Eur J Pediatr (2011) 170:351–358 DOI 10.

1007/s00431-010-1299-z
ORIGINAL PAPER

Health-related quality of life and cognitive functioning in

pediatric short stature: comparison of growth-hormone-naïve,
growth-hormone-treated, and healthy samples
Matthew D. Stephen
&
James W. Varni
&

Christine A. Limbers
&
Michael Yafi
& Rubina A. Heptulla
&
Venkat S. Renukuntla
&
Cynthia S. Bell
&
Patrick G. Brosnan
Received: 10 May 2010 /Accepted: 9 September 2010 /Published online: 1 October 2010 © Springer-Verlag 2010
Abstract The objective of this study was to evaluate the impact of short stature on generic health-related quality of
life (HRQOL) and cognitive functioning in pediatric patients. Eighty-nine youth, 48 who were initially seen
with short stature (SS group) and 41 with a history of short stature being treated with growth hormone (GHT group)
and one of their legal guardians participated in the study. HRQOL and cognitive functioning were assessed using the
PedsQLTM 4.0 Generic Core Scales and PedsQLTM Cogni-
M. D. Stephen (*)
tive Functioning Scale. Comparisons were made between
Department of Pediatrics, Division of Endocrinology,
the study groups and with a previously obtained matched
The Children’s Hospital at Scott & White and The University of Texas Health Science Center - Houston, 2401 S. 31st St.,
Temple, TX 76508, USA
healthy sample. For the GHT group, height Z score was found to be a positive predictor of overall HRQOL while
duration of GHT was found to be a predictor of physical e-mail: mstephen@swmail.sw.org
functioning. For the SS group, the difference between
M. Yafi

.
 P. G. Brosnan Department of Pediatrics, Division of Endocrinology, The University of Texas Health Science Center,
midparental height Z score and height Z score was found to be a negative predictor of overall HRQOL and cognitive
functioning. Comparison with the healthy sample demon- Houston, TX, USA
strated significant negative impact on HRQOL for child
C. S. Bell Department of Pediatrics, Division of Nephrology, The University of Texas Health Science Center,
self-report and on HRQOL and cognitive functioning for parent proxy-report in both study groups. The GHT group
had a significantly higher child self-reported Physical Houston, TX, USA
Functioning score than the SS group (effect size (ES)=
J. W. Varni Department of Pediatrics, College of Medicine, Texas A&M University,

0.52, p<0.05). In conclusion, the GHT group had slightly better HRQOL scores than the SS group, but the difference
was not statistically significant. Both groups College Station, TX, USA
had significantly lower HRQOL and cognitive functioning
J. W. Varni Department of Landscape Architecture and Urban Planning, College of Architecture, Texas A&M University,
scores than healthy sample. Predictors of HRQOL and cognitive functioning found in this study lend support to the
use of the PedsQLTM 4.0 Generic Score Scales and College Station, TX, USA
PedsQLTM Cognitive Functioning Scale in routine assess-
C. A. Limbers Department of Psychology, Baylor University, Waco, TX, USA
ment of children with short stature in order to identify children at increased risk for impaired HRQOL and cognitive
functioning.
R. A. Heptulla

.
V. S. Renukuntla Department of Pediatrics, Division of Endocrinology & Metabolism, Baylor College of
Medicine and Texas Children’s Hospital,
Keywords Quality of life . Short stature . PedsQL . Cognitive functioning Houston, TX, USA
.
Growth hormone
.
Patient-reported outcomes
Introduction
Understanding the stature-exclusive effects of short stature is important [10, 18, 22]. The predominant focus of
psycholog- ical research in children with short stature has been on performance and functioning as outcomes [3].
Children with short stature report more teasing, lower academic achieve- ment test scores, and greater likelihood of
grade repetition than their normal height peers [33–35]. Adults with short stature have shown more difficulties in
education, employ- ment, relationships, and friendships, as compared to those of normal height [34]. While these
studies point to profound psychosocial disadvantages, it is not clear how large these disadvantages are, nor whether
they are due only to societal bias or to biological or functional consequences of growth hormone deficiency [6]. In
addition, study of normal short stature patients (defined as height less than 5% for age and gender not attributable to
illness, hormonal deficiency, or syndrome) has not always supported these deficits [11, 24]. Comparison of these
studies is complicated by variation in diagnoses represented, age at inquiry, use of different psycho- social
measurement instruments, and degree of short stature.
