Implementing ASH Guidelines: Clinical Utility of a Signaling Question for Detecting Cognitive Deficits in Pediatric Sickle Cell Disease

Introduction: Disease-related cognitive deficits are common in sickle cell disease (SCD). ASH 2020 guidelines recommend that clinicians conduct surveillance using simplified signaling questions for concerns about neurodevelopmental disorders. More formal screening is recommended for patients with abnormal surveillance results. While the guidelines suggest possible signaling questions that could be used, there is a lack of empirical research into which questions yield reliable estimates of cognitive impairment. We examined the clinical utility of a caregiver-directed signaling question for identifying cognitive deficits as assessed by a performance-based measure of intelligence (IQ).

Methods: Primary caregivers of children with SCD aged 7-16 years were asked to rate their child's academic performance as below grade level, on grade level, or above grade level relative to their peers. Children completed the Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V), a standardized assessment of IQ. The WISC-V produces standard score (Mean = 100, SD = 15) estimates of global intelligence (Full Scale IQ), verbal abilities (Verbal Comprehension Index or VCI), working memory (Working Memory Index or WMI), and processing speed (Processing Speed Index or PSI). One-way ANOVA was used to examine the degree to which WISC-V scores varied by caregiver-rated academic performance. Analyses were repeated separately for younger children (ages 7-11) and older children (ages 12-16). To determine the clinical utility of caregiver ratings of academic performance, academic performance was dichotomized (below grade level vs. at/above grade level) and WISC-V scores were dichotomized into low functioning (>1 SD below the mean) or normal functioning; sensitivity, specificity, positive predictive value, and negative predictive value estimates were subsequently calculated.

Results: Eighty-nine caregivers of children with SCD (Mean age = 10.42, SD = 2.92; 58% female; 75% HbSS or HbS-beta⁰ thalassemia) reported on their child's academic performance, with the majority described as on grade level (67%), followed by below grade level (21%) and above grade level (11%). Children had a mean IQ of 91.61 (SD = 14.09), VCI of 95.65 (SD = 14.02), WMI of 95.18 (SD = 13.93), and PSI of 87.70 (SD = 14.42). Thirty-four percent of children had a low IQ, 25% had a low VCI, 26% had a low WMI, and 37% had a low PSI. Caregiver-rated academic performance was associated with variance in IQ (F(2,86) = 11.75, p < .001), VCI (F(2,85) = 9.28, p < .001), WMI (F(2,86) = 10.74, p < .001), and PSI (F(2,86) = 10.07, p < .001), with those rated as below grade level reliably scoring lower than those rated as at or above grade level. Differences in median cognitive functioning relative to caregiver ratings of academic performance are depicted in Figure 1. When examining differences by age group (ages 7-11: 65%, n = 58; ages 12-16: 35%, n = 31), results indicated that ratings of academic performance were significantly associated with variance in IQ (F(2,55) = 11.91, p < .001), VCI (F(2,54) = 7.38, p = .001), WMI (F(2,55) = 13.17, p < .001), and PSI (F(2,55) = 8.90, p < .001) for younger children but not older children (all p's > .08). Sensitivity, specificity, and positive and negative predictive value results are presented in Table I.

Conclusions: Cognitive functioning in children with SCD significantly varies by caregiver ratings of academic performance. Children classified by their caregiver as being "below grade level” had lower IQ, verbal abilities, working memory, and processing speed relative to those described as "on grade level” and "above grade level.” Ratings of being below grade level demonstrated good specificity for detecting cognitive impairment but low sensitivity. Asking caregivers of children with SCD to estimate their child's academic performance relative to peers is a simple way to conduct surveillance for cognitive deficits but will result in high rates of false negatives so additional screening tools are needed to identify all children with SCD who have cognitive deficits.

No relevant conflicts of interest to declare.