Publications
669 results found
Riaposova L, Kim SH, Pohl O, et al., 2017, Combination tocolytics on the inhibition of OT-induced contractions of human pregnant myometrium in vitro, 33rd Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), Publisher: OXFORD UNIV PRESS, Pages: 54-54, ISSN: 0268-1161
Kyrgiou M, Bennett P, 2017, Can we prevent preterm birth after radical trachelectomy?, British Journal of Obstetrics and Gynaecology, Vol: 124, Pages: 1737-1737, ISSN: 0306-5456
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.
Foo FL, Collins A, McEniery CM, et al., 2017, Preconception and early pregnancy maternal haemodynamic changes in healthy women in relation to pregnancy viability, Human Reproduction, Vol: 32, Pages: 985-992, ISSN: 1460-2350
STUDY QUESTIONAre there differences in preconception cardiovascular function between women who have a viable pregnancy and those who have a first trimester miscarriage?SUMMARY ANSWERPreconception cardiovascular function of central haemodynamics and arterial function are similar between women who have a viable pregnancy and those who have a first trimester miscarriage.WHAT IS KNOWN ALREADYMiscarriages have been associated with increased long-term cardiovascular disease risk, and arterial and cardiovascular dysfunction has been hypothesised as the common link. It is not known if these risks are present prior to pregnancy or are a reflection of poor arterial and haemodynamic adaptation to pregnancy.STUDY DESIGN, SIZE, DURATIONThis prospective longitudinal preconception cohort study was conducted over 18 months. In total, 367 participants were recruited pre-pregnancy, from which 197 pregnancies were recorded; 39 of these pregnancies ended in first trimester miscarriage. Complete longitudinal data were available for 172 pregnancies (140 viable pregnancies, 32 first trimester miscarriages) from pre-pregnancy to 6 weeks gestation.PARTICIPANTS/MATERIALS, SETTING, METHODSThis was a single site study based at a maternity hospital in London. Healthy women were recruited prior to natural conception and followed up once they became pregnant. All underwent haemodynamic [cardiac output (CO), peripheral vascular resistance (PVR)] and arterial function [aortic augmentation index (AIx) and pulse wave velocity (PWV)] testing prior to pregnancy and at 6 weeks gestation, using non-invasive devices (gas re-breathing method, Innocor® and an occilometric device, Vicorder®). Cross-sectional measurements at pre-pregnancy and 6 weeks gestation and a longitudinal analysis of changes were compared between women who had a subsequent viable pregnancy, and those who had a subsequent first trimester miscarriage.MAIN RESULTS AND THE ROLE OF CHANCEThere were no differences between women desti
Kim SH, Pohl O, Chollet A, et al., 2017, Differential Effects of Oxytocin Receptor Antagonists, Atosiban and Nolasiban, on Oxytocin Receptor-Mediated Signaling in Human Amnion and Myometrium, MOLECULAR PHARMACOLOGY, Vol: 91, Pages: 403-415, ISSN: 0026-895X
One of the most established roles of oxytocin (OT) is in inducing uterine contractions and labor. Apart from inducing contractions, our recent studies showed that OT can also activate proinflammatory pathways in both human myometrial and amnion cells, which suggests that the proinflammatory role of OT should be taken into account when developing tocolytics targeting the OT/oxytocin receptor (OTR) system. The OTR antagonist, atosiban, is currently used therapeutically for the treatment of preterm labor. We previously showed that atosiban fails to inhibit the proinflammatory effects of OT in human amnion; atosiban alone activates nuclear factor-κB (NF-κB) and mitogen activated protein kinases, thus upregulating downstream prolabor genes. In contrast with our findings with atosiban, the presence of the orally active OTR antagonist, nolasiban, reduced the effect of OT on NF-κB and p38 kinase activation in both myometrial and amnion cells. Consistent with the activation of these inflammatory mediators, OT led to increases in the expression of cyclooxygenase-2 and phosphorylated cytosolic phospholipase A2, which was reflected in prostaglandin E2 synthesis. Inhibition of NF-κB activation by nolasiban also translated to suppression of downstream prolabor gene expression, such as cyclooxygenase-2, C-C motif chemokine ligand 2, interleukin-6, and interleukin-8. We also demonstrated that nolasiban treatment alone has no significant stimulatory effect on both the myometrium and amnion. In conclusion, our findings indicate that nolasiban possesses promising potential as a novel tocolytic agent for both acute and maintenance therapy, as it inhibits both myometrial contractions and the proinflammatory effects of OT without the biased agonist effects.
