Health-Related Quality of Life in Pediatric Patients with Functionaland Organic Gastrointestinal Diseases

James W. Varni, PhD1,2, Cristiane B. Bendo, PhD3, Samuel Nurko, MD4, Robert J. Shulman, MD5,6, Mariella M. Self, PhD7,

James P. Franciosi, MD8, Miguel Saps, MD9, and John F. Pohl, MD10, on behalf of the

Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module Testing Study Consortium*

Objective To compare health-related quality of life (HRQOL) in pediatric patients with functional gastrointestinaldisorders (FGIDs) and organic gastrointestinal (GI) diseases with an age-, sex-, and race/ethnicity-matched healthysample across GI diagnostic groups and with one another.Study design The Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-sitestudy by 689 families. Patients had 1 of 7 physician-diagnosed GI disorders: chronic constipation, functionalabdominal pain, irritable bowel syndrome, functional dyspepsia, Crohn’s disease, ulcerative colitis, andgastroesophageal reflux disease. The healthy control sample included 1114 families. School days missed,days in bed and needing care, parent missed workdays, work impact, and healthcare utilization werecompared as well.Results Patients with an FGID or organic GI disease demonstrated lower HRQOL than the healthy controls acrossall dimensions (physical, emotional, social, and school; P < .001 for all), with larger effect sizes for patients with anFGID. Patients with an FGIDmanifested lower HRQOL than those with an organic GI disease. Patients with an FGIDor organic GI disease missed more school, spent more days in bed and needing care, had greater healthcare uti-lization, and had parents whomissedmore workdays with greater work impact (P < .001 for most), with larger effectsizes for the patients with an FGID.Conclusion Patients with an FGID or organic GI disease demonstrate impaired HRQOL compared with healthychildren. HRQOL can be used as a common metric to compare patient outcomes in clinical research and practiceboth within and across groups of patients with FGIDs and organic GI diseases. (J Pediatr 2015;166:85-90).

See editorial, p 11

eneric (general or non–disease-specific) health-related quality of life

From the 1Department of Pediatrics, College ofMedicine, and 2Department of Landscape Architectureand Urban Planning, College of Architecture, TexasA&M University, College Station, TX; 3Department ofPediatric Dentistry and Orthodontics, Faculty ofDentistry, Federal University of Minas Gerais, BeloHorizonte, MG, Brazil; 4Center for Motility andFunctional Gastrointestinal Disorders, BostonChildren’s Hospital, Harvard Medical School, Boston,MA; 5Department of Pediatrics, 6Children’s NutritionResearch Center, and 7Department of Psychiatry,Baylor College of Medicine, Texas Children’s Hospital,Houston, TX; 8Division of Gastroenterology,Hepatology, and Nutrition, Cincinnati Children’sHospital Medical Center, Cincinnati, OH; 9Division ofGastroenterology, Hepatology, and Nutrition, LurieChildren’s Hospital of Chicago, Northwestern UniversityFeinberg School of Medicine, Chicago, IL; and10Department of Pediatric Gastroenterology, PrimaryChildren’s Hospital, University of Utah, Salt Lake City,UT

*A list of PedsQL Gastrointestinal Symptoms Module

G(HRQOL) measurement is increasingly being used to assess the impactof pediatric diseases and treatments from the perspective of pediatric pa-

tients and their parents.1-3 HRQOL is amultidimensional construct, consisting at aminimum of the physical, psychological (including emotional and cognitive), andsocial health dimensions delineated by the World Health Organization.4,5 Well-validated generic HRQOL instruments provide a common metric that facilitatescomparisons across patient groups and benchmarking with healthy populations.6

The emerging paradigm shift toward patient-reported outcomes in clinical tri-als has provided an opportunity to emphasize the importance of pediatric patientself-report measurement as efficacy outcomes.5,7,8 The Pediatric Quality of LifeInventory (PedsQL; available at http://www.pedsql.org.) 4.0 Generic Core Scalesis a reliable and valid measurement instrument that has been used to assess theHRQOL of children with numerous acute and chronic health conditions, aswell as healthy populations.1-3,6,9-11 It has been an explicit goal of the PedsQL

Testing Study Consortium sites is available at www.jpeds.com (Appendix).

J.F. is currently at the Division of Gastroenterology,Hepatology, and Nutrition, Nemours Children’s Hospital,Orlando, FL.

