(2023) 17:23
Shigeyasu et al. BioPsychoSocial Medicine
https://doi.org/10.1186/s13030-023-00278-1

BioPsychoSocial Medicine

Open Access

RESEARCH

Quality of life and physical/psychosocial
factors in children and adolescentswith orthostatic intolerance
Yoshie Shigeyasu1* , Ayumi Okada1, Chikako Fujii1, Chie Tanaka1, Akiko Sugihara2, Makiko Horiuchi2,
Takashi Yorifuji3 and Hirokazu Tsukahara1

Abstract
Background Orthostatic intolerance (OI), which is common in children and adolescents, negatively impacts their
quality of life (QOL) due to physical symptoms that limit work, school, and daily activities. The purpose of this study is
to explore the association of physical and psychosocial factors with QOL scores in children and adolescents with OI.
Methods A cross sectional observational study was conducted. The study participants included 95 Japanese pediatric patients of age 9–15 years who were diagnosed with OI from April 2010 to March 2020. The QOL scores and the
QOL T-scores of children with OI assessed using the KINDL-R questionnaire at the initial visit were compared with conventional normative data. The associations of physical and psychosocial factors with the QOL T-scores were examinedusing multiple linear regression.
Results Pediatric patients with OI had significantly lower QOL scores than healthy children in both elementary(50.7 ± 13.5 vs. 67.9 ± 13.4, p < 0.001) and junior high schools (51.8 ± 14.6 vs. 61.3 ± 12.6, p < 0.001). This finding wasobserved in the physical, mental, self-esteem, friends, and school domains. Total QOL scores were significantly associated with school nonattendance (β =  − 3.2, 95% confidence interval [CI] =  − 5.8 to − 0.5, p = 0.022) and poor relationship with school (β =  − 5.0, 95% CI =  − 9.8 to − 0.4, p = 0.035).
Conclusions These results suggest that the assessment of QOL, including both physical and psychosocial aspects,
especially school factors, needs to be implemented earlier in children and adolescents with OI.
Keywords Quality of life, Orthostatic intolerance, Psychosomatic factors, School nonattendance, Postural orthostatic
tachycardia syndrome, School-aged children, Adolescence*Correspondence:
Yoshie Shigeyasu
shigeyy@s.okayama-u.ac.jp
1
Department of Pediatrics, Okayama University Graduate Schoolof Medicine, Dentistry and Pharmaceutical Sciences, 2‑5‑1, Shikata‑Cho,
Kita‑Ku, Okayama 7008558, Japan
2
Clinical Psychology section, Department of Medical Support, Okayama
University Hospital, 2‑5‑1, Shikata‑Cho, Kita‑Ku, Okayama 7008558, Japan3
Department of Epidemiology, Okayama University Graduate Schoolof Medicine, Dentistry and Pharmaceutical Sciences, 2‑5‑1, Shikata‑Cho,
Kita‑Ku, Okayama 7008558, Japan

Background
Orthostatic intolerance (OI), which is common in children and adolescents, can be defined as having difficultytolerating the upright posture because of symptoms
that abate when the patient returns to the supine position [1, 2]. The clinical symptoms are diverse, including
chronic fatigue, headache, dizziness, exercise intolerance, and syncope because of dysregulation of the autonomic nervous system and cardiovascular compensatory
mechanisms [2–4]. The subtypes of OI include postural
orthostatic tachycardia syndrome (POTS), orthostatic© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of thislicence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​
mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Shigeyasu et al. BioPsychoSocial Medicine(2023) 17:23

hypotension (OH), and vasovagal syncope (VVS), which
are evaluated based on chronic symptoms and orthostatic tests, either the active standing test or the head-up
tilt test [2, 5, 6].
OI is not life-threatening and 86% of patients with
POTS reported improved OI symptoms after 5 years
from diagnosis [7]. In contrast, it can severely impair
work, school, and daily activities [7–9] and reduce QOL[8–13]. Early psychological support is likely to be important in preventing QOL deterioration and associated secondary factors, such as reactive depression, avoidance,and physical deconditioning [14].
In adult studies, multiple physical symptoms havebeen implicated in reduced QOL [10–12]. Compared tophysical factors, the relationship between QOL and psychosocial factors in patients with OI has not been fully
elucidated. Moreover, all previous studies included adultor adolescent patients, and the QOL in children and adolescents with OI remains unclear.
This study aimed to quantify QOL scores and determine the association of physical and psychosocial factors
with QOL in children and adolescents with OI.

