Sudden infant death syndrome (SIDS) is a leading cause of infant death, and prone sleeping is the major risk factor. Prone sleeping impairs arousal from sleep and cardiovascular control in infants at 2-3 months, coinciding with the highest risk period for SIDS. We hypothesized that prone sleeping would also alter cerebrovascular control, and aimed to test this hypothesis by examining responses of cerebral oxygenation to head-up tilts (HUTs) over the first 6 months after birth. STUDY DESIGN AND PARTICIPANTS: Seventeen healthy full-term infants were studied at 2-4 weeks, 2-3 months, and 5-6 months of age using daytime polysomnography, with the additional measurements of blood pressure (BP, Finometer(TM), Finometer Medical Systems, The Netherlands) and cerebral tissue oxygenation index (TOI, NIRO 200, Hamamatsu Photonics KK, Japan). HUTs were performed in active sleep (AS) and quiet sleep (QS) in both prone and supine positions. RESULTS: When infants slept in the prone position, a sustained increase in TOI (P <0.05) occurred following HUTs, except in QS at 2-3 months when TOI was unchanged. BP was either unchanged or fell below baseline during the sustained TOI increase, signifying cerebro-vasodilatation. In contrast, when infants slept supine, TOI did not change after HUTs, except in QS at 2-3 and 5-6 months when TOI dropped below baseline (P <0.05). CONCLUSIONS: When infants slept in the prone position, cerebral arterial vasodilation and increased cerebral oxygenation occurred during head-up tilts, possibly as a protection against cerebral hypoxia. Absence of the vasodilatory response during quiet sleep at 2-3 months possibly underpins the decreased arousability from sleep and increased risk for sudden infant death syndrome at this age. CITATION: Wong F; Yiallourou SR; Odoi A; Browne P; Walker AM; Horne RSC. Cerebrovascular control is altered in healthy term infants when they sleep prone. SLEEP 2013;36(12):1911-1918.