Cost-effectiveness of physical activity intervention in children - results based on the Physical Activity and Nutrition in Children (PANIC) study.

BACKGROUND: We assessed the cost-effectiveness of a 2-year physical activity (PA) intervention combining family-based PA counselling and after-school exercise clubs in primary-school children compared to no intervention from an extended service payer's perspective. METHODS: The participants included 506 children (245 girls, 261 boys) allocated to an intervention group (306 children, 60 %) and a control group (200 children, 40 %). The children and their parents in the intervention group had six PA counselling visits, and the children also had the opportunity to participate in after-school exercise clubs. The control group received verbal and written advice on health-improving PA at baseline. A change in total PA over two years was used as the outcome measure. Intervention costs included those related to the family-based PA counselling, the after-school exercise clubs, and the parents' taking time off to travel to and participate in the counselling. The cost-effectiveness analyses were performed using the intention-to-treat principle. The costs per increased PA hour (incremental cost-effectiveness ratio, ICER) were based on net monetary benefit (NMB) regression adjusted for baseline PA and background variables. The results are presented with NMB and cost-effectiveness acceptability curves. RESULTS: Over two years, total PA increased on average by 108 h in the intervention group (95 % confidence interval [CI] from 95 to 121, p < 0.001) and decreased by 65.5 h (95 % CI from 81.7 to 48.3, p < 0.001) in the control group, the difference being 173.7 h. the incremental effectiveness was 87 (173/2) hours. For two years, the intervention costs were €619 without parents' time use costs and €860 with these costs. The costs per increased PA hour were €6.21 without and €8.62 with these costs. The willingness to pay required for 95 % probability of cost-effectiveness was €14 and €19 with these costs. The sensitivity analyses revealed that the ICER without assuming this linear change in PA were €3.10 and €4.31. CONCLUSIONS: The PA intervention would be cost-effective compared to no intervention among children if the service payer's willingness-to-pay for a 1-hour increase in PA is €8.62 with parents' time costs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776. Registered 4 March 2013 - Retrospectively registered, https://clinicaltrials.gov/ct2/results?cond=&term=01803776&cntry=&state=&city=&dist= .

The effects of a 2-year physical activity and dietary intervention on plasma lipid concentrations in children: the PANIC Study.

PURPOSE: We studied the effects of a physical activity and dietary intervention on plasma lipids in a general population of children. We also investigated how lifestyle changes contributed to the intervention effects. METHODS: We carried out a 2-year controlled, non-randomized lifestyle intervention study among 504 mainly prepubertal children aged 6-9 years at baseline. We assigned 306 children to the intervention group and 198 children to the control group. We assessed plasma concentrations of total, LDL, HDL, and VLDL cholesterol, triglycerides, HDL triglycerides, and VLDL triglycerides. We evaluated the consumption of foods using 4-day food records and physical activity using a movement and heart rate sensor. We analyzed data using linear mixed-effect models adjusted for age at baseline, sex, and pubertal stage at both time points. Furthermore, specific lifestyle variables were entered in these models. RESULTS: Plasma LDL cholesterol decreased in the intervention group but did not change in the control group ( - 0.05 vs. 0.00 mmol/L, regression coefficient (ß) = - 0.0385, p = 0.040 for group*time interaction). This effect was mainly explained by the changes in the consumption of high-fat vegetable oil-based spreads (ß = - 0.0203, + 47% change in ß) and butter-based spreads (ß = - 0.0294, + 30% change in ß), moderate-to-vigorous physical activity (ß = - 0.0268, + 30% change in ß), light physical activity (ß = - 0.0274, + 29% change in ß) and sedentary time (ß = - 0.0270, + 30% change in ß). The intervention had no effect on other plasma lipids. CONCLUSION: Lifestyle intervention resulted a small decrease in plasma LDL cholesterol concentration in children. The effect was explained by changes in quality and quantity of dietary fat and physical activity. CLINICAL TRIAL REGISTRY NUMBER: NCT01803776, ClinicalTrials.gov.

