Publications
671 results found
Al-Memar M, Vaulet T, Nikolic G, et al., 2019, Pain and bleeding in the first trimester and long-term pregnancy outcomes: a prospective cohort study, Publisher: WILEY, Pages: 18-18, ISSN: 1470-0328
Grewal K, Lee Y, Smith A, et al., 2019, Lactobacillus-deplete vaginal microbiota composition is associated with chromosomally normal miscarriage, Publisher: WILEY, Pages: 29-29, ISSN: 1470-0328
Rasheed ZBM, Lee YS, Bennett PR, et al., 2019, Priming of vaginal and amnion epithelial cells with a TLR3 agonist augments TLR2/TLR6 agonist response: a potential synergistic role of viruses and bacteria in preterm labour, Publisher: WILEY, Pages: 156-156, ISSN: 1470-0328
Al-Memar M, Vaulet T, Fourie H, et al., 2019, Intrauterine haematomas in the first trimester and association with adverse pregnancy outcomes, Publisher: WILEY, Pages: 18-19, ISSN: 1470-0328
Chan D, Lee YS, Teoh TG, et al., 2019, Maternal gut microbial-immune interactions during healthy pregnancy, Publisher: WILEY, Pages: 165-165, ISSN: 1470-0328
Brown RG, Al-Memar M, Marchesi JR, et al., 2019, Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabour rupture of the fetal membranes, Translational Research, Vol: 207, Pages: 30-43, ISSN: 1931-5244
Vaginal bacterial community composition influences pregnancy outcome. Preterm prelabor rupture of the fetal membranes (PPROM), which precedes 30% of all spontaneous preterm births, is associated with high vaginal bacterial diversity prior to rupture. The point at which vaginal bacterial diversity is established before PPROM is unknown. In this study, we use metataxonomics to longitudinally characterize the vaginal bacterial composition from as early as 6 weeks of gestation in women at high (n = 38) and low (n = 22) risk of preterm birth who subsequently experience PPROM and in women delivering at term without complications (n = 36). Reduced Lactobacillus spp. abundance and high diversity was observed prior to PPROM in 20% and 26% of women at low and high risk of preterm births respectively, but in only 3% of women who delivered at term. PPROM was associated with instability of bacterial community structure during pregnancy and a shift toward higher diversity predominately occurring during the second trimester. This was characterized by increased relative abundance of potentially pathogenic species including Prevotella, Peptoniphilus, Streptococcus, and Dialister. This study identifies reduced Lactobacillus spp. abundance and increasing vaginal bacterial diversity as an early risk factor for PPROM and highlights the need for interventional studies designed to assess the impact of modifying vaginal bacterial composition for the prevention of preterm birth.
Chan D, Lee YS, Ahmed S, et al., 2019, Local and systemic immune responses in preterm and term pregnancies and their association with the vaginal microbiota, Publisher: WILEY, Pages: E128-E128, 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.
Kim SH, Riaposova L, Ahmed H, et al., 2019, Oxytocin receptor antagonists, atosiban and nolasiban, inhibit prostaglandin F2α-induced contractions and inflammatory responses in human myometrium, Scientific Reports, Vol: 9, ISSN: 2045-2322
Oxytocin receptor antagonists (OTR-A) have been developed as tocolytics for the management of preterm labour due to the significant role of oxytocin (OT) in the onset of both term and preterm labour. Similar to OT, prostaglandins (PGs) play key roles in myometrial contractility and cervical ripening. Inhibition of PG synthesis/activity is used to delay preterm birth. Thus, targeting the PG pathway in combination with an OTR-A may be an effective strategy for delaying preterm delivery. In this study, we examined the effects of atosiban and nolasiban on PGF2α-induced contractions and pro-inflammatory responses in human pregnant myometrium. Both OTR-As, atosiban and nolasiban, inhibited PGF2α-induced contractions in a dose-dependent manner (p < 0.001 and p < 0.01, respectively). These inhibitory effects involved the suppression of PGF2α-mediated increase in intracellular calcium levels. In addition, the OTR-As significantly suppressed PGF2α-induced activation of pro-inflammatory pathways such as NF-κB and mitogen activated protein kinases (MAPKs), and the subsequent expression of contraction-associated-protein, COX-2. We have demonstrated that atosiban and nolasiban not only inhibit contractions elicited by OT, but also inhibit contractions and inflammation induced by PGF2α. This suggests a possible crosstalk between OTR and PG receptor signalling and highlights the importance of understanding G protein-coupled receptor interactions/crosstalk in the development of future tocolytics.
