51 results found
Wu G, Grassi P, MacIntyre D, et al., 2022, N-Glycosylation of cervicovaginal fluid reflects microbial community, immune activity, and pregnancy status, Scientific Reports, Vol: 12, Pages: 1-14, ISSN: 2045-2322
Human cervicovaginal fluid (CVF) is a complex, functionally important and glycan rich biological fluid, fundamental in mediating physiological events associated with reproductive health. Using a comprehensive glycomic strategy we reveal an extremely rich and complex N-glycome in CVF of pregnant and non-pregnant women, abundant in paucimannose and highmannose glycans, complex glycans with 2-4 N-Acetyllactosamine (LacNAc) antennae, and Poly-LacNAc glycans decorated with fucosylation and sialylation. N-glycosylation variations were observed to differ in relation to pregnancy status, microbial composition, immune activation, and pregnancy outcome. Compared to CVF from women experiencing term birth, CVF from women who subsequently experienced preterm birth showed lower sialylation, which correlated to the presence of a diverse microbiome, and higher fucosylation, which correlated positively to pro-inflammatory cytokine concentration. This study is the first step towards better understanding the role of cervicovaginal glycans in reproductive health, their contribution to the mechanism of microbial driven preterm birth, and their potential forpreventative therapy.
Ho AEP, Rasheed ZBM, Norman J, et al., 2022, Rhombencephalitis in Pregnancy-A Challenging Case of Probable Listeria Infection, LIFE-BASEL, Vol: 12
Gimeno-Molina B, Muller I, Kropf P, et al., 2022, The role of neutrophils in pregnancy, term and preterm labour, Life, Vol: 12, ISSN: 2075-1729
Neutrophils are surveillance cells, and the first to react and migrate to sites of inflammation and infection following a chemotactic gradient. Neutrophils play a key role in both sterile inflammation and infection, performing a wide variety of effector functions such as degranulation, phagocytosis, ROS production and release of neutrophil extracellular traps (NETs). Healthy term labour requires a sterile pro-inflammatory process, whereas one of the most common causes of spontaneous preterm birth is microbial driven. Peripheral neutrophilia has long been described during pregnancy, and evidence exists demonstrating neutrophils infiltrating the cervix, uterus and foetal membranes during both term and preterm deliveries. Their presence supports a role in tissue remodelling via their effector functions. In this review, we describe the effector functions of neutrophils. We summarise the evidence to support their role in healthy pregnancy and labour and describe their potential contribution to microbial driven preterm birth.
Rasheed Z, Lee Y, Kim S, et al., 2022, 15-Deoxy-Delta-12,14-prostaglandin J2 modulates pro-labour and pro-inflammatory responses in human myocytes, vaginal and amnion epithelial cells, Frontiers in Endocrinology, Vol: 13, ISSN: 1664-2392
Background: Prematurity is the leading cause of childhood death under the age of five. The aetiology of preterm birth is multifactorial; however, inflammation and infection are the most common causal factors, supporting a potential role for immunomodulation as a therapeutic strategy. 15-Deoxy-Delta-12,14-prostaglandin J2 (15dPGJ2) is an anti-inflammatory prostaglandin and has been shown to delay lipopolysaccharide (LPS) induced preterm labour in mice and improve pup survival. This study exploresthe immunomodulatory effect of 15dPGJ2 on the transcription factors NF-κB and AP-1, pro-inflammatory cytokines, and contraction associated proteins in human cultured myocytes, vaginal epithelial cell line (VECs) and primary amnion epithelial cells (AECs).Methods: Cells were pre-incubated with 32μM of 15dPGJ2 and stimulated with 1ng/mL of IL-1β as an in vitro model of inflammation. Western immunoblotting was used to detect phosphorylated p-65 and phosphorylated c-Jun as markers of NF-κB and AP-1 activation, respectively. mRNA expression of the pro-inflammatory cytokines IL-6, IL-8, and TNF-α was examined, and protein expression of COX-2 and PGE2 were detected by western immunoblotting and ELISA respectively. Myometrial contractility wasexamined ex-vivo using a myograph.Results:15dPGJ2 inhibited IL-1β-induced activation of NF-κB and AP-1, and expression of IL-6, IL-8, TNF-α, COX-2 and PGE2 in myocytes, with no effect on myometrial contractility or cell viability. Despite inhibiting IL-1β-induced activation of NF-κB, expression of IL-6, TNF-α, and COX-2, 15dPGJ2 led to activation of AP-1, increased production of PGE2 and increased cell death in VECs and AECs.Conclusion: We conclude that 15dPGJ2 has differential effects on inflammatory modulation depending on cell type and is therefore unlikely to be a useful therapeutic agent for the prevention of preterm birth.
