Oral Presentations

A toolkit to facilitate community Kangaroo Mother Care (CKMC) practice in Low and Middle-income countries (LMIC).

OR27

Authors

Parris Kerry, Ramokolo Vundli, Gillespie Bronwen, Salam Shumona, Rhoda Natasha, Anumba Dilly

Presented by

Siobhán Gillespie

Affiliations

PRIME member

Background

The United Nations Sustainable Development Goals (SDGs) aim to reduce neonatal mortality rates. KMC has been identified as a significant low-cost intervention to mitigate the effects of preterm birth, though practice remains sporadic in LMICs. Work is ongoing to promote practice in healthcare facilities, however 80% of babies in LMICs are born at home. Action is necessary to protect, promote and support CKMC as a key intervention towards achieving the SDGs.

The aim is to produce a toolkit that facilitates the implementation of CKMC in LMICs, by empowering local healthcare providers to identify local influencing factors.

Method

The toolkit consists of three elements;
– A resource pack containing a report on the evidence base for CKMC, a driver diagram providing a visual display of the factors that influence CKMC & the change ideas that promote successful practice, & a ‘framework for practice’, a practical guide highlighting the factors to consider when implementing CKMC & potential actions needed. This framework for practice contains case studies, poses questions to consider, suggests levels of achievable standards & is adaptable for local contexts.
– Video training resources on KMC, primary drivers influencing CKMC & guidance on how to use the resource pack.
– A CKMC board game for staff, to support the discussion on CKMC implementation & involve ward & community based KMC staff in a less formal setting.

Results

The toolkit will be available as hard copy, or online. It is aimed at nursing management level, but also encourages the involvement of ward & community based KMC staff so ideas are pragmatic & feasible. Local staff will be able to use this toolkit, or elements of it, to identify local influences on the implementation of CKMC & changes that need to be employed in order to address these influences & achieve successful. and embedded practice.

Conclusion

This toolkit enables implementation staff to develop an action plan according to the context of their community & local specific factors that influence practice. The result is an achievable implementation strategy that is successful in promoting CKMC practice.

Advanced MRI parameters to assess normal and pathological lung development in utero: a pilot study

OR6

Authors

Jana Hutter, Alena Uus, Anna Milan, Mary Rutherford, Anne Greenough, Lisa Story

Presented by

Carla Avena-Zampieri

Affiliations

King’s College London St Thomas Hospital (GSTT)

Background

Preterm birth can be associated with significant respiratory sequelae including pulmonary hypoplasia and bronchopulmonary dysplasia particularly when delivery is very preterm, before 32 weeks gestation. In clinical practice, antenatal assessment of pulmonary development is via 2D assessments of lung size or basic volumetry acquired either by ultrasound or MRI. These have been extensively studied as a prognostic marker for adverse neonatal outcomes in fetuses with congenital diaphragmatic hernia but have shown to be less useful for predicting outcome in fetuses at high-risk of preterm birth or with preterm premature rupture of membranes. Moreover, previous measures do not provide any functional information regarding pulmonary development. The advent of advanced MRI techniques, such as motion-corrected T2* relaxometry and diffusion imaging can provide additional information, potentially reflecting tissue perfusion and microstructure. This pilot study aims to apply advanced MRI techniques to characterise normal in-utero pulmonary development across gestation and compare findings in fetuses that subsequently deliver preterm.

Method

Data was retrospectively selected from existing MRI datasets from uncomplicated pregnancies that subsequently delivered at term and a group at high-risk of preterm birth that delivered before 32 weeks (imaged at 20-32 weeks’ gestation). All subjects underwent T2 weighted anatomical imaging, Multi-echo imaging for T2* mapping and diffusion-weighted imaging on a clinical 3T MR scanner. Datasets were post-processed following in-house-developed pipelines performing motion correction using ants, T2* mapping and ADC mapping using mono-exponential decay fitting and Deformable Slice to Volume Reconstruction. Regions of interest containing the lung tissue avoiding the vasculature were manually/automated segmented on the resulting images to generate lung volumes and mean pulmonary T2* values. Statistical analysis was performed using multiple regression, to account for the effects of gestation, and student t-test in SPSS.

Results

Sixteen datasets from uncomplicated pregnancies that delivered at term and 11 from pregnancies that delivered before 32 weeks were analysed.
Mean gestation at MRI of the control group was 27.4 (SD± 3.6) and was 25.6 (SD± 3.1) for the preterm group and mean gestation at delivery (p<0.0001) was respectively 40 (SD± 1.7) for the control and 27.9 (SD± 2.6) for the preterm group. In the control population pulmonary volumes increased between 20 and 32 weeks gestation while mean pulmonary ADC and T2* values appeared constant. There was no difference in mean T2* values or ADC values between fetuses that delivered at term and those that delivered preterm but pulmonary volumes were found to be lower within the preterm cohort.

Conclusion

Our findings of a reduction in pulmonary volume in fetuses that subsequently delivered preterm are in line with our previous work. In contrast to studies from other research groups, we did not find an increase in ADC values with increasing gestational age which may indicate alveolar complexity. This may be due to a different GA range studied or differences in field strength used.
We did find a reduction in T2* values in fetuses that subsequently delivered preterm compared to controls in our previous analysis of the data which may reflect a reduction in metabolic activity of the tissue. This could not be observed here due to the nature of the files the lung masks were segmented on, and the amount of motion still present after reconstruction.
Further work is required to study the influence of vasculature on T2* values during lung maturation and examine the connection with the ADC values obtained. Additional datasets are being analysed to explore these relationships in more detail and correlate findings with specific findings with neonates that experience respiratory sequelae.

Amniotic Fluid Sludge on Transvaginal Ultrasound and its Relationship to fFN and Preterm Birth

OR11

Authors

Eve Webley, Dr Natalie Suff, Dr Megan Hall, Dr Manju Chandirimani and Prof Andrew Shennan

Presented by

Eve Webley

Affiliations

Department of Women’s and Children’s Health, King’s College London, St Thomas’ Hospital

Background

Preterm birth (PTB) is the leading cause of global under five mortality, however predicting delivery and outcome is notoriously difficult. Currently used clinical biomarkers include cervical length (CL) and fetal fibronectin (fFN). Amniotic fluid sludge (AFS), thought to indicate intra-amniotic infection, has recently been investigated as a possible biomarker of PTB risk. Chorioamnionitis and poorer neonatal outcomes are strongly related to reduced gestational age, therefore improved prediction of PTB may facilitate an improvement in early neonatal care.

This study aims to analyse whether the presence of AFS correlates with fFN levels, PTB risk and early neonatal outcomes. It is hypothesised that women presenting with AFS will have increased fFN levels and increased risk of PTB. Furthermore, it is theorised that there will be a reduction in neonatal birthweight and increase in NICU admission in infants born to women presenting with AFS.

Method

A retrospective cohort study analysing the effects of AFS presence on PTB risk in high-risk asymptomatic women with a short (<25mm) cervical length (CL) at St Thomas’ hospital, London. AFS was detected through transvaginal ultrasound scans and quantitative fFN measured using a Hologic 10qi system.

Results

147 women with short CL were identified, 54 of whom presented with AFS. Presence of AFS was associated with reduced CL (14.06mm vs 19.39mm, p < 0.0001) and increased fFN (125.3ng/ml vs 55.39ng/ml, p = 0.038). Women presenting with AFS were also at increased risk of delivery <24 gestational weeks (17% vs 4.2% p = 0.0156) and delivered infants with a reduced mean gestational birthweight (2439g vs 2786g, p = 0.0188). However, women presenting with AFS were not significantly more likely to deliver before 34 (30% vs 19%, p = 0.1621) or 37 gestational weeks (37% vs 33%, p = 0.5886). The rates of NICU admission (22% vs 17%, p >0.999) and mean Apgar scores at five minutes (8.68 vs 8.75, p = 0.6228) were similar between infants born to women with and without AFS at all gestations. Logistic regression analysis further concluded that AFS presence was not independently associated with increased risk of PTB 24+0-36+6 weeks (aOR = 0.7710).

Conclusion

In our cohort of high-risk asymptomatic women with short CL, the presence of AFS is associated with increased fFN levels and risk of extremely premature delivery. However, the addition of AFS to currently used clinical biomarkers does not improve the prediction of PTB <37 weeks or appear to influence early neonatal outcomes.

Antenatal corticosteroid use in women with gestational diabetes and preterm birth: a cohort study in Scotland’s largest obstetric unit

OR25

Authors

Sarah Clunie, Emily M Frier, Niamh Mclennan, Sarah J Stock, Rebecca M Reynolds

Presented by

Sarah Clunie

Affiliations

Sarah Clunie: Year 6 Medical student, University of Edinburgh, Chancellor’s Building, 49 Little France Crescent, Edinburgh, EH16 4SB Emily M Frier & Niamh Mclennan: Clinical Research Fellow in Obstetrics & Gynaecology, MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ. Corresponding author email: Emily.Frier@ed.ac.uk Sarah J Stock: Wellcome Trust Clinical Career Development Fellow, Reader and Honorary Consultant Maternal and Fetal Medicine, Usher Institute, University of Edinburgh, NINE Edinburgh BioQuarter, 9 Little France Road, Edinburgh, EH16 4UX Rebecca M Reynolds: Professor of Metabolic Medicine, Centre for Cardiovascular Science, Queen’s Medical Research Institute, Edinburgh, EH16 4TJ

Background

Antenatal corticosteroids (ACS) are recommended for women at risk of imminent preterm birth (PTB), to reduce risk of adverse neonatal outcomes. Corticosteroids impair maternal glucose tolerance; administration of ACS to women with diabetes poses risks. Limited evidence exists regarding ACS use in pregnancies complicated by gestational diabetes mellitus (GDM). We aimed to evaluate ACS use in women with GDM with PTB and to determine the association of ACS exposure with neonatal and maternal outcomes.

