Association between hydroxycarbamide exposure and neurocognitive function in adolescents with sickle cell disease

Patients with sickle cell disease (SCD) are at increased risk for neurocognitive impairments. While disease-modifying treatment, such as hydroxycarbamide (hydroxyurea), may decrease this risk, it has not been systematically investigated in children with SCD. We screened neurocognitive functioning in 103 adolescents with SCD (16–17 years, 50% female) and compared outcomes between patients with a history of exposure to hydroxycarbamide (n = 12 HbSC/HbSβ⁺ thalassaemia; n = 52 HbSS/HbSβ⁰ thalassaemia) and those never treated with hydroxycarbamide (n = 31 HbSC/HbSβ⁺ thalassaemia; n = 8 HbSS/HbSβ⁰ thalassaemia). Demographic distributions were similar between the groups. After adjusting for socioeconomic status, the hydroxycarbamide group had significantly higher scores on nonverbal IQ (HbSC/HbSβ thalassaemia: P = 0·036, effect size [d] = 0·65), reaction speed (HbSS/HbSβ⁰ thalassaemia: P = 0·002, d = 1·70), sustained attention (HbSS/HbSβ⁰ thalassaemia: P = 0·014, d = 1·30), working memory (HbSC/HbSβ⁺ thalassaemia: P = 0·034, d = 0·71) and verbal memory (HbSC/HbSβ⁺ thalassaemia: P = 0·038, d = 0·84) when compared to those who did not receive hydroxycarbamide. In patients with HbSS/HbSβ⁰ thalassaemia, longer treatment duration with hydroxycarbamide was associated with better verbal memory (P = 0·009) and reading (P = 0·002). Markers of hydroxycarbamide effect, including higher fetal haemoglobin (HbF), higher mean corpuscular volume (MCV) and lower white blood cell count (WBC), were associated with better verbal fluency (HbF: P = 0·014, MCV: P = 0·006, WBC: P = 0·047) and reading (MCV: P = 0·021, WBC: P = 0·037). Cognitive impairment may be mitigated by exposure to hydroxycarbamide in adolescents with SCD.