Polygenic Risk Scores and the Risk of Childhood Overweight/Obesity in Association With the Consumption of Sweetened Beverages: A Population-Based Cohort Study.

Background: Sugar-sweetened beverage (SSB) and non-nutritive sweetened beverage (NNSB) consumption is associated with obesity and are targets for population-level dietary interventions. In children (<16 years), we evaluate whether SSB or NNSB consumption is associated with subsequent (2 years later) overweight and/or obesity, and the effect of consumption on subsequent overweight/obesity differs by BMI polygenic risk score (BMI-PRS). Methods: The nationally representative Longitudinal-Study-of-Australian-Children had biennial data collection from birth (n = 5107) until age 14/15 years (n = 3127). At age 11/12 years, a comprehensive biomedical assessment, including PRS assessment, was undertaken (n = 1422). Parent- or self-reported beverage consumption (SSBs: soft drinks, energy drinks, and/or juice; NNSBs: diet drinks) was measured as any/none over previous 24 hours. BMI-PRS was derived using published results (high PRS ≥75th percentile). At ages 4/5-14/15 children were classified as having obesity, overweight/obesity, or not having overweight/obesity using BMI z-score (CDC cut points). Results: SSB consumption had limited association with subsequent overweight/obesity. NNSB consumption was associated with ∼8% more children with subsequent overweight/obesity at most ages. In older children with high BMI-PRS, associations between NNSB consumption and subsequent overweight/obesity strengthened with age [at age 14-15 for high BMI-PRS, difference in proportion with overweight/obesity among NNSB consumers vs. nonconsumers = 0.38 (95% confidence interval: 0.22 to 0.55, p ≤ 0.001)]. There was limited association between SSB consumption and BMI-PRS. Conclusion: NNSB consumption was associated with increased risk of overweight/obesity for children with greater genetic risk at older ages (12-15 years). Focused intervention among children with high genetic risk could target NNSB consumption; however, reverse causality (children with genetic risk and/or high BMI consume more NNSBs) cannot be excluded.

Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). METHODS: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. RESULTS: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. CONCLUSIONS: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.

Childhood BMI and Fasting Glucose and Insulin Predict Adult Type 2 Diabetes: The International Childhood Cardiovascular Cohort (i3C) Consortium.

OBJECTIVE: To examine childhood BMI, fasting glucose, and insulin in relation to incident adult type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We used data from the International Childhood Cardiovascular Cohort (i3C) Consortium. Data included childhood (age 3-19 years) measurements obtained during the 1970s-1990s; a health questionnaire, including self-report of adult T2DM (occurrence age, medication use) obtained at mean age 40 years; and a medical diagnosis registry (Finland). RESULTS: The sample included 6,738 participants. Of these, 436 (6.5%) reported onset of T2DM between ages 20 and 59 (mean 40.8) years, and 86% of them reported use of a confirmed antidiabetic medication. BMI and glucose (age and sex standardized) were associated with incident T2DM after adjustment for cohort, country, sex, race, age, and calendar year of measurement. Increasing levels of childhood BMI and glucose were related to an incrementally increased risk of T2DM beginning at age 30 years, beginning at cut points <95th percentile for BMI and <100 mg/dL for glucose. Insulin was positively associated with adult T2DM after adjustment for BMI and glucose and added to T2DM discrimination. CONCLUSIONS: Childhood BMI and glucose are predictors of adult T2DM at levels previously considered to be within the normal range. These easy-to-apply measurements are appealing from a clinical perspective. Fasting insulin has the potential to be an additional predictor.

Associations of Breastfeeding, Maternal Smoking, and Birth Weight With Bone Density and Microarchitecture in Young Adulthood: a 25-Year Birth-Cohort Study.

