BACKGROUNDThe sense of smell is fully developed in newborns and plays an important role in their early development. There are several approaches to studying olfactory processing in the newborn brain, including EEG, fMRI, and near-infrared spectroscopy (NIRS). Understanding the processing of olfactory stimuli in the newborn brain is of fundamental importance for the development of supportive therapeutic odorant delivery, e.g. for weaning by gavage, and for adapting it to the developing brain. This study aimed to investigate the effect of different odors (milk, farnesol odor, and water as a control) on changes in brain activation in newborns in two different brain regions.METHODSNewborns older than 72 h and below an age of seven days were divided into two groups with different optode positioning strategies of NIRS, group I parietal and group II frontal. Olfactory stimulation was administered using milk, farnesol (floral odor), and water as a control.RESULTSA total of 26 newborns participated in the study. In the final analysis, 19 children were included. Allthough the optode positioning does not differ significantly, in group I, farnesol stimulation resulted in a significant increase in oxygenated hemoglobin compared to the control, while milk odor showed a decreased amplitude, particularly in the more parietal optode position. In group II, a significant difference was observed between the milk odor and the control, in the frontal areas.CONCLUSIONSThis study revealed significant changes in hemoglobin oxygenation, indicating neuronal activation following different olfactory stimulation in both optode positionings. Whereas milk had more impact in frontal areas, the floral odor caused an effect in parietal areas.