Method

65 women with singleton pregnancies and GDM, with PTB between January 2016 and December 2019, were identified from a local database at the Royal Infirmary of Edinburgh. Maternal, neonatal, and ACS data were collected retrospectively from electronic records. Statistical analysis was performed in R studio.

Results

Mean (SD) maternal age and BMI were 32.6 (5.2) years, and 32.6 (8.1) kg/m2, respectively. 37% (24/65) of women were managed with diet alone, while 63% required both metformin and insulin.

Table 1 presents ACS exposure rates, and requirement for Variable Rate Insulin Infusion (VRII). Of 15 women with late PTB who received ACS, 60% received ACS at 35 weeks or later (n=9). 65% of women commenced VRII after ACS exposure (n=20/31), over half of whom had previously been managed by diet or metformin alone (n=11).

On unadjusted analysis, compared to non-exposure, ACS exposure was not associated with a reduction in respiratory distress syndrome (RDS) (8/31 ACS-exposed babies with RDS, 5/34 unexposed babies with RDS, Relative Risk (RR) 1.7, 95% Confidence interval (CI) 0.64-4.8), but was associated with statistically significant increased neonatal unit admission rates (22/31 ACS-exposed babies admitted, 10/34 unexposed babies admitted, RR 2.4, 95%CI 1.37-4.26).

Conclusion

Rates of ACS exposure in GDM with PTB were high in women who gave birth before 35 weeks, in keeping with national guidance. Guidelines do not recommend routine use of ACS beyond 35 weeks’ gestation. This study illustrates the complexities of ACS use in women with GDM, and questions the risk-benefit ratio of ACS in this population. Sample size was small, and results are likely to have been influenced by multiple confounding factors, including indication for ACS.

Our findings outline the uncertainty surrounding the safety of ACS in GDM pregnancies. Larger studies, which include long-term follow up, are required to determine appropriate use of ACS in this complex population.

Asymptomatic women with preterm birth have rising cervicovaginal CXCL10 across mid-trimester

OR12

Authors

Maria D. Papageorgiou, Emmanuel Amabebe, Dilly O.C. Anumba

Presented by

Emmanuel Amabebe

Affiliations

Department of Oncology and Metabolism, University of Sheffield, UK

Background

The CXCR3 receptor chemokines (CXCL9, CXCL10 and CXCL11) are often implicated in chronic placental inflammation (CPI) associated with spontaneous preterm birth (sPTB). Overexpression of these and other chemocytokines in the cervicovaginal space may be indicative of chronic subclinical inflammation and risk of sPTB similar to their role in CPI. Hence, we measured the concentrations of CXCL9, CXCL10, CXCL11, TNF-α, Eotaxin and TNFR1 in cervicovaginal fluid (CVF) of asymptomatic pregnant women across mid-trimester and determined the ability of these chemocytokines to predict risk of sPTB before 37 weeks’ gestation.

Method

CVF samples were collected from 51 asymptomatic high risk pregnant women at two gestational time points (GTPs): GTP1 – 20+0–22+6 weeks, n=51, preterm=17, term=34; and GTP2 – 26+0–28+6 weeks, n=45, preterm=14, term=31. Concentrations of chemocytokines were quantified by multiplexed bead-based immunoassay (Cytometric Bead Array, CBA), while fetal fibronectin (fFN) concentration was determined by 10Q Rapid analysis. The GTP1/GTP2 ratios of cytokines and fFN concentrations were compared between preterm- and term-delivered women using area under the Receiver Operating Characteristics curves (AUC) to predict risk of sPTB.

Results

Four (23%) of the preterm women experienced preterm prelabour rupture of membranes. None of the measured cytokines differed between the groups at GTP1. At GTP2, only TNFR1 was higher in the term compared to preterm women (p=.049) and distinguished both groups (AUC=.88, p=.005, n=12). However, when expressed as a ratio of GTP1/GTP2, only CXCL10 was higher in the preterm than term women and was predictive of sPTB (AUC=.68, p=.044, n=45). Combination of the ratios of CXCL10 and fFN improved sPTB prediction (AUC=.74, p=.007). The concentrations of CXCL11, TNF-α, Eotaxin (in all samples) and TNFR1 (in some samples) could not be determined as they were either below or above the detection limit of the CBA.

Conclusion

These findings suggest increasing CVF CXCL10 with gestation in preterm women may indicate a chronic subclinical inflammation of gestational tissues that increase the risk of sPTB. If confirmed in larger cohort studies, early estimation of CVF CXCL10 alone or in combination with fFN may identify the risk of inflammation-associated sPTB in asymptomatic women and guide preventive and/or therapeutic interventions.

Cerclage, pessary or progesterone to prevent preterm birth in women with prior cervical surgery

OR5

Authors

Angharad Care, Andrew Sharp

Presented by

Faye Platt

Affiliations

University of Liverpool

Background

Women with previous cervical surgery to treat moderate-severe cervical intraepithelial neoplasia are at an increased risk of preterm birth (PTB). PTB is the leading cause of neonatal morbidity and mortality. There are a lack of studies comparing the efficacy of vaginal cerclage, Arabin pessary and vaginal progesterone to prevent PTB in this cohort.

Method

This is a retrospective cohort study of all women attending the specialist PTB clinic at Liverpool Women’s hospital between 2008-2020, with a previous history of either a knife cone biopsy (KCB) or a large loop excision of the transformation zone (LLETZ). Exclusions included trachelectomy, laser procedures, transabdominal cerclage, subsequent pregnancies of the same participant and those missing data. Initial analyses were performed using Chi-squared and one-way ANOVA tests as appropriate in IBM SPSS statistics (Version 26). Univariable and multivariable generalised linear models were then used to determine the impact of clinical factors on each outcome. Separate models were performed for those with and without a previous PTB. All univariable and multivariable analyses were performed in R (version 3).

Results

A total of 441 women were included in the multivariable analysis which demonstrated no statistically significant association between vaginal cerclage (n = 18) or Arabin pessary (n = 48) and gestation time. Progesterone (n = 57) was associated with a decreased gestation time (Est -3.15 (1.059); p-value 0.004) in women with a previous PTB, there was no association in women without a previous PTB.

Conclusion

Interventions to prevent PTB including vaginal cerclage, Arabin pessary and vaginal progesterone that are effective in other high-risk cohorts do not appear to present the same efficacy in women with prior cervical surgery. A large multi-centre randomised controlled study is required to confirm these findings.

Characterising The Cervicovaginal Fluid Metabolite Profiles At 20 – 28 Weeks Gestation Associated With Subsequent Preterm Delivery

OR20

Authors

Megan Cavanagh, Emmanuel Amabebe, Neha S. Kulkarni, Dilly O.C. Anumba

Presented by

Megan Cavanagh

Affiliations

Department of Oncology and Metabolism, University of Sheffield, UK

Background

Vaginal dysbiosis is associated with spontaneous preterm birth (sPTB <37 weeks’ gestation). Metabolite profiling of cervicovaginal (CV) fluid can provide valuable information on host-microbiome interactions. In this study, we characterised the CV metabolome of asymptomatic women with and without sPTB across the second trimester and analysed their associated metabolic pathways, in order to better understand the pathomechanism of sPTB and improve risk stratification.

Method

CV fluid was collected from asymptomatic high-risk pregnant women at two gestational time points (GTPs): GTP1 (20+0–22+6 weeks) n=49, preterm=17, term=32; and GTP2 (26+0–28+6 weeks) n=44, preterm=13, term=31. Samples were eluted in phosphate buffered saline and the aqueous fraction was analysed by Electrospray Ionization Time-of-Flight Mass Spectrometry (Waters Acquity UPLC coupled to a Waters Synapt G2-Si TOF MS). Differences in normalised % total ion count of metabolites between the groups were analysed using the Omu metabolomics analysis R package.

Results

We identified a total of 1842 metabolites, of these, 54 differed from GTP1 to GTP2. At GTP1 20 metabolites differed in term vs preterm. Notably, xanthosine, xanthotoxin, acacetin, athamantin, phloretin, methylglyoxal, urocanate and deoxythymidine monophosphate were higher in the preterm women. At GTP2 9 metabolites differed in term vs preterm. Notably, androsterone, dhurrin, palmitate, pantetheine and zierin were higher in the preterm women. Using an Anova, 18 metabolites were significantly different between all groups. Notably, in preterm women, putrescine, pyruvate and pantothenate significantly increased from GTP1 to GTP2. Pathway analysis showed enriched pathways with an impact score of ≥0.1 in term vs preterm. Specifically, pathways enriched were: glycolysis/gluconeogenesis, inositol phosphate metabolism, ubiquinone terpenoid-quinone in GTP1 and glycolysis/gluconeogenesis arachidonic acid in GTP2.