We have found that early-life exposures are associated with areal bone mineral density (aBMD) at ages 8 and 16 years. This study aimed to assess whether these associations persist into young adulthood when peak bone mass (PBM) is achieved and extend this analysis to microarchitecture. Participants were followed from perinatal period to 25 years old (n = 201). Outcomes were total body, spine, and hip aBMD (by dual-energy X-ray absorptiometry [DXA]), and cortical and trabecular bone measures at the distal radius and tibia (by high-resolution peripheral quantitative computed tomography [HRpQCT]). Early-life exposures including breastfeeding, maternal smoking during pregnancy, and birth weight. Sex, weight, height, vegetables, fruit and calcium intake at age 25 years were regarded as potential confounders in the analysis. There were significant interactions between period of gestation and early-life exposures for bone measures, so all analyses were stratified by period of gestation. Breastfeeding was beneficially associated with hip and total body aBMD, total, cortical and trabecular volumetric BMD (vBMD), cortical thickness, porosity, trabecular number (Tb.N), separation (Tb.Sp), and bone volume fraction (Tb.BV/TV) at radius and/or tibia at age 25 years in participants born prematurely (ß ranged from -0.92 to 0.94), but there were no associations in those born at term. Maternal smoking had no association with any DXA/HRpQCT measures in those born prematurely but was detrimentally associated with inner transitional zone porosity and Tb.N (ß = 0.40 and ß = -0.37, respectively) in those full-term participants. Associations of birth weight with bone measures did not persist after adjustment for weight gain since birth. Breastfeeding was associated with a lower risk of lower limb fractures and maternal smoking had a deleterious association with upper limb fractures. In conclusion, breastfeeding and maternal smoking may have effects on peak bone microarchitecture whereas the association with birth weight is countered by subsequent growth. © 2020 American Society for Bone and Mineral Research.

Associations of retinal microvascular caliber with large arterial function and structure: A population-based study of 11 to 12 year-olds and midlife adults.

OBJECTIVE: We examined associations between retinal microvascular and large arterial phenotypes to explore relationships between the micro- and macro-vasculature in childhood and midlife. METHODS: Participants were 1288 children (11-12 years, 50.9% female) and 1264 adults (mean age 44 years, 87.6% female) in a cross-sectional population-based study. Exposures were retinal arteriolar and venular caliber quantified from retinal images. Outcomes included arterial function (pulse wave velocity; carotid arterial elasticity) and structure (carotid intima-media thickness). Multivariable regression models were performed adjusting for age, sex, and family socioeconomic position. RESULTS: In children, one standard deviation wider arteriolar caliber was associated with slower pulse wave velocity (-0.15 SD, 95% CI -0.21, -0.09) and higher elasticity (0.13 SD, 95% CI 0.06, 0.20); per SD wider venular caliber was associated with faster pulse wave velocity (0.09 SD, 95% CI 0.03, 0.15) and lower elasticity (-0.07 SD, 95% CI -0.13, -0.01). The size of adult associations was approximately double. Wider arteriolar caliber was associated with smaller carotid intima-media thickness (-0.09 SD, 95% CI -0.16, -0.03) in adults but not children. Venular caliber and carotid intima-media thickness showed little evidence of association. CONCLUSIONS: Narrower retinal arterioles and wider venules are associated with large arterial function as early as mid-childhood. Associations strengthen by midlife and also extend to arterial structure, although effect sizes remain small.

Do body mass index and waist-to-height ratio over the preceding decade predict retinal microvasculature in 11-12 year olds and midlife adults?

BACKGROUND/OBJECTIVES: Microvascular changes may contribute to obesity-associated cardiovascular disease. We examined whether body mass index (BMI) and waist-to-height ratio (WHtR) (1) at multiple earlier time points and (2) decade-long trajectories predicted retinal microvascular parameters in mid-childhood/adulthood. METHODS: Participants/design: 1288 11-12 year olds (51% girls) and 1264 parents (87% mothers) in the population-based Child Health CheckPoint (CheckPoint) module within the Longitudinal Study of Australian Children (LSAC). LSAC exposure measures: biennial BMI z-score and WHtR for children at five time points from age 2-3 to 10-11 years and self-reported parent BMI at six time points from child age 0-1 years to 10-11 years. CheckPoint outcome measures: retinal arteriolar and venular caliber. ANALYSES: BMI/WHtR trajectories were identified by group-based trajectory modeling; linear regression models estimated associations between BMI/WHtR at each time point/trajectories and later retinal vascular caliber, adjusted for age, sex, and family socioeconomic status. RESULTS: In time point analyses, higher child BMI/WHtR from age 4 to 5 years was associated with narrower arteriolar caliber at the age of 11-12 years, but not venular caliber. For example, each standard deviation higher in BMI z-score at 4-5 years was associated with narrower arteriolar caliber at 11-12 years (standardized mean difference (SMD): -0.05, 95% confidence interval (CI): -0.10 to 0.01); by 10-11 years, associations had doubled to -0.10 (95% CI: -0.16 to -0.05). In adults, these finding were similar, except the magnitude of BMI and arteriolar associations were similar across all time points (SMD: -0.11 to -0.13). In child and adult BMI trajectory analyses, less favorable trajectories predicted narrower arteriolar (p-trend < 0.05), but not venular (p-trend > 0.1), caliber. Compared with those in the average BMI trajectory, SMDs in arterial caliber for children and adults in the highest trajectory were -0.25 (95% CI: -0.44 to -0.07) and -0.42 (95% CI: -0.73 to -0.10), respectively. Venular caliber showed late associations with child WHtR, but not with BMI in children or adults. CONCLUSIONS: Associations of decade-long high BMI trajectories with narrowed retinal arteriolar caliber emerge in children, and are clearly evident by midlife. Adiposity appears to exert its early adverse life course impacts on the microcirculation more via arteriolar than venular mechanisms.