A 2 year physical activity and dietary intervention attenuates the increase in insulin resistance in a general population of children: the PANIC study.

AIMS/HYPOTHESIS: We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children. METHODS: We carried out a 2 year non-randomised controlled trial in a population sample of 504 children aged 6-9 years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4 day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-IR were analysed using the intention-to-treat principle and linear mixed-effects models after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The measures of physical activity, sedentary time, diet and body composition at baseline and 2 year follow-up were entered one-by-one as covariates into the models to study whether changes in these variables might partly explain the observed intervention effects. RESULTS: Compared with the control group, fasting insulin increased 4.65 pmol/l less (absolute change +8.96 vs +13.61 pmol/l) and HOMA-IR increased 0.18 units less (+0.31 vs +0.49 units) over 2 years in the combined physical activity and dietary intervention group. The intervention effects on fasting insulin (regression coefficient ß for intervention effect -0.33 [95% CI -0.62, -0.04], p = 0.026) and HOMA-IR (ß for intervention effect -0.084 [95% CI -0.156, -0.012], p = 0.023) were statistically significant after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR. CONCLUSIONS/INTERPRETATION: The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2 years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition. TRIAL REGISTRATION: ClinicalTrials.gov NCT01803776 Graphical abstract.

Associations of dietary carbohydrate and fatty acid intakes with cognition among children.

OBJECTIVE: To investigate the cross-sectional associations of dietary carbohydrate and fatty acid intakes with cognition in mid-childhood. DESIGN: Dietary carbohydrate and fatty acid intakes were assessed using 4-d food records, and cognition was evaluated using the Raven's Coloured Progressive Matrices (RCPM) score. The cross-sectional associations of dietary carbohydrate and fatty acid intakes with cognition were investigated using linear regression analyses adjusted for age, sex, body fat percentage, household income, parental education and daily energy intake. SETTING: The baseline examinations of the Physical Activity and Nutrition in Children study. PARTICIPANTS: A population-based sample of 487 children (250 boys, 237 girls) aged 6-8 years living in the city of Kuopio, Finland. RESULTS: A higher dietary intake of fructose (standardised regression coefficient, ß = 0·24, P < 0·001), total fibre (ß = 0·16, P = 0·02) and soluble fibre (ß = 0·15, P = 0·02) was associated with a higher RCPM score in boys. Other dietary carbohydrates and fatty acids, including total carbohydrates, glucose, sucrose, starch, insoluble fibre, total fat, SFAs, MUFAs, PUFAs, palmitic acid (C16), stearic acid (C18), linoleic acid (C18:2), α-linoleic acid (C18:3), arachidonic acid (C20:4), EPA (C20:5n-3) and DHA (C22:6n-6), were not associated with the RCPM score in boys. Dietary carbohydrates or fatty acids were not associated with the RCPM score in girls. CONCLUSIONS: Higher dietary fructose and fibre intakes were associated with better cognition in boys, but not in girls. Dietary fatty acids were not related to cognition in boys or in girls.

GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

Associations of IGF-1 and Adrenal Androgens with Cognition in Childhood.

BACKGROUND: Little is known about the association between adrenarche and cognition in general populations of children. We therefore studied the associations of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), testosterone, insulin-like growth factor-1 (IGF-1), and adrenarche with cognition among prepubertal children. METHODS: These cross-sectional analyses are based on baseline data of the Physical Activity and Nutrition in Children Study. A total of 387 children (183 girls, 204 boys) were included in the analyses. Raven's Coloured Progressive Matrices (CPM) score was used to assess nonverbal reasoning. Serum adrenal androgens and IGF-1 concentrations were measured and clinical signs of androgen action were evaluated. RESULTS: Higher IGF-1 among boys (ß = 0.149, p =0.033) was related to a better Raven's CPM score after adjustment for age and parental education. Adrenal androgens in girls or boys or IGF-1 in girls were not associated with the score. There were no differences in Raven's CPM score between children with biochemical adrenarche (DHEAS ≥1.08 µmol/L; ≥40 µg/dL) or with clinical signs of androgen action and children without them. CONCLUSION: The results suggest that higher serum IGF-1 among boys is related to better cognition in prepubertal children. We could not provide evidence for the associations of adrenal maturation with cognition in prepubertal children.

