Table 1 shows the demographics for this study population at enrollment. Overall, 165 participants enrolled in the study (50.9% male). The mean age of the population was 19.7 years (SD 7.9 years), and ages ranged from 12 to 48 years. The overall mean height at enrollment was 157.2 cm (SD 13.2 cm), the mean height for men at enrollment was 163.2 cm (SD 12.8 cm) and the mean height for women at enrollment was 151.3 cm (SD 10.7 cm). At enrollment, the mean weight of all participants was 76.8 kg (SD 30.7 kg), with a median of 72.3 kg, but there was very high variability (weights ranged from 33.2 kg to 207.7 kg). The mean BMI at enrollment was 31.4 kg/m2, median BMI of 28.6 kg/m2, also with high variability (BMI ranged from 13.2 kg/m2 to 88.0 kg/m2). At enrollment, the BMI categories were 0.6% underweight (1/161), 32.3
% normal weight (52/161), 14.9% overweight (24/161), and 52.2% obese (84/161), and did not differ for under 18 compared to 18+ age groups (Table 2). The overall distribution of BMI categories did not significantly change over time (p-value 0.95), so the majority of this study population was obese at every time point (52.2% at baseline, 53.5% at three months, and 52.9% at six months).
Table 1: Characteristics of 165 study participants with Prader-Willi syndrome in a remote six-month text-based study
Characteristics
|
Study Participants (n=165)
n (%)
|
Sex (Male)
|
84 (50.9)
|
Age at enrollment (years), mean +SD
|
19.7 + 7.9
|
Age range (years)
|
12 - 48
|
Age categories
|
|
12-17
|
88 (53.3)
|
18+
|
77 (46.7)
|
Height at Enrollment (cm), mean +SD
|
157.2 + 13.2
|
Missing
|
12 (7.3)
|
Weight at Enrollment (kg), mean +SD
|
76.8 + 30.7
|
Weight at Enrollment (kg), median
|
72.3
|
Missing
|
2 (1.2)
|
Weight Range at Enrollment (kg)
|
33.2 – 207.7
|
BMI at enrollment, mean + SD
|
31.4 + 12.7
|
BMI at enrollment, median
|
28.6
|
Missing
|
4 (2.4)
|
BMI Range at Enrollment
|
13.2-88.0
|
SD standard deviation, cm centimeters, kg kilograms
|
Table 2: BMI category distribution at enrollment among 165 study participants with Prader-Willi syndrome
BMI-for-age categories
|
12-17 years old,
n (%)
|
18 years or older,
n (%)
|
Total
|
Underweight
|
1 (1.2)
|
0 (0)
|
1 (0.6)
|
Normal Weight
|
29 (33.3)
|
23 (31.1)
|
52 (32.3)
|
Overweight
|
10 (11.5)
|
14 (18.9)
|
24 (14.9)
|
Obese
|
47 (54.0)
|
37 (50.0)
|
84 (52.2)
|
Missing
|
|
|
4 (2.4)
|
BMI categories for adolescents 20 years and younger were calculated using the gender-specific body mass index-for-age percentiles from the US CDC. Adult BMI categories were assigned from the US CDC categories.
|
Table 3 shows the growth hormone therapy use in the study population. Almost 60% (98/165) of the population was currently on GH therapy during the study. Those younger than 18 were significantly more likely to currently be on GH therapy (78.4% versus 37.7%, p<0.0001) and ever have been on GH therapy (93.2% versus 72.7%, p=0.0004) compared to those who are 18 or older. The mean number of years that the study population had been on GH therapy was 9.51 (SD 6.48), and the mean percentage of life on GH therapy was 56.7% (SD 37.7%). While the number of years on GH therapy was not statistically different between age groups, those younger than 18 years had a statistically significantly higher percentage of their life on GH therapy (70.5% vs. 40.8%) compared to those 18 years or older (p<0.0001).
