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Factors Associated with Health-Related Quality of Life in Children with Intestinal Failure
ORIGINAL ARTICLES Factors Associated with Health-Related Quality of Life in Children with Intestinal Failure Victoria C. Neam, BA1, Assaf P. Oron, PhD2, Deepthi Nair, MS1, Todd Edwards, PhD3, Simon P. Horslen, MB, ChB1,4, and Patrick J. Javid, MD1,4 Objective To evaluate disease-specific and age-related factors contributing to health-related quality of life (HRQOL). in children with intestinal failure.
Study design A prospective study of HRQOL was performed in a regional intestinal rehabilitation program. Parent-proxy Pediatric Quality of Life Inventory surveys were administered annually to families of 91 children with intestinal failure over a 6-year period. Survey data was stratified by age and compared with pediatric HRQOL data in healthy and chronically ill populations. Linear mixed-effect models using multivariable regression were constructed to identify associations with HRQOL. Results A total of 180 surveys were completed by 91 children and their families. HRQOL scores were lowest for children ages 5-7 years (P < .001) and 8-12 years (P < .01), and these changes were primarily related to school dimension scores. In multivariable regression, age of 5 years and older and developmental delay were independently associated with lower HRQOL scores. The trend toward lower HRQOL scores parallels reference data from healthy and chronically ill children, although patients with intestinal failure scored lower than both populations at school age. Conclusions Children with intestinal failure experience lower parent-proxy HRQOL scores in the 5-7 and 812 year age groups primarily related to school dimension scores. Multicenter data to validate these findings and identify interventions to improve QOL for children with intestinal failure are needed. (J Pediatr 2019;-:1-6).
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ong-term survival of children with intestinal failure now routinely approaches 90% in most dedicated, multidisciplinary intestinal rehabilitation programs.1-5 However, the improvement in mortality and long-term outcomes is associated with clinical complexities such as chronic dependence on parenteral nutrition, the ongoing need for hospitalization and surgical procedures, and extreme dietary modification. It is likely that many of the strategies to improve the care of this population also impact the health-related quality of life (HRQOL) of children and their families.6,7 Indeed, the assessment of HRQOL in children with intestinal failure, and the identification of interventions to improve HRQOL, have become priorities in the field. Previous reports from our program and others have evaluated HRQOL in children with intestinal failure at a single time point.6-10 Most, but not all, of these studies have demonstrated that HRQOL in pediatric intestinal failure is lower when compared with healthy children. However, data on changes in HRQOL with age in this population and a detailed analysis of disease-related factors associated with lower HRQOL are lacking. Moreover, prior publications have not compared HRQOL scores in the intestinal failure population with other children with chronic illness. Beginning in 2011, our program has been performing annual measurements of HRQOL in patients and families in our intestinal rehabilitation program. We have acquired HRQOL data that encompasses multiple age ranges and are relevant given the long-term survival of these patients into school age and beyond. The aim of this work was to identify targets for intervention to improve HRQOL in this patient population.
Methods A prospective, cross-sectional study was performed to assess HRQOL of children ages 6 months to 18 years receiving care at the intestinal rehabilitation program at Seattle Children’s Hospital from August 2011 to April 2017. Inclusion criteria encompassed English- or Spanish-speaking children and families with intestinal failure actively receiving care in the intestinal rehabilitation program. Intestinal failure was defined as any child with inadequate bowel function that required parenteral From the Seattle Children’s Hospital, Seattle, WA; 1
2
Institute for Disease Modeling, Bellevue; 3University of Washington School of Public Health; and 4University of Washington School of Medicine, Seattle, WA
HRQOL PedsQL
Health-related quality of life Pediatric Quality of Life Inventory
The authors declare no conflicts of interest. 0022-3476/$ - see front matter. ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jpeds.2019.08.049
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nutrition for ³3 consecutive months at any point in their lifetime secondary to anatomic short bowel length or problems with intestinal motility or absorption. Exclusion criteria included children <6 months of age, current inpatient status, surgery or inpatient hospitalization within 1 month of survey participation (other than central venous line placement or removal), and discharge from first hospitalization within 3 months. These exclusion criteria were chosen to include families who were able to spend time caring for their child in a nonacute care setting and to avoid bias in survey intake from recent illness or hospital admission. Measures and Procedures The Pediatric Quality of Life Inventory (PedsQL) 4.0 surveys were used to assess HRQOL in our population.11-14 The PedsQL Infant Scales include a 36-item report for infants ages 1-12 months and a 45-item report for children 1324 months.12 Each survey is divided into dimensions pertaining to physical functioning and symptoms, as well as emotional, social, and cognitive functioning.13 The PedsQL Generic Core Scales include parent proxy reports that assess perception of the child’s HRQOL. The surveys are age specific with versions for toddler (2-4 years), young child (57 years), child (8-12 years), and teen (13-18 years) age groups. The PedsQL Generic Core Scales are composed of 23-items that include questions regarding physical, emotional, social, and school functioning.13 For the various PedsQL surveys used, an unweighted 5-point Likert scale from 0 to 4 (0 [never], 1 [almost never], 2 [sometimes], 3 [often], 4 [almost always]) is used for each question. After obtaining informed consent, parent participants were asked to complete an age-appropriate infant scale or parent proxy report. Beginning 1 year after the initial survey, families were approached annually to complete an ageappropriate survey. The initial informed consent covered ongoing survey assessment. A trained research coordinator was available to help administer the surveys to all participants as needed. Participants were given the option to complete surveys on an iPad in clinic or paper surveys in clinic or at home. Previous data have shown that the method of survey delivery does not impact survey results.13 A total of 20 surveys (11%) were completed at home and returned via mail. At each survey time point, demographic and clinical variables were collected retrospectively from review of the electronic medical record including physician notes, operative reports, and nutrition plans. Bowel length data were determined by detailed review of internal and outside operative reports for each patient when available. All aspects of this study were approved by the Seattle Children’s Hospital Institutional Review Board (application number 13660). Statistical Analyses All completed surveys were scored according to the official PedsQL guidelines.13 Items were reverse scored and linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50,
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3 = 25, 4 = 0), so that higher scores indicate better HRQOL. In addition to the calculation of total scores, we analyzed data by individual dimension scores including physical, emotional, social, and school functioning. The psychosocial health summary score (including emotional, social, and school functioning scores), and physical health summary score (including the physical functioning score) were calculated. Categorical variables were tabulated with percent breakdown reported. Continuous demographic variables were summarized as median, IQR, and/or range. Test scores were summarized as mean and SD. Data were stratified by established age ranges as defined by the PedsQL survey methodology. In addition, we used published reference values for the PedsQL in both healthy and chronically ill pediatric populations to compare our scores using general t tests.11,12 The healthy comparison data published by Varni et al represents a cohort of children seen for well-child checks whose parents or medical records did not mention the presence of a chronic illness.11 Our chronic illness comparison data includes a cohort of children and teens ages 1 month to 12 years receiving care in clinics and hospitals for chronic physical and/or mental health conditions lasting ³6 months and published by Varni et al.12 The diagnoses included in the chronic illness group included cancer, asthma, cardiac condition, diabetes, rheumatic disease, gastrointestinal problems, cerebral palsy, attention deficit hyperactivity disorder, sickle cell anemia, and renal disease. Finally, we investigated the association between demographic and clinical factors on survey scores using multivariable linear mixed-effects models accounting for the grouping of surveys by patient using a random intercept term. For this analysis, bowel length was used as a continuous variable and log base 2 transformed so that the model coefficient represents the change in survey score with doubling of bowel length irrespective of baseline. The model adjusted for patient age, ethnicity, etiology of intestinal failure, parenteral nutrition dependence, number of hospital admissions within the previous year, and bowel length when available.
