child cohort study version date: dec 2019

CHILD Cohort Study

Version Date: Dec 2019 Protocol Objective: The purpose of the following protocol is to describe specific procedures performed during the conduct of the continuing CHILD research project. Distribution of the protocol will be to the investigators and institutions named in the CHILD Study. Permission to distribute to other parties requires written permission from the Principal Investigator(s).

2 CHILD Study Follow-up Protocol Version date: 4 Dec 2019

Amendments: Any changes to the content, questionnaires and protocols will be submitted in writing to the Director of the Study, Dr. Padmaja Subbarao, or to the Research Manager, Dr. Diana Lefebvre. Content change requests will be reviewed by the Director and the Executive team and amendments to the CHILD Study protocol will be recorded below.

Log of Protocol Versions and Amendments

Date of Update Description of Update Current Version Date

26 January 2018 New protocol for continuing the CHILD Study beyond age 5 years

11 May 2018

4 Dec 2019 Name and logo change to study 4 Dec 2019


TABLE OF CONTENTS

Study Synopsis 4

Organizational Chart 4

National Director and Site Leaders 5

Section 1: Executive Summary 6

National Coordinating Centre – Hamilton 7 Senior Study Centre Coordinators 8 Study Objectives 9 Study Design 9 Inclusion/Exclusion Criteria 9 Study Timelines 10 Study Outcomes 11

Section 2: Study Participant Activities

Assessments at age 8 years 1. Parent-completed questionnaires 12 2. Child-completed questionnaires 14 3. 8-Year clinic visit 14

A. Visit summary for accompanying parent(s) 14 B. Visit summary for study child 15 C. Questionnaires administered to child in clinic 15

4. Clinic tests A. Tests for accompanying parent(s) 16 B. Tests for study child 16

5. Biological sample collection 18 6. Participant Engagement Activities 19 7. Health Chart Review and Database Linkages 19

Data Management and Data Entry 19 Reimbursement 20 Shipping Biological Samples to Central Storage 20 References 20

Section 3: Working Groups and Committees

Scientific Working Groups 22 CHILD Committees 24

FIGURES

Figure 1: CHILD Study timeline 10 Figure 2: Overlap of childhood conditions with early life origins 11

TABLES: Table 1: Data collection summary from recruitment to age 8 years 27 Table 2: CHILD Study questionnaires 8 years 28 Table 3: Standard operating procedures 8 years 29


Study Synopsis

This national longitudinal birth cohort study was developed in 2006-7 to examine gene-environment factors in relation to children’s health and development, specifically in relation to allergy and asthma. The study was developed in response to the RFA from CIHR in 2005, entitled “Indoor Air Exposures, Genes, and Gene-Environment Interactions in the Etiology of Asthma and Allergy in Early Childhood”.

Subsequent to this initial mandate, the CHILD Study is continuing beyond the 5-year follow-up, broadening the scope to include investigations relevant to development of other chronic non-communicable diseases with probable early life origins. Assessments are anticipated for all participating children at ages 8, 11 and 14 years, these ages reflecting childhood and adolescent development before, during and following puberty.

ORGANIZATIONAL CHART


NATIONAL DIRECTOR AND SITE LEADERS

National Director

Padmaja Subbarao The Hospital for Sick Children Division of Respiratory Medicine 555 University Avenue Toronto, Ontario M5G 1X8 [email protected] Tel: 416-813-6247 or 416-813-2196 (Admin)

Pediatricians / Site Leaders Toronto Theo Moraes

The Hospital for Sick Children Division of Respiratory Medicine 555 University Avenue Toronto, Ontario M5G 1X8 [email protected] Tel: 416-813-7654 ext 5125

Manitoba Allan Becker (lead) University of Manitoba AE101-840 Sherbrook Street Winnipeg, MB R3A 1S1 [email protected] Tel: 204-787-2455

Meghan Azad (co-lead) University of Manitoba 501G John Buhler Research Centre 715 McDermot Avenue Winnipeg, MB R3E 3P4 [email protected] Tel: 204-975-7754

Edmonton Piush Mandhane 8308 114 St, 2-034 RTF Edmonton, AB T6G 2V2 [email protected] Tel: 780-407-2753

Vancouver Stuart Turvey Division of Infect. & Immun Diseases BC Children’s Hospital Child and Family Research Institute 371-950 West 28th Avenue Vancouver, BC, V5Z 4H4 [email protected] Tel: 604-875-2345

mailto:[email protected]







SECTION 1: EXECUTIVE SUMMARY In December 2007, following international peer review, CIHR awarded $6M over 6 years to a consortium of investigators led by Professor Malcolm Sears, McMaster University. This Canadian longitudinal birth cohort study, launched in 2008, focused primarily on the environment and gene-environment interactions, underlying the development of allergies and asthma in childhood. CIHR funding was matched by $6M from the Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence. A network of over 40 investigators, the majority already members of the AllerGen Network of Centres of Excellence, came together under the overall direction of Dr. Sears, now Founding Director of CHILD. The majority of these initial 40 are continuing as research investigators in this expanded study, while several new investigators have joined the team. Disciplines represented include pediatric and adult respirology, population health, epidemiology, cardiovascular health, metabolic disorders, obesity, allergy and immunology, infectious diseases, environmental assessment, pulmonary physiology, genomics, nutrition, molecular biology, psychology, air quality, sociology, sleep, neuroimmunology, neurodevelopment, biostatistics and bioethics. The CHILD Study recruited 3,623 pregnant women in 4 provinces across Canada, of whom 3,495 gave birth to children eligible for the study and provided some baseline data. Infants were studied at birth, at a home visit at 3-4 months, and at clinic visits at ages 1, 3 and 5 years. Additional questionnaires were answered electronically at 6 months, 1½, 2, 2½ and 4 years.

Indoor and outdoor environmental exposures (questionnaires, home inspections, dust sampling) were assessed, along with immunological studies, genetic and epigenetic testing of DNA from child and parents, and longitudinal measures of pulmonary function, airway inflammation, nutrition and infections, focusing particularly on the critical window of the first year of life. Environmental assessments included sampling indoor allergens, endotoxin, beta (1,3)-D-glucans, phthalates, hopanes, and tobacco smoke. Outdoor exposure assessment employed land use regression techniques and other methodologies supported by Geographic Information Systems. Environmental and biologic materials were stored for later analyses. The study was powered on the primary outcome of diagnosed asthma, but intermediate outcomes of food allergy, allergic eczema, atopy and recurrent wheeze were assessed throughout.

Storage of biological material has allowed testing of multiple hypotheses and promoted the formulation and testing of novel hypotheses not conceived when the study began. The study has not only provided unique Canadian data essential to determining environmental effects on childhood allergy and asthma but has also enabled examination of important parental health research questions.

