GH treatment halted decline of certain cognitive skills in children with Prader-Willi syndrome

Growth hormone treatment in children with Prader-Willi syndrome prevented deterioration of some cognitive skills while improving abstract verbal reasoning and visuospatial skills, according to data from a randomized controlled trial.

“Before the start of GH treatment, older age had a significant negative effect on cognition. Also, untreated controls showed a deterioration of cognitive functioning. These findings indicate that cognitive functioning of untreated children with [Prader-Willi syndrome] deteriorates over time compared with healthy children. Our study shows that GH treatment prevents this deterioration,” the researchers wrote.

Elbrich P.C. Siemensma, MD, researcher for the Dutch Growth Research Foundation in the Netherlands, and colleagues designed a 2-year randomized controlled GH trial, followed by a 4-year longitudinal study on GH treatment, in 21 boys and 29 girls aged 3.5 to 14 years.

Cognitive functioning was measured every 2 years by four short forms of the Wechsler Preschool and Primary Scale of Intelligence-Revised, Dutch version (WPPSI-R) or the Wechsler Intelligence Scale for Children-Revised, Dutch version (WISC-R), depending on patient age.

Subtests in vocabulary, similarities (verbal IQ subtests), block design and picture arrangement (performance IQ subtests) of the WISC-R were used in children aged older than 7 years. For children aged younger than 7 years, picture arrangement was replaced with picture completion under the WPPSI-R.

After 4 years of GH treatment, the mean standard deviation score on the similarities (+0.4; 95% CI, –0.1 to 0.7) and block design (+0.3; 95% CI, 0.07-0.6) subtests were significantly higher than at baseline. Vocabulary subtests (P=.01) and total IQ (P=.03) were similar to baseline at 4 years.

Block design subtest scores were significantly lower among children with a maternal uniparental disomy at baseline (P=.01); however, these patients had a larger increment on this subtest during 4 years of GH treatment vs. patients with a deletion, the researchers wrote.

Higher increases in similarities (P=.04) and block design (P<.0001) were significantly associated with lower baseline scores.

The researchers wrote that their findings suggest that GH should be administered at an early age to prevent deterioration. However, older children who are lagging may benefit even more from GH treatment.

Disclosure: The researchers report receiving an independent research grant from Pfizer for the investigator-initiated trial.