Work

Sustained neurocognitive improvement with hydroxyurea in Ugandan children with sickle cell anemia

Year: 2026

Type: article

Abstract: ABSTRACT Neurocognitive impairment is common in children with sickle cell anemia (SCA) and worsens with age. We determined effects of multi-year dose-intensified hydroxyurea therapy on neurocognitive functioning in children ages 3-9 years in a 2.5-year, single-arm, open-label treatment trial in Uganda. We compared age and sex-normalized neurocognitive scores for overall cognition, attention and executive function at trial completion versus enrollment. Primary outcomes were age-adjusted neurocognitive z-scores and the proportion with neurocognitive impairment at completion compared to entry. Overall, 264 participants, mean age 5.6±1.7 years, were enrolled. In all, four died, four sustained overt strokes, four withdrew or were lost to follow-up. Of 252 participants who completed the trial, the proportion with any neurocognitive impairment decreased from 18 (9.0%) to 5 (2.5%), N=199, p=0.005. In specific domains, mean overall cognition z-scores improved from -0.53±1.10 to 0.15±1.10, p<0.001, approximately equivalent to 8-11 gained IQ points, and the number with impaired overall cognition decreased from 16 (8%) to 4 (2%), N=199, p<0.001. For attention, mean z-scores improved from -0.08±1.01 to 0.51±0.91, p<0.001 and the number with impaired attention decreased from 3 (2.1%) to 1(0.7%), N=146, p<0.001. Improved cognition and attention were each strongly associated with higher entry scores and better weight-for-age, along with hemoglobin level and socio-economic status. In contrast, these were not associated with either test of executive function. These novel findings in a substantial sample of children support use of hydroxyurea for neurocognitive function protection and emphasize the importance of increased access to hydroxyurea for all children with SCA in sub-Saharan Africa. NCT04750707

Source: Blood Global Hematology

DOI: 10.1016/j.bglo.2026.100163