Burden of oral diseases predicts development of excess weight in early adolescence: a 2-year longitudinal study.

Dental caries, gingivitis, and excess weight are highly prevalent, interconnected chronic conditions. The association of oral health with the development of adiposity among children is sparsely addressed. We examined the association of oral health to the development of excess weight and central obesity in early adolescence during a 2-year follow-up period. This prospective study was conducted with 2702 children aged 9-12 years at baseline from the Finnish Health in Teens study. Their weight development was followed up for 2 years. Body mass index with age- and sex-specific cut-offs and the waist-height ratio indicated weight status and central obesity. Oral health data (caries experience and gingivitis/calculus) were collected from outpatient records of public dental services. Having both caries experience and gingivitis/calculus was considered burden of oral diseases. Of the sample, 74% were caries-free but 70% exhibited gingivitis and/or calculus, and 20% had both caries experience and gingivitis/calculus. During the follow-up period, 5.3% (n = 124) and 4.7% (n = 118) of the children became overweight/obese or centrally obese, respectively. Having both caries experience and gingivitis/calculus associated with the development of excess weight in a fully adjusted model (HR 1.75, 95% CI 1.03-2.97) but not of central obesity. Caries experience or gingivitis/calculus alone did not associate with adiposity development. CONCLUSION: Having burden of oral diseases without excess weight at early adolescence could imply future weight gain; thus, normal-weight individuals with both caries experience and gingivitis/calculus could be targeted with preventive measures. Our findings warrant further research to explore whether oral diseases and the development of obesity merely share risk factors or if their relationship is of causal nature. WHAT IS KNOWN: • Association of excess weight with caries experience and gingivitis is known to exist both cross-sectionally and longitudinally in children and adolescents. WHAT IS NEW: • Burden of oral diseases, that is, having both caries experience and gingivitis/calculus, was associated with becoming overweight or obese 2 years later during early adolescence. • Normal-weight individuals with burden of oral diseases at early adolescence could be targeted with preventive measures against excess weight gain.

Vitamin D supplementation for improving bone density in vitamin D-deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D-deficient children are unclear. OBJECTIVES: This study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D-deficient individuals. METHODS: This is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1-19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup. RESULTS: Eleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty. CONCLUSIONS: Clinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets). This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772.

Interaction between genetic susceptibility to obesity and food intake on BMI in Finnish school-aged children.

Diet modulates the genetic risk of obesity, but the modulation has been rarely studied using genetic risk scores (GRSs) in children. Our objectives were to identify single nucleotide polymorphisms (SNPs) that drive the interaction of specific foods with obesity and combine these into GRSs. Genetic and food frequency data from Finnish Health in Teens study was utilized. In total, 1142 11-year-old subjects were genotyped on the Metabochip array. BMI-GRS with 30 well-known SNPs was computed and the interaction of individual SNPs with food items and their summary dietary scores were examined in relation to age- and sex-specific BMI z-score (BMIz). The whole BMI-GRS interacted with several foods on BMIz. We identified 7-11 SNPs responsible for each interaction and these were combined into food-specific GRS. The most predominant interaction was witnessed for pizza (p < 0.001): the effect on BMIz was b - 0.130 (95% CI - 0.23; - 0.031) in those with low-risk, and 0.153 (95% CI 0.072; 0.234) in high-risk. Corresponding, but weaker interactions were verified for sweets and chocolate, sugary juice drink, and hamburger and hotdog. In total 5 SNPs close to genes NEGR1, SEC16B, TMEM18, GNPDA2, and FTO were shared between these interactions. Our results suggested that children genetically prone to obesity showed a stronger association of unhealthy foods with BMIz than those with lower genetic susceptibility. Shared SNPs of the interactions suggest common differences in metabolic gene-diet interactions, which warrants further investigation.

Pre-Diagnostic Saliva Microbiota of School-Aged Children Who Developed Type 1 Diabetes or Inflammatory Bowel Diseases.

