Imperial College London

ProfessorPhillipBennett

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Clinical Professor
 
 
 
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Contact

 

+44 (0)20 7594 2176p.bennett

 
 
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Assistant

 

Miss Kiran Dosanjh +44 (0)20 7594 2176

 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

607 results found

Grewal K, MacIntyre DA, Bennett PR, 2021, The reproductive tract microbiota in pregnancy., Biosci Rep, Vol: 41

The reproductive tract microbiota plays a crucial role in maintenance of normal pregnancy and influences reproductive outcomes. Microbe-host interactions in pregnancy remain poorly understood and their role in shaping immune modulation is still being uncovered. In this review, we describe the composition of vaginal microbial communities in the reproductive tract and their association with reproductive outcomes. We also consider strategies for manipulating microbiota composition by using live biotherapeutics, selective eradication of pathogenic bacteria with antibiotics and vaginal microbiota transplantation. Finally, future developments in this field and the need for mechanistic studies to explore the functional significance of reproductive tract microbial communities are highlighted.

Journal article

Pruski P, Dos Santos Correia G, Lewis H, Capuccini K, Inglese P, Chan D, Brown R, Kindinger L, Lee Y, Smith A, Marchesi J, McDonald J, Cameron S, Alexander-Hardiman K, David A, Stock S, Norman J, Terzidou V, Teoh TG, Sykes L, Bennett P, Takats Z, MacIntyre Det al., 2021, Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth, Nature Communications, ISSN: 2041-1723

Journal article

Kyrgiou M, Bowden SJ, Athanasiou A, Paraskevaidi M, Kechagias K, Zikopoulos A, Terzidou V, Martin-Hirsch P, Arbyn M, Bennett P, Paraskevaidis Eet al., 2021, Morbidity after local excision of the transformation zone for cervical intra-epithelial neoplasia and early cervical cancer, Best Practice and Research: Clinical Obstetrics and Gynaecology, Vol: 75, Pages: 10-22, ISSN: 1521-6934

The awareness that cervical intra-epithelial neoplasia (CIN) treatment increases the risk of preterm birth has led to major changes in clinical practice. Women with CIN have a higher baseline risk of prematurity but local treatment further increases this risk. The risk further increases with increasing cone length and multiplies for repeat excisions; it is unclear whether small cones confer any additional risk to CIN alone. There is no evidence to suggest that fertility is affected by local treatment, although this increases the risk of mid-trimester loss. Caution should prevail when deciding to treat women with CIN of reproductive age. If treatment is offered, this should be conducted effectively to optimise the clearance of disease and minimise the risk of recurrence. Colposcopists should alert women undergoing treatment that this may increase the risk of preterm birth and that they may be offered interventions when pregnant. The cone length should be clearly documented and used as a risk stratifier.

Journal article

Chan D, Bennett PR, Lee YS, Teoh TG, Adan M, Ahmed SM, Brown RG, David AL, Lewis H, Gimeno-Molina B, Norman JE, Stock SJ, Terzidou V, Kropf P, Botto M, MacIntyre DA, Sykes Let al., 2021, Microbial-Driven Preterm Labour Involves Crosstalk between the Innate and Adaptive Immune Response., Publisher: SPRINGER HEIDELBERG, Pages: 108A-109A, ISSN: 1933-7191

Conference paper

Norman JE, Norrie J, MacLennan G, Cooper D, Whyte S, Chowdhry S, Cunningham-Burley S, Neilson AR, Mei XW, Smith JB, Shennan A, Robson SC, Thornton S, Kilby MD, Marlow N, Stock SJ, Bennett PR, Denton Jet al., 2021, The Arabin pessary to prevent preterm birth in women with a twin pregnancy and a short cervix: the STOPPIT 2 RCT, HEALTH TECHNOLOGY ASSESSMENT, Vol: 25, Pages: 1-+, ISSN: 1366-5278

Journal article

Fourie H, Al-Memar M, Vaulet T, Kyriacou C, Bennett P, Timmerman Det al., 2021, The ability of plasma proteins to predict pregnancy outcome in the first trimester, Publisher: WILEY, Pages: E37-E37, ISSN: 1470-0328