Mitra A, MacIntyre D, Lai J, et al., 2017, The impact of excisional treatment for cervical intraepithelial neoplasia on the vaginal microbiota, 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: Sage Publications, Pages: 89A-89A, ISSN: 1071-5576
Kim SH, Ahmed H, Riaposova L, et al., 2017, Both OTR Antagonists, Atosiban and Nolasiban, Inhibits PGE(2)/PGF(2 alpha)-Induced Contractions of Human Pregnant Myometrium In Vitro., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 245A-245A, ISSN: 1933-7191
Brown R, Lee Y, Kindinger L, et al., 2017, Vaginal dysbiosis following preterm prelabour rupture of the fetal membranes is associated with funisitis and the emergence of specific pathobionts, Publisher: WILEY, Pages: 31-31, ISSN: 1470-0328
Lewis H, Pruski P, Kindinger L, et al., 2017, Desorption electrospray ionisation mass spectrometry permits identification of vaginal mucosal metabolome signatures associated with preterm birth risk, Publisher: WILEY, Pages: 135-135, ISSN: 1470-0328
Chan DCY, Brown RG, Bennett P, 2017, Positive predictors of pregnancy outcome following rescue cervical cerclage, Publisher: WILEY, Pages: 28-28, ISSN: 1470-0328
Al-Memar M, Bobdiwala S, Lee Y, et al., 2017, Association between vaginal microbiome dysbiosis and miscarriage, Publisher: WILEY, Pages: 65-65, ISSN: 1470-0328
Bobdiwala S, Al-Memar M, Lee Y, et al., 2017, Ectopic pregnancy is associated with increased vaginal bacterial diversity and reduced <i>Lactobacillus</i> species dominance, Publisher: WILEY, Pages: 63-64, ISSN: 1470-0328
Lewis H, Pruski P, Kindinger L, et al., 2017, Relationship Between Yeast, Vaginal Microbiota Composition and Pregnancy Outcomes., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 65A-65A, ISSN: 1933-7191
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Khanjani S, West C, Brosens JJ, et al., 2017, Reprogramming of the hCG Signaling Profile in Human Endometrial Stromal Cells from Recurrent Miscarriage Patients, 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 227A-228A, ISSN: 1933-7191
West C, Kim SH, Khanjani S, et al., 2017, Oxytocin Activates Pro-Inflammatory Pathways in Decidualised Human Endometrial Stromal Cells., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 162A-162A, ISSN: 1933-7191
Lee YS, Marianoglou M, Hanton F, et al., 2017, D-Lactic Acid Inhibits Basal Inflammatory Pathways in Human Vaginal Epithelial Cells., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 241A-241A, ISSN: 1933-7191
Lei K, Georgiou EX, Yulia A, et al., 2017, Progesterone and the Repression of Myometrial Inflammation: The Roles of MKP-1 and the AP-1 System., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 107A-107A, ISSN: 1933-7191
Brown RG, Lee YS, Smith A, et al., 2017, Vaginal Dysbiosis Increases Risk of Preterm Membrane Rupture, Funisitis and Neonatal Sepsis., 64th Annual Scientific Meeting of the Society-for-Reproductive-Investigation (SRI), Publisher: SAGE PUBLICATIONS INC, Pages: 64A-64A, ISSN: 1933-7191
Kim SH, Bennett PR, Terzidou V, 2017, Advances in the role of oxytocin receptors in human parturition., Molecular and Cellular Endocrinology, Vol: 449, Pages: 56-63, ISSN: 1872-8057
Oxytocin (OT) is a neurohypophysial hormone which has been found to play a central role in the regulation of human parturition. The most established role of oxytocin/oxytocin receptor (OT/OTR) system in human parturition is the initiation of uterine contractions, however, recent evidence have demonstrated that it may have a more complex role including initiation of inflammation, regulation of miRNA expression, as well as mediation of other non-classical oxytocin actions via receptor crosstalk with other G protein-coupled receptors (GPCRs). In this review we highlight both established and newly emerging roles of OT/OTR system in human parturition and discuss the expanding potential for OTRs as pharmacological targets in the management of preterm labour.
