Brain volume in pediatric patients with sickle cell disease: evidence of volumetric growth delay?

BACKGROUND AND PURPOSE Despite the large body of data available about somatic growth delay in patients with sickle cell disease (SCD), virtually nothing is known about the effect of the disease on volumetric growth of the brain. This study was designed to test a hypothesis that children with SCD have a disease-related delay in brain volumetric growth compared with healthy children. METHODS A cross-sectional study design was used to evaluate 83 children with SCD and 43 age-similar healthy children, including 27 patient siblings. Brain volume was measured by segmenting and classifying MR imaging data, by using at least three separate image sets (T1-, T2-, and proton density-weighted MR images). A linear model was used to compare the various brain volumes with the covariates of group (patient versus control) and age, with age treated as a continuous variable. RESULTS With age controlled for, no significant difference was noted in total brain volume between patients and control subjects at age 9.5 years. However, patients showed a deficit specifically in gray matter volume (P=.005), without significant differences in white matter or ventricular volume. The deficit in patient gray matter was greater in central gray matter (P <.005) than in cortical gray matter (P <.02). In healthy control subjects, gray matter volume decreased significantly with age (P <.005), probably due to myelination of white matter tracts. In patients with SCD, gray matter volume did not change with age. CONCLUSION Volumetric growth of brain gray matter may be delayed in children with SCD, suggesting that there may be neurodevelopmental consequences of this disease.