Altered commensal microbiota composition has been associated with pediatric type 1 diabetes mellitus (T1D) and inflammatory bowel diseases (IBD), but the causal relationship is still unclear. To search for potential pre-diagnostic biomarkers for pediatric T1D or IBD, we compared microbiota in saliva samples in a nested case-control design comprising children developing T1D (nchildren = 52) or IBD (nchildren = 21) and controls with a similar age, sex, and residential area (nchildren = 79). The pre-diagnostic saliva microbiota alpha- and beta-diversity of children who would develop T1D (nsamples = 27) or IBD (nsamples = 14) minimally varied from that of controls. The relative abundances of Abiotrophia were higher, while those of Veillonella, Actinomyces, Megasphaera, Butyrivibrio, and Candidatus ancillula were lower in children who would develop T1D. Within 2 years before diagnosis, the metabolic PWY-5677 pathway (converting succinate into butyrate) was lower in pre-T1D samples than in controls (q = 0.034). No significant pre-IBD differences were found. In conclusion, saliva microbiota diversity or composition were not successful predictors for pediatric T1D nor IBD. Intriguingly, the succinate fermentation pathway was predicted to be lowered before the onset of T1D. Thus, investigating functional pathways might provide a better approach in searching for biomarkers for autoimmune disease in the future.

Exposure to proton pump inhibitors is associated with the development of pediatric autoimmune diseases.

Proton pump inhibitors (PPIs) have been associated with decreased gut microbiota diversity. Disrupted gut microbiota composition has been reported in several autoimmune diseases (ADs), such as type 1 diabetes mellitus (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD). We investigated whether PPIs are associated with the development of ADs in children and concluded that PPI exposures could be related to the onset of ADs, especially IBD and potentially AIT as well.

Delayed bedtime on non-school days associates with higher weight and waist circumference in children: Cross-sectional and longitudinal analyses with Mendelian randomisation.

Sleep duration has been linked with obesity in population-based studies. Less is known about bedtimes and, especially, if discrepancy between bedtimes on school and non-school days associate with adiposity in children. The associations of self-reported bedtimes with the body mass index z-score (BMIz) and waist-to-height ratio (WtHr) were examined among children with a mean (SD) age of 11.2 (0.85) years in cross-sectional (n = 10,245) and longitudinal (n = 5085) study settings. The causal relationship of whether BMIz contributes to bedtimes, was further examined in a subset of 1064 participants by exploiting Mendelian randomisation (MR). After adjusting for sleep duration and other confounders, every 0.5 h later bedtime on non-school nights and a delay in bedtime in non-school nights compared with school nights associated with 0.048 (95% CI 0.027; 0.069) and 0.08 (95% CI 0.056; 0.105) higher BMIz as well as 0.001 (95% CI 0; 0.002) and 0.004 (95% CI 0.003; 0.005) with higher WtHr, respectively. Moreover, every 0.5-h delay in bedtime in non-school nights compared with school nights associated with 0.001 (95% CI 0; 0.002) greater increase in WtHr in the 2.5 years follow-up. Thus, a 2-h delay in bedtime at the age of 11 years corresponds with a 0.6 cm increase in waist circumference. The MR analysis did not indicate an opposite causal relationship: higher BMIz was not causing delayed bedtimes. Later bedtime on non-school days and discrepancy in bedtimes associated with increased BMIz and WtHr, while longitudinally these predicted higher WtHr, independently of sleep duration. Promoting early bedtimes, especially on weekends, should be considered in obesity prevention among school-aged children.

Antibiotic exposures and the development of pediatric autoimmune diseases: a register-based case-control study.

BACKGROUND: Antibiotics have been associated with several individual autoimmune diseases (ADs). This study aims to discover whether pre-diagnostic antibiotics are associated with the onset of ADs in general. METHODS: From a cohort of 11,407 children, 242 developed ADs (type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis (JIA), or inflammatory bowel diseases) by a median age of 16 years. Antibiotic purchases from birth until the date of diagnosis (or respective date in the matched controls n = 708) were traced from national registers. RESULTS: Total number of antibiotic purchases was not related to the onset of ADs when studied as a group. Of specific diagnoses, JIA was associated with the total number of antibiotics throughout the childhood and with broad-spectrum antibiotics before the age of 3 years. Intriguingly, recent and frequent antibiotic use (within 2 years before diagnosis and ≥3 purchases) was associated with the onset of ADs (OR 1.72, 95% CI 1.08-2.74). Regardless of frequent use in childhood (40% of all antibiotics), penicillin group antibiotics were not related to any ADs. CONCLUSIONS: Use of antibiotics was relatively safe regarding the overall development of ADs. However, broad-spectrum antibiotics should be used considerately as they may associate with an increased likelihood of JIA. IMPACT: Increasing numbers of antibiotic purchases before the age of 3 years or throughout childhood were not associated with the development of pediatric autoimmune diseases. Broad-spectrum antibiotics were related to the development of autoimmune diseases, especially juvenile idiopathic arthritis in children, while penicillin group antibiotics were not. The use of broad-spectrum antibiotics in children should be cautious as they may carry along a risk for autoimmune disease development.

