Eur J Pediatr (2011) 170:351358

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-nave,
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

C. A. Limbers
Department of Psychology, Baylor University,
Waco, TX, USA

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
PedsQL 4.0 Generic Core Scales and PedsQL Cognitive Functioning Scale. Comparisons were made between
the study groups and with a previously obtained matched
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
functioning. For the SS group, the difference between
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 demonstrated significant negative impact on HRQOL for child
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
Functioning score than the SS group (effect size (ES)=
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
had significantly lower HRQOL and cognitive functioning
scores than healthy sample. Predictors of HRQOL and
cognitive functioning found in this study lend support to
the use of the PedsQL 4.0 Generic Score Scales and
PedsQL Cognitive Functioning Scale in routine assessment 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 Childrens Hospital,
Houston, TX, USA

Keywords Quality of life . Short stature . PedsQL .

Cognitive functioning . Growth hormone . Patient-reported
outcomes

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
M. D. Stephen (*)
Department of Pediatrics, Division of Endocrinology,
The Childrens Hospital at Scott & White and The University
of Texas Health Science Center - Houston,
2401 S. 31st St.,
Temple, TX 76508, USA
e-mail: mstephen@swmail.sw.org
M. Yafi : P. G. Brosnan
Department of Pediatrics, Division of Endocrinology,
The University of Texas Health Science Center,
Houston, TX, USA
C. S. Bell
Department of Pediatrics, Division of Nephrology,
The University of Texas Health Science Center,
Houston, TX, USA
J. W. Varni
Department of Pediatrics, College of Medicine,
Texas A&M University,
College Station, TX, USA
J. W. Varni
Department of Landscape Architecture and Urban Planning,
College of Architecture, Texas A&M University,
College Station, TX, USA

352

Introduction
Understanding the stature-exclusive effects of short stature is
important [10, 18, 22]. The predominant focus of psychological research in children with short stature has been on
performance and functioning as outcomes [3]. Children with
short stature report more teasing, lower academic achievement test scores, and greater likelihood of grade repetition
than their normal height peers [3335]. Adults with short
stature have shown more difficulties in education, employment, 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 psychosocial 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
patients 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 parentchild 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 intercorrelations between child self-report and parent proxyreport. We administered the internationally widely used

Eur J Pediatr (2011) 170:351358

Pediatric Quality of Life Inventory (PedsQL) 4.0

Generic Core Scales and PedsQL Cognitive Functioning
Scale to evaluate the generic HRQOL and cognitive
functioning of those with stature concerns. The PedsQL
Measurement Model integrates both generic and diseasespecific 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 treatmentspecific questionnaires, this limits the ability for comparison 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 Childrens 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 deficiencies, untreated metabolic disturbance (i.e., inadequately
treated primary endocrine disorder such as thyroid disease), 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.

352

Introduction
Understanding the stature-exclusive effects of short stature is
important [10, 18, 22]. The predominant focus of psychological research in children with short stature has been on
performance and functioning as outcomes [3]. Children with
short stature report more teasing, lower academic achievement test scores, and greater likelihood of grade repetition
than their normal height peers [3335]. Adults with short
stature have shown more difficulties in education, employment, 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 psychosocial 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
patients 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 parentchild 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 intercorrelations between child self-report and parent proxyreport. We administered the internationally widely used

Eur J Pediatr (2011) 170:351358

Pediatric Quality of Life Inventory (PedsQL) 4.0

Generic Core Scales and PedsQL Cognitive Functioning
Scale to evaluate the generic HRQOL and cognitive
functioning of those with stature concerns. The PedsQL
Measurement Model integrates both generic and diseasespecific 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 treatmentspecific questionnaires, this limits the ability for comparison 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 Childrens 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 deficiencies, untreated metabolic disturbance (i.e., inadequately
treated primary endocrine disorder such as thyroid disease), 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.

