Publications
669 results found
Norman JE, Marlow N, Messow C-M, et al., 2018, Does progesterone prophylaxis to prevent preterm labour improve outcome? A randomised double-blind placebo-controlled trial (OPPTIMUM) Introduction, HEALTH TECHNOLOGY ASSESSMENT, Vol: 22, Pages: 1-+, ISSN: 1366-5278
Pohl O, Chollét A, Kim SH, et al., 2018, OBE022, an oral and selective prostaglandin F2α receptor antagonist as an effective and safe modality for the treatment of preterm labor, Journal of Pharmacology and Experimental Therapeutics, ISSN: 0022-3565
Preterm birth is the major challenge in obstetrics affecting ~10% of pregnancies. Pan-prostaglandin synthesis inhibitors (NSAID) prevent preterm labor and prolong pregnancy but raise concerns about fetal renal and cardiovascular safety. We conducted preclinical studies examining the tocolytic effect and fetal safety of the oral prodrug candidate OBE022 and its parent OBE002, both potent and highly selective antagonist of the contractile PGF2α prostaglandin receptor (FP). Efficacy of OBE022 and OBE002, alone and in combination with other tocolytics, was assessed in human tissues and pregnant animal models for inhibition of uterine contraction and delay of parturition. Selective safety of OBE022 and/or OBE002, compared to NSAID indomethacin, was assessed on renal function, closure of the ductus arteriosus and inhibition of platelet aggregation. In in vitro studies, OBE002 inhibited spontaneous, oxytocin- and PGF2α-induced human myometrial contractions alone and was more effective in combination with atosiban or nifedipine. In in vivo studies, OBE022 and OBE002 reduced spontaneous contractions in near-term pregnant rat. In pregnant mice, OBE022 delayed RU486-induced parturition and exerted synergistic effects in combination with nifedipine. OBE022 and/or OBE002 did not show the fetal side effects of ductus arteriosus constriction, impairment of kidney function or inhibition of platelet aggregation observed with indomethacin. Orally active OBE022 and OBE002 exhibits potent tocolytic effects on human tissues ex vivo and animal models in vivo without causing the adverse fetal side effects seen with indomethacin. Selectively targeting the FP receptor in combination with existing tocolytics may be an effective strategy for preventing or delaying preterm delivery.
Tay J, Foo L, Masini G, et al., 2018, Cardiac output in pre eclampsia is associated with the presence of fetal growth restriction, not gestation at onset: a prospective cohort study, American Journal of Obstetrics and Gynecology, Vol: 218, Pages: 517.e1-517.e12, ISSN: 0002-9378
BACKGROUND AND OBJECTIVES: Pre-eclampsia (PE) and fetal growth restriction (FGR) are considered to be placentally-mediated disorders. The clinical manifestations are widely held to relate to gestation age at onset with early- and late-onset PE considered to be phenotypically distinct. Recent studies have reported conflicting findings in relation to cardiovascular function, and in particular cardiac output, in PE and FGR. STUDY DESIGN: We investigated maternal cardiovascular function in relation to clinical subtype in 45 pathological pregnancies (14 'PE only', 16 'FGR only', 15 'PE and FGR') and compared these with 107 healthy person observations. Cardiac output (CO) was the primary outcome measure, and was assessed using an inert gas rebreathing method (Innocor®), from which peripheral vascular resistance was derived (PVR); arterial function was assessed by Vicorder ®, a cuff-based oscillometric device. Cardiovascular parameters were normalised for gestational age in relation to healthy pregnancies using Z scores, thus allowing for comparison across the gestational range 24-40 weeks. RESULTS: Compared with healthy control pregnancies, women with PE had higher CO Z scores (1.87 ± 1.35; p=0.0001) and lower PVR Z scores (-0.76± 0.89; p=0.025); those with FGR had higher PVR Z scores (0.57± 1.18; p=0.04) and those with both PE and FGR had lower CO Z scores (-0.80 ± 1.3; p= 0.007) and higher PVR Z scores (2.16 ± 1.96; p=0.0001). These changes were not related to gestational age of onset. All those affected by PE and/or FGR had abnormally raised augmentation index (AIx) and pulse wave velocity (PWV). Furthermore, in PE, low CO was associated with low birthweight and high CO with high birthweight. (r=0.42, p=0.03). CONCLUSIONS: PE is associated with high CO, but if PE presents with FGR, the opposite is true; both conditions are, nevertheless, defined by hypertension. FGR without PE is associated with high PVR. Though 'early' and 'l
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
Sassine AJ, Sivarajasingam SP, Cocker ATH, et al., 2018, Erythrocyte oleic acid is correlated with increasing natural killer cells in maternal blood, 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Elsevier, Pages: 319A-319A, 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
Foo L, Mahendry A, McEniery C, et al., 2018, Pre-conception maternal haemodynamics is associated with subsequent development of pre-eclampsia (PE) or fetal growth restriction (FGR), RCOG World Congress, Publisher: WILEY, Pages: 12-12, ISSN: 1470-0328
