• Activation of a TLR9 mediated innate immune response in preeclampsia.

      Williamson, Rachel D; McCarthy, Fergus P; Kenny, Louise C; McCarthy, Cathal M (Scientific Reports, 2019-04-11)
      Preeclampsia is a multisystemic disorder leading to the development of a placental ischemic microenvironment with a resultant increase in oxidative stress. There is evidence that mitochondrial dysfunction and the innate immune system both play a role in the pathophysiology of this disease. Mitochondrial DAMPs such as mtDNA bind specifc pattern recognition receptors such as Toll-like receptor 9 (TLR9) on the endosomal surface of immune cells, in particular neutrophils, subsequently activating them and triggering an innate response. We hypothesised that the exaggerated innate immune response seen in preeclampsia is provoked by dysfunctional mitochondria. Here we provide evidence that TLR9 activity is signifcantly increased at time of disease in women with preeclampsia. Furthermore, we show activation of neutrophil markers, Calprotectin, Myeloperoxidase (MPO), and IL-8 are signifcantly increased at time of disease compared to uncomplicated pregnancies. This research supports a potential role of TLR9 activation of an innate immune response evident in preeclampsia which may possibly be initially triggered by dysfunctional mitochondria.
    • Animal models of preeclampsia; uses and limitations.

      McCarthy, F P; Kingdom, J C; Kenny, L C; Walsh, S K; Anu Research Centre, Department of Obstetrics & Gynaecology, University College, Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland., fergusmccarthy@gmail.com (2012-01-31)
      Preeclampsia remains a leading cause of maternal and fetal morbidity and mortality and has an unknown etiology. The limited progress made regarding new treatments to reduce the incidence and severity of preeclampsia has been attributed to the difficulties faced in the development of suitable animal models for the mechanistic research of this disease. In addition, animal models need hypotheses on which to be based and the slow development of testable hypotheses has also contributed to this poor progress. The past decade has seen significant advances in our understanding of preeclampsia and the development of viable reproducible animal models has contributed significantly to these advances. Although many of these models have features of preeclampsia, they are still poor overall models of the human disease and limited due to lack of reproducibility and because they do not include the complete spectrum of pathophysiological changes associated with preeclampsia. This review aims to provide a succinct and comprehensive assessment of current animal models of preeclampsia, their uses and limitations with particular attention paid to the best validated and most comprehensive models, in addition to those models which have been utilized to investigate potential therapeutic interventions for the treatment or prevention of preeclampsia.
    • Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant.

      McCarthy, Fergus P; Giles, Michelle L; Rowlands, Shelley; Purcell, Kara J; Jones, Cheryl A; Anu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland. (2012-01-31)
      BACKGROUND: Cytomegalovirus (CMV) is a herpesvirus and the most common cause of congenital infection in developed countries. Congenital CMV infection can have devastating consequences to the fetus. The high incidence and the serious morbidity associated with congenital CMV infection emphasise the need for effective interventions to prevent the antenatal transmission of CMV infection. OBJECTIVES: The aim of this review was to assess the benefits and harms of interventions used during pregnancy to prevent mother to fetus transmission of CMV infection. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2010). SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi RCTs investigating antenatal interventions for preventing the transmission of CMV from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion. MAIN RESULTS: We identified six studies from the search. None of these studies met the pre-defined criteria for inclusion in this review. AUTHORS' CONCLUSIONS: To date, no RCTs are available that examine antenatal interventions for preventing the transmission of CMV from the infected mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Further research is needed to assess the efficacy of interventions aimed at preventing the transmission of CMV from the mother to fetus during pregnancy including a long-term follow-up of exposed infants and a cost effective analysis.
    • Antenatal management of the expectant mother and extreme preterm infant at the limits of viability.

      Khan, R; Burgoyne, L; O'Connell, M; Dempsey, E M; Neonatal Intensive Care Unit, Cork University Maternity Hospital, Wilton, Cork. (2012-01-31)
      We explored the opinions of healthcare providers on the antenatal management and outcome of preterm delivery at less than 28 weeks gestation. An anonymous postal questionnaire was sent to health care providers. The response rate was 55% (74% Obstetrician, 70% neonatologist). Twenty four weeks is the limit at which most would advocate intervention. At 23 weeks 67% of neonatologists advocate antenatal steroids. 50% of all health care providers advocate cardiotocographic monitoring at 24 weeks gestation. Written information on survival and long-term outcome is provided by 8% of the respondents. Neonatologists (50%) were more likely than obstetrician (40%) to advocate caesarean section at 25 weeks. We conclude that 24 weeks is the limit at which most would advocate intervention. Significant variation exists both between and within each health care group at less than 25 weeks. Establishment and provision of national outcome data may aid decision making at the limits of viability.
    • Are fathers underused advocates for breastfeeding?