J.V. holds the copyright and the trademark for thePedsQL and receives financial compensation from theMapi Research Trust, a nonprofit research institute thatcharges distribution fees to for-profit companies that usethe PedsQL. The other authors declare no conflicts ofinterest.

0022-3476/$ - see front matter. Copyright ª 2015 Elsevier Inc.

All rights reserved.

http://dx.doi.org/10.1016/j.jpeds.2014.08.022

CC Chronic constipation

CD Crohn’s disease

FAP Functional abdominal pain

FD Functional dyspepsia

FGID Functional gastrointestinal disorder

GI Gastrointestinal

HRQOL Health-related quality of life

IBS Irritable bowel syndrome

PedsQL Pediatric Quality of Life Inventory

85

THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 166, No. 1

Measurement Model12 to develop and test brief measures forthe broadest age group empirically feasible, specificallyincluding child self-reporting for the youngest childrenpossible.13 The items chosen for inclusion were initiallyderived from the measurement properties of the child self-report scales, and the parent proxy report scales were con-structed to directly parallel the child self-report items.Thus, the development and testing of the PedsQL as a pedi-atric patient-reported outcome explicitly emphasizes thechild’s perceptions.6

The PedsQL 4.0 Generic Core Scales also has been used tomeasure the HRQOL of pediatric patients with functionalgastrointestinal disorders (FGIDs) and organic gastrointes-tinal (GI) diseases.14-21 However, previous studies used theolder Rome II diagnostic criteria for FGIDs, had substantiallysmaller sample sizes overall and particularly for individual GIdiagnostic groups, were single-site studies, and/or included amore limited age range, which in combination limit thegeneralizability of their findings. To our knowledge, thegeneric HRQOL of a geographically diverse large sample ofpediatric patients with FGIDs (using Rome III diagnosticguidelines22) and organic GI diseases has not been previouslycompared with a large age-, sex-, and race/ethnicity-matchedhealthy sample encompassing an age range of 2-18 years forparent proxy report and 5-18 years for patient self-report.

To address these significant gaps in the literature, we usedthe PedsQL 4.0 Generic Core Scales to investigate the HRQOLof pediatric patients with 7 FGIDs and organic GI diseases andcompare it with that of an age-, sex-, and race/ethnicity-matched healthy control sample. We hypothesized that pa-tients with FGIDs and organic GI diseases would manifestlower HRQOL than the matched healthy controls. We furtherhypothesized that patients with FGIDs would manifest lowerHRQOL than patients with organic GI diseases. Finally, we hy-pothesized that patients with GI disorders would miss moreschool days, spend more days sick in bed or too ill to play,require more days for a parent/caregiver to care for themowing to physical or mental health issues, and use morehealthcare services than healthy children. We anticipatedthat the parents of these children would report missing morework days and report a greater impact on their work and abil-ity to concentrate than parents of healthy children.

Methods

Pediatric patients aged 5-18 years and parents of pediatric pa-tients aged 2-18 years with a physician-diagnosed GI disorderusing International Classification of Disease, Ninth Revision,Clinical Modification diagnosis codes and/or Rome IIIcriteria for FGIDs for 7 GI diagnostic groups, includingboth functional (chronic constipation [CC], functionalabdominal pain [FAP], irritable bowel syndrome [IBS], andfunctional dyspepsia [FD]) and organic diseases (Crohn’sdisease [CD], ulcerative colitis, and gastroesophageal refluxdisease), were recruited from 9 pediatric tertiary care GI clin-ical sites across the US for the PedsQLGastrointestinal Symp-toms Module field test study.23 Only patients with a single

86

primary diagnosis were included. Participants completedthe PedsQL 4.0 Generic Core Scales during the field test asan aspect of the validation of the new PedsQL Gastrointes-tinal Symptoms Module scales.23 Written parental informedconsent and child assent (when age appropriate) for the useof these data were obtained during the field test study.23

The research protocol was approved by the Institutional Re-view Board at each site before data collection.The age-, sex-, and race/ethnicity-matched healthy sample

was derived from the PedsQL 4.0 Generic Core Scales initialfield test and a State Children’s Health Insurance Programevaluation in California.10,24 Children were assessed in phy-sicians’ offices during well-child visits, by telephone, or viaa statewide mailing.

