A head start for the preterm born children in Switzerland: A Geneva-Zurich joint research consortium

Early life events such as low birth weight affect 14 million newborns every year worldwide and premature birth occurs in 400'000 newborns per year in Europe alone. In Switzerland, about 800 infants are born preterm each year. Low birth weight and preterm birth both affect early brain development significantly and lead to reduced skill formation and impairment of socio-cognitive development, with a clear impact on economic and academic success and quality of life of these individuals. Hence, the focus of research lies in prevention of injury to the developing brain and its consequences. Indeed, neuroprotection for preterm infants has become one of the most important aspects of care provided to preterm infants. Such neuroprotection includes molecular strategies and/or care interventions to prevent brain injury and to support normal development of the immature brain. Between 2005 and 2012 such a neuroprotective multicenter RCT has taken place initiated in Zurich in collaboration with Geneva (“Does erythropoietin improve outcome in preterm infants” (NCT00413946), PI Prof. HU Bucher, CO-PI P Hüppi). This initial collaborative project has lead to two main publications in the prestigious journal of JAMA, one lead by the Geneva investigators [1] and one lead by the Zurich investigators [2]. Additionally, quantitative MR results were published lead by the Zurich investigators [3]. Building on the established collaboration we are now assessing the long-term effects on early erythropoietin on higher-order cognitive functions at 8 to 11 year of age as a follow-up project (EpoKids (SNF 320030_169733 PI C Hagmann [4]). Both sites are further investigating other neuroprotective interventions, for example creative music therapy [5], erythropoetin for the repair of injury [6] and the brain effects of music exposure [7] and nutrition [8, 9] on brain development. The proposed project will investigate how the brain networks grow depending on the administered neuroprotection. More specifically, MR brain connectomics analysis will be performed and the connectomes will be mapped between the treatment groups. In order to do so, a digital platform will be build up to share MR analysis software and data between the two institutions. Protecting the preterm brain remains a major challenge of pediatrics, and teaming up the efforts of both institutions with their experts in the field will provide advancement of science and clinical care in both institutions as well as training opportunities for students of both institutions. Participants: PD Dr. med. Cornelia Hagmann, University of Zurich Prof. Dr. med. Petra Hüppi, University of Geneva   References
  1. Leuchter, R.H., et al., Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA, 2014. 312(8): p. 817-24.
  2. Natalucci, G., et al., Effect of Early Prophylactic High-Dose Recombinant Human Erythropoietin in Very Preterm Infants on Neurodevelopmental Outcome at 2 Years: A Randomized Clinical Trial. JAMA, 2016. 315(19): p. 2079-85.
  3. O'Gorman, R.L., et al., Tract-based spatial statistics to assess the neuroprotective effect of early erythropoietin on white matter development in preterm infants. Brain, 2015. 138(Pt 2): p. 388-97.
  4. Wehrle, F.M., et al., Long-term neuroprotective effect of erythropoietin on executive functions in very preterm children (EpoKids): protocol of a prospective follow-up study. BMJ Open, 2018. 8(4): p. e022157.
  5. Haslbeck, F.B., et al., Creative music therapy to promote brain structure, function, and neurobehavioral outcomes in preterm infants: a randomized controlled pilot trial protocol. Pilot Feasibility Stud, 2017. 3: p. 36.
  6. Ruegger, C.M., et al., Randomized controlled trials in very preterm infants: does inclusion in the study result in any long-term benefit? Neonatology, 2014. 106(2): p. 114-9.
  7. Lordier, L., et al., Music processing in preterm and full-term newborns: A psychophysiological interaction (PPI) approach in neonatal fMRI. Neuroimage, 2018.
  8. Beauport, L., et al., Impact of Early Nutritional Intake on Preterm Brain: A Magnetic Resonance Imaging Study. J Pediatr, 2017. 181: p. 29-36 e1.
  9. Schneider, J., et al., Nutrient Intake in the First Two Weeks of Life and Brain Growth in Preterm Neonates. Pediatrics, 2018.