Methods
Participants and measures

In this cross sectional observational study, the medical
records of 95 outpatients aged between 9–15 years who
were diagnosed with OI at the Department of Child Psychosomatic Medicine in the Okayama University Hospital, Japan from April 2010 to March 2020 were reviewed.
Basic clinical information at the initial visit was extracted
from the electronic medical records, including age, sex,
school year, the period from the onset, subtypes andseverity of OI, experiences already diagnosed with OI,
and comorbidities.
OI was diagnosed based on symptoms and the active
standing test, defined by the Japanese Clinical Guidelines [5, 15]. Other disorders that could cause similar clinical symptoms of orthostatic intolerance were
excluded based on the guidelines. In the active standing
test, blood pressure and heart rate were measured threetimes after 10 min of rest in the supine position andfive times upon standing (after 1, 3, 5, 7, and 10 min),and the initial recovery time of blood pressure fromthe fall after standing up was measured. We evaluatedsubtypes depending on the result of the active standing test. The subtypes included the following four forms[5]: (1) instantaneous orthostatic hypotension (INOH),(2) POTS, (3) neurally mediated syncope (NMS), and(4) delayed orthostatic hypotension (delayed OH). If
the patients had orthostatic symptoms but did not meetthe four subtypes, cerebral blood flow was measured
using near-infrared spectroscopy in the active standing

Page 2 of 9

test. The orthostatic cerebral hypoperfusion type was
evaluated in which cerebral oxygenated hemoglobin
decreases by more than 4 μmol/l [15]. According to theseverity, it is divided into severe or mild forms. In theJapanese guidelines, only INOH and POTS are defined
as severe and mild forms, depending on the degree ofheart rate increase or initial recovery time of bloodpressure using the active standing test [5]. Participants
with severe forms of INOH and POTS were assigned
to the severe group, whereas those with mild forms of
INOH and POTS, delayed OH, and orthostatic cerebral
hypoperfusion were assigned to the mild group. Physical diseases as comorbidities were diagnosed based on
the ICD-10 [16]. Psychiatric disorders and neurodevelopmental disorders as comorbidities were diagnosed
using the fifth edition of the Diagnosis and Statistical
Manual of Mental Disorders [17].
Quality of life questionnaire

We used the Japanese version of KINDL-R to assess
the health-related QOL [18, 19]. The self-administered
KINDL-R questionnaire [20] is a German-language tool
designed to study the health-related QOL in children
and adolescents by evaluating the following subscales:
physical wellbeing, emotional wellbeing, self-esteem,
and family-, friend-, and school-related QOL. Each ofthese six subscales consists of four items that are each
rated on a 5-point Likert scale. The mean scores foreach subscale and a total QOL score are calculated ona scale from 0 to 100, with higher values corresponding to better/higher QOL. The KINDL-R questionnaire
is validated in Japanese. The following versions of the
KINDL-R questionnaire are available as self-reportmeasures for different age groups: Kid-KINDL [18] forchildren in elementary schools, and Kiddo-KINDL [19]for adolescents in junior high schools (Japanese version). The data were standardized for 3702 and 2306
students, respectively, out of 4607 students from 19 elementary schools and 2926 students from 9 junior highschools in Japan, who responded that they had no disease currently under treatment at a hospital.
Children and adolescents filled in the KINDL-R questionnaire at the first visit. A total of 21 patients out of
95 did not answer enough items on each subscale. Thus,
blank subscale and total QOL scores could not be calculated, and only subscale scores answered were includedin the results. We also converted the QOL scores to ageand sex-matched T-scores with a mean of 50 and standard deviation (SD) of 10 using reference values from 6008
healthy Japanese children and adolescents [3702 elementary school students by Kid-KINDL [18] and 2306 juniorhigh school students by Kiddo-KINDL [19].

