Subjects
Two stage stratified cluster sampling was used to include participants from two counties in Chongqing that represent urban and rural areas; then, two regions per county were randomly selected, and finally, 3067 children (including 2808 children entered the cohort in 2014, and 130 children and 129 children transferred into the target schools in 2015 and in 2019) were informed and included if they satisfied the inclusion criteria. In addition, a birth-cohort in which retrospective and prospective variables were adjusted to evaluate the correlation of QoL and personality with MS. Participants who met all the following criteria were recruited: (1) aged between 6 and 9 years in 2014, (2) resided in the target region for more than 6 months, (3) did not have serious diseases (e.g., nephropathy, cardiovascular disease or cancer), and (4) obtained consent from the parents and children for participation. The sample size was calculated with the following parameters: α level of 0.05, power of 90%, prevalence of MS components of 15% and the prevalence in population 10%, using the formula ; assuming an attrition rate of 20%, 1859 participants were ultimately needed, and 1961 subjects were ultimately included in this study (as shown in Figure 1). At baseline, all participants completed SES and family health history questionnaires and were recruited mainly from grade one and grade two from primary public-schools screening of children whose families were interested in health research. The questionnaires were administered and collected by the teachers. The Institutional Review Board at the Children’s Hospital of Chongqing Medical University gave its approval for the study. Informed consent was provided by all subjects and parents/guardians.
Demographic Variables
Demographic information, SES and prenatal variables included maternal preconception obesity, increased body mass index (BMI) of mother during pregnancy, birth with caesarean section, premature delivery (<37 weeks), birth weight, breastfeeding, gestational hypertension (GH) and gestational diabetes were collected.
The validity and reliability of the demographic questionnaire were checked, and were described in detail in a previous publication[21]. The demographic questionnaire was filled by the parents or guardians of the children after standard training by the research group and the detail instruction of the questionnaire was given to the parents or guardians.
Physical Examination
Anthropometric measurements were conducted both in 2014 and in 2019 by well-trained pediatric nurses, and the protocol for these measurements was described in a previous publication[21]. Waist circumference (WC) was used as an alternative measure of central adiposity. Hip circumference was measured twice horizontally at the level of the pubic symphysis in the front and the gluteus maximus in the back, with the participant standing upright and with their legs together and placing their arms naturally at their sides; the mean value was used.
Blood pressure (BP) was measured on three separate occasions with an OMRON arm-type electronic sphygmomanometer (HEM7051) using an appropriately sized BP cuff placed on the subject’s right arm, with the subject in a seated position, which was described detailed in a previous publication[21].
Biochemical Indexes
The biochemical markers of FBG, HDL-C, TG, low density lipoprotein cholesterol (LDL), total cholesterol (TC) were measured in 2014 and in 2019. Venous blood (3 ml) was drawn from each subject in the morning after at least 12 hours of fasting and 24 hours of abstaining from high-fat and spicy foods. The biochemical markers were measured within 2 hours after venous blood was drawn and the protocol was introduced in detail in our previous publication [21].
Measurement of QoL and Eysenck’s Personality Questionnaire (EPQ)
The QoL questionnaire for adolescents consists of 49 items, including 4 factors (psychosocial function, physical and mental health, living environment and QoL satisfaction) and 13 dimensions, such as self-satisfaction, relationship of teacher and pupil, physical feeling, companionship, parenthood, physical activity ability(PAA), learning ability and attitude, self-esteem, negative emotion, attitude towards doing homework, opportunity for activity, living convenience and others (picky-eating and surroundings), which was detailed expressed in supplementary figure 1. The order of presentation of the 49 items was randomized. Children rated the statements on a 4-point scale, and the direction of response (positive or negative) varied item by item to limit response bias. Individual item values were recoded prior to analysis so that the direction was consistent. Responses were summed and normalized according to the age-, sex- and region-specific norms of Chinese into a score T(range, 0-100), using the function of T=50+(X-M)/SD×10, with higher scores suggesting a better QoL status [22].