Associations of central obesity and habitual food consumption with saliva microbiota and its enzymatic profiles - a pilot study in Finnish children.

Background: Variation in diversity and composition of saliva microbiota has been linked to weight status, but findings have been inconsistent. Focusing on clinically relevant conditions such as central obesity and using advanced sequencing techniques might fill in the gaps of knowledge. Aims: We investigated saliva microbiota with shallow metagenome sequencing in children with (n = 14) and without (n = 36) central obesity. Additionally, we examined the role of habitual food consumption on microbial enzymatic repertoire. Methods: Data comprised 50 children (50% male) with a mean age of 14.2 (SD 0.3) years, selected from the Finnish Health in Teens (Fin-HIT) cohort. Dietary scores for consumption frequency of sweet treats (STI), dairy products (DCI) and plants (PCI) were derived based on a self-administered food frequency questionnaire. Central obesity was defined based on waist-height ratio using the cut-off 0.5. Saliva samples were subjected to whole-metagenome shotgun sequencing, and taxonomic and functional profiling was achieved with METAnnotatorX2 bioinformatics platform. Results: Groups had an average 20 (95% CI 14-27) cm difference in waist circumference. We identified the lack of Pseudomonas guguagenesis and Prevotella scopos, oulorum and oris as putative biomarkers associated with central obesity and observed a total of 16 enzymatic reactions differing between the groups. DCI was associated with the highest number of enzyme profiles (122), followed by STI (60) and DCI (25) (Pearson correlation p < 0.05). Intriguingly, STI showed a high positive/negative correlation ratio (5.09), while DCI and PCI showed low ratios (0.54 and 0.33, respectively). Thus, the main driver of enzymatic reactions was STI, and the related pathways involved nitrate metabolism induced by Haemophilus parainfluenzae and Veilonella dispar among others. Conclusion: Clinically relevant differences in central obesity were only modestly reflected in the composition of saliva microbiota. Habitual consumption of sweet treats was a strong determinant of enzymatic reactions of saliva microbiota in children with and without central obesity. The clinical relevance of these findings warrants further studies.

Associations of diet quality, food consumption, eating frequency and eating behaviour with dental caries experience in Finnish children: a 2-year longitudinal study.

We examined cross-sectional and longitudinal associations of dietary factors with caries experience in a population sample of 487 children aged 6-9 years at baseline examinations of the Physical Activity and Nutrition in Children (PANIC) Study. Altogether, 406 of these children attended 2-year follow-up examinations. Food consumption and eating frequency were assessed using 4-day food records, diet quality using the Baltic Sea Diet Score (BSDS) and eating behaviour using the Children's Eating Behavior Questionnaire. Caries experience was examined clinically. The cross-sectional associations of dietary factors with caries experience at baseline were analysed using linear regression and the longitudinal associations of dietary factors with a change in caries experience over follow-up using generalised mixed-effects regression adjusted for other risk factors. A higher consumption of high-fibre grain products (standardised regression coefficient ß = -0·16, P = 0·003) and milk (ß = -0·11, P = 0·025) and higher BSDS (ß = -0·15, P = 0·007) were associated with lower caries experience, whereas a higher consumption of potatoes (ß = 0·11, P = 0·048) and emotional overeating (ß = 0·12, P = 0·025) were associated with higher caries experience. Higher snacking frequency (fixed coefficient ß = 0·07, P = 0·033), desire to drink (ß = 0·10, P = 0·046), slowness in eating (ß = 0·12, P = 0·027) and food fussiness (ß = 0·12, P = 0·018) were associated with higher caries experience, whereas enjoyment of food (ß = -0·12, P = 0·034) and higher BSDS (ß = -0·02, P = 0·051) were associated with lower caries experience.

