Youth with functional abdominal pain disorders have more sleep disturbances. A school-based study

Abstract

Background

There is a bidirectional relationship between sleep and pain disturbances. Sleep disturbances increase the risk for chronic pain, while chronic pain can interfere with sleep. Hence, we assessed the subjective sleep characteristics of youth with functional abdominal pain disorders (FAPDs) compared to healthy youth and examined associations with gastrointestinal symptoms.

Methods

We included youth ages 10-18 years without a sleep or organic GI disorder diagnosis from a large private school. Participants completed demographics, sleep history, and validated questionnaires: sleep quality (ASWS-SF), insomnia (PISI), daytime sleepiness (ESS), sleep disturbance (PROMIS SD), sleep-related impairment (PROMIS SRI), and Rome 4 diagnostic questionnaire. Cases (FAPDs) completed abdominal pain index (API), nausea severity (NSS), anxiety, depression (PROMIS), and functional disability (FDI). Parents filled sleep hygiene metrics (SHIP). Cases were matched 1:1 with controls based on age and gender.

Results

Of 120 youth (60 cases and 60 controls), the mean age was 13.5 ± 1.9y and 50% were females. Youth with FAPDs had higher insomnia, sleep disturbance, sleep-related impairment, daytime sleepiness, sleep hygiene, gasping, and nightmares than healthy youth (p<0.05). Higher insomnia severity was associated with worse abdominal pain (r=0.41, p<0.01), higher daytime sleepiness with a family history of disorders of gut-brain interaction (DGBIs, OR=14.7, p=0.002) and higher sleep-related impairment (OR=5.6, p=0.02) and depression (OR=6.1, p=0.01) with black race.

Conclusion

Youth with FAPDs have worse sleep than healthy youth and multiple sleep parameters are associated with abdominal pain. Future studies could focus on determining mechanisms by which sleep disturbances affect abdominal pain and vice versa.

Graphical Abstract

Youth with functional abdominal pain disorders have worse sleep than healthy youth and sleep disturbances are associated with abdominal pain. This highlights the need for investigation of mechanisms by which sleep disturbances affect abdominal pain and vice versa.

INTRODUCTION

Disorders of Gut-Brain Interaction (DGBIs) are one of the most common pediatric gastrointestinal disorders. DGBIs include functional abdominal pain disorders (FAPDs), notably functional dyspepsia (FD), irritable bowel syndrome (IBS), abdominal migraine, and functional abdominal pain – not otherwise specified (FAP-NOS)].¹ FAPDs affect up to 25% of youth and adolescents worldwide.² Youth with FAPDs often present with significant pain and disability. Literature on FAPDs in South American populations has historically been sparse. However, emerging data shows that South American youth have a higher FAPDs prevalence rate (16.8%)³ compared with North American (13.4%)³ and European (10.5%) samples.³ Colombian youth with FAPDs present with high levels of somatic complaints and anxiety, along with diminished coping efficacy.^4-6

Sleep disruption (e.g., insomnia, poor sleep quality) is also prevalent in youth with FAPDs,^7-12 and may interact bidirectionally with pain. For example, pain may disrupt normal sleep patterns and negatively impact perceptions of sleep quality, and in turn, sleep disturbances may enhance pain sensitivity and risk for future pain.^13,14 Data suggests sleep impacts pain more often than vice versa.¹⁵ Psychological constructs such as anxiety and depression may also mediate the relationship between sleep and pain. Poor sleep quality and insomnia have been described, but there is limited data on other sleep complaints such as parasomnia, sleep-disordered breathing, and daytime sleepiness, and the impact of these complaints with pain, disability, and psychological distress in youth with FAPDs, especially in South American populations.^16,17 Moreover, demographic, and other social factors (e.g., attending private schools¹⁶ and divorced parental status^18,19) affect the prevalence and severity of DGBIs in Colombian youth. However, sleep disturbances and their impact on these constructs have not been investigated.

For the current study, we used several subjective measures tapping different sleep domains (sleep disturbance and related impairment, insomnia, daytime sleepiness) in Colombian youth diagnosed with FAPDs and healthy youth. We hypothesized that youth with FAPDs would report worse sleep disturbance, sleep-related impairment and insomnia, as well as greater daytime sleepiness compared to healthy youth. We also examined the associations of measured sleep domains with physical and psychological symptoms. We hypothesized that worse sleep disturbance, sleep-related impairment and insomnia, as well as greater daytime sleepiness would be associated with worse gastrointestinal (GI) symptoms and psychological functioning.

METHODS

Approval was obtained from the Institutional Review Board and Human Subjects Committee of Hospital Universitario del Valle of Cali, Colombia, as well as the Academic Authority of a large private school in Cali, Colombia. Youth 10 to 18 years of age without any self-reported organic GI and sleep disorders were recruited. Cases included those who met the Rome IV criteria¹ for non-episodic FAPDs (FD, IBS, and FAP-NOS). Controls were healthy youth without any self-reported medical concerns and in good health. They were matched 1:1 with cases based on age and gender. Youth received instructions from the research team to complete the study questionnaires. At the end of the instruction session, youth were encouraged to ask for clarification on questions or wording they may have not understood. A research team member was present during study completion to assure confidentiality and provide assistance in case the participants had difficulties completing the questionnaires. Participants completed demographic data including age, gender, race, household structure, and questions related to birth, past, medication and family history. According to WHO guidelines, height and weight were collected using a stadiometer and digital scale.²⁰ The body mass index (BMI) was calculated according to the Quetelet index = weight (kilograms)/height (meters squared).²¹ Malnutrition per WHO classification included overweight plus obesity (more than +1 SD according to BMI).²⁰

Participants completed validated questionnaires about sleep, a survey on their sleep history, pre-sleep activities over the past two weeks (answering yes/no to reading books or doing homework, eating, playing video games, watching television, relaxing, talking on the phone, using a computer or another electronic device), and current stress level (numeric rating scale 1-10). Cases completed validated questionnaires regarding their GI symptoms and psychological functioning (Appendix A). Parents completed a questionnaire about their child’s sleep hygiene.

Spanish translation and validation of questionnaires:

All questionnaires were initially developed in English. For use in the study, the questionnaires were translated into Spanish and then adapted into the local language by three bilingual physicians of the Functional International Digestive Epidemiological Research Survey (FINDERS). The Spanish versions were also reverse translated for reliability evaluation by comparing the original English versions of each questionnaire with the translated version. Focus groups of school-aged youth verified their understanding of the terms used in the questionnaire. A portion (10%) of records were compared with their original forms to evaluate potential transcription errors. We performed validation and internal consistency of the new team-translated Spanish version of the questionnaires.