A number of authors have argued that improving quality of life is the ultimate goal of healthcare. Health-related
quality of life (HRQOL) is a multidimensional construct, consisting at minimum of the physical, psychological
(including emotional and cognitive), and social health dimensions delineated by the World Health Organization
[37]. HRQOL, which assesses a patient’s subjective perception of the impact of disease and treatment on health and
well-being, has been increasingly acknowledged as an important outcome in children with short stature [2, 3].
Overall, generic HRQOL scales used among growth-hormone (HGH)-treated subjects with short stature have failed
to demonstrate a significant difference as compared to healthy subjects [3, 35]. However, there remains a relative
dearth of studies that have assessed generic HRQOL in pediatric short stature using well-validated HRQOL
measures [2]. In addition, the existing studies have a number of methodological limitations including small sample
size and an absence of data on parent–child agreement [2, 3]. Thus, further studies are needed to assess the impact of
actual height, perceived height, and psychological adaptation on HRQOL among children with short stature [2, 3].
The primary objective of the present study was to better define the impact of actual height on HRQOL in children
and adolescents being seen for short stature and to assess whether there were differences in HRQOL between those
initially being evaluated for short stature and those currently being treated with growth hormone for short stature.
Further, we sought to compare these two groups to a previously obtained healthy sample and examine inter-
correlations between child self-report and parent proxy- report. We administered the internationally widely used
352 Eur J Pediatr (2011) 170:351–358
Pediatric Quality of Life InventoryTM (PedsQLTM) 4.0 Generic Core Scales and PedsQLTM Cognitive
Functioning Scale to evaluate the generic HRQOL and cognitive functioning of those with stature concerns. The
PedsQLTM Measurement Model integrates both generic and disease- specific instruments [17, 25]. A growing
number of disease-specific instruments have been developed from this model [8, 9, 16, 27, 28]. Advantages of using
a generic instrument include the ability to make comparisons between multiple medical conditions and healthy
population norms [31]. Though there are short-stature-specific and treatment- specific questionnaires, this limits the
ability for compari- son between groups and healthy samples [2].
The central hypothesis of this study was that generic HRQOL in children and adolescents initially seen with
untreated short stature would be impaired when compared to both patients with a history of short stature who had
been treated with HGH for at least 1 year and a previously obtained healthy sample. We also explored the impact of
short stature and treatment status on cognitive functioning.
Methods
Population
We performed a cross-sectional multidimensional analysis of study participants and their consenting parent/legal
guardian who were seen in the pediatric endocrinology clinics at the University of Texas Health Science Center at
Houston and at Texas Children’s Hospital/Baylor College of Medicine with confirmed, untreated short stature (SS
group) and those with a history of short stature currently being treated with HGH for at least 1 year (GHT group).
Youth aged 5 to 18 years were included in the study with their consenting parent/legal guardian. Exclusion criteria
included failure to thrive (defined as weight Z score less than height Z score), multiple pituitary hormone deficien-
cies, untreated metabolic disturbance (i.e., inadequately treated primary endocrine disorder such as thyroid dis-
ease), syndromic short stature (i.e., Turner Syndrome, Noonan Syndrome), and an inability to complete the
questionnaires.
Short stature was defined as height more than the two standard deviations (SDs) below the mean for age and
gender. Participants had to meet this criterion either at enrollment for the untreated SS group or prior to beginning
HGH for the GHT group. We evaluated our short stature participants on HGH at least 1 year into therapy in order to
allow participants to witness some stature effects of HGH. This study was approved by the institutional review
boards at each participating center. Informed consent and assent were obtained from all participants.
Measures and procedures
Patients being treated with growth hormone were screened prior to their appointment to determine if they met
inclusion criteria. Patients initially being seen for evaluation of short stature were screened at check-in, once
anthropometric data was available. Those meeting criteria were approached and respective consent/assent was
obtained if the parent and patient agreed to participate.