Continuing funding has been received through CIHR Project Grants and Team Grants, and through AllerGen NCE, together with grants from several other funding agencies, universities, foundations and private donors. The study has also been supported by Environment Canada, Health Canada and Canada Mortgage and Housing Corporation.

The availability of data from pregnancy and a wealth of early childhood data has allowed expansion of CHILD to study Developmental Origins of Health and Disease (DOHaD). Proposed future studies will explore origins of overweight/obesity, diabetes, cardiovascular disease, together with neurodevelopmental and sleep issues, while maintaining longitudinal studies of allergy and asthma.


NATIONAL COORDINATING CENTRE – HAMILTON

Diana Lefebvre Tel: 905-525-9140 ext. 24564 Research Manager Fax: 905-521-6132 McMaster University [email protected] 1280 Main Street West MDCL 3120 Hamilton ON L8S 4K1 Aimee Dubeau Tel: 416-813-7765 Project Manager Fax: 416-813-6246 The Hospital for Sick Children [email protected] Division of Respiratory Medicine 555 University Avenue Toronto, ON MGG 1X8 Vera Dai Tel: 416-813-7765 Statistical Analyst Fax: 416-813-6246 The Hospital for Sick Children [email protected] Division of Respiratory Medicine 555 University Avenue Toronto, ON MGG 1X8 Tyler Freitas Tel: 905-525-9140 ext. 24469 CHILD Data Manager Fax: 905-521-6132 McMaster University [email protected] 1280 Main Street West MDCL 3120 Hamilton ON L8S 4K1

Padmaja Subbarao Tel: 416-813-6167

CHILD Director [email protected] The Hospital for Sick Children Division of Respiratory Medicine 555 University Avenue Toronto, ON M5G 1X8





SENIOR STUDY CENTRE COORDINATORS

Toronto

Yaminee Charavanapavan Tel: 416-813-7765 Site Coordinator Fax: 416-813-6246 The Hospital for Sick Children [email protected] 686 Bay Street, Rm 08-9850 Toronto, ON M5G 1X8

Winnipeg

Phillip Snarr Tel: 204-789-3677 Site Coordinator Fax: 204-789-3986

John Buhler Research Centre [email protected] 504H – 715 McDermot Avenue Winnipeg, MB R3E 3P4

Edmonton

Joyce Chikuma Tel: 780-407-8084 Site Coordinator Fax: 780-401-8262 8308 114 Street, 2-034 RTF [email protected] Edmonton, AB T6G 2V2

Vancouver

Linda Warner Tel: 604-875-2000 x 7884 Site Coordinator [email protected] BC Children’s Hospital Research Institute 950 West 28th Avenue Vancouver, BC V5Z 4H4






SECTION 2: OVERVIEW

STUDY OBJECTIVES

The primary objective of this Canadian national longitudinal birth cohort study was to determine the roles of a range of environmental factors and their interactions with genetic and host factors in the development of allergy and asthma in children. This required multiple objective measurements especially focusing on the indoor environment (home inspection, dust collection), child responses (immune function, endocrine, pulmonary function, infections, allergies and clinical assessment) and genetic factors, together with extensive questionnaire data (demographics, family history, diet, activity, housing environment, psychosocial environment and stress) in a prospective longitudinal birth cohort of 3,495 children recruited in pregnancy in a general population.

These data now form the basis for a continuing and expanded study of childhood and adolescent health, focused on Developmental Origins of Health and Disease (DOHaD), for a wide range of chronic non-communicable diseases including asthma and allergic disorders, overweight/obesity, cardiovascular disease, metabolic disorders including diabetes, and neurodevelopment.

STUDY DESIGN

This study will continue to follow the fully recruited and carefully phenotyped general population based prospective cohort of 3,495 children and families recruited across 4 centres in Canada. The expectation is that the cohort will be reassessed at age 8 (pre-puberty), 11 (pubertal) and 14 years (post-pubertal).

The longitudinal design of the CHILD Study has allowed prospective evaluation of multiple indoor and outdoor environmental exposures, serial measurements of immunological responses, anthropometrics, nutrition, lung function and airway inflammation, infections, allergies, socioeconomic factors, stressful environments, genetics and epigenetic phenomena, and specific clinical outcomes primarily related to allergy and asthma.

Following this established national birth cohort will allow tracking of the timing of a wide variety of potentially important exposures and health events from pregnancy into adolescence. Linkage with rich Canadian health databases and possibly other cohort studies will allow the study of many other health outcomes apart from those for which the study was originally established.

INCLUSION AND EXCLUSION CRITERIA AGE 8-9 YEARS

INCLUSION:

• All children eligible and enrolled in the original CHILD study who have not been officially withdrawn are eligible for this continuing study.

• No new children will be enrolled. • Children who have missed assessments throughout the first 5 years remain eligible unless withdrawn. • Children who have moved from their original centre remain eligible.

EXCLUSION:

• Children who have been previously withdrawn by the investigator or by the parent(s)


STUDY TIMELINES

1. CHILD STUDY (PRENATAL TO 5 YEARS): Dec 2007 Approval of Initial Funding Jan 2008 – May 2008 Funding to Universities, Startup process Sept 2008 – Dec 2008 Vanguard Recruitment of 220 mothers Jan 2009 – June 2009 Review Vanguard, Assess study collection tools, procedures July 2009 – Oct 2012 Recruitment of General cohort Jan 2010 – Mar 2018 Clinical assessments up to age 5 years

2. CHILD STUDY Follow-up:

Dec 2017 – Mar 2018 Clinical assessments of 8-9-year olds, Vanguard cohort Mar 2018 – Mar 2021 Clinical assessments of 8-9-year olds, General cohort

Figure 1: CHILD Study Timeline


STUDY OUTCOMES Multiple health and disease outcomes will be assessed, including:

• Asthma • Allergic rhinitis • Atopic dermatitis • Food allergy • Lung function • Diabetes • Overweight/obesity • Metabolic disorder • Neurodevelopment • Sleep patterns • Sleep-disordered breathing

Many of these conditions show evidence for overlap, and have significant data indicating that early childhood conditions impact development and persistence (the Developmental Origins of Health and Disease [DOHaD] hypothesis).

Figure 2: Overlap of childhood conditions with early life origins


SECTION 2: STUDY PARTICIPANT ACTIVITIES ASSESSMENTS AT AGE 8 YEARS 1. Parent-Completed Questionnaires

The majority of questionnaires will be completed online by the parent or guardian prior to the clinic visit. Paper copies of the questionnaires will be sent to parents if requested. The estimated time for completion of all questionnaires is 2-3 hours, which can be spread over days or weeks. Questionnaires will be available for completion from 3 months before the child’s visit and up to 6 months after the child’s 8th birthday.