Measures:

Participants completed the Rome 4 Diagnostic Questionnaire for DGBIs (R4DQ),²² Adolescent Sleep Wake Scale – Short Form (ASWS-SF),^23,24 Pediatric Insomnia Severity Index (PISI),²⁵ Epworth Sleepiness Scale for Children (ESS),²⁶ Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Sleep Scales [PROMIS Ped SF v1.0 Sleep Disturbance (PROMIS SD) 8a²⁷ and PROMIS Ped SF v1.0 Sleep-Related Impairment (PROMIS SRI) 8a²⁷]. Parents completed the Sleep Hygiene Inventory for Pediatrics (SHIP).²⁸ Cases completed the Abdominal Pain Index (API),²⁹ Nausea Severity Scale (NSS),³⁰ Functional Disability Inventory (FDI),³¹ and PROMIS Pediatric Anxiety-Short Form,³² and Depression-Short Form scales.³² Further descriptions of these measures are provided in Appendix A.

Statistical Analyses

Descriptive statistics were calculated by groups (FAPDs and controls) on all variables, including frequencies and proportions for categorical variables and means, medians, standard deviations (SD), and ranges for continuous variables. Distributions of continuous variables were assessed for normality using the Shapiro-Wilk test, boxplots, and histograms, and data was transformed as necessary. Comparison between groups of subjects diagnosed with FAPDs and healthy youth was performed using the chi-square or Fisher’s exact test when appropriate (for categorical data) and t-test (for continuous data after proper transformation if needed). For non-normally distributed data, the appropriate non-parametric test (e.g., Wilcoxon rank-sum test) was used. Multiple linear or logistic regression models were used to investigate the effect of baseline and demographic characteristics on sleep measures and adjusted for multiple comparisons using variable selection techniques (e.g., backward or stepwise regression) to determine the most critical factors. Confounding factors were also controlled by stratifying variables and adjusting the models, ensuring that observed differences in sleep measures between groups (FAPDs and controls) were not attributable to uncontrolled variables.

Given a 10% prevalence of FAPDs, a predicted odd’s ratio (OR) of 2, a 95% confidence interval, and a projected statistical power of 80%, 60 cases and controls were calculated prior to the start of the study. Missing covariates were present within total sleep hours, activities done before sleep, and birth history (<10% of total data). Imputation (replacement of missing data with specific values to allow statistical analysis that includes all participants and not just those who do not have any missing data) methods were applied when necessary to these elements. To control confounding factors, stratification of variables was carried out. Model fit was also assessed. A p-value of ≤0.05 was considered significant.

The internal consistency and validation of the team-translated Spanish version of the questionnaires was measured using Cronbach’s alpha. All statistical analyses were conducted using Stata version 16.1 (StataCorp, College Station, Texas).

RESULTS

Demographics, baseline social factors and diagnoses

Of 855 potential participants, 87 had FAPDs (Figure 1). Of these, 27 participants were excluded due to incomplete questionnaire responses, leaving 60 youth. We also recruited 60 age and gender-matched healthy controls. The mean age for FAPDs and controls were 13.5 years ± 1.8 (10.7 - 17.9 years) and 13.6 years ± 1.9 (11.0 - 18.5 years), respectively (Table 1). Both groups had an equal number of female and male participants (50%). Most participants in both groups were of mixed race. Thirty-five percent of youth with FAPDs and 26.7% of healthy participants were malnourished based on BMI. Among youth with FAPDs, 14.6% reported a history of premature birth, 31.7% had delivery via cesarean section, 13.3% of youth were an only child, 45.0% had first-born child status, 63.3% had divorced parents, 10.8% had a family history of DGBIs and 6.7% had a previous history of dengue viral infection (Table 1). More FAPD cases had divorced or separated parents compared to healthy peers (p=0.03). The rest of the baseline social factors did not differ between the groups (p>0.05). Within FAPDs cases, 93.4% of youth had FD, and 3.3% had IBS and FAP-NOS each. Participants were on analgesics such as acetaminophen and hyoscine butylbromide, antacids, anti-allergy medications, albuterol, vitamins, contraceptives, and anti-fungal medication. Medications did not differ in both groups (p>0.05, Supporting information 1).

Figure 1. Flow Chart of Study Recruitment.

QPGS-IV: Rome 4 Diagnostic Questionnaire, DGBIs: Disorders of Gut-Brain Interaction, FAPDs: Functional Abdominal Pain Disorders.

Table 1.

Demographic and social factors

Measure	All participants (n = 120)	FAPDs (n = 60)	Healthy youth (n = 60)	P value
Age *	13.5 ± 1.9y (10.7–18.5)	13.5 ± 1.8y (10.7–17.9)	13.6 ± 1.9y (11.0–18.5)
10-12 years	32 (26.7)	16 (26.7)	16 (26.7)	0.58
13-18 years	88 (73.3)	44 (73.3)	44 (73.3)
Gender
Female	60 (50.0)	30 (50.0)	30 (50.0)	0.57
Male	60 (50.0)	30 (50.0)	30 (50.0)
Race
Mixed race	65 (54.2)	34 (56.7)	31 (51.7)	0.36
White	39 (32.5)	16 (26.7)	23 (38.3)	0.12
Black	10 (8.3)	5 (8.3)	5 (8.3)	0.63
Native	6 (5.0)	5 (8.3)	1 (1.7)	0.10
Nutritional status BMI
Normal	83 (69.2)	39 (65.0)	44 (73.3)	0.22
Malnutrition **	37 (30.8)	21 (35.0)	16 (26.7)
Cesarean	33 (27.5)	19 (31.7)	14 (23.3)	0.21
Prematurity	17 (17.5)	7 (14.6)	10 (20.4)	0.31
Only child	15 (12.5)	8 (13.3)	7 (11.7)	0.50
First born child	53 (44.2)	27 (45.0)	26 (43.3)	0.50
Parents divorced/separated	65 (54.2)	38 (63.3)	27 (45.0)	0.03
Family history of DGBIs	5 (6.8)	4 (10.8)	1 (2.7)	0.18
Previous history of dengue	5 (4.2)	4 (6.7)	1 (1.7)	0.18

^*Data is formatted as mean ± standard deviation (range). All other data is formatted as value (percentage).

^**Malnutrition = Weight more than +1 Standard Deviation or −2 Standard Deviation from normal weight per WHO classification. FAPDs: Functional Abdominal Pain Disorders, DGBIs: Disorders of Gut-Brain Interaction.

Internal consistency of the translated questionnaires

The Cronbach’s alpha values for the Spanish translated questionnaires are provided in Appendix A. The internal consistency of most of the translated surveys were comparable to the original questionnaires.