Shigeyasu et al. BioPsychoSocial Medicine(2023) 17:23

Evaluation of psychosocial factors

The following psychosocial factors were selected fromthe reference to the psychosocial evaluation for pediatric psychosomatic disorders [21]. The psychosocial status, which includes the number of parents living withchildren, family psychiatric disorders, academic grades,
relationship with school, school nonattendance, social
problems, and activities outside of school, were takenfrom the parents’ medical interview sheet at the timeof the initial visit. The number of parents living withchildren was defined by the number of parents living
together. Academic grades and relationship with school
were divided into good or not-good based on the parents’ subjective responses in the initial medical questionnaire. Social problems were divided by whether
or not they had bullying or interpersonal problems.
School nonattendance was considered if the OI patient
was absent from school for more than half of the pastmonth.
Statistical analysis

After the descriptive analysis, we used a t-test to compare the (raw) QOL scores as well as the QOL T-scores
between children with OI and healthy children. The reference values of the healthy children were obtained fromthe above-mentioned references [18, 19] and almost
normally distributed [22]. We also compared the QOL
T-scores separated by demographic groups (i.e., sex,
school levels, and comorbidity) among children with
OI and performed the t-test to examine the difference.
We then examined the associations of physical and psychosocial factors with the QOL T-scores using multiple
linear regression. Multiple regression analysis was performed with QOL T-scores as dependent variables andeach psychosocial factor (binary) as independent variables, controlling for sex (binary), school levels (binary:elementary school; junior high school), and presence ofcomorbidities (binary). The variance inflation factors(VIFs) were tested to identify the degree of multicollinearity in all models. The VIFs of the nine items as physical and psychosocial factors, as well as three items related
to characteristics were less than 1.5, indicating no multicollinearity. We estimated regression coefficients (β) with
95% confidence intervals (CIs). All statistical analyses
were performed using JMP 10 (SAS Institute Inc., Cary,
NC, USA). P values less than 0.05 were considered statistically significant.
Ethical approval

This study was approved by the Ethics Committee of
the Okayama University Graduate School of Medicine,

Page 3 of 9

Dentistry, and Pharmaceutical Science and Okayama
University Hospital (No. 2006–005).

Results
Patient demographics and orthostatic intolerance status

A total of 95 participants were included in this study(Fig. 1). Patient demographics and OI data are presented in Table 1. The average age was 12.9 ± 1.4 years,
47 were male, and 19 were enrolled in elementary
school. The mean period from onset to the first visit was
9.9 ± 8.3 months. Comorbidities with physical diseases in
28 cases include irritable bowel syndrome, allergic rhinitis, migraine, atopic dermatitis, functional dyspepsia,
chronic sinusitis, obesity, ventricular septal defect, scoliosis, precocious puberty, nephropathy IgA, and Marfan
syndrome.
Quality of life and T‑scores

Mean and SD for each of the separate KINDL-R subscales
and total QOL scores and T-scores are shown in Table 2.
Patients with OI had significantly lower QOL scoresthan healthy children, in both elementary (50.7 ± 13.5
vs. 67.9 ± 13.4, p < 0.001) and junior high school students(51.8 ± 14.6 vs. 61.3 ± 12.6, p < 0.001). In the six subscales,
the QOL T-score for physical wellbeing was the lowest,
38.2 ± 14.3. Emotional wellbeing, self-esteem, friend-,and school-related QOL T-scores were significantly
lower than the healthy group.
Females reported lower QOL T-scores in friend- andschool-related subscales compared with males. Elementary school students reported more impairment in physical and friend-related QOL compared to junior highschool students. Patients with comorbid neurodevelopmental disorders had lower emotional, self-esteem, family, and total QOL scores than those without comorbidity(Table 3).
Physical and psychosocial factors associated with qualityof life

Table 4 showed the associations of physical and psychosocial factors with the QOL T-scores. PhysicalQOL was affected by experiences already diagnosed
with OI (β =  − 2.9, 95%CI =  − 5.8 to − 0.1, p = 0.044)
and school nonattendance (β =  − 3.8, 95%CI =  − 6.9
to − 0.7, p = 0.016). Emotional QOL was associated withschool nonattendance (β =  − 2.9, 95%CI =  − 5.7 to − 0.1,
p = 0.048) and social problem (β =  − 3.2, 95%CI =  − 6.3
to − 0.2, p = 0.039). Friend-related and total QOL
was affected by the relationship with school (friend:β =  − 10.7, 95%CI =  − 15.3 to − 6.1, p < 0.001; total QOL:β =  − 5.0, 95%CI =  − 9.8 to − 0.4, p = 0.035) and school
nonattendance (friend: β =  − 3.7, 95%CI =  − 7.0 to − 0.4,

