ESPE Yearbook of Paediatric Endocrinology

Horm Res Paediatr 2025;98:164–173 PMID: 38368858. doi: 10.1159/000536466

Brief Summary: This study investigated key aspects of energy balance in children with Prader-Willi syndrome (PWS) receiving long-term growth hormone (GH) treatment in the Dutch PWS Cohort Study.

Previous research reported lower resting energy expenditure (REE) in children with PWS, untreated with GH, primarily attributed to their abnormal body composition, specifically their reduced lean body mass (LBM). This lower metabolic rate, combined with an intense drive for food (hyperphagia), places them at high risk for obesity. While GH treatment improves body composition in children with PWS, there is limited data on the long-term effects of GH treatment on REE and energy intake.

Therefore, this study examined REE (mREE), energy intake, and body composition over an extended period of GH treatment in 52 children with PWS, all confirmed by methylation analysis. They had a mean age of 8.53 years and a median GH-treatment duration of 7 years. REE was measured by open-circuit indirect calorimetry using a ventilated hood system, which is considered the method of choice. Dietary energy intake was calculated from a 3-day dietary record completed by parents. LBM and fat mass (FM) were measured using dual-energy X-ray absorptiometry (DXA) scans. Measured REE was also compared to predicted REE calculated using the Schofield equation, a widely used method based on age, sex, weight, and height. Normal REE was defined as 90% to 110% of the predicted value.

GH-treatment duration was not associated with mREE when corrected for sex, age, height, and pubertal stage. This suggests that long-term GH treatment does not influence mREE directly. LBM was associated with higher mREE, but FM% was not. This aligns with previous studies indicating that LBM is a crucial determinant of REE. When compared to predicted REE using the Schofield equation, only 50% of the children had a normal REE. Specifically, 17.3% had low REE, and 32.7% had high REE. This indicates that predictive equations like Schofield’s can either overestimate (by an average of 214 kcal/day for those with decreased REE) or underestimate (by an average of 207 kcal/day for those with elevated REE) mREE. A key finding was that mean energy intake was lower than daily energy requirements (DER) for age- and sex-matched healthy children (p < 0.001); this deficit increased with age: not reduced in infants (<3.5 years), 23-36% lower in children aged 3.5-12 years, and 49% lower at age 12-18 years. Despite this lower total energy intake, the macronutrient distribution (carbohydrate, protein, fat) was within the acceptable range.

This study is the first to measure REE, by indirect calorimetry and energy intake, in a large cohort of children with PWS undergoing long-term GH treatment. The findings confirm that mREE in children with PWS increases with age, but long-term GH treatment does not directly influence mREE. The strong association between LBM and mREE underscores the importance of therapies that improve or maintain LBM, such as GH treatment, and also highlights the need to focus on stimulating physical activity to achieve this. For clinical practice, the study emphasizes that relying solely on predictive equations for REE can be inaccurate. Therefore, indirect calorimetry is the best option for precisely determining REE when available, to ensure accurate dietary advice for individual patients.

The authors acknowledge limitations, such as not including an untreated control group (due to ethical considerations given the known benefits of GH treatment) and the potential for underreporting in dietary records. However, it provides valuable insights into the energy metabolism of long-term GH-treated children with PWS, reinforcing the role of LBM in energy expenditure and the necessity of strict dietary control for weight management.

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