Conference paper

Bayar E, Zarasvand S, Adan M, Sykes L, Lee Y, Parks T, Lee P, MacIntyre D, Bennett Pet al., 2021, Acceptability of live vaginal biotherapeutics in a cohort of pregnant women, Publisher: WILEY, Pages: E32-E33, ISSN: 1470-0328

Conference paper

Budwig L, Brown R, Lee YS, Mountain K, Gimeno-Molina B, Adan M, Bayar E, MacIntyre DA, Bennett PR, Sykes Let al., 2021, The Use of Peripheral Blood Neutrophil Counts in the Prediction of Funisitis Following Preterm Prelabour Rupture of Membranes., Publisher: SPRINGER HEIDELBERG, Pages: 116A-116A, ISSN: 1933-7191

Conference paper

Grewal K, Lee Y, Smith A, Brosens J, Al-Memar M, Bourne T, Kundu S, MacInytre D, Bennett Pet al., 2021, Lactobacillus deplete vaginal microbial composition is associated with chromosomally normal miscarriage and local inflammation, Publisher: OXFORD UNIV PRESS, Pages: 56-56, ISSN: 0268-1161

Conference paper

Fourie H, Al-Memar M, Smith A, Ng S, Lee Y, Timmerman D, Bourne T, MacIntyre D, Bennett Pet al., 2021, The relationship between systemic oestradiol and vaginal microbiota composition in miscarriage and normal pregnancy, Publisher: OXFORD UNIV PRESS, Pages: 311-312, ISSN: 0268-1161

Conference paper

Grewal K, Lee YS, Smith A, Brosens JJ, Bourne T, Al-Memar M, Kundu S, MacIntyre DA, Bennett Pet al., 2021, Euploid Miscarriage Is Associated with Lactobacillus spp. Deplete Vaginal Microbial Composition and Local Inflammation., Publisher: SPRINGER HEIDELBERG, Pages: 77A-77A, ISSN: 1933-7191

Conference paper

Bonnardel F, Haslam SM, Dell A, Feizi T, Liu Y, Tajadura-Ortega V, Akune Y, Sykes L, Bennett PR, MacIntyre DA, Lisacek F, Imberty Aet al., 2021, Proteome-wide prediction of bacterial carbohydrate-binding proteins as a tool for understanding commensal and pathogen colonisation of the vaginal microbiome, npj Biofilms and Microbiomes, Vol: 7, Pages: 1-10, ISSN: 2055-5008

Bacteria use carbohydrate-binding proteins (CBPs), such as lectins and carbohydrate-binding modules (CBMs), to anchor to specific sugars on host surfaces. CBPs in the gut microbiome are well studied, but their roles in the vagina microbiome and involvement in sexually transmitted infections, cervical cancer and preterm birth are largely unknown. We established a classification system for lectins and designed Hidden Markov Model (HMM) profiles for data mining of bacterial genomes, resulting in identification of >100,000 predicted bacterial lectins available at unilectin.eu/bacteria. Genome screening of 90 isolates from 21 vaginal bacterial species shows that those associated with infection and inflammation produce a larger CBPs repertoire, thus enabling them to potentially bind a wider array of glycans in the vagina. Both the number of predicted bacterial CBPs and their specificities correlated with pathogenicity. This study provides new insights into potential mechanisms of colonisation by commensals and potential pathogens of the reproductive tract that underpin health and disease states.

Journal article

Mowla S, Bennett P, MacIntyre D, 2021, The vaginal microbiome, NEW GENETIC DIAGNOSTIC TECHNOLOGIES IN REPRODUCTIVE MEDICINE 2E, Editors: Simon, Rubio

There is now substantial evidence implicating the vaginal microbiome in reproductive tract health and disease. As technology has developed, our ability to characterise the composition of the vaginal microbiome has improved providing new insights into how commensal and pathogenic microbes interact with the host to protect against, or potentiate pathology and disease. In this chapter we discuss the current understanding of what shapes the structure of the vaginal microbiome throughout a woman’s life span, how it can be characterised and how specific microbiota-host interactions at the mucosal interface may influence reproductive success or failure.