Shigeyasu et al. BioPsychoSocial Medicine(2023) 17:23

Page 4 of 9

Fig. 1 Diagnostic criteria for orthostatic intolerance in this study. a: based on reference 5. b: based on references 15. BP, blood pressure; INOH,
instantaneous orthostatic hypotension; SBP, systolic blood pressure; delayed OH, delayed orthostatic hypotension; HR, heart rate; POTS, postural
orthostatic tachycardia syndrome; OI, orthostatic intolerance

p = 0.029; total QOL: β =  − 3.2, 95%CI =  − 5.8 to − 0.5,
p = 0.022).

Discussion
Quality of life in children and adolescents with orthostatic
intolerance

To our knowledge, this study is the first report that quantifies the QOL scores in children and adolescents withOI. Similar to the results of several previous studies inadults [8, 9, 12, 13], the QOL of the pediatric patientswith OI was significantly lower than that of the healthygroup. Compared with other chronic diseases [headache[23], type 1 diabetes [24], asthma [25]] assessed by QOL
with KINDL-R, low scores in OI are noted.
Several previous studies have examined the QOL ofphysical versus mental parameters in adult patientswith POTS [8–14]. Physical QOL in patients with
POTS is reduced in these studies. One of them reported

Shigeyasu et al. BioPsychoSocial Medicine(2023) 17:23

Page 5 of 9

Table 1 Demographic and clinical characteristics of the patientswith OI
Characteristics
Patients, n

95

Age (years), Mean (SD)12.9 (1.4)

Sex, nMale

47

Female48

School level, nElementary school (9–12 years)

19

Junior high school (13–15 years)

76

Period until the first visit (months), Mean (SD)

9.9 (8.3)

Experience already diagnosed with OI, n
Yes

43

No

52

Comorbidities, nPhysical diseases

28

Psychiatric disorders

7

Neurodevelopmental disorders

40

OI Orthostatic intolerance, SD Standard deviationthat physical QOL scores are as low as that in chronic
obstructive pulmonary disease and congestive heart failure [9]. On the contrary, mental QOL remains controversial. Some studies revealed that mental parameters
did not significantly differ between patients and healthy
subjects [9, 13], and other studies showed significant
impairment in both physical and mental QOL in patientscompared with healthy subjects [8, 10–12].
In this study, we investigated six parameters of QOL.
QOL in children with OI was significantly reduced in

multiple parameters, including physical wellbeing, emotional wellbeing, self-esteem, friend, and school parameters. The results showed that OI had a multidisciplinary
impact on child and adolescent patients. Moreover,elementary school students and the female group represented lower QOL scores. Younger adult patients with
POTS were reported to have lower functional capacity
than expected compared to older patients [13]. Similarly,
younger children can be more susceptible to environmental influences.
Therefore, we suggest that QOL should be assessed as
the first step to evaluating both the physical and the psychosocial aspects.
Association of physical and psychosocial factors
with quality of life

In recent years, multiple physical factors associated with
QOL in adult patients with POTS were reported. For
instance, QOL scores were linked to some symptoms,
such as sleep impairment, lightheadedness, dizziness,headache, and concentration difficulties [10–12]. Additionally, even patients with mild OI symptoms had significantly reduced QOL [10]. No correlation of QOL scoreswith heart rate or blood pressure was reported [10, 11].
In this study, there was no clear association between
QOL and severity of OI including the degree of heart rateincrease or initial recovery time of blood pressure.
In the adult field, there have been few studies on psychosocial factors related to QOL in patients with OI.
In this study, five factors were found to be significantly
related to QOL: experiences already diagnosed with
OI, family with psychiatric disorders, relationship withschool, school nonattendance, and social problems. In

Table 2 KINDL-R QOL raw scores and T-scores for OI patients and healthy controlsnPhysicalEmotional

Self-esteem

FamilyFriends

SchoolTotal

Mean (SD)QOL scores (Kid KINDL: elementary school students)
OIb

Healthy ­controls

1941.0 (18.2)#

67.8 (18.1)**

25.4 (28.4)#

67.4 (20.3)

45.1 (18.4)#

44.1 (22.2)**

50.7 (13.5)#

3702

77.2 (16.9)

79.3 (17.5)