Results Ninety-one children and their families were enrolled, and a total of 180 surveys were performed. Forty-seven participants (52%) completed multiple surveys including 44 participants with 2 surveys, 23 with 3 surveys, 15 with 4 surveys, and 3 with 5 surveys. The distribution of surveys by age group is illustrated in Figure 1, and demographic data are presented in Table I. Fifty-six children (62%) were male, and the median age at first survey was 3 years (range, 0.517.0 years). The most common etiologies of intestinal failure were gastroschisis (n = 29 [32%]) and necrotizing enterocolitis (n = 26 [29%]). Bowel length data were available for 72 children, and remaining bowel length was 42 cm (range, 1-250 cm). Seventy-one children (78%) were dependent on parenteral nutrition for ³1 survey, and
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ORIGINAL ARTICLES
Figure 1. Survey distribution. The distribution of completed parent-proxy PedsQL surveys by age group is illustrated. The survey number is graphically represented. n = the number of participants in each age group.
109 (61%) surveys were performed in children actively receiving parenteral nutrition. HRQOL Scores and Comparison to Reference Populations HRQOL scores in children with intestinal failure are presented in Table II. In all age groups, children with
Table I. Descriptive statistics for demographic and clinical characteristics Characteristics
No. (%)
Race/ethnicity White non-Hispanic 42 (46) Black non-Hispanic 6 (7) Hispanic 25 (27) Asian/Pacific Islander 5 (5) Other 13 (14) Diagnosis Gastroschisis 29 (32) Necrotizing enterocolitis 26 (29) Midgut volvulus 7 (8) Intestinal atresia 11 (12) Hirschsprung disease 5 (5) Other* 13 (14) Bowel length, cm (n = 180) 1-20 46 (26) 21-40 44 (24) 41-60 29 (16) >60 36 (20) Missing 25 (14) Admission in year before survey time point (n = 180) None 74 (41) 1 31 (17) 2-3 45 (25) ³4 30 (17) Parenteral nutrition dependent at any survey time point (n = 180) 109 (61) Developmental delay 22 (24) *Other diagnoses included congenital short bowel, intestinal pseudoobstruction, meconium peritonitis, and microvillus inclusion disease.
intestinal failure demonstrated lower total HRQOL scores when compared with a healthy reference population. When compared with a reference population of chronically ill children, infants with intestinal failure had higher total and psychosocial scores and there were no differences in scores for toddlers ages 1-4 years. Among school-aged children with intestinal failure, total HRQOL scores were lower than chronically ill children at ages 5-7 years ( 7.8; P = .02) and 8-12 years ( 6.1; P = .08). Our study population had similar physical health summary scores when compared with chronically ill children except for lower scores in patients aged 5-7 years ( 7.8; P = .02). Psychosocial health summary scores were lower in both the 5- to 7-year ( 7.2; P = .005) and 8- to 12-year age groups ( 8.3; P = .01). When the data were analyzed at the survey dimension level, children with intestinal failure demonstrated dramatically lower scores in school functioning at 5-7 years ( 12.4; P < .001) and 8-12 years (difference, 25.6; P < .001) compared with the chronically ill reference population (Figure 2; available at www.jpeds.com).
PedsQL: Results by Age HRQOL scores in children with intestinal failure generally followed the age-related trends previously established for healthy and chronically ill children (Figure 2). Total HRQOL scores were noted to be highest in the infant and toddler age groups. HRQOL scores for children ages 57 years and 8-12 years (P < .01) were significantly lower, even after controlling for other variables on regression analysis. Although this trend mirrored the data from reference populations, HRQOL scores in our population were shifted lower in school-aged children secondary, at least in part, to sizable decreases in school dimension scores.
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Table II. PedsQL infant scales or generic core scales compared with reference data for healthy and chronically ill children Characteristics
Total score Physical health summary Psychosocial health summary Total score Physical health summary Psychosocial health summary Total score Physical health summary Psychosocial health summary Total score Physical health summary Psychosocial health summary Total score Physical health summary Psychosocial health summary
Intestinal failure study population
Healthy children11,12
Infants with intestinal failure (1-12 months; n = 28) 74.9 (12.7) 74.3 (13.0) 75.3 (14.5) Toddlers with intestinal failure (13-24 months; n = 12) 73.5 (12.2) 74.6 (13.1) 72.8 (13.1) Toddlers with intestinal failure (2-4 years; n = 51) 77.0 (14.8) 78.2 (18.7) 76.3 (15.1) Children with intestinal failure (5-7 years; n = 50) 63.4 (14.2) 62.1 (22.6) 64.2 (14.0) Children with intestinal failure (8-12 years; n = 29) 64.4 (15.4) 69.9 (24.7) 61.5 (16.6)
Varni et al 2011 (n = 246)
P value
Chronically ill children11,12
P value
Varni et al 2011 (n = 41)
82.5 (10.0) 85.0 (9.5) 80.5 (12.6) Varni et al 2011 (n = 141)
<.001 <.001 <.001
68.0 (13.9) 69.5 (13.5) 66.8 (16.7) Varni et al 2011 (n = 23)
.041 .146 .032
85.6 (8.7) 88.8 (7.7) 83.1 (11.0) Varni et al 2007 (n = 2922)
<.001 <.001 <.001
69.9 (10.4) 72.8 (14.4) 67.7 (10.3) Varni et al 2007 (n = 617)
.366 .720 .212
87.8 (12.1) 89.8 (15.4) 86.5 (12.3) Varni et al 2007 (n = 2318)
<.001 <.001 <.001
77.3 (18.4) 76.6 (24.8) 77.7 (16.5) Varni et al 2007 (n = 704)
.920 .637 .571
79.4 (16.1) 80.0 (20.9) 79.1 (15.5) Varni et al 2007 (n = 2956)
<.001 <.001 <.001
71.2 (18.5) 70.9 (25.5) 71.4 (17.8) Varni et al 2007 (n = 1380)
.004 .017 .005
80.2 (16.3) 82.7 (20.5) 78.9 (16.3)
<.001 <.001 <.001
70.5 (18.4) 72.0 (24.7) 69.8 (18.0)
.080 .659 .014
Data reported as mean (SD).