Conclusion

These findings demonstrate that the CV metabolome transitions throughout the second trimester before symptoms of sPTB appear. Infection-associated metabolites that significantly differ in women with sPTB such as putrescine and pyruvate could be utilised to improve risk stratification in future studies.

Differential Response of Gestational Tissues to TLR3 Viral Priming Prior to Exposure to Bacterial TLR2 and TLR2/6 Agonists

OR19

Authors

Zahirrah B. M. Rasheed1,2, Yun S. Lee1,3, Sung H. Kim1,3, Ranjit K. Rai 1 , Camino S. M. Ruano1,4, Eberechi Anucha1 , Mark H. F. Sullivan1 , David A. MacIntyre1,3 , Phillip R. Bennett 1,3 and Lynne Sykes 1,3

Presented by

Lynne Sykes

Affiliations

1 Imperial College Parturition Research Group, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom, 2 Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia, 3 March of Dimes European Preterm Birth Research Centre, Imperial College London, London, United Kingdom, 4INSERM U1016 Institut Cochin, Paris, France

Background

Infection/inflammation is an important causal factor in spontaneous preterm birth (sPTB). Most mechanistic studies have concentrated on the role of bacteria, with limited focus on the role of viruses in sPTB. Murine studies support a potential multi-pathogen aetiology in which a double or sequential hit of both viral and bacterial pathogens leads to a higher risk preterm labour. This study aimed to determine the effect of viral priming on bacterial induced inflammation in human in vitro models of ascending and haematogenous infection.

Method

Vaginal epithelial cells, and primary amnion epithelial cells and myocytes were used to represent cell targets of ascending infection while interactions between peripheral blood mononuclear cells (PBMCs) and placental explants were used to model systemic infection. To model the effect of viral priming upon the subsequent response to bacterial stimuli, each cell type was stimulated first with a TLR3 viral agonist, and then with either a TLR2 or TLR2/6 agonist, and responses compared to those of each agonist alone. Immunoblotting was used to detect cellular NF-κB, AP-1, and IRF-3 activation. Cellular TLR3, TLR2, and TLR6 mRNA was quantified by RT-qPCR. Immunoassays were used to measure supernatant cytokine, chemokine and PGE2 concentrations.

Results

TLR3 (“viral”) priming prior to TLR2/6 agonist (“bacterial”) exposure augmented the pro-inflammatory, pro-labour response in VECs, AECs, myocytes and PBMCs when compared to the effects of agonists alone. In contrast, enhanced anti-inflammatory cytokine production (IL-10) was observed in placental explants. Culturing placental explants in conditioned media derived from PBMCs primed with a TLR3 agonist enhanced TLR2/6 agonist stimulated production of IL-6 and IL-8, suggesting a differential response by the placenta to systemic inflammation compared to direct infection as a result of haematogenous spread. TLR3 agonism generally caused increased mRNA expression of TLR3 and TLR2 but not TLR6.

Conclusion

This study provides human in vitro evidence that viral infection may increase the susceptibility of women to bacterial-induced sPTB. Improved understanding of interactions between viral and bacterial components of the maternal microbiome and host immune response may offer new therapeutic options, such as antivirals for the prevention of PTB.

Does the use of lubricating gel on the speculum affect fetal fibronectin results? An audit from a large inner-city preterm birth surveillance clinic.

OR13

Authors

Naomi Carlisle and Andrew H Shennan

Presented by

Hannah Fligelstone

Affiliations

Department of Women and Children’s Health, School of Life Course Sciences, King’s College London

Background

Fetal fibronectin is a biochemical test widely used in preterm surveillance clinics to assess a woman’s risk of preterm birth. Manufacturer (Hologic®) guidelines advise against using lubricating gels on the speculum whilst collecting the cervicovaginal sample.
The aim of this audit was to evaluate whether the use of lubricating gel on the speculum during a quantitative fetal fibronectin (qfFN) test has any effect on the result, and to thereby determine whether the use of gel can in fact be recommended, to ease potential pain and discomfort for the patient, contrary to current manufacturer guidance.

Method

Data was collected in a preterm surveillance clinic in a large inner-city hospital via convenience sampling from January-September 2019. The data collected for each participant included maternal age, ethnicity, whether lubricating gel was used, gestation at appointment, qfFN result and delivery outcome. Some participants attended multiple appointments within the audit timeframe, and data was analysed from each individual appointment. Each appointment was therefore considered as a separate case within the dataset. In the sample demographics, individual participants were included only once.

Results

857 cases from 407 women were included in the analysis. 470 (54.8%) cases had qfFN tests without lubricating gel, the remaining 387 (45.7%) having used lubricating gel. The mean qfFN results for these groups were 39ng/mL and 29ng/mL respectively, and the medians 4ng/mL and 5ng/mL respectively. Initial analysis with Mann-Whitney U showed the two groups had significantly different qfFN results (p=0.045) but the effect size was very small (r=0.069). Chi-square testing suggested the spread of qfFN results over 4 categories (<10, 10-49, 50-199 and ≥200 ng/mL) was the same within the gel used and the gel not used groups (p=0.056). Mann-Whitney U tests in subsets based on delivery outcomes also provided insufficient evidence to suggest statistically significantly different qfFN results between the two groups (term: p=0.077, spontaneous preterm: p=0.763, non-spontaneous preterm: p=0.203).

Conclusion

Although initial analysis suggested a statistically significant difference in qfFN results when gel was used compared to when not used, the effect size was minimal, suggesting the difference may not be of clinical significance. Furthermore, subsequent analysis found no significant difference in qfFN results. The evidence from this audit suggests that using gel on the speculum does not affect the qfFN results significantly enough to change clinicians’ interpretation and resulting advice to the patient. These results are notable, providing the potential to ease the discomfort women currently experience during speculum examination without gel.

Evaluation of the Perinatal Excellence to Reduce Injury in Premature Birth (PERIPrem) project.

OR16

Authors

McBain, H. & Tuvey, S on behalf of the PERIPrem Steering Group

Presented by

Hayley McBain

Affiliations

South West Academic Health Science Network

Background

Preterm birth is the single biggest cause of neonatal mortality and morbidity in the UK. Novel treatments are currently being trialled, but there are also evidence-based practices that could be implemented with immediate effect. The PERIPrem project, brings together 11 evidence-based care practices into a bundle of care, with implementation achieved through range of techniques with Quality Improvement at its core. This evaluation aimed to understand the impact of the PERIPrem approach on implementation of a standardised bundle of care to mothers who deliver their babies at less than 34+0 weeks gestation across 12 acute trusts in the West and South West of England. Along with the barriers and enablers to implementation.

Method

This was a convergent parallel mixed methods evaluation, which included a quasi-experimental approach to evaluating intervention effectiveness and parallel qualitative study with healthcare professionals delivering the project. Quantitative data on adherence to the bundle elements was collected over the implementation phase (Sept 2020 to June 2021, during the COVID-19 pandemic) and analysed for changes across this period and in comparison, to data from Jan 2019. Qualitative data were analysed using framework and thematic analysis.

Results

A total of 693 babies were born during the project. When data were compared with 2019, there were statistically significant improvements in the percentage of eligible interventions mothers/babies received (Table 1), in the proportion of mothers/babies who were fully optimised and for 10 of 11 interventions in the percentage of eligible mothers/babies who received that bundle element. Enablers to implementation included fostering a positive perinatal team dynamic, access to evidence-based adaptable resources and coaching, senior leadership and trust endorsement and appropriate project leadership. Barriers to implementation included the complexity and size of the bundle, procedural knowledge, the mental capacity of staff and limited protected time.

Conclusion

Despite the challenges to implementation, this evaluation has demonstrated that through quality improvement methods, fostering team relationships and proactive support and resources the PERIPrem approach is associated with significant improvements in the delivery of care for preterm babies.

Fluidity of Equipoise at Research Sites in a Maternity Pilot RCT: Influences on Clinician Decision-Making

OR9

Authors

Eleanor Molloy (1), Katie Morris (1, 2, 3), Victoria Hodgetts-Morton (1,3), Nicole Pilarski (1, 3), Catherine A. Hewitt (2) and Laura Jones (1) on behalf of CSTICH-2 Collaboration

Presented by

Eleanor Molloy

Affiliations

(1) Institute for Applied Health Research, University of Birmingham (2) Birmingham Clinical Trials Unit (3) Birmingham Women’s Hospital

Background

The C-STICH2 pilot randomised controlled trial (RCT) included a nested Qualitative Process Evaluation (QPE). The QPE explored facilitators and barriers to trial recruitment for randomisation to Emergency Cervical Cerclage (ECC) which has an uncertain evidence base. Historically, RCT designs have been used less often with pregnant participants or in maternity settings for reasons including ethical and recruitment complexity. RCT recruitment assumes clinical equipoise exists. Clinical equipoise is defined as genuine uncertainty about an intervention. This may be personal equipoise, where individual clinicians have no preference for one treatment over another, or community equipoise where the clinical community has a lack of consensus about a specific treatment. The ability of recruiters to convey this equipoise is also key to participant recruitment.

