Research by staff affiliated to the Coombe Women & Infants University Hospital

Recent Submissions

  • How Much Greater is Obstetric Intervention in Women with Medical Disorders in Pregnancy When Compared to the General Population?

    Keane, R.; Manning, C.; Lynch, C.; Regan, C.; Byrne, B. (Irish Medical Journal, 2019-10)
    The purpose of this study was to compare obstetric and neonatal outcomes between women attending a specialised maternal medicine service and the general obstetric population.
  • Maternal sepsis is an evolving challenge

    Turner, Michael J.; UCD Centre for Human Reproduction, Coombe Women and Infants University Hospital, Dublin, Ireland. (Wiley, 2019-04-26)
    Despite major advances in the last century, particularly in high resource settings, maternal sepsis remains a common and potentially preventable cause of direct maternal death globally. A barrier to further progress has been the lack of consensus on the definition of maternal sepsis. Publications from two recent multidisciplinary consensus conferences, one on sepsis in the non-pregnant adult and the other on sepsis in the pregnant woman, concluded that the criteria for diagnosing sepsis should be clinically-based, applicable at the bedside, and should not be laboratory-based. Informed by reviews of the evidence, in 2017 WHO published a new definition of maternal sepsis based on the presence of suspected or confirmed infection. It also announced a Global Maternal and Neonatal Sepsis Initiative to identify the diagnostic criteria for the early identificati on, epidemiology, and disease classification of maternal sepsis. Standardizing the criteria for maternal sepsis optimizes clinical audit and research. It may facilitate the evaluation of the role of different clinical parameters and biomarkers in the diagnosis, earlier recognition and management of maternal infection and sepsis. Further work is required to develop an international consensus on the criteria for diagnosing maternal sepsis and any associated organ dysfunction.
  • Intramuscular versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery: randomised controlled trial.

    Adnan, Nita; Conlan-Trant, Rebecca; McCormick, Ciara; Boland, Fiona; Murphy, Deirdre J (BMJ, 2018-09-04)
    To determine whether intravenous oxytocin is more effective than intramuscular oxytocin at preventing postpartum haemorrhage at vaginal delivery. Double blind placebo controlled randomised trial. University affiliated maternity unit in the Republic of Ireland. 1075 women aged 18 years or older, at term with a singleton pregnancy who were aiming for a vaginal delivery with an actively managed third stage of labour.
  • Is birth weight the major confounding factor in the study of gestational weight gain?: an observational cohort study.

    O'Higgins, Amy C; Doolan, Anne; McCartan, Thomas; Mullaney, Laura; O'Connor, Clare; Turner, Michael J (BMC Pregnancy & Childbirth, 2018-06-07)
    Much interest has been focussed on both maternal obesity and gestational weight gain (GWG), particularly on their role in influencing birth weight (BW). Several large reviews have reported that excessive GWG is associated with an increase in BW Women were enrolled at their convenience before 18 weeks gestation. Height and weight were measured accurately at the first antenatal visit and BMI calculated. Maternal weight was measured again after 37 weeks gestation. The weight of the baby was measured at birth. Relationships were tested using linear regression analysis, chi-squared tests and t-tests as appropriate. Of the 522 women studied, the mean BMI was 25.3 kg/m The positive correlation between GWG in pregnancy and BW can be accounted for by the contribution of fetal weight to GWG antenatally without a contribution from increased maternal adiposity. There was a wide range of BW irrespective of the degree of GWG and obese women had a lower GWG than non-obese women. These findings help explain why Randomized Controlled Trials (RCTs) designed to reduce GWG have failed to decrease BW and suggest there is no causative link between excessive GWG and increased BW.
  • Maternal body mass index and the prevalence of spontaneous and elective preterm deliveries in an Irish obstetric population: a retrospective cohort study.

    Vinturache, Angela; McKeating, Aoife; Daly, Niamh; Sheehan, Sharon; Turner, Michael; Centre for Human Reproduction, University College Dublin, Coombe Women and Infants University Hospital, Dublin, Ireland (BMJ, 2017-10-15)
    To estimate the association between maternal body mass index (BMI) and risk of spontaneous preterm delivery (sPTD) and elective preterm delivery (ePTD) in singleton and multiple pregnancies. Retrospective cohort study. Electronic records of all deliveries from 2009 through 2013 in a tertiary university hospital were abstracted for demographic and obstetrical information. A total of 38 528 deliveries were included. Participants with missing data were excluded from the study. BMI was calculated from the measurement of height and weight at the first prenatal visit and categorised. Sonographic confirmation of gestational age was standard.
  • Intramuscular oxytocin versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery (LabOR trial): study protocol for a randomised controlled trial.