53.7 (24.6)

68.9 (19.6)

69.8 (18.0)

58.4 (20.0)

67.9 (13.4)

QOL scores (Kiddo KINDL: junior high school students)
OIb

Healthy ­controls

7649.1 (25.3)#

67.3 (22.1)*

20.6 (21.5)#

71.5 (21.2)

60.6 (24.9)#

44.5 (22.8)#

51.8 (14.6)#

2306

65.9 (17.8)

72.3 (17.7)

35.4 (22.1)

66.7 (21.1)

71.0 (17.0)

52.6 (12.6)

61.3 (12.6)

95c

38.2 (14.3)#

44.1 (12.6)#

42.3 (9.7)#

51.3 (10.1)

42.1 (14.5)#

45.0 (11.7)#

41.2 (11.2)#

6008

50 (10)50 (10)50 (10)50 (10)50 (10)50 (10)50 (10)T-scoresa
OIb

Healthy ­controls

Significant difference for the t-test: *p < 0.05, **p < 0.01, #p < 0.001
QOL Quality of life, OI Orthostatic intolerance, SD Standard deviationaT-score was calculated and compared with age- and sex-matched normative datab

Healthy controls data for reference 18 and 19c

QOL scores include missing data; of 95, 1 in physical, 2 in emotional, 1 in self-esteem, 2 in family, 8 in friends, 16 in school, and 21 in total are missing

76

Junior high school

67

No

88

No

55

No

QOL Quality of life, OI Orthostatic intolerance, SD Standard deviation

Significant difference for t-test, * p < 0.05, ** p < 0.01

40

Yes

Comorbidity with neurodevelopmental disorders

7

Yes

Comorbidity with psychiatric disorders

28

Yes

Comorbidity with physical diseases

19

Elementary school

School level

47
48

Male

FemaleSexnTable 3 QOL T-score and demographic variable of OI patients

38.6 (14.3)

37.6 (14.7)

37.8 (14.8)

44.0 (6.8)

37.6 (14.9)

39.6 (13.4)

40.6 (14.3)

29.0 (10.8)**

37.2 (15.1)

39.2 (13.8)

Physical46.2 (12.4)

41.3 (12.6)*

44.1 (12.9)

44.6 (10.0)

45.1 (12.5)

41.7 (13.1)

44.6 (13.1)

42.5 (11.0)

46.1 (11.6)

42.2 (13.5)

Emotional

44.1 (9.7)

39.8 (9.5)*

42.2 (10.0)

43.7 (7.3)

42.1 (10.1)

42.7 (9.2)

42.8 (9.5)

40.2 (11.0)

42.1 (9.6)

42.4 (10.0)

Self-esteem

53.9 (9.3)

48.3 (10.5)*

51.3 (10.2)

54.5 (9.7)

52.8 (9.9)

48.7 (10.3)*

52.3 (10.0)

48.6 (10.5)

52.4 (9.4)

50.7 (10.9)

Mean (SD)Family42.5 (15.9)

41.4 (13.0)

43.2 (13.9)

23.7 (15.7)*

42.0 (15.1)

42.1 (13.7)

43.6 (15.2)

36.6 (10.4)**

46.7 (12.8)

42.8 (10.0)

44.8 (12.0)

48.5 (3.7)

44.5 (11.8)

46.1 (11.8)

45.1 (12.1)

44.3 (10.6)

49.1 (10.9)
39.5 (10.7)**

45.6 (12.9)

School38.3 (15.5)*

Friends

43.4 (11.2)

38.3 (11.0)*

41.3 (11.4)

39.3 (12.2)

41.5 (11.6)

40.3 (10.9)

42.1 (11.6)

37.8 (9.9)

39.3 (12.1)

42.5 (10.7)

Total

Shigeyasu et al. BioPsychoSocial Medicine(2023) 17:23
Page 6 of 9

43

Yes

22

44

51

No

Yes

64

Yes

73

31

No

Yes

9

Not good

No

86

23

Good

72

Not good

17

Good

78

Yes

38.4

38.0

35.2

39.2

36.2

42.3

34.2

38.6

39.2

37.9

41.4

37.5

33.8

No

39.5

74

35.0

41.0

36.5

39.2

a single parent 21

two parents

52

33

Severe

No

62

Mild

T-scorePhysicalEmotional

41.9

42.7

45.0

T-score

46.2

40.6

44.5

43.5

44.3

40.4

45.0

43.9

44.2

0.7(-2.2, 3.6)

