Cohort Profile: The Quebec Adipose and Lifestyle Investigation in Youth Cohort

The epidemic rise in the prevalence of obesity and in particular, paediatric obesity has led to concerns that the complications of excess adiposity may well reverse the favourable trends in cardiovascular disease (CVD) mortality observed over the past half-century. Although recent reports suggest that the prevalence of overweight and obesity may have reached a plateau, at least in the USA,1,2 the continued exposure to excess body fat over prolonged periods of time may have serious deleterious effects on the health and well-being of populations and may lead to a decrease in life expectancy among younger generations.3,4 In the late 1990 s, in response to this perceived threat, we designed and conducted the Quebec Child and Adolescent Health and Social Survey, a province-wide representative sample survey of the health and well-being of Quebec youth.5 Among participants aged 9, 13 and 16 years, we observed high prevalence of excess weight, elevated blood pressure (BP)6 and of the metabolic syndrome.7 These concerningly high levels of CVD risk factors even at the youngest age of 9 years stimulated the research questions that led to the creation of the QUebec Adipose and Lifestyle Investigation in Youth (QUALITY) Cohort. Our overarching objective is to describe the natural history of the development of childhood obesity and its metabolic and cardiovascular consequences and to understand their determinants. The specific objectives of QUALITY are: (i) to increase understanding of the natural history of excess weight and its associated cardiometabolic consequences (dyslipidaemia, hyperinsulinaemia, dysglycaemia, inflammation, elevated BP, sympathetic overactivity) in youth at risk for the development of obesity;4,8 (ii) to investigate the relative importance of the genetic, biological, environmental and psycho-social determinants of excess weight and its associated cardiometabolic consequences. Determinants of particular interest include social factors (socio-economic status, family composition, built environment), behavioural factors (eating behaviour, physical activity, smoking, sleep, stress), biological factors (adverse fetal environment, body fat distribution, growth trajectory, aerobic fitness), metabolic factors (insulin sensitivity, adipocytokines) and genetic/familial factors (family history, parental characteristics, gene variations);4,9–13 (iii) to examine the relation between obesity, cardiometabolic complications and subclinical markers of atherosclerosis;14 and (iv) to examine whether obesity and its associated risk factors are related to children's oral health.15 The QUALITY cohort is funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, as well as the Fonds de la recherche en santé du Québec. The multidisciplinary study team comprises over 20 researchers with a wide variety of relevant expertise as well as research fellows, students and staff (www.etudequalitystudy.ca). The QUALITY cohort used a school-based sampling strategy to identify potential participants. Eligible participants consisted of Caucasian children of Western European ancestry aged 8–10 years with at least one obese biological parent [i.e. body mass index (BMI) ≥30 kg/m2 or waist circumference >102 cm in men and >88 cm in women, based on self-reported measurements of height, weight and waist circumference] and both biological parents available to participate in the baseline assessment. Only Caucasian families were recruited to reduce genetic admixture. Families were not eligible to participate if the mother was pregnant or breastfeeding at the baseline evaluation, or if the family had pending plans to move out of the province. Children with any of the following were also excluded: (i) a previous diagnosis of type 1 or 2 diabetes; (ii) a serious illness, psychological condition or cognitive disorder that hindered participation in some or all of the study components; (iii) treatment with anti-hypertensive medication or steroids (except if administered topically or through inhalation); and (iv) following a very restricted diet (<600 kcal/day). About 400 000 recruitment flyers were distributed over 3 consecutive years to parents of children in Grades 2–5, in 1040 primary schools (89% of schools approached) including 44 private schools situated within 75 km of Montreal, Quebec City and Sherbrooke in the province of Quebec, Canada. Families interested in participating were invited to contact the research coordinator for additional information, to confirm eligibility and to set an appointment with the research team; 1320 of 3350 families who contacted the coordinator met the inclusion criteria. A total of 634 families including one child and two biological parents, or 1902 subjects, participated in the baseline visit (48% of eligible families; Figure 1). Reasons for non-participation at baseline among eligible families were: (i) not interested in the study, 81%; (ii) one biological parent did not agree to participate or was not available, 11%; (iii) child refused to participate, 4%; (iv) lived too far from a study centre, 2%; (v) not enough time to participate, 1%; and (vi) other, 1%. Recruitment and participation in the QUALITY Cohort. aFamilies were removed from study because child or parents were unable