    Adnan, Nita; Boland, Fiona; Murphy, Deirdre J; Academic Department of Obstetrics and Gynaecology, Trinity College, University of Dublin & Coombe Women & Infants University Hospital, Dublin 8, Ireland/ Department of General Practice, Royal College of Surgeons in Ireland, Dublin 2, Ireland (Biomed Central, 2017-11-15)
    Primary postpartum haemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality worldwide. The most common cause of primary PPH is uterine atony. Atonic PPH rates are increasing in developed countries despite routine active management of the third stage of labour. In less-developed countries, primary PPH remains the leading cause of maternal death. Although the value of routine oxytocics in the third stage of labour has been well established, there is inconsistent practice in the choice of agent and route of administration. Oxytocin is the preferred agent because it has fewer side effects than other uterotonics with similar efficacy. It can be given intravenously or intramuscularly; however, to date, the most effective route of administering oxytocin has not been established. A double-blind randomised controlled trial is planned. The aim of the study is to compare the effects of an intramuscular bolus of oxytocin (10 IU in 1 mL) and placebo intravenous injection (1 mL 0.9% saline given slowly) with an intravenous bolus of oxytocin (10 IU in 1 mL given slowly over 1 min) and placebo intramuscular injection (1 mL 0.9% saline) at vaginal delivery. The study will recruit 1000 women at term (>36 weeks) with singleton pregnancies who are aiming for a vaginal delivery. The primary outcome will be PPH (measured blood loss ≥ 500 mL). A study involving 1000 women will have 80% power at the 5% two-sided alpha level, to detect differences in the proportion of patients with measured blood loss > 500 ml of 10% vs 5%. Given the increasing trends of atonic PPH it is both important and timely that we evaluate the most effective route of oxytocin administration for the management of the third stage of labour. To date, there has been limited research comparing the efficacy of intramuscular oxytocin vs intravenous oxytocin for the third stage of labour. ISRCTN Registry, ISRCTN14718882 . Registered on 4 January 2016. Pilot commenced 12.12.2015; trial commenced 04.01.2016. The protocol (Ref 012012) was approved by the National Maternity Hospital Research Ethics Committee on 10.06.2015 and the Research Ethics Committee of the Coombe Women & Infants University Hospital (Ref 26-2015) on 09.12.2015.
  • Screening For Gestational Diabetes Mellitus Selectively in a University Maternity Hospital

    O’Malley, EG; O’Duill, M; McArdle, C; Kennedy, RAK; Reynolds, CM; Turner, MJ (Irish Medical Journal, 2018-06)
    Gestational diabetes mellitus (GDM) is one of the commonest complications of pregnancy. The prevalence varies depending, for example, on the diagnostic criteria, the screening test used, laboratory standards and the population studied. However, the prevalence is increasing globally due to the increasing levels of maternal obesity. The detection of GDM is important because there are clinical consequences. The woman has an increased risk of pre-eclampsia and of developing Type 2 diabetes mellitus (T2DM) in later life. Up to 70% of those women with GDM develop T2DM by 28 years after the affected pregnancy2. In a pregnancy complicated by GDM there is an increased risk of fetal macrosomia and polyhydramnios due to fetal hyperglycaemia3. This is associated with an increased risk of shoulder dystocia and caesarean delivery4. Neonatal hypoglycaemia may develop due to increased insulin production secondary to intrauterine hyperglycaemia. The offspring also have an increased risk in their childhood and adult life for the development of diabetes, obesity and metabolic syndrome5.
  • Burden of Severe Respiratory Syncytial Virus Disease Among 33-35 Weeks' Gestational Age Infants Born During Multiple Respiratory Syncytial Virus Seasons.

    Anderson, Evan J; Carbonell-Estrany, Xavier; Blanken, Maarten; Lanari, Marcello; Sheridan-Pereira, Margaret; Rodgers-Gray, Barry; Fullarton, John; Rouffiac, Elisabeth; Vo, Pamela; Notario, Gerard; et al. (Wolters Kluwer Health, 2017-02)
    Moderate-late preterm infants, 33-35 weeks' gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants.
  • National Variation in Caesarean Section Rates: A Cross Sectional Study in Ireland.

