Growth Hormone Effects in Infants and Toddlers with Prader-Willi Syndrome: Does Early Intervention Make a Difference? a,b
Barbara Y. Whitman1, Susan E. Myers1, Aaron Carrel2, Dave Allen2
1 Department of Pediatrics, Saint Louis University, St. Louis, MO 2 University of Wisconsin, Madison, WI
Abnormal body composition and growth hormone deficiency are well documented aspects of Prader-Willi syndrome. The authors and others have documented the beneficial effects of growth hormone replacement therapy (GHRT) on anthropometrics (including linear growth, head size, foot and hand length), body composition (including percent body fat and lean body mass), bone density, physical performance (including muscle strength and pulmonary function), and mood and behavior (including improved mood, attention, cooperativeness and sociability) in individuals with PWS between the ages of four and 21 years.
Obesity in those affected with Prader-Willi syndrome has its onset in the toddler years at a mean age of 2 years. The multifactorial etiology includes centrally-driven hyperphagia, a decreased perception of satiety, decreased resting energy expenditure and reduced physical activity. Long before obesity develops, however, body composition abnormalities are evident. Body fat determined by skin-fold measurements is elevated even in underweight infants with PWS and an accompanying reduced lean body mass (LBM) contributes to the infantile hypotonia. The majority of infants have a normal birth length, however, there is a gradual deceleration of linear growth during childhood with short stature observed in the majority by 12 years. We have sought to study infants during this critical period, evaluating the benefits of GHRT on these early body composition and developmental abnormalities.
In this presentation we will compare growth, body composition and developmental parameters in 4- to 5-year old children treated with growth hormone (Genotropin, 1-1.5 mg/m2/d) for 24-36 months with baseline measurements of previously studied children initiating treatment at ages 4 to 6 ½ years.
Preliminary comparison data indicate that children treated since infancy have improved linear growth (ht-Z score 0.832 vs -1.06) associated with higher IGF-1 values (434 vs. 88ng/ml), normal lean body mass (101 vs. 88% of normal values for age), and significantly less absolute and age-adjusted body fat as measured by DEXA scans (32 vs. 44% body fat; 2 vs. 2.9-fold increase over normal values for age). Parental reports revealed significantly earlier emergence of language (15 vs 20 mos.), and a tendency toward earlier independent walking. Differential gender effects are observed for several parameters. These preliminary data sHuggest that early GHRT offers multiple benefits for infants and toddlers with Prader-Willi syndrome.
Study of Growth Hormone Intervention for Infants and Toddlers with Prader-Willi syndrome partially supported by Pharmacia/Pfizer
Study of Growth Hormone Intervention for Young Children and Adolescents with Prader-Willi syndrome partially supported by Genentech