Kindinger LM, Bennett PR, Lee YS, et al., 2017, The interaction between vaginal microbiota, cervical length and vaginal progesterone treatment for preterm birth risk, Microbiome, Vol: 5, Pages: 1-14, ISSN: 2049-2618
Background:Preterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing we undertook a prospective study in women at risk of preterm birth(n=161) to assess 1) the relationship between vaginal microbiotaand cervical length in the second trimester and preterm birth-risk, and 2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix.Results:Lactobacillus iners dominance at 16 weeks gestation was significantly associated with both a short cervix <25mm (n=15, P<0.05), andpreterm birth <34+0 weeks (n=18, 38P<0.01; 69% PPV).In contrast, L. crispatus dominance was highly predictive of term birth (n=127, 98% PPV). Cervical shortening and preterm birthwere not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28 and 34 weeks)was then undertaken in women receiving vaginal progesterone (400mg/OD, n=25) versus controls (n=42).Progesterone did not alter vaginal bacterial community structurenor reduce L. iners-associated preterm birth (<34 weeks). Conclusions:L. iners dominance of the vaginal microbiota at 16 weeks gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about ‘infection risk’ associated with use of a vaginal pessary during high-risk pregnancy can be reassured.
Usman S, Foo L, Tay J, et al., 2017, Use of magnesium sulfate in preterm deliveries for neuroprotection of the neonate, Obstetrician and Gynaecologist, Vol: 19, Pages: 21-28, ISSN: 1744-4667
Key content The prevalence of preterm birth is increasing and owing to advances in neonatal care, more infants are surviving. However, in parallel with this, the incidence of cerebral palsy (CP) is also rising. Magnesium sulfate (MgSO4) is currently recommended for use in women who are at risk of giving birth at less than 30–32 weeks of gestation for neuroprotection of their infants. The exact mechanism of action remains unclear. Meta‐analyses report encouraging results that are consistent with a modest but tangible benefit for the use of MgSO4, and suggest a number needed to treat (NNT) to prevent one in 46 cases of CP in infants born preterm before 30 weeks of gestation and one in 63 cases of CP in infants born preterm before 34 weeks of gestation.Learning objectives To gain an understanding of the risk of neurodisability in infants delivered preterm. To become familiar with the main studies assessing the use of MgSO4 for neuroprotection in preterm deliveries. To become aware of the relevant international guidelines.Ethical issues Concerns have been raised regarding the higher number of perinatal deaths reported with the use of MgSO4 in the MagNET study. This was not substantiated in the Cochrane review. Given that MgSO4 is a safe, readily available and inexpensive drug, even if there were only to be modest benefits from its use, the risk–benefit ratio is in favour of its use.
