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Health Related Quality of Life in Children with Short Stature

Seham Fathy Azab 1, Ashgan Abdalla Alghobashy2, Ahmed Nagy Elsafty3

1 Professor of Pediatrics, Faculty of Medicine – Zagazig University, Egypt , 2 Professor of Pediatrics, Faculty of Medicine – Zagazig University, Egypt, 3 M.B.B.CH, Egypt

Corresponding Author: Ahmed Nagy Elsafty

Introduction:

Short stature is a term applied to a child whose height is 2 standard deviations (SD) or more below the mean for children of that sex and chronologic age (and ideally of the same racial-ethnic group).

This corresponds to a height that is below the 2.3rd percentile. Short stature may be either a variant of normal growth or caused by a disease (1).

The most common causes of short stature beyond the first year or two of life are familial (genetic) short stature and delayed (constitutional) growth, which are normal, non-pathologic variants of growth. The goal of the evaluation of a child with short stature is to identify the subset of children with pathologic causes (such as Turner syndrome, inflammatory bowel disease or other underlying systemic disease, or growth hormone deficiency). The evaluation also assesses the severity of the short stature and likely growth trajectory, to facilitate decisions about intervention, if appropriate (1) Abstract

Background: Short stature is a term applied to a child whose height is 2 standard deviations (SD) or more below the mean for children of that sex and chronologic age (and ideally of the same racial-ethnic group).

HRQOL is increasingly seen as an important outcome in clinical medicine. HRQOL includes subjective physical, emotional and social aspects of well-being and functioning from the patient’s perspective and extends to the perspective of other persons. The present work aimed to assess the psychological outcomes and health related quality of life (HRQOL) for pediatrics with short stature (SS). Methods: HRQOL for SS patients, in 392 school children were evaluated. Results: According to our study as regarding socio- demographic characteristics of the studied children, it included 392 patients with SS; 223 of them were females (56.89%) and 169 of them were male (43.11 %) with age ranging between 12 to 18 years. The mean

±SD age of the patients was 15.77 ± 1.41 years. Number of children in urban was 191(48.72 %) and in rural was 201 (51.28%). In preparatory school were 199 (50.77%) and in secondary school were 193 (49.23%).

Child order ranged from 1-5 with mean ±SD 2.41±1.01. Number of children in the family ranged from 1-6 with mean ±SD 3.87±1.19. Our results showed as regarding school performance students with short were classified into bad n 96 (24%), good 278(70.92%) and excellent 18 (4.59%). Also, when comparing different WHO QOL domains according to school performance of children with SS, we founded that the performance of children with SS at school was great, there was a positive reflection at scores of the different WHO QOL domains but didn't reach a statistically significant. As regarding socio-economical state of the patient’s family, the Mean ±SD monthly income of the family 2557.91 ±957.666. according to Number of chambers in the house mean ±SD 2.96 ± 0.75, and Crowding index included 5 in room 12 (3.06%), 3-4 in room n180(45.92%), 2 in room 132 (33.67%) and less than 2 in room 68(17.35%).We also founded that number of working mothers 73 (18.62%) and not working 319(81.38%) while number of working fathers 314(80.1%) and not working 78(19.9%).Our study founded that residence distribution at children with SS in relation to different WHO QOL domains was of no significant value although it was in favor with urban residency.

Conclusion: Pediatric patients with SS have lower HRQOL compared to healthy individuals especially in physical, psychological and environmental aspects. Social domain is the most affected among SS children.

Keywords: Short stature-Health-related quality of life-Evaluation.

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The fast-technological development, particularly single nucleotide polymorphism array, array- comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure according to a diagnostic classification centered on the epiphyseal growth plate. Disorders in hormone signaling , paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes and chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature (2).

HRQOL is increasingly seen as an important outcome in clinical medicine. HRQOL includes subjective physical, emotional and social aspects of well-being and functioning from the patient’s perspective and extends to the perspective of other persons (3)

Very few instruments have been developed in the area of pediatric endocrinology, and assessments of well-being and functioning from the perspectives of children and adolescents are needed.

Specifically, there is a lack of validated instruments to assess HRQOL in children and adolescents diagnosed with SS (4)

The present work aimed to assess the psychological outcomes and health related quality of life (HRQOL) for pediatrics with short stature (SS)

Patients and Methods

Cross-sectional study was carried out at Gharbia governorate preparatory and secondary school children in Gharbia governorate

Inclusion criteria

1.

school children who meet the diagnosis of SS according to definition of WHO for short stature of child height below or equal 3rd percentile on WHO Growth chart in children of same gender and chronological age.

