- The Irish Childhood Diabetes National Register (ICDNR)
The National Register of Type 1 Diabetes in Childhood and adolescence was established in January 2008 by Professor Edna Roche in the Discipline of Paediatrics of the University of Dublin with the support ofTallaght Hospital. It collaborates with all paediatric endocrinologists, paediatricians and diabetes nurses and paediatric centres nationally caring for those with Type 1 diabetes. The ICDNR collaborates nationally and internationally with adult endocrinologists, the Irish endocrine society, the NI Diabetes Register and Eurodiab. The ICDNR provides accurate and robust data regarding epidemiology in Type 1 diabetes supporting research, clinical care and health planning.
Principal Investigator: Professor Edna Roche
Research Nurse: Ms Amanda McKenna RN (Child and Adult), MSc
Collaborators and Steering Group: Professor Hilary Hoey, Professor Myra O'Regan, Ms Kerry Ryder, Ms Helen Fitzgerald (ANP), Ms Amanda McKenna.
Funding Agency: The National Children's Hospital Foundation.
- Downloadable Forms here
The Irish Childhood Diabetes National Register is a full Member of and participant in the epidemiological research studies of the Eurodiab group, an international collaboration of diabetes registers.
- National DKA Prevention Campaign
Diabetic Ketoacidosis (DKA) is a severe potentially fatal metabolic decompensation that can occur in Type 1 diabetes, particularly at disease onset. The presence of DKA at disease diagnosis is now thought to have long term implications for disease outcome and its prevention is an important therapeutic target.
The ICDNR in collaboration with Diabetes Ireland and the Institute of Technology, Tallaght are leading a multicomponent broad based National DKA Prevention Campaign.
- The Hvidoere International Childhood Diabetes Study Group
The Hvidore Study Group is an international group of paediatric endocrinologists /diabetologists
covering paediatric centres from 18 countries across Europe, Japan and North America. Its aim is to share and compare data with the overall objective of improving the treatment of childhood diabetes. The group undertake international multicentre studies in childhood diabetes. Professors Hilary Hoey and Edna Roche are members of the Hvidore Group and Professor Roche sits on the Hvidoere Steering Group. The National Children's Hospital, Tallaght is the Irish centre in the Hvidore study group. We participate in a range of international collaborative studies in Type 1 diabetes, such as, metabolic control and quality of life and the longitudinal study of the remission phase in type 1 diabetes.
A significant number of international research projects have been completed and more are in progress from this group, these include: a longitudinal study of metabolic control, immunological markers, molecular aspects and quality of life on over 2,000 children from 22 countries around the world, including Europe, North America, Australia and Japan. Including the development of international quality of life instruments for children, adolescents, parents and health professionals caring for young people with diabetes, led by Professor Hilary Hoey who developed these new international quality of life instruments in collaboration with Professor Hannah McGee, RCSI; and Professor Michael Fitzgerald, TCD for the assessment of Quality of life in adolescent with diabetes and Quality of Life and family burden of parents of children with diabetes. These questionnaires have been translated into 17 languages and the ongoing research is being conducted in 22 international centres in Europe, North America, Australia and Japan.
Paediatric Endocrinology, Growth and Development
- Childhood Growth
International Trial of Small for gestational age infants Northern European Small for Gestational Age Study (NESGAS) and Nesgas Extension studies; The Discipline of Paediatrics in the National Children's Hospital in Tallaght is the Irish centre for the North European International Trial of Children Born Small for Gestational Age (NESGAS Study). NESGAS is an international, multi-centre, randomised paediatric clinical trial on the efficacy and safety of Growth Hormone treatment in children born small for gestational children (SGA) without catch up growth. This is an international collaboration of the Universities of Copenhagen, Dublin, Cambridge, Birmingham, Manchester, Glasgow and Stockholm. This extensive longitudinal study commenced in 2005 is providing key insights into growth, development, insulin sensitivity, body composition, genetics and bone health in those born SGA. We are directing the bone health component of this study.
Principal Investigator: Professor Edna Roche and Professor Hilary Hoey
Trial Co-ordinator and Research Nurse: Ms Elaine O'Mullane RGN, RM
Funding Agency: Unrestricted Grant from Novo Nordisk
- GROWTH - 1OS International Outcome Study
lnteiriational Study of the efficacy, safety and side effects of Growth Hormone treatment in childhood and adolescence.