Method

Semi-structured interviews were undertaken with healthcare professionals (HCPs) involved in trial recruitment. Interviews were audio-recorded, transcribed, and analysed using qualitative thematic analysis.

Results

23 HCPs participated in interviews. Fluidity of equipoise was interpreted as one of the main themes from the QPE. This fluidity was impacted by: (1) the influence of gestation; (2) obstetric history; (3) standard site practice, and (4) HCPs previous experiences of ECC. Where there was perceived community equipoise across the clinical body, actual offering of trial entry was influenced by personal and clinical equipoise. Equipoise varied within and across study sites, and was demonstrated to be fluid at different time points (gestation at presentation) and influenced by (changing) clinical presentations of prospective participants.

Conclusion

For many experienced HCPs equipoise was shown to be fluid. Where HCPs had a treatment preference for a particular patient, they may choose not to offer trial entry. This removes potential participants’ decision-making capacity. HCPs may use language and terminology about the interventions which conveys their own preferences. Where this happens at sites, more junior, or less experienced HCPs may default to a position of proxy equipoise, therefore the likelihood of pre-priming around one intervention increases.

Clinical equipoise around complex and rare pregnancy related conditions may be fluid, and is influenced by gestation at presentation and complex obstetric histories. Equipoise should be considered carefully as it can impact the nuances of recruitment, particularly in more challenging maternity setting trials. Further research is needed around the potential consequences of equipoise fluidity.

This project is funded by the NIHR HTA (project number 16/151/01). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

High Stage and Grade of Maternal and Fetal Inflammatory Responses Are Associated With Low Placental CXCL10

OR23

Authors

Kerry M. Parris, Emmanuel Amabebe and Dilly O. Anumba

Presented by

Kerry Parris

Affiliations

Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

Background

Placental inflammatory response (PIR) begins as a maternal inflammatory response (MIR) that leads to fetal inflammatory response (FIR) if acute chorioamnionitis increases in severity. Chronic placental inflammation (CPI) is less well-understood and often unrelated to infection unlike the more common acute chorioamnionitis. CXCL10 is a marker of CPI and could mediate inflammatory responses that can affect birth outcomes. Therefore, we examined the relationship between placental CXCL10 levels, MIR and FIR, and neonatal outcome in term and preterm-delivered women.

Method

CXCL10 level was measured by ELISA in full thickness placental tissues from term (n=9) and preterm-delivered (n=9) women. Histological assessment according to the Amsterdam Consensus Statement was used to determine the presence, stage and grade of PIRs. Neonatal outcome was measured by APGAR score. Associations of PIRs, APGAR score and CXCL10 levels were determined by Spearman’s correlation coefficient (ρ).

Results

CXCL10 levels did not differ between term vs preterm women. 6/9 of the preterm women had preterm premature rupture of membranes. Stages and grades of MIR and FIR correlated positively in both groups. However, a negative correlation between CXCL10 levels and both stages and grades of MIR and FIR was only observed in term women (Table 1). Moreso, there was no correlation between CXCL10 and MIR or FIR in the total cohort. Neither MIR, FIR nor CXCL10 correlated with APGAR score.

Conclusion

These preliminary data indicate that irrespective of delivery outcome, severe histologically-diagnosed PIR depicted by high stage and grade of MIR and FIR correlate with low placental CXCL10. This negative correlation suggests the observed inflammatory responses in this cohort may be acute and driven by immune mediators other than CXCL10 that require confirmation in larger studies.

How are hospitals in England caring for women at risk of preterm birth? The influence of national guidance on preterm birth prevention practice in England

OR10

Authors

Naomi Carlisle1, Angharad Care2, Dilly O C Anumba3, Sonia Dalkin4, Jane Sandall1 & Andrew H Shennan1

Presented by

Naomi Carlisle

Affiliations

1 Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, 10th Floor North Wing, St Thomas’ Hospital, Westminster Bridge Road, SE1 7EH, United Kingdom 2 Centre for Women and Children’s Health Research, University of Liverpool, Liverpool Women’s Hospital, Liverpool, UK 3 Academic Unit of Reproductive and Developmental Medicine, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK 4 Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK

Background

NHS England published the Saving Babies Lives Care Bundle Version 2 (SBLCBv2) in March 2019, which is the first-time national guidance has formally mentioned specialist preterm birth prevention clinics.
A survey was undertaken to identify how many preterm birth prevention clinics are currently in England, to identify current national management in caring for women who are asymptomatic and high-risk of preterm birth, and to identify current national management of women who arrive symptomatically in threated preterm labour.

Method

An online survey comprising of 27 questions was developed and sent to 187 units that provide maternity care in England. The survey was sent out from February 2021 – July 2021.

Results

Data was obtained from 96 units (94 units that offer obstetric-led intrapartum care, and 2 units that provides maternity-led intrapartum care and/or antenatal/community care).

Asymptomatic high risk women
Overall, 78/96 units (81%) reported that they had a preterm birth prevention clinic. SBLCBv2 has had a considerable impact in the increase of preterm birth prevention clinic services, with the majority (61%) of sites reporting that the NHS England publication influenced their unit in setting up their clinic. Most sites, 65%, also felt that their referral criteria had changed because of SBLCBv2.
This questionnaire found only one common risk factor across all clinics (which was having a previous spontaneous preterm birth or mid-trimester loss). The preferred treatment for a short cervical length was a cerclage (braided suture) (38/86, 44%), followed by a cerclage (monofilament suture) (16/86, 19%).
When asked what hindered the implementation of their clinic, over half of respondents (56%, 40/72) highlighted capacity issues. These ranged from too many referrals to cope with, a lack of appropriate clinical space, a lack of staff, and/or a lack of resources. This included 19% (14/72) who specifically mentioned a lack of clinicians able to scan and/or scanning equipment.

Symptomatic women
Most sites, 69%, (64/93) utilise quantitative fetal fibronectin to assess symptomatic women at risk of preterm labour. Over half of respondents utilise the QUiPP App when assessing symptomatic women (47/93, 51%) and for 78% of these sites (36/46) it is recommended in local guidance.

Conclusion

We have now identified 78 preterm birth surveillance clinics in England, a staggering 160% increase in 4 years (Care et al., 2019).
While SBLCBv2 has succeeded in promoting preterm prevention care and clinics, it has not achieved standardised care across England. Variations in practice still exist at every step of the preterm pathway.

Care, A. et al. (2019) ‘The influence of the introduction of national guidelines on preterm birth prevention practice: UK experience’, BJOG: An International Journal of Obstetrics & Gynaecology. John Wiley & Sons, Ltd (10.1111), 0(0). doi: 10.1111/1471-0528.15549.

Integrating mental health screening in a specialist preterm clinic

OR24

Authors

Jenny Carter1,2; Debbie Finucane2; Vicky Robinson2; Andrew Shennan1,2

Presented by

Jenny Carter

Affiliations

1. King’s College London 2. Guy’s and St Thomas’ NHS Foundation Trust

Background

Anxiety is associated with increased risk of preterm birth (Becker et al 2021; Wolgast 2021) and suicide remains a major cause of maternal death (MBRRACE, 2020). Many women at risk of preterm birth suffer with anxiety and we sought ways to monitor and address this in women seen in our preterm clinic.

Method

We worked with King’s Health Partners IMPARTS (Integrating Mental and Physical Healthcare: Research, Training and Services) team, to implement a novel method for screening and supporting women in our clinic. Working with IMPARTS and our PPI group, we developed a protocol, decided on validated instruments (GAD7 – anxiety, PHQ9 – depression and PROMIS10 – wellbeing and QoL), self-help materials, care pathways and warning system if anyone expressed suicidal ideation. On arrival for their appointment, women are given a leaflet with QR code and invited to complete the questionnaire using their mobile phone. If they prefer, they can use our dedicated tablet device. Their answers, which are transferred directly to their hospital electronic patient record, are reviewed by the clinician before they call the women into the room, along with any recommended care pathways. We reviewed the screening results of women attending for specialist preterm care since IMPARTS launch in July 2021.

Results

296 questionnaires were completed by 168 women between 1st July and 20th September 2021. The number of visits per woman ranged from 1-6. Using data from the visit with the highest scores, screening indicated mild to very high levels of anxiety in 22% of women (37/168), and depressive symptoms in 19% (32/168). Screening indicated 8 women were experiencing “Probable major depression” and 3 reported thoughts that they “would be better off dead or…hurting [themselves]…” more than half the days (n=1) or nearly every day (n=2) (Table).

Conclusion

We believe this innovative screening programme is worthwhile and we have been able to support several women in obtaining the extra care they needed. In two very serious cases, we may have prevented suicide. Future plans include using this screening method to gather data for research purposes, as well as evaluation of our preterm service. Additional fields have been added to the PCN database, allowing us to relate screening scores with other clinical factors and outcomes, as well as health economic analysis using the PROMIS10 scores.

Interventions to prevent spontaneous preterm birth in high-risk women with singleton pregnancy: A systematic review and network meta-analysis.

OR2

Authors

Angharad Care, clinical lecturer1*, and Sarah J Nevitt, senior research associate2, Nancy Medley, research manager1, Sarah Donegan, lecturer2, Laura Goodfellow, clinical lecturer1, Lynn Hampson, information specialist3, Catrin Tudur Smith, professor2, Zarko Alfirevic, professor1.