2.

Both sexes were included.

3.

Age 12-18 years.

Exclusion criteria:

- Children with any other chronic diseases, dysmorphic appearance or disabilities that affect their quality of life

4. Sample size:

Assuming that total number of preparatory and secondary school children was 125000 and prevalence of short stature was 15% sample was calculated to be 196 children using EPI Info 7 program with test power 80% CI (Confidence Interval ) 95% sample size was 196 multiblied by 2. So the sample size was 392

Methods:

Evaluation of a child with short stature A. history taking

B. examination

To exclude dysmorphic appearance or disabilitis ,,any chronic illness that affects quality of life examining body abnormality appearance

B)-HRQOL questionnaire:

It was held using the Organization's WHOQOL-BREF quality of life assessment (5), An Arabic translation was used.

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The questionnaire consisted of 26 items but one item about appreciation of sexual life was discarded putting into consideration the young age of the studied group. The questionnaire was administered to both patients themselves, if they had enough reading ability. In younger patients, we will interview them with help of the available parent. The investigator himself will explain each question.

The items assessing four main domains that cover the aspects proposed to judge QOL.

The assessed domains had included:

•Physical health:

Feeling that physical pain prevents from doing what needed by the patient, the need for medical treatment to function in daily life, having enough energy for everyday life, being satisfied with sleep, ability to perform daily living activity and capacity for learning

•Psychological health:

The patient’s ability to accept his/her bodily appearance, how much the patient enjoys life, patient’s ability to concentrate, patient’s satisfaction with him/herself, feeling that life is meaningful and how often the patient has negative feelings such as blue mood, despair, anxiety and depression.

•Social relationships:

Satisfaction with personal relationships, satisfaction with support taken from patient’s friends.

•Environmental domain:

How safe the patient feels in his/her daily life including: satisfaction with physical environment of the patient, satisfaction with the conditions of patient’s living place, satisfaction with transport, satisfaction with the access to health services, having the opportunity for leisure activities, the availability of the information that the patient needs in day-to-day life and how feeling safe in the daily life.

Scoring and Classification System:

-WHOQOL-BREFF

The four domain scores denote an individual’s perception of QOL in each particular domain. Scores are scaled in a positive direction, with higher scores denoting higher QOL.

Items were related on a 5-point Likert scale and the raw scores obtained were transformed twice. The first converts' raw scores to range between 4-20, and the second converts domain scores to a 0-100 scale for ease of interpretation and comparison with the WHOQOL-100 according to instructions given in the user’s manual.

Scores were calculated according to the standard method as instructed in the WHOQOL Brief manual. The mean score of items within each domain was used to calculate the domain score. Instructions for checking data and computing domain scores were used. Higher score indicates better health.

STATICAL ANALYSIS

Data were coded and entered using the statistical package SPSS version 23. Data was summarized using mean, standard deviation, median, minimum and maximum for quantitative variables and frequencies (number of cases) and relative frequencies

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(percentages) for categorical variables. Comparisons between groups were done using unpaired t test when comparing 2 groups and analysis of variance (ANOVA) with multiple comparisons post hoc test when comparing more than 2 groups. For comparing categorical data, Chi square (2) test was performed. Exact test was used instead when the expected frequency is less than 5. Correlations between quantitative variables were done using Pearson correlation coefficient.P-values less than 0.05 were considered as statistically significant.

Results:

Table 1 illustrates socio-demographic characteristics of the studied group. The study included 392 patients with SS; 223 of them were females (56.89%) and 169 of them were male (43.11 %) with age ranging between 12 to 18 years. The mean ±SD age of the patients was 15.77 ± 1.41 years. Number of children in urban was 191(48.72 %) and in rural was 201 (51.28%). in preparatory school were 199 (50.77%) and in secondary school were 193 (49.23%). Child order ranged from 1-5 with mean ±SD 2.41±1.01. Number of children in the family ranged from 1-6 with mean ±SD 3.87±1.19.

Table 2: mean value ± SD of height of patients was 143.28±4.90. mean value ± SD of their weight was 44.41 ± 5. 18. Mean value ± SD of body mass index was 23.20 ± 3.82.

Table 3 & figure 1: According to school performance students with short were classified into bad n 96 (24%), good 278 (70.92%) and excellent 18 (4.59%).

