Neurocognitive functioning in preschool children with sickle cell disease

Abstract

Background Children with sickle cell disease (SCD) experience neurodevelopmental delays; however, there is limited research with preschool‐age children. This study examined neurocognitive risk and protective factors in preschoolers with SCD. Procedure Sixty‐two patients with SCD (60% HbSS/HbSβ0‐thalassemia; 40% HbSC/HbSβ+‐thalassemia) between the ages of 3 and 6 years (mean = 4.77 years) received a neuropsychological evaluation as routine systematic surveillance. Patients were not selected for disease severity, prior central nervous system findings, or existing cognitive concerns. Thirty‐four patients (82% HbSS/HbSβ0‐thalassemia) were prescribed hydroxyurea (HU) at the time of their neuropsychological evaluation. On average, these patients had been prescribed HU at 2.15 (standard deviation = 1.45) years of age. The average dose was 28.8 mg/kg/day. Besides genotype, there were no group differences in medical or demographic factors based on HU treatment status. Results Patients with HbSS/HbSβ0‐thalassemia scored below normative expectations on measures of intelligence, verbal comprehension, and school readiness (false discovery rate‐adjusted p‐value [pFDR] < .05). Age, sickle genotype, and HU treatment exposure were not associated with measured neurocognitive outcomes (pFDR > .05). Greater social vulnerability at the community level was associated with poorer performance on measures of intellectual functioning, verbal comprehension, visuomotor control, and school readiness, as well as parent report of executive dysfunction (pFDR < .05). Greater household socioeconomic status was positively associated with academic readiness. Conclusions Preschoolers with severe SCD (HbSS/HbSβ0‐thalassemia) perform below age expectations on measures of intelligence and academic readiness. Sociodemographic factors were stronger drivers of neurocognitive performance than disease severity or disease‐modifying treatment. Neurodevelopmental interventions targeting the home and broader community environment are needed.

Working memory and school readiness in preschool children with sickle cell disease compared to demographically matched controls

“…43 Due to these neurocognitive difficulties, preschool children with SCD are at risk for poor school readiness when they enter kindergarten. 30 These school readiness skills, including literacy and numeracy, are highly predictive of later academic performance and grade retention. Consistent with our hypotheses, preschool children with SCD had worse performance on measures of school readiness and working memory relative to matched controls.…”

“…Five studies examined performance across specific domains of neurocognitive functioning in preschool-aged children with SCD. [29][30][31][32][33] Only two of these studies included a control group, and conclusions were limited by a small sample (22 cases with SCD). 31,32 Performance on neurocognitive measures was related to SES but not SCD genotype or laboratory values.…”

“…31,32 Performance on neurocognitive measures was related to SES but not SCD genotype or laboratory values. 29,30 Prior studies have suggested a neuroprotective effect of hydroxycarbamide (hydroxyurea), 34,35 but these findings have not been documented in young children (<5 years of age) with SCD. 30,36 Despite the prevalence of working memory impairments found in school-aged children with SCD and the documented association between working memory ability and academic success in the general population, limited research has specifically demonstrated working memory deficits in preschool children with SCD.…”

Comment on: Effects of hydroxyurea on brain function in children with sickle cell anemia

“…For example, a 2021 study by Heitzer et al incorporated younger nursery school age groups with an average dose slightly higher than this study. 4 Although these results have been hypothesized before, different studies still report discrepancies. For example, transcranial Doppler velocity was increased in internal branch of carotid artery and ACA, which is associated with deterioration of psychomotor functions apart from neurocognitive functions.…”

Sluggish Cognitive Tempo in Pediatric Sickle Cell Disease

“…Slowed processing speed, attention difficulties, and executive dysfunction are often identified as salient neurocognitive symptoms beginning in the preschool period, often continuing into adulthood (7). Neurodevelopmental syndromes have also been linked to disease severity in SCD with as many as half of all preschool-age children showing evidence of developmental delay with elevated rates of neurodevelopmental issues persisting into adolescence (8)(9)(10)(11).…”