Each participant and consenting parent/legal guardian was provided the PedsQLTM 4.0 Generic Core Scales and
the PedsQLTM Cognitive Functioning Scale. The PedsQLTM 4.0 Generic Core Scales (23 questions) evaluates
Physical Functioning (eight questions), Emotional Functioning (five questions), Social Functioning (five questions),
and School Functioning (five questions) and has been validated in numerous pediatric medical conditions and in
healthy youth [31, 32]. The PedsQLTM Cognitive Functioning Scale (six questions) asks questions regarding
memory and attention. Additionally, the consenting parent/legal guardian completed the PedsQLTM Family
Information Form which requests extensive sociodemographic data [30].
The PedsQLTM scales are answered using a five-point Likert scale, except for participants less than 8 years who
use a three-point Likert scale. Age appropriate scales were used (ages 5–7 years, 8–12 years, and 13–18 years).
Likert scale scores are converted to a score ranging from 0 to 100 (“100” indicating better HRQOL). Permission to
use the questionnaires was provided by MAPI Research Trust (http://www.mapi-trust.org) through the PedsQLTM
domain (http://www.pedsql.org).
Participants were requested not to discuss questions or share answers among themselves. For younger children
who needed help reading, the questions were read aloud by a research assistant or parent (with a research assistant in
room). Careful attention was made to limit distractions. During the consent/assent process, care was taken not to
introduce concerns about short stature with the participants. It was stressed to all participants to leave questions
blank that they felt uncomfortable answering.
Sample size and statistical analysis
Sample estimations were difficult to determine secondary to lack of data using the PedsQLTM in either patients with
short stature or those being treated with growth hormone. Previous studies using the PedsQLTM suggest the need
for at least 50 subjects per group and preferably 100 subjects to reach satisfactory statistical power [31]. Though
many patients are referred for short stature, relatively few screened were more than the 2 SDs below the mean for
age and gender at initial consult (for SS group) or prior to initiating HGH (for GHT group). Consequently, we
include
Eur J Pediatr (2011) 170:351–358 353
effect size (ES) calculations in order to identify trends in the data.
Statistical analyses were performed using SPSS 17 (SPSS, Chicago, IL) [21]. Means and standard deviations
were calculated to compare study groups. T tests and Fisher’s exact tests were performed to evaluate for differences
between groups. The healthy sample HRQOL data was taken from previously reported data [26, 29] and matched for
age, gender, and race/ethnicity using SPSS random sample case selection command [21]. The healthy cognitive
func- tioning data were not able to be matched secondary to inadequate sample size [13]. Comparison of scale score
means between groups was performed using effect sizes [4]. ES was calculated by dividing the difference between
the group means by the pooled standard deviation of the study population. ES less than 15 is considered to represent
a negligible difference. Further, ES can be defined as small (0.2), medium (0.5), and large (0.8) [4]. ES is a way of
demonstrating the magnitude of differences between means with a higher score signifying a greater difference.
Intraclass Correlation Coefficients (ICC) were utilized to evaluate agreement between child self-report and parent
proxy-report [14]. The ICC provides an index of absolute agreement given that it takes into account the ratio
between subject variability and total variability [5, 14]. Correlation coefficients are designated as ≤0.40 poor to fair
agreement, 0.41–0.6 moderate agreement, 0.61–0.8 good agreement, and 0.81–1 excellent agreement [1, 36].
Linear regression analysis was performed to predict the effect(s) of multiple factors on scale scores. Specifically,
we used linear regression analyses to predict the effect(s) of age, gender, race/ethnicity, diagnosis, enrollment height
Z score, difference between midparental height Z score and baseline height Z score, current growth velocity, and
duration of growth hormone therapy on scale scores.
Results
Baseline characteristics
Over 16 months, we recruited a total of 89 patients. Of these, 48 had short stature initially being evaluated (SS
group), while 41 had a history of short stature currently being treated with HGH (GHT group). The characteristics of
each group were similar including gender, race/ethnicity, and parent’s educational level and are summarized in
Table 1. Not surprisingly, the GHT group was slightly older than those being initially evaluated with short stature.
