Poster Sessions

Exploring the Role of Artificial Intelligence Algorithms in the Detection of Spontaneous Preterm Births

P01

Authors

Mariam Labib*, Brenda F Narice*, Mengxiao Wang, Joanna Shepherd, Zi-Qiang Lang, Dilly O Anumba
Brenda-7.jpg

Presenter

Brenda F Narice

Affiliations

Clinical Medicine, School of Medicine and Population Health, The University of Sheffield

*First co-authors

Abstract

Background

Preterm birth (PTB) is a global concern, being a leading cause of perinatal morbidity and mortality. Main risk factors include maternal demographics, obstetric history, pregnancy complications, and medical conditions. The key predictor is previous PTB, posing a challenge for nulliparous women.

Using retrospective data, we aimed to develop a universal predictive model for spontaneous preterm birth delivery <37 weeks based on information readily available to the woman which does not rely on the availability of either cervical length and/or foetal fibronectin .

Method

A logistic regression model was developed employing maternal demographics and obstetric history using anonymized preterm and full-term birth data of a total of 1017 cases. Statistical analysis was done to obtain the most predictive factors.

Results

The retrospective model, which was based on 7 variables [maternal age, BMI, race, smoker, gestational type, substances, and obstetric history], exhibited an AUC of 0.76 (95% CI: 0.71-0.83) for the testing set, with a sensitivity and specificity of 0.71 and 0.78 respectively.

Conclusion

The retrospective model holds potential especially for settings with no access to cervical length and/or expensive biochemical tests but requires prospective testing and further external validation before its true clinical value can be determined.

Intermediate PPC role in the reduction of Pre-term Births.

P03

Authors

Shallini Patni, Sarah Harman, Tracey Ashford
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Presenter

Shalini Patni

Affiliations

RCOG, Clinical Guideline No.1 (B)

RCOG, Clinical Guideline No.7

RCOG, Clinical Guideline No. 44

Guide to Effective Care in Pregnancy and Childbirth. 3rd ed. Oxford: Oxford University Press;2000

Preterm delivery. lancet 2002; 360: 1489-97

Am J Obstet Gynecol 2000;182:1458-67

Abstract

Background

Preterm birth is the most important single determinant of adverse infant outcome, in terms of both survival and quality of life.

Prevention and treatment of preterm labour is important, not as an end in itself, but as a means of reducing adverse events for the child. The aim of this audit was to determine whether the newly set up dedicated intermediate Pre-term prevention clinic’s guidelines are being met.

To identify any further areas for improvement and importantly to assess the effectiveness of PPC intermediate.

Method

It was a prosepctive cohort study over a 12month period. 126 patirents were identified from the intermediate PPC Data register with 114 being seen. Data on age, parity, investigations and outcomes were collected and analysed.

114 were seen due to numbers reducing from DNA’s, Declining investigation and incorrect referrals.

Risk Factors ranged from previous delivery at fully dialted by Caesarean section, Previous LLETZ and /or Cone Biopsy and Uterine Anomalies.

Results

Risk: 38 Prev C/S at Fully dialted

59 LLETZ, 14 Cone

2 Bicornuate uterus

1 Combination of factors

Findings: 107 of the women had a CX length of >2.5cm

15 women were referred to the Consultant Led PPC Clinic for assessment on the same day with 7 of those being discharged with a normal CX length, 7 required Progesterone, 1 required CX cerclage and Progesterone.

Of the 114 ladies seen those who required intervention were:

LLETZ = 5

C/S Fully =2

104 ladies went on to have a Term Delivery (37 weeks+)

7 had a pre-term delivery (34+1 – 36+6)

3 women had a pre-term delivery 24-34 weeks.

105 babies had a BW of >2.5Kg

5 babies 2-2.5Kg

2 babies 1-1.5Kg

1 baby 0.5-1Kg

Conclusion

Discussion Points:

13 women came to Intermediate PPC after having a LLETZ procedure which was then followed by at least one Term delivery prior to this pregnancy referral. Of those women none went on to have a pre-term birth.

If a woman has had treatment to the CX but then has gone on to have a term delivery, does she need to be seen in the PPC clinic in subsequent pregnancies??

Safety and Success Rates of Amniocentesis in cases of threatened preterm labour and preterm prelabour rupture of membranes: A systematic review and meta-analysis.

P04

Authors

Daniel Short1, Shreya Sheth1, Meredith Kelleher2, Nishel Shah1, Victoria Male 1, Suhas Kallapur3, Anna David4, Mark Johnson1.
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Presenter

Daniel Short

Affiliations

1 Department of Metabolism, Digestion, and Reproduction, Imperial College London

2 Division of Reproductive and Developmental Sciences, Oregon National Primate Research Centre

3 Division of Neonatology, University of California Los Angeles

4 Elizabeth Garrett Anderson Institute for Women's Health, University College London

Abstract

Background

Preterm birth (PTB), defined as birth before 37 weeks of gestation, is the leading cause of death of children under the age of five years worldwide. Globally there has been no change in the PTB rate between 2010 and 2020, when rates were calculated to be 9.8% and 9.9% of all livebirths respectively.

The analysis of amniotic fluid has been advocated to identify the mechanisms driving threatened preterm labour (tPTL). Amniocentesis is largely considered to be safe, but care provider concerns about complications in the setting of tPTL exist. This systematic review critically reviewed the data regarding safety and outcomes of amniocentesis in cases of premature rupture of membranes (PPROM) and tPTL.

Method

This systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA).

All English language, peer-reviewed human studies where amniocentesis was used to sample the amniotic fluid of patients presenting with tPTL or PPROM and published between January 1990 and March 2022 were included. Data on the uptake rates, success rates, and safety profile associated with amniocentesis in this context of tPTL or PPROM were analysed. Studies eligible for inclusion in the systematic review were randomised control trials, cohort studies, and case-control studies. Conference abstracts and abstracts with no full text were excluded.

Results

10215 studies were returned after searches were conducted in MEDLINE, EMBASE, EMCARE, Web of Science, and SCOPUS databases using free text and Medical Subject Headings (MESH). 399 studies were assessed for eligibility with 15 studies being included in the final review The main reason for exclusion was an absence of safety data.

Four studies gave information on uptake rates of amniocentesis in cases of PPROM and tPTL, with a range of 55% in an observational study to >99% in centres offering it as part of routine care.

Eleven studies detailed success rates of amniocentesis, with all centres reporting >90% success rates. However, in some centres a “successful” amniocentesis was deemed to be a retrieval of >0.5ml.

Three studies reported risks associated with amniocentesis. In total, there were four reported complications in a series of 1119 cases (0.35%). These were all transitory and no long-lasting impact on the mother or fetus.

Conclusion

This systematic review found that amniocentesis in cases of PPROM or tPTL is a safe and feasible procedure. These data should give care providers confidence to counsel patients appropriately.

Underexpression of activating receptors by uterine NK cells is associated with failures of placental implantation

P05

Authors

Ee Von Woon, Dimitrios Nikolaou, Kate MacLaran, Julian Norman-Taylor, Priya Bhagwat, Antonia O Cuff, Mark R Johnson, Victoria Male
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Presenter

Viki Male

Affiliations

Department of Metabolism, Digestion and Reproduction, Imperial College London (Woon, Cuff, Johnson, Male)

The Fertility Centre, Chelsea and Westminster Hospital, London (Woon, Nikolaou, MacLaran, Norman-Taylor)

Department of Cellular Pathology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London (Bhagwat)

Abstract

Background

Insufficient placental implantation is associated with disorders of pregnancy that ultimately lead to preterm birth, including pre-eclampsia, intrauterine growth restriction and preterm labour. The uterine mucosa is rich in uterine NK cells, which are thought to promote placental implantation and individuals who possess the gene encoding the NK cell activating receptor, KIR2DS1, are at lower risk of pre-eclampsia. We will test the hypothesis that uterine NK cell expression of KIR2DS1 is associated with lower risk of pregnancy disorders characterised by failures of implantation.

Method

We recruited two cohorts: 1. Fertile controls attending to have a contraceptive coil fitted (n =11); 2. Patients attending the fertility clinic for recurrent implantation failure (n = 3), recurrent miscarriage (n = 4) or unexplained infertility (n = 9). Matched peripheral blood and endometrial samples were obtained during mid-luteal phase and immune cells were isolated, stained for uterine NK cell markers, KIR2DS1/L1 and CD107a (as an indicator of activity) and examined by flow cytometry.

Results

In preliminary findings, expression of KIR2DS1/L1 was significantly lower in both uterine (p = 0.01) and circulating (p = 0.02) NK cells in the implantation failure group. Uterine NK cells were also significantly less active in the implantation failure group (p = 0.02). However, we found no significant association between either of these measures and pregnancy outcomes.

Conclusion

Our findings are consistent with previous studies suggesting that lack of expression of NK cell activating receptor KIR2DS1 is associated with failures of implantation. However, the antibody we used could not distinguish between KIR2DS1 and the closely related inhibitory receptor KIR2DL1. We are addressing this in current work. We also found lower uterine NK cell activity associated with implantation failure. However, our finding that neither uterine NK cell KIR2DS1/L1 expression nor activity predicted pregnancy outcome raises the possibility that the association is not causal. Current work on larger cohorts aims to address this.

In utero transfers out of Great Western Hospital: Updates and improvements implemented following a review of patient care

P06

Authors

Saba Jameel, Coral Backhurst, Alex Van Der Meer

Presenter

Saba Jameel

Abstract

Background

Background

In utero transfers (IUT) are required when a woman is likely to deliver a baby that requires expertise or facilities not immediately available at the local unit. This may be as a result of prematurity, specific medical conditions in mother or baby, or cot availability in NICU. Babies born less than 27/40 are 1.3 times more likely to die if born outside non-tertiary centres. Ex utero transfers are those that occur immediately after birth. They are associated with increased neonatal morbidity and mortality and some of these may represent missed opportunities for in utero transfers.

Aims

To review factors that play a role in IUT in order to propose improvements to guidelines, ensuring timely and appropriate transfer for pregnant mothers at risk. Improve patient experience of IUT and decrease time spent arranging IUT after clinical review. Finally, aiming to decrease the number of unnecessary transfers.

Method

Methods

An initial retrospective study that identified 50 pregnant women that required IUT from December 2020 to December 2022 was conducted. This information was gathered from electronic notes on Maternity Medway. These notes were analyzed to look at Gestational age (GA) at presentation, time of review by MW, time of senior obstetric review and time of transfer. Also studied was compliance to the PERIPrem bundle such as whether steroids and/or magnesiumsulphate were given and whether expressing breast milk (EBM) was discussed.

Results

34 women presented with GA <27/40. The most common reason for presentation was TPTL (37%), PVB (36%) and SRM (17%). Documentation around onset of symptoms was poor, 18 women did not have their onset of symptoms documented. Steroid administration: 31 received, 15 not documented. 9 women received a loading dose of magnesium sulphate. Expressing breast milk was discussed in 8 cases, with no documentation in the other cases included. Further challenges that were identified included Staffing issues, calling Cot lines, SCUBU and delivery suite bed for mothers and time taken to make ambulance arrangements.

Conclusion

Due to issues identified in this study, GWH have updated the IUT form. This now includes a detailed assessment including VE and CTG concerns as well as specific times for administration of medications (steroids and MgSO4). To tackle delays in transfer, early involvement of SoNAR transport services is now advised. They have 12 hourly data on cot availability across the South-West region. Education around the PERIPrem bundle has also been rolled out with an aim to review adherence to the bundle.

Laparoscopic Uterine Cerclage : Safe and Effective?

P07

Authors

Ciaran Barclay, Ken Ma, Kingshuk Majumder, Nikolaos Tsampras, Andy Pickersgill, Edmond Edi-osagie
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Presenter

Clare Mullan

Affiliations

Saint Mary's Hospital, Oxford Road, Manchester

Abstract

Background

Study Objective : To determine the safety and efficacy of all cases of laparoscopic uterine cerclage performed in a tertiary referral centre over a 14 year time period.

Method

Design : Retrospective Cohort Study.

Setting : Tertiary referral centre and University Teaching Hospital.

Patients or Participants : All patients who underwent laparoscopic uterine cerclage from March 2010 to September 2023. 30 patients identified.

Interventions : Laparoscopic insertion of uterine cerclage

Results

A total of 30 cases were identified. 30/30 patients presented with a history of recurrent pregnancy loss or extreme premature labour (below 26 weeks). Indication included further mid-trimester loss or extreme premature labour despite elective cervical cerclage (17/30), failed rescue cerclage (4/30) and a short cervix on ultrasound or failure to insert cervical cerclage (6/30). One intraoperative complication was noted in the form of a uterine perforation sutured at the time with no sequelae. Mean operating time was 98 minutes (Range 52-146). No post-operative complications or readmissions were noted. Of the 21 patients who underwent surgery greater than 12 months ago, there were 14 spontaneous conceptions (14/21 patients), 2 first trimester miscarriages and 12 livebirths after 37 weeks gestation by elective or emergency caesarean section. In the 2 patients who suffered a miscarriage the first had a surgical evacuation without complication, the second required no intervention. 2 of the laparoscopic insertion of uterine cerclages were performed in patients already pregnant, the first at 9 weeks gestation, with no complications, delivered by caesarean section at 37+0 weeks gestation. The second at 12 weeks gestation, with no complications and an ongoing pregnancy now 17 weeks gestation with a cervical length greater than 45mm on ultrasound.

Conclusion

Laparoscopic uterine cerclage remains a novel technique with a strict inclusion criteria requiring regular surveillance and audit of outcomes. There are currently no robust randomized control trials comparing management options for women with recurrent pregnancy loss after elective cervical cerclage. Despite the small numbers our results indicate that this technique has a good safety profile and efficacy in livebirths rates >34 weeks. Our results supports expansion of this service at a regional level through multi-disciplinary assessment to enable this technique becoming an established practice.

Optimising Bacterial Co-Culture with Vaginal Epithelial Cells.

P08

Authors

Rebecca S. Posner, Sogol Salamipour, Victoria Horrocks, Sarah J. Chapple, A. James Mason, Rachel M. Tribe
Rebecca-Posner_Headshot.jpg

Presenter

Rebecca Posner

Affiliations

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

Institute of Pharmaceutical Science, School of Cancer and Pharmaceutical Sciences, King's College London, UK

Department of Vascular Biology & Inflammation, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, UK

Abstract

Background

The cervicovaginal environment (microbiome, innate immune system, and metabolome) is an important contributor to a healthy pregnancy. Risk of premature birth (PTB) is associated with changes in resident microbial community, altered immune responses and inflammation. However, the mechanistic pathways leading to PTB have yet to be fully established. It is hypothesised that the microbiota modifies both vaginal epithelial (VE) barrier integrity and host innate immune response, and that the resulting inflammation increases risk of cervical shortening ± ascending infection [1].

The aim of this study was to use our robust and physiologically relevant 3D VE cell (VEC) model to test this hypothesis in vitro. We have validated optimum and physiologically relevant growth conditions for VECs and bacteria prior to coculture.

Method

VK2 E6/E7 cells were cultured in keratinocyte serum-free media (KSFM) in transwell inserts with an air-liquid interface (± normoxic conditions, n=3 independent replicates/group/experiment). Trans-epithelial electrical resistance (TEER) was measured. Cells were fixed for histological and immunofluorescent staining and imaging. The impact of bacterial growth medium (brain heart infusion, BHI) and bacterial supernatant on VEC integrity was assessed. Bacterial growth in BHI and KSFM was assessed using optical density measurements. Supernatant was collected for further metabolite analysis using nuclear magnetic resonance.

Results

This model displays multilayers and produces glycogen. There was an increase in barrier integrity from day 2 to day 10 (TEER from 7.44 Ω.cm2 to 53.35 Ω.cm2, p<0.01). To determine toxicity levels, different concentrations of BHI with and without bacterial supernatant from Lactobacillus acidophilus, L. crispatus, Gardnerella vaginalis (GV) 10287 and GV KC2 were added to VK2 cells for 24 hours. The CellTiter 96 MTS viability assay showed no significant difference between the conditions and compared to control cells exposed to KSFM for 24 hours. To ensure the success of co-culture of VECs with bacteria, anaerobic bacteria (GV 10287, GV KC3, and Prevotella bivia, PB) was sub-cultured at 5% oxygen in both BHI and KSFM as monocultures, and in cocultures (GV strains with PB). Growth was detected for all strains. When PB was cocultured with GV, the optical density was similar to GV alone.

Conclusion

Our model is physiologically relevant. This provides the groundwork for assessing the impact of bacterial metabolites and bacterial co-culture on VEC structural integrity and host response.

Nurturing New Beginnings – Challenges and Outcomes of setting up a Preterm Birth Prevention Clinic

P09

Authors

Humaeel Abbas Ali, Orly Huff, Sayantana Patra-Das
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Presenter

Humaeel Abbas Ali

Affiliations

Zubaida Abubakar

Husna Marjan

Eziaha Ogbuagu

Priya Chowdhury

Delaram Zadeh

Bahei Desouki

Department of Obstetrics and Gynaecology

Homerton University Hospital, London

Abstract

Background

Great strides have been taken by NHS England to curtail perinatal mortality rates due to prematurity as nearly 58,000 babies are born preterm in the UK annually. This underscores the need for specialized services and prevention strategies embodied in Element 5 of the Saving Babies Lives Care Bundle version 3. Homerton University Hospital manages a substantial annual birthrate of 5600 babies with level 3 neonatal care, catering to a diverse population. Historically, the unit relied on history indicated cervical cerclage and progesterone administration. In 2020, a specialized preterm birth prevention clinic was established evolving from a surveillance clinic to an independent entity with a preterm birth lead team. The second audit below evaluates the clinic’s adherence to guidelines, appropriateness of referrals, preterm delivery rates and compares against national benchmarks.

Method

Retrospective data collected from January 2021 to December 2022, were recorded and analyzed, employing a variety of graphs for visual representation. Referral criteria were based on risk factors outlined in Appendix F of Saving Babies Lives Care Bundle.

Results

Among the 222 patients assessed, data from 205 were included to ensure accuracy. The preterm birth rates in 2021 and 2022 (8.2% and 7.3% respectively) align with National standards. The most common reason for referral was a previous LLETZ procedure (46%) and the preterm delivery rate was 5.9% surpassing other referral criteria. Fully dilated cesarean was the second common reason for referral (17%). Twelve women had a cervical cerclage, 50% of them being history indicated; 58% delivering preterm. Progesterone was prescribed for 25 women of which 36% subsequently delivered prematurely. 22% of women seen due to previous fully dilated cesarean were referred late.

Conclusion

The establishment of a dedicated preterm birth prevention clinic has significantly improved care in a condensed timeframe. Patient feedback was instrumental in refining clinic operations, leading to an improved information leaflet. Recent incorporation of predictive tools like Fetal fibronectin and the QuiPP app, has enhanced management of both symptomatic and asymptomatic women; with ongoing data analysis. Dedicated study days and training initiatives for obstetric registrars in preterm birth prevention and cervical length assessment have been implemented. This audit underscored the need for improved referral pathways for BAME population. Highlighting appropriate referral indications and disseminating this information amongst colleagues is imperative to avoid unnecessary referrals. This clinic commits to a multidisciplinary approach in refining preterm birth prediction and prevention aligning with Saving Babies Lives care Bundle objectives to reduce perinatal mortality.