The Composition and Functional Capacities of Saliva Microbiota Differ Between Children With Low and High Sweet Treat Consumption.

Excess sugar consumption-common in youth-is associated with poor health. Evidence on the relationship between sugar consumption and the oral microbiome, however, remains scarce and inconclusive. We explored whether the diversity, composition, and functional capacities of saliva microbiota differ based on the consumption of select sugary foods and drinks ("sweet treats"). Using 16S rRNA gene sequencing, we characterized saliva microbiota from 11 to 13-year-old children who participated in the Finnish Health in Teens (Fin-HIT) cohort study. The sample comprised children in the lowest (n = 227) and highest (n = 226) tertiles of sweet treat consumption. We compared differences in the alpha diversity (Shannon, inverse Simpson, and Chao1 indices), beta diversity (principal coordinates analysis based on Bray-Curtis dissimilarity), and abundance (differentially abundant operational taxonomic units (OTUs) at the genus level) between these low and high consumption groups. We performed PICRUSt2 to predict the metabolic pathways of microbial communities. No differences emerged in the alpha diversity between low and high sweet treat consumption, whereas the beta diversity differed between groups (p = 0.001). The abundance of several genera such as Streptococcus, Prevotella, Veillonella, and Selenomonas was higher in the high consumption group compared with the low consumption group following false discovery rate correction (p < 0.05). Children with high sweet treat consumption exhibited higher proportions of nitrate reduction IV and gondoate biosynthesis pathways compared with the low consumption group (p < 0.05). To conclude, sweet treat consumption shapes saliva microbiota. Children who consume a high level of sweet treats exhibited different compositions and metabolic pathways compared with children who consume low levels of sweet treats. Our findings reveal novel insights into the relationship between sugary diets and oral microbiota.

Targeted Exome Sequencing of Genes Involved in Rare CNVs in Early-Onset Severe Obesity.

Context: Rare copy number variants (CNVs) have been associated with the development of severe obesity. However, the potential disease-causing contribution of individual genes within the region of CNVs is often not known. Objective: Screening of rare variants in genes involved in CNVs in Finnish patients with severe early-onset obesity to find candidate genes linked to severe obesity. Methods: Custom-made targeted exome sequencing panel to search for rare (minor allele frequency <0.1%) variants in genes affected by previously identified CNVs in 92 subjects (median age 14 years) with early-onset severe obesity (median body mass index (BMI) Z-score + 4.0). Results: We identified thirteen rare heterozygous variants of unknown significance in eleven subjects in twelve of the CNV genes. Two rare missense variants (p.Pro405Arg and p.Tyr232Cys) were found in SORCS1, a gene highly expressed in the brain and previously linked to diabetes risk. Four rare variants were in genes in the proximal 16p11.2 region (a frameshift variant in TAOK2 and missense variants in SEZ6L2, ALDOA and KIF22) and three rare missense variants were in genes in the 22q11.21 region (AIFM3, ARVCF and KLHL22). Conclusion: We report several rare variants in CNV genes in subjects with childhood obesity. However, the role of the individual genes in the previously identified rare CNVs to development of obesity remains uncertain. More studies are needed to understand the potential role of the specific genes within obesity associated CNVs.

Body Mass Index, Physical Activity, and Body Image in Adolescents.

Body image dissatisfaction is a concern for adolescents' mental and physical well-being, and the role of body mass index (BMI) and physical activity (PA) in it is still unclear. This study investigates the associations of BMI and PA with body image, separately for boys and girls, in a large sample of Finnish adolescents. We also examine the associations of BMI with body image in varying PA levels. A total of 10,496 adolescents (girls 52.6%) were included in the analyses. Body image was assessed using a pictorial tool, and categorized as wishing for a smaller body, being satisfied, and wishing for a bigger body. BMI (kg/m2) was categorized as thin, normal weight, and overweight/obese. Self-reported PA was divided into three similar-sized categories as low, moderate, and high PA levels. Adjusted ordinal regression analyses were conducted. Our results show that adolescents with thinness had higher odds of wishing for a bigger body compared to their normal-weight peers, while adolescents with overweight/obesity had smaller odds of wishing for a bigger body. Adolescents in low and middle PA levels had lower odds of wishing for a bigger body compared to adolescents in the high PA level. Yet, the PA level modified the associations between BMI and body image, especially in adolescents with thinness and more so in girls than in boys. These findings highlight the need to pay attention to healthy weight gain and PA in adolescents to support their body image satisfaction.