• Child Health: • Asthma/Allergy: colds, cough, wheezing, rhinitis, eczema/atopic dermatitis, food/environmental

allergy • Cardiometabolic: cardiovascular risk factors, metabolic disorders such as diabetes, obesity • Neurodevelopment: behaviour, depression, anxiety, impairment • General: other medical conditions the child may have had, unscheduled doctor visits, emergency

room visits, hospitalizations, vaccinations • Tanner puberty staging: A short questionnaire (separate questionnaires for boys and girls) based on the

Tanner staging system of physical development of external sex characteristics will be completed by a parent prior to the clinic visit by selecting the most appropriate illustration of their child’s current pubertal development. Parental selections will be reviewed by a trained healthcare professional conducting the clinic visit.

• Maternal health and lifestyle: Health conditions ever, and in last year; respiratory symptoms; allergies; lifestyle including smoking, and family structure. The social influences of physical activity will be assessed with questions related the mother’s physical activities such as frequencies of engagement in various indoor and outdoor activities as well as sedentary behaviours.

• Paternal health and lifestyle: Health conditions ever, and in last year; respiratory symptoms; allergies; lifestyle including smoking, and family structure. The social influences of physical activity will be assessed with questions related the father’s physical activities such as frequencies of engagement in various indoor and outdoor activities as well as sedentary behaviours.

• Medication: Medication logs will be used by the parent to record prescribed medications used by the child.

• Nutrition: A child food frequency questionnaire will request information on frequency of eating different groupings of food to assess dietary patterns. Further questions relate to the child’s consumption of artificial sweeteners, supplements such as vitamins and botanicals, family eating and activity habits and behaviours, and food packaging and preparation.

• Home and Environment: A comprehensive questionnaire will request information regarding the child’s current residence including moisture and ventilation, pests and bugs, cooking and appliance emissions, cleaning products used in the home, hobbies generating fumes in the home, smoke exposure (including tobacco, cannabis, e-cigarettes), exposure to domestic and farm animals, child’s school location and time-location information, time spent in transit, and usual modes of transport. Outdoor air exposure modeling will be based upon available monitoring data and land-use regression (LUR) techniques; green space, blue space and walkability around the primary residence will be assessed using standardized tools. Previous residences are noted. The amount and type of physical activity a child engages in is dependent upon many factors, including the physical and social environment in their neighbourhood, particularly with respect to unstructured physical activity such as playing in local parks, greenspaces and school yards, as well as

https://en.wikipedia.org/wiki/Child_development


walking or biking to destinations. Understanding how children and their parents perceive their neighbourhood’s environment (e.g., barriers to physical activity) and how this influences behaviour will allow researchers to determine ways to improve neighbourhoods, thus informing public policies related to urban/suburban planning and future interventions. Questions will obtain information about the specific activities the child engages in outside of school hours including organized sports and information about the child’s neighbourhood will be collected to assess possible barriers to the child engaging in physical activities. In addition, questions about physical education at school and time engaged in and social influences on sedentary activities (e.g., watching television or playing video games).

• Sleep: Patterns of sleeping, snoring, episodes of apnea, attentiveness, behaviour related to sleep and daytime sleepiness scale.

• Child Behaviour, School Performance and Neurodevelopment: The CHILD Study is continuing to explore psychosocial factors including the mental and physical health of families, and how they come to influence the well-being and health status of their child using validated psychosocial questionnaires. The age of 8 years marks the initiation of a high-risk period for mental health. With the onset of puberty, rates of anxiety and depression amongst both boys and girls increase rapidly and reach their peak at 17 to 24 years of age. At 8 years, more common disorders include disruptive behaviour disorders (mostly in boys) and a low rate of anxiety disorders (equally distributed between boys and girls). However, the risk factors that predict a trajectory through adolescence of increasing anxiety and mood symptoms are not well understood. Identification of modifiable risk factors prior to the onset of increasing trajectories is essential to develop interventions. A second and related issue is the relationship between “impairment” and disability. There are many children who are impaired and without a mental health disorder while other children fit criteria for mental health disorder but do not suffer from any impairment. Understanding the prevalence of impairment and/or disability (defined as difficulties getting along with peers, poor school performance, difficulty getting along with family, active participation in community activities and recreation) is important, innovative and has potential policy implications. Finally, bidirectional relationships between mental health, impairment and physical health such as obesity, poor sleep and restricted physical activity, as well as contextual variables such as parenting, timing of puberty, and cognitive variables predicting poor school performance will be studied. Other innovative variables include daily hassles, screen time, experience of failure and family history. Assessment of mental health will include scales for anxiety and depression prodromes during this risk period. The questionnaires that parents will be asked to complete include: Scales to assess obsessive-compulsive problems, stress problems, sluggish cognitive tempo, and

positive qualities (Child Behaviour Check List (CBCL) (1) (for ages 6-18 years). Assessment of the child’s school performance (Parent’s Ratings of Everyday Cognitive and

Academic Abilities (PRECAA) questionnaire) (2, 3) Assessment of general family functioning (selected questions from the McMaster Family

Assessment Device) (4) Assessment of parenting style (selected questions from the Alabama Parenting Questionnaire)

(5), Measures of global impairment of the child will be assessed by examining interpersonal relations,

broad psychopathological domains, functioning in schoolwork, and use of leisure time (Columbia Impairment Scale) (6),

Screening tool to measure parent’s perception of child’s depression quotient (Center for Epidemiological Studies Depression Scale for Children, CES-DC) (7, 8)

Parent reported bullying experienced by child (9). • Psychosocial: These assessments of psychosocial status deal with issues that may cause sensitivities in

some parents; to ensure parents feel safe, respected and valued, they may opt out of answering specific questions, or indicate they would appreciate follow-up with study staff. Four sets of psychosocial factors


will be explored: socioeconomic status (objective and subjective), social support/social capital, stress, and maternal depression. Socioeconomic scale:

• Resource-based SES. Parents will be asked about family assets, including income, savings, housing status (rent/own), number of bedrooms, and number of cars owned. Answers to each question will be standardized (z-scored for the sample) and the z-scores summed to create one composite asset score.

• Education SES. Years of education, and highest educational degree attained for each parent. • Subjective SES. Using the MacArthur Scale of Subjective Social Status parents will be asked to

place their household (relative to their community) on a ladder, with higher rungs indicate higher status.

