Effect of High-dose Vitamin A Supplementation in Children With Sickle Cell Disease: A Randomized, Double-blind, Dose-finding Pilot Study.

Suboptimal vitamin A status (serum retinol <30 µg/dL) is associated with poor clinical outcomes in children with the hemoglobin-SS disease (HbSS), and supplementation with the recommended daily allowance of retinol is ineffective in improving vitamin A status. In a single-center randomized blinded dose-finding pilot study, we compared vitamin A and nutritional status in children with HbSS to healthy children and explored the impact of high-dose supplementation on the primary outcome serum vitamin A status. Exploratory outcomes included hematologic, nutritional, immunologic, and muscle function status in children with HbSS. A mixed-effects linear regression model evaluated associations between vitamin A dose, serum retinol, and exploratory outcomes. Twenty healthy children participated, and 22 subjects with HbSS were randomized to oral 3000 or 6000 IU/d retinol for 8 weeks; 21 subjects completed all evaluations. Serum retinol, growth, and nutritional status were all suboptimal in HbSS subjects at baseline, and supplementation did not change vitamin A status. Fetal hemoglobin (Δ=2.5, 95% confidence interval [CI], 0.5-4.3), mean corpuscular volume (Δ=2.7, 95% CI, 0.7-4.7), mean corpuscular hemoglobin (Δ=1.4, 95% CI, 0.5-2.3), and mean corpuscular hemoglobin concentration (Δ=0.5, 95% CI, 0.1-0.9) all improved with supplementation. Mild improvements in erythrocyte indices, growth status, and muscle function occurred independent of hydroxyurea use.

Positive blood cultures in sickle cell disease: time to positivity and clinical outcome.

PURPOSE: To prospectively identify all cases of bacteremia in children with sickle cell disease (SCD), establish time to positivity for various microorganisms, correlate clinical findings with microbiology data, and determine the antibiotic resistance pattern of the pneumococcal isolates. METHODS: All positive blood cultures from children with SCD followed at the Children's Hospital of Philadelphia from January 1993 through May 2001 were included. Isolates were classified as pathogen or contaminant. Demographic and clinical information was abstracted from the medical records. Time to positivity and antibiotic resistance data were generated in the microbiology laboratory. RESULTS: One hundred forty-one positive blood culture bottles were obtained during distinct febrile episodes. Thirty-nine percent contained pathogens and 61% contained contaminants. The average time to positivity was 17.1 hours in the pathogen group and 29.5 hours in the contaminant group (P < 0.0001). Streptococcus pneumoniae was the most common pathogen (42% of total), with a mean patient age of 3.5 years. Gram-negative rods were the second most common organism (28% of total), with a mean patient age of 8.1 years. Thirty-one percent of the pneumococcal isolates were resistant to penicillin. Thirty-five percent of the pneumococcal isolates grew from children with a focus of infection. Acute chest syndrome was noted in 26% of patients with a positive blood culture for S. pneumoniae. Sixty-seven percent of Salmonella isolates and 50% of Staphylococcus aureus isolates grew from patients who developed osteomyelitis. CONCLUSIONS: The average time to positivity for pathogens can be used in conjunction with other factors to determine the length of observation required for children with SCD who present with febrile illness. Chest radiographs should be obtained on children with SCD who are bacteremic with S. pneumoniae. Bone scans should be obtained on children with SCD who are bacteremic with Salmonella or S. aureus.