Adiposity Criteria in Assessing Increased Cardiometabolic Risk in Prepubertal Children.

Objective: Adiposity induces the clustering of cardiometabolic risk factors, and pediatric adiposity is a better indicator for adulthood cardiometabolic diseases than pediatric metabolic syndrome. However, the observed prevalence of pediatric adiposity depends on the methods and cut-points used. Therefore, we aimed to define diagnostic criteria for adiposity which enable more valid identification of prepubertal children at increased cardiometabolic risk. Methods: The participants were 470 prepubertal children (249 boys) aged 6-8 years. The measures of adiposity included body mass index-standard deviation score (BMI-SDS), waist-to-height ratio (WHtR) and body fat percentage (BF%) assessed by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). Criteria for adiposity were determined by increased cardiometabolic risk. Cardiometabolic risk factors which correlated with BF% assessed by DXA in the upper but not lower half of BF% (serum insulin and plasma high-density lipoprotein cholesterol, triglycerides, gamma-glutamyl transferase, high-sensitivity C-reactive protein and uric acid) were included in the cardiometabolic risk score (CMS). We computed receiver operating characteristics curves for the measures of adiposity using the ≥90th percentile of CMS as a measure of increased cardiometabolic risk, and local regression curves were graphed to demonstrate the associations of the measures of adiposity with CMS. Results: In girls, WHtR of 0.445 (area under curve 0.778, its 95% confidence interval 0.65-0.91, sensitivity and specificity 0.73) and BF% of 19.5% assessed by BIA (0.801, 0.70-0.90, 0.73) were the best overall criteria for increased cardiometabolic risk. In boys, BMI-SDS of 0.48 (0.833, 0.75-0.92, 0.76) was the best overall criterion for increased cardiometabolic risk. While local regression curves in girls showed that WHtR of 0.445 corresponds well to a point where CMS began to increase, in boys local regression curves suggest that CMS began to increase even at a lower level of BMI-SDS than 0.48. Moreover, the diagnostic ability of the measures of adiposity to exclude increased cardiometabolic risk was poorer than the ability to detect it. Conclusions: In general, the measures of adiposity have sufficient diagnostic accuracy to be utilized as the screening tool for increased cardiometabolic risk. The observed cut-points for adiposity were lower than the traditional cut-points for adiposity.

Peak oxygen uptake cut-points to identify children at increased cardiometabolic risk - The PANIC Study.

We aimed to develop cut-points for directly measured peak oxygen uptake ( V ˙ O 2 peak ) to identify boys and girls at increased cardiometabolic risk using different scaling methods to control for body size and composition. Altogether 352 children (186 boys, 166 girls) aged 9-11 years were included in the analyses. We measured V̇O2peak directly during a maximal cycle ergometer exercise test and lean body mass (LM) by bioelectrical impedance. We computed a sex- and age-specific cardiometabolic risk score (CRS) by summing important cardiometabolic risk factors and defined increased cardiometabolic risk as >1 standard deviation above the mean of CRS. Receiver operating characteristics curves were used to detect V̇O2peak cut-points for increased cardiometabolic risk. Boys with V̇O2peak <45.8 mL kg body mass (BM)-1  min-1 (95% confidence interval [CI] = 45.1 to 54.6, area under the curve [AUC] = 0.86, P < 0.001) and <63.2 mL kg LM-1  min-1 (95% CI =52.4 to 67.5, AUC = 0.65, P = 0.006) had an increased CRS. Girls with V̇O2peak <44.1 mL kg BM-1  min-1 (95% CI = 44.0 to 58.6, AUC = 0.67, P = 0.013) had an increased CRS. V̇O2peak scaled by BM-0.49 and LM-0.77 derived from log-linear allometric modeling poorly predicted increased cardiometabolic risk in boys and girls. In conclusion, directly measured V ˙ O 2 peak <45.8 mL kg BM-1  min-1 among boys and <44.1 mL kg BM-1  min-1 among girls were cut-points to identify those at increased cardiometabolic risk. Appropriately controlling for body size and composition reduced the ability of cardiorespiratory fitness to identify children at increased cardiometabolic risk.

