Eligibility CriteriaInclusion Criteria for Screening
1. Participant must have sickle cell anemia (hemoglobin SS) or sickle Beta-zero (null) thalassemia (hemoglobin S-B0) as confirmed at the local institution by hemoglobin analysis after six months of age.
2. Participant must be 9 to 48 months of age. All screening procedures except MRI can be completed between 9 and 12 months of age, with the exception of the MRI, for which the child must have reached the age of 12 months.
3. Informed consent must be signed by the participant's legally authorized guardian acknowledging written consent to join the study.
Exclusion Criteria for Screening
1. History of a focal neurologic event lasting more than 24 hours with medical documentation or a history of prior overt stroke.
2. Other neurological problems, such as neurofibromatosis, lead poisoning, non-febrile seizure disorder, or tuberous sclerosis.
3. Known human immunodeficiency virus (HIV) infection.
4. Treatment with anti-sickling drugs or hydroxyurea within 3 months or anticipated treatment during the course of the study.
5. Chronic blood transfusion therapy, ongoing or planned.
6. Poor adherence likely per his/her hematologist and study coordinator based on previous compliance in clinic appointments and following advice.
7. Presence or planned permanent (or semi-permanent) metallic structures attached to their body. (e.g., braces on teeth), which their physicians believe will interfere with the MRI of the brain.
8. History of two or more TCD studies with a velocity ≥ 200 cm/sec by the non-imaging technique, or ≥185 cm/sec for the imaging technique or a indeterminate TCD.
9. Significant cytopenias [absolute neutrophil count (ANC) <1500/ul, platelets <150,000/ul, reticulocytes <80,000/ul, unless the hemoglobin is > 9 g/dl]. Cytopenias will be considered transient exclusions.
10. Other significant organ system dysfunction
11. Known allergy or intolerance of hydroxyurea
12. Significant prematurity (gestational age of < 32 weeks)
Inclusion Criteria for MRI of the Brain with Sedation
1. The parents or guardians must provide consent for sedation.
Exclusion Criteria for MRI of the Brain with Sedation
1. Failure to pass MRI screening checklist
2. Obstructive sleep apnea [OSA] and receiving therapy [e.g. continuous positive airway pressure], or being evaluated or followed by a specialist for management of severe OSA
3. Less than 12 months of age.
4. Allergic reactions such as urticaria or bronchospasm or previous adverse reactions to propofol, eggs, or soy products, if used at the participating center.
5. Allergy or previous adverse reaction to pentobarbital, if used at the participating center
6. Known major chromosomal abnormalities
7. Known airway abnormalities that would increase the risk of sedation/anesthesia.
8. Room air oxygen saturation greater than or equal to 5% below the participant's baseline on the day of the MRI with sedation.
9. Room air oxygen saturation <90% on the day of the MRI with sedation.
10. Hemoglobin <6.5 g/dl (must be measured within 30 days of MRI).
11. Temperature >38˚ C on the day of sedation
8. Upper or lower respiratory infection, active bronchospasm, acute chest syndrome, splenic sequestration or other acute complications of sickle cell disease other than pain in the last 4 weeks (from resolution of symptoms) 9. Pain crisis within two weeks requiring treatment with opiates
Inclusion Criteria for Randomization
1. Participant must be 12 to 54 months of age
2. Participant must have successfully completed screening procedures (TCD, MRI of the brain, neurology exam, and cognitive evaluation)
Exclusion Criteria for Randomization
1. Participants whose MRI show a silent or overt cerebral infarct.
2. Participants who have a non-imaging TCD study with a velocity ≥ 185 cm/sec or a TCD that is indeterminate.
3. Participants with abnormal kidney function (creatinine > 0.8 mg/dl)
4. Significant cytopenias [absolute neutrophil count (ANC) <1500/ul, platelets <150,000/ul, reticulocytes <80,000/ul, unless the hemoglobin is > 9 g/dl]. Cytopenias will be considered transient exclusions.