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.

Clinical Manifestations of Sickle Cell Anemia: Infants and Children

“…Children with SCD on chronic transfusion therapy have been shown to have normalization of growth . Infants with HbSS treated with hydroxyurea for 2 years on the BABY HUG study had no signifi cant differences in height and weight compared to both untreated infants with HbSS and World Health Organization standards (Rana et al 2014 ). Long-term follow-up of a Platt et al ( 1984 ) small number of individuals with HbSS treated with hydroxyurea since infancy suggests that hydroxyurea can normalize later growth and development in SCD (Hankins et al 2014 ).…”

Allogeneic donor availability for hematopoietic stem cell transplantation in children with sickle cell disease

“…Patients with SCD at Children's National have a weight distribution similar to the population in standard growth charts. CDC growth chart data were used to construct a function that gave a weight corresponding to a Z‐score and age .…”

Current Standards of Care and Long Term Outcomes for Thalassemia and Sickle Cell Disease

“…Chronic anemia, poor nutrition, increased metabolic rate and renal loss of nutrients have been posited to lead to growth failure in children with SCD. Contemporary management of SCD with early hydroxyurea, monitoring and supplementation of nutrients (such as zinc and vitamin D) and appropriate use of age-, sex-, and ethnicity-matched growth charts can help maintain normal or near normal growth in most patients, thereby potentially improving quality of life [56, 57]. …”

“…Likewise, there is no evidence of impaired growth or development in children treated with hydroxyurea. Long term monitoring studies are on-going [56, 76]. Table 3.7 reviews dosing and monitoring guidelines for hydroxyurea.…”