Associations of Dehydroepiandrosterone Sulfate With Cardiometabolic Risk Factors in Prepubertal Children.

Context: Premature adrenarche (PA) has been associated with overweight and insulin resistance, but the associations of serum dehydroepiandrosterone sulfate (DHEAS) concentration with other cardiometabolic risk factors are uncertain. Objective: To examine the associations of serum DHEAS concentration with several cardiometabolic risk factors in children. Design: Cross-sectional data from the Physical Activity and Nutrition in Children Study. Participants: Population sample of 207 girls and 225 boys aged 7.6 ± 0.4 years. Main Outcome Measures: Cardiometabolic risk factors by serum DHEAS concentration. Results: DHEAS correlated positively with body mass index standard deviation score, body fat percentage, lean body mass, high-sensitivity C-reactive protein (hs-CRP), and alanine aminotransferase (ALT) when adjusted for age and sex. The associations of DHEAS with hs-CRP and ALT disappeared when adjusted also for body fat percentage. When further adjusted for birth weight SD score, DHEAS correlated negatively with low-density lipoprotein (LDL) cholesterol and LDL/high-density lipoprotein (HDL) cholesterol ratio. LDL cholesterol was lower in children with DHEAS ≥40 µg/dL than in those with DHEAS <40 µg/dL, adjusted for age, sex, and body fat percentage (86.5 vs 92.3 mg/dL, P = 0.029). This association strengthened after further adjustment for birth weight SD score (85.3 vs 92.3 mg/dL, P = 0.012). Conclusion: Higher DHEAS is not associated with an increased cardiometabolic risk in prepubertal children. Instead, it may be protective, evidenced by an association with lower LDL cholesterol and LDL/HDL cholesterol ratio. The increased cardiometabolic risk in PA shown in many studies may be due to low birth weight and childhood overweight associated with PA.

Serum 25-Hydroxyvitamin D, Plasma Lipids, and Associated Gene Variants in Prepubertal Children.

Context: The associations of serum 25-hydroxyvitamin D [25(OH)D] with plasma lipids remain controversial in children. Objective: To examine the associations and interactions of 25(OH)D and related gene variants with lipids in children. Design: Cross-sectional. Setting: Kuopio, Finland. Participants: Population sample of 419 prepubertal white children aged 6 to 8 years. Main Outcome Measures: 25(OH)D, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. Results: Serum 25(OH)D was negatively associated with total cholesterol (ß = -0.141, P = 0.004), LDL cholesterol (ß = -0.112, P = 0.023), HDL cholesterol (ß = -0.150, P = 0.002), and triglycerides (ß = -0.104, P = 0.035) adjusted for age and sex. Associations of 25(OH)D with total cholesterol, LDL cholesterol, and HDL cholesterol remained after adjustment for adiposity, physical activity, sedentary behavior, diet, daylight time, and parental education. Children in the highest quartile of 25(OH)D had the lowest total cholesterol (P = 0.022) and LDL cholesterol (P = 0.026) adjusted for age and sex. Cytochrome P450 family 2 subfamily R member 1 (CYP2R1) rs12794714, CYP2R1 rs10741657, and vitamin D binding protein (DBP) rs2282679 were associated with 25(OH)D adjusted for age and sex. CYP2R1 rs12794714 was associated with total cholesterol and LDL cholesterol and C10orf88 rs6599638 with HDL cholesterol adjusted for age, sex, and 25(OH)D. The gene variants did not explain or modify the associations of 25(OH)D with lipids. Conclusions: 25(OH)D was independently and inversely associated with total cholesterol, LDL cholesterol, and HDL cholesterol. CYP2R1 rs12794714, CYP2R1 rs10741657, and DBP rs2282679 were associated with 25(OH)D. CYP2R1 rs12794714 was associated with total cholesterol and LDL cholesterol and chromosome 10 open reading frame 88 (C10orf88) rs6599638 with HDL cholesterol independent of 25(OH)D. None of the gene variants modified the associations of 25(OH)D with lipids. Further studies are needed to detect the mechanisms for the associations of 25(OH)D with lipids.