Cardiovascular health and retinal microvascular geometry in Australian 11-12 year-olds.

Traditional retinal microvascular parameters (smaller arteriolar and greater venular caliber) are associated with cardiovascular risk factors, pre-clinical vascular phenotypes and clinical cardiovascular events in adults. Although novel retinal microvascular geometric parameters showed analogous associations in adults, less is known whether these parameters are associated with cardiovascular health from childhood. In a population-based cross-sectional study in children (n = 1126, mean age 11.4 years, 50.3% girls), we examined associations of cardiovascular risk factors and pre-clinical arterial phenotypes with retinal geometric parameters. Cardiovascular parameters included body mass index (BMI), an inflammatory marker (GlycA), low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, systolic (SBP) and diastolic blood pressure, large artery functional (pulse wave velocity, PWV and carotid arterial elasticity) and structural (carotid intima-media thickness) phenotypes. Retinal geometric parameters (fractal dimension (Df) and tortuosity) were quantified from retinal images. Multivariable regression models were performed and adjusted for potential confounders. Higher values for BMI, SBP and PWV showed weak associations with lower (i.e. worse) arteriolar but not venular Df (standardized mean difference (SMD) ranging from -0.07 to -0.09, 95% CIs -0.15 to -0.01). Higher HDL was associated with greater arteriolar Df (SMD 0.07, 95% CI 0.01 to 0.13). Only higher SBP was associated with higher (i.e. worse) arteriolar but not venular tortuosity (SMD 0.09, 95% CI 0.02 to 0.16). In generally healthy children, some risk factors and pre-clinical arterial phenotypes show small associations with retinal geometric parameters. In childhood, emerging relationships between microvascular parameters and cardiometabolic risk may be better described by retinal vascular caliber than by geometric parameters.

Socioeconomic position over the life course from childhood and smoking status in mid-adulthood: results from a 25-year follow-up study.

BACKGROUND: It remains unclear how life course socioeconomic position (SEP) variations impact later smoking status. We aimed to investigate the associations using a novel methodology - a structured regression framework and to explore the potential underlying mechanisms. METHODS: Data were from an Australian national cohort (n = 1489). SEP was measured in childhood (aged 7-15 years), young- (aged 26-36 years) and mid-adulthood (aged 31-41 years), including highest parental occupation in childhood and self-occupation in young- and mid-adulthood. Smoking status was self-reported in mid-adulthood. Four smoking-related variables in childhood including exposure to parental smoking, smoking experimentation, self-rated importance to be a non-smoker and intention to smoke were tested as potential mediators. A structured life course modelling approach was used to select the best-fit life course model(s). The log multinomial model was used to estimate the smoking risk in mid-adulthood with never smokers as the excluded category. RESULTS: 63.6% of participants were classified as stable non-manual occupation across the life course from childhood. The sensitive period and the accumulation model described the data equally as well as the saturated model. In the sensitive period model, compared to the non-manual group, those who had highest parental occupation of manual had a 21% lower risk of being former smokers and a 32% greater risk of being current smokers in mid-adulthood, and those who were occupied manually in mid-adulthood reported a 55% greater risk of being current smokers in mid-adulthood. In the accumulation model, compared to those who consistently reported non-manual occupations across the life course, those with manual occupations for longer had higher risk of being current smokers in mid-adulthood, with a 43% risk increase per time point in a manual occupation. Exposure to parental smoking and intention to smoke during childhood explained up to 40.2% of the excess risk of being current smokers in mid-adulthood associated with manual occupations in the sensitive period and the accumulation model. CONCLUSIONS: Childhood, young- and mid-adulthood are all important, but SEP in childhood and mid-adulthood may be of more importance in determining mid-adulthood smoking status. Exposure to parental smoking and intention to smoke in childhood seems to moderately mediate the associations.