    Sinnott, Sarah-Jo; Brick, Aoife; Layte, Richard; Cunningham, Nathan; Turner, Michael J (PLoS One, 2016)
    Internationally, caesarean section (CS) rates are rising. However, mean rates of CS across providers obscure extremes of CS provision. We aimed to quantify variation between all maternity units in Ireland.
  • Differences in nulliparous caesarean section rates across models of care: a decomposition analysis.

    Brick, Aoife; Layte, Richard; Nolan, Anne; Turner, Michael J (BMC health services research, 2016)
    To evaluate the extent of the difference in elective (ELCS) and emergency (EMCS) caesarean section (CS) rates between nulliparous women in public maternity hospitals in Ireland by model of care, and to quantify the contribution of maternal, clinical, and hospital characteristics in explaining the difference in the rates.
  • Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.

    Gasch, Claudia; Ffrench, Brendan; O'Leary, John J; Gallagher, Michael F (BioMed Central, 2017)
    It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.
  • Barriers and facilitators to implementing addiction medicine fellowships: a qualitative study with fellows, medical students, residents and preceptors.

    Klimas, J; Small, W; Ahamad, K; Cullen, W; Mead, A; Rieb, L; Wood, E; McNeil, R (Biomed Central, 2017)
    Although progress in science has driven advances in addiction medicine, this subject has not been adequately taught to medical trainees and physicians. As a result, there has been poor integration of evidence-based practices in addiction medicine into physician training which has impeded addiction treatment and care. Recently, a number of training initiatives have emerged internationally, including the addiction medicine fellowships in Vancouver, Canada. This study was undertaken to examine barriers and facilitators of implementing addiction medicine fellowships.
  • Aspirin In The Prevention Of Pre-Eclampsia: Where Are We Now?

    Khalid A,; Byrne, B M (Irish Medical Journal, 2018-03)
    Pre-eclampsia is a pregnancy specific multi-systemic disorder that causes maternal and perinatal morbidity and mortality worldwide. It is estimated to complicate between three to five percent of pregnancies and contributes to 8 to 10% of all preterm births1,2. Aspirin inhibits cyclooxygenase in platelets and endothelium in a fashion that alters the balance between the vasoconstrictor thromboxane and the vasodilator prostacyclin. This potentiates vasodilatation and reduces platelet aggregation, contributors to the endothelial dysfunction seen in preeclampsia. Over 100 clinical trials have examined whether or not Aspirin, when prescribed from early pregnancy, can prevent pre-eclampsia, and the consensus is that it reduces the incidence by approximately 10 to 24 % in women that are deemed to be at risk3,4.
  • The prevention of neural tube defects in Ireland

    McKeating, A; Turner, M.J (Irish Medical Journal, 2017-06)
  • A National Audit of Smoking Cessation Services in Irish Maternity Units

    Reynolds C.M.E.; Egan B; Cawley S; Kennedy , R; Sheehan S R; Turner M.J (Irish Medical Journal, 2017-06)
    There is international consensus that smoking cessation in the first half of pregnancy improves foetal outcomes. We surveyed all 19 maternity units nationally about their antenatal smoking cessation practices. All units recorded details on maternal smoking at the first antenatal visit. Only one unit validated the self-reported smoking status of pregnant women using a carbon monoxide breath test. Twelve units (63%) recorded timing of smoking cessation. In all units women who reported smoking were given verbal cessation advice. This was supported by written advice in 12 units (63%), but only six units (32%) had all midwives trained to provide this advice. Only five units (26%) reported routinely revisiting smoking status later in pregnancy. Although smoking is an important modifiable risk factor for adverse pregnancy outcomes, smoking cessation services are inadequate in the Irish maternity services and there are variations in practices between hospitals.
  • Team Objective Structured Bedside Assessment (TOSBA) as formative assessment in undergraduate Obstetrics and Gynaecology: a cohort study.