Sleep-related measures in youth with FAPDs and healthy youth

Youth with FAPDs had higher insomnia symptoms (p=0.001), daytime sleepiness (p=0.002), overall sleep disturbance (p<0.0001), overall sleep impairment (p=0.0001), and parent-reported sleep disruptions (p=0.01) than healthy youth (Table 2). A larger number of youth with FAPDs had moderate sleep disturbance (p<0.0001) and severe sleep impairment (p=0.02) based on PROMIS sleep disturbance and sleep-related impairment measures, respectively, than healthy youth. A larger number of healthy youth were categorized in the slight sleep disturbance (p<0.0001) and slight sleep impairment (p=0.003) categories than youth with FAPDs. However, self-reported quality of sleep behaviors (ASWS-SF) did not differ between youth with FAPDs and healthy youth (p=0.32).

Table 2.

Sleep-related measures in youth with FAPDs and healthy youth

Measure	All participants (n = 120)	FAPDs (n = 60)	Healthy youth (n = 60)	P value
Subjective sleep quality (ASWS-SF) *	4.1 ± 0.9 (1.1–5.9)	4.1 ± 0.9 (1.8–5.7)	4.0 ± 1.0 (1.1–5.9)	0.32
Going to bed *	3.7 ± 1.2 (1.0–6.0)	3.7 ± 1.2 (1.3–6.0)	3.6 ± 1.2 (1.0–6.0)	0.78
Falling asleep and re-initiating sleep *	4.7 ± 1.3 (1.0–6.0)	4.9 ± 1.2 (2.0–6.0)	4.6 ± 1.4 (1.0–6.0)	0.38
Returning to wakefulness *	2.9 ± 1.4 (1.0–6.0)	3.1 ± 1.4 (1.0–6.0)	2.8 ± 1.4 (1.0–6.0)	0.32
Insomnia symptoms (PISI) *	10.9 ± 6.9 (1.0–29.0)	12.9 ± 6.6 (2.0–29.0)	8.9 ± 6.5 (1.0–29.0)	0.001
Daytime sleepiness (ESS) *	8.2 ± 4.7 (0.0–21.0)	9.5 ± 4.7 (1.0–21.0)	6.9 ± 4.3 (0.0–19.0)	0.002
Criteria for EDS **	33.0 (27.5)	20.0 (33.3)	13.0 (21.7)	0.11
Criteria for high EDS	11.0 (9.2)	7.0 (11.7)	4.0 (6.7)	0.26
Self-reported sleep difficulties (PROMIS SD, T-Score) *	55.8 ± 9.5 (36.6–80.3)	59.6 ± 7.9 (42.1–75.4)	52.1 ± 9.6 (36.6–80.3)	<0.0001
None to slight	62.0 (51.7)	17.0 (28.3)	45.0 (75.0)	<0.0001
Mild	17.0 (14.2)	12.0 (20.0)	5.0 (8.3)	0.06
Moderate	33.0 (27.5)	27.0 (45.0)	6.0 (10.0)	<0.0001
Severe	8.0 (6.7)	4.0 (6.7)	4.0 (6.7)	0.64
Sleep impact on daytime functioning (PROMIS SRI, T-Score) *	57.7 ± 10.3 (37.4–84.0)	61.3 ± 10.2 (37.4–84.0)	54.1 ± 9.2 (37.4–79.6)	0.0001
None to slight	54.0 (45.0)	19.0 (31.7)	35.0 (58.3)	0.003
Mild	19.0 (15.8)	9.0 (15.0)	10.0 (16.7)	0.50
Moderate	33.0 (27.5)	21.0 (35.0)	12.0 (20.0)	0.05
Severe	14.0 (11.7)	11.0 (18.3)	3.0 (5.0)	0.02
Parent-reported Sleep Hygiene (SHIP) *	23.5 ± 5.4 (15.0–43.0)	24.7 ± 5.6 (15.0–43.0)	2.3 ± 5.0 (15.0–35.0)	0.01

^*Data is formatted as mean ± standard deviation (range). All other data is formatted as value (percentage). ASWS-SF: Adolescent Sleep Wake Scale – Short Form, PISI: Pediatric Insomnia Severity Index, ESS: Epworth Sleepiness Scale, EDS: Excessive Daytime Sleepiness

^**Presence of EDS denotes ESS score >10, PROMIS SD: Patient Reported Outcomes Measurement Information System Sleep Disturbance, PROMIS SRI: Patient Reported Outcomes Measurement Information System Sleep-Related Impairment, SHIP: Sleep Hygiene Inventory for Pediatrics, FAPDs: Functional Abdominal Pain Disorders.

Sleep history in youth with FAPDs and healthy youth

Youth with FAPDs had higher rates of gasping/snorting/choking (p=0.03), longer time to fall asleep (p=0.05), nightmares (p=0.01), and daytime sleepiness (p=0.002) compared to healthy youth (Table 3). Healthy youth tended to have greater total hours of sleep than youth with FAPDs (p=0.07). There were no differences in snoring (p=0.29), respiratory pauses (p=0.69), or tonsillectomy and adenoidectomy (p=0.16) between youth with FAPDs and healthy youth. Similarly, neither group differed in the time to waking up (p=0.16) and sleeping in their bedroom (p>0.05). Furthermore, no differences in screaming (p=0.34) and sleepwalking (p=0.31) or restless leg movements before sleep/at bedtime (p=0.20) and during sleep (p=0.39) were observed between the two groups.

Table 3.

Sleep history in youth with FAPDs and healthy youth

Measure	All participants (n = 120)	FAPDs (n = 60)	Healthy youth (n = 60)	P value
Sleep apnea
Gasping/snorting/choking	8.0 (6.7)	7.0 (11.7)	1.0 (1.7)	0.03
Snoring	15.0 (12.5)	9.0 (15.0)	6.0 (10.0)	0.29
Respiratory pauses	4.0 (3.3)	2.0 (3.3)	2.0 (3.3)	0.69
Tonsillectomy and adenoidectomy	10.0 (8.3)	7.0 (11.7)	3.0 (5.0)	0.16
Insomnia
Time to fall asleep: > 30 minutes	31.0 (25.8)	20.0 (33.3)	11.0 (18.3)	0.05
Time to waking up: 15-30 minutes	19.0 (15.8)	12.0 (20.0)	7.0 (11.7)	0.16
Parasomnia
Nightmares	20.0 (16.7)	15.0 (25.0)	5.0 (8.3)	0.01
Daytime sleepiness	57.0 (47.5)	37.0 (61.7)	20.0 (33.3)	0.002
Screaming	6.0 (5.0)	4.0 (6.7)	2.0 (3.3)	0.34
Sleepwalking	4.0 (3.3)	3.0 (5.0)	1.0 (1.7)	0.31
Hours of sleep	(n = 113)	(n = 56)	(n = 57)
Total hours of sleep *	7.3 ± 1.2	7.2 ± 1.0	7.5 ± 1.3	0.07
Sleep in your own room
Every night	95.0 (79.2)	46.0 (76.7)	49.0 (81.7)	0.33
Most nights	8.0 (6.7)	5.0 (8.3)	3.0 (5.0)	0.36
Rarely	6.0 (5.0)	3.0 (5.0)	3.0 (5.0)	0.66
Never	11.0 (9.2)	6.0 (10.0)	5.0 (8.3)	0.50
Restless legs
Before sleep/at bedtime	31.0 (25.8)	18.0 (30.0)	13.0 (21.7)	0.20
During sleep	14.0 (11.7)	6.0 (10.0)	8.0 (13.3)	0.39

^*Data is formatted as mean ± standard deviation. All other data is formatted as value (percentage). FAPDs: Functional Abdominal Pain Disorders.

