Neurdevelopmental Deficits Among 80 Infants and Toddlers with Sickle Cell Disease

Neurocognitive deficits by school age in children with sickle cell disease (SCD), with and without a history of stroke, has been well established. However, little is understood with respect to the onset and course of these deficits in early childhood and how these may relate to SES and disease status. We are undertaking a 4-year mixed cross-sectional longitudinal study of early neurodevelopmental status in children younger than 4 years of age with SCD. The primary aims are to: (1) characterize the prevalence and nature of the developmental deficits in infants and toddlers while controlling for socio-economic status (SES); (2) examine the moderating effects of sickle cell phenotype, hematologic severity, and parent characteristics on developmental outcome. The current presentation is based on the first 80 baseline neurodevelopmental evaluations.

Children 3 ½ years of age or younger with SCD of any phenotype were eligible to participate. Comprehensive neurodevelopmental evaluations using the Bayley Scales of Infant Development were conducted when the child reached specific age levels (9, 15, 21, 30, and 40 months), with an ultimate planned sample size of a minimum of 45 children with SCD at each of the five age levels. Demographics and data regarding phenotype, hematologic variables, and occurrence of pain crises were obtained separately.

To date, 199 children have been enrolled in the study. We have conducted 205 evaluations and completed data analysis of the baseline data for 80 patients. Of those 80, phenotype distribution was representative of the sickle cell population (HbSS=56%, HbSC=31%). Gender was balanced (51% female). As expected, race/ethnicity of most children was African/African American (95%), about 5% Hispanic/Biracial. Maternal education attainment was high, as almost half of the mothers (48%) were college graduates.

Mean Mental Index was 84.2 (sd=13.5) and Motor Index was 89.1 (sd=14.4) (compared to published norm means of 100, sd=15). Fourteen children (17.5%) had a significant delay (Index score > 2 sd below the mean) on either the Mental or Motor Index, with 7 children significantly delayed on both. Lower SES, based on maternal education attainment, was not sufficient to explain developmental delay. Poor performance was present in 10% of children whose mothers were college graduates. Male children were at significantly greater risk for delays, controlling for SES, pain crisis, pneumonia/ACS, and %hemoglobin. Odds ratio of significant developmental delay was >9 times more likely among those who had vaso-occlusive pain episode, controlling for SES, gender, pneumonia/ACS, and hemoglobin concentration. Of note, none of the children had been identified as delayed by their primary care physician or sickle cell provider.

Early cognitive and motor delays are present in SCD and not sufficiently explained by lower SES. Increased vulnerability of male gender is consistent with other at-risk populations, but has not been previously addressed in SCD research. Significant developmental delay in children with chronic illness may go unrecognized by primary care practices, medical specialty clinics, or parents. The importance of routine neurodevelopmental assessment for children with chronic medical disease, and SCD in particular, is clear.

This study was funded by the NHLBI as a Patient Services Project within the Washington Area Comprehensive Sickle Cell Center.

No relevant conflicts of interest to declare.