MeasuresPedsQL 4.0 Generic Core Scales. The 23-item PedsQL4.0 Generic Core Scales encompasses 4 domains: PhysicalFunctioning (8 items), Emotional Functioning (5 items), So-cial Functioning (5 items), and School Functioning (5items).24 The Physical Health Summary Score is the sameas the Physical Functioning Scale. To create the PsychosocialHealth Summary Score, the mean is computed as the sum ofthe items divided by the number of items answered in theEmotional, Social, and School Functioning Scales. The scalesuse parallel child self-report and parent proxy report formatsfor children aged 5-18 years, and a parent proxy reportformat for children aged 2-4 years. The questions assesshow much of a problem each item has been during the pre-vious month. Items are reverse-scored and linearly trans-formed to a scale of 0-100, with higher scores indicatingbetter HRQOL. Scale scores are computed as the sum ofthe items divided by the number of items answered (whichaccounts for missing data). If more than 50% of the itemsin the scale are missing, then the scale score is notcomputed.25 This accounts for the differences in sample sizesfor the scales reported in Tables I-III (Table II available atwww.jpeds.com).

PedsQL Family Information Form Impact Items. Par-ents completed the PedsQL Family Information Form, whichcontains demographic information including the child’s dateof birth, sex, and race/ethnicity and parental education.24 Theform also contains an impact section that elicits informationon the following: “In the past 30 days.” “howmany days didyour child miss from school due to physical or mentalhealth?,” “how many days was your child sick in bed or tooill to play?,” and “how many days did your child need some-one to care for him/her due to physical or mental health?”;“In the past 12 months, has your child had.” “any overnightvisits to the hospital?” or “any emergency room/urgent carevisits?”; “If yes, how many times?”; “In the past 30 days,how many days have you missed from work due to yourchild’s physical or mental health?”; “Has your child’s healthinterfered with.” “your daily routine at work” or “yourability to concentrate at work?” These last 2 items are scoredon the PedsQL Likert scale (ranging from “never” to “almost

Varni et al

Table

I.PedsQ

LGenericCore

Scales

scoresofpediatricpatientswithFGID

s,patientswithorganicGIdiseases,andHC

GenericCoreScales

FGIDs(a)

OrganicGIdiseases

(b)

HC(c)

Difference,

avs

cDifference,

bvs

cDifference,

avs

bEffect

size,

avs

cEffect

size,

bvs

cEffect

size,

avs

ba

Mean

(SD)

aMean

(SD)

aMean

(SD)

Childself-report

n=281

n=298

n=936

Totalscore

0.90

70.2(17.0)

0.91

78.0(14.6)

0.89

85.6(11.9)

15.4*

7.6*

7.8*

1.05

0.57

0.49

PhysicalHealth

0.82

73.1(20.3)

0.82

80.5(16.6)

0.77

89.6(12.1)

16.5*

9.1*

7.4*

0.99

0.63

0.40

PsychosocialHealth

0.86

68.6(17.8)

0.87

76.6(15.7)

0.86

83.5(13.6)

14.9*

6.9*

8.0*

0.94

0.47

0.48

EmotionalFunctioning

0.78

66.4(23.6)

0.81

74.7(21.1)

0.78

81.3(17.9)

14.9*

6.6*

8.3*

0.71

0.34

0.37

SocialFunctioning

0.74

79.2(19.5)

0.82

87.3(16.1)

0.78

87.4(15.9)

8.2*

0.1

8.1*

0.46

0.01

0.45

SchoolFunctioning

0.75

60.3(22.4)

0.78

67.8(20.5)

0.72

81.8(16.1)

21.5*

14.0*

7.5*

1.10

0.76

0.35

Parentproxyreport

n=356

n=301

n=1106

Totalscore

0.93

70.5(19.1)

0.93

75.6(17.5)

0.91

85.2(12.8)

14.7*

9.6*

5.1†

0.90

0.63

0.28

PhysicalHealth

0.88

72.1(22.8)

0.90

77.9(21.1)

0.85

88.7(15.2)

16.6*

10.8*

5.8†

0.86

0.59

0.26

PsychosocialHealth

0.91

69.7(19.9)

0.90

74.4(17.6)

0.87

83.3(13.6)

13.6*

8.9*

4.7†

0.80

0.57

0.25

EmotionalFunctioning

0.85

65.3(24.3)

0.86

71.3(21.7)

0.80

81.9(16.4)

16.6*

10.6*

6.0†

0.80

0.55

0.26

SocialFunctioning

0.84

79.4(21.0)

0.80

82.8(19.2)

0.81

87.2(16.4)

7.8*

4.4†

3.4

0.41

0.25

0.17

SchoolFunctioning

0.83

63.0(24.8)

0.83

68.9(22.4)

0.75

80.6(17.0)

17.6*

11.7*

5.9†

0.83

0.59

0.25

HC,healthycontrols.

