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BACKGROUND: The literature on cognitive and academic outcomes for children with sickle cell disease (SCD) who experience perinatal risk factors is limited. We aimed to evaluate if low birthweight (LBW), gestational age, and history of neonatal intensive care unit (NICU) admission were associated with neurocognitive functioning, grade retention, or receipt of early intervention or formal educational support in children with SCD. PROCEDURES: This prospective birth cohort study included 336 participants, ages 8-18, with SCD, who received cognitive testing as part of standard of care and whose caregivers completed behavioral rating scales. Multivariable generalized linear regression models were used to examine associations between perinatal risks and outcome variables, after adjusting for demographic and medical covariates. RESULTS: The prevalence of NICU admission and LBW were 12.03% and 13.50%, respectively. Lower birthweight, earlier gestational age, and NICU admission were associated with worse working memory performance and receipt of early intervention services. Lower birthweight and NICU admission were also associated with slower processing speed. History of NICU admission was associated with caregiver ratings of hyperactivity and emotional dysregulation. The effects of perinatal risk factors on neurocognitive, academic, or educational outcomes were not dependent on SCD genotype. CONCLUSIONS: History of LBW or NICU admission was associated with worse cognitive outcomes and increased use of early intervention services among children with SCD. Early identification of perinatal risk factors will help identify children who will benefit from formal developmental or neuropsychological evaluations to manage the comorbidity of SCD and perinatal risks and facilitate increased intervention.
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Anemia de Células Falciformes , Humanos , Anemia de Células Falciformes/complicaciones , Femenino , Masculino , Niño , Adolescente , Factores de Riesgo , Estudios Prospectivos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Recién Nacido de Bajo Peso , Embarazo , Edad Gestacional , Estudios de SeguimientoRESUMEN
Sickle cell disease (SCD) is an inherited blood disorder that is associated with developmental delays and neurocognitive deficits. This review details key findings related to neurocognitive outcomes for children and adults with emphasis on the impact of neurological correlates and disease severity. Associations between neurocognition, demographic factors and social determinants of health are also reviewed. Emerging literature has reported on the neurocognitive impact of SCD in children and adolescents in Africa and Europe, including children from immigrant communities. Neurocognitive deficits are linked to poor functional outcomes, including transition from paediatric to adult care, medication adherence and unemployment. Integrating neuropsychology into multidisciplinary care for individuals with SCD can assist with identification and management of neurocognitive concerns, intervention development, individualized care plan development and continued multidisciplinary research.
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Anemia de Células Falciformes , Transición a la Atención de Adultos , Adolescente , Adulto , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/terapia , Niño , Cognición , Humanos , Neuropsicología , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Transcranial doppler (TCD) ultrasonography can be used to identify stroke risk in children with sickle cell anemia. Previous studies have reported mixed findings on neurocognitive outcomes in children with elevated TCD. This study examined associations between TCD velocity and neurocognitive outcomes in children and adolescents without prior history of stroke. PROCEDURE: Participants were selected from the Sickle Cell Clinical Research Intervention Program cohort. The highest recorded mean maximum TCD velocity was selected for analysis, along with participant's most recent data from serial neurocognitive surveillance. RESULTS: A total of 200 children with sickle cell anemia completed neurocognitive testing (109 males, 91 females; mean age 12.7 years [SD = 3.56]). Most participants were prescribed hydroxyurea (72%) at the time of neurocognitive testing and nearly 16% had a history of chronic transfusions prior to neurocognitive evaluation. Mean age at time of highest TCD value was 6.6 years (SD = 2.5) and 13.5% of screenings were abnormal (≥200 cm/s). Mean interval between TCD and most recent neurocognitive evaluation was 6.1 years (±3.5). There were no significant differences in the interval between TCD and neurocognitive testing across normal, conditional, and abnormal groups. Maximum TCD velocity was not significantly associated with neurocognitive outcomes in multivariate models. CONCLUSIONS: History of elevated TCD in the absence of overt stroke should not be considered a risk factor for poor neurocognitive outcomes in children and adolescents with sickle cell anemia on modern disease-modifying therapy.
