Paediatrics II

301401, 302049, 302060, 303009, 302032

brain injury, brain maturation, breast milk, cardiovascular risk, developmental outcome, FOXO3 modulating drugs, neonatal neuroimaging, neonatal neuroscience, and Preterm infants

Characterization of risk predictors for adverse outcomes in preterm infants

Monitoring of preterm brain maturation and diagnosis of brain injury (aEEG, GM, MRI, NIRS), biomarker identification

Investigating the effects of prematurity, neonatal growth and feeding practices on cardiovascular risk factors

Analysis of brain development and injury mechanisms and development of substances for neuroprotection and the treatment of newborn brain injury

Analysis of FOXO3-modulating drugs

The Department of Neonatology at the Medical University of Innsbruck is a perinatal centre that provides the highest possible level of care. We offer treatment for all preterm and critically ill neonates in Tyrol, including a standardized follow-up programme until age 5. We undertake a combination of basic and clinical research, aiming at the early identification of infants at risk of adverse outcome and the improvement of long-term outcomes. Our clinical research includes the characterization of neurodevelopmental and cardiovascular outcomes of very preterm infants until school age and the definition of risk predictors of adverse outcomes. We apply multimodal methods to monitor brain activity (aEEG, NIRS), brain maturation (GM) and brain injury (MRI), evaluate the role of nutrition/growth and study the optimization of perinatal resuscitation (e.g. stabilization of the preterm infant before umbilical cord clamping). In combination with clinical research, we are evaluating laboratory biomarkers to obtain a better understanding of brain development and injury mechanisms, to diagnose brain injury and to predict long-term outcomes. We participate in a worldwide collaboration for quality improvement – the Vermont Oxford Network – with the aim of following key neonatal outcomes and continuously improving patient care. We have close national and international collaborations with perinatal centres and with local neuroscience and cardiovascular science groups.

Improvements in neonatal intensive care medicine in recent decades have substantially reduced preterm infant mortality. However, infants born prematurely remain at a high risk of neurodevelopmental delay and lifelong handicap. There are no causal therapeutic strategies for neonatal brain injury, so clinical management focuses on optimal perinatal care and on the early identification of infants at a high risk of adverse outcomes.

Clinical Research Projects

Neonatal Neuroscience

Gande N., Griesmaier E., Hammerl M., Hochmayr C., Höck M., Messner A., Mitterer W., Müller K., Neubauer V., Pupp Peglow U., Posod A., Sappler M., Schreiner C., Staudt A., Winkler I., Kiechl-Kohlendorfer U.

Evaluation of brain maturation, brain injury and neurodevelopmental outcome

To improve the neurodevelopmental prognosis in preterm and critically ill neonates, we use an integrative approach that combines clinical parameters, electrophysiological monitoring and advanced imaging techniques. Our multidimensional strategy provides a comprehensive assessment of brain development and of the risks of neurological impairments. With a combination of amplitude-integrated electroencephalography (aEEG), cerebral ultrasound (cUS), near-infrared spectroscopy (NIRS), general movements assessment (GMA) and magnetic resonance imaging (MRI)

we are investigating diagnostic tools to enhance the prediction of short- and long-term outcomes. By incorporating clinical variables (gestational age, birth weight, gender, cytomegalovirus infection, medication) into this diagnostic toolkit, we aim to identify markers that are predictive of later developmental outcomes.

Cardiovascular Science

Cardiovascular Follow-Up of Very Preterm Infants (NeoVasC)

Mitterer W., Hochmayr C., Posod A., Neubauer V., Griesmaier E., Kiechl-Kohlendorfer U.

Prematurity is an established risk factor for cardiovascular disease in adult life. The early detection of cardiovascular risk predictors is crucial for effective prevention programmes. Our research group is assessing both traditional and novel cardiovascular risk factors from birth until preschool age, focusing in particular on the protective effect of exclusive human milk feeding on cardiovascular risk.