Effectsizesaredesignated

assm

all(0.20),medium

(0.50),or

large(0.80).Higherscores

equalbetterHRQOL.

*P<.001;†P<.01,basedon

Gam

es-How

ellposthoctestsaftersignificant

omnibusWelch’s1-way

ANOVA

Ftests(allP#

.001)forallG

enericCoreScalesforboth

child

self-reportandparentproxyreport.

January 2015 ORIGINAL ARTICLES

Health-Related Quality of Life in Pediatric Patients with Functiona

always”) and reverse-scored, with higher scores indicatinglower impact or better functioning.

Statistical AnalysesThe Cronbach a coefficient was used to determine scale in-ternal consistency reliability.26 Scales with an internal consis-tency reliability of $0.70 are recommended for comparingpatient groups, and an internal consistency reliability crite-rion of 0.90 is recommended for analyzing individual patientscores.27 One-way ANOVA was used to compare patientgroups with one another and with the healthy controls. TheWelch ANOVA with the Games-Howell post hoc test wereused because the homogeneity of variances assumption wasnot supported by the Levene test. The Games-Howell posthoc test was used only when there was a significant omnibusWelch ANOVA F test result,28 indicating significant differ-ences among the groups for a particular scale. The Games-Howell post hoc test was used to determine which GI groupsdiffered from the healthy controls for each scale, as well as toidentify whether the 2 GI groups differed from each other. Todetermine the magnitude of the anticipated differences, effectsizes were calculated.29 Effect sizes for differences in meansare designated as small (0.20), medium (0.50), or large(0.80) in magnitude.29 The Welch ANOVA with theGames-Howell post hoc test were similarly used to comparethe 7 individual GI subgroups with the healthy sample, aswell as with one another.Because these were exploratory analyses with small sample

sizes for some of the GI subgroups, the number of statisticaltests conducted was not controlled for. For the family impactitems, the Pearson c2 test was used to test for differences inproportions when expressed as percentages. Effect sizes forthe Pearson c2 statistic are designated as small (0.10), me-dium (0.30), or large (0.50) in magnitude when expressedas the Pearson r.29 The Welch ANOVA with Games-Howellpost hoc test were used to compare the GI groups with thehealthy sample, as well as with one another. Because the com-parisons between the GI groups were exploratory analyses, wedid not control for the number of statistical tests conducted.

Results

A total of 689 patient families (584 children aged 5-18 yearsand 682 parents of children aged 2-18 years) participated inthe field test study. The average age of the 318 boys (46.2%)and 371 girls (53.8%) was 11.43 years (SD, 4.58; range, 2.0-18.9). The racial/ethnic distribution was 517 (75.0%) whitenon-Hispanic, 68 (9.9%) Hispanic, 63 (9.1%) black non-Hispanic, 13 (1.9%) Asian/Pacific Islander, 1 Native Amer-ican (0.1%), and 27 (3.9%) other. With respect to parenteducation, 6.1% of mothers and 9.8% of fathers did notcomplete high school, 12.8% of mothers and 16.1% of fa-thers had a high school degree, 26.1% of mothers and20.5% of fathers completed some college, 33.1% of mothersand 24.7% of fathers had a college degree, and 17.7% ofmothers and 17.1% of fathers had a graduate or professionaldegree (missing, 4.5% mothers and 13.1% fathers). Data

l and Organic Gastrointestinal Diseases 87

Table

III.

PedsQ

Fam

ilyInform

ationForm

impactitem

sin

pediatricpatientswithFGID

s,patientswithorganicGIdiseases,andHC

Impact

item

sFG

IDs(n

=368),

mean(SD)(a)

OrganicGIdiseases

(n=317),mean(SD)(b)

HC*(n

=1114),

mean(SD)(c)

Difference,

avs

cDifference,

bvs

cDifference,

avs

bEffect

size,

avs

cEffect

size,

bvs

cEffect

size,

avs

b

Daysmissedfrom

schoolinpast30

d,mean(SD)†

4.1(7.2)

3.5(6.3)

0.8(2.0)

3.3z

2.7z

0.6

0.62

0.58

0.09

Dayssick

inbed/tooilltoplay

inpast30

d,mean(SD)†

3.8(6.9)

2.8(5.5)

0.7(1.9)