Principal Investigator: Professor Edna Roche
Research Nurse: Ms Elaine O'Mullane RGN, RM
Funding Agency: Novo Nordisk
- The Irish National Growth Standards were developed by Professor Hilary Hoey based on data from over 7,000 Irish children. These include standards on height, weight and height velocity from birth to 18 years and also standards for skinfold thickness and head circumference. These standards are now applied throughout the country in primary, secondary and tertiary care. The Department let the Irish component of the European Longitudinal growth study on children from birth to 3 years to evaluate the effects of feeding, socio-economic environment, disease, genetic and geographical determinants, serum zinc on growth and the construction of European growth standards was performed by the department of paediatrics.
- Growing Up in Ireland
The Discipline of Paediatrics is a key participant and contributed to the development of the proposal and protocol in the Growing up in Ireland National Longitudinal Study of Children which is being undertaken jointly by the University of Dublin, Trinity College and the Economic and Social Research Institute of Ireland co-directed by Professor James Williams, ESRI and Professor Sheila Greene, Professor of Childhood Research and Director of the Children's Research Centre at Trinity College with the health component led by Professor Tom O'Dowd.
- Prader Willi Syndrome
The National Children's Hospital is the main tertiary centre delivering care to children and adolescents with the rare condition of Prader Willi Syndrome led by Professor Edna Roche, a large cohort attend the academic clinical PWS service. This care is delivered in innovative age banded multidisciplinary dedicated PWS clinics with support and collaboration from paediatric endocrinology nursing, paediatric psychology, physiotherapy, speech and Language therapy, dietetics, respiratory, orthopaedics, ENT and paediatric dentistry. Dr Judith Meehan has undertaken an extensive study of children with Prader Willi Syndrome exploring management, efficacy and safety of growth hormone, body composition, quality of life and family burden. There is close collaboration with the adult endocrinology service led by Professor James Gibney and life-long care with on-site collaborative transition of care. Extensive Prader Willi Syndrome research is in progress to improve clinical care and outcomes. A major report regarding PWS in Ireland has been prepared in collaboration with Professor Louise Gallagher, TCD. The current research focus is on growth, body composition, orthopaedic issues, associated endocrinopathy, service need and healthcare utilisation, and treatment outcome.
The National Children's Hospital Foundation has provided funding to support a dedicated dietitian to the service and Pfizer healthcare has provided an unrestricted grant to support the clinical service.
- Turner's Syndrome
A large cohort of patients with Turner Syndrome, attend the academic clinical Turner Syndrome service in dedicated clinics. Research areas include: Growth, Puberty, Bone Health and Quality of Life in Turner Syndrome.
Principal Investigator: Professor Edna Roche
Researcher: Dr Montasser Nadeem
A further study exploring endothelial dysfunction in Turner Syndrome is due to commence in 2018, in collaboration with Professor Clodagh O'Gorman, University of limerick and Dr Declan Cody, OLCHC.
- Down syndrome registry: Children with DS can experience a wide variety of associated health conditions resulting in avoidable secondary disability and chronic health problems. Despite probably the highest rate of DS
worldwide, no robust data exist to inform services or clinical care for those with DS. To meet this need with the support of Down Syndrome Ireland and the National Children's Hospital Foundation we developed the unique National Register for DS, which incorporates a prospective study. The
Register will provide for the first time accurate data to inform appropriate healthcare planning and clinical audit, permitting monitoring of the MMG implementation nationally.
Principal Investigator: Professor Edna Roche (Chair), Professor Eleanor Molloy
Research Nurse: Ms Fiona McGrane RGN
Funding Agency: National Children's Hospital Foundation
- DISCO project: Down Syndrome Inflammation and Systemic Multiorgan Outcomes
This project will explore multiorgan dysfunction focussing on immunodeficiency and altered immune cell responses in children with DS and will commence in 2017 with funding from National Childrens Hospital Foundation. (2017-20)
- DREAM project: This project will explore multiorgan dysfunction including cardiac, haematological, endocrine and GI issues and their composite association with neurodevelopmental outcome in children with DS. (2017-20)
- National Clinical Guidelines: We have established a National Resource Centre with extensive international research projects on Down Syndrome which have been performed by Dr Joan Murphy. The Discipline has undertaken the definitive national study of children and young people with Down syndrome and established national medical guidelines for this group. The Discipline of Paediatrics co-hosted the World Congress on Down Syndrome in Dublin in July 2009, of which Professor Hoey was Chairman of the Scientific Committee and Dr Joan Murphy Honorary Secretary. Professor Roche and Ms Fiona McGrane are members of the steering committee of the Down's Syndrome Medical Interest Group of Ireland and UK (DSMIG).