Eur J Pediatr (2011) 170:351358

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 PedsQL 4.0 Generic Core Scales and
the PedsQL Cognitive Functioning Scale. The PedsQL
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 PedsQL Cognitive Functioning Scale (six
questions) asks questions regarding memory and attention.
Additionally, the consenting parent/legal guardian completed
the PedsQL Family Information Form which requests
extensive sociodemographic data [30].
The PedsQL 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 57 years, 812 years, and 1318 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 PedsQL 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 PedsQL in either patients with
short stature or those being treated with growth hormone.
Previous studies using the PedsQL 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

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 Fishers
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 functioning 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,
0.410.6 moderate agreement, 0.610.8 good agreement,
and 0.811 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 parents 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

354

Eur J Pediatr (2011) 170:351358

Table 1 Sociodemographic characteristics of patients (by Group)

Age (in months)

Gender

SS groupa

GHT groupb

Standard

Standard

Mean

SD

136.25

34.24

Male
Female
Race/ethnicity
White, non-Hispanic
White, Hispanic
Black, non-Hispanic
Other
Highest level of education (by either parent)
Less than high school
High school/some college
College or above

Count

48

Mean

SD

156.56

26.13

Count

41

p
0.003
NS

34
14

70.80
29.20

34
7

82.90
17.10

29
12
2
5

60.40
25.00
4.20
10.40

26
11
1
3

63.40
26.80
2.40
7.30

1
15
30

2.20
32.60
65.20

2
7
31

5
17.50
77.50

NS

NS

NS not significant
a

Short stature group

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

Height (cm)
Height Z score
Weight (kg)
Weight Z score
Growth velocity (cm/year)c
Midparental height (cm)c

129.16
2.56
28.97
2.1
5.43
168.27

123.15
4.55
26.63
4.45
8.76
170.38

Midparental height Z score

0.65

0.53

p
0.05
<0.0001
<0.0001
<0.0001
<0.0001
NS
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

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-

Table 3 Enrollment data for growth-hormone-treated group (GHT

group)
Height (cm)
Height Z score
Weight (kg)
Weight Z score
Diagnosis
Growth hormone deficiency
Idiopathic short stature

144.25
1.62
38.28
1.34
23 (56.1%)
18 (43.9%)

Eur J Pediatr (2011) 170:351358

355

tioning score in the GHT group was found to be 4.1(SD=

1.59) points higher for every 1 SD taller (p=0.014) and
0.32 (SD=0.12) points higher for every month longer of
HGH (p=0.011). The average duration of HGH was
36.55 months (SD=18.67). For the regression analyses, no
significant differences were demonstrated based on age,
gender, race/ethnicity, or diagnosis (for the GHT group).
Short stature group (not treated with HGH) compared
to healthy sample
Table 4 presents PedsQL Generic Core Scales and
PedsQL Cognitive Functioning Scale comparisons between the short stature (not treated with HGH) and healthy
sample. Child self-report revealed significant impairment
on the total HRQOL score (p<0.001) including the physical
(p<0.001), psychosocial (p<0.001), emotional (p<0.05),
and social (p<0.001) domains in the SS group compared to
the healthy sample. There was no significant difference
between school and cognitive functioning scores.
Parent proxy-report did not demonstrate the significant
physical function impairment seen in the child self-report,
but did suggest a lower cognitive functioning (p<0.001) as
compared to the healthy sample. Though the difference in

parent proxy-report of the total HRQOL score (p<0.05)

was not as large as for child self-report, parents did
recognize similar concerns to their children with regards
to psychosocial health (p< 0.01), emotional functioning
(p <0.001), and social functioning (p <0.001).
Growth-hormone-treated group compared to healthy sample
Table 4 contains PedsQL Generic Core Scales and
PedsQL Cognitive Functioning Scale comparisons between the short stature growth-hormone-treated group and
healthy sample. Child self-report in the GHT group showed
differences between the GHT group and healthy sample,
smaller but similar to the differences between the SS group
and the healthy sample, except that there was not a
significant difference in the physical functioning domain.
There was lesser, yet still significant, difference in the total
HRQOL score (p<0.05) and the emotional (p<0.05), and
social domains (p<0.05). Parent proxy-report scores for the
GHT group showed significantly lower scores in psychosocial (p < 0.05) and emotional domains (p < 0.05) as
compared to the healthy sample as well as an impairment
in cognitive functioning (p<0.001) comparable to that in
the SS group.