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
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
Rasheed ZBM, San Martin CR, Sullivan MHF, et al., 2019, The Placenta Exhibits Selective Immune Response in an In Vitro Model of Haematogenous Multi- Pathogen Induced Preterm Labour., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 74A-74A, ISSN: 1933-7191
Chan D, Lee YS, Teoh TG, et al., 2019, Maternal Gut Microbial-Immune Interactions during Healthy Pregnancy., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 121A-121A, 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
Hanton FD, Lee Y, Gunstone H, et al., 2019, The Role of Lactate Acidification on Inflammatory Pathway Activation in Vaginal Epithelial Cells., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 345A-345A, ISSN: 1933-7191
Kim SH, MacIntyre DA, Bennett PR, et al., 2019, The Effects of Blood Storage on Plasma miRNA Expression Profiles., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 285A-286A, ISSN: 1933-7191
Al-Memar M, Vaulet T, Fourie H, et al., 2019, Impact of Intrauterine Haematoma on Pregnancy Outcomes., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 378A-378A, ISSN: 1933-7191
Riaposova L, Kim SH, Hanyaloglu A, et al., 2019, Prostaglandin F2α-Mediated Pro-Inflammatory Signalling in Human Myometrium., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 308A-308A, ISSN: 1933-7191
Mowla S, Xie J, Bennett P, et al., 2019, Characterisation of Vaginal Cytokine Expression During ART: A Cohort Study., 66th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 256A-256A, ISSN: 1933-7191
Norman JE, Marlow N, Messow C-M, et al., 2019, Corrigendum: Does progesterone prophylaxis to prevent preterm labour improve outcome? A randomised double-blind placebo-controlled trial (OPPTIMUM), Health Technology Assessment, Vol: 22, Pages: 305-334, ISSN: 1366-5278
Tay J, Masini G, McEniery CM, et al., 2019, Uterine and fetal placental Doppler indices are associated with maternal cardiovascular function, American Journal of Obstetrics and Gynecology, Vol: 220, Pages: 96.e1-96.e8, ISSN: 0002-9378
BackgroundThe mechanism underlying fetal-placental Doppler index changes in preeclampsia and/or fetal growth restriction are unknown, although both are associated with maternal cardiovascular dysfunction.ObjectiveWe sought to investigate whether there was a relationship between maternal cardiac output and vascular resistance and fetoplacental Doppler findings in healthy and complicated pregnancy.Study DesignWomen with healthy pregnancies (n=62), preeclamptic pregnancies (n=13), preeclamptic pregnancies with fetal growth restriction (n=15), or fetal growth restricted pregnancies (n=17) from 24–40 weeks gestation were included. All of them underwent measurement of cardiac output with the use of an inert gas rebreathing technique and derivation of peripheral vascular resistance. Uterine and fetal Doppler indices were recorded; the latter were z scored to account for gestation. Associations were determined by polynomial regression analyses.ResultsMean uterine artery pulsatility index was higher in fetal growth restriction (1.37; P=.026) and preeclampsia+fetal growth restriction (1.63; P=.001) but not preeclampsia (0.92; P=1) compared with control subjects (0.8). There was a negative relationship between uterine pulsatility index and cardiac output (r2=0.101; P=.025) and umbilical pulsatility index z score and cardiac output (r2=0.078; P=.0015), and there were positive associations between uterine pulsatility index and peripheral vascular resistance (r2=0.150; P=.003) and umbilical pulsatility index z score and peripheral vascular resistance (r2= 0.145; P=.001). There was no significant relationship between cardiac output and peripheral vascular resistance with cerebral Doppler indices.ConclusionUterine artery Doppler change is abnormally elevated in fetal growth restriction with and without preeclampsia, but not in preeclampsia, which may explain the limited sensitivity of uterine artery Doppler changes for all these complications when considered in aggregate. Fur
Channon RB, Pavagada S, Chang JYH, et al., 2019, Point-of-care nucleic Acid sensors via paper-based oligonucleotide-templated reactions, Pages: 815-816
This paper describes a new and inexpensive approach for specific sensing of endogenous concentrations of miRNAs extracted from blood, based on a fluorogenic oligonucleotide templated reaction (OTR) on a lateral flow assay (LFA). Our method is then applied to develop the first early screening test for Preterm birth.