Social support/social capital: The Social Provision Scale, a simple, well-validated 24-item scale in 5 dimensions (attachment, social integration, reassurance of worth, reliable alliance, guidance, opportunity for nurturance), will be administered to parents to ascertain potential mediators in the stress-outcome relationship.

Parenting stress: • Parental Stress questionnaire includes Perceived Stress Scale (measure the degree to which

situations in one’s life are appraised as stressful) and stress associated with parenting. Parental and child depression:

• Prescription and health care utilization data bases will be accessed. • CES-D questionnaire (10) will assess depression in the mother. • CES-DC questionnaire will evaluate the mother’s assessment of her child’s depression.

2. CHILD-COMPLETED QUESTIONNAIRES There are two questionnaires that will be available online for completion by the child prior to the clinic visit. Parents are encouraged to allow their child to answer these questions on her/his own with support only if the s/he requires assistance to read and/or understand the questions:

• Screen for Child Anxiety Related Disorders (Child Screen; self-report): This questionnaire (SCARED) consists of 41 questions which have been validated to screen for childhood anxiety disorders including general anxiety disorder, separation anxiety disorder, panic disorder, and social phobia (11). In addition, it assesses symptoms related to school phobias.

• Physical activity (self-report): A short, validated questionnaire will be completed by the child to assess the types of activities (sports and sedentary activities), frequency of participation in activities, and level of physical activities undertaken by the child in school and outside of school hours.

3. CLINIC VISIT

Clinic visit: This will be arranged at a time convenient to the family and will allow for weekend and possibly evening assessments.

Duration: The entire visit is anticipated to last 3-4 hours

Venue: Hospital or attached clinic/research space


A. Visit summary for accompanying parent(s): • Staff review of completeness and coherence of questionnaire data provided by parents • Anthropometrics - height, weight, hip and waist circumferences • Blood pressure • Body composition using Bioimpedance analysis (Tanita scale outputs: % body fat, % body water,

muscle mass, physique rating, basal metabolic rate, metabolic age, bone mass, and visceral fat rating) • Blood for Next Generation Sequencing technologies (i.e., exome and whole genome sequencing,

epigenetics (methylation) and “omics” analysis platforms) • Saliva for Next Generation Sequencing technologies (i.e., exome and whole genome sequencing,

epigenetics (methylation) and “omics” analysis platforms) • Saliva (if not able to provide blood) • Skin allergy tests (if not previously performed in CHILD) • Spirometry (if not previously performed in CHILD)

B. Visit summary for study child:

• Pediatrician administered clinical history of cough, wheeze, rhinitis, rash, food allergy, other medical problems

• Physical examination of the child • Record diagnoses of asthma, allergic rhinitis, atopic dermatitis • Anthropometrics – height, weight, mid-arm, hip and waist circumferences • Blood pressure • Skinfold measurements (subscapular, tricep) • Body composition using bioimpedance analysis (Tanita scale output: % body fat) • Body image (child selection of best schematic) • Skin allergy tests • Nasal swab for viral metabolomics and nasal microbiome analyses • Nasal brushing for epigenetics (DNA methylation) analyses • Blood for Next Generation Sequencing technologies (i.e., exome and whole genome sequencing,

epigenetics (methylation) and “omics” analysis platforms) • Saliva for Next Generation Sequencing technologies (i.e., exome and whole genome sequencing,

epigenetics (methylation) and “omics” analysis platforms) • Spirometry / Methacholine challenge test • 7-day accelerometry to assess sleep and sleep disturbances • 7-day GPS localization for time-location-activity determinations of physical activity

C. Questionnaires administered to child in clinic:

The CHILD Study will ask the 8-year-old children to complete some questionnaires by themselves, rather than or in addition to having the parents answer on behalf of their child. To accommodate reading comprehension, these questionnaires will be completed by the child at the clinic visit where CHILD Research Assistants will be available to aid her/him. It is important that the assessments of mental illness, which include anxiety, depression, and bullying questions from various validated sources, be completed by the child without parental influence. The child will be asked to complete the following:

• Childhood Asthma Control Test (CACT) for children 4-11 years will be scored by the child if they have current diagnosed asthma. The first 4 questions are completed by the child, and the last 3 questions by the parent. CACT is provided by Asthma Action America through GlaxoSmithKline.


• Child Body Image (self-report): A chart with visual renditions of body image is used for boys and girls separately and includes questions about her/his own perceived height, weight and shape compared to other children. In addition, there are questions relating to privacy and the current parent-child relationship. A Research Assistant will be available to help the child read/understand the questions, if needed.

• Centre for Epidemiological Studies Depression scale for Children (CES-DC): Depression will be assessed using the Depression Scale (7) comprised of 20 questions administered to the child in private during the clinic visit. These questions are also asked of the parent and the answers from the parent and child will be compared.

• Columbia Impairment Scale (CIS): This scale includes questions of how the child is doing overall in terms of getting along with others, enjoying life, behaviour, school work and relationships with adults (6). CIS comprises 13 questions administered to the child in private during the clinic visit.

• Bullying experiences at school: Anxiety generated by exposure to bullying will be assessed using a 10-question validated questionnaire (12) which will be administered to the child in private during the clinic visit.

4. CLINIC TESTS

A. Tests for Accompanying Parent(s): • Blood Pressure: Systolic and diastolic blood pressure measurements will be obtained in triplicate

using standardized tools. • Body Composition (Tanita scale): Bioimpedance analysis (BIA) is a means of measuring body

composition by measuring bioelectrical impedance in the body. Unlike Body Mass Index (BMI) measures, BIA differentiates between lean and fat mass. Fat within the body allows almost no electricity to pass through, while electricity passes easily through water, much of which is found in muscles. The degree of difficulty with which electricity passes through a substance is known as the electrical resistance, and the percentage of fat and other body constituents can be inferred from measurements of this resistance. The Tanita Body Composition Analyzer scale is an FDA approved device that measures body composition using a weak, high frequency current (50 kHz, 90 μA) that passes from leg to leg. For parents accompanying their child to the clinic visit, we plan to use a Tanita scale to estimate the body composition and record the following outputs: weight, % body fat, % body water, muscle mass, physique rating, basal metabolic rate, metabolic age, bone mass, and visceral fat rating. Individuals who have pacemakers or other internal medical devices will be excluded from this test.

• Skin Allergy Tests: Skin prick testing will be performed on parents only if they were not previously done prior to age 8 years. The allergens tested will be cat, dog, four molds, grass, weeds, trees, two house dust mites, cockroach, cow’s milk, egg white and peanut, together with positive and negative controls.

• Spirometry: Lung function testing (spirometry) will only be performed on mother and father if it was not previously done prior to age 8 years.