Activities before sleep in youth with FAPDs and healthy youth

Youth with FAPDs had higher stress levels than healthy youth (p=0.01, Table 4). There were no significant differences in activities before going to sleep, such as reading a book or doing homework (p=0.26), eating (p=0.22), video games (p=0.11), watching television (p=0.29), relaxing (p=0.50), talking on the phone (p=0.23), and using a computer or another electronic device (p=0.36) between youth with FAPDs and healthy youth. Similarly, the two groups had no differences in caffeinated beverage consumption before sleeping (p=0.50) and time between dinner and sleep (p=0.35).

Table 4.

Activities before sleep in youth with FAPDs and healthy youth

Measure	All participants (n = 120)	FAPDs (n = 60)	Healthy youth (n = 60)	P value
Stress level *	5.8 ± 2.9	6.4 ± 2.7	5.1 ± 2.9	0.01
Differences in activity before going to sleep
Reading a book or homework	28.0 (23.3)	12.0 (20.0)	16.0 (26.7)	0.26
Eating	37.0 (30.8)	21.0 (35.0)	16.0 (26.7)	0.22
Video games	33.0 (27.5)	20.0 (33.3)	13.0 (21.7)	0.11
Watching television	48.0 (40.0)	22.0 (36.7)	26.0 (43.3)	0.29
Relaxing	41.0 (34.2)	20.0 (33.3)	21.0 (35.0)	0.50
Talking on the phone	63.0 (52.5)	34.0 (56.7)	29.0 (48.3)	0.23
Using a computer or another electronic	55.0 (45.8)	29.0 (48.3)	26.0 (43.3)	0.36
Caffeinated drinks before going to sleep	109.0 (90.8)	54.0 (90.0)	55.0 (91.7)	0.50
Time between dinner and sleep	n = 117	n = 57	n = 60
Mean ± SD *	3.1 ± 1.7	3.2 ± 2.0	2.9 ± 1.4	0.35

^*Data is formatted as mean ± standard deviation. All other data is formatted as value (percentage). FAPDs: Functional Abdominal Pain Disorders.

Correlations between sleep and other clinical measures

Among youth with FAPDs, greater abdominal pain symptoms based on the API were moderately positively correlated with insomnia symptoms (r=0.41, p<0.01) and weakly correlated with daytime sleepiness (r=0.38, p<0.01), Table 5. Anxiety (r= 0.34, p<0.01) and depression (r=0.33, p<0.01) weakly correlated with sleep-related impairment, while disability weakly correlated with sleep quality (r=0.33, p<0.01) and sleep hygiene (r=0.32, p<0.05).

Table 5.

Correlations between sleep and other clinical measures

Measure	ASWS-SF	PISI	ESS	PROMIS SD	PROMIS SRI	SHIP
API	0.10	0.41**	0.38**	−0.08	−0.02	0.18
NSS	0.19	0.26*	0.26*	−0.20	0.02	0.22
PROMIS anxiety	−0.17	−0.15	−0.008	0.28*	0.34**	0.07
PROMIS depression	−0.19	−0.17	−0.12	0.14	0.33**	0.07
FDI	0.33**	0.11	0.18	−0.05	−0.01	0.32*

Data is formatted as Pearson correlation. * denotes p<0.05. ** denotes p<0.01.

ASWS-SF: Adolescent Sleep Wake Scale – Short Form, PISI: Pediatric Insomnia Severity Index, ESS: Epworth Sleepiness Scale, PROMIS SD: Patient Reported Outcomes Measurement Information System Sleep Disturbance, PROMIS SRI: Patient Reported Outcomes Measurement Information System Sleep-Related Impairment, SHIP: Sleep Hygiene Inventory for Pediatrics, API: Abdominal Pain Index, NSS: Nausea Severity Scale, PROMIS: Patient Reported Outcomes Measurement Information System, FDI: Functional Disability Inventory.

Associations of demographic and other social factors with sleep and other clinical measures

Younger age was associated with more sleep-related impairment (OR=3.2, p=0.006, Table 6) and anxiety (OR=2.4, p=0.03, Table 7) compared to older youth. Females had a positive association with excessive daytime sleepiness (OR=3.1, p=0.008) and a negative association with anxiety (OR=0.4, p=0.01). Sleep-related impairment (OR=5.6, p=0.02) and depression (OR=6.1, p=0.01) had a positive association with black race. Only child status had a negative association with sleep disturbance (OR=0.3, p=0.04). High levels of excessive daytime sleepiness were positively associated with a family history of DGBIs (OR=14.7, p=0.002). First-born child status, history of cesarean section or premature birth, previous history of dengue, and parental marital status were not associated with sleep measures.

Table 6.