      Kenosi, M; Hawkes, C P; Dempsey, E M; Ryan, C A (Irish Medical Journal (IMJ), 2011-11)
      Fathers' knowledge base and attitudes influence breastfeeding practice. We aimed to evaluate if Irish fathers felt included in the breastfeeding education and decision process. 67 fathers completed questionnaires, which assessed their role in the decision to breastfeed, knowledge regarding the benefits of breastfeeding and attitude towards breastfeeding.Forty-two (62.7%) of their partners were breastfeeding. Antenatal classes were attended by 38 (56.7%); 59 (88.1%) discussed breastfeeding with their partners and 26 (38.8%) felt that the decision was made together. Twelve (48%) fathers of formula fed infants were unaware that breastfeeding was healthier for the baby. Most fathers (80.6%) felt that breastfeeding was the mother's decision and most (82.1%) felt that antenatal information was aimed at mothers only. Irish fathers remain relatively uninformed regarding the benefits of breastfeeding. This may contribute to their exclusion from the decision to breastfeed. Antenatal education should incorporate fathers more, and this may result in an improvement in our breastfeeding rates.
    • At what price? A cost-effectiveness analysis comparing trial of labour after previous Caesarean versus elective repeat Caesarean delivery.

      Fawsitt, Christopher G; Bourke, Jane; Greene, Richard A; Everard, Claire M; Murphy, Aileen; Lutomski, Jennifer E; National Perinatal Epidemiology Centre, Cork, Ireland ; School of Economics, University College Cork, Cork, Ireland. (2013)
      Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland.
    • Banked preterm versus banked term human milk to promote growth and development in very low birth weight infants.

      Dempsey, Eugene; Miletin, Jan; Neonatology, Cork University Maternity Hospital, Cork, Ireland. (2012-01-31)
      BACKGROUND: Human milk banking has been available in many countries for the last three decades. The milk provided from milk banking is predominantly term breast milk, but some milk banks provide preterm breast milk. There are a number of differences between donor term and donor preterm human milk. OBJECTIVES: To determine the effect of banked preterm milk compared with banked term milk regarding growth and developmental outcome in very low birth weight infants (infants weighing less than 1500 g). SEARCH STRATEGY: We used the standard methods of the Cochrane Neonatal Review Group, including a search of the Cochrane Neonatal Group specialized register and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, January 2010). We searched the computerised bibliographic databases MEDLINE (1966 to February 2010), EMBASE (1988 to February 2010) and Web of Science (1975 to February 2010). We searched reference lists of all selected articles, review articles and the Oxford Database of Perinatal Trials. We also searched abstracts from neonatal and pediatric meetings (PAS electronic version from 2000 to 2009, ESPR hand search from 2000 to 2009). We applied no language restrictions. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing banked donor preterm milk with banked donor term milk regarding growth and developmental outcomes in very low birth weight infants DATA COLLECTION AND ANALYSIS: We planned to perform assessment of methodology regarding blinding of randomisation, intervention and outcome measurements as well as completeness of follow-up. We planned to evaluate treatment effect using a fixed-effect model using relative risk (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT) for categorical data and using mean, standard deviation and weighted mean difference (WMD) for continuous data. We planned an evaluation of heterogeneity. MAIN RESULTS: No studies met the inclusion criteria. AUTHORS' CONCLUSIONS: There are no randomised trials that compare preterm banked milk to banked term milk to promote growth and development in very low birth weight infants.
    • Benchmarking care for very low birthweight infants in Ireland and Northern Ireland.

