Systemic Inflammation and Neurocognitive Deficits in School-Age Children with Sickle Cell Disease.

Sickle cell disease (SCD) causes inflammation that contributes to poor clinical outcomes, including cerebrovascular disease (CVD). CVD can take several forms in SCD, including neurocognitive deficits without visible cerebral infarction. The role of chronic inflammation in cognitive development in SCD has received little attention to-date. We aimed to study novel markers of systemic inflammation: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the systemic inflammation index (SII) to describe developmental trends and relationships to cognitive outcomes in SCD at early elementary school-age. Sixty-one children with SCD and no history of stroke were identified who completed an early elementary school age cognitive screening. Biological variables, including absolute neutrophil, lymphocyte, platelet counts, reticulocyte percentage, and hemoglobin levels were collected from routine blood lab data to assess chronic inflammation and anemia severity. Values from routine blood draws were examined over three years prior to screening. Cognitive measures included tests of processing speed, visual motor, language, and early academic skills. Seven children were excluded due to lack of biological variables (final sample: n = 55 children; mean age = 6.4 ± 0.5 years; 60% male; 81.8% severe SCD genotypes). Slope values indicated that SII levels increased with older age. There was an inverse relationship between hemoglobin and SII [r= -.32, p=.02]. Significant differences emerged in levels of SII for severe (M = 534.28, SD = 290.4) versus moderate (M = 309.35, SD = 143.74; t(53)=2.37, p=.02] genotypes, but not for NLR or PLR. T-tests revealed no significant differences in NLR, PLR, or SII values with cognitive test scores or between positive and negative overall screenings. Observed effect sizes were small. SII appeared to have the most validity evidence as a marker of chronic inflammation in SCD; however, there were no observed relationships between chronic inflammation and neurocognitive performance in this age range.