HQ-CT scores for participants with PWS compared to typically developing individuals
Data on HQ-CT scores in the PWS population were obtained from participants in the “PATH for PWS” natural history study (NCT03718416), a registry-based prospective study of individuals with PWS, age 5 and above, with data entered by the parent or primary caregiver of the person with PWS (the respondent). At enrollment into “PATH for PWS”, the HQ-CT was completed for 646 individuals with PWS. Of those, participants were excluded from this analysis if they were receiving an experimental drug as part of a clinical trial, if the respondent indicated that the participant had experienced a major life change (e.g., change in living condition or health status) in the past 6 months, or if the respondent was not “very familiar” with the participant’s daily activity. After excluding participants for these reasons, the HQ-CT scores for 459 individuals with PWS were analyzed. The demographics of the participants is shown in Table 1. The genetic subtype of PWS participants were 55% deletion, 32% uniparental disomy, 2% imprinting defect, 1% other (e.g., translocation, atypical deletion), and 10% don’t know/not reported.
For typically developing individuals, 605 respondents (parent/caregiver) reported on 734 individuals in an electronic survey that included the HQ-CT questionnaire. Responses were excluded if the participant had any neurodevelopmental disorder, if they had a medical condition or took a medication that would impact appetite, if they were not in the daily care of the respondent, or if the individual was under the age of 5 or over the age of 26. Thus, HQ-CT scores for 614 typically developing children and young adults were included in this analysis. Table 1 shows the demographics of these individuals. Respondents were also asked to indicate whether the individual they were reporting on lived with someone with PWS. Most of the typically developing participants did not live with someone with PWS (73.8%) and were not related to someone with PWS (66.6%).
The HQ-CT scores by age category (5–11, 12–17, 18 +) of individuals with PWS compared to typically developing individuals is shown in Fig. 1. Among the 459 participants with PWS, the overall mean HQ-CT score was 10.13 (SD: 7.94), and the total scores ranged from 0 to 36. Among 614 typically developing participants, the overall mean HQ-CT score was 3.43 (SD: 3.50), and the total scores ranged from 0 to 22. The mean HQ-CT score was significantly higher among the participants with PWS compared to the typically developing participants (t = 18.63, p < 0.0001). An increasing linear trend in mean HQ-CT score was found as compared to age in persons with PWS, while scores decreased with age in typically developing children and young adults. For each age category, PWS individuals had a statistically significantly higher mean HQ-CT total score compared to typical individuals (5–11-year-olds: 9.31 vs. 3.82, t = 12.35, p < 0.0001, 12–17-year-olds: 9.82 vs. 2.31, t = 9.63, p < 0.0001, 18 + year olds: 11.21 vs. 1.34, t = 6.30, p < 0.0001, respectively).
Table 2 shows the bivariate analysis of sociodemographic characteristics and mean HQ-CT score among the individuals with PWS. There was no statistically significant difference in mean HQ-CT total score by age category or by PWS genetic subtype. There was a statistically significant difference in mean HQ-CT total score by current weight category (underweight: 8, normal weight: 8.74, overweight: 8.42, obese: 12.15, F = 7.5, p < 0.00001). In assessing the post-hoc tests, those in the obese category had a higher mean HQ-CT total score than both those with normal weight (p = 0.0004), and those in the overweight category (p = 0.0007).
Table 3 shows the bivariate analysis of sociodemographic characteristics and mean HQ-CT score among the typically developing participants. There was a statistically significant difference in mean HQ-CT total score by age category (5–11-year-olds: 3.82, 12–17-year-olds: 2.31, 18 + year olds: 1.34, F = 14.45, p < 0.0001). In assessing the post-hoc tests, those in the 5–11-year-old group had a higher mean HQ-CT total score than both those in the 12–17-year-old group (p = 0.0001), and those in the 18 + year old group (p = 0.0005). There was also a statistically significant difference in mean HQ-CT total score by current weight category (underweight: 3.5, normal weight: 3.16, somewhat overweight: 5.77, obese: 7.5, F = 11.28, p < 0.00001). In assessing the post-hoc tests, those in the ‘somewhat overweight’ category had a higher mean HQ-CT total score than both those with normal weight (p < 0.0001), and those in the underweight category (p = 0.0085). There was no statistically significant difference in mean HQ-CT total score by PWS living status or PWS relationship status.