Book chapter

Whelan E, Kalliala I, Semertzidou A, Raglan O, Bowden S, Markozannes G, Cividini S, Kechagias K, McNeish I, Marchesi J, MacIntyre D, Bennett P, Tsilidis K, Kyrgiou Met al., 2021, Risk factors for ovarian cancer: an umbrella review of the literature, Publisher: WILEY, Pages: 71-71, ISSN: 1470-0328

Conference paper

Semertzidou A, MacIntyre D, Marchesi J, Bennett P, Kyrgiou Met al., 2021, The role of genital tract microbiota continuum in endometrial malignancy, Publisher: WILEY, Pages: 115-116, ISSN: 1470-0328

Conference paper

Raglan O, MacIntyre D, Mitra A, Lee YS, Smith A, Assi N, Nautiyal J, Purkayastha S, Gunter MJ, Gabra H, Marchesi JR, Bennett P, Kyrgiou Met al., 2021, The association between obesity and weight loss after bariatric surgery on the vaginal microbiota, Microbiome, Vol: 9, Pages: 1-17, ISSN: 2049-2618

Background: Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery.Methods: Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery. Results: The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillus spp., and Gardnerella- spp. depleted) VMB, compared with non-obese subjects (p<0.001). Obese women had higher relative abundance of Dialister species (p<0.001), Anaerococcus vaginalis (p=0.021) and Prevotella timonensis (p=0.020) and decreased relative abundance of Lactobacillus crispatus (p=0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α, and TNFα levels were all higher among obese women, however only IL-1β and IL-8 correlated with VMB species diversity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery, however 75% of these women remained obese at six months. Prior to surgery there was no relationship between body mass index (BMI) and VMB structure, however post-surgery women with a Lactobacillus-dominant VMB had a significantly lower BMI than those with a high diversity VMB.Conclusions: Obese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compared to non-obese women. Bariatric surgery does not change the VMB, however, those with the greatest

Journal article

Coomarasamy A, Gallos ID, Papadopoulou A, Dhillon-Smith RK, Al-Memar M, Brewin J, Christiansen OB, Stephenson MD, Oladapo OT, Wijeyaratne CN, Small R, Bennett PR, Regan L, Goddijn M, Devall AJ, Bourne T, Brosens JJ, Quenby Set al., 2021, Sporadic miscarriage: evidence to provide effective care, The Lancet, Vol: 397, Pages: 1668-1674, ISSN: 0140-6736

The physical and psychological effect of miscarriage is commonly underappreciated. The journey from diagnosis of miscarriage, through clinical management, to supportive aftercare can be challenging for women, their partners, and caregivers. Diagnostic challenges can lead to delayed or ineffective care and increased anxiety. Inaccurate diagnosis of a miscarriage can result in the unintended termination of a wanted pregnancy. Uncertainty about the therapeutic effects of interventions can lead to suboptimal care, with variations across facilities and countries. For this Series paper, we have developed recommendations for practice from a literature review, appraisal of guidelines, and expert group discussions. The recommendations are grouped into three categories: (1) diagnosis of miscarriage, (2) prevention of miscarriage in women with early pregnancy bleeding, and (3) management of miscarriage. We recommend that every country reports annual aggregate miscarriage data, similarly to the reporting of stillbirth. Early pregnancy services need to focus on providing an effective ultrasound service, as it is central to the diagnosis of miscarriage, and be able to provide expectant management of miscarriage, medical management with mifepristone and misoprostol, and surgical management with manual vacuum aspiration. Women with the dual risk factors of early pregnancy bleeding and a history of previous miscarriage can be recommended vaginal micronised progesterone to improve the prospects of livebirth. We urge health-care funders and providers to invest in early pregnancy care, with specific focus on training for clinical nurse specialists and doctors to provide comprehensive miscarriage care within the setting of dedicated early pregnancy units.

