Publications
669 results found
Al-Memar M, Caccitore S, Bobdiwala S, et al., 2016, Urine metabolomic changes by gestational age in early pregnancy and differences in the metabolome in viable pregnancies that miscarry compared to those that remain viable, Publisher: WILEY-BLACKWELL, Pages: E1-E1, ISSN: 1470-0328
Kindinger L, MacIntyre D, Lee Y, et al., 2016, Cervical cerclage using braided suture induces vaginal dysbiosis, inflammation and is associated with increased rates of preterm birth, Publisher: WILEY-BLACKWELL, Pages: E4-E4, ISSN: 1470-0328
Brown R, Kindinger L, Lee Y, et al., 2016, Characterisation of the vaginal microbiome in patients subsequently experiencing preterm prelabour rupture of membranes, Publisher: WILEY-BLACKWELL, Pages: E2-E3, ISSN: 1470-0328
Kindinger LM, Kyrgiou M, MacIntyre DA, et al., 2016, Preterm Birth Prevention Post-Conization: A Model of Cervical Length Screening with Targeted Cerclage, PLOS One, Vol: 11, ISSN: 1932-6203
Women with a history of excisional treatment (conization) for cervical intra-epithelial neoplasia (CIN) are at increased risk of preterm birth, perinatal morbidity and mortality in subsequent pregnancy. We aimed to develop a screening model to effectively differentiate pregnancies post-conization into low- and high-risk for preterm birth, and to evaluate the impact of suture material on the efficacy of ultrasound indicated cervical cerclage. We analysed longitudinal cervical length (CL) data from 725 pregnant women post-conization attending preterm surveillance clinics at three London university Hospitals over a ten year period (2004–2014). Rates of preterm birth <37 weeks after targeted cerclage for CL<25mm were compared with local and national background rates and expected rates for this cohort. Rates for cerclage using monofilament or braided suture material were also compared. Of 725 women post-conization 13.5% (98/725) received an ultrasound indicated cerclage and 9.7% (70/725) delivered prematurely, <37weeks; 24.5% (24/98) of these despite insertion of cerclage. The preterm birth rate was lower for those that had monofilament (9/60, 15%) versus braided (15/38, 40%) cerclage (RR 0.7, 95% CI 0.54 to 0.94, P = 0.008). Accuracy parameters of interval reduction in CL between longitudinal second trimester screenings were calculated to identify women at low risk of preterm birth, who could safely discontinue surveillance. A reduction of CL <10% between screening timepoints predicts term birth, >37weeks. Our triage model enables timely discharge of low risk women, eliminating 36% of unnecessary follow-up CL scans. We demonstrate that preterm birth in women post-conization may be reduced by targeted cervical cerclage. Cerclage efficacy is however suture material-dependant: monofilament is preferable to braided suture. The introduction of triage prediction models has the potential to reduce the number of unnecessary CL scan for women at low risk of
Kyrgiou M, Athanasiou A, Paraskevaidi M, et al., 2016, Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. Editorial Comment, Obstetrical & Gynecological Survey, Vol: 71, Pages: 646-648, ISSN: 1533-9866
Local cervical treatment for preinvasive cervical disease such as cervical intraepithelial neoplasia (CIN) has been associated with an increased risk of preterm birth, perinatal morbidity, and mortality in a later pregnancy. This meta-analysis aimed to investigate the impact of treatment for cervical preinvasive and early invasive disease on obstetric outcomes and to see how this risk could be modified by the cone depth and comparison group.
Mitra A, Macintyre DA, marchesi, et al., 2016, The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?, Microbiome, Vol: 4, ISSN: 2049-2618
The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon analysis of bacterial 16S rRNA genes permits in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture based microbiological techniques. The Human Papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence, and the development of cervical precancer and cancer. In this review we summarise the current literature, and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.