LLETZ Talk About Depth: Regional Data on Antenatal Cervical Length Screening in Individuals with Previous 11-15 Millimetre Large Loop Excision of Transformation Zone.

Authors

Dr Jennifer Newton FY2, Dr Jennifer Bisland ST2
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Presenter

Alexandra Patience

Affiliations

Department of Obstetrics, Royal Victoria Infirmary.

NHS Newcastle Upon Tyne Hospitals

Abstract

Background

In 2019, Saving Babies Lives version 2 (SBLv2) outlined national recommendations for those who required referral to preterm birth clinics for ultrasound surveillance of cervical length (CL) during pregnancy. This included women who had a history of a single large loop excision of the transformation zone (LLETZ) with a depth greater than 10mm.

This was updated July 2023, with Saving Babies Lives version 3 (SBLv3) adjusting this recommendation. Now, only those with a single LLETZ depth greater than 15mm require referral to preterm birth clinics. This was introduced despite no new evidence regarding the risk of preterm birth following LLETZ at different depths.

Method

We retrospectively reviewed notes of women who had undergone antenatal surveillance in preterm birth clinics, exclusively for the indication of a single LLETZ depth between 11-15mm, between October 2022 and March 2023, across 8 maternity units in the North East of England and North Cumbria. Those with any additional risk factors that required preterm screening were therefore excluded, as were women where the depth of LLETZ biopsy was unknown.

Data was collected locally, anonymised and centrally collated. Information was gathered on the number identified with a short cervix <25mm, any interventions received, pregnancy complications including PPROM and outcomes including gestation at delivery, mode of delivery and onset of labour.

Results

Of the eighty-seven screened women, six (7%) were found to have a short cervical length of ≤25mm and an intervention was discussed to reduce preterm birth risk. One extra patient was offered progesterone based on a reduction in cervical length from 37 to 26mm. Of the six women with CL <25, two opted for conservative management (delivered at 39/40 and IOL 36/40), two were given progesterone alone (delivered 37/40 and 32/40), one had progesterone and cervical stitch (delivered 39/40) and the final patient opted for both progesterone and stitch, but experienced PPROM prior to stitch insertion and delivered at 23+6/40.

Conclusion

It is unclear why the screening threshold for a single previous LLETZ was increased between SBLv2 and SBLv3. From our region, we have demonstrated that 7% of the 11-15mm screened group were identified as having a short cervix, were counselled and offered an intervention to reduce their individual risk of preterm birth.

Given not only the significant morbidity associated with prematurity, but also the financial implications of preterm birth on healthcare services, combined with the relatively low cost of cervical length screening, we suggest it is worth reconsidering the cost-effectiveness of excluding this particular group of women from review in preterm birth clinics.

Pregnancy outcome of pregnancy after cervical Cerclage; Carlisle Experience

P11

Authors

Agnus Moorthiraj, Emma Savage, Fola Awodiya, Samanthika Madies, Femi Ajibade, Ravimohan Velauthapillai.
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Presenter

Agnus Moorthiraj

Affiliations

Cumberland Infirmary Hospital

North Cumbria Integrated Care NHS Foundation Trust

Abstract

Background

Cervical cerclage remains one of the preventive strategies of preterm birth. Preterm birth screening of pregnant women is based on the RCOG & National guidelines for preterm delivery prevention. Women with moderate risk factors are offered Trans- vaginal (TV) scan monitoring of cervical length, and progesterone or cerclage if cervical length is < 25mm. Multifactorial development in RCOG training programme has reduced the development and maintenance of skillset for Management of at risk group. Local capacity or availability of early neonatal facilities can be a challenge for patients presenting with preterm birth in rural hospitals like in Carlisle. The aim of the study is to look at the outcome and effectiveness of locally applied sutures in at risk pregnancy including the indication, length of gestation post-procedure and pregnancy outcome. The study was at the Cumberland Infirmary Hospital, Carlisle.

Method

A retrospective analysis of the data over a period of 18 months was done. 12 women out of 2619 antenatal bookings needed cervical cerclage in the unit. These 12 (0.5%) deliveries were part of the 2200 deliveries over 18 months. All of them were ultrasound indicated and were followed up in the preterm prevention clinic. McDonald sutures were inserted for all women.

Results

8/12 (66.7%) had cervical suture application

4/12 (33.3%) had progesterone and Cervical suture.

2/12 (16.6%) had progesterone initially followed by Cervical suture.

11/12 (91.6 %) of the sutures were applied locally.

1/12 (8.3%) suture applied in another unit.

Gestation at delivery

1/12(8.3%) delivered before 34 weeks – rescue suture, applied at another unit at 18 weeks.

3/12(25%) delivered between 34-37 weeks.

8/12(66.7%) delivered over 37 weeks.

Number of weeks post cerclage till delivery Number of women Percentage of women

11 1 8.3%

14 1 16.6%

15 2 16.6%

16 2 16.6%

17 2 16.6%

18 2 16.6%

19 2 16.6%

1/12 (8.3%) needed full neonatal optimisation due to gestation less than 34 weeks.

Conclusion

This result shows that cervical cerclage is still a reliable method of preventing preterm birth (66.6% delivery) in a small District General Hospital (DGH).

The result also shows that surgical application of suture by experienced team in DGH setting is safe (91.6%). The combined progesterone and cerclage approach is equally as effective in situation of rescue cerclage. The study has limitation of sample size. There is need to conduct a full study to look at the effect of combined progesterone and cervical suture in high-risk patients.

Pregnancy outcomes in women with a surgically short cervix with no history of preterm birth.

P12

Authors

Lia Roth, Helena Bartels, Gillian Corbett, Larissa Lüthe, Siobhan Corcoran
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Presenter

Lia Roth

Affiliations

Heidelberg University,

The National Maternity Hospital Ireland,

University College Dublin

Abstract

Background

Preterm birth is the most common cause of perinatal morbidity and mortality. This study aimed to explore the pregnancy outcomes of pregnant women stratified by cervical length after significant cervical surgical treatment without history of preterm birth. The primary outcome was preterm birth.

Method

This is a descriptive, retrospective cohort study analysing a large series of patients at high risk of preterm birth who attended a specialist preterm birth clinic in a tertiary referral centre. Inclusion criteria were: consecutive patients who attended the pre-term birth clinic between September 2019 – March 2023 who had a significant cervical surgical history (two or more LLETZ or a cone biopsy) and gave birth in our centre. Odd’s ratio (OR) with 95% confidence intervals (CI) were calculated.

Results

201 patients met inclusion criteria, of whom 12% (n=25) gave birth pre-term. Women with a cervical length <2.5 cm without history of preterm birth (n=44) were treated with either an Arabin pessary (30%, n=13), a vaginal cerclage (5%, n=2) or an abdominal cerclage (45%, n=20), and 73% (n=32) received (additional) vaginal progesterone, whereas 9% (n=4) were only under surveillance. The preterm birth rate in this group was 20% (n=9), with a mean (±SD) gestational age at delivery of 37±3 weeks. 11% (n=5) of neonates required treatment in the neonatal intensive care unit.

Conclusion

In women with a cervical length <2.5 cm (n=18) who had a prior history of preterm birth, 39% (n=7) delivered preterm again. The risk of preterm birth in women with a cervical length <2.5 cm with or without a history of preterm birth was not significantly different (OR=2.5; CI 0.7-8.1). In women with a cervical length >2.5 cm without history of preterm birth (n=104) the preterm birth rate was 7% (n=7). Only 28 % of these patients received an intervention to prevent preterm birth, indicating that this group has a better outcome a priori. As expected, overall the risk of preterm birth was significantly higher for women with a cervix <2.5cm (OR=0.3; CI 0.1-0.8). In conclusion, we present a large cohort of women with a history of significant cervical surgery who attended a dedicated preterm birth clinic. Women with a cervical length >2.5 cm without history of preterm birth have a similar preterm birth rate to the background population of the unit. Those with cervical length <2.5cm with abdominal cerclage also had a low rate of preterm birth.

A retrospective analysis of Cerclage versus cerclage + progesterone in a tertiary unit over a calendar year

P13

Authors

Asena Akdeniz, Dr Natalie Suff, Dr Manju Chandiramini
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Presenter

Nicole Moriarty

Affiliations

Kings College London, Guys and St. Thomas' NHS trust, London

Abstract

Background

1 in 7 babies in the UK are born preterm or less than 37 weeks gestation. Being born early can have lifeling implications, 1 in 3 of these babies have cerebral palsy, and prematurity is the leading cause of mortality in the first year of life. The interventions offered to women at risk of preterm birth include surgery (insertion of a cervical cerclage or stitch) and medication (giving a hormonal pessary, or progesterone) in addition to surveillance in the second trimester of pregnancy. While numerous previous studies, including the 2019 EPPPIC: meta-analysis have shown that progesterone can be effective in reducing preterm birth, its use in combination with preventative surgery (cerclage), for patient benefit has not yet been proven. Our study assessed whether combining both surgery and medication reduces the risk of preterm birth in a high risk cohort of women.

Method

A retrospective analysis of patients who underwent a Transvaginal Cerclage in a Tertiary birth in London, UK in 2022, comparing outcomes of women who have been treated with a preventative cerclage, or cerclage and vaginal progesterone was undertaken. Primary outcome was births occurring at less than 37+0 weeks.

Data was extracted from electronic patient records. Dates of surgery were 1st January 2022 to 31st December 2022 inclusive. Multiple pregnancies, transabdominal cerclages, and rescue cerclages were excluded from analysis.

Results

970 women had preterm birth clinic appointments in 2022. Of these, 152 received cerclages during 2022. 70 women’s charts were reviewed once exclusion criteria was applied. Of these, 42 received cerclage alone, and 27 received cerclage and progesterone.

Of the dial therapy group (n=27), 15 (54%) had a preterm birth <37 weeks, 12 (43%) of which were <34/40. Mean gestational ages at delivery in the combined treatment group was 32/40 (SD 7) The cerclage only group (n=42) had 13 (30%) preterm births, mean GA at delivery was 35/40 (SD 5.6). 10 (23%) of the preterm births occurred <34/40.

Conclusion

No reduction in incidence of preterm birth in at-risk women who are treated with both cervical cerclage, and concomitant vaginal progesterone, compared with cerclage alone was demonstrated. Combination therapy was less effective than cerclage only, however it is possible the that women receiving both interventions were a higher risk group. Going forwards, we would recommend a large, randomised control trial to explore this further.

Preterm Optimisation: A Retrospective analysis

P14

Authors

Dr. Nicole Moriarty, Rebecca Kettleman, Dr M. Chandiramani
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Presenter

Nicole Moriarty

Affiliations

Kings College London,

Guys and St. Thomas NHS Trust

Abstract

Background

Preterm Births, defined as delivery prior to 37 weeks’ gestation, occurring in 11% of pregnancies worldwide. Prematurity is the leading cause of neonatal mortality and morbidity, resulting in significant psychological impact on families, their children, and huge financial costs to society.

The British Association of Perinatal Medicine introduced the Saving babies lives care bundles in 2019, and an updated version 3 was presented In Spring 2023. Part of this bundle emphasises the management of preterm birth, as optimisation of women and their babies has shown to significantly improve neonatal outcomes.

Method

Aim: To assess the delivery of pharmacological interventions- Antenatal Corticosteroids (ACS), Benzylpenicillin and Magnesium Sulphate (MgS04)- for optimisation of preterm labour in a London maternity unit.

Study Design: A retrospective chart analysis of preterm deliveries in St Thomas’ hospital in 2022 using the electronic maternity records was performed. Women who delivered between 22+0 and 34+6 weeks were included. Excluded were women delivering outside this gestational range; intrauterine death (IUD); medical termination of pregnancy (MTOP); fatal foetal abnormalities; women progressed to term.

Results

191 women were included, who delivered between 22+0 and 34+6 weeks during 2022. Table 1 shows the numbers of women administered 1st dose of medication, subsequent dose and optimised within the appropriate time frame for delivery.

Initial dose of antenatal corticosteroids was achieved in 168 (88%) preterm infants, however only 68 (36%) received these within the optimal timing window. Antibiotic prophylaxis was commenced in 54 (28%) of the cohort, a further 14 (7%) were given antibiotics to treat chorioamnionitis. Three women received vancomycin as they were penicillin allergic. Magnesium sulphate was commenced in 111 (58%) preterm births. When we examined births <30 weeks in keeping with recommendations for preterm neuroprotection, 43/76 (57%) had received optimal magnesium sulphate infusion prior to delivery.

Conclusion

Optimal Antenatal medication administration for preterm birth optimisation is a complex timing window that has many variables. Quality improvement interventions are recommended to improve timing of administration.

Improving the care of families at risk of Preterm Birth with the introduction of a designated Preterm Birth clinic.

P15

Authors

Dr Moorthiraj, Mr Adeleke, Mr Ravimohan
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Presenter

Emma Savage

Abstract

Background

PreTerm Birth (PTB) is the leading cause of neonatal mortality and morbidity and the national ambition is to reduce the PTB rate to 5% by 2025. It was introduced as part of Saving Babies Lives Care Bundle v2 and v3. Compliance with this element is expected to reduce the PTB rate and also improve the optimisation and stabilisation of the preterm infant. This is especially critical when the maternity unit is not a tertiary centre and has a very rural population and demographic; adding complexities when planning and providing pre-term care.

It was identified through clinical observation that women at risk of preterm birth were not being appropriately risk assessed or seen in a specialist clinic in line with SBLCB.

Method

A PTB specialist midwife post was introduced, with the remit of introducing a designated PTB prevention clinic for women who were at intermediate or high risk of PTB using the risk assessment within SBLCB. This clinic has a designated specialist midwife and an obstetric consultant with specialist knowledge around preterm birth. An initial risk assessment in line with SBLCB was developed for the booking appointment, initially paper and then electronic to improve the referral process. Allowing early assessment of the risks. They were assigned to the appropriate pathway. All women received a 1:1 phone contact outlining the service and recommended pathway, prior to 12 weeks. They were also offered a face to face consultation in the PTB clinic. They then commenced on the appropriate pathway. Referrals have been compared from the same 6 month period within the year prior to the PTB clinic commencing.

Results

Since introduction of the specialist PTB midwife and the PTB clinic, there has been a comparable rate of high risk woman but a reduction in women on the intermediate pathway, from 9.5% to 6.2%. This due to the more specific referral pathway. There was also a reduction in the number of women who smoked on the PTB pathway from 28% to 18%. Smoking is discussed at the initial contact with women by the PTB midwife. Feedback from women has been routinely sought through ‘your voice matters’, positive themes include continuity of carers in the clinic, having a contactable PTB midwife and feeling well cared for.

Conclusion

Through having a designated preterm birth specialist midwife and a specific PTB clinic has allowed care to be stream lined and more efficient optimising capacity. The referral system has allowed the prompt identification and review of woman at increased risk of PTB allowing appropriate individual centred care to be delivered. Feedback from the clinic has been very positive. Plans are in place to extend this further by having the PTB midwife be trained in Cervical Length scanning which will ensure women receive a greater level of holistic care,

Service Evaluation of Uterine anomalies referred to Liverpool Women’s Hospital (LWH) Preterm Birth Clinic (PTBC)

P16

Authors

E Medford, G Morgan, R McFarland, A Care
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Presenter

Elizabeth Medford

Affiliations

Centre for Women's Health Research, University of Liverpool.

Liverpool Women's Hospital.

Abstract

Background

Uterine anomalies are associated with a higher risk of spontaneous preterm birth (sPTB). However, identifying those patients with a known uterine anomaly (UA) who will then subsequently deliver preterm is an ongoing challenge. The gold standard practice of serial cervical length (CL) screening has shown to be ineffective in this at-risk group. Additionally, there is no known effective management options to reduce the incidence of sPTB in this cohort.

Despite this, since 2019 NHS England guidance has specified uterine anomalies require CL surveillance under a dedicated PTBC in the Saving Babies’ Lives (SBL) bundle.

Method

A service evaluation was completed on all referrals to LWH PTBC for a UA who delivered between June 2022 and October 2023.

The objective was to identify; 1) the proportion of referrals for UA to our PTBC 2) compliance with SBL guidance, 3) sPTB rate is in this cohort and 4) the detection rate of CL surveillance for sPTB.

Results

Our service received a total of 437 referrals over 17-months. Referrals with a known UA as the only SBL risk factor contributed to 5% (24/437) of these, and had a sPTB<34w rate of 17% (4/24). The proportions of UA by type and their sPTB risk are; 1) bicornuate 14/24 (sPTB<34w n=1 (7%) at 33w+1d), 2) unicornuate 4/24 (sPTB<34w n=1 (25%) at 33w+1d), 3) didelphys 5/24 (sPTB25mm on discharge from PTBC surveillance. No cervical cerclages or pessaries in this group. No sPTB <28 weeks. sPTB<34w cases (n=4); All had CL screening, 1 required treatment (VP) and 3 did not have a short cervix during surveillance. All 4 cases had a long cervix at the point of discharge from PTBC.

Conclusion

There is a variance in sPTB<34w risk between type of UA, the greatest risk is with uterine didelphys and the lowest risk is with bicornuate. CL surveillance appears ineffective in detecting those at risk with a UA. 75% (3/4) of sPTB<34w never had a short cervix (≤25mm). Treatment for a short CL (3/24) was used infrequently in this population. These findings suggest SBL guidance should be reviewed for women with uterine anomalies.

The Distribution of Vape Shops and Stockists in Dublin City in Relation to Maternity and Paediatric Services Utilising the Pobal HP Deprivation

P17

Authors

Nessa Hughes, Carmen Regan, Kate Frazer, Paul Bellew, Howard Jones, Des Cox
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Presenter

Eibhlín Frances Healy

Affiliations

The Coombe Hospital, Dublin 8, Ireland.

Royal College of Surgeons, Dublin 2, Ireland.

University College Dublin, Dublin 4, Ireland.

Ordnance Survey Ireland, Dublin 8, Ireland.

HSE Digital Intelligence Unit, Stevens's Hospital, Dublin 8, Ireland.

Abstract

Background

Vaping is increasingly viewed by the public as a reasonable option to assist smoking cessation and is endorsed by public policy in England to support smokers attempting to stop during pregnancy. However, the risks of vaping in pregnancy and its impact on early childhood are unclear; the potential for nicotine addiction is a serious consideration. We hypothesised that there would be an over-representation of vape shops in areas of higher deprivation as defined by the HP Pobal Deprivation Index (1).

Method

We aimed to ascertain the distribution of vape shops and stockists in relation to maternity and paediatric services in Dublin, and to map these locations onto areas of different socioeconomic advantage and disadvantage utilising data from the Central Statistics Office. We collaborated with Ordnance Survey Ireland and the Health Service Executive (HSE) to create a digital map. We identified the locations of vape shops via a structured, electronic search carried out by two researchers using search platforms, Google Street view and online businesses directories. A database was collated using Excel; geocoded; and mapped with Geohive software.