Early Vascular Ageing in YOUth (EVA4YOU)

Messner A., Nairz J., Hochmayr C., Gande N., Staudt A., Kiechl-Kohlendorfer U.

The EVA4YOU study builds on the knowledge gained from the EVA study. It aims to improve the vascular health of 15/16-year-old Tyrolean pupils and apprentices and to elucidate the mechanisms of early vascular ageing. We are investigating the impact of prematurity, neonatal growth characteristics and feeding practices on early vascular ageing and hope to elucidate the associations with additional risk markers for cardiovascular diseases.

Experimental Research Projects

Neonatal Research Laboratory

Posod A., Griesmaier E., Winkler I., Hochmayr C., Mayer E., Huber E., Urbanek M.

The Neonatal Research Laboratory is advancing the understanding and management of neonatal health, with a particular emphasis on brain development, injury mechanisms and the identification of biomarkers. Our interdisciplinary approach combines fundamental research and clinical studies to address critical challenges in neonatal care.

Major research topics:

• Neonatal brain injury
• Exploring the mechanisms and consequences of neonatal brain injury, including encephalopathy of prematurity and hypoxic-ischemic encephalopathy. We use various in vivo and in vitro models to assess neuroprotective and therapeutic strategies to mitigate injury and promote recovery

  

  

• Clinical research on biomarker discovery to improve the diagnosis, prognosis and personalized care for neonates.
• Breast milk and immunological health
• Examining the complex composition of breast milk and its potential protective properties. We are exploring a range of bioactive components, such as antibodies and immunoregulatory molecules, to understand their roles in neonatal development and resilience.
• Identifying cardiovascular and neurological biomarkers to evaluate risks and long-term outcomes in very preterm infants, with a particular focus on early childhood stages.
• Oxygen Dissociation Curve (ODC)
• Exploring ODC shifts in perinatal asphyxia and preterm infants to understand the impact of foetal haemoglobin on oxygen delivery and neonatal outcomes.

Our work bridges basic research and clinical applications, contributing to improved outcomes for the most vulnerable neonatal populations.

Pharmacological inhibition of the transcription factor FOXO3

In neuroblastoma, an aggressive childhood tumour, cancer stem cells initiate treatment failure. The transcription factor FOXO3, a regulator of cancer stem-cell maintenance, triggers migration, autophagy and chemoresistance in high-stage neuroblastoma. We are investigating the impact on cancer stem cells and on therapy-resistant tumour cells of the pharmacological inhibition of FOXO3 by small molecular weight compounds.

Clinical Research Projects

Neonatal Neuroscience

Griesmaier E, Hammerl M, Sappler M, Zimmermann M, Gande N, Winkler I, Kiechl-Kohlendorfer U, Neubauer V. Growth and cognitive outcome in very preterm infants with postnatal cytomegalovirus infection. NEONATOLOGY. 2024 Dec 11:1-14; [Epub ahead of print]; PubMed: 39662062 doi: 10.1159/000542820

Sappler, Maria; Neubauer, Vera; Posod, Anna; Schreiner, Christina; Kiechl-Kohlendorfer, Ursula; Griesmaier, Elke: Early Brain Activity in Very Preterm Infants of Mothers with Gestational Diabetes Mellitus: A Pilot Study. NEONATOLOGY. 2024; 121(3); 342-350. PubMed: 38346405 doi: 10.1159/000536182

Schreiner, Christina; Staudt, Anna; Neubauer, Vera; Kiechl-Kohlendorfer, Ursula; Griesmaier, Elke: Amplitude-integrated electroencephalography showed alterations in cerebral activity in monochorionic twins with twin-to-twin transfusion syndrome. ACTA PAEDIATRICA. 2024; [Epub ahead of print]; PubMed: 39652525 doi: 10.1111/apa.17532