The International Childhood Cardiovascular Cohort (i3C) consortium outcomes study of childhood cardiovascular risk factors and adult cardiovascular morbidity and mortality: Design and recruitment.

Although it is widely thought that childhood levels of cardiovascular (CV) risk factors are related to adult CV disease, longitudinal data directly linking the two are lacking. This paper describes the design and organization of the International Childhood Cardiovascular Cohort Consortium Outcomes Study (i3C Outcomes), the first longitudinal cohort study designed to locate adults with detailed, repeated, childhood biological, physical, and socioeconomic measurements and a harmonized database. I3C Outcomes uses a Heart Health Survey (HHS) to obtain information on adult CV endpoints, using mail, email, telephone, and clinic visits in the United States (U.S.) and Australia and a national health database in Finland. Microsoft Access, REsearch Data Capture (REDCap) (U.S.), LimeSurvey (Australia), and Medidata™ Rave data systems are used to collect, transfer and organize data. Self-reported CV events are adjudicated via hospital and doctor-released medical records. After the first two study years, participants (N = 10,968) were more likely to be female (56% vs. 48%), non-Hispanic white (90% vs. 80%), and older (10.4 ±â€¯3.8 years vs. 9.4 ±â€¯3.3 years) at their initial childhood study visit than the currently non-recruited cohort members. Over 48% of cohort members seen during both adulthood and childhood have been found and recruited, to date, vs. 5% of those not seen since childhood. Self-reported prevalences were 0.7% Type 1 Diabetes, 7.5% Type 2 Diabetes, 33% hypertension, and 12.8% CV event. 32% of CV events were judged to be true. I3C Outcomes is uniquely able to establish evidence-based guidelines for child health care and to clarify relations to adult CV disease.

DHA mediates the protective effect of fish consumption on new episodes of depression among women.

In a longitudinal cohort study of young Australian adults, we reported that for women higher baseline levels of fish consumption were associated with reduced incidence of new depressive episodes during the 5-year follow-up. Fish are high in both n-3 fatty acids and tyrosine. In this study, we seek to determine whether n-3 fatty acids or tyrosine explain the observed association. During 2004-2006, a FFQ (nine fish items) was used to estimate weekly fish consumption among 546 women aged 26-36 years. A fasting blood sample was taken and high-throughput NMR spectroscopy was used to measure 233 metabolites, including serum n-3 fatty acids and tyrosine. During 2009-2011, new episodes of depression since baseline were identified using the lifetime version of the Composite International Diagnostic Interview. Relative risks were calculated using log-binomial regression and indirect effects estimated using the STATA binary_mediation command. Potential mediators were added to separate models, and mediation was quantified as the proportion of the total effect due to the mediator. The n-3 DHA mediated 25·3 % of the association between fish consumption and depression when fish consumption was analysed as a continuous variable and 16·6 % when dichotomised (reference group: <2 serves/week). Tyrosine did not mediate the association (<0·1 %). Components in fish other than n-3 fatty acids and tyrosine might be beneficial for women's mental health.

Associations between alcohol consumption and cardio-metabolic risk factors in young adults.