Table 4 & figure 2: As soon as the performance of children with SS at school was great; there was a positive reflection at scores of the different WHO QOL domains but didn't reach a statistically significant.

Table 5: The mean value ± SD of physical domain was 67.40 ± 18.10. the mean value ± SD of psychological domain 56.17 ± 17.64. The mean value ± SD of social domain 76.89 ± 12.91.

Table 6 & figures (3, 4, 5, 6): Characteristics of the patient’s family it was founded that number of working mothers 73 (18.62%) and not working 319(81.38%) while number of working fathers 314 (80.1%) and not working 78(19.9%). According to the age of mothers (years) showed that mean ±SD 42.29 ± 5.11 and the age of father in years with mean ± SD 48.5 ± 5.89. Level of mother education included number of illiterate 80 (20.41%), number of certificates of literacy 38 (9.69%), n of primary 58 (14.8%), n of preparatory 86 (21.94%), secondary 100 (25.51%) and college 30 (7.65%). according to level of father education included N Illiterate 28 (7.14%), n certificate of literacy 58 (14.8%), n primary 45 (11.48%), preparatory 99 (25.26%), n secondary 110 (28.06%) and college 52 (13.27%).

Table 7 & figures (7, 8): The Mean ±SD monthly income of the family 2557.91

±957.666. according to number of chambers in the house mean ±SD 2.96 ± 0.75, and crowding index included 5 in room 12 (3.06%), 3-4 in room n180 (45.92%), 2 in room 132 (33.67%) and less than 2 in room 68 (17.35%).

Table 8 & figure 9: There was no statistically significant difference between residence distribution regarding WHO QOL domains.

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Table 1: Socio-demographic characteristics of the studied group

N %

Sex Female 223 56.89

Male 169 43.11

Residence Urban 191 48.72

Rural 201 51.28

Age Preparatory 199 50.77

Secondary 193 49.23

Age Mean ±SD 15.77 ± 1.41

Number of children in the family Mean ±SD 3.87±1.19

Child order Mean ±SD 2.41±1.01

SD: standard deviation

Table 2: characteristics of children with SS according to the anthropometric measures

Mean ± SD

Height 143.28 ± 4.90

Weight 44.41 ± 5.18

BMI 23.20 ± 3.82

Table 3: Comparison between students with short stature according to performance at school

School Performance

N %

Bad 96 24.49

Good 278 70.92

Excellent 18 4.59

Total 392 100.00

Figure 1: Comparison between students with short stature according to performance at school

Bad 96 24.49%

Good 278 70.92%

Excellent 18 4.59%

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Table 4: Comparison between different WHO QOL domains according to school performance of children with SS.

Domain School Performance

P value

Bad Good Excellent

Physical 62.41 ± 19.71 65.87 ± 15.11 72.54 ± 26.33 0.061 Psychological 52.31 ± 16.42 56.40 ± 17.88 60.21± 18.11 0.068 Social 75.22 ± 18.13 78.28 ± 14.39 81.47 ± 6.50 0.152 Environmental 58.44 ± 19.33 62.11 ± 11.99 67.18 ± 24.66 0.095

Fig 2: Comparison between different WHO QOL domains according to school performance of children with SS

Table 5: WHOQOL-BREF quality of life assessment of the patients

Domain Mean ± SD

Physical domain 67.40 ± 18.10

Psychological domain 56.17 ± 17.64

Social domain 76.89 ± 12.91

Environmental domain 61.30 ± 18.94

Table 6: Characteristics of the patient’s family

N %

Work of mother working 73 18.62

not working 319 81.38

Work of father working 314 80.10

not working 78 19.90

Age of mother (years) mean ±Sd 42.29 ± 5.11

0 20 40 60 80 100 120

Physical Psychological Social Environmental

Mean ±SD

Bad Good Excellent

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Age of father (years) mean ±Sd 48.5 ± 5.89

Level of mother education

Illiterate 80 20.41

certificate of literacy 38 9.69

primary 58 14.80

preparatory 86 21.94

secondary 100 25.51

College 30 7.65

Level of father education

Illiterate 28 7.14

certificate of literacy 58 14.80

primary 45 11.48

preparatory 99 25.26

secondary 110 28.06

College 52 13.27

Figure 3: percentage of working of mothers

Figure 4: percentage of working of fathers

Working 73 18.62%

Not working 319 81.38%

Working 314 80.10%

Not working 87 19.90%

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Figure 5: Levels of mothers' education percentage