Norman JE, Norrie J, Maclennan G, et al., 2018, Open randomised trial of the (Arabin) pessary to prevent preterm birth in twin pregnancy with health economics and acceptability: STOPPIT-2-a study protocol, BMJ OPEN, Vol: 8, ISSN: 2044-6055
Pruski P, Lewis H, Lee Y, et al., 2018, Assessment of microbiota:host interactions at the vaginal mucosa interface, Methods, Vol: 149, Pages: 74-84, ISSN: 1046-2023
There is increasing appreciation of the role that vaginal microbiota play in health and disease throughout a woman’s lifespan. This has been driven partly by molecular techniques that enable detailed identification and characterisation of microbial community structures. However, these methods do not enable assessment of the biochemical and immunological interactions between host and vaginal microbiota involved in pathophysiology. This review examines our current knowledge of the relationships that exist between vaginal microbiota and the host at the level of the vaginal mucosal interface. We also consider methodological approaches to microbiomic, immunologic and metabolic profiling that permit assessment of these interactions. Integration of information derived from these platforms brings the potential for biomarker discovery, disease risk stratification and improved understanding of the mechanisms regulating vaginal microbial community dynamics in health and disease.
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.
Cartwright R, Jarvelin M, Miotla P, et al., 2018, Genome wide association study identifies two novel loci associated with female stress and urgency urinary incontinence, 50th European-Society-of-Human-Genetics (ESHG) Conference, Publisher: NATURE PUBLISHING GROUP, Pages: 93-93, ISSN: 1018-4813
Carter J, Tribe RM, Sandall J, et al., 2018, The Preterm Clinical Network (PCN) Database: a web-based systematic method of collecting data on the care of women at risk of preterm birth, BMC Pregnancy and Childbirth, Vol: 18, ISSN: 1471-2393
BackgroundDespite much research effort, there is a paucity of conclusive evidence in the field of preterm birth prediction and prevention. The methods of monitoring and prevention strategies offered to women at risk vary considerably around the UK and depend on local maternity care provision. It is becoming increasingly recognised that this experience and knowledge, if captured on a larger scale, could be a utilized as a valuable source of evidence for others. The UK Preterm Clinical Network (UKPCN) was established with the aim of improving care and outcomes for women at risk of preterm birth through the sharing of a wealth of experience and knowledge, as well as the building of clinical and research collaboration. The design and development of a bespoke internet-based database was fundamental to achieving this aim.MethodFollowing consultation with UKPCN members and agreement on a minimal dataset, the Preterm Clinical Network (PCN) Database was constructed to collect data from women at risk of preterm birth and their children. Information Governance and research ethics committee approval was given for the storage of historical as well as prospectively collected data. Collaborating centres have instant access to their own records, while use of pooled data is governed by the PCN Database Access Committee. Applications are welcomed from UKPCN members and other established research groups. The results of investigations using the data are expected to provide insights into the effectiveness of current surveillance practices and preterm birth interventions on a national and international scale, as well as the generation of ideas for innovation and research. To date, 31 sites are registered as Data Collection Centres, four of which are outside the UK.ConclusionThis paper outlines the aims of the PCN Database along with the development process undertaken from the initial idea to live launch.