PedsQL: Multivariable Regression Model A multivariable regression model was constructed to identify associations between HRQOL scores and clinical measures (Table III). After controlling for age, sex, ethnicity, parenteral nutrition dependence, recent hospital admissions, diagnosis, and bowel length, only age >5 years (P < .01) and developmental delay (P < .01) were associated with lower HRQOL scores. Bowel length, the need for parenteral nutrition, the etiology of intestinal failure, and prematurity were not predictive of HRQOL scores in this model. The same regression model was applied to the psychosocial functioning score. Similar to our results for the total score, children age 5 years and older (P < .001) and developmental
Table III. Multivariable regression results Effects
Difference 95% CI
Infant vs toddler Age 1 vs toddler Age 5-7 vs toddler Age 8-12 vs toddler Hispanic vs White All other vs White Parenteral nutrition dependence NEC vs gastroschisis Intestinal atresia vs gastroschisis Volv/HD/other* vs gastroschisis Developmental delay Longer bowel length ³2 hospital admissions
4.4 ( 5.4 ( 11.9 ( 9.3 ( 4.7 ( 5.6 ( 2.0 ( 5.7 ( 6.6 ( 4.9 ( 9.9 ( 1.1 ( 0.5 (
11.1 to 2.2) 13.7 to 2.8) 17.2 to 6.5) 16.1 to 2.4) 1.7 to 11.0) 12.5 to 1.2) 7.6 to 3.5) 1.1 to 12.6) 2.1 to 15.4) 2.9 to 12.7) 16.2 to 3.6) 0.6 to 2.9) 4.7 to 5.6)
P value .190 .197 <.001 .008 .148 .107 .469 .099 .135 .221 .002 .213 .862
HD, Hirschsprung disease; NEC, necrotizing enterocolitis; Volv, midgut volvulus. *Other: congenital short bowel, intestinal pseudoobstruction, meconium peritonitis, microvillus inclusion disease.
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delay (P = .003) were independently associated with lower Psychosocial Functioning HRQOL scores.
Discussion A diagnosis that was once associated with a high risk of mortality at an early age, namely, intestinal failure, has become a chronic disease. There is widespread agreement within the field of pediatric intestinal failure that assessment of the quality of life of these children and their families should be a priority. These data may contribute to the long-term care of these patients and may also help to define the natural history of the disease. Our previous data from 23 families of children with intestinal failure found lower HRQOL scores than healthy peers beginning in the toddler age group and continuing to early school age.6 The small sample size and limited age range limited significant associations between demographic or disease-specific factors and HRQOL. These data show that school-aged children with intestinal failure have lower HRQOL scores even when compared with children with chronic illness. HRQOL scores in children with intestinal failure follow a similar pattern seen in both healthy and chronically ill children starting at 5 years of age. Parent proxy HRQOL scores are lower in all 3 populations, although scores for children with intestinal failure are shifted lower compared with both reference populations. The fact that these patterns were seen with a generic instrument like the PedsQL, which is not designed specifically for patients with gastrointestinal disease, makes these differences more noteworthy. Neam et al
- 2019 The changes in HRQOL scores in school-age children are striking and were not anticipated at the onset of this study. The school dimension addresses the frequency of the child having trouble paying attention in class and keeping up with schoolwork, forgetting things in school, and missing school because of not feeling well or needing to go to the doctor. Children with intestinal failure face many unique challenges as they progress in school. Their diet may be restrictive compared with their peers, and many patients may not eat at all. The presence of central lines and gastrostomy tubes can be a risk during physical education and recess, as well as another reminder that they are different from other children. Our patients may miss school frequently for hospital admissions, clinic appointments, and surgical procedures. Fatigue owing to a lack of sleep from nightly parenteral nutrition infusions and abnormal stooling patterns may also play a role. All of these differences at school may negatively impact the socialization of the child. Indeed, the challenges associated with nutritional support in the schoolage child have recently been addressed in a special report by the American Society for Parenteral and Enteral Nutrition.14 In a recent review of long-term HRQOL in neonatal surgical disease, children reported improved quality of life with increasing age in all diagnoses with the exception of necrotizing enterocolitis.15 This subgroup, which may share clinical attributes with our study population, showed generalized declines in all dimensions of the PedsQL survey over time. Given these data and in recognition of these unique challenges for the school-aged child with intestinal failure, our intestinal rehabilitation team includes a dedicated social worker to work with patients and their families. This individual focuses on adjustment to school as one of their priorities in appropriately aged children. In addition, our program has recently started a family support group, and the topic of school challenges is routinely discussed. No other patient-specific factors were associated with quality of life scores apart from patient age and developmental delay. Although it can be hypothesized that the ongoing need for parenteral nutrition or shorter remnant bowel lengths would be associated with lower HRQOL, this pattern was not demonstrated in our data. One interpretation of these data is that children and families learn to live with intestinal failure at all levels of severity as they accommodate to the condition. In this way, it may not be the disease itself that impacts quality of life, but rather life changes that present unique challenges to this population and their families. Alternatively, it is possible that a larger study cohort is required to identify associations between HRQOL scores and these clinical variables. Nonetheless, these findings have important implications in discussing the long-term prognosis of pediatric intestinal failure with families especially in children with risk factors for developmental delay. In our regression model, children with developmental delay demonstrated lower HRQOL scores at every age range and in nearly every HRQOL dimension.