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Anemia de Células Falciformes , Accidente Cerebrovascular , Adolescente , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico por imagen , Anemia de Células Falciformes/tratamiento farmacológico , Velocidad del Flujo Sanguíneo , Transfusión Sanguínea , Niño , Femenino , Humanos , Hidroxiurea/uso terapéutico , Masculino , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/etiología , Ultrasonografía Doppler TranscranealRESUMEN
Individuals with sickle cell disease (SCD) experience neurocognitive decline, low medication adherence, increased unemployment, and difficulty with instrumental activities of daily living (IADL). The relationship between self-perceived cognitive difficulties and IADLs, including employment, school enrollment, independence, engagement in leisure activities, and medication adherence is unknown. We hypothesized that self-reported difficulties across neurocognitive areas would predict lower IADL skills. Adolescent and adult participants of the multi-site Sickle Cell Disease Implementation Consortium (SCDIC) (n = 2436) completed patient-reported outcome (PRO) measures of attention, executive functioning, processing speed, learning, and comprehension. Cognitive symptoms were analyzed as predictors in multivariable modeling. Outcome variables included 1) an IADL composite that consisted of employment, participation in school, reliance on others, and leisure pursuits, and 2) hydroxyurea adherence. Participants reported cognitive difficulty across areas of attention (55%), executive functioning (51%), processing speed (57%), and reading comprehension (65%). Executive dysfunction (p < 0.001) and sometimes or often experiencing learning difficulties (p < 0.001 and p = 0.04) and poor comprehension (p = 0.000 and p = 0.001), controlled for age (p < 0.001), pain (p < 0.001), and hydroxyurea use (p = 0.001), were associated with poor IADL skills. Executive functioning difficulties (p = 0.021), controlled for age (p = 0.013 for ages 25-34), genotype (p = 0.001), and hemoglobin (p = 0.004), predicted hydroxyurea non-adherence. Analysis of PRO measures indicated that cognitive dysfunction is prevalent in adolescents and adults with SCD. Cognitive dysfunction translated into clinically meaningful outcomes. PRO of cognitive symptoms can be used as an important adjunct clinical tool to monitor symptoms that impact functional skills, including engagement in societal activities and medication adherence.
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Actividades Cotidianas , Anemia de Células Falciformes/complicaciones , Disfunción Cognitiva/etiología , Adolescente , Adulto , Anemia de Células Falciformes/tratamiento farmacológico , Antidrepanocíticos/uso terapéutico , Femenino , Humanos , Hidroxiurea/uso terapéutico , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Adulto JovenRESUMEN
Objective: Sickle cell disease (SCD) is an inherited hematologic disorder that impacts approximately 100,000 Americans. This disease is associated with progressive organ damage, cerebral vascular accident, and neurocognitive deficits. Recent guidelines from the American Society of Hematology (ASH) recommend cognitive screening with a psychologist to help manage cerebrovascular risk and cognitive impairment in this population. SCD patients benefit from neuropsychology services and several institutions already have programs in place to monitor cognitive risk. Program Description: We describe a longitudinal neurocognitive evaluation program at our institution that serves all patients with SCD, regardless of disease severity or referral question. The Sickle Cell Assessment of Neurocognitive Skills (SCANS) program was established in 2012. We outline the program's theoretical framework, timepoints for evaluation, test battery, logistics, patient demographics, integration with research programming, and multidisciplinary collaboration to support optimal outcomes. Program Outcomes: Our program has provided 716 targeted neuropsychological evaluations for patients over the last decade. Nearly 26% of patients in the program have been followed longitudinally. The most common diagnoses generated across cross-sectional and longitudinal evaluations include cognitive disorder (n = 191), attention-deficit/hyperactivity disorder (n = 75), and specific learning disorder (n = 75). Approximately 87% of patients who participated in SCANS during late adolescence successfully transitioned from pediatric to adult care. Conclusion: We discuss considerations for developing programming to meet the needs of this population, including tiered assessment models, timing of evaluations, scope, and reimbursement. Program models that utilize prevention-based tiered models or targeted evaluations can assist with serving large volumes of patients.
