Jenny Carter

Quantitative Fetal Fibronectin to Predict Preterm Birth in Asymptomatic Women at High Risk

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

Development and validation of a tool incorporating cervical length and quantitative fetal fibronectin to predict spontaneous preterm birth in asymptomatic high‐risk women

To develop a predictive tool for spontaneous preterm birth (sPTB) in asymptomatic high‐risk women that includes quantification of fetal fibronectin (fFN) along with cervical length (CL) measurement and other clinical factors.

Development and validation of a predictive tool for spontaneous preterm birth incorporating cervical length and quantitative fetal fibronectin in asymptomatic high‐risk women

To develop a predictive tool for spontaneous preterm birth (sPTB) in asymptomatic high‐risk women that includes quantification of fetal fibronectin (fFN) along with cervical length (CL) measurement and other clinical factors.

Prospective cohort study investigating the reliability of the AmnioSense™ method for detection of spontaneous rupture of membranes

Objectiveu2002 This study investigated the reliability, sensitivity and specificity of a commercially available absorbent pad, AmnioSense™, compared with speculum examination for detection of spontaneous ruptured membranes (SRM).

Prior ultrasound-indicated cerclage: how should we manage the next pregnancy?

OBJECTIVEnTo determine the subsequent need for cerclage and pregnancy outcome, in women with a prior ultrasound-indicated cerclage.nnnSTUDY DESIGNnAnalysis of a prospectively collected database from November 2010 to July 2014 from 15 Preterm Surveillance clinics across the UK was performed. Women with an index and previous singleton pregnancy with an ultrasound-indicated cerclage were eligible for inclusion (n=55). Previous ultrasound-indicated cerclage was defined as cerclage inserted prior to 24 weeks for cervical length <25 mm as detected by transvaginal ultrasound. Women were managed in their subsequent pregnancy with either history-indicated cerclage, transvaginal ultrasound surveillance of cervical length with cerclage if <25 mm or transabdominal cerclage at the discretion of the physician. Exact logistic regression was used to estimate the odds ratio on the chance of delivery before 34 weeks. Adjustments were made for major risk factors for prematurity: previous spontaneous preterm birth, previous late miscarriage (16+0 to 23+6 weeks) and previous cervical surgery; both individually and in combination.nnnRESULTSnOf the 55 eligible women, 23 underwent history-indicated cerclage, 23 underwent transvaginal ultrasound cervical length surveillance and 8 underwent abdominal cerclage in the index pregnancy. Of those that had ultrasound surveillance, 13 (57%) did not require cerclage and all delivered after 34 weeks. Of those that had a history-indicated cerclage, six delivered before 34 weeks. Therefore, women that received a history-indicated cerclage had greater risk of preterm birth compared to women that underwent ultrasound surveillance with cerclage insertion only if cervical shortening was detected (OR 0.09 95% CI 0.00-0.74, p=0.02). Adjustments for risk factors for preterm birth did not significantly affect this risk.nnnCONCLUSIONnIn women with prior ultrasound-indicated cerclage, who undergo cervical surveillance in the next pregnancy, the majority will not require intervention for a short cervix. Those women receiving a history-indicated vaginal cerclage were more likely to deliver preterm; this cannot be explained by their risk status. All women receiving an abdominal elective cerclage had good outcomes. Ultrasound surveillance is appropriate in women with a prior ultrasound-indicated cerclage who do not require an abdominal cerclage.

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

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

What is the impact of preconception abdominal cerclage on fertility: evidence from a randomized controlled trial

There is documented concern that cerclage may cause cervical stenosis or changes to the cervical mucus, which may reduce fertility. The aim of this study is to determine whether placement of a preconception abdominal cerclage affects fertility.

Full dilation cesarean section: a risk factor for recurrent second‐trimester loss and preterm birth

A previous cesarean section at full dilation (FDCS) is a risk factor for preterm birth. To provide insight into the risk to subsequent pregnancies, this cohort study compares the outcomes of pregnant women with a previous preterm birth associated with either a prior FDCS or a prior term vaginal delivery.

