Submit an Abstract
Accommodation
Register

Oral Presentations

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.

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.

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.

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.

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.