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PURPOSE: Neurocognitive impairment is a common and debilitating complication of sickle cell disease (SCD) resulting from a combination of biological and environmental factors. The catechol-O-methyltransferase (COMT) gene modulates levels of dopamine availability in the prefrontal cortex. COMT has repeatedly been implicated in the perception of pain stimuli and frequency of pain crises in patients with SCD and is known to be associated with neurocognitive functioning in the general population. The current study aimed to examine the associations of genetic variants in COMT and neurocognitive functioning in patients with SCD. PATIENTS AND METHODS: The Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort was used as a discovery cohort (n = 166). The genotypes for 5 SNPs (rs6269, rs4633, rs4818, rs4680, and rs165599) in COMT were extracted from whole genome sequencing data and analyzed using a dominant model. A polygenic score for COMT (PGSCOMT) integrating these 5 SNPs was analyzed as a continuous variable. The Cooperative Study of Sickle Cell Disease (CSSCD, n = 156) and the Silent Cerebral Infarction Transfusion (SIT, n = 114) Trial were used as 2 independent replication cohorts. Due to previously reported sex differences, all analyses were conducted separately in males and females. The Benjamini and Hochberg approach was used to calculate false discovery rate adjusted p-value (q-value). RESULTS: In SCCRIP, 1 out of 5 SNPs (rs165599) was associated with IQ at q<0.05 in males but not females, and 2 other SNPs (rs4633 and rs4680) were marginally associated with sustained attention at p<0.05 in males only but did not maintain at q<0.05. PGSCOMT was negatively associated with IQ and sustained attention at p<0.05 in males only. Using 3 cohorts' data, 4 out of 5 SNPs (rs6269, rs4633, rs4680, rs165599) were associated with IQ (minimum q-value = 0.0036) at q<0.05 among male participants but not female participants. The PGSCOMT was negatively associated with IQ performance among males but not females across all cohorts. CONCLUSION: Select COMT SNPs are associated with neurocognitive abilities in males with SCD. By identifying genetic predictors of neurocognitive performance in SCD, it may be possible to risk-stratify patients from a young age to guide implementation of early interventions.
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Anemia de Células Falciformes , Catecol O-Metiltransferasa , Polimorfismo de Nucleótido Simple , Humanos , Catecol O-Metiltransferasa/genética , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/psicología , Masculino , Femenino , Adulto , Adulto Joven , Estudios Longitudinales , Adolescente , Genotipo , Cognición/fisiología , Persona de Mediana EdadRESUMEN
BACKGROUND: Transition-age patients with sickle cell disease (SCD) are at risk for poor outcomes associated with incomplete transition readiness and neurocognitive deficits. Study objectives were to: 1) test if a SCD-specific measure of self-management skills was associated with transition outcomes and 2) evaluate if caregiver-reported executive functioning was associated with self-management skills and transition outcomes among youth with SCD. RESEARCH DESIGN AND METHODS: Youth/caregivers were selected from a longitudinal cohort study. Caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF); caregivers and youth completed the Self-Management Skills Checklist (SMSC) at a median age of 16.8 ± 0.6 years. Non-parametric tests compared SMSC and transition outcomes. Regression assessed the incremental validity of SMSC in predicting transition outcomes. RESULTS: In total, 95 participants (54% male, 55% severe genotype) completed the SMSC assessment. Most participants (87%) transferred to adult care within six months and 87% were retained for at least 12 months. BRIEF and caregiver-reported SMSC assessments were weakly, negatively correlated (ρ = -0.25, p = 0.0392) but were not significant in predicting transition outcomes (p > 0.05). CONCLUSIONS: The SMSC and executive function did not predict adult care engagement. Development of readiness assessments that predict care engagement and reflect self-efficacy is important for monitoring transition-aged patients with SCD.
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Anemia de Células Falciformes , Transición a la Atención de Adultos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Cuidadores , Estudios Longitudinales , Aceptación de la Atención de SaludRESUMEN
Congenital heart disease (CHD) is among the most prevalent birth defects in the United States. Given that children with CHD are at risk for differences with development, learning, and psychosocial functioning, effective intervention becomes a central tenant of recommendations following neuropsychological consultation and evaluation. The primary focus of this review is to summarize available interventions for children and adolescents with CHD. The existing CHD literature has concentrated on early developmental services, psychopharmacological treatment, and need for academic supports. The literature is limited with regard to intervention studies that target cognitive deficits and psychosocial difficulties. To address this discrepancy, efficacious interventions that have been used to mitigate these concerns within other medical groups are also discussed in an effort to provide options for alternative recommendations and services. The current paper is intended to facilitate comprehensive care for cardiac patients by providing clinicians with a review of the available intervention literature, as well as potential interventions that may serve as supplemental strategies in the interim.