Hydroxyurea and growth in young children with sickle cell disease

Abstract

Background: Growth impairment is a known complication of sickle cell disease. Effects of hydroxyurea (HU) on growth in very young children are not known.

Methods: Height, weight, BMI, and head circumference (HC) were compared with World Health Organization (WHO) standards in BABY HUG, a multicenter, randomized, double-blinded, placebo-controlled 2-year clinical trial of HU in 193 children 9 to 18 months of age. Anthropometric data were closely monitored and converted to z scores by using WHO standardized algorithms for descriptive analyses. The treatment and placebo groups were compared longitudinally by using a mixed model analysis.

Results: At entry, the z scores of BABY HUG children were higher than WHO norms. After 2 years of HU or placebo treatment, there were no significant differences between the groups, except for the mean HC z scores at study exit (HU: +0.8 versus placebo: +1.0, P = .05). Baseline z scores were the best predictors of z scores at study exit. The absolute neutrophil count, absolute reticulocyte count, and total white blood cell count had significant negative correlations with growth measures.

Conclusions: Both groups had normal or near normal anthropometric measures during the study. The HC z scores at study entry and exit were slightly greater than WHO norms. Higher baseline white blood cell count, absolute reticulocyte count, and absolute neutrophil count were associated with poorer growth. The significance of the slightly lower HC in the treatment group at study exit is not clear. Trends toward normalization of weight and height and effects on HC will be monitored in ongoing BABY HUG follow-up studies.

Keywords: BMI; children; growth; head circumference; height; hydroxyurea; sickle cell disease; weight.

FIGURE 1

Longitudinal comparison of WHO standardized height z scores between children treated with HU and placebo. Z scores for height, weight, BMI, and HC were calculated by using SAS macros downloaded from the WHO Web site and controlled for gender and age. Data were averaged within each 3-month interval after treatment assignments with the baseline measurement used as the time 0. Student’s t test was used for comparison with the WHO normal population. Proc MIXED was used to analyze longitudinal data. BABY HUG children were larger than the WHO population on all parameters at the beginning of the study, and there was no difference between the treatment groups except for the BMI that was larger at each observation point in the HU group (trend not significant). There were no significant differences between the treatment groups for height, weight, and BMI at exit. The HC in the treatment group was slightly smaller but still within normal limit at the end of the study. Baseline z scores were the best predictors of z scores for all growth parameters.

FIGURE 2

Longitudinal comparison of WHO standardized weight z scores between children treated with HU and placebo. Z scores for height, weight, BMI, and HC were calculated by using SAS macros downloaded from the WHO Web site and controlled for gender and age. Data were averaged within each 3-month interval after treatment assignments with the baseline measurement used as the time 0. Student’s t test was used for comparison with the WHO normal population. Proc MIXED was used to analyze longitudinal data. BABY HUG children were larger than the WHO population on all parameters at the beginning of the study, and there was no difference between the treatment groups except for the BMI that was larger at each observation point in the HU group (trend not significant). There were no significant differences between the treatment groups for height, weight, and BMI at exit. The HC in the treatment group was slightly smaller but still within normal limit at the end of the study. Baseline z scores were the best predictors of z scores for all growth parameters.

FIGURE 3

Longitudinal comparison of WHO standardized BMI z scores between children treated with HU and placebo. Z scores for height, weight, BMI, and HC were calculated by using SAS macros downloaded from the WHO Web site and controlled for gender and age. Data were averaged within each 3-month interval after treatment assignments with the baseline measurement used as the time 0. Student’s t test was used for comparison with the WHO normal population. Proc MIXED was used to analyze longitudinal data. BABY HUG children were larger than the WHO population on all parameters at the beginning of the study, and there was no difference between the treatment groups except for the BMI that was larger at each observation point in the HU group (trend not significant). There were no significant differences between the treatment groups for height, weight, and BMI at exit. The HC in the treatment group was slightly smaller but still within normal limit at the end of the study. Baseline z scores were the best predictors of z scores for all growth parameters.

FIGURE 4

Longitudinal comparison of WHO standardized HC z scores between children treated with HU and placebo. Z scores for height, weight, BMI, and HC were calculated by using SAS macros downloaded from the WHO Web site and controlled for gender and age. Data were averaged within each 3-month interval after treatment assignments with the baseline measurement used as the time 0. Student’s t test was used for comparison with the WHO normal population. Proc MIXED was used to analyze longitudinal data. BABY HUG children were larger than the WHO population on all parameters at the beginning of the study, and there was no difference between the treatment groups except for the BMI that was larger at each observation point in the HU group (trend not significant). There were no significant differences between the treatment groups for height, weight, and BMI at exit. The HC in the treatment group was slightly smaller but still within normal limit at the end of the study. Baseline z scores were the best predictors of z scores for all growth parameters.