Mitra A, MacIntyre D, Lee Y, et al., 2016, Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity, Blair Bell Research Society Annual Academic Meeting, Publisher: Wiley, Pages: E11-E12, ISSN: 1470-0328
Kyrgiou M, Mitra A, Athanasiou A, et al., 2016, The risk of preterm birth after treatment for cervical pre-invasive and early invasive disease increases with increasing cone depth: a systematic review and meta-analysis, Blair Bell Research Society Annual Academic Meeting, Publisher: Wiley, Pages: E8-E8, ISSN: 1470-0328
Balinskaite V, Aylin P, Bennett P, et al., 2016, Estimating the risk of adverse birth outcomes in pregnant women undergoing non-obstetric surgery using routinely collected NHS data: an observational study, Estimating the risk of adverse birth outcomes in pregnant women undergoing non-obstetric surgery using routinely collected NHS data: an observational study, Publisher: NIHR Journals Library
Background:Previous research suggests that non-obstetric surgery is carried out in 1–2% of allpregnancies. However, there is limited evidence quantifying the associated risks. Furthermore, of theevidence available, none relates directly to outcomes in the UK, and there are no current NHS guidelinesregarding non-obstetric surgery in pregnant women.Objectives:To estimate the risk of adverse birth outcomes of pregnancies in which non-obstetric surgerywas or was not carried out. To further analyse common procedure groups.Data Source:Hospital Episode Statistics (HES) maternity data collected between 2002–3 and 2011–12.Main outcomes:Spontaneous abortion, preterm delivery, maternal death, caesarean delivery, longinpatient stay, stillbirth and low birthweight.Methods:We utilised HES, an administrative database that includes records of all patient admissions andday cases in all English NHS hospitals. We analysed HES maternity data collected between 2002–3 and2011–12, and identified pregnancies in which non-obstetric surgery was carried out. We used logisticregression models to determine the adjusted relative risk and attributable risk of non-obstetric surgicalprocedures for adverse birth outcomes and the number needed to harm.Results:We identified 6,486,280 pregnancies, in 47,628 of which non-obstetric surgery was carried out.In comparison with pregnancies in which surgery was not carried out, we found that non-obstetric surgerywas associated with a higher risk of adverse birth outcomes, although the attributable risk was generallylow. We estimated that for every 287 pregnancies in which a surgical operation was carried out there wasone additional stillbirth; for every 31 operations there was one additional preterm delivery; for every25 operations there was one additional caesarean section; for every 50 operations there was oneadditional long inpatient stay; and for every 39 operations there was one additional low-birthweight baby.Limitations:We
Pohl O, Guillaume P, Bennett P, et al., 2016, OBE002, a selective prostaglandin F2α receptor antagonist for the treatment of preterm labor, does not impair renal function in the newborn rabbit, 52nd Congress of the European-Societies-of-Toxicology (EUROTOX), Publisher: ELSEVIER IRELAND LTD, Pages: S128-S128, ISSN: 0378-4274
Pohl O, Spezia F, Gervais F, et al., 2016, Selective antagonism of the prostaglandin F2α receptor does not cause constriction of the ductus arteriosus in fetal rats, 52nd Congress of the European-Societies-of-Toxicology (EUROTOX), Publisher: ELSEVIER IRELAND LTD, Pages: S134-S134, ISSN: 0378-4274
Pohl O, Guillaume P, Bennett P, et al., 2016, OBE002, a selective prostaglandin F2 alpha receptor antagonist for the treatment of preterm labor, does not impair renal function in the newborn rabbit, 52nd Congress of the European-Societies-of-Toxicology (EUROTOX), Publisher: ELSEVIER IRELAND LTD, Pages: S128-S128, ISSN: 0378-4274
Pohl O, Spezia F, Gervais F, et al., 2016, Selective antagonism of the prostaglandin F2 alpha receptor does not cause constriction of the ductus arteriosus in fetal rats, 52nd Congress of the European-Societies-of-Toxicology (EUROTOX), Publisher: ELSEVIER IRELAND LTD, Pages: S134-S134, ISSN: 0378-4274
Norman JE, Marlow N, Messow CM, et al., 2016, Vaginal Progesterone Prophylaxis for Preterm Birth (the OPPTIMUM Study): A Multicentre, Randomized, Double-Blind Trial, Obstetrical and Gynecological Survey, Vol: 71, Pages: 517-518, ISSN: 0029-7828
Mitra A, Kindinger L, Kalliala I, et al., 2016, Obstetric complications after treatment of cervical intraepithelial neoplasia, British Journal of Hospital Medicine, Vol: 77, Pages: C124-C127, ISSN: 1750-8460
Kindinger LM, MacIntyre DA, Lee YS, et al., 2016, Relationship between vaginal microbial dysbiosis, inflammation and pregnancy outcomes in cervical cerclage, Science Translational Medicine, Vol: 8, ISSN: 1946-6242
Preterm birth, the leading cause of death in children under five, may be caused by inflammation triggered by ascending vaginal infection. About two million cervical cerclages are performed annually to prevent preterm birth. The procedure is thought to provide structural support and maintain the endocervical mucus plug as a barrier to ascending infection. Two types of suture material are used for cerclage: monofilament or multifilament braided. Braided sutures are most frequently used, though no evidence exists to favor them over monofilament sutures. In this study we assessed birth outcomes in a retrospective cohort of 678 women receiving cervical cerclage in 5 UK university hospitals and showed that braided cerclage was associated with increased intrauterine death (15% v 5%, P = 0.0001) and preterm birth (28% v 17%, P = 0.0006) compared to monofilament suture. To understand the potential underlying mechanism, we performed a prospective, longitudinal study of the vaginal microbiome in women at risk of preterm birth because of short cervical length (≤25 mm) who received braided (n=25) or monofilament (n=24) cerclage under otherwise comparable circumstances. Braided suture induced a persistent shift towards vaginal microbiome dysbiosis characterized by reduced Lactobacillus spp. and enrichment of pathobionts. Vaginal dysbiosis was associated with inflammatory cytokine and interstitial collagenase excretion into cervicovaginal fluid and premature cervical remodeling. Monofilament suture had comparatively minimal impact upon the vaginal microbiome and its interactions with the host. These data provide in vivo evidence that a dynamic shift of the human vaginal microbiome toward dysbiosis correlates with preterm birth.