Presented by

Angharad Care

Affiliations

1) Harris Preterm Birth Research Centre, Department of Women and Children’s Health, University of Liverpool and Liverpool Women’s Hospital, Liverpool, L8 7SS. 2) Department of Health Data Science, University of Liverpool, Liverpool, UK 3) Cochrane and Pregnancy Childbirth Group, Department of Women and Children’s Health, University of Liverpool, Liverpool, UK.

Background

Randomised clinical trials of all available treatment options for women at risk of PTB is unfeasible. Network meta-analysis (NMA) provides a tool to overcome these challenges. By evaluating all available evidence within a network linked by comparisons made through RCT data, the NMA produces estimates of the relative effects for each treatment compared with all others. It is possible to calculate the probability of one treatment being the best for a specific outcome.

Our objective was to compare the efficacy of bed rest, cervical cerclage (McDonald, Shirodkar or unspecified type of cerclage), cervical pessary, fish oils or omega fatty acids, nutritional supplements (zinc), progesterone (intramuscular (IM), oral or vaginal), prophylactic antibiotics, prophylactic tocolytics, combinations of interventions, placebo or no treatment (control) to prevent sPTB in women at high risk of sPTB.

Method

Design
Systematic Review with Bayesian network meta-analysis

Data Sources
The Cochrane Pregnancy and Childbirth Group’s Database of Trials. Sources included are CENTRAL, Medline, Embase, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials.

Eligibility Criteria for Selecting Studies
Randomised controlled trials (RCTs) of pregnant women who are at high risk of sPTB due to a history of sPTB or short cervical length. No language or published date restrictions were made.

Outcomes
We analysed 7 maternal outcomes and 11 fetal outcomes in line with published core outcomes for PTB research; Relative treatment effects (Odds Ratios [OR] and 95% Credible Intervals [CrI] and certainty of evidence are presented for outcomes PTB before 34 weeks and perinatal death.

Results

Sixty-one trials (17,273 pregnant women) contributed data to analysis for at least one outcome. The summary of findings table for the maternal outcome of PTB < 34 weeks is shown in the attached table. For the outcome of perinatal death, 30 trials (12,119 pregnant women) contributed data to the network. Vaginal progesterone (VP) was the only treatment that demonstrated clear evidence of benefit for this outcome (OR 0.66; 95% CrI 0.44-0.97, moderate certainty). In addition, 17OHPC (OR 0.78, CrI 0.50-1.21, moderate certainty of evidence), McDonald cerclage (OR 0.59, CrI 0.33-1.03, moderate certainty of evidence) and unspecified cerclage (OR 0.77, CrI 0.53-1.11, moderate certainty of evidence) may reduce perinatal death rates, but CrIs could not exclude the possibility of harm. Compared to controls, only progesterone treatments are associated with reduction in neonatal respiratory distress syndrome, neonatal sepsis, necrotising enterocolitis, and admission to NICU.

Conclusion

VP should be considered the preventative treatment of choice for women with singleton pregnancy identified to be at risk of sPTB due to a history of sPTB or short cervical length. Future RCTs should be using VP as a comparator to identify better treatments.

Large-scale characterisation of the pregnancy vaginal microbiome and sialidase activity in a low-risk Chinese population

OR21

Authors

Sherrianne Ng (1,2), Muxuan Chen (3,4), Samit Kundu (1,2), Xuefei Wang (5), Zuyi Zhou (3,4), Zhongdaixi Zheng (6), Wei Qing (3,4), Huafang Sheng (3,4), Yan Wang (5), Yan He (3,4), Phillip R. Bennett (1,2), David A. MacIntyre (1,2) and Hongwei Zhou (3,4,7).

Presented by

Sherrianne Ng

Affiliations

1 Imperial College Parturition Research Group, Imperial College London, London, United Kingdom. 2 March of Dimes European Prematurity Research Centre, Imperial College London, London, United Kingdom. 3 Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China. 4 Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. 5 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China. 6 School of Public Health, Southern Medical University, Guangzhou, Guangdong, China. 7 State key laboratory of Organ Failure Research, Southern Medical University, Guangzhou, Guangdong, China.

Background

The pregnancy vaginal microbiota is important for shaping maternal and neonatal health outcomes. Vaginal microbiomes dominated by Lactobacillus species are associated with protection against preterm birth (PTB), whereas high diversity, Lactobacillus spp. depleted compositions (e.g. bacterial vaginosis) are associated with increased PTB risk. Despite most PTBs occurring in Asia and ethnicity being recognised as a potential confounder of the relationship between vaginal microbiome and PTB, few studies have characterised the pregnancy vaginal microbiota in Asian populations. In this study, we aimed to characterise the vaginal microbiota of large cohort of pregnant Chinese women and explore relationships between bacterial composition, sialidase activity, vaginal leukocyte presence and PTB.

Method

Pregnant Chinese women were recruited from Nanfang Hospital, Guangzhou, China, from January 2015 to December 2018. Vaginal swabs from 2796 low-risk pregnant women were collected in addition to kit and environmental controls. The V4 region of bacterial 16S rRNA was sequenced. A total of 2689 samples passed library size and microbiome classification criteria. The vaginal microbiome structure and composition was characterised for samples collected in the first and second trimesters (n=2646) and in a subset (n=819), the relationship between microbiota composition, sialidase activity and/or leukocyte presence was assessed using logistic regression. Statistical tests included Mann-Whitney Test for continuous variables and Fisher’s Exact Test for categorical groups.

Results

Majority of pregnant Chinese women had vaginal microbiomes dominated by Lactobacillus (2275/2646, 85.89%), specifically L. crispatus (1058/2646, 39.98%) or L. iners (952/2646, 35.98%). Women with high sialidase activity (n=36) had significantly higher proportions of Lactobacillus spp. depleted microbiomes, with enrichment of BV-associated genera including Gardnerella, Prevotella and Atopobium, compared to women with low sialidase activity (n=783, p=2.403e-13). Women with high leukocyte counts (n=572) had higher prevalence of Lactobacillus dominated microbiomes compared to women with low leukocyte counts (n=247), and this was mostly driven by significantly higher relative abundance of L. iners (p<0.01). Lactobacillus spp. depleted microbiomes, high sialidase activity and/or high leukocyte counts was not associated with increased risk of PTB.

Conclusion

The vaginal microbiome in the women in our cohort was most commonly dominated by L. crispatus, similar to European Caucasian and Chinese but different from Hispanic, African American and Indian women. This provides further evidence that microbiota-host interactions during pregnancy are influenced by ethnicity and/or geographical differences. The underlying differences in microbiome compositions and/or host immune responses of Chinese women may account for lower rates of PTB in this population.

Mechanotransduction mechanisms in human preterm fetal membranes after trauma

OR15

Authors

Costa Eleni, 2Thrasivoulou Chris, Deprest Jan A, Becker David L, David Anna L and Chowdhury Tina T.

Presented by

Eleni Costa

Affiliations

Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK. Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK. Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium. Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore, 308232. Elizabeth Garrett Anderson Institute for Women’s Health, University College London, Medical School Building, Huntley Street, London WC1E 6AU

Background

Iatrogenic preterm premature rupture of the fetal membranes (PPROM) complicates fetal diagnosis or surgery, leading to membrane rupture in up to 40% of cases. We developed an in vitro bioreactor model to investigate the effects of cyclic tensile strain (CTS) in preterm human amniotic membrane (AM) before and after trauma.

Method

Preterm human fetal membranes (FM) were collected from n=16 donors undergoing preterm elective caesarean section (28+3 – 34+6 weeks of gestation). Preterm AM explants were traumatized with a needle (0.8 mm diameter) and subjected to 24 hours intermittent CTS (2%, 1 Hz frequency). Cell morphology, migration and differentiation of mesenchymal cells were examined using IMF confocal microscopy for Cx43 and αSMA or nuclear deformation with DAPI. Collagen microstructure in preterm AM was examined by SHG imaging. The changes in Cx43 and αSMA expression by cells in the amniotic epithelial layer were compared to the fibroblast layer in tissues close to the placenta (PAM) or the cervix (CAM). GAG synthesis normalised to DNA levels were quantified by DMMB and Hoechst assay. Elastin, hydroxyproline and PGE2 assays were performed using purchased kits.

Results

After CTS or trauma, preterm AM showed a dense region of mesenchymal cell migration to the wound edge in CAM and PAM specimens. In wound edge preterm AM after CTS, collagen fibres were highly polarised and aligned parallel to the axis of the wound edge and the direction of applied strain, with greater Cx43 puncta preferentially expressed by mesenchymal cells (Fig. 1). In the fibroblast layer, nuclear cell contraction and myofibroblast differentiation increased in wounded CAM and PAM specimens after CTS or trauma. The mechanotransduction mechanism appeared to bring together the wound edges with greater crosslinking of collagen fibres in wounded preterm AM specimens (Fig. 1), similar to the purse string contraction model. But even after stimulation with CTS for 24 hours, the wound only partially closed. Unstrained control AM was not polarised and fibres were randomly interwoven (Fig. 1, Left panel). CTS significantly increased GAG synthesis, elastin concentration and PGE2 release when compared to unstrained control preterm AM specimens, with differences dependent on tissue region and pregnancy outcome.