Associations of demographic and other social factors with sleep measures

Measure	EDS				High level of EDS				PROMIS SD				PROMIS SRI
	No (n = 87)	Yes (n = 33)	OR (95%CI)	P value	No (n = 109)	Yes (n = 11)	OR (95%CI)	P value	No (n = 58)	Yes (n = 62)	OR (95%CI)	P value	No (n = 66)	Yes (n = 54)	OR (95%CI)	P value
Age groups
Older (13 - 18 years)	60.0	28.0	1.0 (0.1 – 1.2)	0.08	79.0	9.0	1.0 (0.05 – 3.1)	0.50	43.0	45.0	1.0 (0.4 – 2.6)	0.85	55.0 (83.3)	33.0 (61.1)	1.0 (1.3 – 8.2)	0.006
Younger (10 – 12 years)	27.0	5.0	0.4 (0.1 – 1.2)		30.0	2.0	0.6 (0.05 – 3.1)		15.0	17.0	1.1 (0.4 – 2.6)		11.0 (16.7)	21 (38.9)	3.2 (1.3 – 8.2)
Gender
Male	50.0	10.0	1.0 (1.2 – 8.2)	0.008	57.0	3.0	1.0 (0.7 – 17.9)	0.11	30.0	30.0	1.0 (0.5 – 2.5)	0.71	29.0	31.0	1.0 (0.3 – 1.3)	0.14
Female	37.0	23.0	3.1 (1.2 – 8.2)		52.0	8.0	2.9 (0.7 – 17.9)		28.0	32.0	1.1 (0.5 – 2.5)		37.0	23.0	0.6 (0.3 – 1.3)
Race
Black
No	78.0	32.0	1.0 (0.005 – 2.1)	0.20	100.0	10.0	1.0 (0.02 – 9.6)	0.92	54.0	56.0	1.0 (0.3 – 7.3)	0.58	64.0	46.0	1.0 (1.0 – 55.4)	0.02
Yes	9.0	1.0	0.3 (0.005 – 2.1)		9.0	1.0	1.1 (0.02 – 9.6)		4.0	6.0	1.4 (0.3 – 7.3)		2.0	8.0	5.6 (1.0 – 55.4)
White
No	57.0	24.0	1.0 (0.3 – 1.8)	0.45	74.0	7.0	1.0 (0.2 – 5.1)	0.77	41.0	40.0	1.0 (0.6 – 3.1)	0.47	45.0	36.0	1.0 (0.5 – 2.5)	0.86
Yes	30.0	9.0	0.7 (0.3 – 1.8)		35.0	4.0	1.2 (0.2 – 5.1)		17.0	22.0	1.3 (0.6 – 3.1)		21.0	18.0	1.1 (0.5 – 2.5)
Mixed
No	43.0	12.0	1.0 (0.7 – 4.3)	0.20	50.0	5.0	1.0 (0.2 – 4.5)	0.98	23.0	32.0	1.0 (0.3 – 1.4)	0.19	26.0	29.0	1.0 (0.3 – 1.2)	0.12
Yes	44.0	21.0	1.71 (0.7 – 4.3)		59.0	6.0	1.0 (0.2 – 4.5)		35.0	30.0	0.6 (0.3 – 1.4)		40.0	25.0	0.6 (0.3 – 1.2)
Native
No	83.0	31.0	1.0 (0.1 – 9.9)	0.74	103.0	11.0	n/a		56.0	58.0	1.0 (0.3 – 22.0)	0.45	63.0	51.0	1.0 (0.2 – 9.6)	0.80
Yes	4.0	2.0	1.3 (0.1 – 9.9)		6.0	0.0			2.0	4.0	1.9 (0.3 – 22.0)		3.0	3.0	1.2 (0.2 – 9.6)
Birth history
Delivery via cesarean section
No	64.0	22.0	1.0 (0.5 – 3.6)	0.45	78.0	8.0	1.0 (0.2 – 4.3)	0.93	44.0	42.0	1.0 (0.6 – 3.6)	0.32	49.0	37.0	1.0 (0.6 – 3.2)	0.49
Yes	23.0	11.0	1.4 (0.5 – 3.6)		31.0	3.0	0.9 (0.2 – 4.3)		14.0	20.0	1.5 (0.6 – 3.6)		17.0	17.0	1.3 (0.6 – 3.2)
Premature birth
No	56.0	24.0	1.0 (0.3 – 4.3)	0.67	71.0	9.0	1.0 (0.01 – 4.1)	0.51	40.0	40.0	1.0 (0.2 – 2.3)	0.50	46.0	34.0	1.0 (0.3 – 3.1)	0.92
Yes	11.0	6.0	1.3 (0.3 – 4.3)		16.0	1.0	0.5 (0.01 – 4.1)		10.0	7.0	0.7 (0.2 – 2.3)		10.0	7.0	0.9 (0.3 – 3.1)
Sibling status
Only child
No	79.0	26.0	1.0 (0.7 – 9.2)	0.07	97.0	8.0	1.0 (0.5 – 14.9)	0.12	47.0	58.0	1.0 (0.06 – 1.1)	0.04	55.0	50.0	1.0 (0.1 – 1.5)	0.13
Yes	8.0	7.0	2.7 (0.7 – 9.2)		12.0	3.0	3.0 (0.5 – 14.9)		11.0	4.0	0.3 (0.06 – 1.1)		11.0	4.0	0.4 (0.1 – 1.5)
First-born child
No	50.0	17.0	1.0 (0.5 – 3.1)	0.56	62.0	5.0	1.0 (0.4 – 7.0)	0.47	30.0	37.0	1.0 (0.3 – 1.6)	0.38	34.0	33.0	1.0 (0.3 – 1.5)	0.29
Yes	37.0	16.0	1.3 (0.5 – 3.1)		47.0	6.0	1.6 (0.4 – 7.0)		28.0	25.0	0.7 (0.3 – 1.6)		32.0	21.0	0.7 (0.3 – 1.5)
Parental marital status
Parents divorced or separated
No	42.0	13.0	1.0 (0.6 – 3.6)	0.38	50.0	5.0	1.0 (0.2 – 4.5)	0.98	23.0	32.0	1.0 (0.3 – 1.4)	0.19	28.0	27.0	1.0 (0.3 – 1.6)	0.41
Yes	45.0	20.0	1.4 (0.6 – 3.6)		59.0	6.0	1.0 (0.2 – 4.5)		35.0	30.0	0.6 (0.3 – 1.4)		38.0	27.0	0.7 (0.3 – 1.6)
Family and past history
Family history of DGBIs
No	51.0	18.0	1.0 (0.4 – 53.5)	0.10	66.0	3.0	1.0 (0.8 – 180.6)	0.002	33.0	36.0	1.0 (0.04 – 5.7)	0.60	36.0	33.0	1.0 (0.01 – 3.0)	0.23
Yes	2.0	3.0	4.3 (0.4 – 53.5)		3.0	2.0	14.7 (0.8 – 180.6)		3.0	2.0	0.6 (0.04 – 5.7)		4.0	1.0	0.3 (0.01 – 3.0)
Previous history of dengue
No	84.0	31.0	1.0 (0.1 – 16.5)	0.52	105.0	10.0	1.0 (0.04 – 30.0)	0.39	54.0	61.0	1.0 (0.004 – 2.4)	0.15	62.0	53.0	1.0 (0.01 – 3.1)	0.25
Yes	3.0	2.0	1.8 (0.1 – 16.5)		4.0	1.0	2.6 (0.04 – 30.0)		4.0	1.0	0.2 (0.004 – 2.4)		4.0	1.0	0.3 (0.01 – 3.1)

Data is formatted as value. EDS: Excessive Daytime Sleepiness, PROMIS SD: Patient Reported Outcomes Measurement Information System Sleep Disturbance, PROMIS SRI: Patient Reported Outcomes Measurement Information System Sleep-Related Impairment, OR: Odds Ratio, CI: Confidence Interval, DGBIs: Disorders of Gut-Brain Interaction.

Table 7.