or refused to complete most or all of data collection for baseline assessment after providing consent to participate The QUALITY cohort was not intended to be representative of the Quebec population of families with children aged 8–10 years. Comparison of baseline characteristics with those of a representative sample of Quebec children of similar age shows that children in the QUALITY cohort are of higher socio-economic status, more likely to live with both parents, to reside in urban regions, to be overweight or obese, to have a worse lipid profile and to report less time watching television (Table 1). Comparison of characteristics of the QUALITY cohort participants at baseline with those of a representative sample of Quebec youth aged 9 years in 1999 aRestricted to 9-year-old children and their parents in the Quebec Child and Adolescent Health and Social Survey. For the child questionnaire n = 1267, for the parent questionnaire n = 1065 and for the fasting blood samples n = 783. bBased on the Center for Disease Control (CDC) age- and sex-adjusted z-scores. †P-value for t-test. SD, standard deviation. Comparison of characteristics of the QUALITY cohort participants at baseline with those of a representative sample of Quebec youth aged 9 years in 1999 aRestricted to 9-year-old children and their parents in the Quebec Child and Adolescent Health and Social Survey. For the child questionnaire n = 1267, for the parent questionnaire n = 1065 and for the fasting blood samples n = 783. bBased on the Center for Disease Control (CDC) age- and sex-adjusted z-scores. †P-value for t-test. SD, standard deviation. Families are followed up every 2–3 years in a full-day visit at the Unité de recherche clinique du Centre Hospitalier Universitaire (CHU) Sainte-Justine in Montreal and Hôpital Laval in Quebec City. Data collection includes interviewer-administered questionnaires for children (Table 2), self-administered questionnaires for parents (Table 3), biological and physiological measurements for both children and parents and other objective measures (Table 4). Variables assessed in children by interviewer-administered questionnaires at Visits 1, 2 and planned for Visit 3 Variables assessed in children by interviewer-administered questionnaires at Visits 1, 2 and planned for Visit 3 Variables assessed in self-administered questionnaires to both parents at Visits 1, 2 and planned for Visit 3 aAt Visits 1 and 2, includes questions on perceptions related to the household's financial situation. Variables assessed in self-administered questionnaires to both parents at Visits 1, 2 and planned for Visit 3 aAt Visits 1 and 2, includes questions on perceptions related to the household's financial situation. Child and parent biological, physiological and other objectively assessed measurements at Visits 1, 2 and planned for Visit 3 aAt Visit 3, the oral glucose tolerance test is done with blood drawn at 30, 60, 90 and 120 min post glucose load BP, blood pressure; DEXA, density measured by dual energy X-ray absorptiometry. Child and parent biological, physiological and other objectively assessed measurements at Visits 1, 2 and planned for Visit 3 aAt Visit 3, the oral glucose tolerance test is done with blood drawn at 30, 60, 90 and 120 min post glucose load BP, blood pressure; DEXA, density measured by dual energy X-ray absorptiometry. At the initial visit, parents provided the child's ‘health booklet’ issued to all Quebec parents of newborn children and in which are recorded birthweight, birth length, gestational age and subsequent weights and heights measured during routine medical visits. At each study visit, anthropometric measurements are taken according to standardized protocols5,16,17 with children and parents dressed in light indoor clothing without shoes, using a stadiometer for height, an electronic scale for weight, a standard measurement tape for waist circumference (mid-distance between the last floating rib and the iliac crest at the end of a normal expiration) and Lange-type calipers (AMG Medical Inc, Montréal, Canada) for triceps and subscapular skinfold thickness. In children, fat mass, fat-free mass, percent body fat, fat distribution (upper body, lower body and trunk fat masses) and bone mineral density are determined with dual energy X-ray absorptiometry (DEXA, Prodigy Bone Densitometer System, DF+14664, GE Lunar Corporation, Madison, WI, USA).18 Stage of sexual maturity is scored by trained nurses according to Tanner.19,20 At each clinic visit, blood is obtained from both children and parents by venepuncture after an overnight fast. In children a 180-min oral glucose tolerance test (OGTT) is performed and blood is collected 30, 60, 90, 120 and 180 min after an oral glucose dose of 1.75 g/kg body weight (up to a maximum of 75 g). Fasting blood samples were obtained for 99% of children and parents at baseline. Samples are centrifuged, aliquotted and stored at −80°C until analysed. All biochemistry analyses are conducted at the Department of Clinical Biochemistry of the CHU Sainte-Justine that participates regularly in provincial and international quality control programmes and is accredited by the International Federation of Clinical Chemistry. BP is measured on the right arm with the participants sitting at rest for at least 5 min, using an oscillometric