Lewis H, Pruski P, Brown R, et al., 2018, Rapid mucosal metabolome profiling by desorption electrospray ionization MS (DESI-MS) for prediction of preterm pre-labour rupture of membranes (PPROM), RCOG World Congress 2018, Publisher: Wiley, Pages: 24-24, 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
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
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
Hanton F, Foley J, Lee YS, et al., 2018, Impact of Lactate Acidification on Inflammatory Pathway Activation in Vaginal Epithelial Cells., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 115A-116A, ISSN: 1933-7191
Lewis HV, Pruski P, Brown RG, et al., 2018, Rapid Mucosal Metabolome Profiling by Desorption Electrospray Ionization MS (DESI-MS) for Prediction of Preterm Pre-Labour Rupture of Membranes (PPROM)., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 65A-65A, ISSN: 1933-7191
Brown RG, Chan D, Lee Y, et al., 2018, Rescue Cervical Cerclage is Associated with Good Neonatal Outcomes in Asymptomatic Women Who Are Not Colonised by <i>Gardnerella Vaginalis</i>., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 112A-112A, ISSN: 1933-7191
Khanjani S, Islam R, Khalid J, et al., 2018, Plasma microRNAs Identified as Novel Markers of Embryo Implantation., 65th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 110A-110A, ISSN: 1933-7191
MacIntyre DA, Brown R, Marchesi J, et al., 2018, Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin, BMC Medicine, Vol: 16, ISSN: 1741-7015
Background: Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection prophylactic antibiotics are widely used. The evolution of vaginal microbiota composition associated with PPROM and the impact of antibiotics on bacterial composition is unknown. Methods: We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures.Results: In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion, was present prior to the rupture of fetal membranes in approximately a third of cases (0% versus 27%, P= 0.026) and persisted following membrane rupture (31%, P= 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P= 0.00009) particularly in women initially colonised by Lactobacillus species. Lactobacillus depletion and increased relative abundance of Sneathia spp. was associated with subsequent funisitis and early onset neonatal sepsis. Conclusions:Our data show that vaginal microbiota composition is a risk-factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.
Cacciatore S, Tenori L, Luchinat C, et al., 2017, KODAMA: an R package for knowledge discovery and data mining, Bioinformatics, Vol: 33, Pages: 621-623, ISSN: 1367-4803
Summary: KODAMA, a novel learning algorithm for unsuper-vised feature extraction, is specifically designed for analysing noisy and high-dimensional data sets. Here we present an R package of the algorithm with additional functions that allow improved interpretation of high-dimensional data. The pack-age requires no additional software and runs on all major plat-forms.Availability and Implementation: KODAMA is freely available from the R archive CRAN (http://cran.r-project.org). The soft-ware is distributed under the GNU General Public License (ver-sion 3 or later).
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.
Edey LF, Georgiou H, O'Dea KP, et al., 2017, Progesterone, the maternal immune system and the onset of parturition in the mouse, Biology of Reproduction, Vol: 98, Pages: 376-395, ISSN: 1529-7268
The role of progesterone (P4) in the regulation of the local (uterine) and systemic innate immune system, myometrial expression of connexin 43 (Cx-43) and cyclooxygenase 2 (COX-2) and the onset of parturition was examined in: 1) naïve mice delivering at term; 2) E16 mice treated with RU486 (P4-antagonist) to induce preterm parturition; and 3) in mice treated with P4 to prevent term parturition.In naïve mice, myometrial neutrophil and monocyte numbers peaked at E18 and declined with the onset of parturition. In contrast, circulating monocytes did not change and although neutrophils were increased with pregnancy, they did not change across gestation. The myometrial mRNA and protein levels of most chemokines/cytokines, Cx-43 and COX-2 increased with, but not before, parturition.With RU486-induced parturition, myometrial and systemic neutrophil numbers increased before and myometrial monocyte numbers increased with parturition only. Myometrial chemokine/cytokine mRNA abundance increased with parturition, but protein levels peaked earlier at between 4.5 and 9h post RU486. Cx-43, but not COX-2, mRNA expression and protein levels increased prior to the onset of parturition.In mice treated with P4, the gestation-linked increase in myometrial monocyte, but not neutrophil, numbers was prevented and expression of Cx-43 and COX-2 was reduced. On E20 of P4 supplementation, myometrial chemokine/cytokine and leukocyte numbers, but not Cx-43 and COX-2 expression, increased.These data show that during pregnancy P4 controls myometrial monocyte infiltration, cytokine and prolabour factor synthesis via mRNA dependent and independent mechanisms and, with prolonged P4 supplementation, P4 action is repressed resulting in increased myometrial inflammation.