Journal article

Coomarasamy A, Dhillon-Smith RK, Papadopoulou A, Al-Memar M, Brewin J, Abrahams VM, Maheshwari A, Christiansen OB, Stephenson MD, Goddijn M, Oladapo OT, Wijeyaratne CN, Bick D, Shehata H, Small R, Bennett PR, Regan L, Rai R, Bourne T, Kaur R, Pickering O, Brosens JJ, Devall AJ, Gallos ID, Quenby Set al., 2021, Recurrent miscarriage: evidence to accelerate action, LANCET, Vol: 397, Pages: 1675-1682, ISSN: 0140-6736

Journal article

Quenby S, Gallos I, Dhillon-Smith R, Podesek M, Stephenson M, Fisher J, Brosens J, Brewin J, Ramhorst R, Lucas E, McCoy R, Anderson R, Daher S, Regan L, Al-Memar M, Bourne T, MacIntyre D, Rai R, Christiansen O, Sugiura-Ogasawara M, Odendaal J, Devall A, Bennett P, Petrou S, Coomarasamy Aet al., 2021, Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss, The Lancet, Vol: 397, Pages: 1658-1667, ISSN: 0140-6736

Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5–18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3–11·4%), two miscarriages is 1·9% (1·8–2·1%), and three or more miscarriages is 0·7% (0·5–0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need

Journal article

Cartwright J, Frankin L, Tikkinen K, Kallila I, Miotla P, Rechberger T, Offiah I, McMahon S, O'Reilly B, Lince S, Kluivers K, Post W, Poelmans G, Palmer M, Wessels H, Wong A, Kuh D, Kivimaki M, Kumari M, Mangino M, Spector T, Guggenheim J, Lehne B, De Silva M, Evans D, Lawlor D, Karhunen V, Mannikko M, Marczak M, Bennett P, Khullar V, Jarvelin M, Walley A, on behalf of the IGNITE Consortiumet al., 2021, Genome wide association study identifies two novel loci associated with female stress and urgency urinary incontinence, The Journal of Urology, ISSN: 0022-5347

Background:Genome-wide association studies (GWAS) have not identified replicable genetic risk loci for stress or urgency urinary incontinence.Methods:We carried out a discovery stage case control GWAS in three independent discovery cohorts of European women (n=8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in six additional studies of European ancestry (n=4,069). We collected bladder biopsies from women with incontinence to further investigate bladder expression of implicated genes and pathways (n=50) and used symptom questionnaires for phenotyping. We conducted meta-analyses using inverse variance fixed effects models in METAL, and whole transcriptome analyses using Affymetrix arrays, with replication with TaqMan PCR.Results:In the discovery stage we identified 16 single nucleotide polymorphisms (SNPs) genotyped or imputed at five loci that reached genome-wide significance (p<5x10-8). In replication, rs138724718 on chromosome 2, near the macrophage receptor with collagenous structure (MARCO) gene (replication p=0.003) associated with stress incontinence. In addition, rs34998271 on chromosome 6 near the Endothelin 1 (EDN1) gene (replication p=0.0008) associated with urgency incontinence. In combined meta-analyses of discovery and replication cohorts, associations with genome-wide significance for these two SNPs were confirmed. Transcriptomics analyses showed differential expression of 7 of 19 genes in the endothelin pathway between stress and urgency incontinence (p<0.0001).Conclusion:We uncovered two new risk loci near the genes Endothelin 1 (EDN1), associated with urgency incontinence and Macrophage Receptor with Collagenous Structure (MARCO), associated with stress incontinence. These loci are biologically plausible given their roles in smooth muscle contraction and innate host defense respectively.

Journal article

Bowden S, Bodinier B, Kalliala I, Zuber V, Vuckovic D, Doulgeraki T, Whitaker M, Wielscher M, Cartwright R, Tsilidis K, Bennett P, Jarvelin M-R, Flanagan J, Chadeau M, Kyrgiou M, FinnGen consortiumet al., 2021, Genetic variation in cervical preinvasive and invasive disease: a genome-wide association study, The Lancet Oncology, Vol: 22, Pages: 548-557, ISSN: 1213-9432