Results

We identified 40 vape speciality shops and 127 vape stockists (total n= 167) within the confines of the M50. Additionally, we noted that disposable vapes were sold in a variety of locations out with ‘normal’ retail units, ie. phone shops, pop-up shops, however these were excluded from analysis due to reproducibility. 89 vape stockists were located in areas denoted to be affluent or very affluent, 79 were noted to be located in areas of marginal to severe disadvantage. These findings are represented on the digital map (Fig. 1).

Conclusion

Although there appears to be an ‘equal’ distribution of vape shops across Dublin, detailed interrogation of our map indicates a higher proportion of vape shops are located at the fringes and intersection of affluence and deprivation, with evidence of clustering around paediatric and maternity services. This may indicate a positive finding that people in these areas are switching to vaping over smoking. Or, this could be interpreted as vape companies attempting to capture a population already addicted to nicotine for commercial benefit. More research is needed on vaping habits in pregnancy to determine the impact on the woman, fetus and infant.

References:

1. Haase T, Pratschke J. The 2016 Pobal HP Deprivation Index for Small Areas (SA): Introduction and Reference Tables, 2017.[Online].

Successes and Challenges of a New Preterm Birth Prevention Service – An Audit of Patient Outcomes at Barnet Hospital

P18

Authors

Orly Huff, Gregory Premetis
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Presenter

Orly Huff

Affiliations

Ayanthi Gunasekera, Maureen Darko

Abstract

Background

Preterm birth prevention has been nationally prioritised through strategic publications from the Preterm Clinical Network and Saving Babies Lives. Barnet Hospital delivers 5600 babies a year offering level 2 neonatal care, and is part of the Royal Free London NHS Foundation Trust. A new preterm birth prevention clinic was launched in 2021 for women at risk of preterm birth, where cervical length screening and individualised clinical management are provided together. This superseded the previous mainstay of departmental cervical length scanning and antenatal clinic follow up, and provided specialist care to the standard expected nationally and available elsewhere in the trust.

Method

Data was collected prospectively, recorded and analysed on an Excel spreadsheet. Data presented is from the 2022 audit.

Results

108 women were seen from January-December 2022. The most common reason for referral was previous late miscarriage(28%). Others included previous preterm birth(23%); previous fully dilated Caesarean section(12%); incidental short cervix(10%); previous 2 LLETZ/cone biopsy(8%); previous PPROM(6.4%); and others(13%). Mean gestation at first visit was 16+4 weeks and mean number of visits was 3 (range 1-8). The total number of cervical cerclages was 40(37%), of which 25 were ultrasound-indicated. Progesterone was given in 73% women. There were 3 late miscarriages, one of whom declined progesterone or cerclage despite a short cervix. There were 11 preterm births, however five were above 36 weeks.

Conclusion

This service has provided women with streamlined specialist care, a dedicated midwife and a new patient information leaflet published in 2023. Anecdotally, women have given positive feedback however a formal patient satisfaction survey is planned to involve women in the service development. Challenges include limited capacity, with a plan to expand the clinics from alternate weekly to weekly. Furthermore, as the clinic is currently on Thursdays, cerclages often occur on Friday or over the weekend. Dedicated cervical cerclage lists by a team of consultants would ameliorate this problem. Specialist consultant training in abdominal cerclage via regional centres is also planned. The use of progesterone prophylactically is comparatively higher than other units, and this will be examined with a view to rationalising this and re-auditing outcomes. Further training in cervical length scanning is planned for the sonographers to provide this at the anomaly scan for appropriate women. Finally, inappropriate referrals constitute a large workload for the specialist midwife, where further staff education on the referral criteria will help improve this.

Cervical remodelling as a predictor for preterm birth

P19

Authors

1. H Rosen O’Sullivan 2. N Suff 3. C Valensin 4. R Tribe 5. A Shennan.
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Presenter

Hannah Rosen O'Sullivan

Affiliations

King's College London

Abstract

Background

Cervical stromal tissue is majority extracellular matrix (ECM). It undergoes a significant remodelling process during pregnancy. Cervical softening, the first remodelling phase, begins from early in the first trimester and continues until term. Matricellular proteins (MCP) are non-structural proteins within the cervical ECM which influence matrix organisation and consequently tissue strength.

It is hypothesised that premature cervical remodelling could lead to premature birth. This study uses a novel device to measure cervical stiffness (CS) during pregnancy and aims to evaluate whether cervical softening is associated with preterm birth. It also aims to quantify levels of MCP in the cervicovaginal fluid to determine if they are correlated with CS measurements and risk of preterm birth.

Method

– Observational study. Serial CS measurements taken at up to 5 gestational timepoints from asymptomatic women at high risk of spontaneous preterm birth.

– CS measurements taken using an aspiration device (Pregnolia system), which consists of a control unit, tubing and single use sterile probe. The probe is placed on the anterior lip of the cervix during speculum examination. A weak vacuum is created which aspirates the cervical tissue to a depth of 4mm the amount of pressure required to do this is recorded as the CS value (mbar). Paired cervical length, quantitative fetal fibronectin and high vaginal swabs taken.

– Multiplex ELISA assays used to determine matricellular protein levels at different gestational time points.

Results

– 168 women included, 90 delivered, data collection ongoing.

– CS significantly lower in women delivering preterm compared to term (mean CS term 70.94 mbar, mean CS preterm 38.17 mbar, p=0.03).

– AUC for cervical stiffness as a predictive test for spontaneous preterm birth <37 weeks = 0.8, compared with the AUC for cervical length = 0.7 and fetal fibronectin = 0.7.

– There was a trend towards lower CS measurements in those developing a short cervix and requiring intervention.

– Matricellular protein levels are quantifiable in the CVF and change with advancing gestation, and there is correlation with CS measurements. This analysis in ongoing and a comparison will be made between matricellular protein levels in term and preterm deliveries.

Conclusion

CS measurements appear to be a good predictive test for risk of spontaneous preterm birth <37 weeks in a high-risk asymptomatic population and warrants ongoing investigation.

Matricellular proteins are quantifiable in the CVF and correlated with CS values. They may have potential as a new biomarker to predict premature cervical remodelling and preterm birth.

Pregnancy outcomes after insertion of cervical cerclage: a single centre study

P20

Authors

Dr Latha Vinayakarao
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Presenter

Khaing Thu Thu

Affiliations

University Hospitals Dorset NHS Foundation Trust

Abstract

Background

Preterm deliveries are associated with significant morbidity and mortality of the new-borns. Women who are at a higher risk of preterm birth should be managed in preterm birth prevention clinics as per saving babies’ lives version 3. Moreover, cerclage is one of the prophylactic intervention options for prevention of preterm birth. In University Hospitals Dorset NHS Foundation Trust (UHD), cervical cerclage is preferred method of cerclage, and it is done as a day-case procedure. This study aims to compare pregnancy outcomes after insertion of cervical cerclages in UHD under different indications with recommendations from Royal College of Obstetricians and Gynaecologists (RCOG)Green-top Guideline (number 75).

Method

Patients who underwent insertion of cervical cerclage between January 2020 and June 2023 at UHD were identified using the theatre code (R121). Out of the 47 patients who underwent the procedure, 4 were excluded as they continued their care elsewhere and a further 6 patients were excluded because they have not yet delivered at the time of submission of the abstract. Data was collected retrospectively on the 37 patients by reviewing their notes on Medway and Badgernet.

Results

In accordance with the saving babies’ lives version 3, 70.2% of the patients were identified as high risk of preterm birth, 24.4% as intermediate risk and 5.4% as low risk. Consequently, 7 patients underwent history-indicated cervical cerclage, 26 patients underwent ultrasound-indicated cervical cerclage and 4 patients had insertion of emergency cervical cerclages. The average period between insertion of cervical cerclage to delivery is 125.84, 129.84 and 124.65 days for ultrasound-indicated, history-indicated and emergency cervical cerclages respectively. There is no statistical difference in the average period between history-indicated or ultrasound-indicated cerclage (p=0.11). Furthermore, out of the 37 ladies, 8 women had preterm deliveries in current pregnancy and 3 of them were the ladies who underwent emergency cervical cerclage.

Conclusion

While awaiting results from the SuPPoRT trial, cerclage has remained one of the mainstay options of prophylactic intervention for prevention of preterm birth. In UHD, patients are extensively counselled regarding the management options for preterm birth in ladies who have existing risk factors. It is important to facilitate informed decision making of patients as they may have preferences for different treatment options available.

The Role of Skeletal Muscle Ryanodine Receptor Type 1 (RYR1) in Uterine Vascular and Myometrial Smooth Muscle Function During Pregnancy

P21

Authors

Mistry Arti, Knock Greg, Jungbluth Heinz, Tribe Rachel M

Presenter

Affiliations

King’s Health Partners Institute for Women and Children’s Health

Abstract

Background

Mutations in RYR1 encoding the skeletal muscle ryanodine receptor are a common cause of neuromuscular disorders but have also been implicated in a mild bleeding disorder characterised by severe menorrhagia, post-partum and postoperative bleeding. Excessive bleeding suggests a role of RyR1 in vascular smooth muscle function, an observation experimentally tested and corroborated by Lopez et al. (2016).

Hypothesis
The presence of a gain-of-function Ryr1 mutation in pregnancy will lead to enhanced vasorelaxation of vascular smooth muscle cells and altered contractility of myometrium. This will impact on fetal and placental development and influence the length of gestation and parturition.

Method

Utilizing the Ryr1Y522S/+ mouse model in late-stage pregnancy (gestation day 18.5), vascular smooth muscle function was investigated using wire myography with a pharmacological approach (phenylephrine, carbachol and dantrolene). Myometrial function was studied using video recordings to determine gestation length, isometric tension recordings of spontaneous myometrial contractions and RNAseq to investigate gene expression changes in the pregnant myometrial tissue. Fetal and placental weight measurements were made on gestation day 18.5. Histological techniques were used to study placental morphology.

Results

Paradoxically, uterine artery vasodilatory capacity (logIC50) was reduced in vessels from heterozygous Ryr1Y522S/+ (mixed litter) dams (10-6.597±0.135, n=20) compared to vessels from wildtype (wildtype litter) dams (10-7.275±0.292, n=22), P=0.0457, but was reversed by dantrolene. The frequency of non-pregnant myometrial contractions was greater in Ryr1Y522S/+ tissue (0.0512±0.00389 Hz) compared to wild-type tissue (0.03046±0.00488 Hz), P=0.0046. The duration of non-pregnant myometrial contractions was conversely decreased in heterozygous tissue (22.91±1.416 s) compared to wild-type tissue (45.71±5.106 s), P=0.0014. Gestation length of Ryr1Y522S/+ mouse pregnancies was not statistically different to that of the wild-type mouse (P=0.8452). The Ryr1Y522S/+ mouse had fewer fetuses in a litter (7.364±0.305, n=22) compared to wild-type littermates (8.481±0.223, n=27), P=0.0248, and lower fetal:placental weight ratios (9.36±0.420, n=11) compared to wild-type (10.88±0.2445, n=16), P=0.0132. The RyR1 protein localised to the junctional zone of the placenta (n=10).

Conclusion

Through these studies we have shown that the maternal Ryr1 Y522S influences uterine artery vasodilation and myometrial contraction, suggesting a physiological role of RyR1 in smooth muscle function, which contributes to fetal-placental growth.

Dietary Amino Acids, Carbohydrates, Vaginal delivery and Breastfeeding are Important Maternal factors for the Vaginal Microbiome in Pregnancy; Results of the Microbemom Randomised Controlled Trial

P22

Authors

Gillian A. Corbett1,2, Rebecca Moore1, Conor Feehily4,5, Sarah Louise Killeen1, Eileen O’Brien 1,6, Douwe Van Sinderen4 7, Elizabeth Matthews8, Roisin O’Flaherty8,9, Pauline M Rudd8,10, Radka Saldova8,11, David MacIntyre12, Siobhan Corcoran 1,2 Paul Cotter 3,4, Fionnuala M. McAuliffe*1,2

Presenter

Gillian Corbett

Affiliations

1. UCD Perinatal Research Centre, UCD School of Medicine, University College Dublin, National Maternity Hospital, Dublin 2, Ireland

2. National Maternity Hospital, Dublin 2, Ireland

3. Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland

4. APC Microbiome, National University of Ireland, Cork, Ireland

5. Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom

6. Department of Nutrition, Technological University Dublin, Dublin 7, Ireland

7. School of Microbiology, University College Cork, Ireland

8. NIPRT GlycoScience Group, National Institute for Bioprocessing Research, Dublin, Ireland

9. Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland

10. Bioprocessing Technology Institute, AStar, Singapore, Singapore

11. College of Health and Agricultural Science (CHAS), UCD School of Medicine, University College Dublin, Dublin 4, Ireland

12. March of Dimes Prematurity Research Centre, Division of the Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion, and Reproduction, Imperial College London, London, United Kingdom

Abstract

Background

The vaginal microbiome is a key player aetiology of spontaneous preterm birth. This study aimed to illustrate how maternal environmental factors influence vaginal microbiota composition in pregnancy, which may highlights modifiable factors to improve the vaginal microbiome, and reduce the risk of preterm birth.

Method

Participants of the MicrobeMom randomised controlled trial who had vaginal microbial sampling were included (Sept 2016 – July2019). After shotgun metagenomic sequencing, heat maps of relative abundance data were generated. Community state type was assigned and alpha diversity was calculated. Demography, obstetric history, wellbeing, exercise and dietary patterns were collected and compared against vaginal microbial parameters.

Results

Vaginal samples from 119 participants generating average of 565,192 high quality paired end reads (median 350,006) using metagenomic sequencing. Amino acids lysine, leucine, valine and alanine (precursors to short-chain-fatty acids) were associated with beta diversity (Adjusted-R2 0.077, p = 0.023, AdjustedR2 0.051, p = 0.048, Adjusted-R2 0.057, p=0.028, Adjusted-R2 0.064, p value = 0.018). Dietary carbohydrates, maltose and glycaemic load, previous vaginal delivery and history of breastfeeding were associated with vaginal microbial beta diversity (Adjusted-R2 0.057, p = 0.038, Adjusted-R2 0.061, p=0.033, Adjusted-R2 0.065, p = 0.022, Adjusted-R2 0.070, p=0.001; Adjusted-R2 0.053, p = 0.005, respectively). Carbohydrates, starch and maltose were positively correlated with increased alpha diversity (+0.001 per carb g, p = 0.032; +0.002 per starch g; +0.044 per maltose g, p = 0.043). CST I was associated with lower intake or carbohydrates, starch, glycaemic load and lower rates of previous vaginal delivery or prior breastfeeding.

Conclusion

Dietary amino acids were associated with vaginal microbial beta diversity. Macronutrients, previous vaginal delivery and prior breastfeeding were associated with beta diversity, alpha diversity and community state type assignment. These data provide a novel snapshot into the associations between maternal environment, nutrition and the vaginal microbiome. These findings highlight the therapeutic potential of the maternal diet to optimise vaginal microbial composition and alteration of pregnancy outcome including risk of spontaneous preterm birth.

Diagnostic accuracy of clinical judgement versus PAMG-1 biomarker test for PROM: Single centre study

P23

Authors

LP-1.jpg

Presenter

Leanne Petherbridge

Abstract

Background

AmniSure, which has a sensitivity of 98.9% and specificity of 100%, is a rapid non-invasive diagnostic tool which detects the placental alpha microglobulin-1 protein (PAMG-1) using specific monoclonal antibodies.

The rationale for the audit is to reduce misdiagnosis of PROM/PPROM and to increase confidence in health professionals diagnosis when current findings of a speculum examination are equivocal.

Method

To compare the results of clinical judgement and the diagnostic test kit AmniSure when the speculum examination is equivocal for 3 months.

Record data and results of all patients an AmniSure test is used on for 3 months from 14.4.23 – 14.7.23.

Follow up on results after 14.7.23 for each patient AmniSure is used on to see if test is disputed by looking at the delivery records to check ROM – Delivery date.

Compare all Amnisure data results used in the ADU setting only for the said 3 months to the attendees seen in the ADU setting only from 14.4.22 – 14.7.22 with a query of PROM/PPROM and diagnosing using the then current methods of speculum examination only.

Gain feedback from health professionals using AmniSure to see if confidence is increased by communicating verbally with ADU team members.

Results

During the 3-month data collection study 121 AmniSure tests were used on women who attended with a query of PROM/PPROM when the health professionals clinical judgement of diagnostic accuracy using speculum examination alone was questionable.

Out of the 121 AmniSure diagnostic tests used 91 tests were negative,

30 tests were positive and only 1 test result was disputed.

Conclusion

Our results show clinical judgement when using a speculum examination alone is not accurate and clinical uncertainty reported in our single-centre study supports the existing literature of a high incidence of uncertainty when diagnosing PROM using clinical judgement alone.

False negatives and false positives both can have serious consequences for mum & baby and due to the use of AmniSure during the 3 months data collection period we can safely say that the 121 women tested received appropriate follow up plans of care. Furthermore, our analysis showed that monetary and time related costs for staff and the hospital have been reduced as a result of AmniSure testing.

In view of this, AmniSure has now been implemented into current practice for use when speculum examinations are equivocal and health professionals have reported feeling more confident with their diagnosis.

AmniSure use will be audited again in 2024.

To explore the Delivery of Optimally Timed Antenatal Corticosteroids for Foetal Lung Maturation in Women Delivering Preterm at Guy’s and St Thomas’ NHS Foundation Trust

P24

Authors

Manju Chandiramani, Nicole Moriarty
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Presenter

Rebecca Ketteman

Affiliations

King's College London, Guy's and St Thomas' Hospital

Abstract

Background

Antenatal corticosteroid (ACS) administration is an important intervention, improving outcomes and reducing morbidity and mortality in preterm neonates by accelerating lung maturation. Optimal timing is defined as steroid course completed between 24 hours and 7 days prior to delivery. Steroids beyond this range or repeated course of steroids have less impact on neonatal wellbeing. Our aim was to analyse the women who delivered preterm in 2022 at Guy’s and St Thomas’ Hospital and critically explore ACS administration, identifying cohorts of women (by gestation or delivery indication) where we could improve the timing of steroid administration. Our recommendations could also inform part of the Maternal National Safety Improvement Programme (MatNeoSIP).

Method

A retrospective chart analysis of preterm deliveries between 1st January 2022 and 31st December 2022 using the electronic maternity records was performed. Women who delivered between 22+0 and 34+6 weeks were included. Exclusion criteria were women delivering outside this gestational range; intrauterine death (IUD); medical termination of pregnancy (MTOP) and fatal foetal abnormalities. We additionally did not include women who received steroids and progressed to term.

