Growth measurements in Ugandan children with sickle cell anaemia from a hydroxyurea (hydroxycarbamide) treatment trial relative to unaffected sibling controls

Abstract

Children with sickle cell anaemia (SCA) in sub-Saharan Africa (SSA) frequently experience impaired growth. Hydroxyurea (hydroxycarbamide) improves growth in higher resourced countries, but its effects on growth and body composition have not been evaluated in SSA. In an open-label, single-arm, 30-month dose-escalated hydroxyurea trial in Ugandan children aged 3 to <10 years (N = 264, mean age 5.6 ± 1.7 years), participant anthropometrics were compared to non-SCA sibling controls using global age- and sex-normalized z-scores. Body composition was determined using bioelectrical impedance analysis (BIA), comparing their z-scores to those generated from the controls (N = 110). Prospectively, SCA growth parameters on hydroxyurea paralleled and correlated with haemoglobin levels but remained lower than controls for weight, height and body mass index for age. Notably, growth of the SCA participants enrolled at ages 3 to <5 years did not differ from controls; instead, all group differences were attributable to those enrolled at ages 5 to <10. Further analyses revealed that growth trajectories of SCA age-dependent weight and height improved from being significantly lower than controls at trial entry to similarity at completion. Fat-free mass improved, although it and the fat mass both remained lower than that of the controls. Findings suggest that hydroxyurea promotes healthier growth and may improve body composition in children with SCA in SSA; earlier treatment initiation had a greater impact.

Keywords: body composition; children; growth; hydroxyurea; sickle cell anaemia.

FIGURE 1

Trial growth indices comparing children with sickle cell anaemia (SCA) to the controls overall and by age subgroup at study months 0 and 30. z-scores were age- and sex-normalized by the World Health Organization global standards. For each panel, the same age span was used for both the SCA participants and controls, and included 80 controls in the 3 to <10 year group, 30 in the 3 to <5 year group, and 50 in the 5 to <10 year group. Panels A–C represent z-scored weight-for-age, D–F represent height-for-age and G–I represent BMI-for-age.

FIGURE 2

Trajectory of growth parameters comparing sickle cell anaemia (SCA) and control groups at trial entry and 30-month completion, by raw data. At entry, all 264 individuals with SCA and 80 controls included. At completion, 251 individuals with SCA ad 73 controls (aged 5.5 to <13 years) included in the trial completion analysis. Panels A and B represent raw data for weight-for-age, C and D are height-for-age, and E and F are BMI-for-age.