp. and low alpha-diversity, unlike Northern American populations, a significant number of pregnant women this British population had a L. jensenii-dominated microbiome characterised by low alpha-diversity. L. jensenii was predominantly observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples from Black women. This study reveals new insights into biogeographical and ethnic effects upon the pregnancy and postpartum vaginal microbiome and has important implications for future studies exploring relationships between the vaginal microbiome, host health and pregnancy outcomes.

Raised trappin2/elafin protein in cervico-vaginal fluid is a potential predictor of cervical shortening and spontaneous preterm birth.

Early spontaneous preterm birth is associated with inflammation/infection and shortening of the cervix. We hypothesised that cervico-vaginal production of trappin2/elafin (peptidase inhibitor 3) and cathelicidin antimicrobial peptide (cathelicidin), key components of the innate immune system, are altered in women who have a spontaneous preterm birth. The aim was to determine the relationship between cervico-vaginal fluid (CVF) trappin2/elafin and cathelicidin protein concentrations with cervical length in woman at risk of spontaneous preterm birth. Trappin2/elafin and cathelicidin were measured using ELISA in longitudinal CVF samples (taken between 13 to 30 weeks' gestation) from 74 asymptomatic high risk women (based on obstetric history) recruited prospectively. Thirty six women developed a short cervix (<25 mm) by 24 weeks' and 38 women did not. Women who developed a short cervix had 2.71 times higher concentrations of CVF trappin2/elafin from 14 weeks' versus those who did not (CI 1.94-3.79, p<0.0005). CVF trappin2/elafin before 24 weeks' was 1.79 times higher in women who had a spontaneous preterm birth <37 weeks' (CI: 1.05-3.05, p = 0.034). Trappin2/elafin (>200 ng/ml) measured between 14+0-14+6 weeks' of pregnancy predicted women who subsequently developed a short cervix (n = 11, ROC area = 1.00, p = 0.008) within 8 weeks. Cathelicidin was not predictive of spontaneous delivery. Vitamin D status did not correlate with CVF antimicrobial peptide concentrations. Raised CVF trappin2/elafin has potential as an early pregnancy test for prediction of cervical shortening and spontaneous preterm birth. This justifies validation in a larger cohort.