Publications
193 results found
Sein E, Belsi A, Morgenstern C, et al., 2023, The early determinants of career choices for medical students following an obstetrics and gynaecology placement: mixed methods study, BJOG: an International Journal of Obstetrics and Gynaecology, ISSN: 1470-0328
ObjectiveTo explore the impact of attending a clinical placement in considering a career in obstetrics and gynaecology.DesignMixed methods study.SettingLondon Medical School.PopulationFifth year medical students attending a clinical placement in obstetrics and gynaecology.MethodsBetween January 2021 and January 2022, questionnaires were used and semi-structured focus groups conducted, which were audio-recorded. Descriptive statistics were conducted and a framework analysis on transcribed focus groups.Main outcome measureThe impact of the clinical placement on career choice.ResultsSix main themes were identified from the analysis; three contributing to considering a career in obstetrics and gynaecology; pregnancy is not an illness, extraordinary experience of observing childbirth and variable specialty and three themes emerged contributing to not considering a career; lack of work–life balance, high stakes specialty and the emotional toll. Even at an undergraduate level, medical students exhibited concerns about the long-term feasibility of achieving work–life balance and avoiding professional burnout, which was partly attributed to the responsibility of looking after both the woman and their baby.ConclusionsObstetrics and gynaecology is perceived as an exciting and variable speciality by medical students. Students’ experiences on the labour ward during a clinical placement appear to contribute to the consideration of a career in obstetrics and gynaecology. Students should be given opportunities to discuss their concerns about obstetrics, particularly over the potential psychological impact of adverse/traumatic birth events. It is crucial to provide a realistic introduction to obstetrics, to recruit enthusiastic junior doctors who will be resilient to the pressures of the speciality, to avoid burnout and minimise attrition rates.
Mountain K, MacIntyre D, Chan D, et al., 2023, ABO blood group antigens and preterm birth risk, 12th International Workshop Reunion Island Reproductive Immunology, Immunological tolerance and Immunology of preeclampsia, Publisher: ELSEVIER IRELAND LTD, Pages: 37-37, ISSN: 0165-0378
Riaposova L, Kim SH, Hanyaloglu A, et al., 2023, Prostaglandin F2alpha requires activation of calcium-dependent signalling to trigger inflammation in human myometrium, Frontiers in Endocrinology, Vol: 14, Pages: 1-19, ISSN: 1664-2392
Introduction: Preterm birth is one of the major causes of neonatal morbidity and mortality across the world. Both term and preterm labour are preceded by inflammatory activation in uterine tissues. This includes increased leukocyte infiltration, and subsequent increase in chemokine and cytokine levels, activation of pro-inflammatory transcription factors as NF-κB and increased prostaglandin synthesis. Prostaglandin F2α (PGF2α) is one of the myometrial activators and stimulators.Methods: Here we investigated the role of PGF2α in pro-inflammatory signalling pathways in human myometrial cells isolated from term non-labouring uterine tissue. Primary myometrial cells were treated with G protein inhibitors, calcium chelators and/or PGF2α. Nuclear extracts were analysed by TranSignal cAMP/Calcium Protein/DNA Array. Whole cell protein lysates were analysed by Western blotting. mRNA levels of target genes were analysed by RT-PCR.Results: The results show that PGF2α increases inflammation in myometrial cells through increased activation of NF-κB and MAP kinases and increased expression of COX-2. PGF2α was found to activate several calcium/cAMP-dependent transcription factors, such as CREB and C/EBP-β. mRNA levels of NF-κB-regulated cytokines and chemokines were also elevated with PGF2α stimulation. We have shown that the increase in PGF2α-mediated COX-2 expression in myometrial cells requires coupling of the FP receptor to both Gαq and Gαi proteins. Additionally, PGF2α-induced calcium response was also mediated through Gαq and Gαi coupling.Discussion: In summary, our findings suggest that PGF2α-induced inflammation in myometrial cells involves activation of several transcription factors – NF-κB, MAP kinases, CREB and C/EBP-β. Our results indicate that the FP receptor signals via Gαq and Gαi coupling in myometrium. This work provides insight i
Sein E, Patel R, Terzidou V, et al., 2023, Early determinants of career choice in obstetrics and gynaecology: Mixed methods study, Publisher: WILEY, Pages: 141-141, ISSN: 1470-0328
Sein E, Patel R, Terzidou V, et al., 2023, Early determinants of career choice in obstetrics and gynaecology: Mixed methods study, Publisher: WILEY, Pages: 141-141, ISSN: 1470-0328