      Murphy, B P; Armstrong, K; Ryan, C A; Jenkins, J G; Department of Neonatology, Cork University Maternity Hospital, Wilton, Cork,, Ireland. brendanpaul.murphy@hse.ie (2012-01-31)
      BACKGROUND: Benchmarking is that process through which best practice is identified and continuous quality improvement pursued through comparison and sharing. The Vermont Oxford Neonatal Network (VON) is the largest international external reference centre for very low birth weight (VLBW) infants. This report from 2004-7 compares survival and morbidity throughout Ireland and benchmarks these results against VON. METHODS: A standardised VON database for VLBW infants was created in 14 participating centres across Ireland and Northern Ireland. RESULTS: Data on 716 babies were submitted in 2004, increasing to 796 babies in 2007, with centres caring for from 10 to 120 VLBW infants per year. In 2007, mortality rates in VLBW infants varied from 4% to 19%. Standardised mortality ratios indicate that the number of deaths observed was not significantly different from the number expected, based on the characteristics of infants treated. There was no difference in the incidence of severe intraventricular haemorrhage between all-Ireland and VON groups (5% vs 6%, respectively). All-Ireland rates for chronic lung disease (CLD; 15-21%) remained lower than rates seen in the VON group (24-28%). The rates of late onset nosocomial infection in the all-Ireland group (25-26%) remained double those in the VON group (12-13%). DISCUSSION: This is the first all-Ireland international benchmarking report in any medical specialty. Survival, severe intraventricular haemorrhage and CLD compare favourably with international standards, but rates of nosocomial infection in neonatal units are concerning. Benchmarking clinical outcomes is critical for quality improvement and informing decisions concerning neonatal intensive care service provision.
    • Blood carbon dioxide levels and adverse outcome in neonatal hypoxic-ischemic encephalopathy.

      Nadeem, Montasser; Murray, Deirdre; Boylan, Geraldine; Dempsey, Eugene M; Ryan, C Anthony; Neonatal Intensive Care Unit, Cork University Maternity Hospital, Cork, Ireland. (2012-01-31)
      We investigated pCO(2) patterns and the relationship between pCO(2) levels and neurodevelopmental outcome in term infants with hypoxic-ischemic encephalopathy. Blood gases during the first 72 hours of life were collected from 52 infants with hypoxic-ischemic encephalopathy. Moderate hypocapnia (pCO(2) <3.3 kPa), severe hypocapnia (pCO(2) <2.6 kPa), and hypercapnia (pCO(2) >6.6 kPa) were correlated to neurodevelopmental outcome at 24 months. Normocapnia was documented in 416/551 (75.5%) of samples and was present during the entire 72 hours in only 6 out of 52 infants. Mean (standard deviation) pCO(2) values did not differ between infants with normal and abnormal outcomes: 5.43 (2.4) and 5.41 (2.03), respectively. There was no significant association between moderate hypocapnia, severe hypocapnia, or hypercapnia and adverse outcome (odds ratio [OR] = 1.84, 95% confidence interval [CI] = 0.49 to 6.89; OR = 3.16, CI = 0.14 to 28.45; and OR = 1.07, CI = 0.24 to 5.45, respectively). In conclusion, only one in nine newborns had normocapnia throughout the first 72 hours. Severe hypocapnia was rare and occurred only in ventilated babies. Hypercapnia and hypocapnia in infants with hypoxic-ischemic encephalopathy during the first 72 hours of life were not associated with adverse outcome.
    • Changes in the metabolic footprint of placental explant-conditioned medium cultured in different oxygen tensions from placentas of small for gestational age and normal pregnancies.

      Horgan, R P; Broadhurst, D I; Dunn, W B; Brown, M; Heazell, A E P; Kell, D B; Baker, P N; Kenny, L C; Department of Obstetrics and Gynaecology, University College Cork, Cork, University Maternity Hospital, The Anu Research Centre, Cork, Ireland., richard.horgan@ucc.ie (2012-01-31)
      Being born small for gestational age (SGA) confers significantly increased risks of perinatal morbidity and mortality. Accumulating evidence suggests that an SGA fetus results from a poorly perfused and abnormally developed placenta. Some of the placental features seen in SGA, such as abnormal cell turnover and impaired nutrient transport, can be reproduced by culture of placental explants in hypoxic conditions. Metabolic footprinting offers a hypothesis-generating strategy to investigate factors absorbed by and released from this tissue in vitro. Previously, metabolic footprinting of the conditioned culture media has identified differences in placental explants cultured under normoxic and hypoxic conditions and between normal pregnancies and those complicated by pre-eclampsia. In this study we aimed to examine the differences in the metabolic footprint of placental villous explants cultured at different oxygen (O(2)) tensions between women who deliver an SGA baby (n = 9) and those from normal controls (n = 8). Placental villous explants from cases and controls were cultured for 96 h in 1% (hypoxic), 6% (normoxic) and 20% (hyperoxic) O(2). Metabolic footprints were analysed by Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap Mass Spectrometry (UPLC-MS). 574 metabolite features showed significant difference between SGA and normal at one or more of the oxygen tensions. SGA explant media cultured under hypoxic conditions was observed, on a univariate level, to exhibit the same metabolic signature as controls cultured under normoxic conditions in 49% of the metabolites of interest, suggesting that SGA tissue is acclimatised to hypoxic conditions in vivo. No such behaviour was observed under hyperoxic culture conditions. Glycerophospholipid and tryptophan metabolism were highlighted as areas of particular interest.
    • Child Mortality as Predicted by Nutritional Status and Recent Weight Velocity in Children under Two in Rural Africa.