Results

In 2022 at Guy’s and St Thomas’ 6233 women gave birth, of these 220 delivered between 22+0 and 34+6 weeks. In the final analysis 191 women were included. 23 women (12%) received no ACS. 34 (18%) received a single dose. 134 (70%) received 2 doses prior to delivery, but of these, only 68 (36%) were considered optimally timed, with 34% of women delivering outside the window of maturity. 17 (9%) received a repeat dose of steroids prior to delivery. Women who received steroids at a premature gestation but went on to deliver at term were not included in this study but could be an interesting area for future research in this cohort.

Conclusion

Optimal antenatal steroid administration for preterm birth is a complex timing window that has many variables. Our results identified from this smaller study were akin to other studies undertaken, which is reassuring and emphasises the challenging nature of the topic. However, despite this being a challenge, it is still paramount to provide the best care for preterm births and optimisation of the preterm neonate. Quality improvement interventions, such as improving accuracy of recording steroid data within the unit and education on the definition of steroid maturity, are recommended to improve timing of administration.

Enhancing The Growth Of Preterm And Very Sick Babies’ Using Kangaroo Care Through “Family-Led Care Model And Fatherhood Involvement

P26

Authors

kateregga Bazilio

Presenter

Preterm Infants Parents Network Uganda

Abstract

Background

PIPNU has offered training when the parents are still in hospital, bridged the communication gap between medical team and parents and does follows up visits while home, so far 3051 babies within the last 12 months are being followed.

Method

Uganda has a highest fertility rate with 33% deliveries as preterm (Birth weight <2kg) needing KC for survival furthermore, 90% of population seeking care at Public Health facilities most of which don’t have a community follow up program for mothers with preterm babies. Currently Uganda loss 400 babies per week according to the ministry of health and 50% of the discharged preterm and very sick babies die from home according to the research conducted by Mbarara University. In Kampala for instance, 79% of the preterm babies end up at Kawempe NRH and Mulago NRH these have no community follow up for preterm parents besides facility care. The early neonatal mortality rate being 35% in kampala. 80% of fathers run away from their wives while still in the hospital. The Preterm Infant Parents Network Uganda (PINU) is implementing Kangaroo Care (KMC), father involvement programs and follow up of preterm at home by development of the “Family-Led Care model” an effective way to enhance the health and development of preterm and very sick babies. This is done through: In the hospital(Service pathway) “strengthening KMC practices for preterm and LBW babies at 4 Health facilities through training health workers, engaging mothers and fathers plus other family members in the care of these preterm at the health facility Referral system- linking to the existing community structures, referral systems and strengthen the care by empowering families to continue then care at home, recognize and seek immediate care for danger signs and return to hospitals for follow up clinics. In the Home and Community(practices pathway)-peer to peer care groups encouraging families to return for facility-based follow up clinics, providing guidance, fathers supporting mothers with the care, monitoring the number of feeding, temperature, breathing and checking the danger signs PIPNU implementation is within 2 National Referral Hospitals and 2 Lower Health Center HC IVs in Uganda. Our main objective is to reduce the 29/1000 preterm babies that die weekly with 50% of the discharge babies that die at home due to lack of community-based follow-up programs with effective interventions to improve coping behavior among parents with premature infants to ensure a continuum of care from facility to household.

Results

Since July 2022, 60 KMC ambassadors has been identified, trained, and followed up on the babies and mothers at community and facilities level within the 4 supporting health facility communities, taught health workers, parents, or caregivers on how to perform kangaroo care safely and effectively and providing them with the necessary resources and support to do so at home.

We have established 12 virtual platforms including WhatsApp groups, SMSs campaign groups and a call up center for parents, health workers and KMC ambassadors and mother care groups at community level to have constant engagement with the technical team at the network and specialized hospitals. This has been possible through a developed database (a line list) of parents, caretakers and health workers.

PIPNU has had collaborations with Ministry Health Uganda and its implementing partners in health with intension to leverage on the resources and reach out to as many as possible to health workers and preterm babies’ parents in 2 districts and 4 health facilities. We have collaborated with “ATTA” breast milk community in the establishments and distribution of safe, expressed breastmilk to needy preterm mothers and provided resources for continuous expressing breast milk at community level for these mothers.

The capacity building videos have been produced and distributed to all the 4 health facilities we work with to play at preterm care units, Special Care units, Pediatric wards and Kangaroo care wards, Corners, and rooms.

PIPNU using the Family-Led Care Model has enhanced provider with skills and quality of care within 4 KMC units and empower families to directly participate in the care. Built clinical capacity for 100 health care providers at 4 supported sites responsible for care of early/small newborns using available MOH qualified mentors and trainers in care for sick and small newborns. This has seen increase in the % of documented mothers providing KMC at the 4 health facilities from 43% in July 2022 to now 98% by June 2023.

Revitalized 4 KMC Work Improvement Teams at the 4 health facilities which are using quality improvement methodology (PDSA) to address performance gaps and improve service delivery to the preterm and sick small newborns.

PIPNU has developed, piloted, and scaled a community level reporting forms supporting M&E of the KMC ambassadors(Fathers) and the father care groups reporting monthly tracking three indicators of; number of parent/caregivers/family members done health education, number of preterm weighed and assessed for complications, and mother who keep their appointments of review with the health facilities.

PIPNU has leveraged the existing community structures and referral systems and strengthened care by empowering fathers to provide KMC continue at home, be able to recognize and seek immediate care for danger signs at a health facility.

PIPNU has built family confidence and skills to care for their small/early newborn at home and ensured an active link to the health system.

PIPNU has provided monitoring forms for families to track number of feedings, monitor temperature and breathing, KMC knowledge, provision of supplements, form of breast feeding, HIV syrup, immunization, Retinopathy of prematurity and check for danger signs with father being the lead

Conclusion

The “Family-Led Care model” an effective way to enhance the health and development very sick and preterm babies while at home and increased father involvement from 34% to 52%

Audit of Women with Previous Fully Dilated Caesarean Section (FDCS) When should cervical length assessment commence?

P27

Authors

Fozia Rehman Khan, Sabooh AL-OMARI, Louise MICHIE

Presenter

Dr Fozia R Khan

Affiliations

Department of Obstetrics and Gynaecology, James cook University Hospital, Middlesbrough.

Abstract

Background

For women with a previous FDCS, Saving Babies Lives v2 recommends a single transvaginal cervical length (CL) between 18 and 22 weeks’ gestation. At South Tees, we have been offering two cervical length scans 18-20 and 22-24 weeks since October 2020. The primary aim of this audit was to assess if the cervical length measurements in these women should start earlier at 16 weeks? Secondly, we aimed to assess how many women had a short cervix at the first cervical length scan, how many had interventions, late miscarriage or sPTB, along with the outcomes of women coming through the service with normal cervical lengths.

Method

This is a retrospective review of the preterm prevention clinic database (Oct ‘20 – August ‘22 bookings), assessing women with a previous fully dilated CS as risk factor. The preterm delivery database was reviewed since 2021, which includes all late miscarriages: to find out if previous FDCS was a risk factor.

Results

52 patients from the preterm prevention clinic were included, with full data on 46. 92% of women had CL > 25mm. 6% of women had CL ≤ 25 mm on first measurement, two of those had ultrasound indicated cerclage & the third had CL reassessment after one week & CL increased to normal length. No women had a late miscarriage in the cohort coming through the preterm prevention clinic. Similarly, none of the late miscarriages which occurred in South Tees since 2021 had a previous FDCS as a risk factor.

For women completing CL surveillance with normal measurements, 86% went on to have a term birth, the remaining 14% had sPTB (one was a case of twin pregnancy).

Conclusion

sPTB after FDCS can still take place with normal CL – our audit showed 14% went on to have a preterm birth < 37 weeks and 5% before 34 weeks. It is important to discuss the signs and symptoms of preterm birth at discharge from cervical length surveillance – to come in early for optimisation. There is insufficient evidence from this audit to support an earlier assessment for CL before 18-20 weeks. There was one case who presented prior to this, and subsequently went to term with a cervical cerclage in situ. A regional protocol was agreed for the Northern region: 2 cervical lengths at 19 and 23 weeks. This was implemented in May ‘23. There will be on-going monitoring through the regional preterm database, along with pregnancy outcomes.

Second trimester cervicovaginal fluid progesterone concentrations are not associated with subsequent preterm birth.

P28

Authors

Katia Capuccini 1,2, Gonçalo D. S. Correia 1,2, Lucia Olmo Garcia 3, Ada H Y Armstrong 3, Belen Gimeno-Molina 1,2,4, Lynne Sykes 1,2,4, Charis Uhlson 5, Robert Murphy 6, Zoltan Takats 3,7, Phillip R. Bennett 1,2, and David A. MacIntyre 1,2.
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Presenter

Katia Capuccini

Affiliations

1. Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0NN, United Kingdom.

2. March of Dimes Prematurity Research Centre at Imperial College London

3. The National Phenome Centre at Imperial College London

4. The Parasol Foundation Centre for Women’s Health and Cancer Research

5. University of Colorado Anschutz Medical Campus, School of Medicine

6. Department of Pharmacology, University of Colorado Denver

7. Section of Bioanalytical Chemistry, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0TR, UK

Abstract

Background

Steroid biosynthesis is a key modulator of hormonally-regulated pathways of human parturition. During gestation, placental production of steroids such as progesterone is reflected in increasing circulating concentrations, which can be measured using liquid chromatography mass spectrometry (LC-MS/MS) assays. It is suggested that a subset of preterm deliveries are caused by progesterone deficiency leading to cervical shortening. Vaginal progesterone therapy is widely used for prevention of PTB in women with a sonographic short cervix (≤25 mm) in the mid-trimester. While serum and urine progesterone levels are routinely measured in pregnancy, there is scant data on levels in cervicovaginal fluid (CVF) during pregnancy. The aim of this study was to investigate the CVF steroid profile using an LC-MS/MS based quantitative assay and to compare mid-trimester concentrations of detectable steroids, including progesterone, in women subsequently delivery preterm or at term.

Method

A total of 25 women were recruited and sampled between week 12 and 24 of gestation using a soft-cup device. These women did not receive progesterone therapy during the current pregnancy. A subset (n=5) of women were sampled longitudinally two times during the same time-frame. Steroids were extracted from CVF using liquid-liquid solvent extractions. The prepared extracts were analysed by LC-ESI-MS/MS on an ACQUITY-UPLC system coupled to a Waters Xevo TQ-S mass spectrometer. Absolute concentrations were established for 13 steroid hormones (androstenedione, estriol, β-estradiol, estrone, aldosterone, 21-deoxycortisol, 11-deoxycortisol, corticosterone, 17ɑ-hydroxyprogesterone, 11-deoxycorticosterone, progesterone, testosterone, cortisol).

Results

Only progesterone, androstenedione, and cortisol were detected in CVF above the assay limits of quantification (0.005ng/ml, 0.01ng/ml, 0.05ng/ml respectively). In women experiencing uncomplicated term deliveries (n=19), the median concentration of these steroids was 6.61 ± 8.13 ng/g of CVF for progesterone, 4.16 ± 2.98 ng/g for cortisol, and 0.34 ± 0.21 ng/g for androstenedione. A weak, positive trend between progesterone levels and increasing gestational age was observed (r2=0.15, p=0.02). Analysis of longitudinal samples showed a significant increase in progesterone levels at 24 weeks compared to 12 weeks of pregnancy (p= 0.03). Median mid-trimester CVF steroid concentrations in women subsequently delivering at term (n=15) and preterm (n=9) were comparable for progesterone (11.09 ng/g v 10.92 ng/g, p= 0.51), androstenedione (0.32 ng/g v 0.39 ng/g, p= 0.17) and cortisol (4.20 ng/g v 5.12 ng/g, p= 0.57).

Conclusion

Progesterone, androstenedione, and cortisol are detectable in CVF. Progesterone concentration increases during the second trimester. While validation in a larger cohort is planned, current results indicate that PTB is not associated with CVF progesterone deficiency.

The involvement of Blood Group B in Spontaneous Preterm Birth and Host-Microbiome Interactions

P29

Authors

Mountain K1,2, MacIntyre DA2, Chan D, Hyde A2, Pasint-Magyar J2, Green A2, Lee YS2, Brown R2, David AL3, Dell A2,4, Feizi T2,5, Gimeno_Molina B1,2, Glampson B6, Grassi P2,4, Haslam SM2,4, Liu Y2,5, Lewis HV2, Ng S2, Mayer E6, Norman JE7,8, Stock SJ7, Tajadura-Ortega V2,5, Wu G2,4, Teoh TG2,9, Terzidou V2, Bennett PR2 and Sykes L1,2*
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Presenter

Katie Mountain

Affiliations

1Parasol Centre for Women’s Health and Cancer at Imperial College Healthcare NHS Trust

2March of Dimes Prematurity Research Center at Imperial College London, UK

3Elizabeth Garrett Anderson Institute for Women’s Health, University College London, UK

4Department of Life Sciences, Imperial College London, UK

5Glycosciences laboratory, Department of Metabolism, Digestion and Reproduction of Imperial College London, UK

6 Imperial Clinical Analytics, Research & Evaluation (iCARE), Imperial College London & Imperial College Healthcare NHS Trust, London, UK

7University of Edinburgh Usher Institute, Edinburgh, UK

8Faculty of Health Sciences, University of Bristol, UK

9KK Women’s and Children’s Hospital, Singapore

Abstract

Background

Host-microbial responses are implicated in the aetiology of spontaneous preterm birth (sPTB) yet mechanisms underpinning this remain poorly defined. Microbiota composition and disease risk are associated with histo-blood group antigens. Work previously presented by our group suggests a protective effect of blood group A, and an association between blood group O, host-inflammatory response and early sPTB. The objective of this study was to establish the relationship of blood group B to sPTB.

Method

A cohort of pregnant women identified from healthcare records was obtained (n=59189). In addition, women defined as at risk of sPTB were recruited (n=2084) and cervicovaginal fluid-sampled during pregnancy (12-16 and 20-24 weeks). Bacterial composition was assessed using metataxonomics (n=363), glycan structures using mass spectrometry, and binding of bacteria to blood group glycans was assessed via glycan array.

Results

Blood group B was associated with sPTB (OR 1.15, CI: 1.05-1.28, p=0.005, compared to blood group A). This relationship remained significant when adjusted for ethnicity, parity, previous LLETZ procedures and previous sPTB using logistic regression modelling. In the at risk population, blood group B was associated with cervical shortening and sPTB <34 weeks specifically in women with a previous LLETZ (p=0.022, p = 0.016) but not those with previous sPTB. At both sampling timepoints blood group B women were significantly less likely to have communities dominated by L. crispatus and were enriched for L. iners and diverse communities (p<0.01, p=0.029). Mass spectrometry demonstrated the presence of ABO blood group antigens in vaginal samples. In blood group A women, a high relative proportion of the A glycans in vaginal fluid was associated with L. crispatus colonisation and term birth. Blood group antigens A, B and H (O) demonstrate variable binding with vaginal bacteria including strains of L. crispatus, L. iners, S. agalactiae and G. vaginalis, in glycan microarrays.

Conclusion

Blood group B is associated with sPTB, a relationship particularly evident in women with a previous LLETZ procedure. Blood group B is associated with suboptimal vaginal microbiota compositions associated with early sPTB. This provides further evidence for the important role of vaginal carbohydrates in determining microbiota composition and sPTB risk, and highlights the potential of glycan decoys or L. crispatus live biotherapeutics as therapeutic strategies for the prevention of PTB.

Antenatal Corticosteroids and Delivery – Timing and Use

P30

Authors

M O’Brien1, G Corbett1, C Dignam1, E Keane1, M. Cheung1, F. Byrne1, A. Toher1, S Corcoran1
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Presenter

Maggie OBrien

Affiliations

1 UCD School of Medicine, National Maternity Hospital, Holles Street, Dublin 2, Ireland

Abstract

Background

Antenatal corticosteroids (ANS) are among the most important interventions in the prevention of morbidity and mortality in the preterm infant. Multiple studies have demonstrated a significant reduction in the rate of perinatal death, neonatal death and respiratory distress syndrome. An optimal temporal relationship exists between the administration of steroids and delivery in preterm infants after 24hrs and within 7 days of the administration of steroids. This study aims to examine this temporal relationship and how it relates to the indication for administration of antenatal steroids.

Method

Retrospective cohort study of all pregnancies administered antenatal corticosteroids (ANS) in anticipation of preterm birth between January 2019 and June 2022, at the National Maternity Hospital Dublin. Data were graphically assessed for normality using analysis of mean, median, skewness and kurtosis. Chi-square and one-way ANOVA with Holm Sidak’s multiple comparison tests assessed for statistical differences, accepted at p < 0.05.

Results

1551/26181 pregnant women received ANS between January 2019 and June 2022. For women who received steroids at <34 weeks, the time interval between administration of steroids and subsequent delivery was on average 34 days (median 26.9, IQTR 56.63). Of the preterm infants (<34 weeks), 196 (21%) received steroids within 48 hours of delivery, 131 (14%) between 48hrs and 7 days of delivery, 55 (6%) between 7 and 14 days of delivery. The most common indication for administration of steroids was pains or threatened preterm labour 20.6%. Planned preterm delivery was the most accurate indication for steroids administration 4.41 (3.86 – 4.97) with previous preterm delivery and bleeding being the most inaccurate 45.68 (27.93 – 63.43) and 45.32 (41.19 – 44.45) respectively.

Conclusion

Preterm delivery has been historically difficult to predict and the majority of women who present with threatened preterm labour do not deliver within 7 days. As in this study, only 25% of the patients who presented with pains at less than 34 weeks went on to deliver within the 7 days of administration of antenatal corticosteroids. There is a marked difference in precise timing of steroids at 24 weeks with 85% of patients being given steroids outside of the therapeutic window. There is an opportunity for improvement in the correct timing of administration of antenatal corticosteroids. With 0% of women who received steroids for the indication of “previous preterm delivery” delivering within 7 days. Ill-timed administration of antenatal corticosteroids reduce or eliminate their efficacy and unintended negative consequences can occur. Thus, efforts should be made to reduce the disproportion between administration of corticosteroids and actual time of birth.

Impact of preterm birth clinic on reducing the number of spontaneous preterm deliveries

P31

Authors

Dr Nourhan Gomaa, Miss Aylur Rajasi, Midwife-Jessica Toohey
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Presenter

Nourhan Gomaa

Affiliations

East Kent Hospitals University NHS foundation Trust- Queen Elizabeth the Queen Mother Hospital, Margate

Abstract

Background

The independent preterm birth clinic was established by our trust in 2021. We wanted to determine the efficacy of implementing such a crucial practice and observe its impact on reducing the incidences of preterm birth. We concluded the results by conducting a service evaluation through which we looked into: Reasons of referral to preterm birth clinic , different interventions used (Progesterone pessary, cerclage, Arabin pessary) , risk factors that could contribute to preterm birth. We then evaluated the birth outcomes by following up those women and compared the incidents of preterm birth before and after integrating a separate preterm birth clinic to illicit the changes made.

