Non-invasive biomarkers of fetal brain development reflecting prenatal stress: an integrative multi-scale multi-species perspective on data collection and analysis.
Frasch, M. G., Lobmaier, S., Stampalija, T., Desplats, P., Pallares, M. E., Pastor, V., Brocco, M., Wu, H. T., Schulkin, J., Herry, C., Seely, A., Metz, G. A. S., Louzoun, Y. and Antonelli, M.
(a)Department of Obstetrics and Gynecology, University of Washington, Seattle, USA. Electronic address: mfrasch@uw.edu.
(b)Frauenklinik und Poliklinik, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
(c)Unit of Fetal Medicine and Prenatal Diagnosis, Institute for Mother and Child Health IRCCS Burlo Garofolo, Trieste, Italy.
(d)University of California, Departments of Neurosciences and Pathology, San Diego, USA.
(e)Instituto de Biologia Celular y Neurociencia "Prof. Eduardo De Robertis", Facultad de Medicina, Universidad de Buenos Aires, Argentina.
(f)Instituto de Investigaciones Biotecnologicas - Instituto Tecnologico de Chascomus (IIB-INTECH), Universidad Nacional de San Martin - Consejo Nacional de Investigaciones Cientificas y Tecnicas (UNSAM-CONICET), San Martin, Buenos Aires, Argentina.
(g)Dept. of Mathematics and Dept. of Statistical Science, Duke University, Durham, NC, USA; (h)Mathematics Division, National Center for Theoretical Sciences, Taipei, Taiwan.
(a)Department of Obstetrics and Gynecology, University of Washington, Seattle, USA.
(i)Ottawa Hospital Research Institute, Ottawa, ON, Canada.
(j)Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada.
(k)Bar-Ilan University, Dept. of Applied Mathematics, Israel.
Prenatal stress (PS) impacts early postnatal behavioural and cognitive development. This process of 'fetal programming' is mediated by the effects of the prenatal experience on the developing hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). We derive a multi-scale multi-species approach to devising preclinical and clinical studies to identify early non-invasively available pre- and postnatal biomarkers of PS. The multiple scales include brain epigenome, metabolome, microbiome and the ANS activity gauged via an array of advanced non-invasively obtainable properties of fetal heart rate fluctuations. The proposed framework has the potential to reveal mechanistic links between maternal stress during pregnancy and changes across these physiological scales. Such biomarkers may hence be useful as early and non-invasive predictors of neurodevelopmental trajectories influenced by the PS as well as follow-up indicators of success of therapeutic interventions to correct such altered neurodevelopmental trajectories. PS studies must be conducted on multiple scales derived from concerted observations in multiple animal models and human cohorts performed in an interactive and iterative manner and deploying machine learning for data synthesis, identification and validation of the best non-invasive detection and follow-up biomarkers, a prerequisite for designing effective therapeutic interventions.
Neuroscience & Biobehavioral Reviews : en prensa (2018)