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.
Pikovsky M, Tan MY, Ahmed A, et al., 2021, Euglycaemic ketoacidosis in pregnant women with COVID-19: two case reports, BMC Pregnancy and Childbirth, Vol: 21, ISSN: 1471-2393
Background: Euglycaemic ketoacidosis (EKA) is an infrequent but serious condition which usually follows a period of starvation, severe vomiting or illness in individuals with or without diabetes. Ketoacidosis is associated with materno-fetal morbidity and mortality necessitating prompt diagnosis and management. Physiological increases in insulin resistance render pregnancy a diabetogenic state with increased susceptibility to ketosis. COVID-19 is associated with worse clinical outcomes in patients with diabetes and is an independent risk factor for ketoacidosis in normoglycaemic individuals. Case presentations: We describe two cases of SARS-CoV-2 positive pregnant women presenting with normoglycaemic metabolic ketoacidosis. Both cases were associated with maternal and fetal compromise, requiring aggressive fluid and insulin resuscitation and early delivery.Conclusion: We discuss possible physiology and propose a management strategy for euglycaemic ketoacidosis in pregnancy.
Bonnardel F, Haslam SM, Dell A, et 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.
Zarasvand S, Bayar E, Adan M, et 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.
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.
Bayar E, Bennett PR, Chan D, et al., 2020, The pregnancy microbiome and preterm birth, Springer Seminars in Immunopathology, Vol: 42, Pages: 487-499, ISSN: 1863-2297
Preterm birth is a global health concern and continues to contribute to substantial neonatal morbidity and mortality despite advances in obstetric and neonatal care. The underlying aetiology is multi-factorial and remains incompletely understood. In this review, the complex interplay between the vaginal microbiome in pregnancy and its association with preterm birth is discussed in depth. Advances in the study of bacteriology and an improved understanding of the human microbiome have seen an improved awareness of the vaginal microbiota in both health and in disease.
Rasheed ZBM, Lee YS, Kim SH, et al., 2020, Differential response of gestational tissues to TLR3 viral priming prior to exposure to bacterial TLR2 and TLR2/6 agonists, Frontiers in Immunology, Vol: 11, Pages: 1-27, ISSN: 1664-3224
Background: Infection/inflammation is an important causal factor in spontaneous preterm birth (sPTB). Most mechanistic studies have concentrated on the role of bacteria, with limited focus on the role of viruses in sPTB. Murine studies support a potential multi-pathogen aetiology in which a double or sequential hit of both viral and bacterial pathogens leads to a higher risk preterm labour. This study aimed to determine the effect of viral priming on bacterial induced inflammation in human in vitro models of ascending and haematogenous infection.Methods: Vaginal epithelial cells, and primary amnion epithelial cells and myocytes were used to represent cell targets of ascending infection while interactions between peripheral blood mononuclear cells (PBMCs) and placental explants were used to model systemic infection. To model the effect of viral priming upon the subsequent response to bacterial stimuli, each cell type was stimulated first with a TLR3 viral agonist, and then with either a TLR2 or TLR2/6 agonist, and responses compared to those of each agonist alone. Immunoblotting was used to detect cellular NF-κB, AP-1, and IRF-3 activation. Cellular TLR3, TLR2, and TLR6 mRNA was quantified by RT-qPCR. Immunoassays were used to measure supernatant cytokine, chemokine and PGE2 concentrations.Results: TLR3 (“viral”) priming prior to TLR2/6 agonist (“bacterial”) exposure augmented the pro-inflammatory, pro-labour response in VECs, AECs, myocytes and PBMCs when compared to the effects of agonists alone. In contrast, enhanced anti-inflammatory cytokine production (IL-10) was observed in placental explants. Culturing placental explants in conditioned media derived from PBMCs primed with a TLR3 agonist enhanced TLR2/6 agonist stimulated production of IL-6 and IL-8, suggesting a differential response by the placenta to systemic inflammation compared to direct infection as a result of haematogenous spread. TLR3 agonism generally caused increased m