We further detailedly looked into outcomes of women who had a previous Caesarean section at full dilatation since the incidence of caesarean sections is significantly increasing

Method

Collection of data was done retrospectively by looking at all patients who attended the preterm birth clinic from cross sites (WHH and QEQM) from the years 2022 and 2023 *Total of 314 patients* Data was collected from patient notes and Euroking -74 patients had been commenced on progesterone pessary, 63 had a cervical cerclage, and 3 patients had an Arabin pessary.

17% of patients (81 Patients) were referred for previous CS at full dilation. 9 of which had progesterone pessary, 4 had cerclage and 1 had an Arabin pessary. Only 3 of which had a spontaneous preterm birth between 34-36+6 weeks. No one had an extreme preterm birth below 28 weeks. All remaining (out of 81) others continued their pregnancy to term with a cervical length above 25 mm. 5 patients had a successful VBAC at term.

Results

76 patients out of the 314 are still pregnant and we intend to follow up their pregnancy and observe the outcomes. 4 patients ended up with missed miscarriages and 2 patients has undergone termination of pregnancy.

Out of the 232 patients who delivered: less than 6% had a preterm birth below 34 weeks, 10% had a preterm birth between 34-36+6 weeks and more than 85% achieved term pregnancy.

Conclusion

Our average range of pre-term birth across the years 2028-2023 was 7%, which concludes we are performing in accordance to national statistics, even slightly better. We collected our data up till August 2023 and during this year data suggests that only 185 patient out of 4053 patients had a spontaneous preterm birth.

Introduction of a preterm midwifery service

M01

Authors

Lizzie Kilburn
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Presenter

Gemma Miller

Affiliations

Leeds Teaching Hospitals NHS Trust

Abstract

Background

Leeds Teaching Hospital Trust has a well-established preterm prevention clinic. However, it lacked dedicated midwifery support. The midwifery team was formed with the aim of optimising care, experience, and outcomes for those at risk of preterm birth.

Women at high risk of preterm birth and those delivering prematurely have complex obstetric and emotional needs. The following areas of care were deemed as requiring improvement – antenatal and postnatal care, support with expressing breastmilk (MBM)

• Many women attending the consultant led clinic have previously experienced late miscarriage, extreme preterm birth and neonatal deaths. On the multiparous antenatal pathway, women have no scheduled midwifery contact between 16 and 28. This is often the most anxious time when support is most needed.

• BAPM (2020) highlights that women who have experienced preterm birth need additional postnatal support. A local audit of postnatal care for patients who delivered prematurely showed fragmented and sporadic care.

• MBM significantly improves neonatal outcomes for preterm babies. In July 2022, a local audit revealed that only 30% of babies born under 34 weeks gestation had received MBM within 24 hours of birth

Method

An enhanced antenatal pathway was developed facilitating additional and longer appointments. The pathway offers a flexible, personalised approach to care linking closely with the consultant clinic.

An enhanced outpatient postnatal pathway care was introduced for women who deliver less than 34 weeks. Care is delivered on the neonatal unit facilitating: Increased time with their baby, continuity, and a personalised approach to care.

The Immune Boost QI project was launched with the aim of increasing early access to MBM for babies born under 34 weeks. Working collaboratively with the neonatal team, a whole unit approach was utilised to create a cultural change in practice. The preterm midwives provided education and expressing support in ward areas.

Results

Qualitative patient feedback of the enhanced pathways has been overwhelmingly positive for improving continuity of care and patient experience.

The Immune Boost project has shown significant and sustained improvements in access to early maternal breastmilk. In August 2023, 100% of women expressed within 24 hours of birth for the third consecutive month, with 89% expressing in 6 hours and 44% expressing within 2 hours.

Conclusion

The introduction of a dedicated preterm midwifery service illustrates an innovative approach to care. Working collaboratively, the team is pioneering new ways in achieving service improvement in caring for women at high risk of preterm birth and those delivering prematurely.

Immune Boost: Improving access to early maternal breast milk (MBM) for infants <34 weeks

M02

Authors

ELizabeth Kilburn, Gemma Miller

Presenter

Lizzie Kilburn

Affiliations

Leeds Teaching Hospitals Trust

Abstract

Background

Research consistently highlights that early access to MBM significantly improves neonatal outcomes for preterm babies in terms of morbidity and mortality.

Monthly audits of all births <34 weeks gestation is conducted to monitor compliance of recommendations from NHS England ‘SBLV2 (Saving Babies Lives Version 3) and British Association of Perinatal Medicine (BAPM). In February 2022, 0% of babies received MBM within 2 and 6 hours of birth, with 37.5% within 24 hours.

The immune boost quality improvement project was established to increase the proportion of babies born under 34 weeks receiving MBM within 24 hours of birth, with a further aim to increase the proportion who receive MBM within 6 hours

Method

The methods involved both joint and stand-alone maternity and neonatal initiatives . These included:

– The creation of a multidisciplinary team (MDT) with an allocated lead neonatal nurse, specialist preterm midwives, neonatologist and obstetrician.

– A monthly review of missed cases of MBM administration to highlight opportunities for learning

– An increased education across neonatal and midwifery teams regarding the importance of early expressing and administration of MBM to all babies

– The introduction of colostrum packs in all relevant areas which includes both audio-visual and written information on the benefits of early MBM and essential equipment

– Buccal colostrum being added to neonatal prescribing protocol to embed in practice and encourage its prompt administration

– The Promotion of the QI project through logo, posters and stickers across NNU and midwifery areas to remind, motivate and educate across the MDT.

– Improved methods of time time-critical education regarding the benefits of MBM

-The introduction of practical expressing support provided by the preterm specialist midwives

Results

Since the start of the project there has been a significant improvement in access to early breast milk, with rates since April 2023 consistently between 70-95% in 24 hours. During this same time frame 90-100% of mothers have expressed within 24 hours, with an average of 80% of these mothers expressing within the first 6 hours.

The rates of administration of maternal breastmilk within 24 hours of birth demonstrate consistent and maintained improvements. Over a 6 month period, on average 82% of babies born <34 weeks gestation have received maternal breastmilk within 24 hours.

Conclusion

The success of the Immune Boost project is directly attributable to the effective collaborative MDT approach which employed multiple initiatives across the maternity and neonatal settings. This has resulted in sustained improvements in the access to early maternal breastmilk for infants born < 34 weeks gestation

IL-1β blockade decreased intrauterine inflammation induced by E. coli in pregnant Rhesus macaques, but does not reduce rates of preterm birth

M03

Authors

Daniel Short 1, Pietro Presicce 2, Mark Johnson 1, Suhas Kallapur 2
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Presenter

Daniel Short

Affiliations

1 - Academic Obstetrics and Gynaecology, Department of Metabolism, Digestion, and Reproduction - Imperial College London

2 - Division of Neonatology, University of California Los Angeles

Abstract

Background

Intrauterine infection and inflammation (III) is a major cause of preterm birth. Intrauterine infection results in a cascade of proinflammatory cytokine release resulting in the recruitment and activation of immune cells leading to inflammation driven preterm birth. Key among these cytokines is IL-1β, which has been shown to induce a robust infiltration of neutrophils in the chorion, amnion and decidua. This study aimed to assess the efficacy of IL-1β blockade in a Rhesus macaque (Macaca mulatta) model of preterm IUI.

Method

Twenty normally cycling adult female Rhesus macaques were time mated and received an ultrasound guided intraamniotic inoculation of 1×10^6 colony forming units of E. coli at approximately 80-85% gestation. The target for inoculation was gestational day 140 (range 135-143) where term is approximately 165 days. This provided a model of preterm IUI equating to approximately 32 weeks in the human. The macaques were randomised to receive, alongside their E. coli inoculation, either an antibiotic regimen or the same antibiotic regimen plus a course of the IL-1β antagonist “Anakinra”. Inoculations were received on Day 0, and the experimental end point was Day 4 when the animals were scheduled to undergo surgical delivery of the fetus at hysterotomy, followed by euthanasia and necropsy.

Results

All animals had a positive amniotic fluid culture for E. coli 24 hours following inoculation, and all animals had sterile amniotic fluid cultures 24 hours after antibiotics were commenced. 8/9 animals receiving antibiotics alone, and 7/11 animals receiving antibiotics and Anakinra experienced PTL (Fisher’s Exact P=0.31 not significant). Anakinra significantly reduced the recruitment of neutrophils in to the Chorio-decidua and reduced the expression of IL-6 and IL8 mRNA in the fetal membranes

Conclusion

IL-1β blockade with Anakinra significantly reduced the recruitment of neutrophils into the choriodecidua and decreased intrauterine inflammation in the fetal membranes. There was a reduction in PTL rates in a small set of animals, but this was not statistically significant. Partial efficacy of Anakinra in a Rhesus macaque model of IUI is encouraging and warrants further investigation given the epidemiological data in humans that demonstrates an increased risk of mortality, and adverse neurological, respiratory and gastrointestinal outcomes in preterm fetuses exposed to IUI.

Opsonisation of vaginal microbiota in women at high-risk of delivering preterm

M04

Authors

Belen Gimeno-Molina1,2,3, Yun S Lee1,2, Denise Chan1,2, Ryan L Love1,2, Katherine E Mountain1,2,3, Erna Bayar1,2,3, Marina Botto2,4, Anna L David5, Vasso Terzidou1,2,6, Phillip R Bennett1,2, David A MacIntyre1,2, Pascale Kropf2,7, Maria Carmen Collado8, Lynne Sykes1,2,3,9
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Presenter

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 Centre at Imperial College London, UK

3The Parasol Foundation Centre for Women’s Health and Cancer Research, London, UK

4Deparment of Immunology and Inflammation, Imperial College London, UK

5Elizabeth Garrett Anderson Institute for Women’s Health, University College London, UK

6Chelsea & Westminster Hospital, Imperial College Healthcare NHS Trust

7Department of Infectious Disease, Imperial College London, UK

8Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC)

9St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK

Abstract

Background

There is an association between vaginal microbiota composition and the risk of spontaneous preterm birth (sPTB). Vaginal dominance by Lactobacillus crispatus (Community State Type, CST I) is considered protective, while Lactobacillus spp. depletion (CST IV) confers a higher risk. The mechanisms driving microbial-host immune interactions are poorly understood. Our aim is to determine the role of immunoglobulin recognition (opsonisation) of vaginal microbiota in the context of sPTB.

Method

Cervicovaginal fluid (CVF, n=43) was collected from women at high-risk of PTB. Bacterial composition was assessed using 16S rRNA sequencing. Supernatant was used to measure cytokine and complement proteins by Luminex Multiplex immunoassays. A second matched swab was used to establish the percentage of IgA and IgG opsonisation of cervicovaginal bacteria.

Results

There was a higher percentage of bacteria bound to IgG (median 73.5%) (p=0.0008) and IgA (median 74%) (p=0.0554) in women with L. crispatus vaginal dominance (CST I), compared to women with CST IV dominance (median 20.4%, and 12.58%, respectively). Moreover, there was a negative correlation between binding of bacteria and concentration of complement proteins. Higher percentages of opsonisation were associated with decreased CVF concentrations of C1q, C4, Factor B, Factor D, C3, C3b, C5. Furthermore, women who delivered at term had higher IgG (median 65.90% vs 43.10%, p=0.0174) and IgA (median 68.95% vs 46.75%, p=0.0283) opsonisation compared to women who delivered preterm.

Conclusion

Opsonisation of vaginal microbiota is associated with a reduced inflammatory response. IgA and IgG mediated opsonisation of vaginal microbiota appears to be associated with immune homeostasis. In contrast, the lower opsonisation pattern of CST IV associated species implies immune evasion.

Functional assessment of the kidneys in fetuses that deliver very preterm: an MRI pilot study

M05

Authors

Molly Dillon1,2, Megan Hall1,2, Alena Uus2, Sri Sankaran1, Andrew Shennan1,2, Alexia Egloff1, Jana Hutter2, Lisa Story1,2
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Presenter

Molly Dillon

Affiliations

1 Guy's and St Thomas' NHS Foundation Trust

2 King's College London

Abstract

Background

Preterm birth has well known associations with adverse renal outcomes including an increased risk of renal failure in the neonatal period as well as long term complications such as hypertension and chronic kidney disease. A reduction in nephron number is well reported in such infants. In current clinical practice functional assessment of the fetal kidneys is limited and the ability to predict postnatal outcome is poor. Fetal MRI is a rapidly expanding field and has the ability to not only give structural information, such as renal volume but also an indirect functional assessment of perfusion/oxygenation via a technique called T2* relaxometry. This study aims to compare renal volumes and mean T2* values in a group of fetuses that deliver very preterm with a control group of health pregnancies that subsequently deliver at term.

Method

A case control study utilising prospectively collected datasets over a two year period was performed. All participants had a fetal MRI between 16 and 32 weeks gestation. The control cohort encompassed women with healthy pregnancies who subsequently delivered at term and the preterm cohort included women at high risk of preterm birth (prelabour premature rupture of membranes, bulging membranes or a risk of delivery 50% using the QUIPP App) who delivered <32 weeks gestation. The MRI examination included: T2 weighted images and T2* relaxometry of the thorax in multiple orthogonal planes. T2* maps were created using in house developed pipelines and automated segmentation of renal tissue was performed with manual refinement using ITK-SNAP. Mean renal T2* values were then calculated. Values were compared between the term and preterm cohorts using linear regression analysis in SPSS.

Results

Twenty-two control and 14 preterm datasets were suitable for analysis. Renal volumes increased and mean renal T2* values decreased within increasing gestational age in the control cohort. No difference in renal volume was observed between the two groups but fetuses who subsequently delivered <32 weeks gestation had significantly lower mean renal T2* values (p<0.001)

Conclusion

We have demonstrated that functional assessment of the fetal kidney is a feasible technique and that alternations in renal development may commence prior to preterm birth. Further research is required to correlate antenatal findings with longer term outcomes to assess whether renal T2* relaxometry may be a promising technique to predict adverse renal outcomes in the future.

Novel data in multiple pregnancy population – Cervical stiffness in the second trimester, what does it mean?

M06

Authors

E Medford, J Gent, A Sharp, A Care
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Presenter

Elizabeth Medford

Affiliations

Centre for Women's Health Research, Liverpool Women's Hospital

University of Liverpool

Abstract

Background

Perfect cervical remodelling (CR) is the transition from a rigid to a compliant structure to allow passage of the fetus at the optimum fetal gestation. Cervical softening and ripening become pathological when it results in spontaneous preterm delivery. Methods to assess CR have been explored extensively in the singleton population including advanced ultrasound imaging techniques and mechanical tissue tests.

Within the multiple pregnancy population, which inherently holds a higher risk of preterm birth over the singleton population, the research in CR is limited.

The Pregnolia system is a novel aspiration medical device that objectively quantifies cervical stiffness. In the low-risk singleton population this device identifies cervical softening prior to cervical shortening.

This is the first study to measure cervical stiffness using the Pregnolia system in multiple pregnancies.

Method

SPRUCE is an ongoing prospective cohort study exploring preterm birth in multiple pregnancies. Participants were consented to an optional cervical stiffness assessment using the Pregnolia system alongside the vaginal swab sampling for the SPRUCE study during the second trimester. A triplicate measurement was recorded in each participant. Delivery outcomes were collected from electronic notes.

Results

Of the 62 participants who have completed outcomes for the study, 50 participants agreed to cervical stiffness assessments. An interim analysis of this data has been undertaken and compared to an available data set of cervical stiffness percentiles in singleton pregnancies.

Expected cervical stiffness percentiles for 16 weeks gestation in twin pregnancies has been generated from this data set. All multiple pregnancy cervical stiffness readings across all percentiles are lower when compared to singleton percentile readings at the same gestation. This observed difference did not reach statistical significance (p=0.48).

In this cohort there was an 8%(4/50) spontaneous preterm birth rate. There was no correlation between an isolated cervical stiffness measurement in the second trimester and spontaneous preterm birth in multiple pregnancy.

Conclusion

This original data demonstrates cervical stiffness readings in multiple pregnancies to be lower when compared directly to cervical stiffness in singleton pregnancies during the second trimester. This finding was not statistically significant.

Given the small numbers of spontaneous preterm birth in our cohort, an isolated cervical stiffness measurement was not found to be related to gestational age at delivery in multiple pregnancy.

A further powered study is warranted to validate these initial findings and explore serial cervical stiffness measurements in this cohort.

Further data analysis is planned on the complete data set after SPRUCE study completion.

Psychological and emotional benefits of 3D printed MRI models of the fetus for high-risk preterm birth pregnancies: assessment of feasibly and study design

M07

Authors

Alena U. Uus (1,2), Kun Qian (2), Megan Hall (2,3,4), Jacqueline Matthew (1,2), Mary A. Rutherford (2), Joseph V. Hajnal (1,2), Lisa Story (2,3,4)
uus-2024.jpg

Presenter

Alena Uus

Affiliations

1 - Biomedical Engineering Department, King's College London, St. Thomas’ Hospital, London, UK

2 - Centre for the Developing Brain, King's College London, St. Thomas' Hospital, London, UK

3 - Division of Midwifery and Radiography, City University of London, London, UK

4 - Department of Women & Children’s Health, King's College London, St. Thomas' Hospital, London, UK

Abstract

Background

3D ultrasound models of the fetus are known to positively contribute to parental-fetal bonding and outcomes for perinatal anxiety and depression for mothers with high-risk pregnancies or experiencing a loss. Yet, 3D printing for fetal ultrasound is performed primarily for the face and with limited quality.

Alternatively, MRI provides true 3D spatial information that allows segmentation of the whole fetus. This pilot work investigates the feasibility of printing 3D fetal models from MRI as part of the clinical workflow. We also assess the acceptability of the printed models and the incorporation of feedback from patients at high risk of preterm birth.

Method

MRI datasets: The pilot dataset used in this work includes 3 MRI scans of high-risk preterm birth cases from the “MRI studies for prediction of risks of adverse neonatal outcomes in preterm birth” study [REC: 21/SS/0082] that were acquired on 3T MRI scanner at St. Thomas’ Hospital, London.

3D printing: We used deep learning segmentation of T2-weighted MRI stacks to produce 3D virtual surface models of the whole fetus. Next, we printed models in 50-75% of the real size using plastic materials on UltiMaker printer. The models were placed on a 3D printed stand.

Feedback collection: Clinicians caring for the mothers asked them if they would like to have the 3D model of their baby, and if they would like to share feedback informally.

Results

All 3 mothers approached wanted a printed copy of their baby from their MRI examination. We successfully segmented MRI images and created 3D models for these high-risk cases. The printing took 3-5 hours per model with ~10 cm in height. They had realistic appearance/pose and could be easily held (figure: https://gin.g-node.org/kcl_cdb/fetal_body_mri_atlas/raw/master/info/3d-printing-example.jpg). The models were delivered to the mothers and the feedback (written/verbal) was positive and suggested that a 3D MRI models of a baby could be a meaningful emotional token and support for parents.

After a review of the feedback and advice from a clinical perinatal psychology expert, a formalised questionnaire protocol was devised and incorporated into the study ethics. It included open-ended questions to assess the psychological benefits for antenatal anxiety, depression and fetal-maternal attachment.

