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Background: Cerebral hemodynamics is supposed to be influenced by the different ventilation approach. Ventilation support can be classified as non-invasive (N-CPAP) or invasive (SIMV and HFV), the last known to induce endotrauma. Our aim was the non-invasive NIRS assessment of neonatal absolute cerebral blood flow (CBF) and relative cerebral blood volume changes (DeltaCBV) during synchronized intermittent ventilation (SIMV), or high frequency ventilation (HFV) and nasal continuous positive airways pressure (CPAP)., Methods: An observational study in a tertiary referral NICU. CBF and DeltaCBV changes were assessed in 41 preterm newborn infants with respiratory distress syndrome treated using mechanical ventilation or the CPAP device., Results: Basal chromophore traces enabled DeltaCBV (mL/100 g) changes to be calculated. CBF was calculated in mL/100 g/min from the saturation rise integral and rate of rise [O(2)Hb-HHb]. Median DeltaCBV was 0.07 (range 0.01-0.13) in SIMV group, 0.07 (0.01-0.19) in HFV group and 0.13 (0.10-1.28) in CPAP group. Median CBF was 14.44 (2.70-32.10), 9.20 (2.94-19.58) and 31.69 (13.59-34.93) respectively. A multiple regression model showed a significant correlation between DeltaCBV or CBF and ventilation approach., Conclusion: In the light of our results, we might speculate that, assuming that hemodynamic autoregulation is safe and arterial blood pressure is preserved, ventilation per se influences brain circulation.