Table 3: Growth hormone therapy use among 165 study participants with Prader-Willi syndrome
|
12-17 years old, n (%)
|
18 years or older, n (%)
|
Total
|
Currently on Growth Hormone*
|
|
|
|
Yes
|
69 (78.4)
|
29 (37.7)
|
98 (59.4)
|
No
|
19 (21.6)
|
48 (62.3)
|
67 (40.6)
|
Ever on Growth Hormone*
|
|
|
|
Yes
|
82 (93.2)
|
56 (72.7)
|
138 (83.6)
|
No
|
6 (6.8)
|
21 (27.3)
|
27 (16.4)
|
Number of Years on GH Therapy, mean + SD
|
9.82 + 4.67
|
9.15 + 8.11
|
9.51 + 6.48
|
Percentage of Life on GH Therapy, mean + SD*
|
70.5% + 32.9%
|
40.8% + 36.7%
|
56.7% + 37.7%
|
For Current and Ever: Cochran-Mantel Haenzel; For Number and Percentage: two sample t-tests; * p<0.001
|
Overall, the weight of the study participants increased over the 26 weeks of the study, with the mean weight increasing 1.8 kg, from 76.8 kg to 78.6 kg. Figure 2 shows the plots of individual weight change throughout the study, stratified by sex and age. The mean BMI throughout the study was relatively stable, albeit high (mean BMI of 31.4 kg/m2, median BMI of 28.6 at baseline, mean BMI of 31.3 kg/m2, median BMI of 28.7 at three months, and mean BMI of 31.5 kg/m2, median BMI of 29.0 at six months). The mean percent weight change from baseline to week 25 was +2.35% (Figure 3), median +2.02%. However, the percent weight change in the study population ranged from -20.8% to +31.2% (Figure 4). The percent change in weight for those under 18 was significantly higher than those 18 and older (+3.56% versus +1.00%, p=0.002) (Figure 3). The percent change in weight by weight status was as follows: +3.07% for those with underweight or normal weight, +3.63% for those with overweight, and +1.66% for those with obesity (data not shown).
The mean percent BMI change from baseline to six months was +1.42% (Figure 3), median +0.95%, but the percent BMI change in the study population ranged from -20.8% to +31.2% (Figure 4). The percent change in BMI for those under 18 and those 18 and older did not significantly differ (+1.73% versus +1.07%, p=0.49) (Figure 3). The range of individual percent change in weight and BMI throughout the study population is depicted in Figure 4. A minority of individuals demonstrated a change in weight (20.6% of the study population) and BMI (17.6% of the study population) of greater than 5% (Figure 4).
We next looked at factors that might be influencing weight change during the study period (Supplemental Table 1). Table 4 shows the life changes during the study. Overall, most individuals experienced some type of change during the study, with only 20% reporting no changes. Thirty-three percent had a major life change, 30.1% had a change in food access, 53.4% had a change in their activity level, and 43.2% had a change in their medications.
Table 4: Life changes during the study among 165 study participants with Prader-Willi syndrome
Changes throughout the study
|
Study Participants, n (%)
|
Major Life Change
|
|
Yes
|
55 (33.7)
|
No
|
108 (66.3)
|
Change to Food Access
|
|
Yes
|
49 (30.1)
|
No
|
114 (69.9)
|
Change in Activity Level
|
|
Yes
|
87 (53.4)
|
No
|
76 (46.6)
|
Change in Medications
|
|
Yes
|
70 (43.2)
|
No
|
92 (56.8)
|
Experienced at least one of the previous changes
|
|
Yes
|
130 (79.8)
|
No
|
33 (20.2)
|
We performed bivariate analysis using repeated measures ANOVA for the two main outcomes, weight and BMI, and ANOVA for percent change in weight and BMI to inform our multivariate analysis (Table 5). We found significant main effects of time (BMI), sex (weight), age (weight, BMI, percent change in weight), percentage of life on GH therapy (weight, BMI), major life change (BMI), and change in food access (BMI). Main effects were similar between participants below the age of 18 compared to those 18 and older (not shown).