Central obesity in school-aged children increases the likelihood of developing paediatric autoimmune diseases.

BACKGROUND: The incidences of both paediatric obesity and autoimmune diseases have been increasing, but their relationship with one another is unclear. OBJECTIVE: To determine whether obesity or particular dietary patterns in school-aged children are potential risk factors for autoimmune diseases during adolescence. METHODS: This matched case-control study included 525 children, followed up from a median age of 11.3 to 16.7 years. Of them, 105 children received primary autoimmune diagnoses (diabetes, thyroiditis, arthritis, or inflammatory bowel diseases) after baseline and generated the case group. Four children with matching age, sex, and residential area generated the control group of 420 children. At baseline, age- and sex-specific body mass index categories were acquired and waist-to-height ratio (WHTR) was calculated. Central obesity was present when WHTR ≥0.5. Dietary patterns were analysed using a food frequency questionnaire (FFQ). RESULTS: School-aged children with central obesity were 2.11 (OR, 95% CI 1.11-3.98) times more likely to develop autoimmune diseases before age of 19 years than those without central obesity. Being overweight was not related to the onset of these diseases (OR 1.60, 95% CI 0.89-2.87, nor were dietary patterns. CONCLUSION: Central obesity in school-aged children was related to the development of autoimmune diseases, while being overweight and dietary patterns were not.

Prevalence of Thinness, Overweight, Obesity, and Central Obesity in Finnish School-Aged Children: A Comparison of National and International Reference Values.

INTRODUCTION: The global epidemic of obesity concerns children, and monitoring the prevalence is of highest priority. Body mass index (BMI) with age- and sex-specific cutoff values determines weight status in children, although multiple reference systems exist. Our aim was to compare the prevalence for thinness, normal weight, overweight, and obesity in Finnish school-aged children according to national and international reference values, as well as to determine which cutoff values for overweight agree with the criteria for central obesity. METHODS: This study includes 10,646 children aged 9-12 years from the Finnish Health in Teens cohort. Height, weight, and waist circumference were measured in 2011-2014. BMI (weight [kg]/height [m]2) and the waist-to-height ratio (WHtR; waist [cm]/height [cm]) were calculated. The WHtR cutoff of >0.5 indicated central obesity. We compared the sex-specific prevalence of thinness, overweight, and obesity using the International Obesity Task Force (IOTF), World Health Organization (WHO) and Finnish (FIN) BMI-for-age reference values, as well as these three against central obesity based on the WHtR. RESULTS: The prevalence of thinness, overweight, and obesity were 11.0%, 12.7%, and 2.6%, respectively, using IOTF; 2.6%, 15.9%, and 5.2% using WHO; and 5.1%, 11.4%, and 2.2% using FIN. Overweight and obesity were more common in boys than girls using WHO and FIN, while thinness was more common in girls using IOTF and FIN. IOTF versus WHO exhibited moderate agreement (κ = 0.59), which improved for IOTF versus FIN (κ = 0.74). Of those classified as overweight by WHO, 37% and 47% were regarded as normal weight according to IOTF and FIN, respectively. The prevalence of central obesity was 8.7%, and it was more common in boys than girls. WHO provided the highest sensitivity: 95% of individuals with central obesity were classified with overweight or obesity. Using FIN provided the highest specificity (93%). CONCLUSION: Our findings show that WHO overestimates the prevalence of overweight and obesity, while IOTF overrates thinness. Thus, comparing prevalence rates between studies requires caution. The novelty of this study is the comparison of the cutoff values for overweight with central obesity. The choice of reference system affects the generalizability of the research results.