Mediating effects of motor performance, cardiorespiratory fitness, physical activity, and sedentary behaviour on the associations of adiposity and other cardiometabolic risk factors with academic achievement in children.

We investigated the associations of cardiometabolic risk factors with academic achievement and whether motor performance, cardiorespiratory fitness, physical activity, or sedentary behaviour mediated these associations. Altogether 175 children 6-8 years-of-age participated in the study. We assessed body fat percentage (BF%), waist circumference, insulin, glucose, triglycerides, HDL cholesterol, and systolic and diastolic blood pressure, leptin, alanine aminotransferase, and gamma-glutamyltransferase (GGT). Reading fluency, reading comprehension, and arithmetic skills were assessed using standardized tests. Speed/agility, balance, and manual dexterity test results were used to calculate motor performance score and physical activity was assessed by combined heart rate and movement sensor and cardiorespiratory fitness by maximal cycle ergometer test. In boys, BF% was inversely associated with reading fluency (ß = -0.262, P = 0.007) and reading comprehension (ß = -0.216, P = 0.025). Motor performance mediated these associations. Leptin was inversely related to reading fluency (ß = -0.272, P = 0.006) and reading comprehension (ß = -0.287, P = 0.003). The inverse association of leptin with reading fluency was mediated by motor performance. In girls, GGT was inversely associated with reading fluency independent of confounders (ß = -0.325, P = 0.007). The inverse association of BF% with academic achievement among boys was largely explained by motor performance. Leptin in boys and GGT in girls were inversely associated with academic achievement independent of confounding factors.

Birth weight is associated with dietary factors at the age of 6-8 years: the Physical Activity and Nutrition in Children (PANIC) study.

OBJECTIVE: Low and high birth weight have been associated with increased risk of type 2 diabetes and CVD. Diet could partly mediate this association, e.g. by intra-uterine programming of unhealthy food preferences. We examined the association of birth weight with diet in Finnish children. DESIGN: Birth weight standard deviation score (SDS) was calculated using national birth register data and Finnish references. Dietary factors were assessed using 4 d food records. Diet quality was defined by the Finnish Children Healthy Eating Index (FCHEI). SETTING: The Physical Activity and Nutrition in Children (PANIC) study. SUBJECTS: Singleton, full-term children (179 girls, 188 boys) aged 6-8 years. RESULTS: Birth weight was inversely associated (standardized regression coefficient ß; 95 % CI) with FCHEI (-0·15; -0·28, -0·03) in all children and in boys (-0·27; -0·45, -0·09) but not in girls (-0·01; -0·21, 0·18) after adjusting for potential confounders (P=0·044 for interaction). Moreover, higher birth weight was associated with lower fruit and berries consumption (-0·13; -0·25, 0·00), higher energy intake (0·17; 0·05, 0·29), higher sucrose intake (0·19; 0·06, 0·32) and lower fibre intake (-0·14; -0·26, -0·01). These associations were statistically non-significant after correction for multiple testing. Children with birth weight >1 SDS had higher sucrose intake (mean; 95 % CI) as a percentage of energy intake (14·3 E%; 12·6, 16·0 E%) than children with birth weight of -1 to 1 SDS (12·8 E%; 11·6, 14·0 E%) or <-1 SDS (12·4 E%; 10·8, 13·9 E%; P=0·036). CONCLUSIONS: Higher birth weight may be associated with unhealthy diet in childhood.