We compared the scores of the 9 individual HQ-CT questions in the typically developing individuals to those with PWS. Individuals with PWS had higher mean individual HQ-CT question scores for all 9 questions compared to typical individuals (all p < 0.001, see Supplemental Table 1, Additional File 1). Supplemental Table 2, Additional File 1 shows the bivariate analysis of the individual HQ-CT questions by age categories, PWS living status, and PWS relationship status among the typically developing individuals.
Caregiver interviews for low scoring individuals with PWS
Although both the means and ranges of HQ-CT scores in individuals with PWS were significantly higher than typical individuals and were higher with increasing age, there was a wide range of HQ-CT scores in individuals with PWS. We were interested in a small subset of individuals with PWS who consistently had low HQ-CT scores, even well after the expected onset of hyperphagia5. To better understand the basis of low HQ-CT scores in some adults with PWS, we invited the caregivers of 32 adult PWS participants with HQ-CT scores below 7 at baseline and at their most recent evaluation to participate in a semi-structured interview aimed at understanding the food seeking behaviors of the individual, as well as the food environment. Caregivers of 17 adults with PWS ranging in age from 19 to 61 years of age at the time of enrollment in the PATH for PWS study agreed to participate in the semi-structured interview. Mean HQ-CT scores of these individuals was 3.23 (SD 2.46) at enrollment and 2.35 (SD 1.93) at the most recent data collection point, and 65% of the individuals were overweight or obese. Demographic characteristics of these participants are shown in Table 4 and are consistent with the demographics of the overall PWS sample.
Caregivers were asked about food seeking behaviors in the person with PWS, and strategies, if any, the caregiver employed to manage food intake and food-related behaviors of these individuals. A selection of responses is presented in Table 5. All respondents reported actively managing the food intake of the person with PWS; 100% of the caregivers reported that they prepare the meals or directly assist the person with PWS in meal preparation to ensure appropriate portion control and meal choices. Repetitive snacks and meal choices (driven by the person with PWS) were reported by 41.2% (n = 7) of the caregivers. The majority, 76.5% (n = 13), reported that the individual with PWS had little to no independence with respect to food choices at home or outside of the home. Consistent with the food behaviors of many individuals with PWS, 64.7% (n = 11) of the respondents report their loved one with PWS asked questions about food throughout the day, including the type, timing, and/or portion of food to be served. A common strategy employed by these caregivers was strict routine and structure regarding food, which included strictly scheduled mealtimes and snack times. Disruption to routine was reported by 88.2% (n = 15) of the respondents as almost never happening, further illustrating how caregivers use this strategy for food behavior management. Situations that deviated from routine were reported to cause significant behavioral difficulties in the person with PWS and were therefore avoided.
Limiting social/community engagement where food is present was also frequently reported by respondents. Forty-seven percent (n = 8) of the respondents stated that restaurants and parties with food cause significant distress to the person with PWS, and caregivers reported avoiding these situations to prevent challenging behaviors. Caregivers also frequently report attending social engagements separately as a family, with one caregiver staying home with the person with PWS while the other attends the event or driving separately so one parent can leave with the person with PWS if food behaviors become unmanageable.
A majority of respondents (64.7%, n = 11) implement food security measures in the home, such as locks on refrigerators, pantries, and trash containers, locks on bedroom doors, security cameras and alarms, and physical barriers to the kitchen. Forty-seven percent (n = 8) of respondents report using ‘line of sight’ supervision in which the person with PWS is always within eyesight of the caregiver. Food security measures also extend to outside settings for the majority of participants who routinely spend time in programs and activities outside the home (day programs, camp, employment). Many caregivers themselves report eventually adopting a lifestyle with routine and sameness governing the course of all actions and decisions for the family, to ‘keep the peace’. When considering the possibility of new treatments to manage PWS-associated hyperphagia, most of these caregivers (64.7%, n = 11) indicated that they would be interested in such a treatment if it became available, despite the low HQ-CT score they reported for the individual in their care. The possibility of greater independence for the person with PWS as well as the potential for reduced intensity of caring for the person were the most common reasons for interest in potential hyperphagia therapies.
When asked how hyperphagic behaviors had changed over time for the adult with PWS in their care, most caregivers (53%, n = 9) reported that the food-related behaviors of the person with PWS had stayed about the same, while 12% (n = 2) reported an increase in behaviors and 35% (n = 6) reported decreasing food related behaviors. Of those reporting reduced food related behaviors over time, caregivers cited changes in lifestyle including fewer activities outside the home, school ending, and siblings moving out of the home as contributing to more stability in the management of PWS-associated food behaviors. None of the respondents reported significant lessening of hyperphagia over time in the adult under their care.