Clinical utility of quantitative fetal fibronectin in preterm labour

The consequences of preterm birth continue to devastate lives. The article by Bruijn et al. is welcome because it informs us of exciting developments surrounding the prediction of preterm birth. Prediction is a necessary prerequisite for targeting interventions to enhance clinical efficiency. Bruijn et al. performed a retrospective analysis on frozen fFN samples from 350 symptomatic women with a short cervix (<30 mm), demonstrating that as quantitative fFN (qfFN) increases, the risk of delivery within 7 days escalates (23-fold with levels >500 ng/ml). The data show synergy when combining cervical length (CL) and qfFN, and provide additional clinical information from the previous qualitative positive/negative test. The challenge is whether this can help shape clinical decision-making in threatened preterm labour. The investigators set out to test the hypothesis that using combined qfFN and CL could allow triage of women to low risk (<5% delivery in 7 days). Some women were reclassified using complex modelling but it is not surprising that discrimination into very low risk was not substantial, as this was already a high-risk cohort preselected by short cervix. Their modelling belies the true value of qfFN: like any continuous variable there is an improvement in specificity, ‘rule in’ and PPV as the threshold increases, and conversely ‘rule out’ as it decreases, allowing the clinician to use different thresholds depending on clinical utility. Clinical decisions are not dichotomised into low or high risk but are likely to vary across the risk range. Risk/benefit varies both with the specific intervention and the gestational age at which it is carried out, as does certainty of benefit and costeffectiveness. A calculated risk <5% ie. ‘low risk’ would guide a more conservative approach. However while all patients above this cut off would be considered ‘high risk’, use of steroids, tocolysis, in utero transfer and magnesium sulphate is unlikely to be uniform across the risk range. It may be reasonable not to transfer women with a very short cervix (<5 mm) but low qfFN (<10 ng/ml) (0% risk of delivery <7 days in their cohort), while instigate most interventions if high fFN (100% risk if >200 ng/ml). Conversely, in the longer cervix (>20 mm) 55% delivered in a week if >500 ng/ml, and therefore management could be targeted. The synergistic value of qfFN and CL has been described in a large asymptomatic high-risk cohort (n =1249), neatly presented in an app for widespread use (Kuhrt et al. Ultrasound Obstet Gynecol 2015;10.1002). Although Bruijn et al. routinely used CL and modelled qFFN post-hoc, it is important to remember that many units will not have routine access to cervical length screening, especially for symptomatic patients presenting out of hours. Independent of CL, qfFN performed well within this dataset and in some units this may prove to be the more cost-effective screening tool, without requirement for scanning skills. This is well described in symptomatic women (Abbott et al. Am J Obstet Gynecol 2013;208:122). Predictive models are becoming more sophisticated. The onus is now on clinicians to evaluate whether this improved prediction can impact on patient care, and to establish the correct clinical pathways.

The Preterm Clinical Network (PCN) Database: a web-based systematic method of collecting data on the care of women at risk of preterm birth

BackgroundDespite much research effort, there is a paucity of conclusive evidence in the field of preterm birth prediction and prevention. The methods of monitoring and prevention strategies offered to women at risk vary considerably around the UK and depend on local maternity care provision. It is becoming increasingly recognised that this experience and knowledge, if captured on a larger scale, could be a utilized as a valuable source of evidence for others. The UK Preterm Clinical Network (UKPCN) was established with the aim of improving care and outcomes for women at risk of preterm birth through the sharing of a wealth of experience and knowledge, as well as the building of clinical and research collaboration. The design and development of a bespoke internet-based database was fundamental to achieving this aim.MethodFollowing consultation with UKPCN members and agreement on a minimal dataset, the Preterm Clinical Network (PCN) Database was constructed to collect data from women at risk of preterm birth and their children. Information Governance and research ethics committee approval was given for the storage of historical as well as prospectively collected data. Collaborating centres have instant access to their own records, while use of pooled data is governed by the PCN Database Access Committee. Applications are welcomed from UKPCN members and other established research groups. The results of investigations using the data are expected to provide insights into the effectiveness of current surveillance practices and preterm birth interventions on a national and international scale, as well as the generation of ideas for innovation and research. To date, 31 sites are registered as Data Collection Centres, four of which are outside the UK.ConclusionThis paper outlines the aims of the PCN Database along with the development process undertaken from the initial idea to live launch.