Background: Most uterine cervical high-risk HPV infections (hrHPV) are transient, with only a small 3fraction developing into cervical cancer. Family aggregation studies and heritability estimates suggest 4a significant inherited genetic component. Candidate gene studies and previous genome-wide 5association studies (GWAS) report associations between the human leukocyte antigen (HLA) region 6and cervical cancer. 78Methods: Adopting a genome-wide approach, we compared the genetic variation in women with 9invasive cervical cancer (ICC) and cervical intra-epithelial neoplasia (CIN) grade 3, to that in healthy 10controls using the largest reported cohort of unrelated European individuals (N=150,314)to date. We 11sought for replication in a second large independent dataset (N=128,123). We further performed a two-12sample Mendelian Randomisation approach to explore the role of risk factors in the genetic risk of 13cervical cancer.1415Findings: In our analysis (N=4,769 CIN3 and ICC cases; N=145,545 controls), of the (N=9,600,464) 16assayed and imputed SNPs, six independent variants were found associated with CIN3and ICC. These 17included novel loci rs10175462(PAX8; OR=0.87(95%CI=0.84-0.91); P=1.07x10-9) and rs27069 18(CLPTM1L;OR=0.88(95%CI=0.84-0.92); P=2.51x10-9), and previously reported signals at rs9272050 19(HLA-DQA1;OR=1.27(95%CI=1.21-1.32); P=2.51x10-28), rs6938453 (MICA;OR=0.7920(95%CI=0.75-0.83); P=1.97x10-17), rs55986091 (HLA-DQB1;OR=0.66(95%CI=0.60-0.72); 21P=6.42x10-22) and rs9266183 (HLA-B;OR=0.73(95%CI=0.64-0.83); P=1.53x10-6). Mendelian 22randomisation further supported the complementary role of smoking, age at first pregnancy, and number 23of sexual partners in the risk of developing cervical cancer.2425Interpretation: Our results provide substantial new evidence for genetic susceptibility to cervical cancer, 26including PAX8, CLPTM1LandHLA genes, suggesting disruption in apoptotic and immun

Journal article

Norman JE, Norrie J, MacLennan G, Cooper D, Whyte S, Chowdhry S, Cunningham-Burley S, Mei XW, Smith JBE, Shennan A, Robson SC, Thornton S, Kilby MD, Marlow N, Stock SJ, Bennett PR, Denton Jet al., 2021, Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis, PLOS MEDICINE, Vol: 18, ISSN: 1549-1277

Journal article

Short C-E, Brown R, Quinlan R, Lee Y, Smith A, Marchesi J, Shattock R, Bennett P, Taylor G, MacIntyre Det al., 2021, Lactobacillus-depleted vaginal microbiota in pregnant women living with HIV-1 infection are associated with increased local inflammation and preterm birth, Frontiers in Cellular and Infection Microbiology, Vol: 10, ISSN: 2235-2988

Background: Pregnant women living with HIV-1 infection (PWLWH) have an elevated risk of preterm birth (PTB) of unknown aetiology, which remains after successful suppression of HIV. Women at high risk for HIV have a common bacterial profile which has been associated with poor birth outcomes. We set out to explore factors associated with gestational age at delivery of PWLWH in a UK population.Methods: Prospective study of PWLWH (n = 53) in whom the vaginal microbiota and cervicovaginal cytokine milieu were assessed using metataxonomics and multiplexed immunoassays, respectively. Cross-sectional characterisation of vaginal microbiota in PWLWH were compared with 22 HIV uninfected pregnant women (HUPW) at a similar second trimester timepoint. Within PWLWH the relationships between bacterial composition, inflammatory response, and gestational age at delivery were explored.Findings: There was a high rate of PTB among PWLWH (12%). In the second trimester the vaginal microbiota was more diverse in PWLWH than in HUPW (Inverse Simpson Index, p = 0.0004 and Species Observed, p = 0.009). PWLWH had a lower prevalence of L. crispatus dominant vaginal microbiota group (VMB I, 15 vs 54%) than HUPW and higher prevalence of L. iners dominant (VMB III, 36 vs 9% and VMB IIIB, 15 vs 5%) and mixed anaerobes (VMB IV, 21 vs 0%). Across the second and third trimesters in PWLWH, VMB III/IIIB and IV were associated with PTB and with increased local inflammation [cervicovaginal fluid (CVF) cytokine concentrations in upper quartile]. High bacterial diversity and anaerobic bacterial abundance were also associated with CVF pro-inflammatory cytokines, most notably IL-1β.Interpretation: There is an association between local inflammation, vaginal dysbiosis and PTB in PWLWH. Understanding the potential of antiretroviral therapies to influence this cascade will be important to improve birth outcomes in this population.