B. Tests for Study Child:

• Physical Assessment: A clinical assessment will be conducted by a trained health care professional. This will include a structured history through interaction with the child and the accompanying parent, as well as a limited physical examination. The examining healthcare professional will determine the presence of a history or physical evidence consistent with a diagnosis of asthma, allergic rhinitis, atopic dermatitis/eczema, food allergy and any other overt medical conditions.


• Anthropometrics: Height, weight, mid-arm, hip and waist circumference measurements will be obtained using standard measurement tools.

• Blood Pressure: Systolic and diastolic blood pressure measurements will be obtained in triplicate using standardized tools.

• Skinfold Measurements: Significant, preventable health risks are associated with childhood obesity (excess fat mass) including development of chronic medical conditions into adulthood (13-15). The skinfold measurement test is one of the oldest and most common methods of determining a person's body composition by estimating the amount of fat present under the skin in specific locations. We plan to measure the child’s subscapular and tricep skinfold thicknesses using Harpenden calipers, as was done previously at the 3- and 5-year clinical assessments.

• Body Composition (Tanita scale): For participating children, the Tanita scale will estimate the child’s weight and % body fat only. Children who have pacemakers or other internal medical devices will be excluded from this test.

• Actigraphy: Actigraphy is an objective, non-intrusive, accelerometer-based device that is able to evaluate replicated sleep and wake patterns in a child's natural environment based on activity levels as well as physical activities undertaken by the child (16). We plan to place a device, Actigraph wGT3X-BT, that measures the child’s movements, activity, sleep and light exposure onto the child’s wrist at the end of the clinic visit and ask them to wear the device continuously for 7 consecutive days and nights, to ensure clinical validation for actigraphy (17). Outcome measures include: sleep duration, sleep efficiency, wake after sleep onset (WASO), wake time, bedtime, asleep onset latency, and physical activity levels. A short questionnaire and sleep diary will enable accurate scoring according to the Sleep Behavior Sleep Medicine (SBSM) protocol for data analysis (17). The device will be returned to the study centre in an addressed, postage-paid envelope once testing has been completed. Participants will be offered a summary of the information recorded by the device, compared to the Canadian 24-hour movement guidelines for children and youth (24).

• Global Positioning System (GPS) Time-Location: Physical inactivity is associated with an increased risk of chronic diseases (18). We will employ two approaches to assess potentially relevant environmental characteristics related to physical activity: 1) assessment of environmental perceptions via questionnaires, and 2) objective assessment of the environment using either Global Positioning System (GPS) (19) devices or Geographic Information Systems (GIS). GPS is tool for improving our understanding of the spatial context of physical activity by identifying locations where physical activity takes place and GIS can use routinely available environmental data to describe the characteristics of the surroundings (20, 21). Combining GPS and GIS provides an objective means of examining the relationship between the natural and built environment and location-based physical activity (22, 23). The child will be provided a GPS device, Qstarz BT-Q1000XT, to either wear on a belt or carry in a backpack for 7 consecutive days, after which the device will be returned to the study centre in an addressed, postage-paid envelope.

• Skin Allergy Tests: Skin prick tests will be performed on the forearms and will replicate those used at ages 3 and 5 years. The allergens tested will be cat, dog, four molds, grass, weeds, trees, two house dust mites, cockroach, cow’s milk, egg white and peanut, together with positive and negative controls.

• Lung Function Tests: Spirometry was introduced to the whole cohort at age 5. The child is asked to take the deepest breath possible and then blow hard and fast into the spirometer, in accordance with American Thoracic Society/European Respiratory Society guidelines. If the spirometry test shows clear evidence for airflow obstruction (shown by an FEV1/FVC ratio below LLN based on GLI), salbutamol, the most commonly used medication to relieve asthma, will be administered using an aerochamber and the effect will be measured by repeating spirometry 10 minutes later. The methacholine challenge test for airway responsiveness will not be performed by these children with


baseline airflow obstruction. • Methacholine Challenge Test: This highly standardized test first developed in Canada is used

worldwide to look for ‘twitchy airways’ which are characteristic of asthma. After obtaining acceptable and reproducible baseline lung function values with spirometry, the child will be asked to take several breaths of a saline mist with gradually increasing concentrations of Provocholine (methacholine chloride), a synthetic compound related to the natural body chemical acetylcholine which is released by nerves to make muscles contract, and approved for this use by Health Canada. Breathing the mist of Provocholine may cause the airway to narrow slightly, which is measured by repeating spirometry after each change in concentration (total of 4-6 tests depending on the individual response) until there is a 20% or greater reduction in measured FEV1, or the final dose is administered. If greater than 20% reduction occurs or the final dose has been administered, the test is discontinued, and any airway narrowing is reversed by breathing in 4 inhalations of salbutamol (Ventolin).

5. BIOLOGICAL SAMPLE COLLECTION

A. Parent(s) Samples:

• Blood: Blood (20 mL) will be collected and used for studies of genetics, epigenetics, hormones, markers of nutrition, metabolomics, ‘omics and biomarkers for allergy and inflammation using Next Generation Sequencing technologies (i.e., exome and whole genome sequencing, epigenetics (methylation) and “omics” analysis platforms). The time since the last meal will be recorded.

• Saliva: Saliva will be collected at the clinic visit for genetic analysis if blood is not able to be collected.

B. Child Samples: • Nasal Samples: Two nasal samples will be collected at the clinic visit, 1) using a flocked Copan swab

for viral assays and nasal microbiome sequencing and, 2) using a nasal brush to obtain material for epigenetic analyses.

• Saliva: Saliva will be collected at the clinic visit for genetic analysis using Next Generation Sequencing technologies (i.e., exome and whole genome sequencing, epigenetics (methylation) and “omics” analysis platforms).

• Urine: First morning urine will be collected from the child on the day of the clinic visit using a kit that will be mailed to the family in advance of the visit and brought to the clinic in a biohazard bag with cold pack. If the morning urine was not collected prior to the clinic visit, a second attempt at urine collection will be made at the clinic visit. Planned analyses include urinary metabolomics and viral microbiome profiling.

• Stool: A stool sample will be collected at home, preferably within 24 hours of the clinic visit, using a kit which will be mailed to the family in advance. Stool will be stored in the home freezer in a Biohazard bag and brought to the clinic visit. Stool will be used for microbiome studies, metabolomics and for measures of nutrition.

