Growth hormone therapy: Earlier is better

  Parents of newly diagnosed infants with PWS often wonder at what age to start growth hormone (GH) therapy. Advice from medical professionals is sometimes inconsistent, with some doctors advocating the use of GH as soon as possible after the diagnosis, while others prefer to wait until the baby/toddler starts to fall off his or her growth curve. A paper by Dr. Myers and colleagues suggests both physical and neurodevleopmental advantages when growth hormone is initiated early. Two years of growth hormone therapy in young children with Prader-Willi syndrome: Physical and neurodevelopmental benefits. Myers SE et al. Am J Med Genet, Nov 2006. In this report, the authors studied 25 babies and toddlers (4-37 months) with PWS, and randomized them to either start GH right away or wait a year. They measured of growth and body composition and evaluated cognition and language development of all the children after one year. As expected, babies and toddlers treated with GH right away grew faster and had increased head circumference compared to untreated controls. Body fat was decreased and lean mass increased in treated children. Overall, there was a trend towards improved motor development (independent walking) in GH treated compared to late treated or untreated babies, but, importantly, there was a great deal of individual variation, and the age at independent walking overlapped between the groups. Intriguingly, language and cognition scores progressed more rapidly in GH treated children. (An important note here is that the GH treated group started out a little behind – presumably just due to a small sample size and the random nature of the trial – so after one year, the scores were very similar between the groups). In addition, children receiving GH, on average, spoke their first word earlier than the untreated group (14.0 months vs. 17.2 months). The findings suggest an increased rate of language and cognitive development in GH treated children, although follow up studies and larger groups are needed to confirm. (The children who did not receive GH initially were started on GH therapy after the first year; the effects of GH on this group will be reported later). It may also be interesting to follow the children who were given GH in infancy to see if administration during the first year normalizes body composition, muscle strength and agility as the children grow older; prior studies in children with PWS treated with GH at a later age showed improvements, but not normalization, in these measures.Overall, the GH therapy was well tolerated, but one child showed progression of scoliosis (in general, GH probably doesn’t make the situation worse, since scoliosis is common and often progresses in PWS with or without GH therapy, [Nagai 2006 ]). Parents reported their children on GH therapy were more alert and energetic.Based on this study, the authors recommend prompt referral of newly diagnosed babies to a pediatric endocrinologist for consideration of GH therapy. They suggest an initial dose of 0.3 mg/kg/week in infants less than 2 years old, with a dose of 0.26 mg/kg/wk in those 2 years and older, with continued evaluation by the endocrinologist guiding follow up dosing changes.A couple of precautionary notes: Failure to thrive is a concern in infants with PWS. On the one hand, GH may improve this problem; stronger babies may be able to feed better. On the other hand, the increased energy requirement of a more rapidly growing baby makes it even more important that the child get sufficient calories and nutrition during this critical time. Although there may be a temptation to have a ‘thin’ baby with PWS, this is probably not best for proper development. The authors suggest a goal of maintaining normal weight-for-length or Body Mass Index for age, which may require frequent feedings with fortified breast milk or concentrated formulas in infants, and/or nutritional supplements such as Pediasure for babies over 1 year of age. Finally, this study did not specifically look at the concerns regarding GH therapy and sleep apnea [see previous Sept and March blogs]. The authors concur with the prior recommendation that a sleep study should be considered prior to initiation of GH therapy, with aggressive management of any respiratory infections and wheezing, especially in the fist few months of therapy.