Hydroxyurea Use Associated with Nonverbal and Executive Skills in Sickle Cell Anemia

Abstract

Objective Hydroxyurea (HU) is used in children with sickle cell disease (SCD) to increase fetal hemoglobin (HF), contributing to a decrease in physical symptoms and potential protection against cerebral microvasculopathy. There has been minimal investigation into the association between HU use and cognition in this population. This study examined the relationship between HU status and cognition in children with SCD. Methods Thirty-seven children with SCD HbSS or HbS/β0 thalassaemia (sickle cell anemia; SCA) ages 4:0–11 years with no history of overt stroke or chronic transfusion completed a neuropsychological test battery. Other medical, laboratory, and demographic data were obtained. Neuropsychological function across 3 domains (verbal, nonverbal, and attention/executive) was compared for children on HU (n = 9) to those not taking HU (n = 28). Results Children on HU performed significantly better than children not taking HU on standardized measures of attention/executive functioning and nonverbal skills. Performance on verbal measures was similar between groups. Conclusions These results suggest that treatment with HU may not only reduce physical symptoms, but may also provide potential benefit to cognition in children with SCA, particularly in regard to attention/executive functioning and nonverbal skills. Replication with larger samples and longitudinal studies are warranted.

Neurocognitive functioning in preschool children with sickle cell disease

“…In contrast to studies of school‐age and adolescent patients with SCD, 9,47–49 HU treatment was not significantly associated with neurocognitive performance on any outcome measure. The most obvious explanation for this discrepancy is the limited duration of treatment exposure among our sample.…”

Hydroxyurea treatment and neurocognitive functioning in sickle cell disease from school age to young adulthood

“…[15][16][17] Preliminary evidence suggests that HU treatment is positively associated with neurocognitive functioning. [18][19][20] Prior work by our group demonstrated effects of HU use on measures of verbal reasoning, processing speed and working memory, yet most of these findings did not persist after adjustment for multiple comparisons. 19 Prior studies assessing the relationship between HU treatment and neurocognition are limited by small samples and narrow age ranges.…”

“…19 Prior studies assessing the relationship between HU treatment and neurocognition are limited by small samples and narrow age ranges. [18][19][20] No studies have examined if age of HU initiation affects neurocognitive outcomes or mechanisms of action.…”

Decline in Processing Speed Tells Only Half the Story: Developmental Delay in Children Living with Sickle Cell Disease

“…This difference likely reflects the improvement in treatment for SCD in the last 20–30 years. Many children and young people are now being treated with hydroxyurea [ 55 , 56 , 57 , 58 ] or chronic blood transfusions [ 9 ], with some receiving successful curative treatments [ 59 , 60 ] that may improve cognitive outcomes [ 9 , 55 , 56 , 57 , 58 , 60 , 61 ]. Hydroxyurea may improve cognition as it increases foetal haemoglobin, which reduces haemoglobin S polymerisation and the “sickling” of red blood cells [ 62 ].…”

“…Our findings highlight the need to investigate whether the identified processing speed decline, particularly in the Coding subtest, is present in a current cohort of children receiving more advanced treatment methods. Future research should investigate neuroprotective treatment effects on processing speed development in young people with SCD longitudinally [ 9 , 16 , 58 , 60 , 61 ], with consideration of the role of non-verbal and visuo-spatial abilities in processing speed outcome measurement [ 55 , 56 , 57 ]. This will allow for clinically relevant replication of our longitudinal research design.…”