Prognostic significance of early vaso-occlusive complications in children with sickle cell anemia

Abstract

Sickle cell anemia (SS) is highly phenotypically variable, and early predictors of outcome could guide clinical care. To determine whether early vaso-occlusive complications predicted subsequent adverse outcomes in the Dallas Newborn Cohort, we studied all members with SS or sickle-beta0-thalassemia who presented in their first year of life and had 5 years or more of follow-up. We defined 3 potential early predictors: hospitalizations in the first 3 years of life for (1) painful events other than dactylitis, (2) dactylitis, and (3) acute chest syndrome (ACS). We studied the associations of these predictors with the following late adverse outcomes (occurring after the third birthday): death, first overt stroke, use of disease-modifying therapy, and hospitalizations for pain events and ACS. None of the early events predicted death or stroke. Early pain and ACS both predicted a modest, temporary increase in the number of later painful episodes, but early ACS strongly increased the odds of more frequent ACS throughout childhood. Dactylitis had limited utility as a predictor. Although we still lack a useful prognostic framework for young children with SS, those who experience early ACS might be candidates for higher risk interventions to mitigate or cure their disease.

Figure 1

Associations between early predictors and late episodes of pain. Depicted here are the mean differences in the number of late painful episodes for groups defined by the occurrence or not of each of the 3 early predictors (whiskers are SEs). Mean difference = (mean number of painful episodes in predictor-positive group) − (mean number of painful episodes in predictor-negative group). The mean differences are shown for cumulative, overlapping intervals of follow-up beginning with the third birthday. **P < .01; ***P < .001.

Figure 2

Associations between early predictors and late episodes of ACS. Depicted here are the mean differences in the number of late episodes of ACS for groups defined by the occurrence or not of each of the 3 early predictors (whiskers are SEs). Mean difference = (mean number of ACS episodes in predictor positive group) − (mean number of ACS episodes in predictor negative group). The mean differences are shown for cumulative, overlapping intervals of follow-up beginning with the third birthday *P < .05; **P < .01; ***P < .001.