3.1z

2.1z

1.0

0.61

0.51

0.16

Daysneeded

care

(past30

d),mean(SD)†

4.1(8.2)

2.4(5.8)

0.5(1.9)

3.6z

1.9z

1.7x

0.60

0.44

0.24

Overnightvisittohospitalinpast12

mo,%**

23.7

27.5

5.3

18.4z

22.2z

3.8

0.27

0.30

0.04

Emergency/urgentcare

visitsinpast12

mo,%**

46.4

39.6

21.3

25.1z

18.3z

6.8

0.24

0.17

0.07

Emergency/urgentcare

visitsinpast12

mo,mean(SD)†

2.5(2.4)

1.9(1.8)

1.4(0.7)

1.1z

0.5{

0.6

0.62

0.37

0.28

Parentdays

missedfrom

workinpast30

d,mean(SD)†

1.9(5.1)

1.3(2.8)

0.2(0.8)

1.7z

1.1z

0.6

0.47

0.53

0.15

Parentdaily

workroutineimpacted

inpast30

d,mean(SD)†,††

66.1(29.3)

72.7(27.6)

87.0(26.0)

20.9z

14.3x

6.6{

0.75

0.53

0.23

Parentabilitytoconcentrateatworkinpast30

d†,††

63.0(31.2)

68.7(29.9)

86.1(29.8)

23.1z

17.4x

5.7

0.76

0.58

0.19

*Healthysamplefrom

Varnietal.12,24

†Pvalues

basedon

Gam

es-How

ellposthoctestsafterWelch

1-way

ANOVA.Effectsizesaredesignated

small(0.20),medium

(0.50),andlarge(0.80).

zP<.001.

xP<.01.

{P<.05.

**Pvalues

basedon

thePearsonc2test.Effectsizesaredesignated

small(0.10),medium

(0.30),or

large(0.50).

††These2itemsarescored

onthePedsQLLikertscale(never

toalmostalways),andreverse-scored,with

higher

scores

indicatinglower

impactor

better

functioning.

THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 166, No. 1

88

collection took place between March 2011 andNovember 2013.A total of 1114 families (936 children aged 5-18 years

and 1106 parents of children aged 2-18 years) composedthe matched healthy control sample. The average age ofthe 515 boys (46.2%) and 599 girls (53.8%) was 11.43 years(SD, 3.38; range, 2.0-18.10). The racial/ethnic distributionwas 837 (75.1%) white non-Hispanic, 110 (9.9%) Hispan-ic, 101 (9.1%) black non-Hispanic, 21 (1.9%) Asian/Pa-cific Islander, 1 Native American (0.1%), and 44 (3.9%)other. Parental education level was not available for the to-tal sample, although the State Children’s Health InsuranceProgram sample was representative of low-income fam-ilies.

Internal Consistency ReliabilityThe Cronbach a internal consistency reliability coefficientsfor child self-report and parent proxy report scales exceededthe minimum standard of 0.70 required for group compari-sons (Table I). The total scale score for child self-report andparent proxy report approached or exceeded the reliabilitycriterion of 0.90 recommended for analyzing individualpatient scores.

HRQOL Comparisons between GI Groups andHealthy ControlsPedsQL scores were significantly lower for child self-reportand parent proxy report across all dimensions for patientswith FGIDs and organic GI diseases compared with thehealthy controls (P < .001 for all; Table I), except for childself-reported and parent proxy-reported Social Functioningin patients with organic GI diseases. PedsQL scores weresignificantly lower in patients with FGIDs compared withthose with organic GI diseases (for all, P < .001 for childself-report; P < .01 for parent proxy report), except forparent proxy-reported Social Functioning.For the individual diagnostic groups, all patient groups

had lower scores than the healthy controls on School Func-tioning for patient self-report (Table II). For PhysicalHealth, all patient self-report scores were lower than thescores for healthy controls for the GI groups except forFD and gastroesophageal reflux disease. For the totalscore and Psychosocial Health score, children self-reported lower scores for CC, FAP, IBS, and CDcompared with the healthy controls. For parent proxyreport, all summary and scale scores were lower for eachdiagnostic group compared with the healthy controls,except for FD and for Social Functioning, in which onlyCC and FAP were lower.In the exploratory comparisons across the individual diag-

nostic groups with one another (Table II), patients withFGIDs generally self-reported lower scores than patientswith organic GI diseases, with the exception of FD, andSchool Functioning. In contrast to child self-report, parentproxy report primarily showed only lower FAP scorescompared with CD scores, and no differences in SocialFunctioning scores.