Associations of demographic and other social factors with anxiety and depression

Measure	PROMIS anxiety				PROMIS depression
	No (n = 68)	Yes (n = 52)	OR (95%CI)	P value	No (n = 77)	Yes (n = 16)	OR (95%CI)	P value
Age groups
Older (13 – 18 years)	55.0	33.0	1.0 (1.0–6.1)	0.03	55.0	10.0	1.0 (0.4–5.2)	0.48
Younger (10 – 12 years)	13.0	19.0	2.4 (1.0–6.1)		22.0	6.0	1.5 (0.4–5.2)
Gender
Male	27.0	33.0	1.0 (0.2–0.9)	0.01	43.0	13.0	1.0 (0.04–1.2)	0.06
Female	41.0	19.0	0.4 (0.2–0.9)		34.0	3.0	0.3 (0.04–1.2)
Race
Black
No	64.0	46.0	1.0 (0.5–10.6)	0.27	73.0	12.0	1.0 (1.0–36.5)	0.01
Yes	4.0	6.0	2.1 (0.5–10.6)		4.0	4.0	6.1 (1.0–36.5)
White
No	44.0	37.0	1.0 (0.3–1.7)	0.45	51.0	12.0	1.0 (0.1–2.5)	0.49
Yes	24.0	15.0	0.7 (0.3–1.7)		26.0	4.0	0.7 (0.1–2.5)
Mixed
No	31.0	24.0	1.0 (0.4–2.2)	0.95	33.0	10.0	1.0 (0.1–1.5)	0.15
Yes	37.0	28.0	1.0 (0.4-2.2)		44.0	6.0	0.5 (0.1-1.5)
Native
No	65.0	49.0	1.0 (0.2–10.3)	0.74	74.0	14.0	1.0 (0.3–33.2)	0.17
Yes	3.0	3.0	1.3 (0.2–10.3)		3.0	2.0	3.5 (0.3–33.2)
Birth history
Delivery via cesarean section
No	50.0	36.0	1.0 (0.5–3.0)	0.60	55.0	11.0	1.0 (0.3–4.1)	0.83
Yes	18.0	16.0	1.2 (0.5–3.0)		22.0	5.0	1.1 (0.3–4.1)
Premature birth
No	49.0	31.0	1.0 (0.4–4.6)	0.53	53.0	10.0	1.0 (0.3–12.1)	0.28
Yes	9.0	8.0	1.4 (0.4–4.6)		7.0	3.0	2.3 (0.3–12.1)
Sibling status
Only child
No	58.0	47.0	1.0 (0.2–2.2)	0.40	68.0	13.0	1.0 (0.3–8.3)	0.44
Yes	10.0	5.0	0.6 (0.2–2.2)		9.0	3.0	1.7 (0.3–8.3)
First-born child
No	37.0	30.0	1.0 (0.4–1.9)	0.72	42.0	11.0	1.0 (0.1–1.9)	0.30
Yes	31.0	22.0	0.9 (0.4–1.9)		35.0	5.0	0.5 (0.1–1.9)
Parental marital status
Parents divorced or separated
No	30.0	25.0	1.0 (0.4–1.9)	0.67	35.0	7.0	1.0 (0.3–3.8)	0.90
Yes	38.0	27.0	0.9 (0.4–1.9)		42.0	9.0	1.1 (0.3–3.8)
Family and past history
Family history of DGBIs
No	39.0	30.0	1.0 (0.01–3.6)	0.30	44.0	10.0	n/a
Yes	4.0	1.0	0.3 (0.01–3.6)		4.0	0.0
Previous history of dengue
No	64.0	51.0	1.0 (0.01–3.3)	0.28	74.0	15.0	1.0 (0.02–22.0)	0.67
Yes	4.0	1.0	0.3 (0.01–3.3)		3.0	1.0	1.6 (0.02–22.0)

Data is formatted as value. PROMIS: Patient Reported Outcomes Measurement Information System, OR: Odds ratio, CI: Confidence Interval, DGBIs: Disorders of Gut-Brain Interaction.

After multiple regression analysis, younger age was positively associated with sleep-related impairment (OR=4.7, p=0.03) and anxiety (OR=5.3, p=0.02) and negatively associated with excessive daytime sleepiness (OR=0.1, p=0.03). Females were more likely to have excessive daytime sleepiness (OR=4.6, p=0.02) and less likely to have sleep-related impairment (OR=0.3, p=0.03) and anxiety (OR=0.2, p=0.008). Prematurity was associated positively with anxiety (OR=7.1, p=0.03). Only child status (OR=8.8, p=0.05) and family history of DGBIs (OR=18.6, p=0.05) positively associated with excessive daytime sleepiness and high level of excessive daytime sleepiness, respectively (Supporting information 2).

Discussion

Sleep is a fundamental process that regulates the body’s homeostatic response and physiological functioning.^33,34 Impairments in the ability to obtain restorative sleep can adversely affect the ability to function and regulate emotional functioning. This is particularly critical for youth as it can affect their development.³⁵ Previous studies have indicated that poor sleep can also exacerbate pain and intensify existing pain conditions.³⁶ Our aim was to identify the presence and impact of sleep disturbances in Colombian youth with FAPDs compared to age and gender-matched healthy youth and evaluate associations between sleep and their GI and psychological functioning.

Our study showed a trend for longer self-reported sleep duration in healthy youth compared with youth with FAPDs. Sleep hygiene and activities before bedtime did not differ between the groups. However, youth with FAPDs had worse sleep quality, sleep disturbance, and sleep-related impairment than healthy youth. Our findings are similar to previous studies in children with FAPDs. In non-controlled studies, 45% of children with DGBIs ages 8-17 years (n=283) had one parent reported sleep-related disorder⁷, while 26% of adolescents with pediatric FAPDs (n=278) had sleep disturbances, of which, 8% reported severe sleep disturbances.³⁷ This is comparable to the 6.6% severe sleep disturbances reported in our study. Santucci et al. have described worse sleep quality scores, insomnia severity, sleep disturbance, and sleep-related impairment in a small subset of adolescents 11-19 years with FAPDs than those reported in published normative healthy adolescents (n=20).³⁸ Some of the measures in their study were slightly worse than youth with sleep disorders in chronic illnesses and neurodevelopmental disorders. In another retrospective study by the same group, more than half of the youth aged 11-21 years with FD, a type of FAPD, endorsed subjective sleep complaints.³⁹ Similarly, other prospective studies in adolescents have found worse sleep quality^40,41 and difficulty initiating and maintaining sleep compared to healthy controls.⁴⁰ These sleep disturbances have also been prevalent in younger children with DGBIs (61% of 67 children ages 7-12).⁴²