Sein E, Belsi A, Terzidou V, et al., 2023, The meaning of 'traumatic birth event' to obstetricians: Mixed methods study, Publisher: WILEY, Pages: 142-142, ISSN: 1470-0328
Semertzidou A, Grout-Smith H, Kalliala I, et al., 2023, Diabetes and anti-diabetic interventions and the risk of gynaecological and obstetric morbidity: an umbrella review of the literature, BMC Medicine, Vol: 21, Pages: 1-15, ISSN: 1741-7015
BackgroundDiabetes has reached epidemic proportions in recent years with serious health ramifications. The aim of this study was to evaluate the strength and validity of associations between diabetes and anti-diabetic interventions and the risk of any type of gynaecological or obstetric conditions.MethodsDesign: Umbrella review of systematic reviews and meta-analyses.Data sources: PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, manual screening of references.Eligibility criteria: Systematic reviews and meta-analyses of observational and interventional studies investigating the relationship between diabetes and anti-diabetic interventions with gynaecological or obstetric outcomes. Meta-analyses that did not include complete data from individual studies, such as relative risk, 95% confidence intervals, number of cases/controls, or total population were excluded.Data analysis: The evidence from meta-analyses of observational studies was graded as strong, highly suggestive, suggestive or weak according to criteria comprising the random effects estimate of meta-analyses and their largest study, the number of cases, 95% prediction intervals, I2 heterogeneity index between studies, excess significance bias, small study effect and sensitivity analysis using credibility ceilings. Interventional meta-analyses of randomised controlled trials were assessed separately based on the statistical significance of reported associations, the risk of bias and quality of evidence (GRADE) of included meta-analyses.ResultsA total of 117 meta-analyses of observational cohort studies and 200 meta-analyses of randomised clinical trials that evaluated 317 outcomes were included. Strong or highly suggestive evidence only supported a positive association between gestational diabetes and caesarean section, large for gestational age babies, major congenital malformations and heart defects and an inverse relationship between metformin use and ovarian cancer incidence. Only a fifth
Petrou L, Gatehouse A, Kim SH, et al., 2023, Detection of miR-374a-5p on Magnetic Microbeads as a Predictor of Small for Gestational Age Births, 70th Annual Meeting of the Society for Reproductive Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 208A-209A, ISSN: 1933-7191
Molina BG, Bayar E, Love RL, et al., 2023, Cervical Shortening is Associated with Cervical Neutrophil Migration and Complement Activation, 70th Annual Meeting of the Society for Reproductive Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 94A-95A, ISSN: 1933-7191
Ng S, Mountain KE, Elger T, et al., 2023, Predictive Value of Cervical Length Screening in the Context of Cervical Cerclage: A Cohort Study, 70th Annual Meeting of the Society for Reproductive Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 109A-110A, ISSN: 1933-7191
Kim SH, Arianoglou M, MacIntyre DA, et al., 2023, Validation of Circulating MicroRNA Markers for Prediction of Small-for-Gestational-Age Births, 70th Annual Meeting of the Society for Reproductive Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 166A-167A, ISSN: 1933-7191
Petrou L, Latvanen E, Seichepine F, et al., 2022, Lateral Flow Test (LFT) detects cell-free microRNAs predictive of preterm birth directly from human plasma, Advanced NanoBiomed Research, Vol: 2, ISSN: 2699-9307
Despite extensive research toward the development of point-of-care nucleic acid tests (POC NATs) for the detection of microRNAs (miRs) from liquid biopsies, major hurdles remain including the strict requirement for extensive off-chip sample preprocessing. Herein, a nucleic acid lateral flow test (NALFT) is reported on that enables the direct detection of endogenous miRs from as little as 3 μL of plasma without the requirement for any enzyme-catalyzed target amplification or complex miR extraction steps. This is achieved through integration of a denaturing hydrogel composite material onto the LFT, allowing for near-instantaneous on-chip release of miRs from their carriers (extracellular vesicles or transport proteins) prior to detection. This next-generation LFT is sensitive enough to detect endogenous concentrations of miR-150-5p, a predictive biomarker for preterm birth (PTB) found deregulated in maternal blood from as early as 12th week of pregnancy. Herein, a key step is represented toward a first bedside test for risk-stratification during pregnancy by predicting true outcome at a very early stage. More generally, the universal and versatile nature of this novel sample preprocessing platform can further improve the robustness of existing NALFTs and facilitate their application at the POC.