Kyrgiou M, Athanasiou A, Kalliala IEJ, et al., 2017, Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease., Cochrane Database of Systematic Reviews, Vol: 11, ISSN: 1469-493X
BACKGROUND: The mean age of women undergoing local treatment for pre-invasive cervical disease (cervical intra-epithelial neoplasia; CIN) or early cervical cancer (stage IA1) is around their 30s and similar to the age of women having their first child. Local cervical treatment has been correlated to adverse reproductive morbidity in a subsequent pregnancy, however, published studies and meta-analyses have reached contradictory conclusions. OBJECTIVES: To assess the effect of local cervical treatment for CIN and early cervical cancer on obstetric outcomes (after 24 weeks of gestation) and to correlate these to the cone depth and comparison group used. SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library, 2017, Issue 5), MEDLINE (up to June week 4, 2017) and Embase (up to week 26, 2017). In an attempt to identify articles missed by the search or unpublished data, we contacted experts in the field and we handsearched the references of the retrieved articles and conference proceedings. SELECTION CRITERIA: We included all studies reporting on obstetric outcomes (more than 24 weeks of gestation) in women with or without a previous local cervical treatment for any grade of CIN or early cervical cancer (stage IA1). Treatment included both excisional and ablative methods. We excluded studies that had no untreated reference population, reported outcomes in women who had undergone treatment during pregnancy or had a high-risk treated or comparison group, or both DATA COLLECTION AND ANALYSIS: We classified studies according to the type of treatment and the obstetric endpoint. Studies were classified according to method and obstetric endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CIs) were calculated using a random-effects model and inverse variance. Inter-study heterogeneity was assessed with I2 statistics. We assessed maternal outcomes that included preterm birth (PTB) (spontaneous a
Mitra A, MacIntyre D, Lee Y, et al., 2017, THE VAGINAL MICROBIOTA AFTER EXCISIONAL TREATMENT FOR CERVICAL INTRAEPITHELIAL NEOPLASIA, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 979-979, ISSN: 1048-891X
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kalliala I, Markozannes G, Gunter M, et al., 2017, Obesity and gynaecological and obstetrical conditions: an umbrella review of the literature, British Medical Journal, Vol: 7, ISSN: 0959-8138
Objective To study the strength and validity of associations between adiposity and risk of any type of obstetric or gynaecological conditions.Design An umbrella review of meta-analyses.Data sources PubMed, Cochrane database of systematic reviews, manual screening of references for systematic reviews or meta-analyses of observational and interventional studies evaluating the association between adiposity and risk of any obstetrical or gynaecological outcome.Main outcomes Meta-analyses of cohort studies on associations between indices of adiposity and obstetric and gynaecological outcomes.Data synthesis Evidence from observational studies was graded into strong, highly suggestive, suggestive, or weak based on the significance of the random effects summary estimate and the largest study in the included meta-analysis, the number of cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Interventional meta-analyses were assessed separately.Results 156 meta-analyses of observational studies were included, investigating associations between adiposity and risk of 84 obstetric or gynaecological outcomes. Of the 144 meta-analyses that included cohort studies, only 11 (8%) had strong evidence for eight outcomes: adiposity was associated with a higher risk of endometrial cancer, ovarian cancer, antenatal depression, total and emergency caesarean section, pre-eclampsia, fetal macrosomia, and low Apgar score. The summary effect estimates ranged from 1.21 (95% confidence interval 1.13 to 1.29) for an association between a 0.1 unit increase in waist to hip ratio and risk endometrial cancer up to 4.14 (3.61 to 4.75) for risk of pre-eclampsia for BMI >35 compared with <25. Only three out of these eight outcomes were also assessed in meta-analyses of trials evaluating weight loss interventions. These interventions significantly reduced the risk of caesarean section and pre
Bray R, Cacciatore S, Jimenez B, et al., 2017, Urinary metabolic phenotyping of women with lower urinary tract symptoms, Journal of Proteome Research, Vol: 16, Pages: 4208-4216, ISSN: 1535-3893
Lower urinary tract symptoms (LUTS), including urinary incontinence, urgency and nocturia, affect approximately half of women worldwide. Current diagnostic methods for LUTS are invasive and costly, while available treatments are limited by side effects leading to poor patient compliance. In this study, we aimed to identify urine metabolic signatures associated with LUTS using proton nuclear magnetic resonance (1H NMR) spectroscopy. A total of 214 urine samples were collected from women attending tertiary urogynecology clinics (cases; n = 176) and healthy control women attending general gynecology clinics (n = 36). Despite high variation in the urine metabolome across the cohort, associations between urine metabolic profiles and BMI, parity, overactive bladder syndrome, frequency, straining, and bladder storage were identified using KODAMA (knowledge discovery by accuracy maximization). Four distinct urinary metabotypes were identified, one of which was associated with increased urinary frequency and low BMI. Urine from these patients was characterized by increased levels of isoleucine and decreased levels of hippurate. Our study suggests that metabolic profiling of urine samples from LUTS patients offers the potential to identify differences in underlying etiology, which may permit stratification of patient populations and the design of more personalized treatment strategies.