• Blood: Blood (40 mL; <2.5% of total blood volume for 8-year-old) will be collected at the end of the clinic visit and used for studies of genetics, epigenetics, hormones, metabolomics, ‘omics and biomarkers for allergy, inflammation, and other chronic disease parameters. The time since the last meal will be recorded. A small sample of blood (0.5 mL) will be sent to local clinical laboratories at each site for complete blood counts (CBCs). Planned analyses include Next Generation Sequencing technologies, including Sanger, exome and whole genome sequencing, epigenetics (DNA methylation), and “omics” analysis platforms.

• Teeth: In addition to collecting samples such as blood and urine which might reveal evidence of recent exposures to environmental pollutants, we will also collect baby teeth when they fall out, as these


will yield information about exposure to chemicals over a longer period of time. Current technology allows investigators to look at the teeth to determine exposures even before birth and throughout childhood. Examples of chemicals which can be examined in teeth include lead, manganese, organic flame retardants, and phthalates, all of which may impact child health and development. Materials will be mailed to the home prior to the clinic visit and parents will be asked to send the teeth and a short questionnaire (questions about the age at which the tooth came out and whether it fell out naturally or was removed by a dentist or because of injury) back to the CHILD site office using a prepaid and addressed envelope. At least three, and up to five teeth will be collected and stored for analysis. The Sandbox Project is providing funding for this collection of teeth and a small token gift from the “Tooth Fairy” for the children.

6. PARTICIPANT ENGAGEMENT ACTIVITIES

This research study includes participant engagement activities to involve participants in the governance, priority setting, conduct of research, knowledge translation and evaluation of the study. Parent and child participants will be asked about their opinions/perceptions on their participation in the study and will discuss specific issues and projects that arise from the study through engagement activities i.e. Town Hall Meetings, Participant Engagement Committees (PEC) at the local and national levels, Focus Groups, Feedback Surveys etc. Participants will act as representatives for and receive feedback from each site in order to advocate the voices of families in the study across Canada. Participant engagement activities will not occur at the same time as the study visit, participants will be contacted in the future to participate.

7. HEALTH CHART REVIEW AND DATABASE LINKAGES

Participant’s health charts will be reviewed as part of this study. Information about symptoms, medicines, treatments and clinical tests will be collected. As part of this study we would also like to link the participant’s health card number to a provincial health database to do health services research. This study also involves linking research study data to environmental databases. These databases contain environmental information such as air quality, neighborhood walkability and pollution.

DATA MANAGEMENT AND DATA ENTRY

A web-based electronic data capture system will be used to collect questionnaire data from participating families. This process is password secured and system is encrypted. Questionnaires/forms will only collect de-identified information using the study number. When the questionnaires/ forms collect address and postal code, the fields will be flagged as containing identifying information. Name and email address will be used to send out online questionnaire reminders to participants. All other identifying information will be stored separately from study data, accessed only by local staff who contact participants to schedule appointments.

Participants may experience some anxiety, emotional and/or psychological distress due to the nature of the questions. Such questions can be skipped. If participants would like help with their anxiety, emotional and/or psychological distress, a list of local community mental health resources will be made available to them.

Copies of the allergy skin testing forms will be forwarded to the NCC for data entry. After data review at NCC, corrections or clarifications may be required. The NCC Data Supervisor will send data queries to the sites; queries need to be resolved ideally within 4 weeks. Any corrected data will be entered into the electronic data capture system by the data team at the NCC.


Participants will be asked for future contact related to data updates, participation in new research, focus groups, and celebration events. Participants will also be asked about their preferences for future research of their biobanked data and genomic sequences.

Secondary findings that are medically actionable will be communicated by the study doctor or delegated health care professional, to participants if they are open to it.

Study information will be shared through journal publications, academic conference, newsletters, the study’s website and through social media.

REIMBURSEMENT

Participating study parents will be reimbursed for parking and transportation costs associated with the study visit. Participants will also be offered a $50 gift card for their participation in the study. Participating study children will be offered volunteer hours and a small toy, game or craft for their participation in the study.

SHIPPING BIOLOGICAL SAMPLES TO CENTRAL STORAGE

Biological samples will be collected by the sites. For all samples, except blood and teeth, site staff will process and aliquot samples according to the standard operating procedures into 2 mL Corning cryovials. Blood samples will be shipped via Fedex to a central processing laboratory located in Vancouver, BC. All aliquots, except teeth, will be stored in cryoboxes and kept temporarily at -80 degrees at the sites until shipped to the Clinical Research Laboratory and Biobank in Hamilton, ON via dry liquid nitrogen shippers. Dry Shippers are “charged” by filling them with liquid nitrogen, which is absorbed into the lining. Liquid nitrogen not absorbed after 24 hours is poured off before shipping. The shipper is called a “dry” shipper because it no longer contains hazardous liquid, only vaporous nitrogen. The Dry shipper will keep specimens frozen at -150°C for 7 days from the time of shipment from the Central Storage Facility. The Central Storage Facility will receive the Dry Shippers containing biological specimens, confirm receipt of specimens with the National Coordinating Centre and transfer them into their liquid nitrogen tanks for long-term storage. Teeth samples will be labelled by the sites and shipped to the National Coordinating Centre in Hamilton, ON where they will be stored at room temperature in a locked cabinet. Tracking of all biological samples will be done using OpenSpecimen.

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SECTION 3: WORKING GROUPS AND COMMITTEES

1. SCIENTIFIC WORKING GROUPS To facilitate the many areas of investigations, CHILD has developed various Scientific Working Groups consisting of researchers from related disciplines and specialties to develop the assessments, questionnaires and tools fundamental to meeting the objectives of the CHILD Study. Each Working Group is chaired by a member of the Executive Committee. These groups work in conjunction with the Executive and National Coordinating Centre to develop Standard Operating Procedures for tests, biological sample collections and staff training.

A. Asthma, Allergy and Lung Function Working Group

Chair: PJ Subbarao Members: PJ Subbarao, Allan Becker, Piush Mandhane, Theo Moraes, Stuart Turvey, Thomas Eiwegger, Elinor Simons, Malcolm Sears, Diana Lefebvre, Aimee Dubeau, Stephanie DeLorenzo, Qingling Duan, Kelly McNagny, Michael Kobor

This Working Group advises on the determination of asthma and wheezing phenotypes, the performance of lung function tests and of allergy skin tests. Lung function tests at age 8 years will include spirometry and methacholine challenge testing.

B. Bioinformatics/Statistics Working Group: Chair: Wendy Lou Members: Wendy Lou, Allan Becker, PJ Subbarao, Piush Mandhane, Stuart Turvey, Malcolm Sears, Sara Mostafavi, Diana Lefebvre, Aimee Dubeau, Anna Goldenberg, Lauren Muttucomaroe, Fiona Brinkman, Michael Brudno

Data collection and management, and subsequent data analysis and integration are complex issues under continuing development and review by this Working Group.