The Chinese version of Eysenck’s personality questionnaire[23] consisted of 88 items scored on a 2-point scale (for positive items NO=0 and YES=1), including 4 domains: extraversion (E) (25 items), neuroticism (N) (23 items), psychoticism (P) (18 items), and lie scales (L) (22 items). High scorers on the E scale indicate sociable, exciting, pleasurable, carefree, and aggressive characteristics. A higher score on the N scale is more likely to be a worried and moody person who tends to suffer from emotional and psychosomatic disorders. The P scale was designed to measure behaviour patterns that might be considered schizoid or psychopathic in extreme cases. The L scale assesses response bias. Items in the E, N, P and L domains are summed and normalized to the age- and sex-specific norm into a score ranging from 0 to 100, using the function of T=50+(X-M)/SD×10. People are defined as middle type, tendency type and typical type if the T score (E and N) ranges from 43.3~56.7, 38.5~43.3 or 56.7~61.5, <38.5 or >61.5. People were considered psychotic personality if T score of the P domain >56.7. And we consider it was an invalid response of personality traits if the T score of the L domain was >70.
50 samples were required to fill the same questionnaire twice for one-week interval to check the validity and reliability of the QoL and Eysenck’s Personality Questionnaires before our formal survey. QoL and Eysenck’s Personality Questionnaires were filled by the adolescents after a standard training.
Diagnostic Criteria
The MS of adolescents was defined by the presence of three or more of the following five components [5, 24]: (1) central obesity defined as ⩾90th percentile for age and gender criteria from China[25]; (2) elevated systolic and/or diastolic blood pressure ⩾90th percentile for age, sex and height (according to the study from Jie Mi[26]); (3) hypertriglyceridemia defined as TG ⩾1.24 mmol/L; (4) low serum HDL-C defined as HDL-C ⩽1.03 mmol/L, and (5) impaired fasting glucose (IFG) defined as FBG ⩾5.6 mmol/L. Next, individual MS score was calculated by sum the number of MS components present (range, 0–5).
The definitions of size for gestational age used the global reference for fetal-weight and birthweight percentiles[27]: birth weight at or above the 90th percentile indicated large for gestational age (LGA), and birth weight less than the 10th percentile indicated small for gestational age (SGA), using the parameters of mean birthweight at 40.5 weeks of 3332.93 g and a variation coefficient of 14.36%. Maternal overweight and obesity before pregnancy was indicated by a BMI of 24~27.9 kg/m2 and a BMI ≥ 28 kg/m2, respectively; BMI < 18.5 kg/m2 was defined as a low BMI [28]. According to guidelines of the Institute of Medicine (IOM) for maternal pregnancy weight gain [29], the recommendation is for underweight, normal weight, overweight, and obese women to gain 12.5~18.0 kg, 11.5~16.0Kg, 7.0~11.5 kg, and 5.0~9.0 kg, respectively; if weight gain exceeded that range, weight gain was defined as “above IOM guidelines”, and if weight gain was below that range, was defined as “below the IOM guidelines”.
Statistical Analyses
Differences in anthropometric measures, serum biochemical indexes, QoL and personality score among three groups were assessed using ANOVA, and post-hoc comparison was performed using Student-Newman-Keuls (SNK) test. The χ2 test was used to test the difference in the component ratio of potential risk factors of MS components. Logistic regression model was performed using diagnosed MS components or MS as the dependent variables with QoL and personality traits, as independent variables, and adjusted for covariables. In addition, a generalized linear model (GLM) was used to analyse the correlation of QoL and personality traits scores with MS components levels and MS score, adjusted covariables.
The data analysis was conducted using SAS 9.4 software (Copyright © 2020 SAS Institute Inc. Cary, NC, USA). A significant difference was defined by an α level of 0.05.