The maximal parental education of the families was quite high with over 90% having at least a high school degree
and >65% having at least a college degree. Baseline anthropometric data is provided in Table 2. Though
Table 1 Sociodemographic characteristics of patients (by Group)
SS groupa GHT groupb
Standard Standard
Mean SD Count % Mean SD Count % p
Age (in months) 136.25 34.24 48 156.56 26.13 41 0.003 Gender NS
Male 34 70.80 34 82.90 Female 14 29.20 7 17.10 Race/ethnicity NS
White, non-Hispanic 29 60.40 26 63.40 White, Hispanic 12 25.00 11 26.80 Black, non-Hispanic 2 4.20 1 2.40 Other 5 10.40 3
7.30 Highest level of education (by either parent) NS
Less than high school 1 2.20 2 5 High school/some college 15 32.60 7 17.50 College or above 30 65.20 31 77.50
NS not significant a
Short stature group b
Growth-hormone-treated group
statistically different when comparing height and weight data, children in both groups clearly met the definition of
short stature (all height Z scores less than 2). For the SS group baseline and enrollment height data are the same,
while for the GHT group baseline height data are prior to HGH. Enrollment data including diagnoses for the GHT
group are included in Table 3. Diagnoses were not included for the SS group because many patients did not have a
diagnosis assigned yet and commonly the diagnosis may
Table 2 Baseline anthropometric data
SS groupa GHT groupb p
Height (cm) 129.16 123.15 0.05 Height Z score −2.56 −4.55 <0.0001 Weight (kg) 28.97 26.63 <0.0001 Weight Z score −2.1
−4.45 <0.0001 Growth velocity (cm/year)c 5.43 8.76 <0.0001 Midparental height (cm)c 168.27 170.38 NS Midparental height Z
score −0.65 −0.53 NS
NS not significant a
The height and weight data for the short stature group (SS group) is from enrollment/baseline b
The data for the growth-hormone-treated group (GHT group) is from baseline (prior to starting growth hormone therapy) c
The midparental height and growth velocity data at enrollment for both groups is provided
Table 3 Enrollment data for growth-hormone-treated group (GHT group)
Height (cm) 144.25 Height Z score −1.62 Weight (kg) 38.28 Weight Z score −1.34 Diagnosis Growth hormone deficiency 23
(56.1%) Idiopathic short stature 18 (43.9%)
354 Eur J Pediatr (2011) 170:351–358
change with longer follow-up. Nine patients refused participation in the study.
Linear regression analysis was performed to evaluate for predictors of HRQOL (including individual
components) and cognitive functioning for the child self-report by group. The mean total HRQOL score at
enrollment was 5.34 (SD=2.12) points higher for every one height SD taller in the GHT group (p=0.016) while it
trended toward a positive correlation in the SS group (p=0.072). Mean total HRQOL score was 3.29 (SD=1.49)
points lower for every one height SD greater difference between baseline height Z score and midparental height Z
score in the SS group (p=0.034) while it trended toward a negative correlation in the GHT group (p=0.076). For the
SS group, the cognitive functioning mean was 8.05 (SD=3.58) points higher for every one height SD higher at
baseline/enrollment (p=0.029). The mean Physical Func-
parent tioning score in the GHT group was found to be 4.1(SD=
proxy-report of the total HRQOL score
(p<0.05) 1.59) points higher for every 1 SD taller (p=0.014) and
was not as large as for child self-report, parents did
0.32 (SD=0.12) points higher for every month longer of
recognize similar concerns to their children with
regards HGH (p=0.011). The average duration of HGH was
to psychosocial health (p<0.01), emotional
functioning 36.55 months (SD=18.67). For the regression analyses, no
(p<0.001), and social functioning (p<0.001).
significant differences were demonstrated based on age, gender, race/ethnicity, or diagnosis (for the GHT group).
Growth-hormone-treated group compared to healthy sample
Short stature group (not treated with HGH) compared
Table 4 contains PedsQLTM Generic Core Scales
and to healthy sample
PedsQLTM Cognitive Functioning Scale comparisons be- tween the short stature growth-hormone-treated group
and Table 4 presents PedsQLTM Generic Core Scales and
healthy sample. Child self-report in the GHT group
showed PedsQLTM Cognitive Functioning Scale comparisons be-
differences between the GHT group and healthy
sample, tween the short stature (not treated with HGH) and healthy
smaller but similar to the differences between the SS
group sample. Child self-report revealed significant impairment
and the healthy sample, except that there was not a
on the total HRQOL score (p<0.001) including the physical
significant difference in the physical functioning
domain. (p<0.001), psychosocial (p<0.001), emotional (p<0.05),
There was lesser, yet still significant, difference in
the total and social (p<0.001) domains in the SS group compared to
HRQOL score (p<0.05) and the emotional (p<0.05),
and the healthy sample. There was no significant difference
social domains (p<0.05). Parent proxy-report scores
for the between school and cognitive functioning scores.
