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.

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.

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.

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.

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.

Genetic Risk Score for Serum 25-Hydroxyvitamin D Concentration Helps to Guide Personalized Vitamin D Supplementation in Healthy Finnish Adults.

BACKGROUND: Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D. OBJECTIVES: We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration. METHODS: We performed a genome-wide association study of serum 25(OH)D concentration in the Finnish Health 2011 cohort (n = 3339) using linear regression and applied the results to develop a population-matched genetic risk score (GRS) for serum 25(OH)D. This GRS was used to tailor vitamin D supplementation for 96 participants of a longitudinal Digital Health Revolution (DHR) Study. The GRS, serum 25(OH)D concentrations, and personalized supplementation and dietary advice were electronically returned to participants. Serum 25(OH)D concentrations were assessed using immunoassays and vitamin D intake using FFQs. In data analyses, cross-sectional and repeated-measures statistical tests and models were applied as described in detail elsewhere. RESULTS: GC vitamin D-binding protein and cytochrome P450 family 2 subfamily R polypeptide 1 genes showed genome-wide significant associations with serum 25(OH)D concentration. One single nucleotide polymorphism from each locus (rs4588 and rs10741657) was used to develop the GRS. After returning data to the DHR Study participants, daily vitamin D supplement users increased from 32.6% to 60.2% (P = 6.5 × 10-6) and serum 25(OH)D concentration from 64.4 ± 20.9 nmol/L to 68.5 ± 19.2 nmol/L (P = 0.006) between August and November. Notably, the difference in serum 25(OH)D concentrations between participants with no risk alleles and those with 3 or 4 risk alleles decreased from 20.7 nmol/L to 8.0 nmol/L (P = 0.0063). CONCLUSIONS: We developed and applied a population-matched GRS to identify individuals genetically predisposed to low serum 25(OH)D concentration. We show how the electronic return of individual genetic risk, serum 25(OH)D concentrations, and factors affecting vitamin D status can be used to tailor vitamin D supplementation. This model could be applied to other populations and countries.

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.

Frequent use of selected sugary products associates with thinness, but not overweight during preadolescence: a cross-sectional study.

Convincing evidence suggests that diets laden with added sugar, specifically sugar-sweetened beverages, associate with excess weight in children. The relationships between sugar consumption frequency and BMI remain less well studied. We, therefore, evaluated children's consumption frequency of selected sugary products (n 8461; mean age 11·1 (sd 0·9) years) selected from the Finnish Health in Teens cohort study. Using a sixteen-item FFQ including six sugary products (chocolate/sweets, biscuits/cookies, ice cream, sweet pastry, sugary juice drinks and sugary soft drinks), we calculated a Sweet Treat Index (STI) for the frequency of weekly sugary product consumption and categorised children based on quartiles (Q) into low (Q1, cut-off < 4·0), medium (Q2 + Q3, range 4·0-10·5) and high STI (Q4, cut-off > 10·5), and as thin, normal and overweight/obese based on the measured BMI. Through multinomial logistic regression analyses, we found that subjects with a high STI exhibited a higher risk of being thin (OR 1·20, 95 % CI 1·02, 1·41) and lower risk of being overweight (OR 0·79, 95 % CI 0·67, 0·92), while subjects with a low STI were at higher risk of being overweight (OR 1·32, 95 % CI 1·14, 1·53). High consumption frequencies of salty snacks, pizza and hamburgers most closely were associated with a high STI. Our findings suggest that consuming sugary products at a high frequency does not associate with being overweight. The relationship between a low consumption frequency and being overweight suggests that overweight children's consumption frequency of sugary products may be controlled, restricted or underreported.

Bone health in women with a history of gestational diabetes or obesity.