Serum and Urinary Osteocalcin in Healthy 7- to 19-Year-Old Finnish Children and Adolescents.

Children and adolescents have high bone turnover marker (BTM) levels due to high growth velocity and rapid bone turnover. Pediatric normative values for BTMs reflecting bone formation and resorption are vital for timely assessment of healthy bone turnover, investigating skeletal diseases, or monitoring treatment outcomes. Optimally, clinically feasible measurement protocols for BTMs would be validated and measurable in both urine and serum. We aimed to (a) establish sex- and age-specific reference intervals for urinary and serum total and carboxylated osteocalcin (OC) in 7- to 19-year-old healthy Finnish children and adolescents (n = 172), (b) validate these against standardized serum and urinary BTMs, and (c) assess the impact of anthropometry, pubertal status, and body composition on the OC values. All OC values in addition to other BTMs increased with puberty and correlated with pubertal growth, which occurred and declined earlier in girls than in boys. The mean serum total and carboxylated OC and urinary OC values and percentiles for sex-specific age categories and pubertal stages were established. Correlation between serum and urinary OC was weak, especially in younger boys, but improved with increasing age. The independent determinants for OC varied, the urinary OC being the most robust while age, height, weight, and plasma parathyroid hormone (PTH) influenced serum total and carboxylated OC values. Body composition parameters had no influence on any of the OC values. In children and adolescents, circulating and urinary OC reflect more accurately growth status than bone mineral density (BMD) or body composition. Thus, validity of OC, similar to other BTMs, as a single marker of bone turnover, remains limited. Yet, serum and urinary OC similarly to other BTMs provide a valuable supplementary tool when assessing longitudinal changes in bone health with repeat measurements, in combination with other clinically relevant parameters.

Effect of High-Dose vs Standard-Dose Vitamin D Supplementation on Neurodevelopment of Healthy Term Infants: A Randomized Clinical Trial.

Importance: Vitamin D may be important for neurodevelopment. The optimal daily dose of vitamin D for early brain development is not known. Objectives: To test whether a higher (1200 IU) vs standard (400 IU) dose of vitamin D3 has beneficial effects on neurodevelopment in the first 2 years of life and whether serum 25-hydroxyvitamin D concentration is associated with neurodevelopment. Design, Setting, and Participants: This double-blind, interventional randomized clinical trial involved healthy infants born full-term between January 1, 2013, and June 30, 2014, at a maternity hospital in Helsinki, Finland, at the 60th northern latitude. Two-year follow-up was conducted by May 30, 2016. Data analysis was by the intention-to-treat principle. Data were analyzed from November 1, 2020, to May 31, 2021. Interventions: Randomization of 404 infants to receive 400 IU of oral vitamin D3 supplementation daily and 397 infants to receive 1200 IU of oral vitamin D3 supplementation daily from 2 weeks to 24 months of age. Main Outcomes and Measures: Primary outcomes were child total developmental milestone scores at 12 and 24 months of age measured using the Ages and Stages Questionnaire (total score is calculated as a mean of the 5 subscale scores: total score range, 0-60, where 0 indicates delay in all developmental domains and 60 indicates that the child can master all age-specific skills) as well as externalizing, internalizing, and dysregulation problems and competencies scores at 24 months measured using the Infant-Toddler Social and Emotional Assessment (range 0-2, where 0 indicates no problems or no competencies and 2 indicates a high level of problems or a high level of competencies; variables were standardized to the mean [SD] of 0 [1]). Secondary outcomes were specific skills, problems, and competencies derived from these questionnaires. Results: Of the 987 families recruited, 495 children were randomly assigned to receive 400 IU of vitamin D3, and 492 children were randomly assigned to receive 1200 IU of vitamin D3. A total of 801 families participated in the follow-up at 12 and/or 24 months, with 404 children (207 girls [51.2%]) in the 400-IU group and 397 children (198 girls [49.9%]) in the 1200-IU group. All children were of Northern European ethnicity. No differences were found between the 400-IU group and the 1200-IU group in the mean (SD) adjusted Ages and Stages Questionnaire total score at 12 months (45.0 [7.1] vs 46.2 [7.9]; mean difference [MD], 1.17 [95% CI, -0.06 to 2.38]) or 24 months (50.9 [5.3] vs 51.5 [5.5]; MD, 0.48 [95% CI, -0.40 to 1.36]). No differences were found between the 400-IU group and the 1200-IU group at 24 months in the mean (SD) adjusted Infant-Toddler Social and Emotional Assessment externalizing domain score (-0.07 [1.00] vs 0.07 [0.98]; MD, 0.15 [95% CI, -0.01 to 0.31]), internalizing domain score (0.04 [1.06] vs -0.02 [0.98]; MD, -0.07 [95% CI, -0.24 to 0.1.0]), dysregulation domain score (-0.00 [1.04] vs 0.02 [0.96]; MD, 0.02 [95% CI, -0.14 to 0.18]), or competencies score (-0.02 [1.02] vs 0.01 [1.02]; MD, 0.03 [95% CI, -0.13 to 0.20]). The 1200-IU group did have a higher risk in the adjusted model of scoring 1.5 SDs or more on the externalizing domain score (odds ratio, 2.33 [95% CI, 1.19-4.56]; P = .01). Levels of serum 25-hydroxyvitamin D were not associated with the primary outcomes. Conclusions and Relevance: Higher-than-standard vitamin D3 doses provide no systematic benefits for child neurodevelopment up to 2 years of age. However, the potential disadvantageous effects of higher doses could not be fully excluded; even if minimal, the potential nonbeneficial effects of higher-than-standard doses warrant further studies in which both safety and benefits should be evaluated. Trial Registration: ClinicalTrials.gov Identifier: NCT01723852.