Introduction The benefits of alcohol consumption for cardiovascular and metabolic health may have been overstated due to inappropriate comparisons with abstainers and inadequate control for confounding factors including physical activity and mental health. We examined alcohol consumption and cardio-metabolic health in a cohort of young Australian adults overcoming these limitations. Methods Cross-sectional data of a cohort of 2200 participants (age range 25-36 years) from the 2004-06 Childhood Determinants of Adult Health were used. Alcohol consumption was assessed from questionnaire and cardio-metabolic risk factors were measured in clinics. Linear and log binomial regression were used to examine total alcohol consumption (categories: none 0 g/day; light >0-10 g/day [reference]; moderate >10-20 g/day; heavy >20-30 g/day; very heavy >30 g/day) against dichotomous metabolic syndrome and its components: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure and glucose. Covariates included socio-demographics, smoking, diet, physical activity, fitness, depression and anxiety. Results Of the 2220 participants (48% males, mean (standard deviation) age 29.5 (2.5) years), most were classified in the 'light drinking' group (54.2%), less were in the 'non-drinking' (13.2%), 'heavy' (5.2%) or 'very heavy' (5.5%) drinking groups. Only moderate drinking was associated with a significantly lower prevalence of metabolic syndrome (prevalence ratio = 0.64, p < 0.05) compared with light drinking. Higher levels of alcohol consumption were associated with higher high-density lipoprotein cholesterol (ß = 0.05, ptrend < 0.001). Very heavy compared to light drinkers had higher systolic (ß = 3.01 mm Hg, p < 0.01) and diastolic (ß = 2.07 mm Hg, p < 0.05) blood pressure. Conclusion Moderate alcohol consumption was associated with a lower prevalence of MetS, and more favourable levels of lipids but not glucose or blood pressure even when compared to light consumption and with account for a range of confounding factors.

Partnering and parenting transitions associate with changing smoking status: a cohort study in young Australians.

OBJECTIVES: To examine the effects of partnering and parenting transitions on smoking continuity in young adults. METHODS: A prospective cohort study was conducted involving 1084 young smokers and former smokers who completed questionnaires at baseline (2004-2006, aged 26-36 years) and 5 years later. RESULTS: 233/570 (40.9%) smokers quit and 58/514 (11.3%) former smokers resumed smoking during follow-up. For partnering transitions, compared with remaining not partnered, the likelihood of quitting was higher among men who became (RR 2.84 95% CI 1.62, 4.98) or stayed (RR 2.12, 95% CI 1.18, 3.80) partnered and women who became partnered (RR 1.50, 95% CI 1.03, 2.18). People who became (RR 0.14, 95% CI 0.03, 0.58) or stayed (RR 0.51, 95% CI 0.27, 0.95) partnered had a lower risk of resuming smoking than their continuously not partnered peers. For parenting transitions, having a first child born increased women's probability of quitting smoking relative to remaining childless (RR 1.74, 95% CI 1.30, 2.33), while having additional children did not. CONCLUSIONS: The benefits of partnering were greater for men than women and transition into parenthood was of greater benefit to women.

Accumulated exposure to rural areas of residence over the life course is associated with overweight and obesity in adulthood: a 25-year prospective cohort study.

PURPOSE: This prospective cohort study investigated whether body mass index (BMI) and weight status in mid-adulthood were predicted by trajectories of urban-rural residence from childhood to adulthood. METHODS: Participants aged 7-15 years in 1985 (n = 8498) were followed up in 2004-2006 (n = 3999, aged 26-36 years) and 2009-2011 (n = 3049, aged 31-41 years). Area of residence (AOR) was classified as urban or rural at each time point. BMI and/or weight status was calculated from self-reported weight and height (2009-2011). We tested which of three life-course models ("accumulation," "sensitive period," "mobility") best explained the AOR-BMI and/or weight status association using a novel life-course modeling framework. RESULTS: Accumulation and sensitive period models best described the effect of AOR on mid-adulthood BMI and weight status. Those with greater accumulated exposure to rural areas had a higher BMI (ß = 0.29 kg/m2 per time in a rural area, P = .005) and were more likely obese (relative risk = 1.13 per time in a rural area, P = .002). Living in rural areas at ages 26-30 years was also associated with a higher BMI and obesity in mid-adulthood. CONCLUSIONS: Greater cumulative exposure to rurality and exposure during the "sensitive period" of young adulthood is associated with obesity in middle-aged adults. This study highlights the important contribution of context to the development of obesity over the life course.

Worsening Dietary and Physical Activity Behaviors Do Not Readily Explain Why Smokers Gain Weight After Cessation: A Cohort Study in Young Adults.