- Downloadable Forms here
PROSPER: PaediatRic Otcomes and Serum biomarker Panel in acutE
traumatic bRain injury /concussion to severe traumatic brain injury (2017-20)
Supervisors: Prof Molloy and Dr. Turlough Bolger.
Collaborators: Dr. Stan Koe, Dr. Ciara Martin, Dr. David Webb, Dr. John McHugh, Dr. Roisin McNamara, Dr. Ike Ofakor, Mr. John Caird & Mr. Darrach Crimmins, Dr Veronica O'Keane, Dr. Carol Blackburn, Dr. Michael Barrett & Dr. Sean Walsh, Dr. Aisling Snow, Prof. Cathal Moran, Prof. Arun Bodke , Prof. Jim Meaney, Prof Louise Gallagher
PhD student: Dr. Emer Ryan
Institutions: CUH, Tallaght, OLCH, NMH, TCD
Traumatic brain injury (TBI) is more common in childhood and adolescence than at any other time of life and is one of the most common causes of neurological morbidity and includes concussion. Post concussion syndrome (PCS) combines clinical, cognitive and behavioral symptoms and occurs in one in seven school children sustaining an TBI for three months or longer and is associated with persistent inflammation. At present there are no evidence-based clinical guidelines or accurate early tests to predict PCS in children. We aim to prospectively evaluate novel clinical and biochemical markers neurocognitive function at presentation in the Emergency department and at 6 weeks in children presenting with TBI. We will study the evolution of systemic inflammation associated with traumatic brain injury and correlate with neurocognitive and neuroimaging outcomes. In addition a subgroup of children with TBI and age-matched controls will have 3T MRI performed in SJH by a specialized team with expertise in functional MRI. To complement this project we will retrospectively review the records of children with TBI admitted to the Dublin EDs over a 2 year period to quantify the number of cases with moderate, mild and severe symptoms as well as PCS. Children with severe TBI will be recruited from CUH, which will allow validation of biomarkers and neuroimaging using a spectrum of mild to severe TBI. Finally the group will provide an educational module on the management, assessment and followup of children with TBI. This project will commence in 2017 and is funded by NCHF.
PRISM: PReterm Infection and SysteMic inflammation and neonatal outcomes (2014-7)
PI: E Molloy, Dr. Dave Coghlan, Dr. Denise McDonald, Dr. John Kelleher, Dr. Suzanne Kelleher, Dr. David Rea, Prof J Meaney, Dr. Arun Bodke, Prof. John O'Leary, Prof. Jan Miletin, Dr. Jana Sembrova
PhD student: Dr. Murwan Omer
Institutions: CWIUH, Tallaght hospital, TCD
Background: Despite rapid progress in neonatal intensive care over the past decades, neonatal mortality from sepsis remains unacceptably high and morbidity includes brain injury and developmental delay. Systemic inflammation related to sepsis has been implicated in many common neonatal complications such as brain, lung, or gastrointestinal injury especially in preterm infants. Modulation of inflammatory signalling during sepsis may improve survival in preterm infants and prevent related neurodevelopmental complications. Activated leucocytes, infection and persistent inflammation have been implicated in the pathogenesis of brain injury and also cerebral palsy. Antenatal inflammation and neonatal outcome: We will evaluate antenatal inflammation using placental pathology results and blood culture results from mother and baby. Detailed clinical multiorgan outcomes including novel renal biomarkers and echocardiography will be quantified using the Modified Neonatal Multi -Organ Dysfunction (NEOMOD) score. Neuroimaging with cranial ultrasound and/or MRI will be performed and developmental followup including 2-year Bayley's developmental scales (BSID III). Inflammatory response to infection and immunomodulation: We will examine pro and anti-inflammatory cytokine responses using whole blood from preterm infants over the first few weeks of life and correlate with antenatal inflammation. We will evaluate neonatal inflammatory cell phenotype and activation of the inflammasome, which is crucial for inflammatory responses and host defense to pathogens as well as being implicated in several inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis and atherosclerosis. Immunomodulators such as melatonin and specific inflammasome inhibitors will be assessed in vitro as possible methods to ameliorate persistent inflammation.