ORIGINAL ARTICLES Our data are similar to that from Olieman et al who studied 31 patients with intestinal failure and found that participants scored lower on HRQOL surveys compared with healthy controls.9 This study evaluated HRQOL in pediatric patients with intestinal failure and found lower scores for the intestinal failure cohort in all dimensions except for emotional functioning.10 Our findings differ when compared with the largest assessment of quality of life in pediatric intestinal failure prior to the present study. Mutanen et al evaluated a cohort of 36 patients with intestinal failure and compared their data with age-matched healthy controls.8 Although parent proxy scores were lower in the intestinal failure population, child selfreports of HRQOL differed only in the physical dimension. Their study population was older and included adult participants. In addition, only 6 patients in their study were parenteral nutrition dependent and parenteral nutrition was administered for <1 year. It is possible, then, that our study population experienced more severe intestinal failure that was earlier in its time course, and this may account for differences in HRQOL scores between studies. Limitations exist in this study and its data. Although the data collection was longitudinal in nature, we did not follow individual patients over time to assess patientspecific changes in HRQOL. Instead, we chose to stratify our data by age group because our reference data were organized in a similar format and the PedsQL survey methodology has not been validated at the individual patient level. The data were collected over a 7-year period and clinical changes may have affected patient care during this time. It is difficult to know how these clinical changes may affect HRQOL. For example, although advances in intestinal failure care have improved the overall prognosis, it is possible that these interventions increase the work required of the child or family and may, in turn, decrease the HRQOL of the child and family. The study did not incorporate a prospective control group, but used established reference data in the published literature. This may create bias in our comparative analysis because the reference values may be dated and detailed medical histories for individual participants are not known. Finally, this analysis focused primarily on parent proxy data. A prior study has suggested that children may report improved HRQOL scores on child selfreported surveys.16 These data suggest that HRQOL in this population is lower in school-aged children, but is not associated with bowel length, parenteral nutrition dependence, or diagnosis. HRQOL scores were particular low in the School dimension suggesting there may be utility in local support groups and outreach at the onset of school age in these children and their families. The next steps in this area of investigation include the establishment of a multicenter study assessing HRQOL in this population to validate these data and the development of strategies to improve the quality of life for these children. n Submitted for publication Jun 14, 2019; last revision received Aug 20, 2019; accepted Aug 26, 2019.
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Reprint requests: Victoria C. Neam, BA, Division of Pediatric General and Thoracic Surgery, Seattle Children’s Hospital, Ocean A.9.220, Seattle, WA 98145. E-mail: [email protected]
References 1. Torres C, Sudan D, Vanderhoof J, Grant W, Botha J, Raynor S, et al. Role of an intestinal rehabilitation program in the treatment of advanced intestinal failure. J Pediatr Gastroenterol Nutr 2007;45:204-12. 2. Goulet O, Baglin-Gobet S, Talbotec C, Fourcade L, Colomb V, Sauvat F, et al. Outcome and long-term growth after extensive small bowel resection in the neonatal period: a survey of 87 children. Eur J Pediatr Surg 2005;15:95-101. 3. Javid PJ, Malone FR, Reyes J, Healey PJ, Horslen SP. The experience of a regional pediatric intestinal failure program: successful outcomes from intestinal rehabilitation. Am J Surg 2010;199:676-9. 4. Abi Nader E, Lambe C, Talbotec C, Pigneur B, Lacaille F, GarnierLengline H, et al. Outcome of home parenteral nutrition in 251 children over a 14-year period: report of a single center. Am J Clin Nutr 2016;103: 1327-36. 5. Fullerton BS, Sparks EA, Hall AM, Duggan C, Jaksic T, Modi BP. Enteral autonomy, cirrhosis, and long term transplant-free survival in pediatric intestinal failure patients. J Pediatr Surg 2016;51:96-100. 6. Sanchez SE, McAteer JP, Goldin AB, Horslen S, Huebner CE, Javid PJ. Health-related quality of life in children with intestinal failure. J Pediatr Gastroenterol Nutr 2013;57:330-4. 7. Hukkinen A, Merras-Salmio L, Pakarinen MP. Health-related quality and neurodevelopmental outcomes among children with intestinal failure. Semin Pediatr Surg 2018;27:273-9.
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8. Mutanen A, Kosola S, Merras-Salmio L, Kolho KL, Pakarinen MP. Longterm health-related quality of life of patients with pediatric onset intestinal failure. J Pediatr Surg 2015;50:1854-8. 9. Olieman JF, Penning C, Poley MJ, Utens EM, Hop WC, Tibboel D. Impact of infantile short bowel syndrome on long-term health-related quality of life: a cross-sectional study. J Pediatr Surg 2012;47:1309-16. 10. Pederiva F, Khalil B, Morabito A, Wood SJ. Impact of short bowel syndrome on quality of life and family: the patient’s perspective. Eur J Pediatr Surg 2019;29:196-202. 11. Varni JW, Limber CA, Burwinkle TM. Parent proxy-report of their children’s health-related quality of life: an analysis of 13,878 parents’ reliability and validity across age subgroups using the PedsQL TM 4.0 generic core scales. Health Qual Life Outcomes 2007;5:2. 12. Varni JW, Limbers CA, Neighbors K, Schulz K, Lieu JE, Heffer RW, et al. The PedsQLTM infant scales: feasibility, internal consistency reliability and validity in healthy and ill infants. Qual Life Res 2011;20:45-55. 13. Varni JW, Seid M, Kurtin PS. The PedsQLTM 4.0: reliability and validity of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales in healthy and patient populations. Med Care 2001;39:800-12. 14. Corrigan ML, Huang S, Weaver A, Keeler D, Rahe K, Balint J, et al. Resources for the provision of nutritional support to children in educational environments. Nutr Clin Pract 2017;32:834-43. 15. Amin R, Knezevich M, Lingongo M, Szabo A, Yin Z, Oldham KT, et al. Long-term quality of life in neonatal surgical disease. Ann Surg 2018;268: 497-505. 16. Eiser C, Varni J. Health-related quality of life and symptom reporting: similarities and differences between children and their parents. Eur J Pediatr Surg 2013;172:1299-304.