Conclusion

This pilot study showed feasibility of 3D printing of MRI models of the whole fetus. The printed physical models received positive feedback from mothers in 3 high-risk preterm cases. Our current work focuses on printing for larger cohort and collecting feedback for qualitative analysis of psychological and emotional impact.

Preterm birth and health inequality: assessing the effects of sociodemographic factors in Leeds

M08

Authors

Dr Eleanor Brierley, Dr Amy McIntosh, Elizabeth Kilburn, Gemma Miller, Mr Nigel Simpson, Dr Elizabeth Bonney
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Presenter

Eleanor Brierley

Abstract

Background

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Despite national efforts, the rate of preterm birth has risen (ONS 2022). This poses the question, are we identifying and targeting at-risk groups effectively? This study investigates sociodemographic factors in the Leeds preterm birth population to characterise women and babies at risk in an effort to optimise local service provision, and target interventions to most at-risk patients.

Method

We compared demographic factors (indices of multiple deprivation, age, ethnicity, gestation at booking, employment, safeguarding input, marital status, smoking, body mass index, substance use and accommodation status) across three delivery gestational age: 37 weeks’ gestation. Data was collected from the Leeds electronic records and compiled into a Patient Level Information and Costing System (PLICS) spanning deliveries April 2020- June 2023. 25,454 births occurred between 2020-2023 including 90 stillbirths, 25,184 live births, and 28 neonatal deaths; 1343 were preterm, and 418 were very preterm. Multinomial logistic regression was used in STATA 18.0. Termination of pregnancy was excluded.

Results

Multinomial analysis showed significantly increased likelihood of very preterm birth for age>40 years (RR 1.55, 95% CI 1.01-2.37), current smoking (RR 1.67, 95% CI 1.21-2.30), obesity classes I – III (RR for class III 2.49, 95% CI 1.6-3.88), drug misuse (RR 2.46, 95% CI 1.12-5.43) and certain ethnicities; Black African (RR 1.64, 95% CI 1.10-2.45), Black Caribbean (RR 2.36, 95% CI 1.08-5.17), Indian (RR 1.91, 95% CI 1.08-3.4) and Pakistani (RR 1.99, 95% CI 1.34-2.95). There was significantly increased likelihood of preterm birth for age over 40 years (RR 1.66, 95% CI 1.3-2.12) BMI <18 (RR 1.55, 95% CI 1.11-2.18) and current smoking (RR 1.63, 95% CI 1.37-1.95).

Conclusion

Black African, Black Caribbean, Indian and Pakistani women in Leeds are at an increased risk of very preterm birth. Nationally, stillbirth rates are higher for babies of Black ethnicity (7.52 per 1,000 total births) and babies of Asian ethnicity (5.15 per 1,000 total births) compared with babies of White ethnicity (3.30 per 1,000 total births). Preterm births (before 37 weeks’) account for 75% of stillbirths and late fetal losses (MBRRACE 2021). Other risk factors for preterm birth including smoking, drug use, low/high BMI and increased age are also reflected in the Leeds population. This audit demonstrates how PLICS routine data can be used at local level to understand local health inequalities and identify patient groups that may benefit from targeted interventions.

INSIGHT-2: Mechanistic Studies into Pregnancy Complications and their Impact on Maternal and Child Health.

M09

Authors

Carlotta Valensin (1), Glen Nishku (2), Emilie JM Côté (1, 2), Daniela Pereira-Carvalho (1, 3), Andrew H Shennan (1, 2), Natalie Suff (1, 2), Deena L Gibbons (3), Rachel M Tribe (1).
CarlottaValensin.jpg

Presenter

Carlotta Valensin

Affiliations

(1) Department of Women & Children’s Health, School of Life Course & Population Sciences, King's College London.

(2) Guy's and St Thomas' NHS Foundation Trust.

(3) Peter Gorer Department of Immunobiology, School of Immunology & Microbial Sciences, King's College London.

Abstract

Background

Every year, tens of thousands of women in the UK, and millions globally, face pregnancy complications such as preterm birth (PTB), hypertensive disorders and gestational diabetes. Despite significant advancements in the clinical management of such instances, there are still many unanswered questions about the underlying biological mechanisms and molecular causes of these complications. This highlights the critical need for continued comprehensive scientific investigations aimed at not only unravelling the mechanisms of pregnancy complications, but also elucidating how pregnancy exposures have a long-lasting impact on children’s health outcomes.

Method

Here we introduce the protocol of “INSIGHT-2: Mechanistic Studies into Pregnancy Complications and their Impact on Maternal and Child Health”. Over the course of 5 years, the aim is to collect a range biological samples and clinical data from 1700 pregnant women at any time from the booking of their pregnancy (8 weeks of gestation) to delivery, and from their children up to 2 years of age. We will recruit women from the general antenatal population and women of known higher risk for pregnancy complications. We will also target women whose pregnancies have a risk factor (e.g., diabetes, obesity, metabolic syndrome, autoimmune disorders) for later child health problems. This will include mothers with pre-existing medical conditions (or first-degree relatives (FDRs) or partners with pre-existing conditions), of high body mass index (BMI), and those exposed to infection/inflammation in pregnancy. Mothers and infants will be followed prospectively to monitor their health through the measurement of molecular, protein, and biochemical markers, and clinical data. Different samples collections will depend on the pregnancy complication studied and on the specific research question, but the core protocol ensures aligned samples points so that pregnancies from healthy controls can be recruited and shared across sub-cohorts and allow for different pregnancy complications to be compared and biological mechanisms to be identified and validated.

Results

n/a

Conclusion

The exploration of pre-pregnancy and pregnancy factors that may contribute to disease processes and impact on foetal wellbeing and future health will provide a comprehensive picture of disease mechanisms in both the mother and child, and aid identification of biomarkers for prediction, diagnosis and management of pregnancy complications. In addition, it will provide a valuable longitudinal study of the relationship between the in-utero environment, pregnancy management and outcomes and future maternal and child health.

Acknowledgements:

GSTT CRN Research Team

Funders:

The Borne Foundation

The Leona M. and Harry B. Helmsley Charitable Trust

Live biotherapeutics for preterm birth prevention: vaginal administration of Lactobacillus crispatus CTV-05 in pregnancy leads to persistent colonisation and reduces inflammation

M10

Authors

Bayar E, Love RL, Lee YS, Ng S, Gimeno-Molina B, Parks T, Lee P, Bennett PR, Sykes L, MacIntyre DA
Erna-Pic-PTB.jpg

Presenter

Erna Bayar

Affiliations

March of Dimes European Prematurity Research Centre, Imperial College London.

The Parasol Foundation Centre for Women’s Health and Cancer Research, St Mary’s Hospital, London, W2 1NY

Osel Inc., Mountain View, CA, USA.

Tommy's National Centre for Miscarriage Research, Imperial College London

Abstract

Background

A vaginal microbiota colonised by L. crispatus (Community State Type; CST1) is protective against preterm birth (PTB), whilst both L. iners (CST3) and Lactobacillus deplete, high diversity communities (CST4) associate with increased risk. We determined whether a live vaginal biotherapeutic containing L. crispatus CTV-05 (LACTIN-V) colonises the vagina and reduces local inflammation, to ascertain whether biotherapeutic L. crispatus has potential to reduce PTB risk.

Method

LACTIN-V was administered once daily for five days from 14 weeks gestation, and then once weekly for six weeks to 62 women at high-risk of PTB. Vaginal microbiota was assessed using metataxonomics and cervicovaginal fluid cytokines measured by immunoassays in samples taken pre-treatment, at 15, 18, 20, 28 and 36 weeks. Colonisation was determined via targeted quantitative PCR and a CTV-05 specific amplicon sequence variant (ASV-02).

Results

Pre-treatment, 43% of women had CST1, increasing to 89% and 87% at 8- and 16-weeks post-treatment (p <0.0001). Persistent colonisation, defined as ASV-02 presence at 28 weeks, was seen in 54% (31/57) of women. Colonisers were less likely to have pre-treatment CST1 (p<0.0002), and more likely to have CST3 or 4 (p=0.0179).

Conclusion

LACTIN-V induces persistent colonisation, displacing less favourable bacteria in women whose vaginal microbiota is initially dominated by L. iners or is highly diverse (CST4). This associates with reduced cytokine concentrations. Our data supports the concept that vaginal administration of a live biotherapeutic containing L. crispatus modulates the microbiota and the immune milieu to a protective state, and so could reduce PTB risk.

Does commencing vaginal progesterone in all high-risk women improve spontaneous preterm birth (sPTB) outcomes when compared to USS-surveillance indicated treatment alone?

M11

Authors

Ffion Jones; Angharad Care

Presenter

Ffion Jones

Abstract

Background

Vaginal progesterone (VP) is considered gold-standard treatment for prevention of sPTB in high-risk women. In Liverpool Women’s Preterm Birth Prevention Clinic, currently all women with a history of PTB or PPROM <34+0 weeks are commenced on VP from 16 weeks, with serial monitoring of CL 2-4 weekly until 26 weeks’ gestation. Second line therapy is offered if there is significant ongoing shortening of CL. At present, there is paucity of evidence when defining ‘progesterone failure’ (PF), whether it be by the absolute number (mm) of cervical length measurement, a certain percentage reduction in CL or the significance of funnelling. We compared our current policy to our historic policy of USS indicated vaginal progesterone for short CL (<25mm) in high risk women.

Method

This is a retrospective, observational, cohort study of 773 women attending a dedicated PTB prevention clinic, collated across two datasets spanning Feb 2014 – Sept 2016 (USS indicated VP use; n=137) and August 2017 – June 2023 (VP for all high risk women; n=125). We evaluated which ultrasound criteria clinicians use to determine whether second line treatment is indicated, by analysis of serial CL measurements, coding the critical ‘trigger’ point for second line treatment (ie. PF) and what treatment type appears to be the most effective when compared with USS surveillance alone, as measured by the overall preterm birth rate between groups. Social demographics and medical factors were also evaluated as implicating factors for preterm birth risk.

Results

The overall preterm birth rate for high-risk women receiving VP only was 17.6% (22/125), and 28.5% (8/28) in those requiring additional second line treatment (arabin or cerclage). In comparison, the overall preterm birth rate for high risk women undergoing USS-surveillance was 10.2% (14/137), whereas women under USS-surveillance only identified to have cervical shortening and thus requiring additional treatment (progesterone, arabin or cerclage) commenced later, had a preterm birth rate of 19% (10/52).

Conclusion

From these interim results, implementing a policy of VP given to all high-risk women regardless of cervical length at 16 weeks gestation does not improve overall preterm birth rate. Our work also informs at what critical ‘trigger’ point (measured by % reduction difference in CL) prompts clinicians to offer second-line treatment. These results pose important questions for future research in optimising which patients should be, if at all, offered VP and at what gestation, in combination with the ideal timing of USS-surveillance.

Tommy’s Clinical Decision Support Tool: lessons learned from an early adopter implementation evaluation.

M12

Authors

Dilly Anumba[2], Christy Burden[3], Siobhán Gillespie[4], Victoria Komolafe[5], Samantha Pérez Amack[4], Elaine Sheehan[4], Basky Thilaganathan[6], Maria Viner[7], Hannah Wilson[4], Jane Sandall[1] on behalf of Tommy’s National Centre for Maternity Improvement[8]
JC-profile-picture.jpg

Presenter

Jenny Carter[1]

Affiliations

1. Department of Women and Children’s Health, School of Life Course and Population Sciences, 10th Floor, North Wing, St Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH

2.University of Sheffield, Department of Oncology and Metabolism, JW4/40, Level 4, Jessop Wing, Tree Root Walk, Sheffield, S10 2SF

3. Department of Women’s Health, Southmead Hospital, Bristol, BS10 5NB

4. Royal College of Obstetricians & Gynaecologists, 10-18 Union Street, London, SE1 1SZ

5. Royal College of Midwives, 10-18 Union Street, London, SE1 1SZ

6. Fetal Medicine Unit, St George’s University Hospitals NHS Foundation Trust, Blackshaw Road, London, SW17 0QT

7. Mothers for Mothers, New Fulford Family Centre, Gatehouse Avenue, Bristol, BS13 9AQ

8. Tommy’s National Centre for Maternity Improvement, 10-18 Union Street, London SE1 1SZ

Abstract

Background

The Tommy’s Clinical Decision Support Tool is a web-based application that is used to assess risk of preterm birth and placental dysfunction, and offers both maternity service user and provider interfaces. The Tool utilises validated algorithms and rule engines, which are more accurate than current checklist methods, and instantly recommends best evidenced-based care pathways. This personalisation of assessment and decision support could reduce preterm birth and stillbirth, whilst also addressing variation in care that could result in the higher rates seen in women from ethnic minority and socially deprived groups. This study evaluated the implementation of Tommy’s Tool in four early-adopter hospitals, in order to inform a cluster randomised controlled trial and wider scale-up.

Method

The NASSS framework (Non-adoption or Abandonment of technology by individuals and difficulties achieving Scale-up, Spread and Sustainability) informed analysis. We used online surveys, semi-structured interviews and focus groups to investigate: maternity service user and healthcare professional (HCP) experience; barriers and facilitators to implementation; reach (whether particular groups are excluded and why), fidelity (degree to which the intervention is delivered as intended), and unintended consequences.

Results

1181 maternity service users and 117 HCPs participated in the study, completing 1265 online surveys, as well as 8 focus groups and 29 semi-structured interviews (women: n=24; HCPs: n=23). Overall, the Tool appears acceptable and easy-to-use. Findings influenced developments of the device and implementation strategy, including those aimed at addressing digital and social exclusion. Lessons learned emphasise the importance of: clarity in purpose, scope, potential benefits and evidence base; good communication, particularly when risk assessment results are unexpected; top-level and multidisciplinary buy-in from start; dedicated resources; local champions across professions and settings; preparation for transitional period, including harmonisation of clinical practice guidelines; mitigation of double data entry; optimisation of IT infrastructure; flexibility in training; optimising accessibility and readability of implementation resources.

Conclusion

Tommy’s Clinical Decision Support Tool has the potential to provide more accurate risk assessment ensuring women are on the right care pathway. This could lead to reductions in preterm birth and stillbirth, as well as variation in care. This study gave us the opportunity to evaluate implementation processes in four early adopter sites. We were able to identify barriers and opportunities to inform a cluster randomised controlled trial which will maximise the chance of trial results being conclusive.

Characterisation of the predominate Kv7 channel subunits in human uterine smooth muscle cells as a potential target for preterm birth prevention

M13

Authors

Jenna M Sajous, Kim C Jonas, Rachel M Tribe
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Presenter

Jenna Sajous

Affiliations

King's College London (all three authors)

Abstract

Background

Preterm birth (PTB) is an issue worldwide, associated with significant morbidity and mortality. Approximately 70% of all PTBs occur spontaneously. Despite ongoing efforts to understand the mechanisms responsible for initiating labour, we are yet to find effective solutions to preventing its occurrence pre-term.

The myometrium is primarily composed of smooth muscle cells which coordinate to produce contractions resulting in delivery. Targeting the contractility of these cells could be key to preventing preterm labour. KV7 channels (voltage-gated potassium channels encoded by KCNQ1-5 genes) contribute to regulating cell contractility both by maintaining resting membrane potential and repolarising following cell activation. Previous work in our group has demonstrated expression of these channels in the human myometrium but has not determined their tetramer formation(s). Studies have also demonstrated that spontaneous myometrial contractions are inhibited in the presence of KV7 channel activator ML213. Characterising these channels in the myometrium will give a clearer indicator of potential tocolytic targets. We aim to determine the composition of KV7 channels in the myometrium. We also aim to determine the stability of KCNQ expression in myometrial cell culture.

Method

Lower-segment myometrial samples were collected at the time of caesarean section from term, non-labouring pregnancies (n=16). Cells were dissociated and cultured to the end of passage 5 with n=9 cultured in standard serum (10% fetal bovine serum (FBS)) and n=7 being serum-starved (0.5% FBS) 24 hours before cell RNA extraction. Absolute quantification qPCR was used, and results normalised via GeNorm.

Results

KCNQ expression in non-labouring myometrial tissue was from highest to lowest: KCNQ4>KCNQ3=KCNQ1>KCNQ2=KCNQ5. Expression of all KNCQ isoforms apart from KCNQ5 decreased from tissue to passage 0 (P0) and continued to decrease as passage number increased. No difference was found between serum-starved and non-serum starved cells.

Conclusion

Owing to its high expression, KCNQ4 is likely to be a significant player in myometrial Kv7 channel composition. Myometrial cells in culture appear to lose their smooth muscle cell phenotype over time so will be used for future over-expression studies of KCNQ and KCNE isoform function. As expression significantly drops between tissue samples and P1 in most cases, P0 cells will primarily be used in studies, acknowledging their limitations.

Cervical cerclage technique: Towards agreement? A Delphi Consensus of UK Experts

M14

Authors

Megan Hall1,2, Laura Stirrat3, Graham Tydeman4, Andrew Shennan1, Natalie Suff1
Hall-Mugshot.png

Presenter

Megan Hall

Affiliations

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

2 Department of Perinatal Imaging, St Thomas’ Hospital, King’s College London

3 Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh

4 NHS Fife, Kirkaldy

Abstract

Background

Transvaginal cervical cerclage is reported to be performed in around 1-2% of pregnancies and there is little consensus on technique. We have recently demonstrated a large variety in practice among UK cerclage experts, may partly explain the wide variety of outcomes in clinical studies with a potential impact on patient care, research and education. This study aimed to provide a UK consensus opinion on cerclage technique.

Method

A working group formed of individuals with specialist interest in preterm birth from several hospitals designed a first round Delphi consensus questionnaire. Participants were asked to describe their usual practice. This was sent to all experts who had participated in our previous study. A three-week survey window was given. Agreement was set at 75%, with rate of agreement=(agrees-disagrees)/(agreement+disagreement+uncertainty)x100.

Results

20 experts participated in the survey with 19 completing all questions. Years of experience as a consultant ranged from 2-26 years, and time spent dedicated to preterm birth ranged from 10-100% of the total workload. Most commonly, participants (n=8) reported performing 50/year. 11 experts reported being able to perform both high and low cerclage (defined as with/without bladder reflection), all others reported being able to perform low only. Two experts reported preferentially performing high cerclage, and were excluded from further data-analysis relating to intra-operative technique.

There was agreement that non-traumatic forceps should be used to grasp the cervix, and that a four bite, single low cerclage as high as achievable on the cervix with at least 70% tension (on visual analogue score) through an anterior knot should be performed, and that removal should be ³36 weeks’ without routine regional anaesthesia; it was agreed that tocolysis and postoperative antibiotics should not be offered following a non-emergency cerclage. There was no agreement on other aspects of peri-operative care (eg. catheter use), concurrent progesterone, follow-up care, or management of subsequent PPROM.