Kyrgiou M, Athanasiou A, Paraskevaidi M, et al., 2016, Adverse obstetrical outcomes after local treatment for cervical pre-invasive and early invasive disease according to the cone depth: a systematic review and meta-analysis, BMJ, Vol: 354, Pages: 1-15, ISSN: 0959-8138
Objective: To assess the effect of treatment for CIN on obstetric outcomes and to correlate this to the cone depth and comparison group used.MethodsDesign: Systematic review and meta-analysisData Sources: CENTRAL, MEDLINE, EMBASE from 1948 to April 2016.Eligibility Criteria: Studies assessing obstetric outcomes in women with or without a previous local cervical treatment.Data Extraction & Synthesis: Independent reviewers extracted the data and performed quality assessment using the Newcastle-Ottawa criteria. Studies were classified according to method and obstetric endpoint. Pooled risk ratios (RR) were calculated using a random-effect model and inverse variance. Inter-study heterogeneity was assessed with I2 statistics.Main outcomes and measures: Obstetric outcomes; preterm birth (PTB) (spontaneous and threatened), premature rupture of the membranes (pPROM), chorioamnionitis, mode of delivery, length of labour, induction of delivery, oxytocin use, haemorrhage, analgesia, cervical cerclage & cervical stenosis. Neonatal outcomes; low birth weight (LBW), neonatal intensive care unit (NICU) admission, stillbirth, APGAR scores and perinatal mortality.Results: Seventy-one studies were included (6338982 participants: 65082 treated-6292563 untreated). Treatment significantly increased the risk of overall (<37weeks)(10.7 v 5.4%, RR=1.78[1.60 to 1.98]), severe (<34/32weeks)(3.5 v 1.4%, RR=2.40[1.92 to 2.99]) and extreme (<30/28weeks)(1.0 v 0.3%, RR=2.54[1.77 to 3.63]) PTB. The magnitude of the effect was higher for techniques removing or ablating more tissue (<37weeks: CKC (RR=2.70[2.14 to 3.40]), LC (RR=2.11[1.26 to 3.54)], excision not otherwise specified (NOS) (RR=2.02[1.60 to 2.55]), LLETZ (RR=1.56[1.36 to 1.79]), ablation NOS (RR=1.46[1.27 to 1.66]). The risk of PTB increased with repeat treatment (13.2 v 4.1%, RR=3.78[2.65 to 5.39]) and with increasing cone depth (≤12/10mm: 7.1 v 3.4%, RR=1.54[1.09 to 2.18]; ≥10/12mm: 9.8 v 3.4%, RR=1.93[1.62
Aylin P, Bennett P, Bottle A, et al., 2016, The risk of adverse pregnancy outcomes following non-obstetric surgery during pregnancy: An observational study, BJOG-An International Journal of Obstetrics and Gynaecology, Vol: 123, Pages: 84-84, ISSN: 1471-0528
Migale R, MacIntyre DA, Cacciatore S, et al., 2016, Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics, BMC Medicine, Vol: 14, ISSN: 1741-7015
BACKGROUND: Preterm birth is now recognized as the primary cause of infant mortality worldwide. Interplay between hormonal and inflammatory signaling in the uterus modulates the onset of contractions; however, the relative contribution of each remains unclear. In this study we aimed to characterize temporal transcriptome changes in the uterus preceding term labor and preterm labor (PTL) induced by progesterone withdrawal or inflammation in the mouse and compare these findings with human data. METHODS: Myometrium was collected at multiple time points during gestation and labor from three murine models of parturition: (1) term gestation; (2) PTL induced by RU486; and (3) PTL induced by lipopolysaccharide (LPS). RNA was extracted and cDNA libraries were prepared and sequenced using the Illumina HiSeq 2000 system. Resulting RNA-Seq data were analyzed using multivariate modeling approaches as well as pathway and causal network analyses and compared against human myometrial transcriptome data. RESULTS: We identified a core set of temporal myometrial gene changes associated with term labor and PTL in the mouse induced by either inflammation or progesterone withdrawal. Progesterone withdrawal initiated labor without