Low dose growth hormone treatment in infants and toddlers with Prader-Willi syndrome is comparable to higher dosage regimens

Objective: Evaluate benefit and risk of low dose growth hormone treatment (GHT, 4.5mg/m²/week) in very young children with Prader-Willi Syndrome (PWS).

Design: Prospective longitudinal clinical intervention.

Methods: We evaluated 31 infants (aged 2-12months) and 42 toddlers (13-24months) from the PWS-OZGROW database for height, weight and BMI using the World Health Organization standard deviation scores (SDS_WHO) and PWS specific BMI (SDS_PWS), bone age, insulin-like growth factor 1 (IGF-I) levels and adverse events over 3years of GHT.

Results: At commencement of GHT infants had a lower BMI SDS_WHO (-0.88 vs 0.40) than toddlers, while toddlers had a lower height SDS_WHO (-1.44 vs -2.09) (both P<0.05). All increased height SDS_WHO (2year delta height infants +1.26 SDS, toddlers+1.21 SDS), but infants normalised height sooner, achieving a height SDS of -0.56 within 1year, while toddlers achieved a height SDS of -0.88 in two years. BMI SDS_WHO increased, while BMI SDS_PWS decreased (both P<0.0001) and remained negative. The GHT response did not differ with gestation (preterm 23%) or genetic subtype (deletion vs maternal uniparental disomy). Bone age advancement paralleled chronological age. All children had low serum IGF-I at baseline which increased, but remained within the age-based reference range during GHT (for 81% in first year). Four children had spinal curvature at baseline; two improved, two progressed to a brace and two developed an abnormal curve over the observation period. Mild to severe central and/or obstructive sleep apnoea were observed in 40% of children prior to GHT initiation; 11% commenced GHT on positive airway pressure (PAP), oxygen or both. Eight children ceased GHT due to onset or worsening of sleep apnoea: 2 infants in the first few months and 6 children after 6-24months. Seven resumed GHT usually after adjusting PAP but five had adenotonsillectomy. One child ceased GHT temporarily due to respiratory illness. No other adverse events were reported. Two children substantially improved their breathing shortly after GHT initiation.

Conclusion: Initiation of GHT in infants with 4.5mg/m²/week was beneficial and comparable in terms of auxological response to a dose of 7mg/m²/week. Regular monitoring pre and post GH initiation assisted in early detection of adverse events. IGF-I levels increased with the lower dose but not excessively, which may lower potential long-term risks.