-2.4(-5.8, 1.1)
44.6

43.7

40.1

45.4

-3.8(-6.9, -0.7)* 43.1

-3.6(-8.5, 1.3)

-0.4(-3.9, 3.2)

1.3(-2.4, 5.0)

-2.8(-6.2, 0.7)

-2.9(-5.8, -0.1)* 46.9

-0.7(-3.8, 2.4)

β (95%CI)a

43.5

39.1

42.6

40.0

43.0

41.6

42.4

41.6

42.5

42.9

41.8

41.1

42.9

42.7

0.1(-2.5, 2.8)

42.4

42.1

-3.2(-6.3, -0.2)* 40.8

0.1(-1.9, 2.2)

-0.9(-3.4, 1.5)

-1.2(-3.4, 1.1)

-2.2(-5.7, 1.3)

-1.6(-4.0, 0.8)

-0.4(-3.1, 2.2)

-0.2(-2.7, 2.3)

0.4(-1.7, 2.5)

-0.8(-3.0, 1.4)

β (95%CI)a

Self-esteem
T-score-2.9(-5.7, -0.1)* 41.7

-3.0(-7.4, 1.4)

-0.1(-3.3, 3.1)

2.0(-5.5, 1.2)

0.5(-2.7, 3.7)

2.0(-0.6, 4.6)

-0.7(-3.4, 2.0)

β (95%CI)a

Family

52.9

50.0

49.6

52.1

51.6

51.5

50.5

51.6

48.6

52.4

46.9

52.5

48.5

52.3

54.1

49.3

51.8

51.3

T-score1.3(-0.8, 3.3)

-1.5(-4.0, 1.0)

-0.9(-3.2, 1.4)

-1.6(-5.1, 1.9)

-1.8(-4.3, 0.7)

-2.8(-5.4, -0.2)*-1.4(-3.9, 1.1)

1.9(-0.2, 4.0)

0.7(-1.5, 2.9)

β (95%CI)a

Friends

43.0

41.0

36.3

43.7

39.5

47.2

24.7

44.1

39.9

42.8

41.8

41.1

41.3

42.3

42.5

41.7

38.6

44.1

1.1(-2.0, 4.2)

-2.9(-6.7, 0.8)

-3.7(-7.0, -0.4)*-10.7(-15.3, -6.1)**-1.6(-5.3, 2.1)

-0.3(-4.3, 3.7)

-0.2(-3.9, 3.6)

0.2(-3.0, 3.3)

-3.0(-6.1, 0.2)

T-score β (95%CI)aa

Adjusted for sex, school levels (elementary school or junior high school) and presence of comorbidities

QOL Quality of life, OI Orthostatic intolerance

Missing value are included : of 95 patients, 1 in physical, 2 in emotional, 1 in self-esteem, 2 in family, 8 in friends, 16 in school, and 21 in total are missing.

Significant difference, *p<0.05, **p<0.01

Activities
outside ofschoolSocialproblemSocial factor

SchoolnonattendanceRelationshipwith school

Academic
grade

School factor

Family withpsychiatricdisordersNumberof parents
living withchildren

Family factor

Experiences
alreadydiagnosedwith OI

Severityof OI

Disease factornTable 4 Multiple linear regression analysis for QOL T-scores based on physical and psychosocial factors
School

46.0

43.8

41.4

46.0

44.2

46.3

43.3

45.1

41.1

46.2

46.5

44.7

41.1

46.2

45.6

44.5

45.6

44.6

T-score0.5(-2.0, 3.0)

-0.9(-3.9, 2.0)

-0.2(-2.8, 2.4)

-0.3(-5.0, 4.3)

-1.3(-4.3, 1.7)

1.0(-2.3, 4.3)

-2.4(-5.2, 0.5)

0.1(-2.5, 2.6)

-0.6(-3.2, 2.0)

β (95%CI)a

Total

41.8

40.4

38.4

41.9

39.0

44.6

33.0

41.9

38.0

42.0

38.7

41.7

38.9

41.8

43.0

39.8

40.5

41.5

T-score0.5(-2.2, 3.1)

-1.4(-4.6, 1.9)