INTRODUCTION: The relationship between smoking cessation and weight gain is well established but the underlying mechanisms remain poorly understood. We aimed to determine whether postcessation weight gain was mediated by changing health behaviors. METHODS: A total of 281 smokers self-reported their demographic, smoking, and lifestyle characteristics in 2004-2006 (aged 26-36) and 2009-2011 (aged 31-41). Behaviors considered as potential mediators of weight gain were changes in consumption of breakfast, discretionary foods (servings/d), fruit and vegetables (servings/d), alcohol (g/d), takeaway food (times/wk), Diet Guideline Index score, leisure time physical activity (PA, min/wk), total PA (min/wk), time spent sitting (min/d), and TV viewing (h/d). RESULTS: In total, 124 smokers quit smoking during 5 years follow-up. After adjustment for age, sex, baseline body mass index, education, and follow-up length, smoking cessation was associated with average excess weight gain of 2.09kg (95% CI = 0.35-3.83). Compared with continuing smokers, quitters reported a higher Diet Guideline Index score and less consumption of alcohol at baseline and follow-up (all p < .05). In addition, there was a tendency towards healthier dietary and PA behaviors over 5 years among quitters than continuing smokers except for time spent sitting, although these differences did not reach statistical significance. Adjustment for changes in these behaviors made little difference to the magnitude of postcessation weight gain (ß: 2.32kg, 95% CI = 0.54-4.10). CONCLUSIONS: The weight gain associated with smoking cessation was not explained by worsening dietary and PA behaviors. Future research is needed to elucidate the complex mechanisms and particularly ways it may be prevented. IMPLICATIONS: Fear of weight gain often discourages smokers from trying to quit but guidance on ways to most effectively avoid weight gain is lacking. It is important to identify what causes postcessation weight gain and the ways it may be prevented. The current study explored the effects of several changing dietary and PA behaviors on the relationship between smoking cessation and weight gain in 281 young Australian smokers. We found that quitters tended to adopt healthier dietary and PA behaviors than continuing smokers, so these behaviors did not readily explain the postcessation weight gain. Further investigations of other potential mechanisms are needed.

Determinants of Neonatal Vitamin D Levels as Measured on Neonatal Dried Blood Spot Samples.

BACKGROUND: Vitamin D deficiency is linked to adverse childhood health outcomes, yet data on the distribution and quantifiable determinants of neonatal 25-hydroxyvitamin D3 (25OHD) concentration, a vitamin D biomarker, are limited. OBJECTIVE: Our aim was to identify determinants of neonatal 25OHD concentration, measured using neonatal dried blood spots (DBS). METHODS: A total of 259 ethnically diverse children aged 0-16 years born in Victoria, Australia, were recruited. Data included maternal sun exposure, skin type, 25OHD concentration on stored neonatal DBS, and genotypes at the target genes. Associations were investigated using multiple linear regression models. RESULTS: The median 25OHD concentration was 29.2 nmol/l (IQR 18.0-47.4). Measured 25OHD was <50 nmol/l in almost half of the neonatal sample. Ambient ultraviolet radiation (UVR) 6 weeks before birth was the strongest predictor of neonatal 25OHD, accounting for 23% of its variation. A further 10% was explained by infant genetic variants at GC (rs2282679), the gene encoding the vitamin D binding protein, and DHCR7 (rs12785878), a gene required for synthesis of 7-dehydrocholesterol, a precursor to 25OHD. DBS age explained 7%, and patterns of maternal sun exposure and clothing choices accounted for 4%. A child's skin colour was strongly associated with GC gene variants and not independent of these variants in predicting 25OHD. The final model explained 43% of the total variance in neonatal 25OHD concentration. CONCLUSION: Maternal lifestyle factors and infant genetic variants predict neonatal 25OHD levels; the importance of maternal UVR exposure in late pregnancy is highlighted.

Smoking status and health-related quality of life: a longitudinal study in young adults.