Journal article

Zarasvand S, Bayar E, Adan M, Mountain K, Lewis H, Joash K, Teoh TG, Bennett PR, Das S, Sykes Let al., 2020, Rapid quality improvement in a preterm birth clinic care pathway during the COVID-19 pandemic, BMJ Open Quality, Vol: 9, Pages: 1-9, ISSN: 2399-6641

Background Preterm birth (PTB) occurs in 8% of births in the UK. At Imperial College Healthcare NHS Trust, our PTB prevention clinic manages the care of approximately 1000 women/year. Women referred to the clinic are seen from 12 weeks of pregnancy with subsequent appointments every 2–4 weeks to measure cervical length (CL) using transvaginal ultrasound (TVUS). Women with a history of cervical weakness or short cervix on TVUS are offered a cervical cerclage.Local problem During the COVID-19 outbreak, pregnant women were strongly advised to avoid social mixing and public transport. The National Health Service had to rapidly adopt remote consultation and redesign clinical pathways in order to reduce transmission, exposure and spread among women at high risk of PTB.Methods We focused on Specific, Measurable, Achievable, Realistic and Timebound aims and used a driver diagram to visualise our changes. We used a series of Plan Do Study Act cycles to evaluate and adapt change ideas through the UK’s national lockdown during the COVID-19 pandemic between 23 March and 29 May 2020.Results We reduced the number of face-to-face appointments by 54%. This was achieved by increasing remote telephone consultations from 0% to 64%, and by reducing the intensity of surveillance. The rate of regional anaesthetic was increased from 53% to 95% for cerclage placement in order to minimise the number of aerosol-generating procedures. Patient and staff satisfaction responses to these changes were used to tailor practices. No women tested positive for COVID-19 during the study period.Conclusions By using quality improvement methodology, we were able to safely and rapidly implement a new care pathway for women at high risk of PTB which was acceptable to patients and staff, and effective in reducing exposure of COVID-19.

Journal article

Coomarasamy A, Devall AJ, Brosens JJ, Quenby S, Stephenson MD, Sierra S, Christiansen OB, Small R, Brewin J, Roberts TE, Dhillon-Smith R, Harb H, Noordali H, Papadopoulou A, Eapen A, Prior M, Di Renzo GC, Hinshaw K, Mol BW, Lumsden MA, Khalaf Y, Shennan A, Goddijn M, van Wely M, Al-Memar M, Bennett P, Bourne T, Rai R, Regan L, Gallos IDet al., 2020, Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence, Obstetrical and Gynecological Survey, Vol: 75, Pages: 743-744, ISSN: 0029-7828

Historically, a lack of methodologically strong and generalizable studies has limited policy makers from recommending the use of progesterone supplementation to improve outcomes in women at high risk of miscarriage. The PROMISE and PRISM trials were carried out to rectify this and generate robust evidence on the role of progesterone supplementation to prevent miscarriage.

Journal article

Kim SH, MacIntyre D, Binkhamis R, Cook J, Sykes L, Bennett P, Terzidou Vet al., 2020, Maternal plasma miRNAs as potential biomarkers for detecting risk of small-for-gestational-age births, EBioMedicine, Vol: 62, ISSN: 2352-3964

BackgroundSmall-for-gestational-age fetuses (SGA) (birthweight <10th centile) are at high risk for stillbirth or long-term adverse outcomes. Here, we investigate the ability of circulating maternal plasma miRNAs to determine the risk of SGA births.MethodsMaternal plasma samples from 29 women of whom 16 subsequently delivered normally grown babies and 13 delivered SGA (birthweight <5th centile) were selected from a total of 511 women recruited to form a discovery cohort in which expression data for a total of 800 miRNAs was determined using the Nanostring nCounter miRNA assay. Validation by RT-qPCR was performed in an independent cohort.FindingsPartial least-squares discriminant analysis (PLS-DA) of the Nanostring nCounter miRNA assay initially identified seven miRNAs at 12–14+6 weeks gestation, which discriminated between SGA cases and controls. Four of these were technically validated by RT-qPCR. Differential expression of two miRNA markers; hsa-miR-374a-5p (p = 0•0176) and hsa-let-7d-5p (p = 0•0036), were validated in an independent population of 95 women (SGA n = 12, Control n = 83). In the validation cohort, which was enriched for SGA cases, the ROC AUCs were 0•71 for hsa-miR-374a-5p, and 0•74 for hsa-let-7d-5p, and 0•77 for the two combined.InterpretationWhilst larger population-wide studies are required to validate their performance, these findings highlight the potential of circulating miRNAs to act as biomarkers for early prediction of SGA births.