C. Cardiometabolic Working Group

Chair: Sonia Anand Members: Sonia Anand, Piush Mandhane, Meghan Azad, Katherine Morrison, Todd Alexander, PJ Subbarao, Luc Mertens, Diana Lefebvre, , Aimee Dubeau, Kozeta Miliku

This Working Group advises on the questionnaires, objective measurements and biological samples required to optimally assess cardiometabolic traits at age 8 years, including blood pressure, weight, height, waist circumference, body fat, step test for fitness, activity, screen time amount and type, outdoor play, diet, sleep patterns and duration.

D. Environmental/Exposome Working Group: Chair: Jeff Brook Members: Jeff Brook, Tim Takaro, James Scott, PJ Subbarao, Diana Lefebvre, Aimee Dubeau, Hind Sbihi, CANUE consortium

The Environmental Working Group working with the National Coordinating Centre and Canada Mortgage and Housing Corporation developed Standard Operating Procedures for assessment of environmental exposures at each survey. Questions relate to the home, cleaning methods, heating and cooling, school,


child and family activity, time spent in transit, mode of transport, use of swimming pools, and a multiplicity of chemical and environmental exposures. Outdoor air pollution is estimated by modeling.

E. Genomics Working Group: Chair: Michael Kobor Members: Michael Kobor, Catherine Laprise, PJ Subbarao, Andrew Sandford, Scott Tebbutt, Qingling Duan, Diana Lefebvre, Aimee Dubeau, Ryan Yuen, Tara Paton, Guillaume Pare

The Genomics Working Group advises on sample collection, storage and analysis of genetic material from parents and children, including epigenetics, and the broad field of ‘omics.

F. Immunology Working Group: Co-Chairs: Stuart Turvey, Thomas Eiwegger Members: Stuart Turvey, Thomas Eiwegger, PJ Subbarao, Dean Befus, Theo Moraes, Kent HayGlass, Tobi Kollmann, Judah Denburg, Diana Lefebvre, Aimee Dubeau, Jean Marshall, John Gordon, Kelly McNagny, Bruce Mazer

The Immunology Working Group works with the National Coordinating Centre to develop Standard Operating Procedures for collecting, processing and quality control of blood samples. Blood components will be processed to provide RNA, DNA, whole blood, serum, plasma and peripheral blood mononucleocytes. Immunology investigations will focus on a comprehensive analysis of genetic, epigenetic, gene expression, innate and adaptive immunity and toll-like receptor profiles of children to understand the biological basis of allergic disease.

G. Infection Working Group: Chair: Theo Moraes Members: Theo Moraes, PJ Subbarao, Michael Surette, Stuart Turvey, Diana Lefebvre, Aimee Dubeau, Marek Smieja

A primary focus of this Working Group is the detailed examination of respiratory infections in relation to outcomes of asthma and allergy.

H. Microbiome Working Group: Chair: Stuart Turvey Members: Stuart Turvey, PJ Subbarao, Anita Kozyrskyj, James Scott, Brett Findlay, Michael Surette, Meghan Azad, Marie-Claire Arrieta, Diana Lefebvre, Aimee Dubeau

This Working Group advises on sample collection and analyses for gut and respiratory microbiome studies.

I. Neurodevelopment Working Group:

Chair: Peter Szatmari Members: Peter Szatmari, Piush Mandhane, PJ Subbarao, Jacqueline Pei, Carmen Rasmussen, Christian Beaulieu, Tricia Williams, Evdokia Agnostou, Steven Miller, Michael Meaney, Diana Lefebvre, Aimee Dubeau, Daphne Korczak, Indra Narang, Greg Miller, Anita Kozyrskyj, Jacqueline Pei

The Neurodevelopment Working Group advises on a broad range of assessments to follow the trajectories of mental illness, including anxiety and depression prodromes during development.


J. Nutrition and Endocrine Working Group: Co-Chairs: Meghan Azad, Russell de Souza Members: Meghan Azad, Russell de Souza, Allan Becker, Sonia Anand, PJ Subbarao, Piush Mandhane, Anita Kozyrskyj, Catherine Field, Stephanie Atkinson, Diana Lefebvre, Aimee Dubeau, Wei Perng

The Nutrition Working Group works in conjunction with the National Coordinating Centre to develop assessment tools and implement food frequency questionnaires for the collection of nutritional information in mothers and children.

K. Physical Activity Working Group:

Chair: Jeff Brook Members: Jeff Brook, Greg Evans, Val Carson, Indra Narang, Meghan Azad, Piush Mandhane, PJ Subbarao, Diana Lefebvre, Aimee Dubeau, CANUE Consortium

The Physical Activity Working Group advises on questionnaires and measurement tools to assess the organized and unorganized physical activity of children in relation to disease outcomes.

L. Sleep Working Group: Chair: Piush Mandhane Members: Piush Mandhane, Indra Narang, Jacqueline Pei, PJ Subbarao, Diana Lefebvre, Aimee Dubeau

The Sleep Working Group works in conjunction with the National Coordinating Centre to develop assessment tools and implement questionnaire and objective assessment of sleep duration and disruption together with determination of media consumption.

2. CHILD COMMITTEES

A. Executive Committee:

Chair: PJ Subbarao Members: PJ Subbarao, Meghan Azad, Sonia Anand, Allan Becker, Dean Befus, Jeff Brook, Wendy Lou, Piush Mandhane, Michael Kobor, Theo Moraes, Stuart Turvey, Malcolm Sears (ex-officio), Diana Lefebvre (ex-officio), Aimee Dubeau (ex-officio). The Executive Committee meets by teleconference monthly, and in face-to-face meetings as-needed, to review all aspects of the conduct of the study, to receive reports from the Scientific Working Groups and other committees, to review proposed additional studies, and maintain an overview of direction, concerns and progress of the many components of the study.

B. Biological Sample Committee:

Co-Chairs: Dean Befus, Theo Moraes Members: Dean Befus, Theo Moraes, Meghan Azad, Joseph Macri, Russell de Souza, Jeremy Scott, Judah Denburg, Tobi Kollmann, Jeff Brook, Rick Hegele, Michael Kobor, Jean Marshall, PJ Subbarao Sample requests by researchers for analyses pertinent to the CHILD Study will be reviewed by this Committee who then make a recommendation to the Executive Committee.