Table 5: Significant bivariate analysis of weight, BMI, and percent change in weight with demographic variables
Variable
|
F (df)
|
F
|
P-value
|
Weight
|
Week
|
25,87
|
1.34
|
0.163
|
Sex (ref=Male)
|
1,110
|
6.87
|
0.01**
|
Age
|
1,110
|
10.49
|
0.0016**
|
Percentage of Life on GH Therapy
|
1,109
|
7.40
|
0.0076**
|
Major Life Change
|
1,110
|
1.03
|
0.312
|
Change in Food Access
|
1,110
|
3.39
|
0.0683
|
Change in Activity Level
|
1,110
|
3.63
|
0.0592
|
Change in Medication
|
1,110
|
0.90
|
0.344
|
BMI
|
Week
|
2,155
|
3.13
|
0.046*
|
Sex (ref=Male)
|
1,155
|
0.00
|
0.98
|
Age
|
1,155
|
13.2
|
0.0004**
|
Percentage of Life on GH Therapy
|
1,154
|
34.1
|
<0.0001**
|
Major Life Change
|
1,155
|
3.96
|
0.0485*
|
Change in Food Access
|
1,155
|
7.23
|
0.0080**
|
Change in Activity Level
|
1,155
|
2.87
|
0.092
|
Change in Medication
|
1,155
|
1.58
|
0.21
|
Percent Change in Weight
|
Sex (ref=Male)
|
1,159
|
0.43
|
0.511
|
Age
|
1,159
|
9.79
|
0.0021**
|
Percentage of Life on GH Therapy
|
1,158
|
1.34
|
0.249
|
Major Life Change
|
1.159
|
1.47
|
0.226
|
Change in Food Access
|
1.159
|
0.00
|
0.95
|
Change in Activity Level
|
1,159
|
1.89
|
0.171
|
Change in Medication
|
1,158
|
0.28
|
0.598
|
Percent Change in BMI
|
Sex (ref=Male)
|
1,155
|
2.23
|
0.137
|
Age
|
1,155
|
0.12
|
0.727
|
Percentage of Life on GH Therapy
|
1,154
|
0.32
|
0.575
|
Major Life Change
|
1,155
|
0.32
|
0.572
|
Change in Food Access
|
1,155
|
0.01
|
0.932
|
Change in Activity Level
|
1,155
|
0.00
|
0.951
|
Change in Medication
|
1,155
|
0.35
|
0.557
|
For Weight/BMI: repeated measures ANOVA used, for Percent Change in Weight/BMI: ANOVA; *p<0.05, **p<0.01
|
Variable
|
F (df)
|
F
|
P-value
|
Weight
|
Week
|
25,87
|
1.34
|
0.163
|
Sex (ref=Male)
|
1,110
|
6.87
|
0.01**
|
Age
|
1,110
|
10.49
|
0.0016**
|
Percentage of Life on GH Therapy
|
1,109
|
7.40
|
0.0076**
|
Major Life Change
|
1,110
|
1.03
|
0.312
|
Change in Food Access
|
1,110
|
3.39
|
0.0683
|
Change in Activity Level
|
1,110
|
3.63
|
0.0592
|
Change in Medication
|
1,110
|
0.90
|
0.344
|
BMI
|
Week
|
2,155
|
3.13
|
0.046*
|
Sex (ref=Male)
|
1,155
|
0.00
|
0.98
|
Age
|
1,155
|
13.2
|
0.0004**
|
Percentage of Life on GH Therapy
|
1,154
|
34.1
|
<0.0001**
|
Major Life Change
|
1,155
|
3.96
|
0.0485*
|
Change in Food Access
|
1,155
|
7.23
|
0.0080**
|
Change in Activity Level
|
1,155
|
2.87
|
0.092
|
Change in Medication
|
1,155
|
1.58
|
0.21
|
Percent Change in Weight
|
Sex (ref=Male)
|
1,159
|
0.43
|
0.511
|
Age
|
1,159
|
9.79
|
0.0021**
|
Percentage of Life on GH Therapy
|
1,158
|
1.34
|
0.249
|
Major Life Change
|
1.159
|
1.47
|
0.226
|
Change in Food Access
|
1.159
|
0.00
|
0.95
|
Change in Activity Level
|
1,159
|
1.89
|
0.171
|
Change in Medication
|
1,158
|
0.28
|
0.598
|
Percent Change in BMI