GHT group showed significantly lower scores in
psycho- Parent proxy-report did not demonstrate the significant
social (p<0.05) and emotional domains (p<0.05) as
physical function impairment seen in the child self-report,
compared to the healthy sample as well as an
impairment but did suggest a lower cognitive functioning (p<0.001) as
 in cognitive functioning (p<0.001) comparable to
that in compared to the healthy sample. Though the difference in
the SS group.
Table 4 PedsQLTM 4.0 generic core scales and PedsQL
TM
cognitive functioning scale comparisons between Short Stature (SS
Group), Growth- Hormone-Treated (GHT), and healthy samples for child self-report and parent proxy-report
PedsQLTM scale SS group (a) GHT group (b) Healthy (c) Comparisons Effect sizes
Mean SD Mean SD Mean SD a vs. c b vs. c a vs. b
Child self-report (n=48) (n=41) (n=1,259) Total score 79.28 11.17 82.56 12.16 86.19 11.57 c>a***;c>b* 0.60 0.31 0.29 Physical
83.92 11.97 89.55 9.15 90.28 11.62 c>a***;b>a* 0.55 0.06 0.52 Psychosocial 76.74 12.32 78.54 15.37 84.03 13.25 c>a***;c>b*
0.55 0.41 0.13 Emotional 76.04 17.35 76.83 18.70 82.17 16.97 c>a,b* 0.36 0.31 0.04 Social 76.92 20.20 81.86 18.02 87.98 14.96
c>a***;c>b* 0.73 0.41 0.26 School 77.60 13.64 77.68 16.47 81.96 16.28 – 0.37 0.26 0.01 Cognitivea 78.11 15.49 82.00 16.35
82.78 16.26 – 0.29 0.05 0.24 Parent proxy-report (n=48) (n=41) (n=1535) Total score 78.39 13.86 80.97 11.67 83.67 14.41 c>a*
0.37 0.19 0.20 Physical 86.87 14.37 89.10 13.68 86.86 17.86 – 0.00 0.13 0.16 Psychosocial 75.00 15.43 77.14 13.62 81.94 14.78
c>a**;c>b* 0.47 0.33 0.15 Emotional 71.91 18.95 75.91 17.78 81.78 16.87 c>a***;c>b* 0.58 0.35 0.22 Social 73.10 18.90 80.37
17.08 85.39 17.76 c>a*** 0.69 0.28 0.40 School 77.29 20.73 72.84 16.96 78.57 18.95 – 0.07 0.30 0.23 Cognitivea 78.59 23.08
76.07 20.20 86.62 16.36 c>a,b*** 0.49 0.64 0.12
Healthy Sample Data from references 30, 31, and 32 – indicates no statiscally significant differences *p<0.05, **p<0.01,
***p<0.001 based on independent sample t test. Effects sizes are designated as an all (0.20), medium (0.50), and large (0.80) a
Sample are for the PedsQLTM Cognitive Functioning Scale for child self-report and parent proxy-report for the healthy sample
equals 157
Eur J Pediatr (2011) 170:351–358 355
Short stature group (not treated with HGH) compared to growth-hormone-treated group
Table 4 presents PedsQLTM Generic Core Scales and PedsQLTM Cognitive Functioning Scale comparisons
between the short stature (not treated with HGH) and growth-hormone- treated group. Comparison of child
self-report between the two groups indicated a small non-significant difference in total HRQOL score (ES=0.29,
p>0.05), social functioning (ES=0.26, p>0.05), and cognitive functioning (ES=0.24, p>0.05) and a moderately better
significant physical functioning score in the treated group (ES=0.52, p<0.05). Parent proxy-report revealed a small
non-significant differ- ence in total HRQOL score (ES=0.2, p>0.05), emotional (ES=0.22, p>0.05), and social
functioning (ES=0.4,p>0.05). Interestingly, there was a small non-significant negative effect on school functioning
(ES=0.23, p>0.05) between the groups. There were no significant differences found between the groups on either the
child self-report or parent proxy- report based on age, gender, or race/ethnicity. Additionally, among the GHT
group, there were no significant differences in HRQOL or cognitive functioning scores between those with growth
hormone deficiency or idiopathic short stature.