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
Rasheed ZBM, Martin CRS, Sullivan MHF, et al., 2019, The placenta exhibits selective immune response in an in vitro model of haematogenous multi-pathogen-induced preterm labour, Publisher: WILEY, Pages: 158-158, ISSN: 1470-0328
Cook J, Bennett P, Kim SH, et al., 2019, First trimester circulating MicroRNA biomarkers predictive of subsequentpreterm delivery and cervical shortening, Scientific Reports, Vol: 9, ISSN: 2045-2322
Preterm birth (PTB) is the leading cause of infant death and disability worldwide. The onset of preterm uterine contractions is preceded by asymptomatic cervical remodelling and ripening, which can be seen on trans-vaginal ultrasound as cervical shortening. This study aimed to identify plasma miRNA biomarkers that predict preterm birth and/or cervical shortening. We collected serial plasma samples from pregnant women prospectively from 12 to 22 weeks gestation. The nCounter miRNA assay was used to identify differentially expressed miRNAs associated with spontaneous PTB and/or cervical shortening (n = 16 term no short, n = 13 preterm, n = 24 short). Predictive values of the miRNA biomarkers were confirmed in an independent validation cohort consisting of 96 women who delivered at term, 14 preterm and 21 early cervical shortening at <20 weeks gestation. Nine miRNAs (hsa-let-7a-5p, hsa-miR-374a-5p, hsa-miR-15b-5p, hsa-miR-19b-3p, hsa-miR-23a-3p, hsa-miR-93-5p, hsa-miR-150-5p, hsa-miR-185-5p and hsa-miR-191-5p) were differentially expressed (P < 0.001) in women subsequently experiencing PTB or cervical shortening. Hsa-miR-150-5p had the strongest ability to predict PTB (AUC = 0.8725) and cervical shortening (AUC = 0.8514). Plasma miRNAs in the first trimester can predict PTB and cervical shortening in women at risk of preterm delivery. This is a key period in pregnancy when early identification of PTB risk allows time to deliver outcome-modifying interventions.
Thurairajah S, Alqurashi M, Chan D, et al., 2019, Characterisation of Peripheral Blood Neutrophil Phenotype and Effector Functions during Pregnancy, Labour and in Women at High Risk of Preterm Labour., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 123A-123A, ISSN: 1933-7191
Alqurashi M, Thurairajah S, Adan M, et al., 2019, Characterisation of Normal and Low Density Granulocytes in Pregnancy, Term Labour, and Women at High Risk of Preterm Labour., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 122A-123A, ISSN: 1933-7191
Chan D, Lee YS, Ahmed S, et al., 2019, The Local and Systemic Immune Response in Preterm and Term Pregnancies and Their Association with the Vaginal Microbiota., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 75A-75A, ISSN: 1933-7191
Sykes L, Bennett P, 2018, Efficacy of progesterone for prevention of preterm birth, Best Practice and Research: Clinical Obstetrics and Gynaecology, Vol: 52, Pages: 126-136, ISSN: 1521-6934
Preterm birth (PTB) occurs in 5–18% of pregnancies and is the leading cause of neonatal morbidity, mortality and infant death. Up to 30% of PTBs are due to iatrogenic reasons, but the remainder are due to the spontaneous onset of labour or pre-labour premature rupture of membranes (P-PROM). During pregnancy, the uterus remains quiescent and the cervix remains long and closed. Although the exact mechanisms that lead to spontaneous PTB (sPTB) are not fully understood, it is likely that the terminal pathways that are common to term labour are activated prematurely. Despite continued research efforts to develop preventative strategies, there have been no major advances resulting in the reduction of sPTB rates. Progesterone is the most researched prophylactic agent, yet, there is lack of consistency in the reported beneficial effects for the prevention of PTB and improvement in neonatal outcome. This is likely to stem from the multifactorial aetiology of sPTB, the varied patient cohorts recruited and the use of different preparations and routes of administration for progesterone. This review summarises the scientific rationale supporting the efficacy of progesterone and the results of major randomised controlled trials and finally emphasizes how targeted studies with more detailed patient stratification are essential to understand which population would benefit.