Walker A, Larsen C, Kundu S, et al., 2022, Functional rewiring of G protein-coupled receptor signaling in human labo, Cell Reports, Vol: 40, ISSN: 2211-1247
Current strategies to manage preterm labor center around inhibition of uterine myometrial contractions, yet do not improve neonatal outcomes as they do not address activation of inflammation. Here, we identify that during human labor, activated oxytocin receptor (OTR) reprograms the prostaglandin E2 receptor, EP2, in the pregnant myometrium to suppress relaxatory/Gαs-cAMP signaling and promote pro-labor/inflammatory responses via altered coupling of EP2 from Gαq/11 to Gαi/o. The ability of EP2 to signal via Gαi/o is recapitulated with in vitro OT and only following OTR activation, suggesting direct EP2-OTR crosstalk. Super-resolution imaging with computational modeling reveals OT-dependent reorganization of EP2-OTR complexes to favor conformations for Gαi over Gαs activation. A selective EP2 ligand, PGN9856i, activates the relaxatory/Gαs-cAMP pathway but not the pro-labor/inflammatory responses in term-pregnant myometrium, even following OT. Our study reveals a mechanism, and provides a potential therapeutic solution, whereby EP2-OTR functional associations could be exploited to delay preterm labor.
Mountain K, MacIntyre D, Chan D, et al., 2022, Blood group antigens influence host-microbe interactions and risk of early preterm birth, Publisher: WILEY, Pages: 55-56, ISSN: 1470-0328
Arianoglou M, Kim SH, Bennett PR, et al., 2022, Investigation of the Biological Role of a Novel microRNA (miRNA) Biomarker in the Aetiology of Preterm Birth (PTB), Publisher: SPRINGER HEIDELBERG, Pages: 198-198, ISSN: 1933-7191
MacIntyre DA, Pruski P, Correia G, et al., 2022, Rapid Assessment of Vaginal Microbiota Host Interactions During Pregnancy and Preterm Birth by Direct On-Swab Desorption Electrospray Ionization Mass Spectrometry, Publisher: SPRINGER HEIDELBERG, Pages: 53-53, ISSN: 1933-7191
Petrou L, Kim SH, Bennett PR, et al., 2022, Detection of miR-150-5p Directly from Plasma on a Lateral Flow Assay Identifies Women at Risk of Preterm Birth, Publisher: SPRINGER HEIDELBERG, Pages: 76-77, ISSN: 1933-7191
Chan D, Bennett P, Lee YS, et al., 2022, Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response, Nature Communications, Vol: 13, ISSN: 2041-1723
There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1β and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.