INTRODUCTION: Type 2 diabetes is associated with an increased risk of bone fractures. However, bone health of women with a history of gestational diabetes (GDM) has received little attention. This cross-sectional study compares bone health between premenopausal women with and without a history of GDM, and examines factors associated with bone health in women with a history of GDM or obesity. MATERIAL AND METHODS: We measured areal bone mineral density for total hip, lumbar spine and whole body, and total body fat percentage (fat%) with dual-energy X-ray absorptiometry in 224 women. In addition, we measured bone characteristics of radius and tibia with peripheral quantitative computed tomography. RESULTS: When compared with women without a history of GDM (mean age 39 years [SD 5], body mass index [BMI] 35 kg/m2 [SD 6], fat% 48 [SD 7]), women with a history of GDM (age 41 years [SD 4], BMI 31 kg/m2 [SD 7], fat% 43 [SD 10]) had lower hip and whole body bone mineral densities, and inferior tibia outcomes. However, the differences in bone characteristics disappeared after controlling for age, height, BMI and fat%. After controlling for age, height, BMI and smoking, physical activity and healthier diet were positively associated with bone outcomes, whereas fat%, HbA1c and screen time were negatively associated with bone outcomes. Particularly, fat% showed independent negative associations with whole body bone mineral density and several tibia and radius characteristics. CONCLUSIONS: Fat% is associated with adverse bone health, independently of BMI, in women with a history of GDM or obesity. Promoting healthy lifestyle and reducing fat% in high-risk women could improve bone health and prevent future fractures.

Children's Eating Attitudes Test (ChEAT): a validation study in Finnish children.

PURPOSE: To validate the Children's Eating Attitudes Test (ChEAT) in the Finnish population. MATERIALS AND METHODS: In total 339 children (age 10-15 years) from primary schools in Southern Finland were evaluated at two time points. They answered the ChEAT and SCOFF test questions, and had their weight, height and waist circumference measured. Retesting was performed 4-6 weeks later. Test-retest reliability was evaluated using intra-class correlation (ICC), and internal consistency was examined using Cronbach's alpha coefficient (C-alpha). ChEAT was cross-calibrated against SCOFF and background variables. Factor analysis was performed to examine the factor structure of ChEAT. RESULTS: The 26-item ChEAT showed high internal consistency (C-alpha 0.79), however, a 24-item ChEAT showed even better internal consistency (C-alpha 0.84) and test-retest reliability (ICC 0.794). ChEAT scores demonstrated agreement with SCOFF scores (p < 0.01). The mean ChEAT score was higher in overweight children than normal weight (p < 0.001). Exploratory factor analysis yielded four factors (concerns about weight, limiting food intake, pressure to eat, and concerns about food), explaining 57.8% of the variance. CONCLUSIONS: ChEAT is a valid and reliable tool for measuring eating attitudes in Finnish children. The 24-item ChEAT showed higher reliability than the 26-item ChEAT. LEVEL OF EVIDENCE: Level 5, cross-sectional, descriptive study.

High-Dose Vitamin D Supplementation Does Not Prevent Allergic Sensitization of Infants.

OBJECTIVE: To investigate the effect of vitamin D supplementation dose on allergic sensitization and allergic diseases in infants, and to evaluate whether vitamin D status in pregnancy and at birth are associated with infant allergy outcomes. STUDY DESIGN: Altogether, 975 infants participated in a randomized, controlled trial of daily vitamin D supplementation of 10 µg (400 IU) or 30 µg (1200 IU) from the age of 2 weeks. At 12 months of age, food and aeroallergen IgE antibodies were measured, and the occurrence of allergic diseases and wheezing were evaluated. RESULTS: We found no differences between the vitamin D supplementation groups in food (OR, 0.98; 95% CI, 0.66-1.46) or aeroallergen sensitization at 12 months (OR, 0.76; 95% CI,0.34-1.71). Allergic diseases or wheezing did not differ between groups, except for milk allergy which occurred more often in infants administered 30 µg vitamin D compared with the 10 µg dose (OR, 2.23; 95% CI, 1.00-4.96). Infants with high cord blood 25-hydroxyvitamin D (≥100 nmol/L) had a higher risk of food allergen sensitization compared with those with lower 25(OH)D concentration (75-99.9 nmol/L; OR, 2.00; 95% CI, 1.19-3.39). CONCLUSIONS: High-dose vitamin D supplementation did not prevent allergic sensitization, allergic diseases, or wheezing during the first year of life. In contrast, we observed an increased risk of milk allergy in infants randomized to higher vitamin D supplementation, and an increased risk of allergic sensitization in infants with high cord blood vitamin D status, indicating a possible adverse effect of high concentrations of vitamin D.