PURPOSE: The possibility that tobacco use affects health-related quality of life (HRQoL) has attracted interest. However, a lack of prospective evidence weakens the case for a causal relationship. The aim was to examine the longitudinal relationship between change in smoking status and change in HRQoL in young adults. METHODS: We conducted a population-based cohort study with data collected in 2004-2006 (aged 26-36) and 2009-2011 (aged 31-41). Exposure was change in self-reported smoking status during follow-up. Outcomes were changes in physical and mental HRQoL measured by SF-12. RESULTS: For physical HRQoL (n = 2080), quitters had a 2.12 (95 % confidence interval (CI) 0.73, 3.51) point improvement than continuing smokers, whereas former smokers who resumed smoking had a 2.08 (95 % CI 0.21, 3.94) point reduction than those who maintained cessation. Resumed smokers were 39 % (95 % CI 10, 75 %) more likely to have a clinically significant (>5 point) reduction of physical HRQoL than former smokers who maintained cessation. In contrast, quitters were 43 % (95 % CI 3, 98 %) more likely to have a clinically significant (>5 point) improvement in physical HRQoL than continuing smokers. Change in smoking status was not significantly associated with change in mental HRQoL (n = 1788). CONCLUSIONS: Smoking by young adults was cross-sectionally associated with lower physical HRQoL and longitudinally associated with reductions in physical HRQoL. The expectation of short- to medium-term gains in physical HRQoL as well as long-term health benefits may help motivate young adult smokers to quit.

Polymorphisms affecting vitamin D-binding protein modify the relationship between serum vitamin D (25[OH]D3) and food allergy.

BACKGROUND: There is evolving evidence that vitamin D insufficiency may contribute to food allergy, but findings vary between populations. Lower vitamin D-binding protein (DBP) levels increase the biological availability of serum vitamin D. Genetic polymorphisms explain almost 80% of the variation in binding protein levels. OBJECTIVE: We sought to investigate whether polymorphisms that lower the DBP could compensate for adverse effects of low serum vitamin D on food allergy risk. METHODS: From a population-based cohort study (n = 5276) we investigated the association between serum 25-hydroxyvitamin D3 (25[OH]D3) levels and food allergy at age 1 year (338 challenge-proven food-allergic and 269 control participants) and age 2 years (55 participants with persistent and 50 participants with resolved food allergy). 25(OH)D3 levels were measured using liquid chromatography-tandem mass spectrometry and adjusted for season of blood draw. Analyses were stratified by genotype at rs7041 as a proxy marker of DBP levels (low, the GT/TT genotype; high, the GG genotype). RESULTS: Low serum 25(OH)D3 level (≤50 nM/L) at age 1 years was associated with food allergy, particularly among infants with the GG genotype (odds ratio [OR], 6.0; 95% CI, 0.9-38.9) but not in those with GT/TT genotypes (OR, 0.7; 95% CI, 0.2-2.0; P interaction = .014). Maternal antenatal vitamin D supplementation was associated with less food allergy, particularly in infants with the GT/TT genotype (OR, 0.10; 95% CI, 0.03-0.41). Persistent vitamin D insufficiency increased the likelihood of persistent food allergy (OR, 12.6; 95% CI, 1.5-106.6), particularly in those with the GG genotype. CONCLUSIONS: Polymorphisms associated with lower DBP level attenuated the association between low serum 25(OH)D3 level and food allergy, consistent with greater vitamin D bioavailability in those with a lower DBP level. This increases the biological plausibility of a role for vitamin D in the development of food allergy.

Cohort Profile: The Barwon Infant Study.

The modern environment is associated with an increasing burden of non-communicable diseases (NCDs). Mounting evidence implicates environmental exposures, experienced early in life (including in utero), in the aetiology of many NCDs, though the cellular/molecular mechanism(s) underlying this elevated risk across the life course remain unclear. Epigenetic variation has emerged as a candidate mediator of such effects. The Barwon Infant Study (BIS) is a population-derived birth cohort study (n = 1074 infants) with antenatal recruitment, conducted in the south-east of Australia (Victoria). BIS has been designed to facilitate a detailed mechanistic investigation of development within an epidemiological framework. The broad objectives are to investigate the role of specific environmental factors, gut microbiota and epigenetic variation in early-life development, and subsequent immune, allergic, cardiovascular, respiratory and neurodevelopmental outcomes. Participants have been reviewed at birth and at 1, 6, 9 and 12 months, with 2- and 4-year reviews under way. Biological samples and measures include: maternal blood, faeces and urine during pregnancy; infant urine, faeces and blood at regular intervals during the first 4 years; lung function at 1 month and 4 years; cardiovascular assessment at 1 month and 4 years; skin-prick allergy testing and food challenge at 1 year; and neurodevelopmental assessment at 9 months, 2 and 4 years. Data access enquiries can be made at [www.barwoninfantstudy.org.au] or via [peter.vuillermin@deakin.edu.au].