Foo FL, Masini G, Mceniery C, et al., 2017, OC07.01 Pre-conception maternal haemodynamics is associated with subsequent development of pre-eclampsia (PE) or fetal growth restriction (FGR), ISUOG World Congress 2017, Publisher: Wiley, Pages: 12-13, ISSN: 0960-7692
Norman JE, Bennett P, 2017, Preterm birth prevention - Time to PROGRESS beyond progesterone, PLOS MEDICINE, Vol: 14, ISSN: 1549-1676
Mitra A, Mahajan V, Macintyre D, et al., 2017, Comparison of vaginal microbiota sampling techniques: cytobrush versus swab, Scientific Reports, Vol: 7, ISSN: 2045-2322
Evidence suggests the vaginal microbiota (VM) may influence risk of persistent Human Papillomavirus (HPV) infection and cervical carcinogenesis. Established cytology biobanks, typically collected with a cytobrush, constitute a unique resource to study such associations longitudinally. It is plausible that compared to rayon swabs; the most commonly used sampling devices, cytobrushes may disrupt biofilms leading to variation in VM composition. Cervico-vaginal samples were collected with cytobrush and rayon swabs from 30 women with high-grade cervical precancer. Quantitative PCR was used to compare bacterial load and Illumina MiSeq sequencing of the V1-V3 regions of the 16S rRNA gene used to compare VM composition. Cytobrushes collected a higher total bacterial load. Relative abundance of bacterial species was highly comparable between sampling devices (R2 = 0.993). However, in women with a Lactobacillus-depleted, high-diversity VM, significantly less correlation in relative species abundance was observed between devices when compared to those with a Lactobacillus species-dominant VM (p = 0.0049). Cytobrush and swab sampling provide a comparable VM composition. In a small proportion of cases the cytobrush was able to detect underlying high-diversity community structure, not realized with swab sampling. This study highlights the need to consider sampling devices as potential confounders when comparing multiple studies and datasets.
Balinskaite V, Bottle R, Sodhi V, et al., 2017, The risk of adverse pregnancy outcomes following non-obstetric surgery during pregnancy. Estimates from a retrospective cohort study of 6.5 million pregnancies, Annals of Surgery, Vol: 266, Pages: 260-266, ISSN: 1528-1140
Objective. To estimate the risk of adverse birth outcomes for women who underwent non-obstetric surgery during pregnancy compared with those who did not. Background. Previous research suggests that non-obstetric surgery occurs during 1%-2% of pregnancies. However, there is limited evidence quantifying risks to the mother or pregnancy of such surgery. Methods. We examined maternity admissions using hospital administrative data collected between 1st April 2002 and 31st March 2012 and identified pregnancies where non-obstetric surgery occurred. We used logistic regression models to determine the adjusted relative risk, attributable risk and number needed to harm of non-obstetric surgical procedures for adverse birth outcomes.Results. We identified 6,486,280 pregnancies. In 47,628 of these pregnancies, non-obstetric surgery had occurred. We found that non-obstetric surgery during pregnancy was associated with a higher risk of adverse birth outcomes, although the attributable risk was generally low. We estimated that every 287 surgical operations were associated with one additional stillbirth, every 31 operations associated with one additional preterm delivery, every 39 operations associated with one additional low birth weight baby, every 25 operations associated with one additional caesarean section, and every 50 operations associated with one additional long inpatient stay.Conclusions. Although we have no means of disentangling the effect of the surgery from the effect of the underlying condition, we found that the risk associated with non-obstetric surgery was relatively low, confirming that surgical procedures during pregnancy are generally safe. We believe that our findings improve upon previous research, and are useful reference points for any discussion of risk with prospective patients.
Usman S, Foo L, Tay J, et al., 2017, Authors' reply [Use of magnesium sulfate in preterm deliveries for neuroprotection of the neonate], Obstetrician and Gynaecologist, Vol: 19, Pages: 255-256, ISSN: 1744-4667
Kim SH, Riaposova L, Pohl O, et al., 2017, FP receptor antagonist, OBE002, inhibits both PGF2α- and OT-induced contractions of human pregnant myometrium in vitro, Publisher: OXFORD UNIV PRESS, Pages: 452-452, ISSN: 0268-1161
Khanjani S, West C, Lavery S, et al., 2017, Reprogramming of the hCG signalling profile in human endometrial stromal cells from recurrent miscarriage patients, 33rd Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), Publisher: OXFORD UNIV PRESS, Pages: 353-354, ISSN: 0268-1161
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