Kim SH, MacIntyre D, Sykes L, et al., 2022, Whole blood holding time prior to plasma processing alters microRNA expression profile, Frontiers in Genetics, Vol: 12, ISSN: 1664-8021
MicroRNAs (miRNAs) can exhibit aberrant expression under different physiological and pathological conditions. Therefore, differentially expressed circulating miRNAs have been a focus of biomarker discovery research. However, the use of circulating miRNAs comes with challenges which may hinder the reliability for their clinical application. These include varied sample collection protocols, storage times/conditions, sample processing and analysis methods. This study focused on examining the effect of whole blood holding time on the stability of plasma miRNA expression profiles. Whole blood samples were collected from healthy pregnant women and were held at 4°C for 30 min, 2 h, 6 h or 24 h prior to processing for plasma isolation. Plasma RNA was extracted and the expression of 179 miRNAs were analyzed. Unsupervised principal component analysis demonstrated that whole blood holding time was a major source of variation in miRNA expression profiles with 53 of 179 miRNAs showing significant changes in expression. Levels of specific miRNAs previously reported to be associated with pregnancy-associated complications such as hsa-miR-150-5p, hsa-miR-191-5p, and hsa-miR-29a-3p, as well as commonly used endogenous miRNA controls, hsa-miR-16-5p, hsa-miR-25-3p, and hsa-miR-223-3p were significantly altered with increase in blood holding time. Current protocols for plasma-based miRNA profiling for diagnostics describe major differences in whole blood holding periods ranging from immediately after collection to 26 h after. Our results demonstrate holding time can have dramatic effects on analytical reliability and reproducibility. This highlights the importance of standardization of blood holding time prior to processing for plasma in order to minimize introduction of non-biological variance in miRNA profiles.
Pruski P, Dos Santos Correia G, Lewis H, et al., 2021, Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth, Nature Communications, Vol: 12, ISSN: 2041-1723
The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.
Kyrgiou M, Bowden SJ, Athanasiou A, et 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.
Chan D, Bennett PR, Lee YS, et al., 2021, Microbial-Driven Preterm Labour Involves Crosstalk between the Innate and Adaptive Immune Response., Publisher: SPRINGER HEIDELBERG, Pages: 108A-109A, ISSN: 1933-7191
Kim SH, MacIntyre D, Binkhamis R, et 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.
Kyriacou C, Kim SH, Bobdiwala S, et al., 2020, The assessment of microRNA expression in pregnancies classified as a pregnancy of unknown location, Publisher: WILEY, Pages: E63-E63, ISSN: 1470-0328
Kyriacou C, Kim SH, Bobdiwala S, et al., 2020, MicroRNA Expression in Pregnancy of Unknown Location (PUL)., 67th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 99A-99A, ISSN: 1933-7191
Riaposova L, Kim SH, Hanyaloglu A, et al., 2020, Can Atosiban Inhibit Prostaglandin F2α-driven Inflammation in Myometrium Through C/EBP-β and CREB Signalling?, 67th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SPRINGER HEIDELBERG, Pages: 210A-211A, ISSN: 1933-7191
Pavagada S, Channon RB, Chang JYH, et al., 2019, Oligonucleotide-templated lateral flow assays for amplification-free sensing of circulating microRNAs (vol 55, pg 12451, 2019), CHEMICAL COMMUNICATIONS, Vol: 55, Pages: 13470-13470, ISSN: 1359-7345
Pavagada S, Channon RB, Chang JYH, et al., 2019, Oligonucleotide-templated lateral flow assays for amplification-free sensing of circulating microRNAs, Chemical Communications, Vol: 55, Pages: 12451-12454, ISSN: 1359-7345
Herein we demonstrate the first example of oligonucleotide-templated reaction (OTR) performed on paper, using lateral flow to capture and concentrate specific nucleic acid biomarkers on a test line. Quantitative analysis, using a low-cost benchtop fluorescence reader showed very high specificity down to the single nucleotide level and proved sensitive enough for amplification-free, on-chip, detection of endogenous concentrations of miR-150-5p, a recently identified predictive blood biomarker for preterm birth.