Eating habits and weight status in Finnish adolescents.

OBJECTIVE: To investigate the association between eating habits and weight status in adolescents in Finland. DESIGN: Cross-sectional study. SETTING: The Finnish Health in Teens (Fin-HIT) study is a cohort study conducted in adolescents attending third to sixth grade in 496 schools in forty-four municipalities in Southern, Middle and Northern Finland in 2011-2014. PARTICIPANTS: Analyses included 10 569 adolescents from the Fin-HIT study aged 9-14 years (5005 boys and 5564 girls). Adolescents were categorized by their eating habits: healthy eaters (44·1 %; n 4661), unhealthy eaters (12·3 %; n 1298), and fruit and vegetable avoiders (43·6 %; n 4610); and they were grouped into weight status: underweight (11·1 %), normal weight (73·6 %) and excess weight (15·3 %). RESULTS: We found an increased risk of underweight in fruit and vegetable avoiders (OR = 1·28; 95 % CI 1·12, 1·46). An irregular breakfast pattern showed an inverse association with underweight (OR = 0·70; 95 % CI 0·59, 0·84) and an increased risk of excess weight (OR = 1·56; 95 % CI 1·37, 1·77) compared with a regular breakfast pattern. An irregular dinner pattern was inversely associated with underweight (OR = 0·83; 95 % CI 0·69, 0·99) compared with a regular dinner pattern. CONCLUSIONS: Avoiding fruits and vegetables and following irregular breakfast and dinner patterns were associated with underweight and excess weight in adolescents.

Identifying eating habits in Finnish children: a cross-sectional study.

BACKGROUND: We aimed to identify different eating habits among Finnish children and to evaluate their association with meal patterns, breakfast consumption, and socio-demographic characteristics in a large, nationwide cohort of children. METHODS: We evaluated 10,569 children aged 9-14 years into the Finnish Health in Teens cohort in a cross-sectional design. The hierarchical K-means method was used to identify groups of children with different eating habits, based on five factors obtained through factor analysis of 10 food items. Multiple correspondence analysis was used to show associations between groups with different eating habits and meal patterns, breakfast patterns, gender, age, and language spoken at home. RESULTS: Analyses identified three groups: unhealthy eaters (12.3%), fruit and vegetable avoiders (43.3%), and healthy eaters (44.1%). Most children had regular meal and breakfast patterns. The proportion of boys was higher among unhealthy eaters. Unhealthy eaters also showed irregular meal and breakfast patterns, and had parents with low education level. There was a higher proportion of girls among healthy eaters. Healthy eaters also showed regular meal and breakfast patterns, and had parents with high education level. CONCLUSIONS: Although the number of unhealthy eaters was small, special attention should be still paid to these, mostly male children, as they have poor eating habits and they lack regular eating routine. Skipping breakfast was more common among older children and girls, although girls had healthier eating habits overall. Our results can contribute to public health efforts to improve eating behaviours, especially among children with poor eating habits and those skipping healthy food items.

Picky eating - A risk factor for underweight in Finnish preadolescents.

BACKGROUND: Picky eating (PE) is the most common cause of early-life feeding problems. However, the consequences of PE on food intake and weight development in general populations have not been established. OBJECTIVES: This study aims to investigate the associations of PE and food neophobia (FN) with weight status in 5700 Finnish preadolescents. In addition, we described food consumption by PE/FN status. MATERIAL AND METHODS: We utilised the Finnish Health in Teens (Fin-HIT) cohort of 9-12-year-old preadolescents, who were categorised as having PE and FN based on answers from parental questionnaires. Weight was categorised as underweight, normal weight, and overweight/obesity based on body mass index (BMI) according to IOTF age- and sex-specific cut-offs. Eating patterns were obtained with a 16-item food frequency questionnaire. Multinomial logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: The overall prevalence of PE and FN were 34% and 14%, respectively. PE was inversely associated with overweight/obesity (OR = 0.7; 95% CI 0.6-0.8) and led to a higher risk of underweight (OR = 2.0; 95% CI 1.7-2.4), while this was not observed with FN. Compared with preadolescents without PE/FN, those with PE/FN reported consuming unhealthy foods such as pizza, hamburgers/hot dogs, and salty snacks more frequently (p < 0.0038). By the same token, these preadolescents reported consuming healthy foods such as cooked vegetables, fresh vegetables/salad, fruit/berries, milk/soured milk, and dark bread less frequently. CONCLUSIONS: Among Finnish preadolescents, only PE was associated with a higher risk for underweight and inversely with overweight/obesity. PE and FN were accompanied with unhealthy eating patterns. Management of PE in children may be explored as a potential strategy for improving healthy eating and avoiding underweight in preadolescents.

