The Cooperative Study of Sickle Cell Disease (CSSCD, P2-3) Phases 2 and 3: Followup of Infant Cohort

Objectives:

A total of 709 infants (age less than 6 months) were enrolled during Phase 1 of the Cooperative Study of Sickle Cell Disease (CSSCD), and Phases 2 and 3 of the CSSCD was designed to follow these children for an additional 10 years. The study objectives included: 1) define prospectively the natural history of sickle cell disease; 2) determine the relationships between cognitive and academic functioning and brain status as determined by MRI; 3) determine the cognitive or behavioral markers of silent infarct; 4) determine the relationship of family functioning on the Family Environment Scale (FES) to brain status, cognitive functioning, and social and demographic factors; 5) continue studies that will enhance the state of knowledge on the influence of sickle cell disease on the psychosocial adjustment of children and adolescents.

Background:

Sickle cell disease is a single-gene defect that results in sickle-shaped red blood cells. Although the manifestations of sickle cell disease have been described, variations in the severity and number of manifestations, as well as interactions with other health events, leads to significant gaps in the understanding of the natural history of the disorder. For example, impairments to renal, cardiac, and pulmonary organ function are known to occur in sickle cell patients; however, the descriptions of these outcomes was generally retrospective in nature and occurred when organ damage was severe. In addition, only limited data existed on the social, economic, educational, vocational, and psychological adjustment of patients and families, and as with any chronic disease, impediments to sickle cell patients achieving their educational and vocational goals needs to be elucidated.

Subjects:

Phase 1 of the CSSCD began enrolling patients in 1978 in a multicenter, prospective study on the natural history of sickle cell disease. Participant entry ended in 1981 for all patients greater than six months of age; however, infants continued to be enrolled until 1988. A total of 4,085 participants were enrolled in Phase 1, and 709 patients represented the infant cohort. Of these patients, 450 were enrolled in the Phase 2 followup along with 17 children that were between 6 and 10 months of age at the time of Phase 1 enrollment. Phase 2 followup concluded in 1994 and 378 patients continued to be followed in the Phase 3 continuation. Data collection ended in 1998.

Design:

Routine measurements collected annually during Phase 2 included a history, physical exam, neurological exam, and laboratory measurements (CBC, platelets, fetal hemoglobin). Special studies performed longitudinally during Phase 2 included a Brain MRI, Neuropsychological evaluation and pulmonary function testing. During Phase 3, the laboratory measurements were expanded to include serum creatinine and urinalysis measurements and the special studies included a psychosocial assessment as well as brain magnetic resonance angiography.