Journal article

Bennett PR, Brown RG, MacIntyre DA, 2020, Vaginal microbiome in preterm rupture of membranes, Obstetrics and Gynecology Clinics of North America, Vol: 47, Pages: 503-521, ISSN: 0889-8545

Journal article

MacIntyre D, Bennett P, 2020, Chapter 3 - Microbial signatures of preterm birth, The Human Microbiome in Early Life Implications to Health and Disease, Publisher: Academic Press, ISBN: 9780128180976

Preterm birth remains the primary cause of death in children under the age of 5 years worldwide. A causal relationship between infection and preterm birth has long been recognized. However, recent applications of molecular-based profiling techniques have provided new insights into the relationship between specific bacterial compositions of the lower reproductive tract and subsequent preterm birth risk. In this chapter, we investigate evidence for “microbial signatures” of preterm birth and examine mechanisms by which shifts in microbiome composition could contribute to an infectious etiology of preterm birth. Despite high levels of heterogeneity between studies, vaginal depletion of Lactobacillus spp. and high-diversity communities enriched for potentially pathogenic bacteria are frequently associated with preterm birth, whereas Lactobacillus spp. dominant communities appear to confer protection against preterm birth, particularly when dominated by Lactobacillus crispatus. Strategies focused toward promoting optimal microbial signatures during pregnancy may help reduce rates of preterm birth and improve maternal and neonatal outcomes.

Book chapter

Paraskevaidi M, Cameron SJS, Whelan E, Bowden S, Tzafetas M, Mitra A, Semertzidou A, Athanasiou A, Bennett P, MacIntyre D, Takats Z, Kyrgiou Met al., 2020, Laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) as a metabolomics platform in cervical cancer screening, EBioMedicine, Vol: 60, ISSN: 2352-3964

BackgroundThe introduction of high-risk human papillomavirus (hrHPV) testing as part of primary cervical screening is anticipated to improve sensitivity, but also the number of women who will screen positive. Reflex cytology is the preferred triage test in most settings but has limitations including moderate diagnostic accuracy, lack of automation, inter-observer variability and the need for clinician-collected sample. Novel, objective and cost-effective approaches are needed.MethodsIn this study, we assessed the potential use of an automated metabolomic robotic platform, employing the principle of laser-assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) in cervical cancer screening.FindingsIn a population of 130 women, LA-REIMS achieved 94% sensitivity and 83% specificity (AUC: 91.6%) in distinguishing women testing positive (n = 65) or negative (n = 65) for hrHPV. We performed further analysis according to disease severity with LA-REIMS achieving sensitivity and specificity of 91% and 73% respectively (AUC: 86.7%) in discriminating normal from high-grade pre-invasive disease.InterpretationThis automated high-throughput technology holds promise as a low-cost and rapid test for cervical cancer screening and triage. The use of platforms like LA-REIMS has the potential to further improve the accuracy and efficiency of the current national screening programme.

Journal article

Devall AJ, Gallos ID, Khalaf Y, Mol BWJ, Ross J, Shennan A, Horne AW, Small R, Goddijn M, van Wely M, Stephenson MD, Christiansen OB, Brosens JJ, Bennett P, Rai R, Regan L, Quenby S, Coomarasamy A, Devall AJ, Gallos ID, Khalaf Y, Mol BWJ, Ross J, Shennan A, Horne AW, Small R, Goddijn M, van Wely M, Stephenson MD, Christiansen OB, Brosens JJ, Bennett P, Rai R, Regan L, Quenby S, Coomarasamy Aet al., 2020, Re: Effect of progestogen for women with threatened miscarriage: a systematic review and meta-analysis, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 127, Pages: 1303-1304, ISSN: 1470-0328

Journal article

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