Varni et al

January 2015 ORIGINAL ARTICLES

Impact Items Comparisons Between GI Groups andHealthy ControlsCompared with healthy controls, patients with an FGID ororganic GI disease missed more school, spent more days inbed and needing care, had greater healthcare utilization,and had parents who missed more work days with greaterwork impact (P < .001 for most), with larger effect sizes forpatients with an FGID (Table III). There were fewdifferences between patients with an FGID and those withan organic GI disease.

Discussion

The results of this multicenter study demonstrate that pedi-atric patients with FGIDs and organic GI diseases have signif-icantly lower generic HRQOL compared with healthychildren, with the majority of effects sizes in the mediumto large range. In addition, these children missed moredays from school, had more days in bed/too ill to play, andrequired greater healthcare utilization, and their parents re-ported more days missed from work and a greater impacton their daily work routine and ability to concentrate atwork compared with healthy children and their parents.

Patients with FGIDs as a group self-reported lower HRQOLscores for all dimensions compared with patients with organicGI diseases as a group. For parent proxy report, patients withFGIDs as a group had lower HRQOL scores for all dimensionscompared with those with organic GI diseases as a group,except for no reported differences in Social Functioning. Inanalyzing the differences between the individual diagnosticgroups and the healthy controls, all patient groups self-reported lower School Functioning compared with the healthycontrols. The differences across the other HRQOL dimensionsfor child self-report were more variable, with most of the dif-ferences in comparison with healthy controls demonstratedfor patients with CC, FAP, IBS, and CD. For parent proxyreport, all GI groups manifested lower HRQOL than thehealthy controls, with the exception of FD and Social Func-tioning, in which only the CC and FAP diagnostic groupswere significantly lower compared with the healthy controls.

When analyzing the exploratory comparisons across theindividual diagnostic groups with one another, patientswith an FGID generally self-reported lower HRQOL thanthose with organic GI diseases (except for FD, which maybe explained in part by the smaller sample size). In contrast,parent proxy reports showed fewer differences between thepatients with an FGID and those with an organic disease,with primarily children with FAP reported by parents asmanifesting lower HRQOL compared with children with CD.

Our findings are generally consistent with those of previoussingle-center or smaller-sized studies suggesting impairedgeneric HRQOL in pediatric patients with FGIDs and organicGI diseases compared with healthy controls.14,15,17,18,20,21 Ourmulticenter findings are unique, however, in that wecompared 7 GI disorders across 9 national sites, with a largernumber of GI disorders than previous studies and larger sam-ple sizes for the majority of the individual diagnostic groups.

Health-Related Quality of Life in Pediatric Patients with Functiona

This enabled us to compare these diagnostic groups withboth the healthy controls and one another, revealing differ-ences suggesting that patients with FGIDs manifest lowerHRQOL even when compared with patients with organic GIdiseases. This unique combination of study characteristics,which does not exist in the published literature, increases thegeneralizability of our findings. The dissimilarities betweenchild self-reported and parent proxy-reported HRQOL differ-ences in patients with FGIDs and organic GI diseasescompared with healthy controls and also among the individualdiagnostic groups further underscore the importance ofmeasuring both children’s and parents’ perspectives in clinicalpractice and clinical trials, consistent with recommendationsin the broader HRQOL literature.30

The present study has several strengths, including a rela-tively large overall sample size; a broad age range of partici-pants, including patient self-report for age 5-18 years;FGID diagnoses based on the current Rome III criteria; andthe nationwide representation of the participants (drawnfrom 9 clinical sites throughout the US).Limitations of this study include the lack of information

on families who chose not to participate and the small samplesizes for some of the post hoc analyses, which reduced the sta-tistical power to detect group differences. Information onnonparticipants and participants’ socioeconomic statuswere not available, which may limit the generalizability ofthe findings given the previous demonstration of the associ-ation of socioeconomic status with HRQOL.11 Subjectrecruitment was based on a convenience sampling methodol-ogy. Thus, the sample sizes for the diagnostic groups weredetermined by the patient populations seen in the 9 sitesacross the country and might not be representative of theprevalence rate for each diagnostic subgroup. Althoughonly patients with a single primary diagnosis were includedbased on the predominant symptom, there could have beensome patients in whom a major symptom was accompaniedby the coexistence of other symptoms. Nevertheless, the diag-nostic categorizations were made by board-certified pediatricgastroenterologists based on current diagnostic criteria forFGIDs and organic GI diseases. We were not able to includeall possible GI disorders (eg, celiac disease). Neither treat-ment nor disease status was included, which are importantcovariates to consider for future research. In addition, partic-ipants were recruited from tertiary care centers, which mayoversample for patients with more severe disease than wouldbe found in general pediatric clinics or community samples.Finally, our healthy control sample was derived from previ-ously published data; future research may benefit fromaccruing a contemporaneously matched healthy sample.In conclusion, the present study shows that children with