inflammatory gene activation, yet LPS activation of uterine inflammation was sufficient to override the repressive effects of progesterone and induce a laboring phenotype. Comparison of human and mouse uterine transcriptomic datasets revealed that human labor more closely resembles inflammation-induced PTL in the mouse. CONCLUSIONS: Labor in the mouse can be achieved through inflammatory gene activation yet these changes are not a requisite for labor itself. Human labor more closely resembles LPS-induced PTL in the mouse, supporting an essential role for inflammatory mediators in human "functional progesterone withdrawal." This improved understanding of inflammatory and progesterone influence on the uterine transcriptome has important implications for
Cook J, MacIntyre D, Sykes L, et al., 2016, Prediction of cervical shortening and preterm delivery using specific cell free plasma microRNAs, Publisher: Wiley, Pages: 59-60, ISSN: 1470-0328
Al-Memar M, Cacciatore S, Bobdiwala S, et al., 2016, Urine metabolomic changes by gestational age in early pregnancy and differences in the metabolome in viable pregnancies that miscarry compared to those that remain viable, Publisher: Wiley, Pages: 76-76, ISSN: 1470-0328
Norman JE, Marlow N, Messow CM, et al., 2016, Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial, The Lancet, Vol: 387, Pages: 2106-2116, ISSN: 0140-6736
BackgroundProgesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child.MethodsWe did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22–24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com, number ISRCTN14568373.FindingsBetween Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for
Kindinger L, MacIntyre D, Lees Y, et al., 2016, The impact of progesterone on the vaginal microbiome in high-risk pregnancy with a short cervix, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: Wiley, Pages: 72-72, ISSN: 1471-0528
Cook J, MacIntyre D, Kim SH, et al., 2016, Hsa-miR-146b-3p is functionally modulated by nuclear factor-kappa B in human myometrial cells, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: WILEY-BLACKWELL, Pages: 102-102, ISSN: 1470-0328
Kindinger L, MacIntyre D, Lee Y, et al., 2016, Cervical cerclage using braided suture induces vaginal dysbiosis, inflammation, and is associated with increased preterm birth, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: Wiley, Pages: 8-8, ISSN: 1470-0328
Arulkumaran S, Kim SH, Pohl O, et al., 2016, The inhibition of both spontaneous and oxytocin-induced contractions of human pregnant myometrium by the oxytocin receptor antagonist, OBE001, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: Wiley, Pages: 103-104, ISSN: 1471-0528
Kim SH, Pohl O, Chollet A, et al., 2016, The inhibition of oxytocin-driven pro-inflammatory effects in both human myometrium and amnion by the oxytocin receptor antagonist, OBE001, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: Wiley, Pages: 11-12, ISSN: 1471-0528
Foo L, Gautreau A, Bennett P, et al., 2016, Gestation of pregnancy loss in an observational prospective preconception cohort, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: WILEY-BLACKWELL, Pages: 58-58, ISSN: 1470-0328
Cook J, MacIntyre D, Sykes L, et al., 2016, Expression of specific cell-free plasma microRNAs is associated with cervical shortening in women at risk of preterm birth, British Maternal & Fetal Medicine Society (BMFMS) 18th Annual Conference 2016, Publisher: WILEY-BLACKWELL, Pages: 103-103, ISSN: 1470-0328
Migale R, MacIntyre DA, Cacciatore S, et al., 2016, Relative Contribution of Hormonal and Inflammatory Pathways to Uterine Transcriptome Dynamics in Term and Preterm Labor, 63rd Annual Scientific Meeting of the Society-for-Reproductive-Investigation, Publisher: SAGE PUBLICATIONS INC, Pages: 125A-125A, ISSN: 1933-7191
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.