Growth and pubertal development in transfusion-dependent children and adolescents with thalassaemia major and sickle cell disease: A comparative study

Despite regular blood transfusion and desferrioxamine treatment, growth imp airment and pubertal delay are commonly seen in children and adolescents wi th transfusion-dependent thalassaemia and sickle cell disease (SCD). We eva luated growth parameters and sexual maturation in a large cohort of childre n and adolescents with SCD (n = 110) and thalassaemia (n = 72) receiving ne arly the same protocol of transfusion and chelation, and compared them with those for 200 normal age-matched children, 30 children with constitutional delay of growth (CSS), and 25 children with growth hormone deficiency (GHD ). Before transfusion, haemoglobin concentration had not been less than 9g/ dl in the past 7 years; desferrioxamine was administered for 7-10 years, in cluding by the intramuscular and subcutaneous routes, three times or more p er week. The height standard deviation score (HtSDS), growth velocity (GV) (cm/yr), and growth velocity standard deviation score (GVDSD) of children a nd adolescents with thalassaemia and SCD were significantly decreased compa red to normal children (p less-than 0.01). Forty-nine percent of thalassaem ic patients and 27 percent of patients with SCD had HtSDS less than -2, and 83 percent of thalassaemic patients and 67 per cent of SCD patients had Ht SDS less than -1. Fifty-six percent of thalassaemic children and 51 percent of children with SCD had GVSDS less than -1. The GV, of thalassaemic child ren was significantly slower than that for children with SCD. Children with thalassaemia and SCD had HtSDS and GVSDS comparable to those for children with CSS but higher than those for patients with GHD. Serum ferritin concen tration was correlated significantly with the linear GV in all patients (r = 0.45, p less-than 0.001). The bone age delay did not differ among the thr ee groups with thalassaemia, SCD and CSS, but the delay was significant in the group with GHD. The mid-arm circumference was significantly smaller in children with thalassaemia and SCD than in normal children. The triceps ski n-fold thickness of patients with SCD was significantly decreased compared to thalassaemic and normal children. The upper/lower segment ratio was sign ificantly lower in thalassaemic and SCD patients than in normal children. In thalassaemic patients between the ages of 13 and 21 years a complete lac k of pubescent changes was present in 73 percent of boys and 42 percent of girls. Seventy-four percent of the thalassaemic girls had primary amenorrho ea. Girls with SCD aged between 13 and 21 years had markedly delayed breast development and menarche. Twenty-five percent of boys with SCD above the a ge of 14 years had absence of testicular development. Males with thalassaem ia and SCD who had spontaneous testicular development had significantly sma ller testicular volume than did normal controls. Short children with thalas saemia and SCD had significantly decreased serum insulin-like growth factor 1 (IGF-1) concentrations compared to children with CSS. Collectively, thes e data confirm the high prevalence of impaired growth and pubertal delay/fa ilure in children and adolescents with thalassaemia and SCD. The aetiology of impaired growth includes the contributions of lack of pubertal growth sp urt due to delayed/absent puberty, decreased synthesis of IGF-1 which might be secondary to a disturbed GH-IGF-1 axis and/or under nutrition, probably due to the hypermetabolic status of these children. It is suggested that n ewer protocols of treatment, in addition to optimization of transfusion and chelation requirements, should increase the caloric intake of these patien ts and properly manage their pubertal delay-failure in order to improve the ir adult height.