-3.2(-5.8, -0.5)*-5.0(-9.8, -0.4)*-1.5(-4.8, 1.9)

-1.7(-5.2, 1.7)

-1.2(-4.3, 1.9)

1.1(-1.6, 3.8)

-0.8(-3.5, 2.0)

β (95%CI)a

Shigeyasu et al. BioPsychoSocial Medicine(2023) 17:23
Page 7 of 9

Shigeyasu et al. BioPsychoSocial Medicine(2023) 17:23

particular, school-related factors severely impaired the
QOL of multiple parameters and total scores. One reason for this is that pediatric patients with OI who havedifficulty attending school are deprived of opportunities to learn and built friendships. As a result, theiracademic performance and social functioning may be
adversely affected. This is thought to be a characteristicof pediatric patients with OI. It has been reported thatchildren with psychosomatic disorders have lower selfesteem [26], especially in the academic area [27]. Therefore, in addition to physical treatment, a psychosocial
approach should be emphasized to improve the QOL of
OI patients.
In this study, 42.1% of OI patients had comorbid neurodevelopmental disorders. Neurodevelopmental disorders such as autism spectrum disorder (ASD) andattention-deficit/hyperactivity disorder (ADHD) havebeen reported to be associated with a high prevalenceof comorbidity with migraine, asthma, and other physical disorders [28, 29]. In OI, adult patients with POTS
were reported to score significantly higher than controls on the inattention and ADHD subscales [30]. ASD
is linked to autonomic dysfunction [31]. However, therelationship between OI and neurodevelopmental disorders has not been well reported. The poor QOL in
multiple domains could be the result of the addition ofphysical symptoms and difficulties caused by OI to thedifficulties in their lives caused by neurodevelopmental disorders. Further investigation into the associationof OI with neurodevelopmental disorders is therefore
needed.
Limitations of this study and future directions

There are several limitations to this study. First, allpatients were recruited from a single hospital, so there
may be a problem with the generalizability of the findings. Since this hospital deals with referral patients, thetarget patients may be severely ill and have significant
psychosocial factors. Second, about one-fourth of theparticipants did not completely answer the KINDLR questionnaire, resulting in missing values. This may
have resulted in overestimation or underestimation of
QOL scores. Third, in this study, we did not consider theparental economic status or educational level as psychosocial factors. Further research is needed in the future.

Conclusions
This study found that QOL in children and adolescentswith OI was significantly lower scores than in healthy
children in multiple categories, including physical,
emotional, self-esteem, friend, and school. Moreover,investigations of psychosocial factors revealed that notgood relationships with school, nonattendance school,

Page 8 of 9social problems, and family psychiatric disorders wereassociated with reduced QOL. These findings suggestthat the assessment of QOL including physical and psychosocial factors is valuable. In pediatrics OI, particular attention should be paid to school-related factors.
Abbreviations
ADHD
Attention-deficit/hyperactivity disorder
ASD
Autism spectrum disorderCIConfidence intervaldelayed OH Delayed orthostatic hypotension
INOH
Instantaneous orthostatic hypotension
NMS
Neurally mediated syncope
OH
Orthostatic hypotension
OI
Orthostatic intolerance
POTS
Postural orthostatic tachycardia syndrome
QOL
Quality of lifeSD
Standard deviation
VVS
Vasovagal syncope
VIF
Variance inflation factor
Acknowledgements
We would like to thank all the children and their families who participated inthis study. We thank Dr. Junichi Furusho for permission to use the Japaneseversion of KINDL-R.
Authors’ contributions
YS, AO, CF, CT, AS, and MH contributed to the study’s conception and design.
YS, AO, and CF collected the data. TY supervised the statistical analysis. YS
wrote the first draft of the manuscript and AO and HT revised it critically forimportant intellectual content. All authors contributed to the interpretation of
data; drafting and revision of the manuscript, and approved the final versionof the manuscript.
Funding
This study was supported by JSPS KAKENHI (Grant Number JP19K17364 to YS).
Availability of data and materials
Not applicable.

Declarations
Ethics approval and consent to participate
This study was approved by the Ethics Committee of the Okayama University
Graduate School of Medicine, Dentistry, and Pharmaceutical Science andOkayama University Hospital (No. 2006–005).
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Received: 23 July 2022 Accepted: 24 May 2023

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