Chan DCY, Lee YS, Bura S, et al., 2018, The vaginal microbiota and the adaptive immune system in pregnant and nonpregnant women, Publisher: WILEY, Pages: E32-E32, ISSN: 1470-0328
Rasheed ZBM, Rai RK, Lee YS, et al., 2018, The effect of TLR3 priming on TLR2, 4 and 6 induced activation of NF-kappa band AP-1 in human myometrium, amnion and vaginal epithelial cells, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage, Pages: 188A-188A, ISSN: 1933-7191
Kim SH, Binkhamis R, Cook JR, et al., 2018, A pilot study of circulating miRNAs as potential biomarkers for small-for-gestational-age births, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage, Pages: 282A-282A, ISSN: 1933-7191
Kim SH, MacIntyre DA, Sykes L, et al., 2018, Comparing the Levels of miRNA Expression in Plasma from Blood Collected Using EDTA and Heparin Tubes, and Heparinase-Treated Plasma., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 315A-315A, ISSN: 1933-7191
Chan DCY, Lee YS, Bura S, et al., 2018, Recognition of vaginal microbiota by the adaptive maternal immune system, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage, Pages: 116A-116A, ISSN: 1933-7191
Rasheed ZBM, Rai RK, Anucha E, et al., 2018, TLR3 priming increases TLR4-and TLR6-mediated pro-inflammatory cytokine production in amniocytes, myocytes and vaginal epithelial cells, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage, Pages: 258A-258A, ISSN: 1933-7191
MacIntyre DA, Sykes L, Bennett P, 2017, The human female urogenital microbiome: complexity in normality, Emerging Topics in Life Sciences, Vol: 1, Pages: 363-372, ISSN: 2397-8554
Microbial communities of the urogenital tract have long been recognised to play an important role in disease states. A revolution in methodological approaches is permitting the assessment of complex urogenital tract microbiota–host interactions and the metabolic and protein milieu of the mucosal interface. There is now great potential for significant advances in biomarker discovery and disease risk stratification, and for the elucidation of mechanisms underpinning the microbial community dynamics involved in urogenital tract pathology. Microbiota–host interactions in the female genital tract have a particular significance, because unlike in the male, there is direct communication between the external genitalia, the uterus and the peritoneal cavity. This review examines the microbial community composition at differing sites of the female urogenital tract and its relationship with health and disease. Key factors involved in the modulation of vaginal microbiome stability and structure, such as endocrine, immune and inflammatory pathways, are considered in the context of a woman's life cycle and disease pathogenesis.
Cook JR, Chatfield S, Chandiramani M, et al., 2017, Cerclage position, cervical length and preterm delivery in women undergoing ultrasound indicated cervical cerclage: A retrospective cohort study, PLOS One, Vol: 12, ISSN: 1932-6203
ObjectiveThe objectives were to assess whether anatomical location of ultrasound (USS) indicated cervical cerclage and/or the degree of cervical shortening (cervical length; CL) prior to and following cerclage affects the risk of preterm birth (PTB).MethodA retrospective cohort study of 179 women receiving cerclage for short cervix (≤25mm) was performed. Demographic data, CL before and after cerclage insertion, height of cerclage (distance from external os) and gestation at delivery were collected. Relative risk (RR) and odds ratio (OR) of preterm delivery were calculated according to the anatomical location of the cerclage within the cervix and the CL before and after cerclage as categorical and continuous variables. Partition tree analysis was used to identify the threshold cerclage height that best predicts PTB.Results25% (n = 45) delivered <34 weeks and 36% (n = 65) delivered <37 weeks. Risk of PTB was greater with cerclage in the distal 10mm (RR2.37, 95% CI 1.45–3.87) or the distal half of a closed cervix (RR2.16, 95% CI 1.45–3.87). Increasing absolute cerclage height was associated with a reduction in PTB (OR 0.87, 95% CI 0.82–0.94). A cerclage height <14.5 mm best predicts PTB (70.8%). Increasing CL following cerclage was associated with a reduction in PTB (OR0.87, 95% CI 0.82–0.94). Conversely, the risk of PTB was increased where CL remained static or shortened further following cerclage (RR2.34, 95% CI 1.04–5.25).ConclusionThe higher a cerclage was placed within a shortened cervix, the lower the subsequent odds of PTB. Women whose cerclage is placed in the distal 10mm of closed cervix or whose cervix fails to elongate subsequently, should remain under close surveillance as they have the highest risk of PTB.
Begam Mohammed Rasheed Z, Lee Y, MacIntyre D, et al., 2016, Activation of the TLR 3 receptor: A possible mechanism for virally induced preterm labour, Society for Reproductive Investigation
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