instrument (Dinamap XL, model CR9340, Critikon Company, FL, USA).6 Common carotid intima–media thickness (far wall) is determined on the left and right sides using B-mode ultrasonography with an HDI 5000 (ATL, Philips, Bothwell, WA, USA) apparatus. Post-processing of the ultrasonic signals is performed off-line, at a single site (CHU Sainte-Justine), using computer-assisted image analysis (Eurequa, TSA Company, France).21 Heart rate variability is assessed by time domain and frequency spectral analysis of the electrocardiograph monitoring done during the 3-h period of the OGTT.22 Reading of the electrocardiograph recordings is centralized at a single site (Hôpital Laval). Peak oxygen consumption (VO2peak) is used to estimate aerobic capacity during an incremental cycling test adapted from McMaster protocol23 on an electromagnetic bicycle (Oxycon Pro, Jaeger) until volitional exhaustion with indirect calorimetry measurements taken continuously throughout the test. At baseline, 98% of children performed the cycling test, of whom 75% performed the test to a maximal bout (heart rate >195 beats/min and/or respiratory exchange ratio (VCO2/VO2) >1.0).24 Comprehensive clinical dental examinations are carried out, including collection of plaque samples and gingival crevicular fluid.25 Children's physical activity is measured objectively using 7-day accelerometry (Actigraph LS 7164 activity monitor, Actigraph LLC, Pensacola, FL, USA) in the week following the clinic visit.26 We exclude recordings from days when the accelerometer is worn for <80% of the average time worn on other days such that data are available for 88% of children at baseline. Together with self-report data, accelerometry permits estimation of sleep duration. In addition, a 7-day recall of 28 physical activities adapted from Sallis et al.27 is administered at the clinic visit and twice more by telephone within the year following the clinic visit to capture seasonal variation in physical activity. Whereas accelerometry provides a better measure of overall intensity and duration of physical activities performed and indicates the number of steps per day, the 7-day recalls provide a complementary measure of the types, the variety and the overall frequency of different activities engaged in. Within 8–12 weeks of Visits 1 and 3 (planned), three 24-h diet recalls on non-consecutive days including one weekend day are administered over the telephone by a dietician.28,29 A small disposable kit of food portion models (i.e. graduated cup, bowl, etc.) is provided to participants at the clinic visit, in conjunction with a short training and practice session. Five samples of salivary cortisol are collected at home on a day following the clinic visits (upon awakening, 30 min after awakening, before lunch, before dinner and before going to bed) and mailed to the research team.30 Cortisol assays are done at Trier University, Trier, Germany. At baseline, 93% of children provided at least four saliva samples. Lastly, characteristics of the built and social environments in the residential and school areas relevant to the child were obtained at baseline for families residing in the greater Montreal area (512/630 families) using in-person neighbourhood audits undertaken in geographical zones surrounding each child's residential and school address. Data collection tools and procedures were adapted in large part from validated instruments.31,32 School grounds and interiors were also audited and school principals provided data on health-related programmes and policies within the schools. Additional area-level characteristics such as average household income, distance to nearest food outlets, etc. were computed using 2006 census data as well as administrative and commercial data mapped for the study areas using a Geographic Information System. Measurement quality is ensured by: (i) detailed data collection protocols;33 (ii) central training of personnel from both study sites and regular monitoring of adherence to the protocol; (iii) verification and calibration of all equipment according to standardized protocols; and (iv) repeat studies conducted to quantify measurement variability and identify its sources. Inter-assay coefficients of variation for blood chemistry measurements are presented in Table 5 and inter-rater reliability for selected procedures as measured by inter- and intra-centre correlation coefficients are presented in Tables 6 and 7. Inter-assay coefficient of variation for blood chemistry measurements CV, coefficient of variation. Inter-assay coefficient of variation for blood chemistry measurements CV, coefficient of variation. Between-centre (Montreal and Quebec City) intra-class correlation coefficient (ICC) for the inter-rater reliability of selected measures Between-centre (Montreal and Quebec City) intra-class correlation coefficient (ICC) for the inter-rater reliability of selected measures Intra-centre intra-class correlation coefficient (ICC) for the inter-rater reliability of measures Intra-centre intra-class correlation coefficient (ICC) for the inter-rater reliability of measures Baseline data collection, when youth were aged 8–10 years (Visit 1), was completed between September 2005 and December 2008. The first follow-up, when youth were aged 10–12 years (Visit 2), was completed between September 