Parent/child agreement
ICCs between pediatric patient self-report and parent proxy- report for the SS group (not treated with HGH) across
the PedsQLTM4.0 Generic Core Scales and Cognitive Functioning Scale are as follows: Total Score=0.45
(p<0.001), Physical Health=0.38 (p<0.01), Psychosocial Health=0.44 (p<0.001), Emotional Functioning=0.45
(p<0.0001), Social Functioning=0.56 (p<0.0001), School Functioning=0.37 (p<0.01), Cognitive Functioning=0.21
(p>0.05). These ICCs are in the poor to moderate agreement range. For the GHT group, ICCs between pediatric
patient self- report and parent proxy-report across the PedsQLTM 4.0 Generic Core Scales and Cognitive
Functioning Scale are as follows: Total Score=0.69 (p<0.0001), Physical Health=0.61 (p<0.0001), Psychosocial
Health=0.64 (p<0.0001), Emotional Functioning=0.54 (p<0.0001), So- cial Functioning=0.55 (p<0.0001), School
Functioning= 0.51 (p<0.0001), Cognitive Functioning=0.65 (p<0.0001). These ICCs are in the moderate to good
agreement range.
Discussion
Our study demonstrates HRQOL deficits in youth with marked short stature either untreated (SS group) or treated
with HGH (GHT group), as perceived by pediatric patients themselves and their caregivers, and lends support for
the routine assessment of HRQOL in children with short stature.
356 Eur J Pediatr (2011) 170:351–358
Children in the GHT group and SS group self-reported significantly lower emotional functioning and social func-
tioning than healthy peers, with greater deficits reported in the SS group. Similarly, parents in both the SS group and
GHT group reported significantly lower psychosocial health and emotional functioning for their children com- pared
to parents of healthy children, with greater impair- ments reported in the SS group. Parents in the SS group also
reported significantly lower social functioning for their children compared to parents of healthy children. Overall,
findings from other empirical studies have been mixed with regard to social and emotional problems in children with
short stature [12, 15, 19, 20, 23, 34]. A recent population based study of 712 sixth graders (28 with height less than
10 percentile for age and gender) demonstrated no differ- ences in social, emotional, or behavioral outcomes com-
pared to non-short peers. However, this study only included 11 children with height less than 5 percentile for age
and gender. Theunissen et al. reported impairments in social functioning in a sample of 36 children with ISS when
compared to a normative population [23]. The present study supports some deficits in emotional and social
functioning from the perspective of children and parents in youth with marked short stature untreated and treated
with HGH for at least 1 year, with greater deficits in the untreated group. This highlights the need for parents and
clinicians alike to look for opportunities to support the emotional and social needs of children seeking care for short
stature.
We found that children in the GHT group who had been treated for at least 1 year self-reported significantly
better physical functioning than subjects with short stature initially presenting at the pediatric endocrinology clinics.
This finding is consistent with what we observe clinically in terms of patients and their families remarking that the
child’s physical abilities have improved since starting HGH. Specifically, the GHT group self-reported statistical- ly
better ability to lift something heavy and keeping up with their peers when playing than the SS group (p<0.05).
Results of our linear regression analyses indicated that duration of HGH was a positive predictor of physical
functioning in the GHT group. A prospective cohort study of subjects from their initial visit through their treatment
with HGH would be needed to determine if the physical functioning differences that we found result from therapy
and if there is lasting effect of HGH on HRQOL.
For both the GHT group and SS group, children and parents reported similar school functioning to healthy peers.
