Utility of Caregiver Signaling Questions to Detect Neurocognitive Impairment in Children with Sickle Cell Disease

• Signaling questions improved the detection of patients with SCD and neurocognitive impairment compared to demographic/clinical information.

• Use of signaling questions represents a brief and low-cost method to improve the detection of patients with SCD in need of support.

The American Society of Hematology cerebrovascular guidelines for sickle cell disease (SCD) recommend surveillance using signaling questions to screen for neurocognitive difficulties, though the clinical utility of these signaling questions has yet to be established. This study aimed to determine the clinical utility of caregiver signaling questions for detecting significant neurocognitive impairment (defined as >1.5 standard deviation (SD) below the normative mean on 2 or more measures) and domain-specific impairment (defined as >1.5 SD below the normative mean) in children and adolescents with SCD. Four hundred twenty-one caregivers of children with SCD ages 8-17 years (62% HbSS or HbSβ0 thalassemia) were asked seven signaling questions. Children completed performance-based neurocognitive and academic measures. Children who were reported to have repeated a grade, did not obtain primarily A/B grades in school, have a history of learning difficulties, or whose caregiver endorsed concern for their learning were more likely to have significant neurocognitive impairment and obtained lower scores across all measures (all q<0.05). History of learning difficulties emerged as the most sensitive and specific signaling question for detecting significant neurocognitive impairment (sensitivity=0.64, specificity=0.77) and domain-specific impairment (sensitivity range=0.56-0.77, specificity range=0.63-0.72). Cumulative caregiver report improved prediction of neurocognitive impairment beyond demographic/clinical factors alone. Though performance-based screening for all patients with SCD is the most effective means to identifying those with neurocognitive or academic impairment, use of caregiver signaling questions represents a brief and low-cost method to improve the detection of patients with SCD in need of support.