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Figure 2. Age-related trends in HRQOL scores in children with intestinal failure. PedsQL total scores were lower in our intestinal failure cohort compared with healthy children at every time point. A, Scores for the young child (5-7 years) group were also decreased compared with chronically ill children. B, PedsQL School dimension scores, which demonstrated a significant decrease in older children and were lower than both healthy and chronically ill children.
Factors Associated with Health-Related Quality of Life in Children with Intestinal Failure
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Study design A prospective study of HRQOL was performed in a regional intestinal rehabilitation program. Parent-proxy Pediatric Quality of Life Inventory surveys were administered annually to families of 91 children with intestinal failure over a 6-year period. Survey data was stratified by age and compared with pediatric HRQOL data in healthy and chronically ill populations. Linear mixed-effect models using multivariable regression were constructed to identify associations with HRQOL. Results A total of 180 surveys were completed by 91 children and their families. HRQOL scores were lowest for children ages 5-7 years (P < .001) and 8-12 years (P < .01), and these changes were primarily related to school dimension scores. In multivariable regression, age of 5 years and older and developmental delay were independently associated with lower HRQOL scores. The trend toward lower HRQOL scores parallels reference data from healthy and chronically ill children, although patients with intestinal failure scored lower than both populations at school age. Conclusions Children with intestinal failure experience lower parent-proxy HRQOL scores in the 5-7 and 812 year age groups primarily related to school dimension scores. Multicenter data to validate these findings and identify interventions to improve QOL for children with intestinal failure are needed. (J Pediatr 2019;-:1-6).
L
ong-term survival of children with intestinal failure now routinely approaches 90% in most dedicated, multidisciplinary intestinal rehabilitation programs.1-5 However, the improvement in mortality and long-term outcomes is associated with clinical complexities such as chronic dependence on parenteral nutrition, the ongoing need for hospitalization and surgical procedures, and extreme dietary modification. It is likely that many of the strategies to improve the care of this population also impact the health-related quality of life (HRQOL) of children and their families.6,7 Indeed, the assessment of HRQOL in children with intestinal failure, and the identification of interventions to improve HRQOL, have become priorities in the field. Previous reports from our program and others have evaluated HRQOL in children with intestinal failure at a single time point.6-10 Most, but not all, of these studies have demonstrated that HRQOL in pediatric intestinal failure is lower when compared with healthy children. However, data on changes in HRQOL with age in this population and a detailed analysis of disease-related factors associated with lower HRQOL are lacking. Moreover, prior publications have not compared HRQOL scores in the intestinal failure population with other children with chronic illness. Beginning in 2011, our program has been performing annual measurements of HRQOL in patients and families in our intestinal rehabilitation program. We have acquired HRQOL data that encompasses multiple age ranges and are relevant given the long-term survival of these patients into school age and beyond. The aim of this work was to identify targets for intervention to improve HRQOL in this patient population.
Methods A prospective, cross-sectional study was performed to assess HRQOL of children ages 6 months to 18 years receiving care at the intestinal rehabilitation program at Seattle Children’s Hospital from August 2011 to April 2017. Inclusion criteria encompassed English- or Spanish-speaking children and families with intestinal failure actively receiving care in the intestinal rehabilitation program. Intestinal failure was defined as any child with inadequate bowel function that required parenteral From the Seattle Children’s Hospital, Seattle, WA; 1
2
Institute for Disease Modeling, Bellevue; 3University of Washington School of Public Health; and 4University of Washington School of Medicine, Seattle, WA
HRQOL PedsQL
Health-related quality of life Pediatric Quality of Life Inventory
The authors declare no conflicts of interest. 0022-3476/$ - see front matter. ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jpeds.2019.08.049
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nutrition for ³3 consecutive months at any point in their lifetime secondary to anatomic short bowel length or problems with intestinal motility or absorption. Exclusion criteria included children <6 months of age, current inpatient status, surgery or inpatient hospitalization within 1 month of survey participation (other than central venous line placement or removal), and discharge from first hospitalization within 3 months. These exclusion criteria were chosen to include families who were able to spend time caring for their child in a nonacute care setting and to avoid bias in survey intake from recent illness or hospital admission. Measures and Procedures The Pediatric Quality of Life Inventory (PedsQL) 4.0 surveys were used to assess HRQOL in our population.11-14 The PedsQL Infant Scales include a 36-item report for infants ages 1-12 months and a 45-item report for children 1324 months.12 Each survey is divided into dimensions pertaining to physical functioning and symptoms, as well as emotional, social, and cognitive functioning.13 The PedsQL Generic Core Scales include parent proxy reports that assess perception of the child’s HRQOL. The surveys are age specific with versions for toddler (2-4 years), young child (57 years), child (8-12 years), and teen (13-18 years) age groups. The PedsQL Generic Core Scales are composed of 23-items that include questions regarding physical, emotional, social, and school functioning.13 For the various PedsQL surveys used, an unweighted 5-point Likert scale from 0 to 4 (0 [never], 1 [almost never], 2 [sometimes], 3 [often], 4 [almost always]) is used for each question. After obtaining informed consent, parent participants were asked to complete an age-appropriate infant scale or parent proxy report. Beginning 1 year after the initial survey, families were approached annually to complete an ageappropriate survey. The initial informed consent covered ongoing survey assessment. A trained research coordinator was available to help administer the surveys to all participants as needed. Participants were given the option to complete surveys on an iPad in clinic or paper surveys in clinic or at home. Previous data have shown that the method of survey delivery does not impact survey results.13 A total of 20 surveys (11%) were completed at home and returned via mail. At each survey time point, demographic and clinical variables were collected retrospectively from review of the electronic medical record including physician notes, operative reports, and nutrition plans. Bowel length data were determined by detailed review of internal and outside operative reports for each patient when available. All aspects of this study were approved by the Seattle Children’s Hospital Institutional Review Board (application number 13660). Statistical Analyses All completed surveys were scored according to the official PedsQL guidelines.13 Items were reverse scored and linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50,
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3 = 25, 4 = 0), so that higher scores indicate better HRQOL. In addition to the calculation of total scores, we analyzed data by individual dimension scores including physical, emotional, social, and school functioning. The psychosocial health summary score (including emotional, social, and school functioning scores), and physical health summary score (including the physical functioning score) were calculated. Categorical variables were tabulated with percent breakdown reported. Continuous demographic variables were summarized as median, IQR, and/or range. Test scores were summarized as mean and SD. Data were stratified by established age ranges as defined by the PedsQL survey methodology. In addition, we used published reference values for the PedsQL in both healthy and chronically ill pediatric populations to compare our scores using general t tests.11,12 The healthy comparison data published by Varni et al represents a cohort of children seen for well-child checks whose parents or medical records did not mention the presence of a chronic illness.11 Our chronic illness comparison data includes a cohort of children and teens ages 1 month to 12 years receiving care in clinics and hospitals for chronic physical and/or mental health conditions lasting ³6 months and published by Varni et al.12 The diagnoses included in the chronic illness group included cancer, asthma, cardiac condition, diabetes, rheumatic disease, gastrointestinal problems, cerebral palsy, attention deficit hyperactivity disorder, sickle cell anemia, and renal disease. Finally, we investigated the association between demographic and clinical factors on survey scores using multivariable linear mixed-effects models accounting for the grouping of surveys by patient using a random intercept term. For this analysis, bowel length was used as a continuous variable and log base 2 transformed so that the model coefficient represents the change in survey score with doubling of bowel length irrespective of baseline. The model adjusted for patient age, ethnicity, etiology of intestinal failure, parenteral nutrition dependence, number of hospital admissions within the previous year, and bowel length when available.