Youth with chronic pain conditions such as juvenile idiopathic arthritis, sickle cell disease, migraine, and fibromyalgia have sleep-disordered breathing, parasomnias, and excessive daytime sleepiness.^43-45 These have not been thoroughly investigated in youth with FAPDs. Snoring rates did not differ between youth with FAPDs and healthy youth in our study. This is similar to the findings of a previous study in this population.⁴¹ However, we found that youth with FAPDs had higher rates of gasping, snorting, choking, nightmares, and excessive daytime sleepiness than healthy youth. One study has reported similar findings in youth with FAPDs compared to healthy youth.⁴⁰ While we did not directly measure the rates of diagnosed obstructive sleep apnea, this may allude to increased sleep-disordered breathing in youth with FAPDs that may contribute to worse pain outcomes. Sympathetic hyperreactivity and autonomic imbalances, associated with parasomnias, are often present in youth with FAPDs and may explain the increased nightmares in this population.⁴⁶ Daytime sleepiness can be an extremely bothersome symptom limiting daily functioning and activities at school and, thus, deserves further investigation. These findings highlight the importance of a detailed history regarding sleep symptoms and appropriate evaluation while managing youth with FAPDs to improve their clinical outcomes. Further studies are needed to determine the effect of vacations, geographic location, and other factors affecting sleep. It is imperative to assess the incidence of sleep disorders in this population. Studies utilizing objective measures of sleep, such as actigraphy and polysomnography, would provide more specific information regarding sleep timing, sleep architecture, and sleep continuity for comprehensive sleep assessments.

We found that greater insomnia severity correlated with worse abdominal pain. While insomnia severity has not been studied in youth with DGBIs, sleep problems in these youth have been associated with physical symptoms, including greater abdominal pain^7,37,42,47 and pain interference.⁴¹ Two studies have reported improvements in sleep quality,^38,39 insomnia severity,³⁹ sleep disturbance,³⁹ and sleep-related impairment³⁹ and abdominal pain after four weeks of treatment with auricular neuromodulation.^38,39 One study found that anxiety, depression, pain catastrophizing, and somatic complaints directly and indirectly mediated the effect of sleep disturbance and sleep-related impairment on abdominal pain.³⁸

While we did not examine causal relationships in our study, the strongest temporal association in studies in adults with chronic pain is in favor of sleep deficiency impacting next-day pain in comparison to pain causing disturbed sleep.^15,48 This directionality needs further scrutiny, especially to identify sleep targets for interventions to improve abdominal pain.

Sleep disturbances have shown an association with functional disability, non-GI somatic symptoms, and more frequent emergency room visits in youth with FAPDs.³⁷ Another study showed that emotional symptoms related to DGBIs worsened sleep, which worsened the physical symptoms and ultimately led to greater functional disability.⁷ These findings mirror those found in other pediatric chronic pain conditions where sleep disturbances have been associated with greater pain frequency and related to mood disturbances as well as decreased health-related quality of life.^43,44,49,50 We did not find a strong correlation between disability, anxiety, depression, and sleep disturbances in our cohort. This may be due to inherent differences in these metrics between Colombian and American youth. The average disability scores in our sample are considered mild and lower than those of American youth with FAPDs (5.1 vs 10-15).^51,52 Similarly, anxiety and possibly depression may be less severe in Colombian youth⁵ compared to American youth with FAPDs.⁵²

Gender, age, and race have influenced sleep disturbances in pediatric FAPDs. We found that females with FAPDs were three times more likely to suffer from excessive daytime sleepiness and less likely to suffer from anxiety compared to males. This is similar to the study by Murphy et al., where females had more sleep disturbances.³⁷ Similarly, general population-based studies have also found that older adolescent girls consistently reported significantly shorter sleep duration and decreased sleep efficiency than boys of the same age.⁵³ Younger youth in our study were also three times more likely to suffer from sleep-related impairment and two times more likely to suffer from anxiety compared to older youth. This contrasts with previous studies where older youth had more sleep disturbances.³⁷ Sample differences such as more nightmares and the effect of siblings in our cohort may explain the severity of sleep-related impairment in younger youth. Schurman et al., however, did not find that age was significantly associated with sleep problems.⁷

We also found that black youth with FAPDs were six times more likely to suffer from sleep-related impairment and depression. This is in alignment with a prior study that has shown that African American youth with DGBIs suffered from more sleep disturbance than white youth.⁴¹ Similarly, minority youth with chronic pain have reported decreased sleep, increased somatic complaints, higher levels of functional disability, and increased pain intensity compared to white youth.⁵⁴ Unique to our study, we analyzed the effect of demographic and other characteristics on sleep measures. We found that youth with a family history of DGBIs were 15 times more likely to have excessive daytime sleepiness, those who did not have siblings were less likely to have sleep disturbances. Thus, having siblings could lead to more noise and distractions before and during sleep, especially in smaller houses. This is particularly important since prior studies have accounted for noise before bedtime as a factor for sleep disturbances.⁴⁰

This is the first study to investigate sleep disturbances in Colombian youth with FAPDs and compare them with healthy youth. The prospective design of the study, moderate sample size, and validated child and parent measures made it possible to make meaningful comparisons. We assessed multiple domains of sleep affected in youth with FAPDs and correlated them with demographic and other social factors unique to this population. Spanish translation of questionnaires allowed for questions to be asked in a language the youth and parents understood. The limitations included subjective reports and a lack of objective sleep assessments using polysomnography or actigraphy. Data on other comorbid conditions was limited due to the school-based design as well as generalizability to other regions of Colombia. We also did not follow them longitudinally over time as this would be harder to perform in a school-based study design. Future studies could include longitudinal assessments of sleep, integrating objective sleep techniques such as actigraphy, daily diaries, and polysomnography to detect sleep architecture abnormalities in youth with FAPDs.

Thus, sleep health is under-investigated in youth with FAPDs, and we highlight the importance of investigation of sleep symptoms in youth with FAPDs. There is a dire need to improve the sub-optimal treatment outcomes in youth with FAPDs. Identifying novel sleep targets may enable us to develop new sleep modulating therapies or integrate sleep modulation with standard of care FAPDs treatments to improve GI symptoms in FAPDs.

Appendix A.

This appendix contains further information on the measures used in the study. They are as follows below.

Rome IV Diagnostic Questionnaire (R4DQ)²²:

The R4DQ is a validated questionnaire designed to diagnose DGBIs in children 4-18 years of age. Questions cover the location and frequency of gastrointestinal symptoms as well as related disability and somatic complaints. Based on responses, youth were categorized into different pediatric DGBIs.