Conclusion

Overexpression of Cx43 and aSMA in wounded preterm AM drive structural changes in collagen that influences mechanotransduction and purse string contraction. A combination of inflammatory and mechanical factors may perturb typical mechanotransduction processes mediated by Cx43 signalling. Cx43 could therefore be a potential therapeutic target to prevent inflammation and preterm premature rupture of the fetal membranes after iatrogenic rupture.

Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response

OR18

Authors

Denise Chan1, Phillip R. Bennett1,2, Yun S. Lee1,2, Samit Kundu1,2, TG Teoh2,3, Malko Adan1,2, Saqa Ahmed1, Richard G. Brown1, Anna L. David4, Holly V. Lewis1, Belen Gimeno-Molina1,2, Jane E. Norman5,6, Sarah J. Stock5, Vasso Terzidou1,2,7, Pascale Kropf 2,8, Marina Botto2,9, David A. MacIntyre1,2, Lynne Sykes1,2,3*

Presented by

Belen Gimeno Molina

Affiliations

1Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, UK 2March of Dimes Prematurity Research Center at Imperial College London, UK 3 St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK 4Elizabeth Garrett Anderson Institute for Women’s Health, University College London, UK 5University of Edinburgh Usher Institute, Edinburgh, UK 6Faculty of Health Sciences, University of Bristol, UK 7Chelsea & Westminster Hospital, Imperial College Healthcare NHS Trust, London, UK 8Department of Infectious Diseases, Imperial College London, London, UK 9Department of Immunology and Inflammation, Imperial College London, London, UK

Background

The global preterm birth rate is estimated at over 10%. Inflammation and infection have long been implicated in the aetiology of a significant proportion of spontaneous preterm births (sPTB). Despite Lactobacillus dominance consistently shown to be an important mediator for preterm birth risk, the mechanism for this remains poorly understood. In this study we aim to understand how the maternal host immune system responds to healthy commensals and pathobionts, and how this interaction influences the risk of sPTB, by assessing the vaginal microbial composition and immunophenotyping cervicovaginal fluid (CVF).

Method

Women at high-risk of preterm birth (n=133) were recruited and CVF collected at 12+0 – 16+6 weeks of gestation, as well as two further times (20+0 – 24+6 and 30+0 – 34+6 weeks), unless delivery occurred before. Cytokines (IL-8, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-18, IFN-γ, GM-CSF and TNF-α, complement proteins (C3b, C5, C5a) and mediators of microbial recognition (IgM, IgG1, IgG2, IgG3, IgG4, Ig, IgM, IgG1, IgG2, IgG3, IgG4, IgA) were measured using the multiplex magnetic bead Luminex Immunoassay platform. DNA extraction was performed and the V1-V2 hypervariable region of 16S rRNA gene was amplified. Sequences were taxonomically classified to species level using the STIRRUPS reference database. Measures of microbial diversity: inverse Simpson and Shannon indexes and richness (species observed) were calculated using the Phyloseq package in R. Statistical analyses were performed using Graphpad Prism 9.0.0.

Results

Vaginal depletion of Lactobacillus species was associated with increased mannose binding lectin (MBL) (p<0.0001), IgM (p<0.0001), IgG (p<0.0001), C3b (p<0.0001), C5 (p<0.001), IL-8 (p<0.003), IL-6 (p<0.003) and IL-1β (p<0.0001) and with an increased risk of sPTB (all mediators statistically significant). In women with a diverse composition, those who went on to deliver preterm had an augmented inflammatory response compared to those who delivered at term (IL-8, IL6, IL-1β, C3b and C5 p<0.05; MBL and IgM p<0.01), supporting a dysregulated host immune response. Cervical shortening, which often precedes preterm birth, was associated with Lactobacillus iners and statistically significant elevated levels of IgM, C3b, C5, and IL-6.

Conclusion

These data support the role of the complement system in mediating a local pro-inflammatory milieu in microbial driven cervical shortening and sPTB. We provide a scientific rationale for exploring the potential for complement therapeutics to prevent sPTB.

Neutrophil-to-lymphocyte ratio in women with late miscarriage or preterm birth – a potential diagnostic aid in the clinician’s armamentarium to diagnose placental inflammation/infection and facilitate timely delivery.

OR22

Authors

Carlotta Modestini, Madeleine Trowsdale Stannard, Elsa King, Alex Ridout, Natalie Suff, Andrew Shennan, Manju Chandiramani

Presented by

Carlotta Modestini

Affiliations

Guys and St Thomas’ NHS Foundation Trust

Background

Placental inflammation and infection is often implicated in the onset of late miscarriages and preterm birth and is associated with poor neonatal outcomes. A raised neutrophil-to-lymphocyte ratio (NLR) >6 has been shown to be associated with systemic inflammation in critically ill patients, as well as an independent risk factor for all-cause mortality in the elderly. It remains unclear if the altered immune state in pregnancy lends itself to NLR being used as another tool in the diagnosis of subclinical chorioamnionitis. We sought to determine the relationship between placental inflammation and NLR, as well as other inflammatory markers.

Method

We undertook a retrospective study of all women who gave birth between 16 and 36+6 weeks’ gestation at St Thomas’ Hospital over a two-year period (31/1/2019-31/1/2021). Clinical signs of sepsis (temperature, pulse and respiratory rate), NLR within 24 hours of delivery, C-reactive protein, total white cell count and placental histology were collected. The NLR in women with histological evidence of placental infection/inflammation was compared with those without evidence of infection/inflammation. Performance of the other collected markers were compared.

Results

Clinical data and placental pathology was collected for 613 women. Of these, 97% (592/613) of women had a WCC/CRP undertaken within 24 hours prior of their delivery. 42% (248/592) had confirmed histological chorioamnionitis. The mean NLR was raised in this group compared to those with non-inflammatory placenta (n=344), 9.8 vs 5.7. In women with placentas showing signs of histological chorioamnionitis, 56% had an NLR 6 compared to 27% in those without inflammation.

Conclusion

Further work is underway to determine if test performance in this group of women is superior to that of our traditional clinical signs, whether this can further aid decisions to deliver women before they show overt signs of clinical chorioamnionitis, and whether timely delivery has longer term benefit to the neonate.

Optimising the triaging of women presenting with threatened preterm labour: delivery outcomes following in-utero transfer in Yorkshire and the Humber

OR17

Authors

Sumeyya Tontus(1), Professor Dilly Anumba(1), Dr Catherine Harrison(2)

Presented by

Sumeyya Tontus

Affiliations

1. The University of Sheffield 2. Embrace Yorkshire and Humber Infant and Children Transport Service

Background

In-utero transfers (IUT) are vital for neonatal survival, enabling infants to be born in the right place. However, preterm delivery is difficult to predict, and many transfers are carried out unnecessarily – two previous studies in the region found that only 35.1% and 52% of women delivered within 48 hours of transfer. This has led to increased demand on neonatal transport services. IUTs are also a large burden to the mothers, with women travelling many miles away from their booking hospital to the nearest appropriate neonatal unit. Testing for cervicovaginal biomarkers, such as fetal fibronectin, is an extremely useful method of identifying women at high risk of delivery, with studies finding an extremely high negative predictive value (NPV) for prediction of delivery within 7 days. However, use of these within the region has previously been found to be low. Our study aimed to review the use of in-utero transfers in Yorkshire and the Humber and identify whether the current methods of triaging women presenting with threatened preterm labour (TPTL) require optimising.

Method

This study was a prospective cohort study which analysed all IUT requests facilitated by Embrace (Yorkshire and Humber’s neonatal transport service) over a 6-month period. To obtain delivery outcome data, Embrace staff were instructed to contact receiving delivery suites 48 hours following transfer.

Results

161 IUT requests were analysed. Table 1 shows the number of women transferred from/to each level of neonatal unit, suggesting that 50.37% of requests were due to uplift in care and 49.63% of requests were due to capacity issues at the woman’s booking hospital. Only 29.1% of women delivered within 48 hours of transfer, and women travelled an average of 32.5 miles away from their booking hospital. Fetal fibronectin was the most commonly used predictive biomarker, however predictive testing was used in only 28.8% of women and 10 women were still transferred despite receiving a negative predictive test result.

Conclusion

Delivery outcomes following an IUT are even lower than previously thought, and many women are transferred inappropriately. Predictive testing before transfer is still uncommon, and data showing that women are still transferred after a negative result suggests that clinicians seem to be reluctant to trust the results. The current methods of triaging women in TPTL are in clear need of optimising to minimise the burden on women and the demand on transport services.