Ridout AE, Ibeto L, Ross G, et al., 2019, Cervical length and quantitative fetal fibronectin in the prediction of spontaneous preterm birth in asymptomatic women with congenital uterine anomaly, American Journal of Obstetrics and Gynecology, Vol: 221, Pages: 341.e1-341.e9, ISSN: 0002-9378
BACKGROUND: Congenital uterine anomalies (CUA) are associated with late miscarriage and spontaneous preterm birth (sPTB). OBJECTIVES: Our aim was to 1) determine the rate of sPTB in each type of CUA and 2) assess the performance of quantitative fetal fibronectin (qfFN) and transvaginal cervical length (CL) measurement by ultrasound in asymptomatic women with CUA for the prediction of sPTB at <34 and <37 weeks of gestation. STUDY DESIGN: This was a retrospective cohort of women with CUA asymptomatic for sPTB, from four UK tertiary referral centres (2001-2016). CUAs were categorised into fusion (unicornuate, didelphic and bicornuate uteri) or resorption defects (septate, with or without resection and arcuate uteri), based on pre-pregnancy diagnosis. All women underwent serial transvaginal ultrasound CL assessment in the second trimester (16 to 24 weeks' gestation); a subgroup underwent qfFN testing from 18 weeks' gestation. We investigated the relationship between CUA and predictive test performance for sPTB before 34 and 37 weeks' gestation. RESULTS: Three hundred and nineteen women were identified as having CUA within our high-risk population. 7% (23/319) delivered spontaneously <34 weeks, and 18% (56/319) <37 weeks' gestation. Rates of sPTB by type were: 26% (7/27) for unicornuate, 21% (7/34) for didelphic, 16% (31/189) for bicornuate, 13% (7/56) for septate and 31% (4/13) for arcuate. 80% (45/56) of women who had sPTB <37 weeks did not develop a short CL (<25 mm) during the surveillance period (16-24 weeks). The diagnostic accuracy of short CL had low sensitivity (20.3) for predicting sPTB <34 weeks. Cervical Length had ROC AUC of 0.56 (95% CI 0.48 to 0.64) and 0.59 (95% CI 0.55 to 0.64) for prediction of sPTB <34 and 37 weeks' respectively. The AUC for CL to predict sPTB <34 weeks was 0.48 for fusion defects (95% CI 0.39 to 0.57) but 0.78 (95% CI 0.66 to 0.91) for women with resorption defects. Overall quantitative fetal fibronectin had
Brown R, Chan D, Terzidou V, et al., 2019, Prospective observational study of vaginal microbiota pre- and post-rescue cervical cerclage, BJOG: An International Journal of Obstetrics and Gynaecology, Vol: 126, Pages: 916-925, ISSN: 1470-0328
ObjectiveTo investigate the relationship between vaginal microbiota composition and outcome of rescue cervical cerclage.DesignProspective observational study.SettingQueen Charlotte’s and Chelsea Hospital, LondonPopulationTwenty singleton pregnancies undergoing a rescue cervical cerclage.MethodsVaginal microbiota composition was analysed in women presenting with a dilated cervix and exposed fetal membranes before and 10 days following rescue cervical cerclage and correlated with clinical outcomes.Main outcome measuresComposition of vaginal bacteria characterised by culture independent next generation sequencing.Successful cerclage, defined as those resulting in the birth of a neonate discharged from hospital without morbidity.Unsuccessful cerclage, defined as procedures culminating in miscarriage, intrauterine death, neonatal death or significant neonatal morbidity.ResultsReduced Lactobacillus spp. relative abundance was observed in 40% of cases prior to rescue cerclage compared to 10% of gestational age matched controls (8/20, 40% vs 3/30, 10%, P=0.017). Gardnerella vaginalis was over-represented in women presenting with symptoms (3/7, 43% vs 0/13, 0%, P=0.03, LDA (log 10) and casesculminating in miscarriage (3/6, 50% vs 0/14, 0%, P=0.017). In the majority of cases (10/14, 71%) bacterial composition was unchanged following cerclage insertionand peri-operative interventions.ConclusionsReduced relative abundance of Lactobacillus spp. is associated with premature cervical dilatation, whereas high levels of Gardnerella vaginalis are associated with unsuccessful rescue cerclage cases. The insertion of a rescue cerclage does not affect the underlying bacterial composition in the majority of cases.
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