Khanjani S, MacIntyre DA, Bennett PR, 2017, Pathophysiology of Preterm Birth, Fetal and Neonatal Physiology, 2-Volume Set, Pages: 1732-1737.e2, ISBN: 9780323352338
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Pruski P, MacIntyre DA, Lewis HV, et al., 2016, Medical swab analysis using desorption electrospray ionization mass spectrometry (DESI-MS) – a non-invasive approach for mucosal diagnostics, Analytical Chemistry, Vol: 89, Pages: 1540-1550, ISSN: 0003-2700
Medical swabs are routinely used worldwide to sample human mucosa for microbiological screening with culture methods. These are usually time-consuming and have a narrow focus on screening for particular microorganism species. As an alternative, direct mass spectrometric profiling of the mucosal metabolome provides a broader window into the mucosal ecosystem. We present for the first time a minimal effort/minimal-disruption technique for augmenting the information obtained from clinical swab analysis with mucosal metabolome profiling using desorption electrospray ionization mass spectrometry (DESI-MS) analysis. Ionization of mucosal biomass occurs directly from a standard rayon swab mounted on a rotating device and analyzed by DESI MS using an optimized protocol considering swab–inlet geometry, tip–sample angles and distances, rotation speeds, and reproducibility. Multivariate modeling of mass spectral fingerprints obtained in this way readily discriminate between different mucosal surfaces and display the ability to characterize biochemical alterations induced by pregnancy and bacterial vaginosis (BV). The method was also applied directly to bacterial biomass to confirm the ability to detect intact bacterial species from a swab. These results highlight the potential of direct swab analysis by DESI-MS for a wide range of clinical applications including rapid mucosal diagnostics for microbiology, immune responses, and biochemistry.
Sykes L, Anucha E, Begam Z, et al., 2016, The effect of TLR3 receptor priming on TLR 2, 4 and 6 agonist induced inflammation in placental implants, Society for Reproductive Investigation
Chan D, Lee Y, Teoh TG, et al., 2016, A comparison of TLR 1-9 induced cytokine responses in whole blood collected in the first trimester and at term and matched cord blood, Society for Reproductive Investigation
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
Cacciatore S, Tenori L, Luchinat C, et al., 2016, KODAMA: an R package for knowledge discovery and data mining, Bioinformatics, ISSN: 1367-4803
KODAMA, a novel learning algorithm for unsupervised feature extraction, is specifically designed for analysing noisy and high-dimensional datasets. Here we present an R package of the algorithm with additional functions that allow improved interpretation of high-dimensional data. The package requires no additional software and runs on all major platforms.
Edey LF, O'Dea KP, Herbert BR, et al., 2016, The local and systemic immune response to intrauterine LPS in the prepartum mouse, Biology of Reproduction, Vol: 95, Pages: 1-10, ISSN: 1529-7268
Inflammation plays a key role in human term and preterm labor (PTL). Intrauterine LPS has been widely used to model inflammation-induced complications of pregnancy, including PTL. It has been shown to induce an intense myometrial inflammatory cell infiltration, but the role of LPS-induced inflammatory cell activation in labor onset and fetal demise is unclear. We investigated this using a mouse model of PTL, where an intrauterine injection of 10 μg of LPS (serotype 0111:B4) was given at E16 of CD1 mouse pregnancy. This dose induced PTL at an average of 12.7 h postinjection in association with 85% fetal demise. Flow cytometry showed that LPS induced a dramatic systemic inflammatory response provoking a rapid and marked leucocyte infiltration into the maternal lung and liver in association with increased cytokine levels. Although there was acute placental inflammatory gene expression, there was no corresponding increase in fetal brain inflammatory gene expression until after fetal demise. There was marked myometrial activation of NFκB and MAPK/AP-1 systems in association with increased chemokine and cytokine levels, both of which peaked with the onset of parturition. Myometrial macrophage and neutrophil numbers were greater in the LPS-injected mice with labor onset only; prior to labor, myometrial neutrophils and monocytes numbers were greater in PBS-injected mice, but this was not associated with an earlier onset of labor. These data suggest that intrauterine LPS induces parturition directly, independent of myometrial inflammatory cell infiltration, and that fetal demise occurs without fetal inflammation. Intrauterine LPS provokes a marked local and systemic inflammatory response but with limited inflammatory cell infiltration into the myometrium or placenta.
Mitra A, Paraskevaidis M, Lai J, et al., 2016, Reduction in antimicrobial peptides after excisional treatment for cervical intraepithelial neoplasia: a possible mechanism of subsequent preterm birth?, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 123, Pages: E11-E11, ISSN: 1470-0328
Kindinger L, MacIntyre D, Lee Y, et al., 2016, Understanding the interaction between the cervix and the vaginal microbiome underlying specific aetiologies of preterm birth, Publisher: WILEY-BLACKWELL, Pages: E5-E6, ISSN: 1470-0328
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