Neurocognitive Impairment in Ugandan Children with Sickle Cell Anemia Compared to Sibling Controls: A cross-sectional study

Abstract

ObjectivesTo compare neurocognitive function between children with sickle cell anemia (SCA) and their non-SCA siblings and determine risk factors for poor neurocognition in Uganda.Study DesignThis cross-sectional study assessed children with SCA and their non-SCA siblings for neurocognitive and executive function at a children’s SCA clinic in Kampala. The SCA group also underwent standardized stroke examination and transcranial doppler ultrasound (TCD) for detecting stroke risk. Age-specific z-scores were compared using Wilcoxon-Rank Sum test or Chi-square where appropriate. Linear regression assessed for factors associated with impaired neurocognition.ResultsThe SCA group (n=242) were younger than their siblings (n=127), mean age (SD) 5.44 (2.9) vs. 7.8 (3.3), p<0.0001, had lower hemoglobin 7.32 (1.02) vs. 12.1 (1.45), p=0.001 and higher caretaker education (p=0.02). Overall neurocognitive SCA z-score was −0.69 (1.10) vs. siblings 0.21 (1.46), p<0.001, with lower neurocognitive scores on all subtests and similar findings for executive function among the younger sample. By hemoglobin type, SCA or non-SCA, each younger group scored higher than older children. Compared to siblings, regression modelling among the SCA children revealed significant downward neurocognitive impact of SCA, age, anemia, malnutrition and lower caretaker education. Prior stroke or elevated TCD among the SCA sample exacerbated neurocognitive differences from siblings.ConclusionsNeurocognitive testing in a sample of children with SCA compared to non-SCA siblings revealed poorer SCA-associated neurocognitive functioning which worsened with age. Risk from age, prior stroke and elevated TCD were seen, along with effects from low hemoglobin and caretaker education. These neurocognitive effects suggest need for intervention trials using disease-modifying therapy.