Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)-A randomized, placebo-controlled phase II feasibility/pilot study.

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS-ß0-thalassemia subtypes of SCD age 12-48 months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary-a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary-a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score-SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], p = .2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, p = .072, below the p-value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD.

Current developmental screening practices in young children with sickle cell disease.

Despite recent developmental screening guidelines, rates of neurodevelopmental disorders (NDDs) remain lower than expected in children with sickle cell disease (SCD). A retrospective chart review identified 276 eligible patients; 214 charts were available for developmental screening and 207 charts for autism-specific screening. Developmental surveillance/screening was conducted in 70% of charts and autism-specific screening in 19% of charts. Validated tools were used in 32% of developmental screenings and 92% of autism-specific screenings. Many children (57%) were screened outside recommended ages. In conclusion, children with SCD are not regularly receiving appropriate developmental screening and surveillance by their healthcare providers.

Co-Occurrence of Neurodevelopmental Disorders in Pediatric Sickle Cell Disease.

OBJECTIVE: The objective of this study is to retrospectively determine the co-occurrence, associated characteristics, and risk factors for neurodevelopmental disorders (NDD) in a pediatric sickle cell disease (SCD) clinic population. METHOD: We investigated the co-occurrence and features of NDD in pediatric SCD through a retrospective cohort study conducted between July 2017 and January 2019. The participants were patients with SCD younger than 18 years of age identified from our institutions' clinic rosters and medical records databases. RESULTS: A total of 276 participants were eligible for study inclusion, and 65 participants were found to have various NDD. Children with SCD and NDD were more likely to have a history of multiple SCD-related complications in comparison to children with SCD without NDD. Children with SCD and NDD were more likely to use disease-modifying therapies in comparison to children with SCD without NDD (χ2 27.2, p < 0.001). CONCLUSION: Children with SCD and NDD have higher odds of having certain disease-related complications and higher use of disease-modifying treatments than children with SCD who do not have NDD. Screening and diagnoses of NDD may be relevant to clinical management of pediatric SCD.