2008 and March 2011. Visit 3 is planned for 2012–15 when youth are aged 15–17 years. Four families were removed from the cohort following Visit 1 because the child and/or parents did not complete most or all of the baseline data collection although they initially provided consent. Of the original cohort, 89% (564) completed Visit 2 (Figure 1). Reasons for not participating at Visit 2 are shown in Table 8; the majority of families who did not participate at Visit 2 agreed to be contacted for Visit 3 (47/66, 71%). Visit 2 non-participants were more likely to include younger mothers, and parents with a lower education. By design, both biological parents had to attend Visit 1 (baseline). For Visit 2, both biological parents were present in 42% of cases; children were accompanied by their mother and father in 39 and 19% of cases, respectively. The parent who is at visits is to complete the questionnaire at home and to to the research Reasons for not participating in first (Visit Reasons for not participating in first (Visit Baseline characteristics of children and parents are shown in Table The wide of available data of related to CVD risk For carotid intima–media thickness was associated with waist triceps and subscapular skinfold as well as percent fat mass, percent central fat mass and with exposure to in QUALITY data provide that short sleep duration is an risk for paediatric overweight and These the to sleep duration to the determinants of from the oral health study with children of normal weight, obese and those with the metabolic had higher in the gingival crevicular These undertaken in and suggest that the between condition and oral health may also be present in analyses suggest that of the (i.e. to and (i.e. to of as well as socio-economic characteristics such as area of are associated with children's weight and including physical activity, and Baseline characteristics of the QUALITY cohort families children, based on age- and sex-adjusted if overweight if and obese if For parents, if overweight if kg/m2 kg/m2 and obese if ≥30 glucose is as a fasting blood glucose a previous diagnosis of or treatment to decrease blood using the SD, standard deviation. Baseline characteristics of the QUALITY cohort families children, based on age- and sex-adjusted if overweight if and obese if For parents, if overweight if kg/m2 kg/m2 and obese if ≥30 glucose is as a fasting blood glucose a previous diagnosis of or treatment to decrease blood using the SD, standard deviation. The QUALITY cohort from including detailed of children and both biological parents, a wide of measurements including genetic, biological, behavioural and environmental objective measurements of physical activity, assessment of the physical in the home and school as well as measures of and programmes physical activity and The of measured the of in the development of excess adiposity and its cardiometabolic consequences. detailed and quality procedures measurement in the of the QUALITY cohort measurement and of participants. studies that schools were to other medical and weight control etc.) to because of the recruitment we the initial parental eligibility from the of at least one parent with the metabolic to at least one parent with eligibility a visit, most parents had not for the metabolic was that this additional visit recruitment too for were that they be by These lead to a increase in additional of this strategy is the to examine the potential of the number of parents with metabolic 1 or on the of interest in The measurement which the of the child and parents at the clinic for a day in the eligible families to participate in the baseline assessment. The of some and procedures among children aged 8–10 years at baseline also in some to participate in the We by using to blood and by the of trained and we have to to models including and BP measurement we are studies of and to follow-up, we telephone with families to contact information, we and and small (i.e. bicycle etc.) to children, a study is to families twice a year and we a for families on the QUALITY cohort we have in a and for children and their families at the Although the of QUALITY may be restricted to Caucasian children with a parental history of obesity, this comprises a large of the with school recruitment the of the primary of the QUALITY cohort are to describe the natural history, determinants and consequences of childhood obesity to describe the prevalence of in Quebec, of of prevalence data is not a A central of QUALITY is its including that have funded studies using the cohort to study residential and school built oral the and the between markers and and the metabolic The of the central team over time as well as their to the cohort have in the of the Additional the QUALITY is available at Our study on the natural history of the between excess body fat and cardiometabolic risk factors in a clinical identify children most at risk that be Our study also the of strategy and of at the prevalence of cardiometabolic risk factors in we that this in and models and which may lead to The Canadian Institutes of Health the Heart and Stroke Foundation of the Fonds de la recherche en santé du Québec. The to all the families and the research staff who have their time over the of this of

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