Figure 6: Levels of father education percentage Table 7: Socio-economical state of the patient’s family

N %

Monthly income of the family Mean ±SD 2557.91 ±957.666 Number of chambers in the house Mean ±SD 2.96 ± 0.75

Number of chambers in the house

Two 102 26.02

Three 223 56.89

Four 49 12.50

Five 18 4.59

Crowding index

5 in room 12 3.06

3-4 in room 180 45.92

2 in room 132 33.67

<2 in room 68 17.35

0 5 10 15 20 25 30

%

0 5 10 15 20 25

% 30

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Figure 7: Number of chambers percentage in the house

Figure 8: Crowding index

Table 8: Residence distribution at children with SS in relation to different WHO QOL domains

Domain Residence

P value

Urban Rural

Physical 66.12 ± 16.58 64.19 ± 15.97 0.241 Psychological 57.18 ± 14.36 56.19 ± 18.98 0.562 Social 79.79 ± 16.59 79.11 ± 15.96 0.679 Environmental 60.97 ± 16.88 61.19 ± 10.79 0.877

Two 102 26.02%

Three 223 56.89%

Four 49 12.50%

Five 18 4.59%

5 in room 12 3.06%

3-4in room 180 45.92%

2 in room 132 33.67%

<2 in room 68 17.35%

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Figure 9: residence distribution at children with SS in relation to different WHO QOL domains

Discussion

Our study is a cross sectional study that included 392 children and adolescents with SS. That aimed to assess HRQOL in children and adolescents with SS by using the WHOQOL questionnaire which includes different health related life domains i.e. physical, psychological, social and environmental.

According to our study as regarding socio-demographic characteristics of the studied children, it included 392 patients with SS; 223 of them were females (56.89%) and 169 of them were male (43.11 %) with age ranging between 12 to 18 years. The mean ±SD age of the patients was 15.77 ± 1.41 years.

Number of children in urban was 191(48.72 %) and in rural was 201 (51.28%). In preparatory school were 199 (50.77%) and in secondary school were 193 (49.23%). Child order ranged from 1-5 with mean ±SD 2.41±1.01. Number of children in the family ranged from 1-6 with mean ±SD 3.87±1.19.

Also, Garganta and Bremer showed that a comprehensive history starting in the prenatal and perinatal periods should be obtained. Emphases of the history include maternal health and habits during pregnancy, the duration of gestation, birth weight and length and growth pattern. It is generally recognized that babies of low birth weight with persistent postnatal SS do not have a favorable stature outcome (6)

Our results showed as regarding school performance students with short were classified into bad n 96 (24%), good 278(70.92%) and excellent 18 (4.59%).

Also, when comparing different WHO QOL domains according to school performance of children with SS, we founded that the performance of children with SS at school was great, there was a positive reflection at scores of the different WHO QOL domains but didn't reach a statistically significant.

0 20 40 60 80 100 120

Physical Psychological Social Environmental

Mean ±SD

Urban Rural

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In addition to increasing linear growth, improvement in health-related quality of life (HRQOL) is an important end point in the treatment of short statured youth. Hence, condition-specific psychometric valid instruments that adequately assess HRQOL are needed.

We aimed to confirmatory examine the psychometric performance of the Quality of Life in Short Stature Youth (QoLISSY) questionnaire used in a previously reported prospective randomized open-label trial (7)

Wheeler et al found that children with SS have mean test scores within the range of normal for intelligence, academic achievement, and behavior (ie, within 1 SD of the mean).

However, among the studies that directly compared short children with average-height controls who were otherwise similar to the short children most found that short children had significantly lower academic achievement test scores or a greater likelihood of low scores than controls. Similar results were found in a number of studies that evaluated intelligence (8)

Differences according to socio-demographic characteristics were inspected for information about the potential effects of age and gender on scale scores to be taken into consideration regarding scoring and clinical interpretation in future studies. Differences in mean scale scores between age groups (8–12 and 13–18 years) were only present in the Physical scale of the child self-report (t (47) = −2.55, p = 0.014, α = 0.05). Younger children (M = 74.49 ± 17.84) reported more limitations in their perceived physical QoL than adolescents (M = 85.58 ± 15.57) (9)

As regarding socio-economical state of the patient’s family, the Mean ±SD monthly income of the family 2557.91 ±957.666. according to Number of chambers in the house mean ±SD 2.96 ± 0.75, and Crowding index included 5 in room 12 (3.06%), 3-4 in room n180(45.92%), 2 in room 132 (33.67%) and less than 2 in room 68(17.35%)

We also founded that number of working mothers 73 (18.62%) and not working 319(81.38%) while number of working fathers 314(80.1%) and not working 78(19.9%).