FGIDs and organic GI diseases demonstrate impairedHRQOL and a significant negative impact on daily func-tioning, with greater healthcare utilization compared withhealthy controls. Patients with FGIDs manifested lowerHRQOL compared with those with organic GI disorders,with greater differences from the child’s perspectivecompared with the parent’s perspective, further emphasizing

l and Organic Gastrointestinal Diseases 89

THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 166, No. 1

the importance of patient-reported outcomes from thechild’s perspective.5,7,8,13 A better understanding of the gen-esis of the differences between FGIDs and organic GI diseases,as well as reasons for the discordance between the child andparent perspectives, is needed to develop more tailored inter-ventions aimed at improving the HRQOL of children withFGIDs and organic GI diseases. n

Submitted for publication Apr 24, 2014; last revision received Aug 4, 2014;

accepted Aug 12, 2014.

Reprint requests: James W. Varni, PhD, Professor of Architecture and

Medicine, College of Architecture, Texas A&MUniversity, 3137 TAMU, College

Station, TX 77843-3137. E-mail: jvarni@arch.tamu.edu

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Appendix

PedsQL Gastrointestinal Symptoms Module Testing StudyConsortium sites include:

Center for Health Systems & Design, Colleges of Archi-tecture and Medicine, Texas A&M University, College Sta-tion, TX (PI: James W. Varni, PhD); Division of PediatricGastroenterology, Nationwide Children’s Hospital, OhioState University School of Medicine, Columbus, OH (PI:Jolanda Denham, MD); Department of Pediatrics and Chil-dren’s Nutrition Research Center, Baylor College of Medi-cine, Texas Children’s Hospital, Houston, TX (PIs: RobertJ. Shulman, MD, and Mariella M. Self, PhD); Division ofGastroenterology, Hepatology, and Nutrition, Children’sHospital Colorado, Aurora, CO (PI: Deborah A. Neigut,MD); Center for Motility and Functional GastrointestinalDisorders, Boston Children’s Hospital, Harvard MedicalSchool, Boston, MA (PI: Samuel Nurko, MD); Division ofPediatric Gastroenterology, Children’s Medical Center ofDallas, University of Texas Southwestern Medical School,Dallas, TX (PI: Ashish S. Patel, MD); Division of Gastroen-terology, Hepatology, and Nutrition, Cincinnati Children’sHospital Medical Center, Cincinnati, OH (PIs: James P.Franciosi, MD, Shehzad Saeed, MD, and George M. Zacur,MD); Division of Gastroenterology, Hepatology and Nutri-tion, Lurie Children’s Hospital of Chicago, NorthwesternUniversity Feinberg School of Medicine, Chicago, IL (PI:Miguel Saps, MD); Division of Pediatric Gastroenterology,Hepatology, and Nutrition, Goryeb Children’s Hospital,Morristown Medical Center, Morristown, NJ (PI: BarbaraVerga, MD); and Department of Pediatric Gastroenter-ology, Primary Children’s Hospital, University of Utah,Salt Lake City, UT (PI: John F. Pohl, MD).

January 2015 ORIGINAL ARTICLES

Health-Related Quality of Life in Pediatric Patients with Functional and Organic Gastrointestinal Diseases 90.e1

Table II. PedsQL 4.0 Generic Core Scale scores for child self-report and parent proxy report across individual diagnostic groups in comparison to HC and across theindividual diagnostic groups to each other

Generic Core Scale HC

Diagnostic group

Differences from HC*Differences between diagnostic

groups†CC FAP FD IBS CD UC GERD

Child self-report n = 936 n = 115 n = 114 n = 14 n = 38 n = 191 n = 64 n = 43Total score, mean (SD) 85.6 (11.9) 71.1 (18.5) 69.3 (14.9) 73.7 (18.2) 68.5 (18.1) 76.8 (14.9) 80.1 (14.7) 79.9 (12.9) HC > CC, FAP, IBS, CDz CC < UC, GERDx, FAP < UCz,

