Sickle cell anemia (SCA) complications include neurocognitive difficulties associated with low oxygen saturation (SpO₂) compounded by obstructive sleep apnea (OSA) potentially treatable with continuous Positive Airways Pressure (CPAP). The primary aim of this single-blind, randomized, controlled phase II trial was to investigate in SCA children the effect of Auto-adjusting CPAP (APAP) on cognition, specifically Cancellation, a measure of selective attention and processing speed. Secondary outcomes included change in other cognitive tests, new silent cerebral infarcts (SCIs) or worsening vasculopathy and MRI brain volume change.

Eligible SCA subjects age 8 to 15.999 years, mean SpO2 <90% for <30% of night were randomised to APAP or Standard Care. Outcomes included change in Cancellation, Verbal and Spatial learning  and change in MRI, MRA and brain volumes assessed at baseline and after 6 months blind to treatment assignment.

Results: 30 children with HbSS were randomised to standard care + APAP (n=15) or standard care alone (n=15) for 6 months. Change in Cancellation was generally positive for those on APAP and there was a statistically significant difference for those also on Hydroxyurea. Verbal and spatial memory improved on APAP, the latter significantly. There were no new SCIs but cervical carotid occlusion occurred in one child on standard care. There was no change in gray matter volume but cortical white matter volume decreased in those on APAP with baseline mean overnight SpO2<96% (p=0.013).

Discussion: Selective attention/processing speed and spatial memory improved with APAP. The change in white matter volume may represent reduced oedema.