Study Shows Benefits of Early Growth Hormone Therapy in PWS Children

Starting growth hormone therapy before the first birthday has significant benefits over beginning treatment at an older age in children with Prader-Willi syndrome (PWS), an analysis found.

Children treated early grew taller, with a height similar to healthy children of the same age and sex, and had more favorable lipid (fat) profiles and glucose metabolism.

The study,” Early start of growth hormone is associated with positive effects on auxology and metabolism in Prader-Willi-syndrome,” was published in the Orphanet Journal of Rare Diseases.

Growth hormone therapy (GH) is currently recommended for PWS patients to improve stature, metabolism, and muscle mass, while also lowering weight gain. Previous studies indicated that GH therapy might improve cognitive function, body composition, and health-related quality of life.

In the past, GH therapy was started in early childhood around age 2, typically before the onset of obesity. However, recent findings indicate additional benefits when treatment is started as early as 2 to 6 months old. As such, it is recommended to start GH treatment as soon as possible.

However, studies investigating this recommendation are scarce. 

To explore the topic researchers at the University of Bonn in Germany led an analysis of the medical records of 62 children with genetically confirmed PWS.

The team looked for differences in growth, as well as carbohydrate (sugar) and lipid metabolism, between starting GH therapy during or after the first birthday.

All children were offered GH at diagnosis, with some starting immediately, while others began later, from October 2007 to July 2015. A total of 21 children started GH before completing the first year of life, while 41 began treatment later (up to 2.5 years of age). Before treatment, and twice a year thereafter, the scientists collected blood samples and performed growth measurements.

The participants were primarily of German caucasian descent, with no significant numbers of patients with different ethnic backgrounds. 

Standard deviation scores (SDS) were calculated for height (length), weight, and body-mass-index (BMI). SDS scores reflect the variation from an average value of children of the same age and sex. 

Results revealed that children receiving GH earlier grew taller than those who started later, with different mean height-SDS throughout the entire study period. At age 5, early GH therapy led to a height-SDS of 0.81 vs. 0.54 with later GH treatment.

Notably, compared to values in the later treatment group, height-SDS in the early treatment group was significantly closer to that found in children children without PWS.

No significant differences were found in mean weight-SDS, BMI-SDS, lean body mass, or body fat measures.

Blood levels of the growth factor IGFBP-3 continuously increased (within the normal range) in both groups, but were 0.57 SDS higher in the early treatment group throughout the observation period. Mean IGF-I SDS did not differ between groups. 

During the entire study, low-density cholesterol (LDL), or so-called “bad cholesterol,” was significantly lower in children treated earlier. At age 1, mean LDL level was 79 mg/dl when treated earlier and 90 mg/dl in children treated later. At age 5, mean LDL in early treated patients was 91 vs. 104 mg/dl in the group on GD after age 1. Likewise, children treated younger showed a trend toward lower total cholesterol levels throughout the assessment.

In contrast, no differences were found in high-density cholesterol (HDL) levels — the so-called “good cholesterol” — or in triglycerides. 

Regarding carbohydrate metabolism, the group treated at a younger age showed lower fasting insulin and HOMA-IR — an assessment of insulin resistance — over time, while blood glucose and HbA1c values (glucose over three months) were similar between the two groups at age 5 after being higher in children treated early until 1.5 years. 

“Our results show that early GH onset during the first year of life has statistically significant favorable effects on height-SDS, lipid profile, and glucose metabolism,” the scientists wrote. 

“Therefore, earlier [GH therapy] onset should be recommended to families with children with PWS,” they added.