Physical Activity Among Preadolescents Modifies the Long-Term Association Between Sedentary Time Spent Using Digital Media and the Increased Risk of Being Overweight.

BACKGROUND: This study aimed to examine whether sedentary digital media use in preadolescence increases the risk of being overweight 3 years later, and whether this association differs based on preadolescents' leisure-time physical activity (LTPA) levels. METHODS: The authors conducted a 3-year follow-up study among 4661 participants with a mean (SD) age of 11 (1) years at baseline and 14 (1) years at follow-up. A web-based questionnaire assessed sedentary digital media use and LTPA. The authors categorized baseline LTPA duration into 3 levels: 0 to 5 (low), 6 to 8 (moderate), and ≥9 (high) hours per week. In addition, the authors categorized adolescents as normal weight or overweight/obese at follow-up. RESULTS: Greater amounts of sedentary digital media use at baseline associated with an increased risk of being overweight 3 years later even after adjusting for confounders. This only held for preadolescents with low baseline LTPA (OR = 1.14; 95% confidence interval, 1.05-1.24), but not among those with moderate (OR = 1.02; 0.91-1.15) or high (OR = 0.96; 0.85-1.08) LTPA. CONCLUSIONS: Preadolescent LTPA modified the long-term association between sedentary digital media use and being overweight; specifically, 6 hours per week or more of LTPA mitigated the increased risk of being overweight associated with higher amounts of digital media use.

Sex- and weight-specific changes in the frequency of sweet treat consumption during early adolescence: a longitudinal study.

The transition from childhood to adolescence is a sensitive period, triggering changes in health- and weight-related behaviours including eating habits which likely vary between girls and boys. We aimed to characterise the changes in the frequency of consumption of select sugary foods and drinks ('sweet treats') among 4237 Finnish girls and boys during a 2-year follow-up period. Additionally, we examined four subgroups: children whose weight or waist normalised as well as children whose weight or waist circumference increased during follow-up. An FFQ was completed at 11·1 (sd 0·9) and again at 13·4 (sd 1·1) years of age. A sum variable sweet treat index (STI, range 0-84) captured the weekly consumption frequencies of sweet treats. From baseline to follow-up, the mean STI decreased among girls from 7·1 (95 % CI 6·9, 7·3) to 6·0 (95 % CI 5·9, 6·2) (P < 0·001) and boys from 8·5 (95 % CI 8·3, 8·8) to 7·8 (95 % CI 7·6, 7·8) (P < 0·001), although both sexes increased their chocolate/sweets consumption: girls from 1·3 (95 % CI 1·3, 1·4) to 1·6 (95 % CI 1·5, 1·6) (P < 0·001) and boys from 1·4 (95 % CI 1·3, 1·4) to 1·6 (95 % CI 1·6, 1·7) (P < 0·001), and boys increased their soft drink consumption from 1·4 (95 % CI 1·3, 1·4) to 1·5 (95 % CI 1·4, 1·5) (P = 0·020). We found similar decreases in both the weight and waist subgroups. To conclude, the total frequency of consumption of sweet treats decreased during early adolescence. A similar trend across subgroups suggests that the frequency of consumption of sweet treats is unrelated to becoming overweight.