Participation in clinical trials not associated with improved clinical outcomes

OR8

Authors

Spencer L, Bonney EA, Simpson NAB

Presented by

Lucy Spencer

Affiliations

1Division of Women’s and Children’s Health, School of Medicine, University of Leeds 2Leeds Teaching Hospitals NHS Trust, Leeds

Background

Clinical research creates innovative new treatments and preventative interventions for disease as well as optimising existing medical practice. Trials are reliant upon the recruitment and consent of eligible participants, but evidence suggests participation can also benefit the individual (Nijjar et al, 2017). Preterm birth is an important complication of pregnancy associated with increased morbidity for both mother and baby and increased perinatal mortality. C-STICH is a multicentre open randomised superiority trial comparing two different cervical suture materials on pregnancy outcome. We hypothesised that patients enrolled in C-STICH would have better pregnancy outcomes than eligible non-participants receiving the same cervical cerclage treatment

Method

A retrospective cohort of 385 cervical cerclage procedures performed at Leeds Teaching Hospitals between 2015 and 2020 was generated via theatre log books, a K2 maternity system data search and the C-STICH database. Patients were allocated to either the C-STICH participant group (n=175) or non-participant group (n=210). Inclusion criteria were matched to C-STICH criteria: singleton pregnancy and history or ultrasound indicated cerclage. Those undergoing rescue cerclage, transabdominal cerclage, carrying a multiple pregnancy or previously enrolled in C-STICH were excluded. The primary outcome was pregnancy loss (miscarriage, stillbirth or early neonatal death). Secondary outcomes included length of gestation, birth weight and mode of delivery. Birth weight data was missing from 40 of the non-participant group and four of the C-STICH group. Birth weights were analysed using Hadlock’s tenth centile criteria for estimated fetal weight according to gestational age. Descriptive statistics were used together with Chi-squared analysis to determine intergroup differences.

Results

Pregnancy loss rates did not differ between the two groups: 4% (n=7) in the C-STICH trial participants and 3.3% (n=7) in the non-participant group (p=0.73). The median gestation at birth was 38 completed weeks in both groups. The proportion of babies born ≥37 weeks was 77% in both groups. The proportion of babies born very preterm (<32 weeks) did not differ between the two groups: 3.5% in the C-STICH group and 4.4% in the non-participant group (p=0.68). 42% of live births in the C-STICH group were delivered via caesarean section versus 45% in the non-participant group (p=0.71). There was no significant reduction in small for gestational age babies seen in the C-STICH participant group compared to the non-participant group: 10.5% and 7.5% respectively (p=0.35).

Conclusion

Enrolment in clinical trials may be beneficial for those at risk of preterm birth; however we were unable to find a statistically significant improvement in this cohort. There was a trend toward a longer gestational length, reduced caesarean delivery rates and lower incidence of small for gestational age babies for women participating in this clinical trial.

Pregnancy outcomes in preterm birth prevention services: approaching individualised patient risk profiles

OR28

Authors

Mountain, KE 1,2; Yatham, SY 1; Bayar, E 1,2; Adan, M 1,2; Zarasvand, S 2; Terzidou, V 1,3; Teoh, TG 1,2; Bennett, PR 1,2; Sykes, L 1,2

Presented by

Katie Mountain

Affiliations

1 Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, UK 2 Imperial College Healthcare NHS Trust, London, UK 3Chelsea and Westminster Hospitals NHS Foundation Trust, London, UK

Background

Amidst the context of globally rising rates of preterm birth, the UK has set a target to reduce the preterm birth rate from 8% to 6% by 2025(1). One aspect of the strategy is through provision of prevention services for women identified as at risk of spontaneous preterm birth (sPTB). However, the rates of pregnancy outcomes such as sPTB, mid trimester loss (MTL) and prelabour preterm rupture of membranes (PPROM) for women following such care pathways has not been widely reported, making benchmarking and individualised counselling challenging. The primary objective of this study was to assess outcomes, stratified according to risk factor for sPTB, for women following a preterm birth prevention pathway.

Method

This was a retrospective cohort study of women who were referred to the sPTB Prevention Clinics at St. Mary’s, Queen Charlotte’s, or Chelsea and Westminster Hospitals between 2013 and 2020. Complete data for risk factor(s) for sPTB, interventions, and delivery outcomes were obtained for 2440 women. Cervical length (CL), as measured by transvaginal ultrasound scan (TVUS), was available for 1993 women. The study was registered as a Service Evaluation at Imperial College Healthcare NHS Trust.

Results

The most common single risk factors were previous cervical treatment (CT) (28.8%), previous sPTB (24.5%) and previous MTL (22.3%). 13.7% of women had more than one risk factor. Women with a previous sPTB or MTL were at higher risk of cervical shortening, PPROM and sPTB <37 weeks compared to those with CT (cervical shortening: 24.9 %, 39.6% and 19.4%, p=0.03, p<0.001;PPROM: 9.9%, 6.9% and 5.9% respectively, p=0.018, and sPTB: 28.3%, 23.5% and 13.4%, p<0.0001). The rate of sPTB following ultrasound-indicated cerclage was 23.5% for those with CT compared to 38.1% for those with previous PTB or MTL (p=0.027), supporting potentially greater benefit from cerclage for those with shortening secondary to mechanical weakness in the context of CT. Furthermore, when braided material was used for cerclages in women with a history of previous sPTB or MTL, higher rates of sPTB <34 and <37 occurred compared to those who received monofilament (p=0.03, p=0.01), a relationship not seen in women with CT.

Conclusion

We have demonstrated key differences in pregnancy outcome, depending on the individual’s risk factor for sPTB. With this information, counselling can be individualised to provide an improved standard of care which can be applied to other units with a preterm prevention care pathway.

1. NHSEngland. Saving Babies’ Lives Care Bundle Version 2 2019 https://www.england.nhs.uk/wp-content/uploads/2019/07/saving-babies-lives-care-bundle-version-two-v5.pdf.

Rapid prediction of vaginal microbiota composition in pregnancy by direct on-swab metabolic profiling

OR1

Authors

Katia Capuccini, Pamela Pruski, Gonçalo D. S. Correia, Holly V. Lewis, Denise Chan, Richard G. Brown, Yun S. Lee, Anna L. David, Sarah J. Stock, Jane E. Norman, Vasso Terzidou, T. G. Teoh, Lynne Sykes, Phillip R. Bennett, Zoltan Takats and David A. MacIntyre

Presented by

Katia Capuccini

Affiliations

March of Dimes Prematurity Research Centre at Imperial College London, London, UK Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine Imperial College London, London, UK National Phenome Centre, Imperial College London, London, UK Queen Charlotte’s & Chelsea Hospital, Imperial College London, London, UK Elizabeth Garrett Anderson Institute for Women’s Health, University College London, London, UK MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK Faculty of Health Sciences, University of Bristol, Bristol, UK Chelsea & Westminster Hospital, NHS Trust, London, UK St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK Tommy’s National Centre for Miscarriage Research, Imperial College London, London, UK

Background

The vaginal microbiome plays an important role in reproductive health. Increased vaginal bacterial diversity and Lactobacillus species depletion is associated with progression of cervical cancer and increased risk of miscarriage and preterm birth (PTB). Currently, clinical diagnosis of vaginal infection is largely limited to assessment of clinical symptoms plus time-consuming culture and subjective microscopy investigations. In research settings, molecular approaches can provide compositional information of the vaginal microbiota but are expensive, time consuming and fail to provide insight on host response. We hypothesised that vaginal microbiota composition and host-response are reflected in metabolic milieu of cervicovaginal fluid and that rapid metabolic profiling could provide sufficient biochemical information to predict bacterial composition.

Method

Vaginal swabs were collected longitudinally throughout pregnancy from two independent cohorts (VMET, n=160; 455 swabs; VMET II, n=205; 573 swabs). Metabolic profiles were directly acquired from swabs in less than 3 minutes and without sample preparation using direct on-swab Desorption Electrospray Ionisation Mass Spectrometry (DESI-MS). Linear mixed effect modelling was used to identify metabolic features associated with microbiota composition as determined using metataxonomics. ROC curve analysis and Random Forest classifiers were used to assess the ability of DESI-MS profiles to predict microbiota composition.

Results

The concentration of 113 metabolite features detected in DESI-MS negative and positive ion modes were significantly different between Lactobacillus dominated and depleted samples in independent analyses of both patient cohorts. Robust prediction of genera-level classification was observed across cohorts (VMET/VMET2; AUC 94.1/90.6; sensitivity: 62.0/54.5; specificity: 97.8/96.4). Discrimination between the major vaginal community state types (CSTs; I, III and IV) could also be achieved (VMET/VMET2; AUC 95.76 (94.3–97.7); sensitivity: 69.74(57.5–80.2); specificity 98.28 (97.7–98.9)). High vaginal diversity and instability during pregnancy, defined as shifts between Lactobacillus-dominated and Lactobacillus-depleted communities characterised by metataxonomics, were associated with an increased risk of PTB compared to those women maintaining Lactobacillus-dominance (OR 1.97, 95% CI 1.03–3.66, p= 0.04). A similar trend was observed when stability was predictive by DESI-MS but this did not reach significance (OR 1.47, 95% CI 0.75–2.78, p = 0.25).

Conclusion

Direct on-swab metabolic profiling by DESI-MS provides a rapid approach for identifying preterm birth risk phenotypes associated with the vaginal microbiome. Monitoring microbiota composition in this way could facilitate preterm birth risk stratification, as well as selective targeting and monitoring of preventative treatments.

Recruitment to and feasibility of a challenging maternity RCT: Findings from the C-STICH2 Pilot Qualitative Process Evaluation.

