Working group 3: Clinical designation of nutritional phases
PWS has been classically described as having two nutritional stages: poor feeding, frequently with failure to thrive (FTT) in infancy (Stage 1), followed by hyperphagia leading to obesity in later childhood (Stage 2). In 2011, Miller and collaborators described a much more gradual and complex progression of the nutritional phases. They identified seven different nutritional phases, with five main phases and sub-phases in phases 1 and 2.
Phase 0 occurs in utero, with decreased fetal movements and growth restriction compared to unaffected siblings.
In phase 1 the infant is hypotonic and not obese, with sub-phase 1a characterized by difficulty feeding with or without FTT (ages birth—15months; median age at completion: 9 months). This phase is followed by sub-phase 1b when the infant grows steadily along a growth curve and weight is increasing at a normal rate (median age of onset: 9 months; age quartiles 5–15 months).
Phase 2 is associated with weight gain—in subphase 2a the weight increases without a significant change in appetite or caloric intake (median age of onset 2.08 years; age quartiles 20–31 months;), while in sub-phase 2b the weight gain is associated with a concomitant increased interest in food (median age of onset: 4.5 years; quartiles 3–5.25 years).
Phase 3 is characterized by hyperphagia, typically accompanied by food-seeking and lack of satiety (median age of onset: 8 years; quartiles 5–13 years).
Phase 4 occurs when an individual who was previously in phase 3 no longer has an insatiable appetite and is able to feel full.
The clinical description of nutritional phases is helping the PWS community to better frame clinical research on hyperphagia by providing valuable insights into the natural history of PWS as well as providing a framework for patient selection and outcome assessment in clinical trials.
The overall goal is to establish and validate consensual guidelines for nutritional phases designation that will be adopted at the international level. A validated method (e.g., checklist) that will allow consistent determination of nutritional stage in individuals with PWS, across sites and clinicians, is expected to improve the precision of clinical trials.