Results Ninety-one children and their families were enrolled, and a total of 180 surveys were performed. Forty-seven participants (52%) completed multiple surveys including 44 participants with 2 surveys, 23 with 3 surveys, 15 with 4 surveys, and 3 with 5 surveys. The distribution of surveys by age group is illustrated in Figure 1, and demographic data are presented in Table I. Fifty-six children (62%) were male, and the median age at first survey was 3 years (range, 0.517.0 years). The most common etiologies of intestinal failure were gastroschisis (n = 29 [32%]) and necrotizing enterocolitis (n = 26 [29%]). Bowel length data were available for 72 children, and remaining bowel length was 42 cm (range, 1-250 cm). Seventy-one children (78%) were dependent on parenteral nutrition for ³1 survey, and
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Figure 1. Survey distribution. The distribution of completed parent-proxy PedsQL surveys by age group is illustrated. The survey number is graphically represented. n = the number of participants in each age group.
109 (61%) surveys were performed in children actively receiving parenteral nutrition. HRQOL Scores and Comparison to Reference Populations HRQOL scores in children with intestinal failure are presented in Table II. In all age groups, children with
Table I. Descriptive statistics for demographic and clinical characteristics Characteristics
No. (%)
Race/ethnicity White non-Hispanic 42 (46) Black non-Hispanic 6 (7) Hispanic 25 (27) Asian/Pacific Islander 5 (5) Other 13 (14) Diagnosis Gastroschisis 29 (32) Necrotizing enterocolitis 26 (29) Midgut volvulus 7 (8) Intestinal atresia 11 (12) Hirschsprung disease 5 (5) Other* 13 (14) Bowel length, cm (n = 180) 1-20 46 (26) 21-40 44 (24) 41-60 29 (16) >60 36 (20) Missing 25 (14) Admission in year before survey time point (n = 180) None 74 (41) 1 31 (17) 2-3 45 (25) ³4 30 (17) Parenteral nutrition dependent at any survey time point (n = 180) 109 (61) Developmental delay 22 (24) *Other diagnoses included congenital short bowel, intestinal pseudoobstruction, meconium peritonitis, and microvillus inclusion disease.
intestinal failure demonstrated lower total HRQOL scores when compared with a healthy reference population. When compared with a reference population of chronically ill children, infants with intestinal failure had higher total and psychosocial scores and there were no differences in scores for toddlers ages 1-4 years. Among school-aged children with intestinal failure, total HRQOL scores were lower than chronically ill children at ages 5-7 years ( 7.8; P = .02) and 8-12 years ( 6.1; P = .08). Our study population had similar physical health summary scores when compared with chronically ill children except for lower scores in patients aged 5-7 years ( 7.8; P = .02). Psychosocial health summary scores were lower in both the 5- to 7-year ( 7.2; P = .005) and 8- to 12-year age groups ( 8.3; P = .01). When the data were analyzed at the survey dimension level, children with intestinal failure demonstrated dramatically lower scores in school functioning at 5-7 years ( 12.4; P < .001) and 8-12 years (difference, 25.6; P < .001) compared with the chronically ill reference population (Figure 2; available at www.jpeds.com).
PedsQL: Results by Age HRQOL scores in children with intestinal failure generally followed the age-related trends previously established for healthy and chronically ill children (Figure 2). Total HRQOL scores were noted to be highest in the infant and toddler age groups. HRQOL scores for children ages 57 years and 8-12 years (P < .01) were significantly lower, even after controlling for other variables on regression analysis. Although this trend mirrored the data from reference populations, HRQOL scores in our population were shifted lower in school-aged children secondary, at least in part, to sizable decreases in school dimension scores.
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Table II. PedsQL infant scales or generic core scales compared with reference data for healthy and chronically ill children Characteristics
Total score Physical health summary Psychosocial health summary Total score Physical health summary Psychosocial health summary Total score Physical health summary Psychosocial health summary Total score Physical health summary Psychosocial health summary Total score Physical health summary Psychosocial health summary
Intestinal failure study population
Healthy children11,12
Infants with intestinal failure (1-12 months; n = 28) 74.9 (12.7) 74.3 (13.0) 75.3 (14.5) Toddlers with intestinal failure (13-24 months; n = 12) 73.5 (12.2) 74.6 (13.1) 72.8 (13.1) Toddlers with intestinal failure (2-4 years; n = 51) 77.0 (14.8) 78.2 (18.7) 76.3 (15.1) Children with intestinal failure (5-7 years; n = 50) 63.4 (14.2) 62.1 (22.6) 64.2 (14.0) Children with intestinal failure (8-12 years; n = 29) 64.4 (15.4) 69.9 (24.7) 61.5 (16.6)
Varni et al 2011 (n = 246)
P value
Chronically ill children11,12
P value
Varni et al 2011 (n = 41)
82.5 (10.0) 85.0 (9.5) 80.5 (12.6) Varni et al 2011 (n = 141)
<.001 <.001 <.001
68.0 (13.9) 69.5 (13.5) 66.8 (16.7) Varni et al 2011 (n = 23)
.041 .146 .032
85.6 (8.7) 88.8 (7.7) 83.1 (11.0) Varni et al 2007 (n = 2922)
<.001 <.001 <.001
69.9 (10.4) 72.8 (14.4) 67.7 (10.3) Varni et al 2007 (n = 617)
.366 .720 .212
87.8 (12.1) 89.8 (15.4) 86.5 (12.3) Varni et al 2007 (n = 2318)
<.001 <.001 <.001
77.3 (18.4) 76.6 (24.8) 77.7 (16.5) Varni et al 2007 (n = 704)
.920 .637 .571
79.4 (16.1) 80.0 (20.9) 79.1 (15.5) Varni et al 2007 (n = 2956)
<.001 <.001 <.001
71.2 (18.5) 70.9 (25.5) 71.4 (17.8) Varni et al 2007 (n = 1380)
.004 .017 .005
80.2 (16.3) 82.7 (20.5) 78.9 (16.3)
<.001 <.001 <.001
70.5 (18.4) 72.0 (24.7) 69.8 (18.0)
.080 .659 .014
Data reported as mean (SD).