Body fat mass, lean body mass and associated biomarkers as determinants of bone mineral density in children 6-8years of age - The Physical Activity and Nutrition in Children (PANIC) study.

Lean body mass (LM) has been positively associated with bone mineral density (BMD) in children and adolescents, but the relationship between body fat mass (FM) and BMD remains controversial. Several biomarkers secreted by adipose tissue, skeletal muscle, or bone may affect bone metabolism and BMD. We investigated the associations of LM, FM, and such biomarkers with BMD in children. We studied a population sample of 472 prepubertal Finnish children (227 girls, 245 boys) aged 6-8years. We assessed BMD, LM, and FM using whole-body dual-energy x-ray absorptiometry and analysed several biomarkers from fasting blood samples. We studied the associations of LM, FM, and the biomarkers with BMD of the whole body excluding the head using linear regression analysis. LM (standardized regression coefficient ß=0.708, p<0.001), FM (ß=0.358, p<0.001), and irisin (ß=0.079, p=0.048) were positive correlates for BMD adjusted for age, sex, and height in all children. These associations remained statistically significant after further adjustment for LM or FM. The positive associations of dehydroepiandrosterone sulphate (DHEAS), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), leptin, free leptin index, and high-sensitivity C-reactive protein and the negative association of leptin receptor with BMD were explained by FM. The positive associations of DHEAS and HOMA-IR with BMD were also explained by LM. Serum 25-hydroxyvitamin D was a positive correlate for BMD adjusted for age, sex, and height and after further adjustment for FM but not for LM. LM and FM were positive correlates for BMD also in girls and boys separately. In girls, insulin, HOMA-IR, leptin, and free leptin index were positively and leptin receptor was negatively associated with BMD adjusted for age, height, and LM. After adjustment for age, height, and FM, none of the biomarkers was associated with BMD. In boys, leptin and free leptin index were positively and leptin receptor was negatively associated with BMD adjusted for age, height, and LM. After adjustment for age, height and FM, 25(OH)D was positively and IGF-1 and leptin were negatively associated with BMD. FM strongly modified the association between leptin and BMD. LM but also FM were strong, independent positive correlates for BMD in all children, girls, and boys. Irisin was positively and independently associated with BMD in all children. The associations of other biomarkers with BMD were explained by LM or FM.

Development of corticospinal motor excitability and cortical silent period from mid-childhood to adulthood - a navigated TMS study.

OBJECTIVES: We characterized the maturation of the excitability of the motor cortex and corticospinal tract from childhood to adulthood using electric field (EF) navigated TMS and correlated the results with manual dexterity. METHODS: Both hemispheres of healthy right-handed children (6-9 years, n=10), preadolescents (10-12 years, n=13), adolescents (14-17 years, n=12) and young adults (22-34 years, n=12) of both genders were examined. The optimal cortical representation site and resting motor threshold (rMT) were determined for the abductor pollicis brevis muscle. Motor-evoked potential (MEP) latencies and amplitudes in relaxed and active states, input-output curves and silent period (SP) durations were determined. Manual dexterity was assessed with the Box and Block Test. RESULTS: rMT (in terms of maximal stimulator output or EF strength) decreased with age (P<0.001) and stabilized when reaching adolescence. The MEP amplitude (P=0.037) and latency increased (P<0.001) with age. Input-output curves showed age-dependent changes in several parameters. SP duration decreased with age (P<0.001), and demonstrated hemispheric asymmetry in the children (P=0.030). Manual dexterity correlated negatively with rMT (P<0.001). DISCUSSION: The excitation/inhibition balance develops with age and correlates with manual dexterity. Strong corticospinal inhibition was observed in the children and this was found to decrease with age. Interhemispheric asymmetry was only observed for SP duration in the children. Knowledge of normal development is crucial for the understanding of developmental disabilities and using estimates of effective EF may be advantageous in future pediatric studies.