C. Ethics / Legal Advisors: Members: Tim Caulfield, Nola Reis, Bartha Knoppers

D. Finance Committee:

Chair: PJ Subbarao Members: PJ Subbarao, Allan Becker, Stuart Turvey, Meghan Azad, Theo Moraes, Piush Mandhane, Diana Lefebvre (ex-officio), Aimee Dubeau (ex-officio) This Committee of the Director, Site Leaders and Administrative Manager reviews and determines allocation of available funding across the components of the study

E. Knowledge Mobilization (KMb) Advisory Committee:

Chair: Meghan Azad Members: PJ Subbarao, Meghan Azad, Stuart Turvey, Co-Chair of Stakeholder KMb committee This committee helps to interpret and disseminate study results as they are published, and to translate scientific findings into products and tools to benefit parents and communities, to advance public policy, and to improve clinical applications.

F. Knowledge Mobilization Stakeholder Committee:

Chair: Andrew McColgan Members: Mary Ellen Rayner, Stephanie Bertolo, Andrew McColgan, Sharon Jollimore, Lisa Knisley, Rishma Chooniedass, Shelly Callaghan, Lisa Wolff, Zak Bhamani, Kyla Hildebrand, Chozanne Gryte, Geoff Ball, Leanne Boyd, Rob Santos, Terry Foster

G. Participant Engagement Committee: Chair: Meghan Azad Members: Meghan Azad, Linda Warner, Joyce Chikuma, Aimee Dubeau, Yaminee Charavanapavan, Phillip Snarr, Diana Lefebvre

This committee will ensure that the needs and experiences of parents and participants are included in the management and evolution of the CHILD Study, by bringing participants and study staff together for broad discussion of important participant-related issues. These discussions will help inform development of study visits, analysis and dissemination of study information.

H. Publications Committee:

Chair: Malcolm Sears Members: Malcolm Sears, PJ Subbarao, Stuart Turvey, Allan Becker, Piush Mandhane, Meghan Azad, Theo Moraes, Wendy Lou, Teresa To, Hartmut Grasemann, Catherine Laprise, Jeremy Scott. The Publications Committee reviews and approves or recommends changes to Publication Proposals submitted by investigators, gives final approval for submission of papers to journals, approves abstracts for submission to conferences, and adjudicates on issues of content, authorship and related matters.


I. Scientific Advisory Committee: Chair: Paul O’Byrne Members: Paul O’Byrne, Fernando Martinez, Erika von Mutius, Peter Sly, Felix Ratjen, Mike Raizenne, Terrie Moffitt

The Scientific Advisory Committee meets with members of the Executive annually to review plans, progress, publications, and provide guidance on new directions. The committee may also be invited to provide opinions on proposed additional studies and related matters by email communications throughout the year.


Table 1: Data Collection Summary from recruitment to age 8 years:


Table 2: CHILD Study Questionnaires 8 Years

Format Completion By Questionnaires Code ID

Que

stio

nnai

res

Mother Mother Health, Activity, Family 8 Years MHA8Y Q500 Mother Child Physical Activity 8 Years CPA8Y Q501 Father Father Health, Activity, Family 8 Years FHA8Y Q502 Mother Parenting Family and Child Stress 8 Years PFS8Y Q503 Mother Parental Stress 8 Years PST8Y Q504 Parent Home and Environment 8 Years HEN8Y Q505 Parent Residences 8 Years RES8Y Q506 Parent Family Eating and Activity Habits 8 Years EAH8Y Q507 Parent Socioeconomic Status 8 Years SES8Y Q508 Parent Child Health 8 Years CHL8Y Q509 Parent Child Medications 8 Years CMD8Y Q510 Parent Child Food Frequency 8 Years CFQ8Y Q511 Parent Child Sleep 8 Years CSL8Y Q512 Parent Child Behaviour Checklist 8 Years CBL8Y Q513 Parent Child School Performance 8 Years CSH8Y Q514 Parent + Child Puberty Staging (Boys) 8 Years CTB8Y Q515 Parent + Child Puberty Staging (Girls) 8 Years CTG8Y Q516 Staff Child Clinical Assessment 8 Years CCA8Y Q517 Staff Mother Clinical Assessment 8 Years MCA8Y Q518 Staff Father Clinical Assessment 8 Years FCA8Y Q519 Staff + Child Child Body Image 8 Years CBI8Y Q520 Staff + Child Child Self Assessment 8 Years CAS8Y Q521 Parent + Child Child Screen 8 Years CSA8Y Q530 Parent Child Prescreening 8 Years CPS8Y Q531

Test

s & A

sses

smen

ts Staff Child Skin Test Meds & Supplements 8 Years CSM8Y Q522

Staff Child Skin Prick Test 8 Years CSP8Y Q523 Staff Child Methacholine Challenge 8 Years CMS8Y Q524 Parent + Child Child Actigraph GPS CAG8Y Q525 Provisional Mother Skin Test Meds & Supplements 8 Years MSM8Y Q526 Provisional Mother Skin Prick Test 8 Years MSP8Y Q527 Provisional Father Skin Test Meds & Supplements 8 Years FSM8Y Q528 Provisional Father Skin Prick Test 8 Years FSP8Y Q529

Adm

in Parent Future Contact 8 Years ACF8Y Q532

Parent Reimbursement 8 Years ARF8Y Q533 Parent Withdrawal 8 Years AWF8Y Q534

Biol

ogic

al S

ampl

es

Parent + Child + Staff Child Urine Collection Form CUR8Y Parent + Child + Staff Child Nasal Swab Collection Form CNS8Y Parent + Child + Staff Child Nasal Brush Collection Form CNB8Y Parent + Child + Staff Child Stool Collection Form CFS8Y Parent + Child + Staff Child Blood Collection Form CBL8Y Parent + Child + Staff Child Saliva Collection Form CSA8Y Parent + Child + Staff Child Teeth Collection Form CTH8Y Parent + Staff Mother Blood Collection Form MBL8Y Parent + Staff Mother Saliva Collection Form MSA8Y Parent + Staff Father Blood Collection Form FBL8Y Parent + Staff Father Saliva Collection Form FSA8Y


Table 3: Standard Operating Procedures 8 Years

STANDARD OPERATING PROCEDURES VERSION DATE

Child blood May 2018

Parental Blood May 2018

Stool May 2018

Nasal Swab May 2018

Urine collection May 2018

Teeth collection May 2018

Saliva collection May 2018

Body composition May 2018

Body image, puberty staging May 2018

Anthropometrics May 2018

Allergy Skin Prick Testing Parents May 2018

Spirometry Parents Feb 2019

Allergy Skin Prick Testing Children May 2018

Skin fold measurements May 2018

Spirometry Children May 2018

Methacholine Challenge Feb 2019

Shipping Procedures-Vapour shipper May 2018

Actigraphy/Accelerometry/GPS Feb 2019

Clinical Assessment (child + parents) Feb 2019

child cohort study version date: dec 2019

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