PedsQL: Multivariable Regression Model A multivariable regression model was constructed to identify associations between HRQOL scores and clinical measures (Table III). After controlling for age, sex, ethnicity, parenteral nutrition dependence, recent hospital admissions, diagnosis, and bowel length, only age >5 years (P < .01) and developmental delay (P < .01) were associated with lower HRQOL scores. Bowel length, the need for parenteral nutrition, the etiology of intestinal failure, and prematurity were not predictive of HRQOL scores in this model. The same regression model was applied to the psychosocial functioning score. Similar to our results for the total score, children age 5 years and older (P < .001) and developmental
Table III. Multivariable regression results Effects
Difference 95% CI
Infant vs toddler Age 1 vs toddler Age 5-7 vs toddler Age 8-12 vs toddler Hispanic vs White All other vs White Parenteral nutrition dependence NEC vs gastroschisis Intestinal atresia vs gastroschisis Volv/HD/other* vs gastroschisis Developmental delay Longer bowel length ³2 hospital admissions
4.4 ( 5.4 ( 11.9 ( 9.3 ( 4.7 ( 5.6 ( 2.0 ( 5.7 ( 6.6 ( 4.9 ( 9.9 ( 1.1 ( 0.5 (
11.1 to 2.2) 13.7 to 2.8) 17.2 to 6.5) 16.1 to 2.4) 1.7 to 11.0) 12.5 to 1.2) 7.6 to 3.5) 1.1 to 12.6) 2.1 to 15.4) 2.9 to 12.7) 16.2 to 3.6) 0.6 to 2.9) 4.7 to 5.6)
P value .190 .197 <.001 .008 .148 .107 .469 .099 .135 .221 .002 .213 .862
HD, Hirschsprung disease; NEC, necrotizing enterocolitis; Volv, midgut volvulus. *Other: congenital short bowel, intestinal pseudoobstruction, meconium peritonitis, microvillus inclusion disease.
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delay (P = .003) were independently associated with lower Psychosocial Functioning HRQOL scores.
Discussion A diagnosis that was once associated with a high risk of mortality at an early age, namely, intestinal failure, has become a chronic disease. There is widespread agreement within the field of pediatric intestinal failure that assessment of the quality of life of these children and their families should be a priority. These data may contribute to the long-term care of these patients and may also help to define the natural history of the disease. Our previous data from 23 families of children with intestinal failure found lower HRQOL scores than healthy peers beginning in the toddler age group and continuing to early school age.6 The small sample size and limited age range limited significant associations between demographic or disease-specific factors and HRQOL. These data show that school-aged children with intestinal failure have lower HRQOL scores even when compared with children with chronic illness. HRQOL scores in children with intestinal failure follow a similar pattern seen in both healthy and chronically ill children starting at 5 years of age. Parent proxy HRQOL scores are lower in all 3 populations, although scores for children with intestinal failure are shifted lower compared with both reference populations. The fact that these patterns were seen with a generic instrument like the PedsQL, which is not designed specifically for patients with gastrointestinal disease, makes these differences more noteworthy. Neam et al
- 2019 The changes in HRQOL scores in school-age children are striking and were not anticipated at the onset of this study. The school dimension addresses the frequency of the child having trouble paying attention in class and keeping up with schoolwork, forgetting things in school, and missing school because of not feeling well or needing to go to the doctor. Children with intestinal failure face many unique challenges as they progress in school. Their diet may be restrictive compared with their peers, and many patients may not eat at all. The presence of central lines and gastrostomy tubes can be a risk during physical education and recess, as well as another reminder that they are different from other children. Our patients may miss school frequently for hospital admissions, clinic appointments, and surgical procedures. Fatigue owing to a lack of sleep from nightly parenteral nutrition infusions and abnormal stooling patterns may also play a role. All of these differences at school may negatively impact the socialization of the child. Indeed, the challenges associated with nutritional support in the schoolage child have recently been addressed in a special report by the American Society for Parenteral and Enteral Nutrition.14 In a recent review of long-term HRQOL in neonatal surgical disease, children reported improved quality of life with increasing age in all diagnoses with the exception of necrotizing enterocolitis.15 This subgroup, which may share clinical attributes with our study population, showed generalized declines in all dimensions of the PedsQL survey over time. Given these data and in recognition of these unique challenges for the school-aged child with intestinal failure, our intestinal rehabilitation team includes a dedicated social worker to work with patients and their families. This individual focuses on adjustment to school as one of their priorities in appropriately aged children. In addition, our program has recently started a family support group, and the topic of school challenges is routinely discussed. No other patient-specific factors were associated with quality of life scores apart from patient age and developmental delay. Although it can be hypothesized that the ongoing need for parenteral nutrition or shorter remnant bowel lengths would be associated with lower HRQOL, this pattern was not demonstrated in our data. One interpretation of these data is that children and families learn to live with intestinal failure at all levels of severity as they accommodate to the condition. In this way, it may not be the disease itself that impacts quality of life, but rather life changes that present unique challenges to this population and their families. Alternatively, it is possible that a larger study cohort is required to identify associations between HRQOL scores and these clinical variables. Nonetheless, these findings have important implications in discussing the long-term prognosis of pediatric intestinal failure with families especially in children with risk factors for developmental delay. In our regression model, children with developmental delay demonstrated lower HRQOL scores at every age range and in nearly every HRQOL dimension.