Table 4 PedsQL 4.0 generic core scales and PedsQLTM cognitive functioning scale comparisons between Short Stature (SS Group), GrowthHormone-Treated (GHT), and healthy samples for child self-report and parent proxy-report
PedsQL scale

SS group (a)

GHT group (b)

Healthy (c)

Mean

Mean

Mean

Child self-report
Total score
Physical
Psychosocial
Emotional
Social
School
Cognitivea
Parent proxy-report
Total score
Physical
Psychosocial

(n=48)
79.28
83.92
76.74
76.04
76.92
77.60
78.11
(n=48)
78.39
86.87
75.00

Emotional
Social
School
Cognitivea

71.91
73.10
77.29
78.59

SD

13.86
14.37
15.43

(n=41)
82.56
89.55
78.54
76.83
81.86
77.68
82.00
(n=41)
80.97
89.10
77.14

18.95
18.90
20.73
23.08

75.91
80.37
72.84
76.07

11.17
11.97
12.32
17.35
20.20
13.64
15.49

SD

Comparisons

SD

Effect sizes
a vs. c

b vs. c

a vs. b

11.57
11.62
13.25
16.97
14.96
16.28
16.26

c>a***;c>b*
c>a***;b>a*
c>a***;c>b*
c>a,b*
c>a***;c>b*

0.60
0.55
0.55
0.36
0.73
0.37
0.29

0.31
0.06
0.41
0.31
0.41
0.26
0.05

0.29
0.52
0.13
0.04
0.26
0.01
0.24

11.67
13.68
13.62

(n=1,259)
86.19
90.28
84.03
82.17
87.98
81.96
82.78
(n=1535)
83.67
86.86
81.94

14.41
17.86
14.78

c>a*

c>a**;c>b*

0.37
0.00
0.47

0.19
0.13
0.33

0.20
0.16
0.15

17.78
17.08
16.96
20.20

81.78
85.39
78.57
86.62

16.87
17.76
18.95
16.36

c>a***;c>b*
c>a***

c>a,b***

0.58
0.69
0.07
0.49

0.35
0.28
0.30
0.64

0.22
0.40
0.23
0.12

12.16
9.15
15.37
18.70
18.02
16.47
16.35

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 PedsQL Cognitive Functioning Scale for child self-report and parent proxy-report for the healthy sample equals 157

356

Short stature group (not treated with HGH) compared

to growth-hormone-treated group
Table 4 presents PedsQL Generic Core Scales and
PedsQL Cognitive Functioning Scale comparisons between
the short stature (not treated with HGH) and growth-hormonetreated 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 difference 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 proxyreport 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 proxyreport for the SS group (not treated with HGH) across the
PedsQL 4.0 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 selfreport and parent proxy-report across the PedsQL 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), Social 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.

Eur J Pediatr (2011) 170:351358

Children in the GHT group and SS group self-reported

significantly lower emotional functioning and social functioning 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 compared to parents of healthy children, with greater impairments 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 differences in social, emotional, or behavioral outcomes compared 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
childs physical abilities have improved since starting
HGH. Specifically, the GHT group self-reported statistically 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

Eur J Pediatr (2011) 170:351358

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 childrens 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 childs
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

357

the number of subjects despite inclusion of two highvolume 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 PedsQL 4.0
Generic Core Scales and PedsQL 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 trademark for the PedsQL 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 Inventory.

Funding Funding was provided through an intradepartmental grant

from the University of Texas Health Science Center at Houston.

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