Conclusion

In this first round Delphi, a consensus agreement can be reached on some aspects of surgical technique, there are differences in the care women receive. The high rate of consistency in described intraoperative technique contrasts with our previous findings analysing actual expert technique on a simulator. While best technique is unclear, it must be recognised that women are receiving a variety of practices. Furthermore, this stands to highlight surgical technique as a confounder in all research, even when described. Finally, this raises concerns around the consistency of educational standards.

Which mode of birth is best? A systematic review to compare the impact of preterm vaginal vs caesarean birth on clinical outcomes.

M15

Authors

Katherine Lattey(1), Gemma Clayton(2), Sharia Ijaz(2), Sarah Dawson(2), Jane Norman(3), Abigail Fraser(2)*, Abi Merriel(2,4)*
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Presenter

Abi Merriel

Affiliations

1. North Bristol Trust

2. University of Bristol

3. University of Nottingham

4. University of Liverpool

Abstract

Background

The optimal mode of delivery for women with either an indicated or an imminent preterm birth is controversial, with some who believe that a planned caesarean birth is protective and others believe that it increases risk of morbidity for the infant and mother. There is also evidence suggesting that fetuses at different gestations and with different pathologies may have different optimal modes of birth.

We aimed to assess the effect of preterm mode of birth (caesarean vs vaginal) on maternal and neonatal outcomes.

Method

We searched electronic databases including Medline, Embase, CINAHL and Cochrane controlled trials register until March 2024, for studies comparing vaginal to caesarean birth on outcomes including perinatal death, intraventricular haemorrhages and other causes of neonatal and maternal morbidity, in both singleton and multiple pregnancies born between 22 and 37 weeks gestation with no restriction on presentation. Data were extracted on both actual and planned mode of birth where available. Both randomised controlled trials (RCTs) and non-randomised studies were included. Studies were restricted to publication in English since 1990. Searches were screened and data extracted in duplicate. Evidence from combinable studies was s ynthesized using random-effects meta-analyses, stratified by presentation and planned or actual mode of birth. PROSPERO registration CRD42019097330.

Results

We present here the data for perinatal death only. Forty-four studies included relevant data for the meta-analyses for perinatal death, there were no RCTs. When considering both cephalic and breech births, for planned caesarean compared to planned vaginal birth there were 7 studies contributing to the analysis, they had a summary odds ratio (OR) for perinatal death of 0.41 (95% CI 0.32-0.60). For cephalic and breech presentations, comparing actual caesarean to actual vaginal birth, there were 23 studies providing data for summary OR of 1.10 (95% CI 0.81-1.50). When considering breech babies only, based on 7 studies the actual mode of birth data showed caesarean birth may be protective OR 2.74 (95% CI 1.79 – 4.20), whilst intended birth revealed results in similar direction, based on 4 studies OR 1.46 (95% CI 0.97-2.21). Data on caesarean birth for cephalic babies is much more mixed with fewer studies contributing data.

Conclusion

Caesarean may be protective for perinatal death in breech preterm births, however all evidence is based on unadjusted non-randomised studies. The evidence for cephalic and combined breech/cephalic births is more unclear. A well-designed RCT is required to answer the question about mode of birth for preterm babies.

Assessment of the thymus in fetuses prior to spontaneous extremely preterm birth using functional MRI

M16

Authors

Megan Hall1,2*, Alena Uus2, Ella Kollstad1, Panicos Shangaris1,3,4, Srividhya Sankaran5, Mary Rutherford2, Rachel M. Tribe1, Andrew Shennan1, Jana Hutter2, Lisa Story1,2

Presenter

Megan Hall

Affiliations

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

2 Department of Perinatal Imaging, St Thomas’ Hospital, King’s College London, London, UK

3 Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, UK

4 Fetal Medicine Research Institute, King’s College Hospital, London, UK

5 Department of Obstetrics and Gynaecology, St Thomas’ Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

Abstract

Background

Spontaneous preterm birth complicates ~7% of pregnancies and is the leading cause of neonatal mortality and long-term morbidity globally. Although the exact aetiology is uncertain and likely multifactorial, infection is strongly implicated particularly at earlier gestations. Alterations in the fetal thymus, a gland known to be integral to the fetal inflammatory response, have been documented in fetuses who subsequently deliver spontaneously preterm, although in vivo assessment has been limited to volumetry. Advances in fetal MRI now allow for functional assessment of fetal tissues, including by T2* relaxometry which gives an indirect assessment of fetal oxygenation. This study aims to utilise T2* relaxometry to assess the fetal thymus in uncomplicated pregnancies in the second and third trimesters, and in pregnancies that subsequently deliver very preterm.

Method

Women were recruited who were deemed to be at very high risk of delivery prior to 32 weeks’ gestation and retrospectively excluded if they did not deliver prior to this gestation. A control group of women with low-risk pregnancies were recruited and retrospectively excluded if they developed any pregnancy related complications after scanning. All women underwent a fetal MRI scan on a 3T system incorporating the fetal thorax. T2 and T2* data were aligned and the mean T2* of the thymus tissue determined.

Results

Mean thymus T2* decreased with gestation in control fetuses. In fetuses who went on to deliver prior to 32 weeks’ gestation, thymus volume was reduced as was mean T2* (p=<0.001) as compared to controls. On subgroup analysis, this relationship persisted for among cases affected by PPROM (p=0.002) than those with intact membranes (p=0.067).

Conclusion

This pilot study has successfully demonstrated a reduction in thymus mean T2* value in fetuses who go on to deliver extremely preterm. This is likely secondary to the reduced oxygenation associated with thymic involution and T-cell depletion that occurs secondary to inflammation and infection. The application of T2* imaging for in vivo assessments of the fetal thymus opens a new frontier for understanding the complex antenatal immunological changes linked to preterm birth. While the study has its limitations, it sets the stage for future research that integrates imaging data with cellular and molecular markers, such as T-cell analyses from cord blood, to paint a more complete picture of fetal immune health and its potential long-term ramifications.

TRANSFER: ThReatened preterm birth, Assessment for in utero transfer; 22+0-23+6 weeks’ gestation

M17

Authors

TRANSFER project collaborative
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Presenter

Melanie griffin

Affiliations

Women’s Health Research Department, Level D, St Michael’s Hospital, Southwell St, University of Bristol and Birmingham Centre for Observational and Prospective Studies, University of Birmingham, UK.

Abstract

Background

TRANSFER was established in response to the recommended risk-based approach for decisions about neonatal care pathways following delivery between 22+0 and 23+6 weeks’ gestation. The number of women presenting with threatened preterm birth at this gestation is unknown. This data is essential to facilitate adequate service provision and planning for UK obstetric and neonatal units.

Objectives

1. Identify women presenting with threatened preterm birth between 22+0-23+6 weeks’ gestation.

2. Determine number of women presenting outside an obstetric unit with Level 3 NICU.

3. Determine number of in-utero transfers of women presenting between 22+0 -23+6 weeks’ gestation.

4. Determine number of women who deliver between 22+0 -23+6 weeks’ gestation in a unit without Level 3 NICU.

Method

Methods

Multicentre prospective service evaluation; 90 UK maternity units.

Eligibility: Threatened preterm birth between 22+0-23+6 weeks’ gestation from 17/5/21-30/6/22.

Results

Between 22+0-23+6 weeks’ gestation:

1. 511 women presented with threatened preterm birth to UK obstetric units.

2. 294 (58%) women presented to obstetric units without level 3 NICU.

3. 217 (42%) women required transfer.

4. 46 (9%) women delivered in a unit without a Level 3 NICU (15 (33%) opted for active care pathway).

Geographical location, length of antenatal hospital stay and use of biomarkers to predict preterm birth were recorded. Estimated fetal weight was performed at presentation in 37% of cases and predictive tools (biomarker and/ or cervical length measurement) were recorded in less than a third of all cases.

Conclusion

Women presenting with threatened preterm birth between 22+0-23+6 weeks gestation is higher than anticipated and is likely to be an under-representation of actual number of presentations. This project gives essential data to facilitate adequate service provision and planning for UK obstetric and neonatal units.

Baby’s First Passport: co-produced PERIPrem (Perinatal Excellence to Reduce Injury in Premature Birth) passport to the perinatal team in in a tertiary unit in London, UK

M18

Authors

Nicole Moriarty, Alice Beardmore-Grey, Hannah Shanoon, Rebecca Ketteman, Manju Chandiramani
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Presenter

Nicole Moriarty

Affiliations

Kings College London

Guys and St. Thomas NHS Trust, London

Abstract

Background

The UK has one of the highest infant mortality rates in Western Europe, mainly secondary to preterm birth. To achieve a 50% reduction in stillbirth, maternal mortality, neonatal mortality and serious brain injury by 2025, the Maternity and Neonatal Safety Improvement Programme (MatNeoSIP) facilitated organisational culture change and established a perinatal team. We introduced the co-produced West of England AHSC PERIPrem (Perinatal Excellence to Reduce Injury in Premature Birth) passport, an evidence-based bundle checklist of 11 interventions, for women at risk of preterm birth (22+0 -34+6 weeks) at a tertiary level hospital in London.

Method

Using recommendations from the British Association of Perinatal Medicine, in conjunction with the MatNeoSIP programme, a multidisciplinary perinatal team facilitated adaptation of the passport for the local population. Service users provided qualitative feedback on the revised passport prior to implementation. Ongoing data monitoring of the 11 interventions was undertaken, and staff and service user feedback was gathered.

Results

16 service users provide feedback from our pilot initiative. All the women who responded were currently pregnant and less than 35 weeks gestation. 4 (25%) were primiparous women, 75% were multiparous. 9 (56%) reported a previous preterm delivery <37 weeks gestation. 15/16 (94%) reported that the passport was easy to use. One was unsure. No respondents reported difficulty. When asked if the passport was useful, 12 (75%) were strongly affirmative, and 3 (19%) felt that it probably would be useful. 1 (6%) was unsure. We also asked respondents if they would feel comfortable using the tool to discuss their care, or their babies care if needed. 11 (69%) reported they would feel extremely comfortable, 4 (25%) were. Somewhat comfortable. One service user replied they would be extremely uncomfortable using the passport.

Conclusion

The PERIprem passport for those undergoing interventions in anticipation of preterm birth is a useful tool both for women and their care providers to ensure the care they receive is standardised and optimised.

PROMISES study: a prospective feasibility study of salivary progesterone as a test for detecting risk of preterm birth in rural community settings in India.

M19

Authors

Priyanka Garg1*, Jiadai Mi2*, Nishtha Kathuria1, Paul T Seed2, Pankhuri Sharma1, Simi Khan1, Mohan Ghule1, Ritu Dargan3, Archana Sarkar1, Atul Tayade4, V B Shivkumar5, Sunil Mehra6, Poonam Varma Shivkumar7, Rachel M Tribe2
Picture-1-M19

Presenter

Jia Dai Mi

Affiliations

1Research and Innovation Unit, Mamta Health Institute for Mother and Child, New Delhi, Delhi, India.

2Department of Women & Children's Health, King's College London, London, UK

3Obstetrics and Gynecology, Independent Consultant, MAMTA Health Institute for Mother and Child, 110048, New Delhi, India.

4Department of Radio-Diagnosis, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.

5Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.

6Young People and Sexual and Reproductive Health and Rights Unit, Mamta Health Institute for Mother and Child, New Delhi, Delhi, India.

7Department of Obstetrics and Gynecology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.

Abstract

Background

India faces high rates of preterm birth (PTB) and associated neonatal mortality and morbidity. The scarcity of early detection tools for PTB, coupled with economic and resource limitations, poses substantial challenges, particularly in rural areas of the country. The potential of salivary progesterone as a biomarker for PTB prediction remains controversial, with some studies suggesting that low progesterone levels may indicate PTB risk in asymptomatic women. The PROMISES study aimed to assess the feasibility and efficacy of salivary progesterone as a low-cost biomarker for early PTB risk prediction in rural community settings in Madhya Pradesh, India.

Method

This prospective feasibility study explored the potential use of a low-cost salivary progesterone test for PTB risk prediction in Madhya Pradesh, India. Women were identified in early pregnancy through working closely with the local accredited social health activist workers. A total of 3312 pregnant women with singleton pregnancies were recruited, with the support of local accredited social health activist workers. Early pregnancy identification and gestational assessment (<20 weeks) were conducted via ultrasound scan. Salivary samples were collected at 24-28+6 weeks’ gestation and analysed for progesterone levels using ELISA.

Results

Of the enrolled participants, 2282 had complete gestational data at delivery available, and 954 provided usable saliva samples for progesterone testing. The study observed a PTB rate of 20.11% before 37 weeks, and 8.26% before 34 weeks. However, no significant correlation between low salivary progesterone levels and an increased risk of PTB, yielding odds ratios of 1.19 (95% CI 0.79 to 1.78) for deliveries <37 weeks and 0.90 (95% CI 0.46 to 1.79) for deliveries <34 weeks.

Conclusion

We successfully delivered a complex pregnancy study, and report preterm birth rates, within a rural setting in India. We have demonstrated there is poor predictive value in salivary progesterone for risk of PTB in this cohort. These findings suggest the need for integration of additional biomarkers to enhance the accuracy of PTB risk prediction models. Furthermore, the study emphasises the critical importance of maintaining sample integrity through proper cold chain management during transportation. Future research must continue to focus on developing and validating accessible and cost-effective tools for early PTB risk assessment, particularly in resource-constrained settings.

Funding for this project was provided by the Grand Challenge India, 2015 – All Children Thriving – India partners [BIRAC (Biotechnology Industry Research Assistance Council), DBT (Dept. of Biotechnology) India and BMGF (Bill and Melinda Gates Foundation)].

An Integrated Omic Model to Predict Spontaneous Preterm Birth Risk

M20

Authors

Oluwanifewa Laleye, Jiadai Mi, Yanzhong Wang, Andrew H Shennan, Natasha Hezelgrave Joan Camunas-Soler, Morten Rasmussen, Rachel M Tribe
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Presenter

Oluwanifewa Laleye

Affiliations

Oluwanifewa Laleye, Department of Women and Children’s Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London; 10th Floor North Wing, St Thomas' Hospital Campus, Westminster Bridge Rd., London SE1 7EH, United Kingdom

Jiadai Mi, Department of Women and Children’s Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London; 10th Floor North Wing, St Thomas' Hospital Campus, Westminster Bridge Rd., London SE1 7EH, United Kingdom

Yanzhong Wang, King's College London, School of Life Course and Population Sciences, London, United Kingdom

Andrew H Shennan, Department of Women and Children’s Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London; 10th Floor North Wing, St Thomas' Hospital Campus, Westminster Bridge Rd., London SE1 7EH, United Kingdom

Natasha Hezelgrave, Department of Women and Children’s Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London; 10th Floor North Wing, St Thomas' Hospital Campus, Westminster Bridge Rd., London SE1 7EH, United Kingdom

Joan Camunas-Soler, (1) Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg 405 30, Sweden, (2) Wallenberg Centre for Molecular and Translational Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30, Sweden.

Morten Rasmussen, Mirvie Inc., 820 Dubuque Ave, South San Francisco, CA

Rachel M Tribe, Department of Women and Children’s Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King’s College London; 10th Floor North Wing, St Thomas' Hospital Campus, Westminster Bridge Rd., London SE1 7EH, United Kingdom

Abstract

Background

There is a strong need to discover clinical biomarkers in the first/early second trimester to aid in the identification of women at risk of spontaneous preterm birth (sPTB) in the earlier stages of their pregnancy which would permit earlier intervention/treatment. Discovery-based multiomic studies have great potential to identify novel biomarkers to develop new predictive tests for the identification of sPTB risk. Previous research has identified the ability of cell-free RNA (cfRNA) transcripts to predict sPTB (1). In this work, we have built upon this by adding proteomic data to this model to explore the potential of protein signatures to predict sPTB.

Method

In this study, maternal blood plasma samples (n = 141) were obtained between 12-24 weeks of gestation from the INSIGHT cohort of women. Blood plasma samples were profiled using untargeted cell-free RNA using the Mirvie RNA platform and a targeted protein assay using the Olink Explore 384 Inflammation panel. A logistic regression model has been previously developed for biomarker discovery of cfRNA transcripts (1). Previous discovery identified twenty-five cfRNA transcripts associated with an increased sPTB risk. Proteins of interest to be integrated into the model were selected using a Welch T-test and a threshold for protein inclusion was established at p-values <0.05. A model using proteomic data only and another model integrating both cfRNA and proteomic data were built using a Logistic regression model using leave-one-out cross-validation (LOOCV).

Results

cfRNA sequencing identified over 57,000 transcripts with 25 transcripts already shown to be associated with sPTB risk (1). From the panel of 384 inflammatory proteins, 34 proteins were selected using the threshold for inclusion. Using protein data only, the model achieved a validated LOOCV performance area under the curve (AUC) of 0.68 (95% CI of 0.76 – 0.60) whereas the integrated model achieved a validated LOOCV performance AUC of 0.88 (95% CI of 0.77 – 0.89). Genes and proteins used by the model are shown to be implicated in collagen and extracellular matrix pathways.

Conclusion

The use of both cfRNA and protein markers provides a non-invasive opportunity to understand biological mechanisms and have the potential to predict preterm birth during the second trimester of pregnancy. While inflammatory protein signatures alone show a lesser accuracy in the prediction of sPTB, integration with cfRNA profiles provides better accuracy in predicting the risk of sPTB.

1.Camunas-Soler J et al. Predictive RNA profiles for early and very early spontaneous preterm birth. Am J Obstet Gynecol.2022Jul;227(1):72.e1-72.e16.

International and Regional variation in the use of Emergency Cervical Cerclage in the UK and Europe: Results of an international survey of clinical practice

M21

Authors

Nicole Pilarski(1,2), Emilie van Limburg Stirum(3,4), Janneke van ‘t Hooft(3), Vicky Hodgetts-Morton(1,2), Katie Morris(1,2)
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Presenter

Nicole Pilarski

Affiliations

1. Institute of Applied Health Research, University of Birmingham

2. Birmingham Women's and Children's NHS Foundation Trust

3. Amsterdam UMC location University of Amsterdam, Department of Obstetrics and Gynaecology, Meibergdreef 9, Amsterdam, The Netherlands

4. Amsterdam Reproduction & Development, Amsterdam, The Netherlands

Abstract

Background

The optimal management of women presenting with premature cervical dilatation and exposed unruptured membranes remains uncertain and controversial. Treatment options include emergency cervical cerclage (ECC) or expectant management with or without additional treatments such as progesterone and tocolytics. The aim of this survey was to describe current practice, and explore variations in practice, in the UK and Europe in the management of this condition and the use of ECC. We hypothesise practice will vary between and within regions.

Method

An online survey was distributed by email to delegates registered to attend the 2023 European Spontaneous Preterm Birth (PTB) Congress and members of the UK PTB network. The primary outcome was use of ECC as a treatment option, secondary outcomes included use of additional treatments, gestational age and cervical dilatation limits for ECC insertion, length of stay, and follow up procedures. Descriptive statistics were calculated using STATA for the overall results and to compare between geographical regions.