Winkler, Ira; Sappler, Maria; Gizewski, Elke Ruth; Kiechl-Kohlendorfer, Ursula; Neubauer, Vera; Griesmaier, Elke: Relationship between Brain Function and Microstructural Brain Maturation in Preterm Infants. NEONATOLOGY. 2024; 121(2); 213-221. PubMed: 38052194 doi: 0.1159/000535042

Pichler, Gerhard; Goeral, Katharina; Hammerl, Marlene; Perme, Tina; Dempsey, Eugene M.; Springer, Laila; Lista, Gianluca; Szczapa, Tomasz; Fuchs, Hans; Karpinski, Lukasz; Bua, Jenny; Avian, Alexander; Law, Brenda; Urlesberger, Berndt; Buchmayer, Julia; Kiechl-Kohlendorfer, Ursula; Kornhauser-Cerar, Lilijana; Schwarz, Christoph E.; Gruendler, Kerstin; Stucchi, Ilaria; Schwaberger, Bernhard; Klebermass-Schrehof, Katrin; Schmoelzer, Georg M.; Cosgod III Study Grp: Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): multicentre randomised phase 3 clinical trial. BMJ-BRITISH MEDICAL JOURNAL. 2023; 380; e072313.

Cardiovascular Science

Staudt, Anna; Kiechl, Sophia J.; Gande, Nina; Hochmayr, Christoph; Bernar, Benoit; Stock, Katharina; Geiger, Ralf; Egger, Alexander; Griesmacher, Andrea; Knoflach, Michael; Kiechl-Kohlendorfer, Ursula: Influence of Oral Contraceptives on Lipid Profile and Trajectories in Healthy Adolescents. Data From the EVA-Tyrol Study. JOURNAL OF ADOLESCENT HEALTH. 2024; 75(3); 479-486. PubMed: 39001754 doi: 10.1016/j.jadohealth.2024.04.017

NCD Risk Factor Collaboration [Kiechl-Kohlendorfer, U.; Kiechl, S.; Knoflach, M.; Pechlaner, R.; Ulmer, H.; Willeit, J.; Willeit, P.]: Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults.
LANCET. 2024; 403(10431); 1027-1050. PubMed: 38432237 doi: 10.1016/S0140-6736(23)02750-2

Nairz, Johannes; Messner, Alex; Kiechl, Sophia J.; Winder, Bernhard; Hochmayr, Christoph; Egger, Alexander E.; Griesmacher, Andrea; Geiger, Ralf; Griesmaier, Elke; Pechlaner, Raimund; Knoflach, Michael; Kiechl-Kohlendorfer, Ursula; Early Vasc Ageing YOUth EVA4YOU.: Determinants of non-alcoholic fatty liver disease in young people: Maternal, neonatal, and adolescent factors.
PLOS ONE. 2024; 19(2); e0298800. PubMed: 38386674 doi: 10.1371/journal.pone.0298800

Mitterer, Wolfgang; Komazec, Irena Odri; Huber, Eva; Schaefer, Benedikt; Posod, Anna; Kiechl-Kohlendorfer, Ursula: Young hearts, early risks: novel cardiovascular biomarkers in former very preterm infants at kindergarten age. PEDIATRIC RESEARCH. 2024; [Epub ahead of print]; PubMed: 38658663 doi: 10.1038/s41390-024-03210-7

Messner, Alex; Nairz, Johannes; Kiechl, Sophia; Winder, Bernhard; Pechlaner, Raimund; Geiger, Ralf; Knoflach, Michael; Kiechl-Kohlendorfer, Ursula; EVA4YOU Tyrol Study Grp: Comparison of body mass index and fat mass index to classify body composition in adolescents-The EVA4YOU study.
EUROPEAN JOURNAL OF PEDIATRICS. 2024; 183(5); 2203-2214. PubMed: 38386029 doi: 10.1007/s00431-024-05474-x