Our study founded that residence distribution at children with SS in relation to different WHO QOL domains was of no significant value although it was in favor with urban residency.

Other evidence in support of environmental channels is the decline in the correlation between height and intelligence over time observed in the Scandinavian countries (10)

On the other hand, found a moderate molecular genetic correlation between height and intelligence. Furthermore, the majority of the phenotypic correlation between the traits can be explained by shared genetic influences (11)

In other literature they demonstrated that the short children have lower social competence and show more social problems than children with normal stature. These findings confirm theories which state that physical appearance has an influence on people's social environments, which might in turn influence social and personality development (12).

Conclusion:

Pediatric patients with SS have lower HRQOL compared to healthy individuals especially in physical, psychological and environmental aspects. Social domain is the most affected among SS children.

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References:

1. Rogol, A. D. J. U. O. 2016. Causes Of Short Stature. 14.

2. Wit, J. M., Oostdijk, W., Losekoot, M., Van Duyvenvoorde, H. A., Ruivenkamp, C. A. & Kant, S. G. J. E. J. O. E. 2016. Mechanisms In Endocrinology: Novel Genetic Causes Of Short Stature. 174, R145-R173.

3. Bullinger M, Quitmann J, Power M, Herdman M, Mimoun E, Debusk K, Rohenkohl A. Assessing The Quality Of Life Of Health-Referred Children And Adolescents With Short Stature: Development And Psychometric Testing Of The Qolissy Instrument. Health Qual Life Outcomes, 2013, 11(1), 1.

4. Chaplin Je. Growth-Related Quality Of Life. Horm Res Pediatric .2011;76:51–52.

5. Golami A, Jahormi L, Zari E, Dehghan A. The World Health Organization's Whoqol-Bref Quality Of Life Assessment: Psychometric Properties And Results Of The International Field Trial. A Report From The Whoqol Group. Int J Prev Med.2013;4(7): 809-817

6. Garganta Md, Bremer Aa. Clinical Dilemmas In Evaluating The Short Child.

Pediatric Ann. 2014 Aug;43(8):321-7.

7. Bloemeke, J., Valdez, R. B., Mauras, N., Mericq, V., Ross, J., Permuy, J., Quitmann, J., Bullinger, M. J. J. O. P. E. & Metabolism 2019. Psychometric Performance Of The Quality Of Life In Short Stature Youth (Qolissy) Questionnaire In A Randomized Open-Label Comparator Trial In Idiopathic Short Stature. 32, 1089- 1101.

8. Wheeler P G, Bresnahan K, Shephard B A, Lau J, Balk E M. Short Stature And Functional Impairment A Systematic Review. Arch Pediatr Adolesc Med, 2004;158(3):236-243.

9. Rohenkohl, A., Stalman, S., Kamp, G., Bullinger, M. & Quitmann, J. J. E. J. O.

P. 2016. Psychometric Performance Of The Quality Of Life In Short Stature Youth (Qolissy) Questionnaire In The Netherlands. 175, 347-354

10. Sundet, J. M., Tambs, K., Harris, J. R., Magnus, P., Torjussen, T. M. J. T. R. &

Genetics, H. 2005. Resolving The Genetic And Environmental Sources Of The Correlation Between Height And Intelligence: A Study Of Nearly 2600 Norwegian Male Twin Pairs. 8, 307-311.

11. Marioni, R. E., Batty, G. D., Hayward, C., Kerr, S. M., Campbell, A., Hocking, L. J., Scotland, G., Porteous, D. J., Visscher, P. M. & Deary, I. J. J. B. G. 2014.

Common Genetic Variants Explain The Majority Of The Correlation Between Height And Intelligence: The Generation Scotland Study. 44, 91-96.

12. Visser-Van Balen, H., Geenen, R., Moerbeek, M., Stroop, R., Kamp, G. A., Huisman, J., Wit, J. M. & Sinnema, G. J. H. R. I. P. 2005. Psychosocial Functioning Of Adolescents With Idiopathic Short Stature Or Persistent Short Stature Born Small For Gestational Age During Three Years Of Combined Growth Hormone And Gonadotropin-Releasing Hormone Agonist Treatment. 64, 77-87.

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