Growth hormone prescribing and initial BMI SDS: Increased biochemical adverse effects and costs in obese children without additional gain in height

Abstract

BackgroundRecombinant human growth hormone (rhGH) treatment in children is usually prescribed using actual body weight. This may result in inappropriately high doses in obese children.MethodsRetrospective audit of all paediatric patients treated with rhGH 2010–14 at a tertiary paediatric hospital in the UK. Change in height SDS and IGF-I SDS during the first year of treatment was stratified by initial BMI SDS in a mixed cohort, and a subgroup of GH deficient (GHD) patients. Alternative doses for those BMI SDS ≥2.0 (Obese) were calculated using BSA, IBW and LBW.Results354 patients (133 female) received rhGH, including 213 (60.2%) with GHD. Obesity was present in 40 patients (11.3%) of the unselected cohort, and 32 (15.0%) of the GHD cohort. For GHD patients, gain in height SDS was directly related to BMI SDS, except in obese patients (p<0.05). For both the entire cohort, and GHD patients only, IGF-1 SDS was significantly higher in obese patients (p<0.0001 for both groups). Cross sectional data identified 265 children receiving rhGH, 81 (30.5%) with a BMI-SDS ≥1.75. Alternate prescribing strategies for rhGH prescribing in obese patients suggest a saving of 27% - 38% annually.ConclusionsGain in IGF-I SDS is greater in obese children, and is likely to be related to relatively higher doses of rhGH. Additional gain in height was not achieved at the higher doses administered to obese children. Alternative dosing strategies in the obese patient population should be examined in rigorous clinical trials.

Impact of BMI on peak growth hormone responses to provocative tests and therapeutic outcome in children with growth hormone deficiency

“…However, data on serum IGF-I level in obese individuals are controversial, with studies reporting low 21–24 , high 25–27 , and normal levels 28,29 . Moreover, some studies have reported no relationship between IGF-1 and BMI SDS, and increased IGF-1 in obese GHD which supports our results 30 . This suggests that a modified GH-IGF-1 axis in obese children can only be meaningfully interpreted by measuring free IGF-1 to determine the true effects of BMI considering various factors 31–33 .…”

“…There have been few studies on the impact of BMI on GHT in children with GHD; the studies showed an inverse relationship between BMI and first-year growth response 34 , or vice versa 30 . Hawcutt et al .…”

IL-10/STAT3 is reduced in childhood obesity with hypertriglyceridemia and is related to triglyceride level in diet-induced obese rats

“…According to the BMI reference norm for Chinese children and adolescences, subjects were considered to be obese when the BMI exceeded 95th percentile of the norm [ 17 ]. BMI standard deviation score (SDS-BMI) were calculated according to WHO BMI-for-age (5–19 years) [ 18 ].Subjects were diagnosed with hypertriglyceridemia (serum TG level > 1.7 mmol/L) according to the new International Diabetes Federation definition for Chinese people [ 19 ]. The study protocol was approved by the Ethical Committee of Xi’an Jiaotong University.…”

The Path to Perfect Pediatric Posology — Drug Development in Pediatrics

“…With the inclusion of pediatric subjects as a standard part of clinical development, more data are being collected so that drug development in children has expanded far beyond simple description of a small group of heterogeneous subjects. Beyond studying children of all ages, the problem of the correct dose for obese or underweight children is beginning to get attention. Perhaps more importantly, the advances that are being made to support drug development work in children, including in fragile newborns, can be extended to the study of other vulnerable populations such as pregnant and lactating women .…”