FAP < CD, GERD{, IBS < UC,GERDx

Physical Health, mean (SD) 89.6 (12.1) 75.2 (19.9) 70.8 (18.9) 79.5 (19.4) 71.0 (24.9) 78.6 (17.5) 83.5 (15.1) 84.4 (13.1) HC > CC, FAP, CDz, HC > IBS{,HC > UCx

CC < UC, GERDx, FAP < UC, GERDz,FAP < CDx

Psychosocial Health, mean (SD) 83.5 (13.6) 68.9 (20.1) 68.6 (15.5) 70.6 (18.6) 67.2 (16.9) 75.9 (15.8) 78.2 (16.0) 77.3 (14.8) HC > CC, FAP, IBS, CDz CC < CD, UCx, FAP < CD, UC{,FAP < GERDx, IBS < UCx

Emotional Functioning, mean (SD) 81.3 (17.9) 69.9 (25.1) 65.3 (20.7) 69.6 (25.8) 57.9 (24.6) 74.6 (20.6) 76.0 (21.9) 73.4 (22.4) HC > CC, FAP, IBSz, HC > CD{ FAP < CD{, FAP < UCx, IBS < CD,UC{

Social Functioning, mean (SD) 87.4 (15.9) 74.7 (21.0) 81.3 (18.3) 82.5 (17.0) 85.8 (15.9) 86.3 (16.4) 89.6 (15.2) 88.5 (15.7) HC > CCz, HC > FAPx CC < IBSx, CC < CD, UCz,CC < GERD{, FAP < UCx

School Functioning, mean (SD) 81.8 (16.1) 62.4 (23.7) 59.1 (20.8) 59.6 (21.9) 57.9 (23.8) 66.8 (20.1) 69.0 (22.8) 70.6 (18.8) HC > CC, FAP, IBS, CDz,HC > UC, GERD{, HC > FDx

FAP < CD, GERDx

Parent proxy report n = 1106 n = 183 n = 114 n = 17 n = 42 n = 183 n = 67 n = 51Total score, mean (SD) 85.2 (12.8) 71.9 (20.5) 68.3 (17.9) 71.4 (18.1) 70.0 (16.9) 76.3 (17.7) 75.1 (17.1) 74.0 (17.1) HC > CC, FAP, IBS, CD, UCz,

HC > GERD{FAP < CD{

Physical Health, mean (SD) 88.7 (15.2) 74.5 (23.6) 69.3 (21.4) 73.2 (21.6) 68.8 (22.7) 78.1 (21.2) 78.8 (20.7) 76.0 (21.5) HC > CC, FAP, IBS, CDz,HC > UC, GERD{

FAP < CDx

Psychosocial Health, mean (SD) 83.3 (13.6) 70.5 (21.5) 67.9 (18.6) 70.4 (18.7) 70.7 (16.5) 75.3 (17.9) 73.1 (17.2) 73.1 (17.0) HC > CC, FAP, IBS, CD, UCz,HC > GERD{

FAP < CDx

Emotional Functioning, mean (SD) 81.9 (16.4) 67.2 (24.7) 63.6 (24.4) 67.4 (26.3) 60.8 (20.7) 72.6 (21.8) 68.0 (21.8) 70.8 (21.2) HC > CC, FAP, IBS, CD, UCz,HC > GERDx

FAP < CDx, IBS < CDx

Social Functioning, mean (SD) 87.2 (16.4) 78.0 (21.9) 79.4 (21.2) 79.4 (20.6) 85.1 (16.1) 83.4 (19.5) 83.0 (17.8) 80.5 (19.9) HC > CCz, HC > FAP{

School Functioning, mean (SD) 80.6 (17.0) 64.3 (26.0) 60.4 (23.4) 63.5 (21.8) 65.1 (24.4) 69.8 (22.0) 68.3 (23.8) 66.7 (22.6) HC > CC, FAP, CDz, HC >IBS, UC, GERD{

FAP < CDx

GERD, gastroesophageal reflux disease; HC, healthy controls; UC, ulcerative colitis.Higher scores equal better HRQOL.*Differences between HC and individual GI diagnostic groups.†Differences between the individual GI diagnostic groups.zP < .001; xP < .05; {P < .01, based on Games-Howell post hoc tests after significant omnibus Welch 1-way ANOVA F tests (all P # .001) for all Generic Core Scales for both child self-report and parent proxy report.

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