Foo F, Mahendru A, Masini G, et al., 2018, Association between prepregnancy cardiovascular function and subsequent preeclampsia or fetal growth restriction, Hypertension, Vol: 72, Pages: 442-450, ISSN: 0194-911X
Preeclampsia and fetal growth restriction during pregnancy are associated with increased risk of maternal cardiovascular disease later in life. It is unclear whether this association is causal or driven by similar antecedent risk factors. Clarification requires recruitment before conception which is methodologically difficult with high attrition rates and loss of outcome numbers to nonconception/miscarriage. Few prospective studies have, therefore, been adequately powered to address these questions. We recruited 530 healthy women (mean age: 35.0 years) intending to conceive and assessed cardiac output, cardiac index, stroke volume, total peripheral resistance, mean arterial pressure, and heart rate before pregnancy. Participants were followed to completion of subsequent pregnancy with repeat longitudinal assessments. Of 356 spontaneously conceived pregnancies, 15 (4.2%) were affected by preeclampsia and fetal growth restriction. Women who subsequently developed preeclampsia/fetal growth restriction had lower preconception cardiac output (4.9 versus 5.8 L/min; P=0.002) and cardiac index (2.9 versus 3.3 L/min per meter2; P=0.031) while mean arterial pressure (87.1 versus 82.3 mm Hg; P=0.05) and total peripheral resistance (1396.4 versus 1156.1 dynes sec cm−5; P<0.001) were higher. Longitudinal trajectories for cardiac output and total peripheral resistance were similar between affected and healthy pregnancies, but the former group showed a more exaggerated fall in mean arterial pressure in the first trimester, followed by a steeper rise and a steeper fall to postpartum values. Significant relationships were observed between cardiac output, total peripheral resistance, and mean arterial pressure and gestational epoch. We conclude that in healthy women, an altered prepregnancy hemodynamic phenotype is associated with the subsequent development of preeclampsia/fetal growth restriction.
Short CS, Quinlan R, Bennett P, et al., 2018, Optimising the collection of female genital tract fluid for cytokine analysis in pregnant women, Journal of Immunological Methods, Vol: 458, Pages: 15-20, ISSN: 0022-1759
Introduction: To better understand the immunology of pregnancy, study of female genital tract fluid (FGF) is desirable. However the optimum method of collection of FGF in pregnant women for immunological methods, specifically cytokine measurement, is unknown.Methods:A prospective study of HIV-uninfected pregnant women comparing two methods of FGF collection: polyvinyl acetal sponge collection of cervical fluid (CF) and menstrual cup collection of cervicovaginal fluid (CVF). Samples were collected at 3 time points across the second and third trimesters: 14-21, 22-25 and 26-31 weeks. Multiplex chemi-luminescent assays were used to measure: IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13 and TNF-α. Optimal methodology for cytokine normalisation (sample weight, volume and total protein) was explored. ResultsAll cytokines were measurable in both fluid types. IL-1β, IL-8 and IL-6 were detected at the highest concentrations (ranking order CF > CVF > plasma). CVF collection was simpler, provided the largest volume of sample (median 0.5g) with the potential for undiluted usage, and allowed for self-insertion. CF cytokine concentrations were intrinsically associated with sample weight and protein concentration however CVF cytokines were independent of these. Conclusion:Both methods of collection are robust for measurement of FGF cytokines during pregnancy. We recommend CVF collection using a menstrual cup as a viable option in pregnant women for high dimensional biological techniques.
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
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