Developmental Screening in Pediatric Sickle Cell Disease: Disease-Related Risk and Screening Outcomes in 4 Year Olds

Abstract

Objective Studies of early child development in sickle cell disease (SCD) have found modest associations between disease-related risks and developmental status in infants and toddlers, but such associations are evident by early elementary school. We screened four-year-old children with SCD using two screening strategies to assess if biomedical risk factors for neurologic disease are related to developmental screening outcomes at this intermediate age. Methods Seventy-seven four-year-old children with SCD (M = 4.5 years, SD = 0.3 years) completed developmental screenings at routine hematology visits using child testing (Fluharty Preschool Speech and Language Screenings Test, 2nd edition) and parent-report (Ages and Stages Questionnaire, 2nd edition) procedures. Genotype and other biomedical variables were coded from medical records. Results Children with higher-risk SCD genotypes (n = 52) showed lower performance than children with lower-risk genotypes (n = 25) on a measure related to neurologic disease risk in older children (syntactic processing); genotype risk was also related to rates of positive screenings on parent-reported developmental milestones (52% positive screenings in high-risk genotypes versus 12% in low-risk genotypes). Screening outcomes were also related to transcranial Doppler ultrasound findings assessing cerebral blood flow. Conclusions Developmental screening at age four years may be a useful target age for identifying preschoolers with sickle cell-related neurodevelopmental concerns. Parent-report of developmental milestones and behavioral testing each may have a role in screening for children in need of follow-up services to address potential neurodevelopmental effects from SCD.

Sociodemographic and Biomedical Correlates of Developmental Delay in 2- and 4-Year-Olds with Sickle Cell Disease

“…Seventy-seven 4-year-olds were described in a previous report. 6 In the previous report, we noted that 100 four-year-olds were screened in this time frame; however, we subsequently identified 1 four-year-old child who received an Ages and Stages Questionnaire, second edition (ASQ-2), screening but was categorized as “not screened” in the previous data set. In total, 128 two-year-olds (ages 24–35 months) and 132 four-year-olds (ages 48–59 months) with sickle cell disease (SCD) were seen for routine health maintenance visits during the study time frame (77% participation rate).…”

Utility of the Ages and Stages Questionnaire, third edition, in a comprehensive sickle cell disease clinic.

“…Based on preliminary chi square analyses, limited variability in categorical comparisons using pass, at-risk, and fail categories precluded uses of logistical regression or other categorical comparisons using disease subtype or other demographic variables. In other studies using the ASQ-3, designated screenings for all patients occurred at certain standardized intervals, which allowed for direct statistical comparisons within and across individuals (Hardy et al, 2015; Schatz et al, 2017). In a clinical sample, consistent attendance at specified periods of development may be less feasible due to missed and rescheduled appointments.…”

“…Language, motor abilities, and executive functions (e.g., attention) have been identified as additional risk areas for toddlers and preschoolers with SCD (Drazen, Abel, Gabir, Farmer, & King, 2016; Tarazi, Grant, Ely, & Barakat, 2007). Four-year-old children with higher risk SCD genotype have been found to show more concerns on developmental and language screenings compared to those with lower risk genotype, specifically in syntactic processing, which is associated with later neurocognitive risks (Schatz, Schlenz, Reinman, Smith, & Roberts, 2017). These findings suggest an important role for early identification in young children with SCD.…”

Sluggish Cognitive Tempo in Pediatric Sickle Cell Disease

“…Slowed processing speed, attention difficulties, and executive dysfunction are often identified as salient neurocognitive symptoms beginning in the preschool period, often continuing into adulthood (7). Neurodevelopmental syndromes have also been linked to disease severity in SCD with as many as half of all preschool-age children showing evidence of developmental delay with elevated rates of neurodevelopmental issues persisting into adolescence (8)(9)(10)(11).…”

“…A key disease-specific contributor to these deficits are cerebrovascular complications that interfere with oxygen delivery to the brain. Cerebrovascular effects of SCD can begin in the preschool period and increase steadily in prevalence into adulthood with half or more of all adult patients showing cerebrovascular disease (7,8,12). These disruptions to oxygen delivery are believed to underlie the development of silent cerebral infarction, the most common form of acquired brain injury documented in SCD, and changes in white matter tissue that are linked to cognitive deficits (13)(14)(15).…”