This study is the first of its kind to investigate the real-world variability at baseline and change over 6 months of weight and BMI in a large group of PWS adolescents and adults. Overall, we found that weight and BMI increased over time in this population, with weight increasing by 2.35% (SD 5.3) from baseline to the end of the six-month study, and BMI increasing by 1.42% (SE 0.47). However, there was considerable variability in this study population, both in the initial weight (from 33.2 kg to 207.7 kg) and BMI measurements (from 13.2 kg/m2 to 88.0 kg/m2), as well as the change in weight and BMI over time (both ranged from − 20.8% to + 31.2%). While most participants had relatively stable measurements, approximately 20% of individuals demonstrated a change in weight or BMI of greater than 5% over the study period (Fig. 4).
The average weight gained per year in the United States among adults in the general population has been reported as 0.5 kg to 1 kg in one study (22). Another study reported an average increase of 0.375 kg per year in a 4 year period,(23) whereas National Health and Nutrition Examination Survey (NHANES) data showed a 3.9 kg increase over 16 years among adult men (0.24 kg/yr) and 3.1 kg increase over 16 years among adult women (0.19 kg/yr).(24) Therefore, as the mean weight increase of 1.00% would translate to an increase of 0.84 kg over 6 months in someone with a weight of 84.2 kg (our mean weight at enrollment among participants 18 and older), adults in this PWS population show faster increases in weight compared to the adult United States average.
Data about weight changes is limited in the PWS population, but the current study population showed more stable weight from baseline to week 26 (+ 2.35%) compared to the change from baseline to week 26 in the placebo arm of a recent PWS clinical trial evaluating a drug for hyperphagia and obesity (+ 4.2%).(25) The current study also had lower standard error in our weight change (SE of 0.42%) compared to that same trial (SE of 0.9%).(25) This may reflect a selection bias of individuals enrolling in a clinical trial evaluating a drug for hyperphagia, but additional studies will be needed to determine the differences in the study populations (for example, hyperphagia score).(26)
Overall, the percentage of individuals in this study population with obesity was over 50% at all time points (52.2% at baseline, 53.5% at three months, and 52.9% at six months). This is relatively comparable to the 58.2% of 292 adults with PWS with obesity from the United States in a cross-cultural comparison of PWS populations, as well as 56% of the 102 adults with PWS from the Dutch Prader-Willi Parent Association (27, 28), but is much higher than the obesity rates of the general US population. According to the Centers for Disease Control and Prevention (2015–2016), the percentage of adults aged 20 and over in the general population with obesity was 39.8%, and the percent of adolescents aged 12–19 years with obesity was 20.6% (29). Our PWS adolescent population also had a much higher rate of obesity compared to a national survey of weight status among children aged 10–17 (2017–2018 Child and Adolescent Health Measure Initiative) and compared to a nationally representative study of US adolescents aged 12–19 years from 2013–2014 NHANES surveys (CAMHI rate of obesity: 15.3%, NHANES rate of obesity: 20.6%, our rate of obesity among adolescents under 18: 54%).(30, 31)
The average BMI in our study across all time points was 31.3 kg/m2 (SD 12.41). This is higher than the average BMI among 19 adults with PWS living in Oklahoma (mean BMI for males 27.4, SEM 1.58 and for females 25.7, SEM 2.19),(32) similar to a group of 20 people with PWS aged 16–42 living in Norway (BMI 30.9, SD 6.1)(33) and a group of 14 people with PWS in the United States (mean age: 24.3 years, SD 11.3) participating in a food reward circuitry study (BMI 32.1, SD 7.8),(34) and lower than a study of 73 adults with PWS in France (deletion subtype BMI 40.9 ± 11.5, UPD subtype 34.6 ± 9.6),(35) as well as those enrolled in a pilot study of Exenatide (baseline BMI 41.7, range 34.1–55.0, age range 14.7–24.6 years).(36) The current study has a large study population given the low population prevalence of PWS, with 165 individuals providing at least one weekly weight. Because this study was entirely remote, with no clinic visit necessary, it may have allowed participation of a broader population of participants than those participating in clinical trials, which would create a more generalizable and representative set of results.
As expected, males had a statistically significantly higher weight than females. However, sex was no longer significant with the outcome of BMI, percent change in weight, or percent change in BMI. Age was significantly associated with percent change in weight, as age increases, the percent change in weight decreases. The percent change in weight for those under 18 was + 3.56%, compared to a percent change in weight of + 1.00% for those 18 and older, which may reflect the fact that some participants in the younger population are likely to still be growing.
This study population was on GH therapy on average 56.7% of their lives (SD 37.7%). The average number of years on GH therapy in the entire population was 9.51 (SD 6.48), and 59.4% of this population was currently on GH therapy. Adolescents younger than 18 in our study population were significantly more likely to currently be on GH therapy, have ever been on GH therapy, and have a higher percentage of their life on GH therapy compared to those 18 or older. Currently, the consensus recommendations for GH therapy initiation is to start before the onset of obesity, which can often start before 2 years of age, as the greatest benefits are shown when treatment is initiated early in life.(17, 37) In this study, increasing percentages of life on GH therapy was associated with both decreased weight and decreased BMI. This is consistent with the findings of other studies, where GH therapy was shown to reduce BMI in 141 children and adults with PWS in France (27) as well as children with PWS in the Netherlands.(38) In a study of 14 young PWS patients, cessation of GH therapy statistically increased BMI standard deviation score up to 2 years after stopping GH therapy, therefore long-term use of GH may be helpful to stabilize BMI.(39) However, percentage of life on GH therapy and current use of GH therapy were not associated with percent change in weight or percent change in BMI from the beginning to the end of our study.
We queried the participants about life changes, including changes in living situation, activity level, access to food and changes is medication during the course of the six-month study. The goal was to begin to understand how changes in the environment might impact weight changes over time. Overall, the majority of the population had at least one change (major life change, change in food access, change in activity level, or medication change) while participating in the study. There were some significant bivariate analyses with these changes, but they were not detected in the multivariate analysis. While the impact of these life changes on weight may warrant future research, additional information regarding the context and details of these changes are necessary to draw any conclusions, and were limited in the current text-based study. However, the overall acceptance of the remote study design with text-based reporting was high, suggesting that it would be feasible to collect more detailed data in future studies.
The remote study design also allowed the recruitment of a large number of participants in a short amount of time (approximately 2 months), considering the prevalence of the disorder. We had very high compliance rates throughout the study, suggesting that text-based data collection was readily accepted and highly manageable for the participants. The mean percentage of weeks with a completed weight measurement was 95.1%. Only 2 people returned less than 50% of their weight measurements, and 68% of the study population returned 100% of their weight measurements.