Adolescent Sleep Wake Scale – Short Form (ASWS-SF)^23,24:

The ASWS-SF has been validated (Cronbach’s α = 0.70-0.90)^23,24 to assess the quality of sleep behaviors in adolescents and chronic pain youth ages 11 years and older. ASWS-SF consists of 10 items. Each item is scored using a 6-point scale ranging from 1 (“always”) to 6 (“never”). A total score is obtained by averaging all items on the scale and assessing sleep quality over four main dimensions: falling asleep, reinitiating sleep, returning to wakefulness, and going to bed. Falling asleep and reinitiating sleep were combined, generating three ASWS-SF subscales. Higher scores reflect better sleep quality. Internal consistency for the translated questionnaire was 0.77.

Pediatric Insomnia Severity Index (PISI)²⁵:

PISI is a validated instrument (Cronbach’s α = 0.80)²⁵ to assess insomnia symptoms within the past week in youth 11-18²⁵ years of age. The PISI assesses insomnia symptoms, including sleep onset problems, sleep maintenance problems, daytime sleepiness, and nocturnal sleep duration. PISI consists of 6 items rated on a Likert scale ranging from “never” (0 points) to “always/7 days a week” (5 points). The total score (range 0 to 30) is calculated by summing all items. Higher scores are indicative of greater severity of insomnia. There are age-specific forms but no age-specific norms for scoring. The internal consistency of the translated questionnaire was 0.77.

Epworth Sleepiness Scale for Children (ESS)²⁶:

ESS is a validated measure (Cronbach’s α = 0.73)²⁶ of daytime sleepiness in pediatric populations ages 12-18 years. Survey items rate the probability of falling asleep while performing eight different activities. The measure uses a 4-point Likert scale ranging from 0 (“would never fall asleep”) to 3 (“high chance of falling asleep”). A total score is obtained by adding all items. Higher scores are indicative of more significant daytime sleepiness. A score greater than 10 is considered excessive daytime sleepiness (EDS), and a score greater than or equal to 16 is regarded as a high level of EDS. Internal consistency for the translated questionnaire was 0.69.

Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Sleep Scales

PROMIS Ped SF v1.0 – Sleep Disturbance 8a – Child (Cronbach’s α = 0.92)²⁷ is an 8-item measure of sleep disturbance (PROMIS SD) elements including sleep depth, sleep quality, and restorative impact of sleep. PROMIS Ped SF v1.0 – Sleep-Related Impairment 8a – Child (Cronbach’s α = 0.89)²⁷ is an 8-item measure of sleep-related impairment (PROMIS SRI), including daytime alertness, sleepiness, tiredness, and function over the past week. These measures utilize 5-point response scales and have been validated in children 8-17 years of age. All items are summed to obtain a total score. Higher scores indicate more significant sleep disturbance (mild: 55.0 – 59.9, moderate: 60.0 – 69.9, severe: >70.0) and impairment (mild: 55.0 – 59.9, moderate: 60.0 – 69.9, severe: >70.0). Internal consistency for the translated PROMIS SD and SRI questionnaires was 0.88 and 0.90, respectively.

Sleep Hygiene Inventory for Pediatrics (SHIP)²⁸:

SHIP is a validated tool (Cronbach’s α = 0.84)²⁸ that assesses sleep issues common in youth with headaches. Since these sleep issues are also shared in youth with FAPDs, the frequency of sleep habits was determined by parental report. The SHIP has 15 items, each question has a 3-point Likert scale ranging from “rarely” (occurring 0-1 times per week) and “sometimes” (occurring 2-4 times per week) to “usually” (occurring 5-7 times per week). Higher SHIP scores indicate worse sleep hygiene. Internal consistency for the translated questionnaire was 0.73.

Abdominal Pain Index (API)²⁹:

The API is a valid (Cronbach’s α = 0.83)²⁹ 5-item instrument that assesses the severity, intensity, frequency, and duration of abdominal pain within the past two weeks. The frequency and severity of abdominal pain were rated on a 6-point scale, duration on a 9-point scale, and intensity on an 11-point Likert scale. A composite score was obtained by converting all subscales to a 6-point Likert scale. Internal consistency for the translated questionnaire was 0.84.

Nausea Severity Scale (NSS)³⁰:

NSS is a reliable (Cronbach’s α = 0.88)³⁰ 5-item measure that assesses intensity, duration, the number of days with nausea, and the number of daily nausea episodes within the past two weeks. Frequency and duration of nausea experiences were rated on a 5-point scale, while nausea intensity was rated on an 11-point scale. A composite score was attained by converting all subscales to a 5-point scale. Internal consistency for the translated questionnaire was 0.92.

Functional Disability Inventory (FDI)³¹:

FDI evaluates the effects of symptoms on daily functioning through child self-report and parent-report instruments. The FDI is a validated (Cronbach’s α = 0.77-0.91)³¹ and normed clinical measure of the degree that youth have trouble in physical and psychosocial functioning due to impaired physical health. The instrument contains 15 items related to perceptions of activity limitations during the past 2 weeks. Total scores were determined by summing the ratings for each item. Scores greater than 7 indicated disability. The FDI can be subdivided into minimal (7-12), mild (13-20), moderate (21-29), and severe (≥30) disability. Internal consistency for the translated questionnaire was 0.87.

PROMIS Anxiety, depression³²:

The validated Patient-Reported Outcomes Measurement Systems (PROMIS) for pediatric anxiety (Cronbach’s α = 0.96)³² and depression (Cronbach’s α = 0.95)³² short-form scales were utilized. Higher scores denoted greater anxiety (≥ 55.0) and depression (≥ 55.0). Internal consistency for the two PROMIS translated questionnaires were 0.91 and 0.95, respectively.

Validation and internal consistency of newly translated spanish questionnaires

Measure	Cronbach’s alpha	Internal consistency*
ASWS-SF	0.77	Acceptable
PISI	0.77	Acceptable
ESS	0.69	Questionable
PROMIS SD	0.88	Good
PROMIS SRI	0.90	Good
SHIP	0.73	Acceptable
API	0.84	Good
NSS	0.92	Excellent
FDI	0.87	Good
PROMIS anxiety	0.91	Excellent
PROMIS depression	0.95	Excellent

Data is formatted as value. *Internal consistency: excellent = 0.91–1.00, good = 0.81–0.90, acceptable = 0.71–0.80, questionable = 0.61–0.70, poor = 0.51–0.60, unacceptable = 0.00–0.50. ASWS-SF: Adolescent Sleep Wake Scale – Short Form, PISI: Pediatric Insomnia Severity Index, ESS: Epworth Sleepiness Scale, PROMIS SD: Patient Reported Outcomes Measurement Information System Sleep Disturbance, PROMIS SRI: Patient Reported Outcomes Measurement Information System Sleep-Related Impairment, SHIP: Sleep Hygiene Inventory for Pediatrics, API: Abdominal Pain Index, NSS: Nausea Severity Scale, FDI: Functional Disability Inventory, PROMIS: Patient Reported Outcomes Measurement Information System.

Data Availability Statement:

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.