ORIGINAL ARTICLES Our data are similar to that from Olieman et al who studied 31 patients with intestinal failure and found that participants scored lower on HRQOL surveys compared with healthy controls.9 This study evaluated HRQOL in pediatric patients with intestinal failure and found lower scores for the intestinal failure cohort in all dimensions except for emotional functioning.10 Our findings differ when compared with the largest assessment of quality of life in pediatric intestinal failure prior to the present study. Mutanen et al evaluated a cohort of 36 patients with intestinal failure and compared their data with age-matched healthy controls.8 Although parent proxy scores were lower in the intestinal failure population, child selfreports of HRQOL differed only in the physical dimension. Their study population was older and included adult participants. In addition, only 6 patients in their study were parenteral nutrition dependent and parenteral nutrition was administered for <1 year. It is possible, then, that our study population experienced more severe intestinal failure that was earlier in its time course, and this may account for differences in HRQOL scores between studies. Limitations exist in this study and its data. Although the data collection was longitudinal in nature, we did not follow individual patients over time to assess patientspecific changes in HRQOL. Instead, we chose to stratify our data by age group because our reference data were organized in a similar format and the PedsQL survey methodology has not been validated at the individual patient level. The data were collected over a 7-year period and clinical changes may have affected patient care during this time. It is difficult to know how these clinical changes may affect HRQOL. For example, although advances in intestinal failure care have improved the overall prognosis, it is possible that these interventions increase the work required of the child or family and may, in turn, decrease the HRQOL of the child and family. The study did not incorporate a prospective control group, but used established reference data in the published literature. This may create bias in our comparative analysis because the reference values may be dated and detailed medical histories for individual participants are not known. Finally, this analysis focused primarily on parent proxy data. A prior study has suggested that children may report improved HRQOL scores on child selfreported surveys.16 These data suggest that HRQOL in this population is lower in school-aged children, but is not associated with bowel length, parenteral nutrition dependence, or diagnosis. HRQOL scores were particular low in the School dimension suggesting there may be utility in local support groups and outreach at the onset of school age in these children and their families. The next steps in this area of investigation include the establishment of a multicenter study assessing HRQOL in this population to validate these data and the development of strategies to improve the quality of life for these children. n Submitted for publication Jun 14, 2019; last revision received Aug 20, 2019; accepted Aug 26, 2019.
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Reprint requests: Victoria C. Neam, BA, Division of Pediatric General and Thoracic Surgery, Seattle Children’s Hospital, Ocean A.9.220, Seattle, WA 98145. E-mail: [email protected]
References 1. Torres C, Sudan D, Vanderhoof J, Grant W, Botha J, Raynor S, et al. Role of an intestinal rehabilitation program in the treatment of advanced intestinal failure. J Pediatr Gastroenterol Nutr 2007;45:204-12. 2. Goulet O, Baglin-Gobet S, Talbotec C, Fourcade L, Colomb V, Sauvat F, et al. Outcome and long-term growth after extensive small bowel resection in the neonatal period: a survey of 87 children. Eur J Pediatr Surg 2005;15:95-101. 3. Javid PJ, Malone FR, Reyes J, Healey PJ, Horslen SP. The experience of a regional pediatric intestinal failure program: successful outcomes from intestinal rehabilitation. Am J Surg 2010;199:676-9. 4. Abi Nader E, Lambe C, Talbotec C, Pigneur B, Lacaille F, GarnierLengline H, et al. Outcome of home parenteral nutrition in 251 children over a 14-year period: report of a single center. Am J Clin Nutr 2016;103: 1327-36. 5. Fullerton BS, Sparks EA, Hall AM, Duggan C, Jaksic T, Modi BP. Enteral autonomy, cirrhosis, and long term transplant-free survival in pediatric intestinal failure patients. J Pediatr Surg 2016;51:96-100. 6. Sanchez SE, McAteer JP, Goldin AB, Horslen S, Huebner CE, Javid PJ. Health-related quality of life in children with intestinal failure. J Pediatr Gastroenterol Nutr 2013;57:330-4. 7. Hukkinen A, Merras-Salmio L, Pakarinen MP. Health-related quality and neurodevelopmental outcomes among children with intestinal failure. Semin Pediatr Surg 2018;27:273-9.
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8. Mutanen A, Kosola S, Merras-Salmio L, Kolho KL, Pakarinen MP. Longterm health-related quality of life of patients with pediatric onset intestinal failure. J Pediatr Surg 2015;50:1854-8. 9. Olieman JF, Penning C, Poley MJ, Utens EM, Hop WC, Tibboel D. Impact of infantile short bowel syndrome on long-term health-related quality of life: a cross-sectional study. J Pediatr Surg 2012;47:1309-16. 10. Pederiva F, Khalil B, Morabito A, Wood SJ. Impact of short bowel syndrome on quality of life and family: the patient’s perspective. Eur J Pediatr Surg 2019;29:196-202. 11. Varni JW, Limber CA, Burwinkle TM. Parent proxy-report of their children’s health-related quality of life: an analysis of 13,878 parents’ reliability and validity across age subgroups using the PedsQL TM 4.0 generic core scales. Health Qual Life Outcomes 2007;5:2. 12. Varni JW, Limbers CA, Neighbors K, Schulz K, Lieu JE, Heffer RW, et al. The PedsQLTM infant scales: feasibility, internal consistency reliability and validity in healthy and ill infants. Qual Life Res 2011;20:45-55. 13. Varni JW, Seid M, Kurtin PS. The PedsQLTM 4.0: reliability and validity of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales in healthy and patient populations. Med Care 2001;39:800-12. 14. Corrigan ML, Huang S, Weaver A, Keeler D, Rahe K, Balint J, et al. Resources for the provision of nutritional support to children in educational environments. Nutr Clin Pract 2017;32:834-43. 15. Amin R, Knezevich M, Lingongo M, Szabo A, Yin Z, Oldham KT, et al. Long-term quality of life in neonatal surgical disease. Ann Surg 2018;268: 497-505. 16. Eiser C, Varni J. Health-related quality of life and symptom reporting: similarities and differences between children and their parents. Eur J Pediatr Surg 2013;172:1299-304.
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Figure 2. Age-related trends in HRQOL scores in children with intestinal failure. PedsQL total scores were lower in our intestinal failure cohort compared with healthy children at every time point. A, Scores for the young child (5-7 years) group were also decreased compared with chronically ill children. B, PedsQL School dimension scores, which demonstrated a significant decrease in older children and were lower than both healthy and chronically ill children.
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