Cognition and education benefits of increased hemoglobin and blood oxygenation in children with sickle cell disease.

Background: Among individuals with sickle cell disease (SCD), decreased hemoglobin is associated with lower oxygen saturation (SpO2) and increased risk of stroke, both of which are associated with lower intelligence quotient (IQ) scores. Thus, increasing hemoglobin and SpO2 in individuals with SCD may increase IQ and educational attainment.
Methods: A cohort simulation model was built to determine academic performance and educational attainment based on cognitive function (measured by IQ) of a pediatric SCD cohort randomly assigned to treatment and control groups. The model contained two key stages: childhood (<10 years) and adolescence (≥10 years). In stage 1, increased hemoglobin and increased SpO2 (assigned to the treatment group) were determinants of higher IQ, prevention of IQ deterioration over time. Increased hemoglobin was also a determinant of decreased stroke risk. In stage 2, improvement in adolescent IQ as a result of treatment was a determinant of academic performance.
Results: In a simulated cohort of 2000 children and adolescents with SCD (52.5% female, 50% treated), stroke incidence was predicted to be 44.4% lower among the treated group than the untreated group (4.5% versus 8.1%, respectively). The average IQ among the treated group was estimated to be 91.1 compared with 82.9 in the untreated group (a 9.9% difference; P<0.001). Finally, high school (≥12 years of education) completion rates were estimated to be 64.7% higher among the treated group: 76.1% of the treated group was projected to complete high school compared with 46.2% of the untreated group.
Conclusions: Our model predicts that an average improvement in hemoglobin of 1.1 g/dL (11 g/L) among individuals with SCD may be associated with improved neurocognition and educational outcomes. These improvements may also generate benefits not captured by our model, including improved quality of life, employment, and income.
Competing Interests: Joanna P. MacEwan: Current employee of Genesis Research, former employee of PRECISIONheor, a life sciences research consulting firm paid by Global Blood Therapeutics, Inc., to conduct this study; research funding from NHLBI, HRSA, PCORI, and ASH. Allison A. King: Research funding from Global Blood Therapeutics, Inc. Kim Smith-Whitley: Former employee of Global Blood Therapeutics, Inc., at the time of the study; Andy Nguyen and Irene Agodoa: Former employees at Global Blood Therapeutics, Inc., at the time of the study. Anuj Mubayi: Current employee of The Public Health Company, former employee of PRECISIONheor, a life sciences research consulting firm paid by Global Blood Therapeutics, Inc, to conduct this study. Global Blood Therapeutics, Inc. is a wholly owned subsidiary of Pfizer Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2023 MacEwan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)