Improved survival in homozygous sickle cell disease: lessons from a cohort study.

OBJECTIVE: To examine whether simple interventions in a sickle cell clinic improve survival in sickle cell disease. DESIGN: Survival curve analysis and hazard ratios in a cohort study followed from birth. SETTING: MRC Laboratories (Jamaica) at the University of the West Indies, and Victoria Jubilee Hospital, Kingston, Jamaica. SUBJECTS: 315 patients with homozygous sickle cell disease detected during the screening of 100,000 consecutive non-operative deliveries between June 1973 and December 1981 at the main government maternity hospital, Kingston, Jamaica. INTERVENTIONS: Prophylactic penicillin to prevent pneumococcal septicaemia, parental education in early diagnosis of acute splenic sequestration, close monitoring in sickle cell clinic. MAIN OUTCOME MEASURES: Survival. RESULTS: Survival appeared to improve, the log rank test for trend comparing the first, second, and last third of the study reaching borderline significance (P = 0.05). Combined deaths from acute splenic sequestration and pneumococcal septicaemia-meningitis declined significantly (test for trend, P = 0.02). CONCLUSION: Early diagnosis and simple prophylactic measures significantly reduce deaths associated with homozygous sickle cell disease.

Prepubertal growth and skeletal maturation in children with sickle cell disease.

In a longitudinal study of 298 children with homozygous sickle cell (SS) disease and 157 children with hemoglobin SC disease, between birth and 9 years of age, observations of weight and height were made. These were compared with similar data derived from an age- and sex-matched group of 231 children with a normal hemoglobin (AA) genotype. Growth in children with SC disease was not significantly different from that in normal children, but children with SS disease had statistically significant, and progressive, deficits in both weight and height before 2 years of age. The average deficit approached 1 SD below the normal mean for age by 9 years. Observations of skeletal maturity, based on radiologic assessment of bone age at the wrist, were made on a proportion of these children at 5 and 8 years of age. Children with SS disease were significantly retarded at 8 years but not 5 years, which is consistent with increasing deficit in height. These observations confirm the early impact of SS disease on physical development and provide standards from which clinical expectations of growth may be derived. The relevance of these findings and their relationship to the characteristic delay in pubertal development is discussed together with a review of possible etiologic factors. The benign nature of SC disease is endorsed by the absence of an effect on growth in the prepubertal child.

Pneumococcal and other infections in children with sickle-cell hemoglobin C (SC) disease.

The pattern of infection was compared in 139 children with sickle cell-hemoglobin C (SC) disease and in 250 control children with a normal hemoglobin (AA) genotype ascertained at birth and followed prospectively for periods of zero to six years. Both infection incidence rates and survival curve analysis indicated highly significant increases in serious infection among children with SC disease. Respiratory infection and gastroenteritis were the most common infections, but only respiratory infections were significantly more frequent in SC disease. Pneumococcal bacteremia was confined to the SC group. No hematologic differences were apparent between SC patients with and without a history of serious infection, but infection was significantly more common in patients manifesting early splenomegaly.

Early deaths in Jamaican children with sickle cell disease.

In Jamaican children with homozygous sickle cell (SS) disease diagnosed at birth two-year survival was 87%, compared with 95% in children with sickle cell-haemoglobin C (CS) disease, and 99% in normal controls. Death among those with SS disease occurred most often between the ages of 6 and 12 months. Principal causes were acute splenic sequestration and pneumococcal infection. Neonatal diagnosis of haemoglobinopathies must be followed by close observation if mortality is to be reduced by early diagnosis and treatment of these complications.