Associations of lifestyle factors with serum dehydroepiandrosterone sulphate and insulin-like growth factor-1 concentration in prepubertal children.

OBJECTIVE: Little is known about the relationships of dietary factors, physical activity and sedentary behaviour to dehydroepiandrosterone sulphate (DHEAS) and insulin-like growth factor-1 (IGF-1) concentrations among prepubertal children. Therefore, we studied the associations of these lifestyle factors with serum DHEAS and IGF-1 in children. DESIGN AND SUBJECTS: Cross-sectional analysis of a population sample of 431 prepubertal children aged 6-9 years. MEASUREMENTS: Assessment of dietary factors by food records and physical activity and sedentary behaviour by a combined heart rate and movement monitor and a questionnaire. Measurement of serum DHEAS and IGF-1. RESULTS: Consumption of low-fibre grain products (standardized regression coefficient ß = .118, P = .017) and intake of vegetable protein (ß = .100, P = .045) was positively and consumption of sugar-sweetened beverages (ß = -.117, P = .018) was inversely associated with DHEAS after adjustment for sex, age and body fat percentage. Energy intake (ß = .160, P = .001) was positively associated with IGF-1 adjusting for sex, age and body fat percentage. Vigorous physical activity was inversely associated with DHEAS after adjustment for sex and age (ß = -.120, P = .027), and total (ß = -.137, P = .007), moderate (ß = -.130, P = .012), vigorous (ß = -.136, P = .011) and moderate to vigorous physical activity (ß = -.160, P = .003) were inversely and total sedentary behaviour (ß = .151, P = .003) was positively associated with IGF-1 adjusting for sex and age. None of physical activity measures was associated with DHEAS or IGF-1 after additional adjustment for body fat percentage. CONCLUSIONS: Lifestyle factors have weak and moderate associations with biochemical markers of adrenarche in prepubertal children. These associations indicate body fat independent and dependent influences of diet and physical activity, respectively.

Physical activity, sedentary behaviour, and socioeconomic status among Finnish girls and boys aged 6-8 years.

We studied differences in physical activity (PA), sedentary behaviour (SB), and the types of PA and SB between Finnish girls and boys and children from different socioeconomic backgrounds (SES). We assessed PA, SB, parental education, and household income using detailed questionnaires in a representative population sample of 486 children (238 girls, 248 boys) aged 6-8 years. Girls spent on average 1.7 h/day and boys 2.0 h/day in total PA (p = 0.002). Altogether 66% of girls and 54% of boys had less than 2 h of total PA per day (p = 0.012). Girls had lower levels of unsupervised PA (45 vs. 54 min/day, p = 0.001), supervised PA (1.5 vs. 1.9 h/week, p = 0.009), and PA during school recess (1.8 vs. 1.9 h/week, p = 0.032) than boys. Girls had higher levels of total SB (3.8 vs. 3.4 h/day, p = 0.015) but lower levels of screen-based SB (1.5 vs. 1.9 h/day, p < 0.001) than boys. Lower parental education and household income were associated with lower levels of supervised PA in girls (p = 0.011 and p = 0.008, respectively) and in boys (p = 0.006 and p = 0.003, respectively). Lower parental education and household income were also related to higher levels of screen-based SB in boys (p = 0.005 and p < 0.001, respectively) but not in girls. Girls have lower levels of total, unsupervised, and supervised PA, PA during recess, and screen-based SB but higher levels of total SB than boys. Lower parental education and household income are associated with lower levels of supervised PA in both genders and higher levels of screen-based SB in boys.

Development of cortical motor circuits between childhood and adulthood: A navigated TMS-HdEEG study.