Results

In total 69 responses from 11 countries were received. Two single responses from Australia and Indonesia and duplicate responses from the same institution were excluded. Overall 49 institutions were included in this analysis, of these 18 were in the UK, and 31 in the European Union (Belgium, Denmark, Ireland, Norway, Spain, Sweden, Switzerland, The Netherlands). 39/49 institutions offer ECC (18/18 in the UK). Of the 9 institutions not offering ECC 2/9 cited lack of evidence, 3/9 lack of neonatal intensive care on-site, and 3/9 lack of trained providers as the most important reason. The median gestational limits for offering ECC were from 16 (range 12-18) to 24 weeks (range 20-28). 16/39 institutions in total (8/18 in the UK) would not offer ECC with cervical dilatation >4cm. For adjunctive treatments; 31/39 use tocolytics, 27/39 use progesterone. 24/39 respondents reported a routine inpatient stay of 48 hours after ECC (range from 24 hours after ECC to 28 weeks-gestation). 20/39 offer follow up with transvaginal ultrasound, and 2/20 also use fetal fibronectin post-operatively.

Conclusion

There is wide variation in the use of ECC within and between regions. This survey represents the first summary of clinical practice with ECC. The generalisability of results is likely limited to specialist centres however even within expert PTB services the variations are striking. A future audit of clinical practice would allow comparison between actual and ‘intended’ practice as described here. Robust clinical trials are needed to inform evidence-based national guidelines to standardise and improve care.

Mid-Trimester Losses in Dichorionic Pregnancies: An Overview

M22

Authors

Gent, J, Sharp, A
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Presenter

Joanna Gent

Affiliations

Women's and Children's Department, University of Liverpool, Liverpool Women's NHS Foundation Trust, Liverpool, UK

Abstract

Background

There is a paucity of evidence on mid-trimester pregnancy losses (MTL) in dichorionic twins (DC). These losses are often underreported and overshadowed by increased rates of MTL seen in monochorionic twins (MC) as a consequence of placental sharing. However, DC pregnancies represent 70% of twins and shoulder a significant burden of perinatal morbidity and mortality.

This review aims to provide an overview of the current evidence on MTL rates in DC twins, discuss limitations of this evidence and provide suggestions for improving outcomes.

Method

We performed a literature review on studies published after 2003 on pregnancy loss between 12-24 weeks gestation in DC twins. Additionally, we retrospectively reviewed pregnancy outcomes of DC twin pregnancies booked at the Liverpool Women’s Hospital (LWH) between 2010-2019.

Results

Two large cohort studies of DC twins reported a 2.6% pregnancy loss rate, however these studies included all losses from dating scan to 23+6 weeks gestation. More recently, a retrospective cohort study of 2500 DC twins showed a 0.6% MTL rate between 14-23+6 weeks gestation. Of 1189 DC pregnancies at LWH, a 1.6% MTL rate was observed between 16 and 23+6 weeks.

Conclusion

It is difficult to ascertain the current rate of MTL in DC pregnancies. Whilst the most comprehensive review in 2013 suggested a 0.6% pregnancy loss rate in DC twins, a substantially higher rate was observed at LWH. Importantly, this higher rate may still be an underrepresentation as data was collected from maternity records and therefore may not have captured pregnancies delivered in a gynaecology setting, a common occurrence in gestations <20 weeks. It is therefore reasonable to assume reporting is globally inconsistent and inaccurate. Whilst the aetiology of MTL is multifactorial, a large proportion fall within the spectrum of spontaneous preterm birth (PTB). There is currently no consensus in guidance on screening and intervention for PTB prevention in twins. Evidence suggests that cervical length (CL) at earlier gestations may be predictive of early PTB in twins. Unfortunately, a quarter of UK maternity units do not routinely assess CL in twins and half do not offer specialist clinics for DC twins. The pathology associated with DC twins is significant and often overlooked. Specialist antenatal care should be provided from early in the second trimester and include CL screening. This will not only allow for more accurate data collection to interpret DC MTL outcomes, but also explore the utility of CL screening and its role in MTL.

Embedding the Patient Voice into Preterm Birth Preventative Care: Themes from a Preterm Birth Advisory Council

M23

Authors

Gillian Corbett1-2, Fionnuala McAuliffe1-2, Mandy Daly4, Dylan Keegan5, Larissa Luethe2, Siobhan Corcoran1,2

Presenter

Gillian Corbett

Affiliations

1. UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland

2. National Maternity Hospital, Dublin 2 Ireland

3. Irish Neonatal Health Alliance

4. UCD Clinical Research Centre

Abstract

Background

Preterm birth (PTB) has a deep immediate impact on women but also alters their care and experience in subsequent pregnancies. There is an absence of the pregnant person’s voice in the research surrounding pregnancy at risk of PTB. The aim of the Preterm Birth Advisory Council is to introduce and embed the patient voice into research in PTB prevention.

Method

This was a prospective qualitative study conducted at the National Maternity Hospital (NMH) in Dublin, Ireland. The Preterm Birth Advisory Council (PBAC) was established at the NMH in January 2023. Council members include persons with lived experience of PTB, patient advocate representatives and clinicians involved in PTB preventative care. Topics around PTB prevention were openly discussed with experts by experience, and shared with PTB advocacy groups. Responses were analysed for themes most frequently important to those with lived experience. Ethical approval was granted by NMH Research Ethics Committee.

Results

In total, seven experts by experience gave their views over the course of a three month period. Six themes were observed:

1. Preterm Birth Preventative care as a patient-led care model

2. Lack of awareness and education around risk factors for PTB and tools for its prevention.

3. The potential power of preconceptual counselling in reducing the trauma of an unanticipated adverse outcome such as PTB.

4. The lack of partner’s experience of pregnancy at risk of PTB in research and clinical care.

5. Clinical Outcomes in PTB Research.

6. Traumatic language included reference to mid-trimester pregnancy loss or peri-viability PTB as ‘miscarriage.’

Conclusion

The Preterm Birth Advisory Council aims to place those voices impacted by preterm birth at the centre of research into its prevention. The themes identified may guide activities within this research area in local settings and international platforms.

A Novel Technique for Cervical Cerclage Placement at Laparoscopic Pre-Pregnancy Abdominal Cerclage: Operative outcomes and Impact on Preterm Birth

M24

Authors

Gillian Corbett1-3, Catherine Windrim2, Larissa Leuthe2, N Nankasoor2, Cilian Byrne2, Fionnuala Byrne2, Shane Higgins2,3, Donal Brennan2-3, Vicky O’Dwyer2, Michael Wilkinson2, Donal O’Brien2,3, Siobhan Corcoran2,3
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Presenter

Gillian Corbett

Affiliations

1. UCD Perinatal Research Centre, UCD School of Medicine, University College Dublin, Dublin 2, Ireland

2. National Maternity Hospital, Dublin 2 Ireland

3. University College Dublin, Ireland

Abstract

Background

Abdominal cerclage is an important and efficacious option for women at significant risk of preterm birth. Laparoscopic pre-pregnancy cerclage is associated with lowest peri-operative risk and optimal pregnancy outcomes. Traditional technique for placing cerclage includes bladder reflection and dissection lateral to the lower uterine body to create bilateral peritoneal windows. Novel use of the port closure device to pass suture material has been used in our unit in recent years. Given paucity of data on outcomes for this novel technique, we report both operative and subsequent pregnancy outcomes for port closure device technique compared to traditional dissection technique for cerclage placement at laparoscopic pre-pregnancy abdominal cerclage.

Method

This is a retrospective cohort study at the National Maternity Hospital over the last ten years (2012-2022). All cases of abdominal cerclage were identified using hospital electronic coding system and variables were collected from electronic health records and patient charts. Operative and pregnancy outcomes were compared between surgical techniques. Ethical approval was granted by the National Maternity Hospital.

Results

Over the study period, sixty-two total abdominal cerclages were identified with seventy subsequent pregnancies. These included fifty pre-pregnancy laparoscopic cerclages, forty-eight of which had operative notes available. Traditional technique was used in thirty-three cases and Port Closure Device technique was used in fifteen. Peri-operative factors across groups were similar regarding maternal age, weight at surgery, number of previous abdominal surgeries, entry technique, suture material and rates of bladder reflection. Compared to traditional approach, the port closure device technique was associated with lower blood loss (0.0+-0.0ml vs 12.9+-34.1ml, p=0.003) and shorter hospital length of stay (0.1+-0.4 vs 0.8+-0.8 days, p=0.032). There were trends in shorter operating time (43.1+-15.1 vs 50.7+-18.2 minutes, p=0.513) and less required laparoscopic ports (2.9+0.6- vs 3.5+-0.7 ports, p=0.133), not achieve statistically significance. All six cases of laparoscopic peri-operative complications occurred with the traditional technique (18.2% vs 0.0%, p=0.077). These one uterine perforation, and issues with bladder dissection and creation of peritoneal window including conversion to open, unsuccessful dissection requiring re-operation and post operative urinary retention.

The subsequent livebirth and miscarriage rates were similar between techniques. Interestingly, all cases of preterm birth occurred in the traditional technique group (20.8% vs 0.0%, p=0.278), although this was not statistically significant in these small sub-cohorts. All cases of antenatal admission with TPTL occurred in the traditional technique group (40.0% vs 0.0%, p=0.016), but was not significant in this small sub-cohort.

Conclusion

The novel technique of using port closure device for suture placement at laparoscopic abdominal cerclage is associated with lower blood loss and length of stay and similar livebirth and miscarriage rates. There were also trends in shorter operating times, less laparoscopic port requirement and lower rate of preterm birth.

Effect of mechanical stimulation on Cx43 and collagen integrity in human preterm amniotic membrane defects

M25

Authors

1Costa E, 1Crowther MF, 2Thrasivoulou C, 3Becker DL, 4Deprest JA, 4,5David AL, 1Chowdhury TT.
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Presenter

Mia Crowther

Affiliations

1Centre for Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK.

2Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.

3Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore, 308232.

4Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.

5Elizabeth Garrett Anderson Institute for Women’s Health, University College London, Medical School Building, 74 Huntley Street, London WC1E 6AU

Abstract

Background

Preterm premature rupture of membranes (PPROM) remains a major complication leading to loss of collagen structure and integrity of the fetal membranes. The amniotic membrane (AM) has poor healing capacity due to increased expression of connexin 43 (Cx43) by amniotic mesenchymal cells (AMCs) but not myofibroblasts which are cell populations influenced by the mechanical environment. In the present study, we examined the effects of mechanical stimulation on Cx43 expression and collagen structure in the AM from patients who underwent spontaneous early and late PPROM rupture.

Method

Preterm human placentas were collected from 5 women after spontaneous PPROM (32+0 to 35+0 weeks GA). AM explants were subjected to 2% cyclic tensile strain (CTS) for 24 hours in the presence and absence of Cx43 antisense. At the end of the mechanical stimulation experiment, control and strained explants were fixed in 4% PFA prior to analysis of cell morphology, collagen structure and Cx43 protein expression. Cell type nuclei deformation and Cx43 plaque intensity were quantified in the epithelial and fibroblast layer by a triple immunostaining IMF confocal microscopy. Collagen organisation in AM defects was analysed by SHG imaging.

Results

Preterm human placentas were collected from 5 women after spontaneous PPROM (32+0 to 35+0 weeks GA). AM explants were subjected to 2% cyclic tensile strain (CTS) for 24 hours in the presence and absence of Cx43 antisense (n=12-18 explants). At the end of experiment, control and CTS explants were fixed in 4% PFA prior to analysis of cell morphology, collagen structure and Cx43 protein expression. Cell type nuclei deformation and Cx43 plaque intensity were quantified in the epithelial and fibroblast layer by a triple immunostaining technique and immunofluorescence confocal microscopy. Collagen organisation in AM defects was analysed by SHG imaging.

Conclusion

We observed defect sizes of around 3.5 cm to 7.5 cm diameter after late preterm delivery. In the epithelial layer, mechanical stimulation significantly increased elongation of AECs (p<0.001) and the cells were observed to form Cx43 plaques between cell to cell contacts. In the fibroblast layer, mechanical stimulation increased cytoplasmic expression of Cx43 in myofibroblasts but formed plaques in AMCs. Mechanical stimulation increased collagen SHG intensity and polarisation at the wound edge in an attempt to contract the defect site. However, the amount of collagen detected by the SHG signal was reduced around the wound edge and we observed fibre degeneration in preterm AM defects. In summary, the present study shows that mechanical stimulation increased Cx43 but this was dependent on the cell type. Collagen organisation was reduced in large AM defects after rupture implicating degenerative mechanisms.

Direct on-swab metabolic profiling by DESI-MS for monitoring and stratification of live biotherapeutic intervention during pregnancy.

M26

Authors

Eftychios Manoli 1,2, Gonçalo D. S. Correia 1,2, Erna Bayar 1,2, Belen Gimeno-Molina 1,2,4, Lynne Sykes 1,2,4, Zoltan Takats 3,5, Phillip R. Bennett 1,2, and David A. MacIntyre 1,2
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Presenter

Katia Capuccini

Affiliations

1. Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0NN, United Kingdom.

2. March of Dimes Prematurity Research Centre at Imperial College London

3. The National Phenome Centre at Imperial College London

4. The Parasol Foundation Centre for Women’s Health and Cancer Research

5. Section of Bioanalytical Chemistry, Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0TR, UK

Abstract

Background

Dominance of the vaginal microbiome by Lactobacillus crispatus is associated with term delivery whereas Lactobacillus depletion is a risk factor for preterm birth (PTB). Modulation of the vaginal microbiome towards L. crispatus dominance using live biotherapeutics offers an attractive strategy for reducing PTB risk. We recently showed that vaginal administration of LACTIN-V (Osel, California, USA), a vaginally-derived strain of L. crispatus (CTV-05), is safe and well-tolerated by pregnant women. We aimed to assess the capacity of direct on-swab metabolic profiling by Desorption Electrospray Ionisation-Mass Spectrometry (DESI-MS) to rapidly assess vaginal microbiota-host interactions in patients receiving LACTIN-V during pregnancy. Further, we aimed to determine if cervicovaginal fluid (CVF) metabolic profiles could facilitate prediction of successful colonisation.

Method

Pregnant women at high-risk of spontaneous PTB were recruited as part of the single-arm intervention study, FLIP-1 (n=62). Participants vaginally administered a pre-filled applicator containing L. crispatus CTV-05 (2×10^9 cfu) daily for five consecutive days, followed by six weekly doses. Vaginal swabs were collected before treatment and at 15-, 18-, 20-, 28- and 36-weeks gestation (n=362). Vaginal microbiota were characterised using metataxonomics (V1-V2 regions) on a MiSeq platform and immune profiling performed using Luminex® immunoassays. Direct on-swab DESI-MS analysis was performed using an a small footprint RDa/BioAcccord ToF mass spectrometer (Waters Corp., Wimslow, UK) with a custom rotating swab holder. Linear mixed effect modelling was used to identify metabolic features associated with microbiota composition and inflammatory status. Random Forest classifiers were used to assess the ability of DESI-MS profiles to predict microbiota composition, and colonisation efficacy.

Results

A total of 410 distinct metabolic features significantly differed between Lactobacillus-dominated and depleted samples enabling robust discrimination of genera-level compositions (AUC 0.98; sensitivity: 0.61; specificity: 0.99). Metabolic features robustly discriminated major vaginal community state types (CSTI, III and IV) (AUC >0.98; sensitivity: >0.95; specificity: >0.99). Metabolic profiles of pre-intervention samples allowed good prediction of subsequent colonisation (AUC = 0.71). A random forest classifier was used to identify CVF metabolic features predictive of immune mediator concentration including IL-1β (CV R2 = 0.41) and IL-8 (CV R2 = 0.58).

Conclusion

Direct on-swab analysis by DESI-MS using a compact benchtop mass spectrometer allows for rapid (<2min) and robust prediction of microbial composition and immune status and provides insight into colonization dynamics. We propose the use of Direct on-swab analysis by DESI-MS as an effective point-of-care diagnostic tool for rapid assessment of vaginal microbiota composition and inflammatory status in pregnancy.

Risk of spontaneous preterm birth following preterm full dilatation caesarean section

M27

Authors

Banerjee A(1,2), Glazewska-Hallin A(3), Ivan M(1,2), Story L(3), Suff N(3), Casagrandi D(1,2), Tetteh A(1), Greenwold N(1), Napolitano R(1,2), Shennan AH(3), David AL(1,2)
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Presenter

Amrita Banerjee

Affiliations

1. Department of Maternal and Fetal Medicine, Elizabeth Garrett Anderson Wing, University College London Hospital, London, UK.

2. Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, UK.

3. Department of Women's and Children's Health, St Thomas' Hospital, King's College London, London, UK.

Abstract

Background

Term full dilatation caesarean section (FDCS) is associated with an increased risk of subsequent spontaneous preterm birth (sPTB), probably due to trauma close to or in the cervix. Preterm FDCS may also increase the risk of sPTB but has not been evaluated yet. This study investigated the relationship between recurrent sPTB and a previous preterm FDCS.

Method

This is a retrospective cohort study of singleton pregnant women attending two high-risk preterm birth surveillance clinics (St Thomas’ Hospital and University College London Hospital, London, UK) who had one previous sPTB (24-36+6 weeks’ gestation). Women with a previous preterm FDCS were compared to women with a previous vaginal sPTB. Primary outcome was sPTB and/or late miscarriage (14-23+6 weeks gestation). Secondary outcomes included prophylactic intervention, vaginal progesterone or cervical cerclage. In women with previous preterm FDCS, CS scar distance to internal os was measured using transvaginal ultrasound. We adjusted for sPTB risk factors through logistic regression (age, BMI, ethnicity, smoking, parity, previous sPTB gestation, late miscarriage, uterine anomaly and cervical surgery).

Results

Recurrent sPTB (<37 weeks) occurred in 42.9% (9/21) of women with a previous preterm FDCS compared to 16.8% (31/185) of women with a previous vaginal sPTB; relative risk 2.6 (95% CI 1.4–4.6, p=0.01). The rate of sPTB <32 weeks’ gestation was 14.3% (3/21) in the preterm FDCS group versus 7/185 (3.8%), in the vaginal sPTB group, (aOR 13.9 (95% CI 2.1–93.7), p=0.007). Median gestation of delivery in the pregnancy following preterm FDCS was earlier than in women with a previous preterm sPTB, 37+5 (range 23+6 – 40+2) versus 38+4 (range 25+1 – 42+2) weeks + days, p=0.02). Recurrent sPTB occurred following a transvaginal cervical cerclage in 75% (3/4) of the preterm FDCS group compared to 24.5% (12/49) in the vaginal sPTB group, p=0.06. The CS scar was assessed in 14/21 women with previous preterm FDCS and was visualised in 86%. Median CS scar distance was 1.6mm above internal cervical os.

Conclusion

Women undergoing an FDCS in spontaneous preterm labour have a significantly higher risk of recurrent sPTB at <37 and <32 weeks’ gestation compared to women with a previous vaginal sPTB. These findings are comparable to the risk of sPTB following term FDCS and suggest that a preterm FDCS also compromises cervical function.