OR7

Authors

Eleanor Molloy (1); Katie Morris (1, 2, 3); Victoria Hodgetts-Morton (1, 3); Nicole Pilarski (1, 3), Catherine A. Hewitt (2), Laura Jones (1) on behalf of CSTICH-2 Collaboration

Presented by

Eleanor Molloy

Affiliations

(1) Institute of Applied Health Research, University of Birmingham (2) Birmingham Clinical Trials Unit (3) Birmingham Women’s Hospital

Background

The C-STICH2 Pilot RCT was developed with an embedded qualitative process evaluation (QPE) to explore the feasibility of recruitment to randomisation to Emergency Cervical Cerclage (ECC), or standard practice (expectant management) at 16-27+6 weeks of pregnancy. The QPE explored experiences of recruiting staff and potential or recruited participants to understand if recruitment to the RCT was feasible and acceptable.

Method

Semi-structured interviews took place with healthcare professionals (HCPs) and women who were approached about the trial, and had either agreed to or declined randomisation. Interviews were audio-recorded, transcribed, and analysed using qualitative thematic analysis.

Results

11 women and 23 HCPs were interviewed. Three super-ordinate themes of Fluidity of Equipoise, a Complex Obstetric History, and Influence of Gestation were interpreted. Clinical expertise, standard practice and women’s and HCPs understanding around ECC varied. Women’s decision-making about trial entry was influenced by their own obstetric history. Some women preferred personalised treatment decision-making instead of random allocation. Other women accepted randomisation because they understood the uncertainty around treatment options, and had not been pre-primed. We defined pre-priming as discussion of treatment prior to discussion about the trial or the uncertainty around the evidence base.

Conclusion

Education around the evidence base for staff at sites was considered key to reduce pre-priming and widen recruitment across eligible gestations. Knowing the availability of senior clinicians who can facilitate trial entry may increase trial offering. Clinical equipoise varied across and between sites, being influenced by clinical presentation and HCP experience. Women often supported the need for the trial to increase the evidence base, despite sometimes feeling randomisation was unacceptable for their situation.

Fluidity of clinical equipoise means that some HCPs involved in trial recruitment will not offer participation to eligible participants where they interpret for an individual one intervention potentially offers benefits, despite having overall equipoise for the intervention. Recruitment was challenging but possible with continued trial awareness and education around the evidence base at sites. There was evidence that participation in the trial influenced local site practice. Continuing the RCT alongside an observational study offers more women the chance to participate, whilst adding to the evidence base. Embedding the QPE within the pilot enabled an in-depth understanding of barriers to recruitment, potential improvements in trial processes and information provision.

Funding
This project is funded by the NIHR HTA (project number 16/151/01). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Surgical Training: Transvaginal Cervical Cerclage Simulator

OR26

Authors

Miss Carrie Coary, Dr Natalie Suff, Dr Megan Hall, Dr Graham Tydeman, Professor Andrew Shennan

Presented by

Carrie Coary

Affiliations

Department of Women’s Health, School of Life Course Sciences and Medicine, King’s College London NHS Fife

Background

Preterm birth is a worldwide epidemic affecting 15million births. Currently cervical cerclage placement is the mainstay preventative treatment for cervical insufficiency, one of the main causes of preterm birth. Despite the importance of this procedure, trainees lack opportunity to practise the technique. We describe our experience with a cervical cerclage simulator.

Method

21 Obstetrics & Gynaecology Doctors were recruited for participation. A pre and post simulation survey was designed and distributed. Doctors were split into three groups: Experts, Intermediates or Novices based on previous cerclage placement experience. Participants then underwent cervical cerclage simulation. Following simulation, the cervix was removed, and the stitch measured and analysed. Participants were then asked to answer a post simulation survey and responses were recorded and analysed.

Results

Following simulation, a statistically significant median increase in confidence levels by 2 points was reported within the novice group in both history and ultrasound indicated cerclage and self-evaluation of cerclage placement, (p = 0.0078, p = 0.0156 and p = 0.0156). Experts recorded a median increase in confidence by at least 0.5 points following simulation, however this result was not significant (p >0.9999 and p = 0.6250). Cervical cerclage placement analysis between groups did not report any statistically significant outcomes to indicate successful stitch placement. However, despite being not statistically significant, participants within the Expert group performed better in all areas that would indicated successful stitch placement such as height and diameter of stitch compared to those within the Intermediate and Novice groups.

Conclusion

Using simulation, trainees’ confidences in cerclage placement increased significantly. Participants within the Novice group obtained the greatest significant median increase in confidence level. When evaluation of the simulator model occurred, it scored highly across the board emphasising its appropriateness as a teaching tool. Due to lack of research to allow for comparison, we were unable to generate gold standard measurements indicating successful stitch placement. However, through conduction of further research and use of the Delphi method, we hope to achieve this. Following this, evaluation for increasing competence with multiple sessions using the simulator can be undertaken.

The effect of secretor status and the vaginal microbiome on birth outcome

OR4

Authors

Kundu S, Lee YS, Sykes L, Chan D, Lewis H, Brown RG, Kindinger L, Dell A, Feizi T, Haslam S Liu Y, Marchesi JR, MacIntyre DA and Bennett PR

Presented by

Samit Kundu

Affiliations

a. Institute for Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, United Kingdom b. Institute for Women’s Health, University College London, London, UK c. Department of Life Sciences, Imperial College London, London, UK d. Glycosciences Laboratory, Department of Metabolism Digestion and Reproduction, Imperial College London, London, UK e. Division of Digestive Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, UK.

Background

Histo-blood group antigens (HBGA) are found on a range of cell types and in secretions such as cervical and vaginal. These antigens serve as attachment sites and energy substrates for microbes. The FUT2 gene encodes a fucosyltransferase enzyme, which fucosylates a glycan precursor forming the H antigen. Mutations in FUT2 have been identified that result in non-secretion of HBGA. We hypothesised that the composition of the vaginal microbiota in pregnancy might be influenced by maternal secretor status, with consequences for gestational length.

Method

We sequenced the second exon of the FUT2 gene to infer secretor status and undertook metataxonomic analysis of vaginal swab samples collected longitudinally from a cohort of 313 pregnant women.

Results

We identified 28% of the cohort as non-secretors with the highest proportion in Afro-Caribbean women, 34.6%. Co-occurrence networks showed contrasting patterns of interactions in the microbiota of secretors and non-secretors: Lactobacillus species, in particular L.crispatus, were observed to have a greater proportion of negative edges in the non-secretors. Regression modelling of gestational length showed that non-secretors with Lactobacillus-depleted microbiota in early pregnancy had significantly shorter pregnancies compared with Lactobacillus-dominated non-secretors (p=0.045). This difference in gestational length was not observed in the secretors (p=0.28).

Conclusion

Our results indicate that lactobacilli, particularly L. crispatus, are more refractory to co-colonisation in non-secretors and may offer a greater “protective” effect via competitive exclusion. Given this evidence of a more “protective” role of L.crispatus in non-secretors, this microbe represents a biotherapeutic candidate for these pregnancies. Dominance of the vaginal niche by lactobacilli is a hallmark of vaginal health, but our results demonstrate that this effect is nuanced by host secretor status. An enhanced inflammatory response, previously documented in non-secretors, may provide a mechanism linking gestational length to secretor status and the vaginal microbiota. Stratification by maternal secretor status offers a targeted intervention of “at-risk” pregnancies.

Transcriptomic analysis of the human placenta reveals trophoblast dysfunction and augmented Wnt signalling associated with spontaneous preterm Birth

OR3

Authors

Khondoker M Akram, Neha S Kulkarni, Abbey Brook, Matthew D Wyles, Dilly OC Anumba

Presented by

Khondoker Akram

Affiliations

Academic unit of reproductive medicine, Department of Oncology and Metabolism, The University of Sheffield, UK. Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, UK

Background

Preterm birth (PTB) is the leading cause of death in children under five years of age. Over 15 million babies are born preterm and one million of them die every year worldwide. To date, the trigger and mechanism of spontaneous PTB remain largely unknown. There is limited effectiveness of therapies to prevent the occurrence of PTB, and a paucity of reliable predictive biomarkers. There is therefore the crucial need to improve our understanding of the molecular mechanisms of spontaneous PTB as this may inform improved diagnostics and therapeutics.

Method

To address this need, we conducted RNA-seq transcriptomic and qRT-PCR analysis on placental villous tissue from 20 idiopathic spontaneous preterm and 20 spontaneous term placentas to identify key genes and signalling pathways that are involved in the pathogenesis of PTB.

Results

Our differential gene expression (DEG), gene ontology and pathway analysis revealed several dysregulated genes including OCLN, ARF6, KRT7, SLC6A13, SLC6A17, SLC26A8, KLF8 and FOXA1 which are associated with altered trophoblast functions characterised by aberrant cell motility, differentiation and micronutrients transport. We also detected significant upregulation of pivotal Wnt ligands WNT7A and RSPO4 suggesting an augmentation of the canonical Wnt/β-catenin signalling that may have detrimental effects on trophoblast function. By conducting bioinformatics analysis on DEGs we have identified four key miRNAs, including miR-524-5p, miR-520d-5p, miR-15a-5p and miR-424-5p which were significantly downregulated in the preterm placenta as confirmed by qRT-PCR. These miRNAs may have regulatory roles on the aberrant gene expressions that we have observed. Furthermore, we have identified two potential biomarker candidates, RSPO4 and SLC26A8 that need further exploration.

Conclusion

Together, we provide new molecular insight for better understanding of the pathogenesis of spontaneous preterm birth. Further studies based on these observations may enable the development of new predictive biomarkers and therapies.