Average Lifetime Hemoglobin Concentration Improves Prediction of Cognitive Outcomes in Pediatric Patients with Sickle Cell Anemia

Background: Sickle cell anemia (SCA) is associated with cognitive challenges that often worsen as children age. Previous work has established relationships between hematological markers of disease severity (i.e., hemoglobin concentration) and various neurological outcomes, including cognitive impairment. However, most studies have related static, often isolated hemoglobin concentration (Hb) values obtained from a single time-point closest to data collection. Studies of pediatric patients with phenylketonuria and Type I diabetes have demonstrated that longitudinal change and variability in phenylalanine and glucose, respectively, are better indicators of neurological and cognitive outcomes than a single value alone. Our study aimed to be the first study of pediatric patients with SCA to examine the extent to which indices of Hb control (e.g., lifetime average and variability), collected routinely in this patient group, may provide additional prognostic information. Methods: Data were collected from pediatric patients (aged 4-18 years at enrolment) with and without SCA enrolled on the Sleep Asthma Cohort-III (SAC-III) follow-up study. SAC is a mixed retrospective-prospective study assessing the impact of nocturnal oxygen desaturation on SCA complications. The present investigation assessed participants (see Figure 1 for complete participant demographics) who underwent cognitive evaluation using Wechsler scales measuring domains of IQ, processing speed (i.e., processing speed index [PSI] and Cancellation subtest), and executive function (working memory index [WMI]). Participant demographics and appropriate medical data and history (i.e., hydroxyurea therapy, silent infarction) were obtained via questionnaires and analysis of medical records. Hb (d/L) measures assessed included average lifetime values (i.e., mean and median), variability over the lifetime (i.e., standard deviation), and the single value obtained closest to data collection. Results: Correlation analyses indicated a strong positive relationship between the mean and median Hb values along with large positive associations between the average and contemporaneous values. Small non-significant correlations were demonstrated between variability and average Hb values (see Figure 1). Initial hierarchical linear regression analyses demonstrated that neither hydroxyurea use nor silent infarct (SCI) status were predictors of any cognitive outcomes or Hb values, so they were not included in any further anal