Conclusion: This research will improve the understanding of the systemic inflammatory response in preterm infants and the potential for newer adjunctive therapies. In addition these immune markers will assist in prognosis of multi-organ outcomes in preterm infants. This project is funded by NCHF and TCD.
NEBULA study: NEonatal brain Injury: Understanding systemic InfLAmmation & immunomodulation (2013-7)
PI: E Molloy
Collaborators: Professor William Watson, Dr Amanda O'Neill, Dr. Veronica Donoghue, Drs. Eoghan Mooney & Paul Downey, Prof Geraldine Boylan, Prof Bryan Lynch, Dr. Eva Jiminez, Dr. Denise McDonald, Dr. Suzanne Kelleher and Dr. John Kelleher
PhD student: Dr. Saima Aslam
Institutions: NMH, UCD, TCD, RCSI, UCC
Background: Neonatal brain injury has multifactorial etiology and causes significant neurological morbidity such as cerebral palsy. Therapeutic hypothermia is the only treatment available in term infants with neonatal encephalopathy (altered neurological function). Activated leucocytes, infection and persistent inflammation have been implicated in the pathogenesis of brain injury and cerebral palsy.
Circadian Rhythm and Melatonin: Circadian rhythm plays a key role in innate immune responses and melatonin is an essential regulator. Melatonin has been shown to improve outcomes in combination with hypothermia in animal models of neonatal brain injury. We will explore the mechanism underlying the altered activation of neutrophils and monocytes in neonates with brain injury by examining Circadian rhythm and the use of melatonin for neuroprotection. The key regulators of circadian rhythm BMAL-1 and CRY will be measured in infants with NE and neonatal controls. Persistent Inflammation and Circadian Rhythm: Hypoxia-inducible factor (HIF) 1 alpha is a key transcriptional factor in the hypoxic response and is associated with persistent inflammation. We will examine the role of the hypoxia inducible factor (HIF1 alpha) in persistent or sustained inflammation in NE. We will examine HIF 1 alpha expression in innate immune cells as well as modulation by melatonin.
Conclusion: MRI, clinical and neurodevelopmental outcome will be correlated with circadian rhythm as well as multi-organ dysfunction. This research will improve the understanding of the systemic inflammatory response in infants with brain injury and the potential for therapies such as melatonin in addition to hypothermia.
NIMBUS group: Neonatal Inflammation and Multiorgan dysfunction and Brain injUry reSearch group (2016-9)
PI: Eleanor Molloy, Prof Mary King, Dr. Breda Hayes, Dr. Adrienne Foran, Prof John O'Leary, Dr. Claudine Vavasseur, Prof. Afif El-Khuffash, Prof. Martin White, Prof. Rhona Mahony, Dr. Veronica Donoghue, Dr. Eoghan Mooney, Prof. Jan Miletin , Prof. Naomi McCallion, Prof. Jim Meaney, Dr. Deirdre Sweetman, Dr. Paul Downey, Dr. Orla Franklin, Dr. John McHugh, Dr. David Rea, Prof. John Murphy
PhD student: Dr. Mary O'Dea
Postdoctoral researcher: Dr. Lynne Kelly
Insitutions: NMH, Rotunda, CWIUH, TCD, UCD, RCSI
Neonatal brain injury (NBI) has a heterogenous aetiology with a high economic and social burden. Neonatal encephalopathy describes the babies who require resuscitation at birth and have an abnormal neurological examination. It remains difficult to predict their developmental outcome. Enhanced inflammatory responses are seen in affected infants and correlate with outcomes. Multiorgan dysfunction is common with renal, hepatic, cardiac and haematological abnormalities.We aim to correlate these inflammatory responses with clinical, neurodevelopmental and MRI outcomes to establish biomarkers of brain injury in neonates. Our translational research group includes laboratory scientists and clinicians to evaluate both inflammatory responses and correlate with multiple organ dysfunction. We have incorporated newer modalities for cardiac function (echo speckle tracking, troponin and BNP), brain imaging (EEG, MRI and fMRI), renal biomarkers (eg.NGAL, cystatin c), placental pathology and haematological indices. This research may allow early recognition of brain injury prior to MRI (Day 5-7) so that new therapies as adjuvants to therapeutic hypothermia can be initiated as soon as possible after birth.Developing clinically useful early biomarkers incorporating clinical outcomes are crucial in this group. Although neurological outcomes are evaluated in the short-term in this patient group there is no assessment of longterm cardiac, renal, immune and haematological status and we aim to coordinate followup of these parameters until at 2 years of age. This project is funded by the HRB.