      National Perinatal Epidemiology Center, Anu Research Center, Department of, Obstetrics and Gynecology, Cork University Maternity Hospital, Wilton, Cork,, Ireland. (2012-01-31)
      WHO has released prescriptive child growth standards for, among others, BMI-for-age (BMI-FA), mid-upper arm circumference-for-age, and weight velocity. The ability of these indices to predict child mortality remains understudied, although growth velocity prognostic value underlies current growth monitoring programs. The study aims were first to assess, in children under 2, the independent and combined ability of these indices and of stunting to predict all-cause mortality within 3 mo, and second, the comparative abilities of weight-for-length (WFL) and BMI-FA to predict short-term (<3 mo) mortality. We used anthropometry and survival data from 2402 children aged between 0 and 24 mo in a rural area of the Democratic Republic of Congo with high malnutrition and mortality rates and limited nutritional rehabilitation. Analyses used Cox proportional hazard models and receiver operating characteristic curves. Univariate analysis and age-adjusted analysis showed predictive ability of all indices. Multivariate analysis without age adjustment showed that only very low weight velocity [HR = 3.82 (95%CI = 1.91, 7.63); P < 0.001] was independently predictive. With age adjustment, very low weight velocity [HR = 3.61 (95%CI = 1.80, 7.25); P < 0.001] was again solely retained as an independent predictor. There was no evidence for a difference in predictive ability between WFL and BMI-FA. This paper shows the value of attained BMI-FA, a marker of wasting status, and recent weight velocity, a marker of the wasting process, in predicting child death using the WHO child growth standards. WFL and BMI-FA appear equivalent as predictors.
    • Communication skills in Obstetrics: what can we learn from bereaved parents?

      Nuzum, D; Meaney,S; O’Donoghue, K (Irish Medical Journal, 2017-02)
      Communicating bad news in obstetrics is challenging. This study explores the impact of how bad news was communicated to parents following a diagnosis of stillbirth. Qualitative in-depth interviews were conducted with 12 mothers and 5 fathers, bereaved following stillbirth at a tertiary maternity hospital where the perinatal mortality rate is 5.2/1000. Data were analysed using Interpretative Phenomenological Analysis. How the diagnosis of stillbirth was communicated had a profound and lasting impact on parents. Dominant superordinate themes were Language used, Sensitivity and Diversionary techniques. Parents recalled in detail where and how bad news was broken and language used. Diversionary techniques created a sense of mistrust especially when parents felt information was being withheld. Bereaved parents valued privacy at the time of diagnosis of stillbirth.This study highlights the importance of language, sensitivity and environment where clinicians can learn from the experiences of bereaved parents who value open, sensitive and honest communication. The results of this study highlight the importance of patient-focused communication training for clinicians.
    • Comorbid depression and risk of lower extremity amputation in people with diabetes: systematic review and meta-analysis.

      O'Neill, Sinéad M; Kabir, Zubair; McNamara, Grace; Buckley, Claire Mary (BMJ open diabetes research & care, 2017-08)
      To compare the risk of lower extremity amputation (LEA) in people with diabetes with and without comorbid depression.
    • Comparison of the T-piece resuscitator with other neonatal manual ventilation devices: A qualitative review.

      Department of Neonatology, Cork University Maternity Hospital, Ireland;, Department of Paediatrics and Child Health, University College Cork, Ireland. (2012-01-31)
      AIM: To review the literature surrounding various aspects of T-piece resuscitator use, with particular emphasis on the evidence comparing the device to other manual ventilation devices in neonatal resuscitation. DATA SOURCES: The Medline, EMBASE, Cochrane databases were searched in April 2011. Ongoing trials were identified using www.clinicaltrials.gov and www.controlled-trials.com. Additional studies from reference lists of eligible articles were considered. All studies including T-piece resuscitator use were eligible for inclusion. RESULTS: Thirty studies were included. There were two randomised controlled trials in newborn infants comparing the devices, one of which addressed short and intermediate term morbidity and mortality outcomes and found no difference between the T-piece resuscitator and self inflating bag. From manikin studies, advantages to the T-piece resuscitator include the delivery of inflating pressures closer to predetermined target pressures with least variation, the ability to provide prolonged inflation breaths and more consistent tidal volumes. Disadvantages include a technically more difficult setup, more time required to adjust pressures during resuscitation, a larger mask leak and less ability to detect changes in compliance. CONCLUSIONS: There is a need for appropriately designed randomised controlled trials in neonates to highlight the efficacy of one device over another. Until these are performed, healthcare providers should be appropriately trained in the use of the device available in their departments, and be aware of its own limitations.
    • Compliance with National Institute of Health and Care Excellence risk-based screening for gestational diabetes mellitus in nulliparous women.