However, while children in the SS group and GHT group reported similar cognitive functioning to healthy peers,
their parents rated their cognitive functioning to be significantly lower than healthy peers. These conflicting findings
may represent expectation bias, but should not be trivialized. Investigation of intercorrelations between child
self-report
and parent proxy-report in the present study revealed better overall agreement between parents and children in the
GHT group compared to the SS group. Agreement between parents and children in the SS group was particularly
low on cognitive functioning as compared to the other domains of functioning. Taken together, these data suggests
that evaluating both children’s and parents’ perspectives regarding HRQOL and cognitive functioning should be the
standard for routine assessment in clinical practice and clinical trials for children with short stature since their
different perspectives potentially provide unique information. Unpublished data from our center suggested an
increased prevalence of attention-deficit hyperactivity disorder (ADHD) in our growth-hormone-deficient patients
(personal communication, Vanasse, L and PGB). Other research reports an increased use of ADHD medications
among those being treated with HGH [7]. Further study of the factors contributing to cognitive functioning among
youth with short stature and those being treated with HGH are warranted.
Strengths of our study included efforts to limit bias and inclusion of only those with true short stature (either at
enrollment for the SS group or prior to HGH for the GHT group). The study was sponsored through an institutional
grant without industry sponsorship. Care was made not to introduce concern about short stature to the child or
parent. Patients already on HGH were generally much more receptive of the study, while those initially seeking
attention for short stature were often more hesitant. In fact, a few parents voiced significant concerns about the
potential that by asking questions to their child about their quality of life and cognitive function we might invoke
concerns that were not already there. This attests to the strong societal bias surrounding short stature as well as the
potential parental contribution to this bias. We included only children who met the definition of short stature at
enrollment for the SS group or prior to HGH for the GHT group.
Some parents noted concerns that the questions being asked did not allow them to fully express their concerns. As
discussed, the questionnaires used were not designed specifically for children with short stature. Though parents of
short children expressed anxiety about immediate and long-term effects of short stature, many parents of children
already on HGH voiced concerns about the balance between numerous injections and uncertain increase in stature.
They worried that treatment might hurt their child’s self-perceptions more than improved stature helped.
Limitations of our study included the lack of prospective follow-up of patients. Secondly, our limited sample size
reduced the statistical power of the study and might have increased the Type II error rate between the treated (GHT
group) and untreated (SS group) groups. Setting height entry requirement of at least minus 2 standard deviations
may have provided more interpretable results but reduced
Eur J Pediatr (2011) 170:351–358 357
the number of subjects despite inclusion of two high- volume centers. Excluding these patients improved validity,
but limited numbers.
Baseline height differences between the GHT and SS groups may indicate a difference in underlying diagnosis.
For those in the SS group, a firm diagnosis was often not apparent and not uncommonly may change as the patient is
followed over time. The duration of this study did not allow for final diagnoses to be made in the SS group. Further,
our primary end point was comparison of HRQOL among those in the GHT and SS groups with regards to their
current height and not a specific diagnosis or treatment. Finally, we cannot make any conclusions about the effect(s)
of treatment (i.e., growth hormone) on HRQOL. However, we can make inferences about the differences between
groups (GHT and SS) and as compared to a healthy sample given our primary interest was investigating the impact
of stature on HRQOL, irrespective of diagnosis.
In summary, we found slight differences in HRQOL, particularly physical functioning, between youth being
initially seen with short stature and those with a history of short stature being treated with HGH. Our findings lend
support to the clinical usefulness of the PedsQLTM 4.0 Generic Core Scales and PedsQLTM Cognitive Functioning
Scale in the routine assessment of children with short stature.
Acknowledgments Appreciation is expressed to our patients and their families who made this study possible, and to the various
medical providers who allowed us to enroll their patients in this study. Special thanks to Kyrie Collins RN, Nunilo Rubio MD,
Robyn Klenk RN, FNP-C, MSN and Parvin Yazdani MD who assisted with enrolling patients when the primary investigator was
not available and William Risser MD, PhD for editorial contributions.
Competing Interest Dr. Varni holds the copyright and the trade- mark for the PedsQLTM and receives financial compensation
from the MAPI Research Trust, which is a nonprofit research institute that charges distribution fees to for-profit companies that
use the Pediatric Quality of Life InventoryTM.
Funding Funding was provided through an intradepartmental grant from the University of Texas Health Science Center at
Houston.
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