Motor functions improve during childhood and adolescence, but little is still known about the development of cortical motor circuits during early life. To elucidate the neurophysiological hallmarks of motor cortex development, we investigated the differences in motor cortical excitability and connectivity between healthy children, adolescents, and adults by means of navigated suprathreshold motor cortex transcranial magnetic stimulation (TMS) combined with high-density electroencephalography (EEG). We demonstrated that with development, the excitability of the motor system increases, the TMS-evoked EEG waveform increases in complexity, the magnitude of induced activation decreases, and signal spreading increases. Furthermore, the phase of the oscillatory response to TMS becomes less consistent with age. These changes parallel an improvement in manual dexterity and may reflect developmental changes in functional connectivity. Hum Brain Mapp 38:2599-2615, 2017. © 2017 Wiley Periodicals, Inc.

Associations of Objectively Measured Physical Activity and Sedentary Time With Arterial Stiffness in Pre-Pubertal Children.

PURPOSE: To investigate the relationships of objectively measured physical activity (PA) and sedentary time (ST) to arterial stiffness in prepubertal children. METHOD: Altogether 136 children (57 boys, 79 girls) aged 6-8-years participated in the study. Stiffness index (SI) was assessed by pulse contour analysis based on photoplethysmography. ST, light PA, moderate PA, and vigorous PA were assessed using combined acceleration and heart rate monitoring. We investigated the associations of ST (<1.5METs) and time spent in intensity level of PA above 2-7METs in min/d with SI using linear regression analysis. We studied the optimal duration and intensity of PA to identify children being in the highest quarter of SI using Receiver Operating Characteristics curves. RESULTS: Moderate PA, vigorous PA, and cumulative time spent in PA above 3 (ß=-0.279, p = .002), 4 (ß =-0.341, P<0.001), 5 (ß =-0.349, P<0.001), 6 (ß =-0.312, P<0.001), and 7 (ß =-0.254, p = .005) METs were inversely associated with SI after adjustment for age, sex, and monitor wear time. The cutoffs for identifying children being in the highest quarter of SI <68 min/d for PA exceeding 5 METs and <26 min/d for PA exceeding 6 METs. CONCLUSION: Lower levels of PA exceeding 3-6 METs were related to higher arterial stiffness in children.

Diet quality and academic achievement: a prospective study among primary school children.

PURPOSE: Poor diet quality may impair academic achievement in children, but such evidence is limited. Therefore, we investigated the associations of healthy diet in Grade 1 assessed by Mediterranean Diet Score (MDS), Baltic Sea Diet Score (BSDS), and Finnish Children Healthy Eating Index (FCHEI) with academic achievement in Grades 1-3 in children. METHODS: The participants were 161 Finnish children who were 6-8 years old in Grade 1 and attended in a large ongoing physical activity and dietary intervention study. Dietary factors were assessed using 4-day food records, and MDS, BSDS, and FCHEI were calculated. Academic achievement was assessed by reading fluency, reading comprehension, and arithmetic skill tests. The data were analyzed using linear regression analysis and analysis of covariance adjusted for age, sex, parental education, household income, body fat percentage, physical activity, the PANIC Study group, and total energy intake. RESULTS: MDS was positively associated with reading comprehension in Grade 3 (standardized regression coefficient ß = 0.167, P = 0.032). BSDS was positively associated with reading fluency in Grades 2-3 and reading comprehension in Grades 1-3 (ß = 0.161-0.274, P < 0.05). FCHEI was positively related to reading fluency in Grades 1-2 and reading comprehension in Grades 1-3 (ß = 0.190-0.344, P < 0.05). Children in the highest third of BSDS and FCHEI had better reading fluency and reading comprehension in Grades 1-3 than children in the lowest third (P < 0.05). None of the diet scores was associated with arithmetic skills. CONCLUSIONS: Healthier diet assessed by BSDS or FCHEI in Grade 1 was associated with better reading skills, but not with arithmetic skills, among children in Grades 1-3. Long-term intervention studies are needed to investigate the effects of improvements in diet quality on academic achievement among children. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01803776.