      Murphy, Nicolai M; McCarthy, Fergus P; Khashan, Ali S; Myers, Jenny E; Simpson, Nigel A B; Kearney, Patricia M; Greene, Richard A; Poston, Lucilla; Kenny, Louise C (European journal of obstetrics, gynecology, and reproductive biology, 2016-04)
      To investigate compliance with risk-based screening for Gestational Diabetes Mellitus (GDM) in a nulliparous cohort.
    • Consent for routine neonatal procedures: A study of practices in Irish neonatal units. How do we compare with the gold standard BAPM guidelines?

      Ryan, M A; Ryan, C A; Dempsey, E; O’Connell, R (Irish Medical Journal, 2017-06)
      The Irish National Consent Policy (NCP)¹ proposes that the legal requirement for consent extends to all forms of interventions, investigations and treatment, carried out on or behalf of the Health Service Executive (HSE). This study employs a quantitative descriptive approach to investigate the practices for obtaining consent for an identified group of routine neonatal procedures in neonatal facilities throughout Ireland. The BAPM (British Association of Perinatal Medicine)² guidelines were identified as ‘gold standard’ for the purposes of this study. The results indicated a lack of consistency between participating units pertaining to the modes of consent utilised and notable variances from ‘gold standard’ guidelines. Unanimity was evident for 3 procedures only (administering BCG, 6-in-1, and donor breast milk to infant). Significant findings related to EEG with video recordings, MRI/CT and gastro intestinal imaging, screening of an infant with suspected substance abuse or retinopathy of prematurity screening (ROP), administration of Vitamin K, and the carrying out of a lumbar puncture.
    • The decline of hysterectomy for benign disease.

      Horgan, R P; Burke, G; The Anu Research Centre, Department of Obstetrics and Gynaecology, University, College Cork, Cork University Maternity Hospital, Wilton, Cork., richard.horgan@ucc.ie (2012-01-31)
      Hysterectomy is one of the most common gynaecological surgical procedures performed but there appears to be a decline in the performance of this procedure in Ireland in recent times. We set out to establish the extent of the decline of hysterectomy and to explore possible explanations. Data for hysterectomy for benign disease from Ireland was obtained from the Hospital In-Patient Enquiry Scheme (HIPE) section of the Economic and Social Research Institute for the years 1999 to 2006. The total number of hysterectomies performed for benign disease showed a consistent decline during this time. There was a 36% reduction in the number of abdominal hysterectomy procedures performed.
    • Development and psychometric testing of the clinical leadership needs analysis (CLeeNA) instrument for nurses and midwives.

      Mc Carthy, Vera J C; Murphy, Ashling; Savage, Eileen; Hegarty, Josephine; Coffey, Alice; Leahy-Warren, Patricia; Horgan, Aine; O'Connell, Rhona; Marsh, Lynne; Drennan, Jonathan (Journal of Nursing Management, 2018-08-31)
      The aim of this study is to report the development and psychometric testing of the clinical leadership needs analysis instrument (CLeeNA). Limited emphasis is placed on the clinical leadership needs of nurses and midwives that are fundamental to supporting the delivery of high quality, safe patient care. A development and validation study of CLeeNA was undertaken using cross-sectional data. A sample of 324 registered nurses and midwives completed the questionnaire using a 7-point adjectival scale. Principal component analysis was conducted to explore scale grouping of items (n = 103 items). Principal component analysis, item reduction and parallel analysis on the items of the instrument resulted in seven factors consisting of 56 items. These factors were identified as: Staff and Care Delivery; Technology and Care Initiatives; Self and Team Development; Standards of Care; Financial and Service Management; Leadership and Clinical Practice; Patient Safety and Risk Management.
    • A disappearing neonatal skin lesion.

      Hawkes, Colin Patrick; Bourke, John Francis; Fitzgibbon, James; Dempsey, Eugene Michael; Department of Neonatology, Cork University Maternity Hospital, Cork, Ireland. (2012-01-31)
      A preterm baby girl was noted at birth to have a firm, raised, non-tender skin lesion located over her right hip. She developed three similar smaller lesions on her ear, buttock and right knee. All lesions had resolved by 2 months of age.
    • Does caesarean delivery prevent anal incontinence?

      McLoughlin, Geraldine; Catherine McAuley School of Nursing and Midwifery University College Cork, Ireland. (2011-05)