    Deane, Richard P; Joyce, Pauline; Murphy, Deirdre J (BioMed Central, 2015-10-09)
    Team Objective Structured Bedside Assessment (TOSBA) is a learning approach in which a team of medical students undertake a set of structured clinical tasks with real patients in order to reach a diagnosis and formulate a management plan and receive immediate feedback on their performance from a facilitator. TOSBA was introduced as formative assessment to an 8-week undergraduate teaching programme in Obstetrics and Gynaecology (O&G) in 2013/14. Each student completed 5 TOSBA sessions during the rotation. The aim of the study was to evaluate TOSBA as a teaching method to provide formative assessment for medical students during their clinical rotation. The research questions were: Does TOSBA improve clinical, communication and/or reasoning skills? Does TOSBA provide quality feedback?
  • Aspirin and P2Y12 inhibition attenuate platelet-induced ovarian cancer cell invasion.

    Cooke, Niamh M; Spillane, Cathy D; Sheils, Orla; O'Leary, John; Kenny, Dermot (BioMed Central, 2015-09-09)
    Platelet-cancer cell interactions play a key role in successful haematogenous metastasis. Disseminated malignancy is the leading cause of death among ovarian cancer patients. It is unknown why different ovarian cancers have different metastatic phenotypes. To investigate if platelet-cancer cell interactions play a role, we characterized the response of ovarian cancer cell lines to platelets both functionally and at a molecular level.
  • Endosomal gene expression: a new indicator for prostate cancer patient prognosis?

    Johnson, Ian R D; Parkinson-Lawrence, Emma J; Keegan, Helen; Spillane, Cathy D; Barry-O'Crowley, Jacqui; Watson, William R; Selemidis, Stavros; Butler, Lisa M; O'Leary, John J; Brooks, Doug A (Impact Publishers, 2015-11-10)
    Prostate cancer continues to be a major cause of morbidity and mortality in men, but a method for accurate prognosis in these patients is yet to be developed. The recent discovery of altered endosomal biogenesis in prostate cancer has identified a fundamental change in the cell biology of this cancer, which holds great promise for the identification of novel biomarkers that can predict disease outcomes. Here we have identified significantly altered expression of endosomal genes in prostate cancer compared to non-malignant tissue in mRNA microarrays and confirmed these findings by qRT-PCR on fresh-frozen tissue. Importantly, we identified endosomal gene expression patterns that were predictive of patient outcomes. Two endosomal tri-gene signatures were identified from a previously published microarray cohort and had a significant capacity to stratify patient outcomes. The expression of APPL1, RAB5A, EEA1, PDCD6IP, NOX4 and SORT1 were altered in malignant patient tissue, when compared to indolent and normal prostate tissue. These findings support the initiation of a case-control study using larger cohorts of prostate tissue, with documented patient outcomes, to determine if different combinations of these new biomarkers can accurately predict disease status and clinical progression in prostate cancer patients.
  • Neonatal Brachial Plexus Palsy and Causation

    Turner, M J; Farren, M (Irish Medical Journal, 2016-07)
    A vaginal childbirth is the result of the internal (endogenous) expulsive forces of uterine contractions, usually supplemented by active maternal pushing1. Depending on the clinical circumstances, additional external (exogenous) traction forces may be required from the birth attendant. This blend of internal and external forces varies from birth to birth. Women who have had a previous vaginal delivery, for example, may deliver successfully with uterine contractions alone and the role of the birth attendant may be simply to control and slow the delivery so that trauma to the maternal perineum from stretching by the fetal head is minimised. In contrast, additional traction may be required by an obstetrician at the time of an operative vaginal delivery for fetal distress or dystocia. The strength of the traction required may be increased by clinical factors, for example, fetal macrosomia or malposition. The traction should be axial in the direction of the birth canal, which is a vector combining horizontal and vertical traction at 25-45 degrees below the horizontal when the woman is in the lithotomy position.
  • Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer.

    McEvoy, Lynda M; O'Toole, Sharon A; Spillane, Cathy D; Martin, Cara M; Gallagher, Michael F; Stordal, Britta; Blackshields, Gordon; Sheils, Orla; O'Leary, John J (Springer, 2015)
    Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1α. While HIF-1α has been associated with platinum resistance in a variety of cancers, including ovarian, relatively little is known about the importance of the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer which cause chemoresistance as a result of hypoxia are poorly understood. This study aimed to firstly investigate the effect of hypoxia duration on resistance to cisplatin in an ovarian cancer chemoresistance cell line model and to identify genes whose expression was associated with hypoxia-induced chemoresistance.

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