|
Sex (ref=Male)
|
1,155
|
2.23
|
0.137
|
Age
|
1,155
|
0.12
|
0.727
|
Percentage of Life on GH Therapy
|
1,154
|
0.32
|
0.575
|
Major Life Change
|
1,155
|
0.32
|
0.572
|
Change in Food Access
|
1,155
|
0.01
|
0.932
|
Change in Activity Level
|
1,155
|
0.00
|
0.951
|
Change in Medication
|
1,155
|
0.35
|
0.557
|
For weight, 26 weekly weight measurements were used. For BMI, 3 time points were used (baseline, 3 months, 6 months). For weight/BMI: repeated measures ANOVA used, for percent change in weight/BMI: ANOVA; *p<0.05, **p<0.01
Table 6 shows the multivariable modeling for weight over time and BMI over time. For the outcome of weight, time in the study, sex, and percentage of life on GH therapy were statistically significant fixed effects. For every week increase in the study, participants’ weight significantly increased by 0.06% (95% CI 0.02%-0.09%). This means that at the end of the six-month study, weight had increased by 1.56%. Overall, weight for females in this study was 15% less than males (95% CI 4.4%-24.7%). For every percentage of life on GH therapy increase, weight was decreased by 0.22% (95% CI 0.1%-0.4%). For BMI, percentage of life on GH therapy was a significant fixed effect. For every percent of life on GH therapy increase, BMI was decreased by 0.41% (95% CI 0.2%-0.6%). For the multivariable modeling of percent change in weight, we found that age was a significant fixed effect. For every year increase in age, percent change in weight decreased by 0.20% (SE 0.07), p=0.0029. There were no significant fixed effects for percent change in BMI.
We had very high compliance among participants in this study. The mean percentage of weeks with a completed weight measurement was 95.1%, with no significant difference by age (96.8% for those 18 and older, 93.6% for those younger than 18). Only 2 people returned less than 50% of their weight measurements, and 68% of the study population returned 100% of their weight measurements for all 26 weeks in the study.
Table 6: Multivariate modeling for weight and BMI among 165 study participants with Prader-Willi syndrome
Variable
|
Exponentiated Beta (95% CI)
|
Type 3 GEE Analysis Chi-Square
|
P-value
|
Weight
|
Week
|
1.0006 (1.0002, 1.0009)
|
8.48
|
0.0036**
|
Sex (ref=Male)
|
0.850 (0.753, 0.956)
|
4.83
|
0.028*
|
Percentage of life on GH Therapy
|
0.9978 (0.996, 0.999)
|
4.46
|
0.035*
|
Age
|
1.006 (0.996, 1.017)
|
0.06
|
0.80
|
|
|
|
|
BMI
|
Week
|
1.0003 (0.9999, 1.0007)
|
1.34
|
0.18
|
Percent of Life on GH Therapy
|
0.9959 (0.994, 0.998)
|
14.05
|
0.0002**
|
Age
|
1.0016 (0.994, 1.009)
|
0.09
|
0.77
|
For weight, 26 weekly weight measurements were used. For BMI, 3 time points were used (baseline, 3 months, 6 months). Generalized Estimating Equations used; *p<0.05, **p<0.01