UNICORN study: Underlying mechanisms in Neonatal Immune metaboliC dysregulatiOn and bRain Injury (2016-9)
PI: E Molloy
Collaborators: Prof. Adrienne Foran, Dr. Annie Curtis, Dr. Deirdre Sweetman, Dr. Deirdre Murray, Dr. Ellen Crushell, Prof Ger Boylan, Prof Jim Meaney, Ms Mandy Daly, Prof Richard Porter, Prof Terrie Inder, Dr. Veronica Donoghue
PhD Student: Dr. Mary O'Dea
Institutions: CWIUH, NMh, Rotunda, TCD, RCSI
Background: Neonatal brain injury has a multifactorial aetiology and causes significant neurological morbidity such as cerebral palsy. Therapeutic hypothermia (TH) is the only treatment available for neonatal encephalopathy (NE) but morbidity and mortality rates remain high. There is an urgent need for adjunctive therapies to improve neurodevelopmental outcomes. Persistent inflammation: Persistent systemic inflammation has been implicated in neonatal brain injury and identifying new inflammatory biomarkers will help to determine the aetiology of NE and new adjunctive therapies. There is a narrow therapeutic window to activate neuroprotective therapies during ischaemic reperfusion in NE. Ischaemia reperfusion injury occurs when a hypoxic tissue is reperfused rapidly in NE resulting in oxidative damage, cellular apoptosis and atypical immune responses generated through the production of mitochondrial oxygen species (ROS). We demonstrated that immune cell ROS are produced at abnormally high levels in infants with severe NE and increase over the first week of life despite hypothermia therapy. Babies with NE, children aged 4-6years who had NE and age-matched controls will have inflammatory phenotyping to assess persistent immune dysregulation. Detailed 1.5T MRI, MRS and 3.0T MRI and neurological outcome will be correlated with these results. Mechanisms of persistent inflammation & immunomodulation: Exploring immune activation and persistent dysfunction is crucial in the development of new treatments for NE and brain injury and there are several potential targets including: Hypoxia-inducible factor(HIF-1)-alpha and succinate metabolism. HIF1a is a key transcription factor in the hypoxia response and as well as mitochondrial dysfunction and succinate accumulation is associated with persistent inflammation and may be a potential therapeutic target.
Conclusions: Understanding the function and metabolism of systemic inflammatory cells is important in the pathogenesis of neonatal brain injury to find relevant biomarkers of severity.
CHAMPION Study: Childhood Followup of Multiple organ dysfunction after Neonatal encephalopathy : (2014-7)
PI: E Molloy and D McDonald
Collaborators: D Sweetman, B.ElNazir, D.Coughlan, S.Quinn, C.Mc Donnell, D.Webb, J.Murphy, C.McMahon, O.Franklin,O.Smith,B.Nolan,E.Crushell,V.Donoghue, M.Riordran
Funding: NCH foundation
PhD student: Z.Zareen
Postdoc: V McEneaney
Perinatal global hypoxia ischaemia is associated with neonatal encephalopathy and results in multi-organ dysfunction. Early multi organ dysfunction in neonates with encephalopathy may persist in later childhood, therefore multi-organ and neurodevelopmental follow up studies are required to ensure complete resolution and avoid complications in later childhood. Predictions about long term outcomes following NE are improving both qualitatively and quantitatively. Better insight into multi organ dysfunction post NE can be gained by using novel biomarkers and new diagnostic tools. Further research with multidisciplinary involvement can provide better predictive data and contribute to improved prognosis. In addition, to gain insight into the long-term effects neurodevelopmental effects of NE, follow-up is required throughout the school age as specific cognitive functions continue to develop throughout childhood