Perinatal risk factors for pediatric onset type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis, and inflammatory bowel diseases.

Type 1 diabetes mellitus (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases with unknown risk factors. Using nationwide registers, we searched for their perinatal risk factors. Our study followed up 11,407 children (born 2000-2005) for a median of 16.6 years (from birth to 2018). Of them, 2.15% received primary diagnosis and 0.08% also secondary: 0.89% had DM, 0.60% had AIT, 0.48% had JIA, and 0.25% had IBD. The incidences per 100,000 children/year were 106.1 for DM, 46.0 for AIT, 55.0 for JIA, and 23.7 for IBD. There were more preterm births (< 37 weeks) among children with studied autoimmune diseases compared with the rest of the cohort (8.6% vs. 5.3%, p = 0.035). Among those born preterm, children with studied autoimmune diseases received more postnatal antibiotics compared with other preterm children in the cohort (47.6% vs. 27.7%, p = 0.046). Children with IBD were born to older mothers compared with those without studied diagnoses (33.0 vs 30.2, p = 0.004).Conclusion: Preterm birth was a shared risk factor for autoimmune diseases in our study, especially when combined with postnatal antibiotic treatments. High maternal age was associated with IBD. What is Known: • Type 1 diabetes (DM), autoimmune thyroiditis (AIT), juvenile idiopathic arthritis (JIA), and inflammatory bowel diseases (IBD) are common pediatric autoimmune diseases • It is unclear whether these diseases have shared risk factors, since there are no previous simultaneous epidemiological nor follow-up studies on them in one cohort  What is New: • Preterm births were more common in children with DM, AIT, JIA, or IBD compared with other children in the cohort, and preterm children who developed these diseases recieved more postnatal antibiotics compared with other preterm children • High maternal age was associated with IBD.

High abundance of sugar metabolisers in saliva of children with caries.

Dental caries is a biofilm-mediated, dynamic disease with early onset. A balanced salivary microbiota is a foundation of oral health, while dysbiosis causes tooth decay. We compared the saliva microbiota profiles in children with and without caries. The study consisted of 617 children aged 9-12 years from the Finnish Health in Teens (Fin-HIT) study with available register data on oral health. Caries status was summarised based on Decayed, Missing, and Filled Teeth (DMFT) index in permanent dentition. The children were then classified into the following two groups: DMFT value ≥ 1 was considered as cavitated caries lesions (hereafter called 'caries') (n = 208) and DMFT = 0 as 'cavity free' (n = 409). Bacterial 16S rRNA gene (V3-V4 regions) was amplified using PCR and sequenced by Illumina HiSeq. The mean age (SD) of the children was 11.7 (0.4) years and 56% were girls. The children had relatively good dental health with mean DMFT of 0.86 (1.97). Since sex was the key determinant of microbiota composition (p = 0.014), we focused on sex-stratified analysis. Alpha diversity indexes did not differ between caries and cavity free groups in either sexes (Shannon: p = 0.40 and 0.58; Inverse Simpson: p = 0.51 and 0.60, in boys and girls, respectively); neither did the composition differ between the groups (p = 0.070 for boys and p = 0.230 for girls). At the genus level, Paludibacter and Labrenzia had higher abundances in the caries group compared to cavity free group in both sexes (p < 0.001). Taken together, there were minor differences in saliva microbiota between children with and without caries. Potential biomarkers of caries were the sugar metabolisers Paludibacter and Labrenzia. These bacteria presumably enhance salivary acidification, which contributes to progression of dental caries. The clinical relevance of our findings warrants further studies.