Neonatal Research Laboratory

Hochmayr, Christoph; Winkler, Ira; Hammerl, Marlene; Hoeller, Alexander; Huber, Eva; Urbanek, Martina; Kiechl-Kohlendorfer, Ursula; Griesmaier, Elke; Posod, Anna: Factors Influencing Breast Milk Antibody Titers during the Coronavirus Disease 2019 Pandemic: An Observational Study. NUTRIENTS. 2024; 16(14); 2320. PubMed: 39064762 doi: 10.3390/nu16142320

Hochmayr, Christoph; Toferer, Martha; Hammerl, Marlene; Winkler, Ira; Huber, Eva; Urbanek, Martina; Kiechl-Kohlendorfer, Ursula; Griesmaier, Elke; Posod, Anna: Breast milk anti-S1RBD immunoglobulin concentrations throughout lactation: An observational report.
ACTA PAEDIATRICA. 2024; 113(1); 81-83. PubMed: 37814794 doi: 10.1111/apa.16997

Posod, Anna; Wechselberger, Karina; Pellkofer, Yasmin; Hammerl, Marlene; Urbanek, Martina; Huber, Eva; Kiechl-Kohlendorfer, Ursula; Griesmaier, Elke: Investigation of secretoneurin as a potential biomarker of brain injury in very preterm infants: A pilot study.
PLOS ONE. 2023; 18(4); e0284096.

Transcription factor FOXO3 research group

Hausott, Barbara; Pircher, Lena; Kind, Michaela; Park, Jong-Whi; Claus, Peter; Obexer, Petra; Klimaschewski, Lars: Sprouty2 Regulates Endocytosis and Degradation of Fibroblast Growth Factor Receptor 1 in Glioblastoma Cells. CELLS. 2024; 13(23); 1967. PubMed: 39682716 doi: 10.3390/cells13231967

Salvador, Christina; Salvador, Robert; Kropshofer, Gabriele; Meister, Bernhard; Rock, Marie; Obexer, Petra; Hetzer, Benjamin; Rabensteiner, Evelyn; Crazzolara, Roman: Prophylaxis with enoxaparin and antithrombin III in drug-induced coagulation alterations in childhood leukemia: a retrospective experience of 20 years. THROMBOSIS JOURNAL. 2024; 22(1); 30. PubMed: 38539225 doi: 10.1186/s12959-024-00602-x

Podpeskar, Alexandra; Crazzolara, Roman; Kropshofer, Gabriele; Hetzer, Benjamin; Rabensteiner, Evelyn; Meister, Bernhard; Obexer, Petra; Salvador, Christina: Recommendations for Nutritional Supplementation in Pediatric Oncology: A Compilation of the Facts. NUTRIENTS. 2023; 15(14); 3239.
PubMed: 37513658 doi: 10.3390/nu15143239

Early vascular ageing (NeoVasC and EVA4YOU), part of the excellence initiative (Competence Centers for Excellent Technologies—COMET) of the Austrian Research Promotion Agency FFG: “Research Center of Excellence in Vascular Ageing—Tyrol, VASCage” (K project number 843536) of the Austrian Research Promotion Agency FFG (COMET program), funded by the Austrian Ministry for Transport, Innovation and Technology, the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol (via Standortagentur), Salzburg and Vienna (via Vienna Business Agency). 1,1 Mio. Euro

• NCD Risk Factor Collaboration – Imperial College London
• Gerhard Pichler, Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria.
• Martin Lee, Prolacta Bioscience, Monrovia, CA
• Bea Latal, Child Development Centre, University Children’s Hospital Zurich, Switzerland
• Sven Wellemann, Department of Neonatology, University Children’s Hospital Regensburg, Germany
• Sampsa Vanhatalo, Department of Neurosciences, University of Helsinki, Finland
• Sara Tucci, University Medical Centre Freiburg, Germany
• Jan Kureck, TU Berlin, Germany
• Moon R, Goldberg Center for Community Pediatric Health, Children’s National Medical Center, Washington, US, and Blair PS, University of Bristol, UK (International Society for the Prevention of Infant Death)

Tollinger M, Institute of Organic Chemistry, CMBI- Centre for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria]