Evaluating the Alimentary and Respiratory Tracts in Health and Disease (EARTH) Research Program.

Status

UNKNOWN

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT04071314

Acronym

EARTH

Enrollment

Registered

2019-08-28

Start date

2018-04-18

Completion date

2023-03-13

Last updated

2019-08-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cystic Fibrosis, Healthy, Hirschprung's Disease, Obstructive Sleep Apnea

Keywords

Microbiota, Gastrointestinal Microbiome, Diet, Signs and Symptoms, Quality of Life, Anxiety, Depression

Brief summary

The investigators have established the Evaluating the Alimentary and Respiratory Tracts in Health and disease (EARTH) research program. It provides a structured approach to analysing gastrointestinal and respiratory microbiomes, along with diet and symptomatology, in children with a gastrointestinal and/or respiratory condition with recognised long-term morbidity (e.g. cystic fibrosis, obstructive sleep apnoea, or Hirschsprung's disease). The EARTH program consists of a series of prospective, longitudinal, controlled, observational studies, with each individual study comparing children with a chronic gastrointestinal and/or respiratory condition to healthy controls (HC). It will be conducted in an Australian tertiary paediatric hospital (although the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared to age and gender matched HC across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) a stool sample, (ii) an oropharyngeal swab or sputum sample, (iii) a semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life, and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro- and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will also be compared between children with a condition and HC. The investigators hypothesise that: (i) Children with chronic gastrointestinal and/or respiratory conditions will have altered intestinal and respiratory microbiomes compared to healthy children, and (ii) Diet plays a key role in influencing the intestinal and respiratory microbiomes and this may impact on clinical outcomes, biomarkers of disease, and health-related quality of life.

Detailed description

The objective of this research program is to evaluate and compare children with a chronic gastrointestinal and/or respiratory condition and age and gender matched HC. The primary objectives include analysing the intestinal and respiratory microbiomes (using an integrated omics approach) and dietary intake using validated, food frequency quetsionnaires. The secondary objectives include evaluating: 1. Known inflammatory biomarkers. 2. Symptomatology and health-related quality of life (HRQOL) using validated measures. 3. Phenotypic and clinical information. 4. Sociodemographic factors Additional secondary objectives include correlating within children with the same condition: (i) dietary intake with the intestinal microbiome; (ii) dietary intake with the respiratory microbiome; and (iii) the intestinal and respiratory microbiomes. The investigators hypothesise that: (i) Children with chronic gastrointestinal and/or respiratory conditions will have altered intestinal and respiratory microbiomes compared to healthy children, and (ii) Diet plays a key role in influencing the intestinal and respiratory microbiomes and this may impact on clinical outcomes, biomarkers of disease, and health-related quality of life. To our knowledge, this program will enable the first series of studies comparing the intestinal and respiratory microbiomes and diet in children with chronic gastrointestinal and/or respiratory conditions. Initial results will be hypothesis-generating and used to direct future studies tailored to a specific focus or line of inquiry. Additionally, studies from this research program have potential for direct translation into clinical care as diet is a highly modifiable factor. Study design. The EARTH program provides a framework for a series of prospective, longitudinal, controlled, observational studies, with each individual study comparing children with a chronic gastrointestinal and/or respiratory condition to HC. A single healthy control group will be used for comparison against all conditions. The standardised methodological approach will also allow for comparisons between different health conditions. Procedures. Each participant will be assessed on three occasions over a 12-month period; at study entry, 6- and 12-month follow-up. At each time-point, the following will be collected: * A stool sample; * An oropharyngeal swab or sputum sample (a sputum sample will be obtained in children able to expectorate and an oropharyngeal swab will be collected in children unable to expectorate); * Dietary intake measured using the Australian Child and Adolescent Eating Survey (ACAES) (2 to 18 years) or 24-hour food recall (0 up to 2 years); * A secure, password-protected online survey comprising: i. PedsQL Infant Scales (0-2yr) & Gastrointestinal Symptoms Module (2-18yr),41-43 tailored to age; ii. Rome IV Questionnaire (0 to 18 years); iii. Spence Children's Anxiety Scale (3 to 18 years); iv. Short Mood and Feelings Questionnaires (6 to 18 years); v. Clinical and biochemical results obtained through routine care and hospitalisations (if available); vi. Sociodemographic factors (baseline survey only); * Anthropometrics: height, weight and BMI z-scores.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

No minimum to 18 Years

Healthy volunteers

Yes

Inclusion criteria

* Are aged between 0 and 18 years; * Have been diagnosed with a chronic gastrointestinal and/or respiratory condition defined by consensus diagnostic criteria; or * Are free of any chronic health condition (healthy control group); and * Have a parent(s)/carer(s) who provides informed consent, or are at least 16 years old and provide informed consent.

Exclusion criteria

* Children who have an unrelated coexisting chronic medical illness(es) associated with alterations in dietary intake or suspected alterations in the intestinal and/or respiratory microbiomes; * Inability to comply with study requirements; * Parent(s)/guardian(s) are unable to speak English or do not have a reading level age of at least 12 years.

Design outcomes

Primary

Measure	Time frame	Description
3E.i.12 Diet - diet quality score	Change from baseline at 12 months	Australia recommended food score. Maximum possible score of 73, higher is better (assessed using the ACAES only).
1D.ii.0 Intestinal Microbiome (Viruses) - Shannon index	Baseline	Measurement of alpha diversity (assessed metagenomic sequencing).
1A.ii.6 Intestinal Microbiome (Bacteria) - Shannon index	Change from baseline at 6 months	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
1A.i.0 Intestinal Microbiome (Bacteria) - Richness	Baseline	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
1A.i.6 Intestinal Microbiome (Bacteria) - Richness	Change from baseline at 6 months	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
1A.i.12 Intestinal Microbiome (Bacteria) - Richness	Change from baseline at 12 months	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
1A.ii.0 Intestinal Microbiome (Bacteria) - Shannon index	Baseline	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
1A.ii.12 Intestinal Microbiome (Bacteria) - Shannon index	Change from baseline at 12 months	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
1A.iii.0 Intestinal Microbiome (Bacteria) - UNIFRAC distances	Baseline	Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).
1A.iii.6 Intestinal Microbiome (Bacteria) - UNIFRAC distances	6 months	Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).
1A.iii.12 Intestinal Microbiome (Bacteria) - UNIFRAC distances	12 months	Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).
1A.iv.0 Intestinal Microbiome (Bacteria) - relative abundances of bacteria	Baseline	ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).
1A.iv.6 Intestinal Microbiome (Bacteria) - relative abundances of bacteria	Change from baseline at 6 months	ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).
1A.iv.12 Intestinal Microbiome (Bacteria) - relative abundances of bacteria	Change from baseline at 12 months	ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).
1B.i.0 Intestinal Microbiome (Proteome) - normalised abundances of proteins	Baseline	(assessed using LC-MS).
1B.i.6 Intestinal Microbiome (Proteome) - normalised abundances of proteins	Change from baseline at 6 months	(assessed using LC-MS).
1B.i.12 Intestinal Microbiome (Proteome) - normalised abundances of proteins	Change from baseline at 12 months	(assessed using LC-MS).
1C.i.0 Intestinal Microbiome (Metabolome) - normalised abundances of metabolites	Baseline	(assessed using LC-MS).
1C.i.6 Intestinal Microbiome (Metabolome) - normalised abundances of metabolites	Change from baseline at 6 months	(assessed using LC-MS).
1C.i.12 Intestinal Microbiome (Metabolome) - normalised abundances of metabolites	Change from baseline at 12 months	(assessed using LC-MS).
1D.i.0 Intestinal Microbiome (Viruses) - Richness	Baseline	Measurement of alpha diversity (assessed metagenomic sequencing).
1D.i.6 Intestinal Microbiome (Viruses) - Richness	Change from baseline at 6 months	Measurement of alpha diversity (assessed metagenomic sequencing).
1D.i.12 Intestinal Microbiome (Viruses) - Richness	Change from baseline at 12 months	Measurement of alpha diversity (assessed metagenomic sequencing).
1D.ii.6 Intestinal Microbiome (Viruses) - Shannon index	Change from baseline at 6 months	Measurement of alpha diversity (assessed metagenomic sequencing).
1D.ii.12 Intestinal Microbiome (Viruses) - Shannon index	Change from baseline at 12 months	Measurement of alpha diversity (assessed metagenomic sequencing).
1D.iii.0 Intestinal Microbiome (Viruses) - Bray-Curtis dissimilarity	Baseline	Measurement of beta diversity (assessed metagenomic sequencing).
1D.iii.6 Intestinal Microbiome (Viruses) - Bray-Curtis dissimilarity	6 months	Measurement of beta diversity (assessed metagenomic sequencing).
1D.iii.12 Intestinal Microbiome (Viruses) - Bray-Curtis dissimilarity	12 months	Measurement of beta diversity (assessed metagenomic sequencing).
1D.iv.0 Intestinal Microbiome (Viruses) - relative abundances of viruses.	Baseline	ANCOM analysis (assessed metagenomic sequencing).
1D.iv.6 Intestinal Microbiome (Viruses) - relative abundances of viruses.	Change from baseline at 6 months	ANCOM analysis (assessed metagenomic sequencing).
1D.iv.12 Intestinal Microbiome (Viruses) - relative abundances of viruses.	Change from baseline at 12 months	ANCOM analysis (assessed metagenomic sequencing).
2A.i.0 Respiratory Microbiome (Bacteria) - Richness	Baseline	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
2A.i.6 Respiratory Microbiome (Bacteria) - Richness	Change from baseline at 6 months	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
2A.i.12 Respiratory Microbiome (Bacteria) - Richness	Change from baseline at 12 months	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
2A.ii.0 Respiratory Microbiome (Bacteria) - Shannon index	Baseline	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
2A.ii.6 Respiratory Microbiome (Bacteria) - Shannon index	Change from baseline at 6 months	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
2A.ii.12 Respiratory Microbiome (Bacteria) - Shannon index	Change from baseline at 12 months	Measurement of alpha diversity (assessed using 16S rRNA or metagenomic gene sequencing).
2A.iii.0 Respiratory Microbiome (Bacteria) - UNIFRAC distances	Baseline	Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).
2A.iii.6 Respiratory Microbiome (Bacteria) - UNIFRAC distances	Change from baseline at 6 months	Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).
2A.iii.12 Respiratory Microbiome (Bacteria) - UNIFRAC distances	Change from baseline at 12 months	Measurement of beta diversity (assessed using 16S rRNA or metagenomic gene sequencing).
2A.iv.0 Respiratory Microbiome (Bacteria) - relative abundances of bacteria	Baseline	ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).
2A.iv.6 Respiratory Microbiome (Bacteria) - relative abundances of bacteria	Change from baseline at 6 months	ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).
2A.iv.12 Respiratory Microbiome (Bacteria) - relative abundances of bacteria	Change from baseline at 12 months	ANCOM analysis (assessed using 16S rRNA or metagenomic gene sequencing).
2B.i.0 Respiratory Microbiome (Proteome) - normalised abundances of proteins	Baseline	(assessed using LC-MS).
2B.i.6 Respiratory Microbiome (Proteome) - normalised abundances of proteins	Change from baseline at 6 months	(assessed using LC-MS).
2B.i.12 Respiratory Microbiome (Proteome) - normalised abundances of proteins	Change from baseline at 12 months	(assessed using LC-MS).
2C.i.0 Respiratory Microbiome (Metabolome) - normalised abundances of metabolites	Baseline	(assessed using LC-MS).
2C.i.6 Respiratory Microbiome (Metabolome) - normalised abundances of metabolites	Change from baseline at 6 months	(assessed using LC-MS).
2C.i.12 Respiratory Microbiome (Metabolome) - normalised abundances of metabolites	Change from baseline at 12 months	(assessed using LC-MS).
2D.i.0 Respiratory Microbiome (Viruses) - Richness	Baseline	Measurement of alpha diversity (assessed metagenomic sequencing).
2D.i.6 Respiratory Microbiome (Viruses) - Richness	Change from baseline at 6 months	Measurement of alpha diversity (assessed metagenomic sequencing).
2D.i.12 Respiratory Microbiome (Viruses) - Richness	Change from baseline at 12 months	Measurement of alpha diversity (assessed metagenomic sequencing).
2D.ii.0 Respiratory Microbiome (Viruses) - Shannon index	Baseline	Measurement of alpha diversity (assessed metagenomic sequencing).
2D.ii.6 Respiratory Microbiome (Viruses) - Shannon index	Change from baseline at 6 months	Measurement of alpha diversity (assessed metagenomic sequencing).
2D.ii.12 Respiratory Microbiome (Viruses) - Shannon index	Change from baseline at 12 months	Measurement of alpha diversity (assessed metagenomic sequencing).
2D.iii.0 Respiratory Microbiome (Viruses) - Bray-Curtis dissimilarity	Baseline	Measurement of beta diversity (assessed metagenomic sequencing).
2D.iii.6 Respiratory Microbiome (Viruses) - Bray-Curtis dissimilarity	6 months	Measurement of beta diversity (assessed metagenomic sequencing).
2D.iii.12 Respiratory Microbiome (Viruses) - Bray-Curtis dissimilarity	12 months	Measurement of beta diversity (assessed metagenomic sequencing).
2D.iv.0 Respiratory Microbiome (Viruses) - relative abundances of viruses	Baseline	ANCOM analysis (assessed metagenomic sequencing).
2D.iv.6 Respiratory Microbiome (Viruses) - relative abundances of viruses	Change from baseline at 6 months	ANCOM analysis (assessed metagenomic sequencing).
2D.iv.12 Respiratory Microbiome (Viruses) - relative abundances of viruses	Change from baseline at 12 months	ANCOM analysis (assessed metagenomic sequencing).
3A.i.0 Diet - total energy intake	Baseline	Kilojoules (assessed using a 24-hour recall or ACAES).
3A.i.6 Diet - total energy intake	Change from baseline at 6 months	Kilojoules (assessed using a 24-hour recall or ACAES).
3A.i.12 Diet - total energy intake	Change from baseline at 12 months	Kilojoules (assessed using a 24-hour recall or ACAES).
3B.i.0 Diet - percentage energy from core foods	Baseline	(assessed using a 24-hour recall or ACAES).
3B.i.6 Diet - percentage energy from core foods	Change from baseline at 6 months	(assessed using a 24-hour recall or ACAES).
3B.i.12 Diet - percentage energy from core foods	Change from baseline at 12 months	(assessed using a 24-hour recall or ACAES).
3C.i.0 Diet - total macronutrients intake	Baseline	Grams (assessed using a 24-hour recall or ACAES).
3C.i.6 Diet - total macronutrients intake	Change from baseline at 6 months	Grams (assessed using a 24-hour recall or ACAES).
3C.i.12 Diet - total macronutrients intake	Change from baseline at 12 months	Grams (assessed using a 24-hour recall or ACAES).
3C.ii.0 Diet - macronutrients proportion of total energy intake	Baseline	Percentage (assessed using a 24-hour recall or ACAES).
3C.ii.6 Diet - macronutrients proportion of total energy intake	Change from baseline at 6 months	Percentage (assessed using a 24-hour recall or ACAES).
3C.ii.12 Diet - macronutrients proportion of total energy intake	Change from baseline at 12 months	Percentage (assessed using a 24-hour recall or ACAES).
3D.i.0 Diet - total micronutrients intake	Baseline	Milligrams (assessed using a 24-hour recall or ACAES).
3D.i.6 Diet - total micronutrients intake	Change from baseline at 6 months	Milligrams (assessed using a 24-hour recall or ACAES).
3D.i.12 Diet - total micronutrients intake	Change from baseline at 12 months	Milligrams (assessed using a 24-hour recall or ACAES).
3D.ii.0 Diet - micronutrients proportion of total energy intake	Baseline	Percentage (assessed using a 24-hour recall or ACAES).
3D.ii.6 Diet - micronutrients proportion of total energy intake	Change from baseline at 6 months	Percentage (assessed using a 24-hour recall or ACAES).
3D.ii.12 Diet - micronutrients proportion of total energy intake	Change from baseline at 12 months	Percentage (assessed using a 24-hour recall or ACAES).
3E.i.0 Diet - diet quality score	Baseline	Australia recommended food score. Maximum possible score of 73, higher is better (assessed using the ACAES only).
3E.i.6 Diet - diet quality score	Change from baseline at 6 months	Australia recommended food score. Maximum possible score of 73, higher is better (assessed using the ACAES only).

Secondary

Measure	Time frame	Description
4A.i.0 Faecal biomarkers - calprotectin	Baseline	mg/kg (assessed using an ELISA).
4A.i.6 Faecal biomarkers - calprotectin	Change from baseline at 6 months	mg/kg (assessed using an ELISA).
4A.i.12 Faecal biomarkers - calprotectin	Change from baseline at 12 months	mg/kg (assessed using an ELISA).
4A.ii.0 Faecal biomarkers - M2 pyruvate kinase	Baseline	U/mL (assessed using an ELISA).
4A.ii.6 Faecal biomarkers - M2 pyruvate kinase	Change from baseline at 6 months	U/mL (assessed using an ELISA).
4A.ii.12 Faecal biomarkers - M2 pyruvate kinase	Change from baseline at 12 months	U/mL (assessed using an ELISA).
4A.iii.0 Faecal biomarkers - C-reactive protein	Baseline	mg/L (assessed using an ELISA).
4A.iii.6 Faecal biomarkers - C-reactive protein	Change from baseline at 6 months	mg/L (assessed using an ELISA).
4A.iii.12 Faecal biomarkers - C-reactive protein	Change from baseline at 12 months	mg/L (assessed using an ELISA).
4A.iv.0 Faecal biomarkers - Interleukins	Baseline	IU (assessed using an ELISA).
4A.iv.6 Faecal biomarkers - Interleukins	Change from baseline at 6 months	IU (assessed using an ELISA).
5A.i.0 Symptomatology & HRQOL - PedsQL Infant Scales (ages 1-12 and 13-24 months)	Baseline	Parent report for infants (ages 1-12 months) or (ages 13-24 months). Score out of 100, higher scores indicate better HRQOL.
4A.iv.12 Faecal biomarkers - Interleukins	Change from baseline at 12 months	IU (assessed using an ELISA).
4B.i.0 Respiratory biomarkers - calprotectin	Baseline	mg/kg (assessed using an ELISA).
4B.i.6 Respiratory biomarkers - calprotectin	Change from baseline at 6 months	mg/kg (assessed using an ELISA).
4B.i.12 Respiratory biomarkers - calprotectin	Change from baseline at 12 months	mg/kg (assessed using an ELISA).
4B.ii.0 Respiratory biomarkers - C-reactive protein	Baseline	mg/L (assessed using an ELISA).
4B.ii.6 Respiratory biomarkers - C-reactive protein	Change from baseline at 6 months	mg/L (assessed using an ELISA).
4B.ii.12 Respiratory biomarkers - C-reactive protein	Change from baseline at 12 months	mg/L (assessed using an ELISA).
4B.iii.0 Respiratory biomarkers - Interleukins	Baseline	IU (assessed using an ELISA).
4B.iii.6 Respiratory biomarkers - Interleukins	Change from baseline at 6 months	IU (assessed using an ELISA).
4B.iii.12 Respiratory biomarkers - Interleukins	Change from baseline at 12 months	IU (assessed using an ELISA).
5A.i.6 Symptomatology & HRQOL - PedsQL Infant Scales (ages 1-12 and 13-24 months)	Change from baseline at 6 months	Parent report for infants (ages 1-12 months) or (ages 13-24 months). Score out of 100, higher scores indicate better HRQOL.
5A.i.12 Symptomatology & HRQOL - PedsQL Infant Scales (ages 1-12 and 13-24 months)	Change from baseline at 12 months	Parent report for infants (ages 1-12 months) or (ages 13-24 months). Score out of 100, higher scores indicate better HRQOL.
5A.ii.0 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 2-4 years)	Baseline	Parent report for toddlers (ages 2-4 years). Score out of 100, higher scores indicate better HRQOL.
5A.ii.6 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 2-4 years)	Change from baseline at 6 months	Parent report for toddlers (ages 2-4 years). Score out of 100, higher scores indicate better HRQOL.
5A.ii.12 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 2-4 years)	Change from baseline at 12 months	Parent report for toddlers (ages 2-4 years). Score out of 100, higher scores indicate better HRQOL.
5A.iii.0 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 5-7 years)	Baseline	Parent report for young children (ages 5-7 years) or young child report (ages 5-7 years). Score out of 100, higher scores indicate better HRQOL.
5A.iii.6 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 5-7 years)	Change from baseline at 6 months	Parent report for young children (ages 5-7 years) or young child report (ages 5-7 years). Score out of 100, higher scores indicate better HRQOL.
5A.iii.12 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 5-7 years)	Change from baseline at 12 months	Parent report for young children (ages 5-7 years) or young child report (ages 5-7 years). Score out of 100, higher scores indicate better HRQOL.
5A.iv.0 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 8-12 years)	Baseline	Parent report for children (ages 8-12 years) or child report (ages 8-12 years). Score out of 100, higher scores indicate better HRQOL.
5A.iv.6 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 8-12 years)	Change from baseline at 6 months	Parent report for children (ages 8-12 years) or child report (ages 8-12 years). Score out of 100, higher scores indicate better HRQOL.
5A.iv.12 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 8-12 years)	Change from baseline at 12 months	Parent report for children (ages 8-12 years) or child report (ages 8-12 years). Score out of 100, higher scores indicate better HRQOL.
5A.v.0 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 13-18 years)	Baseline	Parent report for teens (ages 13-18 years) or teen report (ages 13-18 years). Score out of 100, higher scores indicate better HRQOL.
5A.v.6 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 13-18 years)	Change from baseline at 6 months	Parent report for teens (ages 13-18 years) or teen report (ages 13-18 years). Score out of 100, higher scores indicate better HRQOL.
5A.v.12 Symptomatology & HRQOL - PedsQL Gastrointestinal Symptoms Module (ages 13-18 years)	Change from baseline at 12 months	Parent report for teens (ages 13-18 years) or teen report (ages 13-18 years). Score out of 100, higher scores indicate better HRQOL.
5B.i.0 Symptomatology & HRQOL - Rome IV Parent-Report Form for Infants and Toddlers (ages 0-3)	Baseline	29 items for ages 0-12 months. 18 items for ages 1-3 years. Defined diagnostic criteria for functional gastrointestinal disorders in neonates and toddlers: Infant regurgitation, Infant rumination syndrome, Cyclic vomiting syndrome, Infant colic, Functional diarrhoea, Infant dyschezia, Functional constipation.
5B.i.6 Symptomatology & HRQOL - Rome IV Parent-Report Form for Infants and Toddlers (ages 0-3)	6 months	29 items for ages 0-12 months. 18 items for ages 1-3 years. Defined diagnostic criteria for functional gastrointestinal disorders in neonates and toddlers: Infant regurgitation, Infant rumination syndrome, Cyclic vomiting syndrome, Infant colic, Functional diarrhoea, Infant dyschezia, Functional constipation.
5B.i.12 Symptomatology & HRQOL - Rome IV Parent-Report Form for Infants and Toddlers (ages 0-3)	12 months	29 items for ages 0-12 months. 18 items for ages 1-3 years. Defined diagnostic criteria for functional gastrointestinal disorders in neonates and toddlers: Infant regurgitation, Infant rumination syndrome, Cyclic vomiting syndrome, Infant colic, Functional diarrhoea, Infant dyschezia, Functional constipation.
5B.ii.0 Symptomatology & HRQOL - Rome IV Parent-Report Form for Children and Adolescents (4 years of age and older)	Baseline	42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.
5B.ii.6 Symptomatology & HRQOL - Rome IV Parent-Report Form for Children and Adolescents (4 years of age and older)	6 months	42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.
5B.ii.12 Symptomatology & HRQOL - Rome IV Parent-Report Form for Children and Adolescents (4 years of age and older)	12 months	42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.
5B.iii.0 Symptomatology & HRQOL - Rome IV Self-Report Form for Children and Adolescents (10 years of age and older)	Baseline	42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.
5B.iii.6 Symptomatology & HRQOL - Rome IV Self-Report Form for Children and Adolescents (10 years of age and older)	6 months	42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.
5B.iii.12 Symptomatology & HRQOL - Rome IV Self-Report Form for Children and Adolescents (10 years of age and older)	12 months	42 items. Defined diagnostic criteria for functional gastrointestinal disorders in children and adolescents: Cyclic vomiting syndrome, Functional nausea and functional vomiting, Rumination syndrome, Aerophagia, Functional dyspepsia, Irritable bowel syndrome, Abdominal migraine, Functional abdominal pain - not otherwise specified, Functional Constipation, Nonretentive fecal incontinence.
5C.i.0 Symptomatology & HRQOL - Spence Children's Anxiety Scale; Preschool Anxiety Scale (Parent report for ages 0 to 4)	Baseline	34 items. Maximum possible scores of 112. A score 1 SD above mean for a subscale or total score warrants further clinical investigation. A score of 0.5 SD above the mean on total score is indicative of an elevated, but not clinical level of anxiety.
5C.i.6 Symptomatology & HRQOL - Spence Children's Anxiety Scale; Preschool Anxiety Scale (Parent report for ages 0 to 4)	Change from baseline at 6 months	34 items. Maximum possible scores of 112. A score 1 SD above mean for a subscale or total score warrants further clinical investigation. A score of 0.5 SD above the mean on total score is indicative of an elevated, but not clinical level of anxiety.
5C.i.12 Symptomatology & HRQOL - Spence Children's Anxiety Scale; Preschool Anxiety Scale (Parent report for ages 0 to 4)	Change from baseline at 12 months	34 items. Maximum possible scores of 112. A score 1 SD above mean for a subscale or total score warrants further clinical investigation. A score of 0.5 SD above the mean on total score is indicative of an elevated, but not clinical level of anxiety.
5C.ii.0 Symptomatology & HRQOL - Spence Children's Anxiety Scale (Parent report for 5 years and older)	Baseline	38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.
5C.ii.6 Symptomatology & HRQOL - Spence Children's Anxiety Scale (Parent report for 5 years and older)	Change from baseline at 6 months	38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.
5C.ii.12 Symptomatology & HRQOL - Spence Children's Anxiety Scale (Parent report for 5 years and older)	Change from baseline at 12 months	38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.
5C.iii.0 Symptomatology & HRQOL - Spence Children's Anxiety Scale (8 years and older)	Baseline	38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.
5C.iii.6 Symptomatology & HRQOL - Spence Children's Anxiety Scale (8 years and older)	Change from baseline at 6 months	38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.
5C.iii.12 Symptomatology & HRQOL - Spence Children's Anxiety Scale (8 years and older)	Change from baseline at 12 months	38 scored items. Maximum possible scores of 114. A score 1 SD above mean (T-score of ≥ 60) for a subscale or total score is indicative of subclinical or elevated levels of anxiety warranting further clinical investigation.
5D.i.0 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Parent Report on Child, ages 6-18 years).	Baseline	13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.
5D.i.6 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Parent Report on Child, ages 6-18 years).	Change from baseline at 6 months	13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.
5D.i.12 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Parent Report on Child, ages 6-18 years).	Change from baseline at 12 months	13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.
5D.ii.0 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Child Self Report, ages 6-18 years).	Baseline	13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.
5D.ii.6 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Child Self Report, ages 6-18 years).	Change from baseline at 6 months	13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.
5D.ii.12 Symptomatology & HRQOL - Mood and Feelings Questionnaire (Short Version) (Child Self Report, ages 6-18 years).	Change from baseline at 12 months	13 items. Maximum possible scores of 26. Higher scores suggest more severe depressive symptoms. A score of ≥ 12 may indicate the presence of depression in the respondent.
6A.i.0 Phenotypic & Clinical Information - Weight (ages 0 to 20 years)	Baseline	Z-score.
6A.i.6 Phenotypic & Clinical Information - Weight (ages 0 to 20 years)	Change from baseline at 6 months	Z-score.
6A.i.12 Phenotypic & Clinical Information - Weight (ages 0 to 20 years)	Change from baseline at 12 months	Z-score.
6A.ii.0 Phenotypic & Clinical Information - Length (ages 0 to 2 years)	Baseline	Z-score.
6A.ii.6 Phenotypic & Clinical Information - Length (ages 0 to 2 years)	Change from baseline at 6 months	Z-score.
6A.ii.12 Phenotypic & Clinical Information - Length (ages 0 to 2 years)	Change from baseline at 12 months	Z-score.
6A.iii.0 Phenotypic & Clinical Information - Height (ages 2 to 20 years)	Baseline	Z-score.
6A.iii.6 Phenotypic & Clinical Information - Height (ages 2 to 20 years)	Change from baseline at 6 months	Z-score.
6A.iii.12 Phenotypic & Clinical Information - Height (ages 2 to 20 years)	Change from baseline at 12 months	Z-score.
6A.iv.0 Phenotypic & Clinical Information - Weight-for-length (ages 0 to 2 years)	Baseline	Z-score.
6A.iv.6 Phenotypic & Clinical Information - Weight-for-length (ages 0 to 2 years)	Change from baseline at 6 months	Z-score.
6A.iv.12 Phenotypic & Clinical Information - Weight-for-length (ages 0 to 2 years)	Change from baseline at 12 months	Z-score.
6A.v.0 Phenotypic & Clinical Information - Body mass index (ages 2 to 20 years)	Baseline	Z-score.
6A.v.6 Phenotypic & Clinical Information - Body mass index (ages 2 to 20 years)	Change from baseline at 6 months	Z-score.
6A.v.12 Phenotypic & Clinical Information - Body mass index (ages 2 to 20 years)	Change from baseline at 12 months	Z-score.
6B.i.6 Phenotypic & Clinical Information - Number of hospitalisations	6 months	During period from baseline to 6 months.
6B.i.12 Phenotypic & Clinical Information - Number of hospitalisations	12 months	During period from baseline to 12 months.
6B.ii.6 Phenotypic & Clinical Information - Length of hospitalisations	6 months	Days hospitalised during period from baseline to 6 months.
6B.ii.12 Phenotypic & Clinical Information - Length of hospitalisations	12 months	Days hospitalised during period from baseline to 12 months.
6B.iii.6 Phenotypic & Clinical Information - Number of emergency department presentations	6 months	During period from baseline to 6 months.
6B.iii.12 Phenotypic & Clinical Information - Number of emergency department presentations	12 months	During period from baseline to 12 months.

Countries

Australia

Contacts

Primary ContactMichael J Coffey

michael.coffey@unsw.edu.au61293825574

Backup ContactChee (Keith) Y Ooi

keith.ooi@unsw.edu.au61293825512

Outcome results