A novel MYT1L mutation in a patient with severe early-onset obesity and intellectual disability.

The genetic background of severe early-onset obesity is still incompletely understood. Deletions at 2p25.3 associate with early-onset obesity and variable intellectual disability. Myelin-transcriptor-factor-1-like (MYT1L) gene in this locus has been proposed a candidate gene for obesity. We report on a 13-year-old boy presenting with overweight already at 1 year of age (body mass index [BMI] Z-score +2.3) and obesity at 2 years of age (BMI Z-score +3.8). The patient had hyperphagia and delayed neurological, cognitive and motor development. He also had speech delay, strabismus, hyperactivity and intellectual disability. Brain MRI was normal. The parents and sister had normal BMI. Whole-genome sequencing identified in the index patient a novel de novo frameshift deletion that introduces a premature termination of translation NM_015025.2(MYT1L): c.2215_2224delACGCGCTGCC, p.(Thr739Alafs*7) in MYT1L. The frameshift variant was confirmed by Sanger sequencing. Our finding supports the association of MYT1L mutations with early-onset syndromic obesity. The identification of novel monogenic forms of childhood-onset obesity will provide insights to the involved genetic and biologic pathways.

Season, dietary factors, and physical activity modify 25-hydroxyvitamin D concentration during pregnancy.

PURPOSE: The objectives of this cross-sectional study were to define maternal and umbilical cord blood (UCB) 25-hydroxyvitamin D (25(OH)D) to characterize maternal factors modifying 25(OH)D during pregnancy and predict UCB 25(OH)D in two subgroups with Declined [Δ25(OH)D <0 nmol/l] and Increased [Δ25(OH)D >0 nmol/l] 25(OH)D concentration. METHODS: A complete dataset was available from 584 women. 25(OH)D was determined at gestational weeks 6-13 and in UCB. Baseline characteristics were collected retrospectively using questionnaires. Δ25(OH)D was calculated as UCB 25(OH)D-early pregnancy 25(OH)D. Dietary patterns were generated with principal component analysis. Multivariate regression models were applied. RESULTS: Vitamin D deficiency was scarce, since only 1% had 25(OH)D concentration <50 nmol/l both in early pregnancy and in UCB. Shared positive predictors of UCB 25(OH)D in the subgroups of Declined and Increased, were early pregnancy 25(OH)D (P < 0.001) and supplemental vitamin D intake (P < 0.04). For the Increased subgroup summer season at delivery (P = 0.001) and "sandwich and dairy" dietary pattern characterized with frequent consumption of vitamin D fortified margarine and milk products (P = 0.009) were positive predictors of UCB 25(OH)D. Physical activity (P = 0.041) and maternal education (P = 0.004) were additional positive predictors in the Declined group CONCLUSIONS: Maternal and newborn vitamin D status was sufficient, thus public health policies in Finland have been successful. The key modifiable maternal determinants for 25(OH)D during pregnancy, and of the newborn, were supplemental vitamin D intake, frequent consumption of vitamin D fortified foods, and physical activity.

Vitamin D was not associated with survival or cerebrospinal fluid cathelicidin levels in children with bacterial meningitis.

AIM: Vitamin D deficiency impairs the immunological system and has been associated with worse outcomes of infectious diseases, but its role in bacterial meningitis remains unknown. We investigated whether serum 25-hydroxyvitamin D concentrations related to disease outcomes and to cerebrospinal fluid (CSF) cathelicidin concentrations in childhood bacterial meningitis. METHODS: All consecutively enrolled patients in a clinical trial on childhood bacterial meningitis in Latin America in 1996-2003 were considered, and 142 children, with a median age of seven months who had a confirmed bacterial aetiology and frozen serum available for further analyses, were included in this study. Serum 25-hydroxyvitamin D concentrations were determined with a chemiluminescence immunoassay analyser, while CSF cathelicidin was measured by enzyme-linked immunosorbent assay. RESULTS: The median serum 25-hydroxyvitamin D concentration was 96 (range 19-251) nmol/L. No relationship was found with patient survival, but children with any neurological sequelae had lower serum 25-hydroxyvitamin D levels than children without sequelae. Serum 25-hydroxyvitamin D was unrelated to cathelicidin concentrations in CSF. CONCLUSION: Although serum 25-hydroxyvitamin D in children with bacterial meningitis was not associated with survival or CSF cathelicidin concentrations, its relationship with more detailed disease outcomes warrants further study.

25-hydroxyvitamin D correlates with inflammatory markers in cord blood of healthy newborns.

BACKGROUND: Vitamin D is a potent immunomodulator and may play a role in the development of the fetal innate immune functions. The aim of our study was to evaluate inflammatory markers in cord blood of healthy newborns in relation to vitamin D status at birth. METHODS: We studied the concentrations of inflammatory markers, matrix metalloproteinase 8 (MMP-8) and high sensitivity CRP (hs-CRP), and 25-hydroxyvitamin D (25(OH)D) in cord blood of 939 healthy term infants born to mothers of Caucasian origin. We evaluated perinatal factors that affect the concentrations of MMP-8 and hs-CRP, and further explored associations between cord blood 25(OH)D and these inflammatory biomarkers. RESULTS: Majority (99%) of the cohort was vitamin D sufficient (>50 nmol/l or 20 ng/ml). We observed a positive correlation between cord blood 25(OH)D and MMP-8 concentrations, and between 25(OH)D and hs-CRP concentrations. After adjustment for potential confounders (parity, antenatal antibiotic treatment, gestational age, mode of delivery, and maternal prepregnancy BMI), the association of 25(OH)D with MMP-8 and hs-CRP remained significant. CONCLUSION: Cord blood 25(OH)D correlates with inflammatory markers MMP-8 and hs-CRP. The findings may reflect the diverse immunomodulatory functions of vitamin D in the innate immune response of the newborn.

Maternal vitamin D status, gestational diabetes and infant birth size.

BACKGROUND: Maternal vitamin D status has been associated with both gestational diabetes mellitus (GDM) and fetal growth restriction, however, the evidence is inconsistent. In Finland, maternal vitamin D status has improved considerably due to national health policies. Our objective was to compare maternal 25-hydroxy vitamin D concentrations [25(OH)D] between mothers with and without GDM, and to investigate if an association existed between maternal vitamin D concentration and infant birth size. METHODS: This cross-sectional study included 723 mother-child pairs. Mothers were of Caucasian origin, and infants were born at term with normal birth weight. GDM diagnosis and birth size were obtained from medical records. Maternal 25(OH)D was determined on average at 11 weeks of gestation in pregnancy and in umbilical cord blood (UCB) at birth. RESULTS: GDM was observed in 81 of the 723 women (11%). Of the study population, 97% were vitamin D sufficient [25(OH)D ≥ 50 nmol/L]. There was no difference in pregnancy 25(OH)D concentration between GDM and non-GDM mothers (82 vs 82 nmol/L, P = 0.99). Regression analysis confirmed no association between oral glucose tolerance test results and maternal 25(OH)D (P > 0.53). Regarding the birth size, mothers with optimal pregnancy 25(OH)D (≥ 80 nmol/L) had heavier newborns than those with suboptimal pregnancy 25(OH)D (P = 0.010). However, mothers with optimal UCB 25(OH)D had newborns with smaller head circumference than those with suboptimal 25(OH)D (P = 0.003), which was further confirmed as a linear association (P = 0.024). CONCLUSIONS: Maternal vitamin D concentration was similar in mothers with and without GDM in a mostly vitamin D sufficient population. Associations between maternal vitamin D status and birth size were inconsistent. A sufficient maternal vitamin D status, specified as 25(OH)D above 50 nmol/L, may be a threshold above which the physiological requirements of pregnancy are achieved. TRIAL REGISTRATION: The project protocol is registered in ClinicalTrials.gov in November 8, 2012 ( NCT01723852 ).