Associations of childhood adiposity with menstrual irregularity and polycystic ovary syndrome in adulthood: the Childhood Determinants of Adult Health Study and the Bogalusa Heart Study.

STUDY QUESTION: Is high adiposity in childhood associated with menstrual irregularity and polycystic ovary syndrome (PCOS) in later life? SUMMARY ANSWER: Overall, greater childhood BMI was associated with menstrual irregularity, and greater childhood BMI and waist/height ratio (WHtR) in white but not black participants were associated with PCOS in adulthood. WHAT IS KNOWN ALREADY: Increased childhood BMI has been associated with irregular menstrual cycles and PCOS symptoms in adulthood in two longitudinal population-based studies, but no study has reported on associations with childhood abdominal obesity. Few studies have investigated whether there are racial differences in the associations of adiposity with PCOS though there has been some suggestion that associations with high BMI may be stronger in white girls than in black girls. STUDY DESIGN, SIZE, DURATION: The study included 1516 participants (aged 26-41 years) from the Australian Childhood Determinants of Adult Health study (CDAH) and 1247 participants (aged 26-57 years) from the biracial USA Babies substudy of the Bogalusa Heart Study (BBS) who were aged 7-15 years at baseline. At follow-up, questions were asked about menstruation (current for CDAH or before age 40 years for BBS), ever having had a diagnosis of PCOS and symptoms of PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: In CDAH, a single childhood visit was conducted in 1985. In BBS, multiple childhood visits occurred from 1973 to 2000 and race was reported (59% white; 41% black). In childhood, overweight and obesity were defined by international age-sex-specific standards for BMI and WHtR was considered as an indicator of abdominal obesity. Multilevel mixed-effects Poisson regression estimated relative risks (RRs) adjusting for childhood age, highest parental and own education and age at menarche. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of childhood obesity was 1.1% in CDAH and 7.5% in BBS. At follow-up, menstrual irregularity was reported by 16.7% of CDAH and 24.5% of BBS participants. The prevalence of PCOS was 7.4% in CDAH and 8.0% in BBS participants. In CDAH, childhood obesity was associated with menstrual irregularity (RR = 2.84, 95% CI: 1.63-4.96) and PCOS (RR = 4.05, 95% CI: 1.10-14.83) in adulthood. With each 0.01 unit increase in childhood WHtR there was a 6% (95% CI: 1-11%) greater likelihood of PCOS. Overall, in BBS, childhood obesity was associated with increased risk of menstrual irregularity (RR = 1.44, 95% CI: 1.08-1.92) in adulthood. Significant interaction effects between race and childhood adiposity were detected in associations with PCOS. In BBS white participants, childhood obesity was associated with PCOS (RR = 2.93, 95% CI: 1.65-5.22) and a 0.01 unit increase in childhood WHtR was associated with an 11% (95% CI: 5-17%) greater likelihood of PCOS in adulthood. In BBS black participants, no statistically significant associations of childhood adiposity measures with PCOS were observed. LIMITATIONS, REASONS FOR CAUTION: The classification of menstrual irregularity and PCOS was based on self-report by questionnaire, which may have led to misclassification of these outcomes. However, despite the limitations of the study, the prevalence of menstrual irregularity and PCOS in the two cohorts was consistent with the literature. While the study samples at baseline were population-based, loss to follow-up means the generalizability of the findings is uncertain. WIDER IMPLICATIONS OF THE FINDINGS: Greater childhood adiposity indicates a higher risk of menstrual irregularity and PCOS in adulthood. Whether this is causal or an early indicator of underlying hormonal or metabolic disorders needs clarification. The stronger associations of adiposity with PCOS in white than black participants suggest that there are racial differences in childhood adiposity predisposing to the development of PCOS and other environmental or genetic factors are also important. STUDY FUNDING/COMPETING INTEREST(S): The CDAH study was supported by grants from the Australian National Health and Medical Research Council (grants 211316, 544923 and 1128373). The Bogalusa Heart Study is supported by US National Institutes of Health grants R01HD069587, AG16592, HL121230, HD032194 and P50HL015103. No competing interests existed.

An eating pattern characterised by skipped or delayed breakfast is associated with mood disorders among an Australian adult cohort.

BACKGROUND: Meal timing may influence food choices, neurobiology and psychological states. Our exploratory study examined if time-of-day eating patterns were associated with mood disorders among adults. METHODS: During 2004-2006 (age 26-36 years) and 2009-2011 (follow-up, age 31-41 years), N = 1304 participants reported 24-h food and beverage intake. Time-of-day eating patterns were derived by principal components analysis. At follow-up, the Composite International Diagnostic Interview measured lifetime mood disorder. Log binomial and adjacent categories log-link regression were used to examine bidirectional associations between eating patterns and mood disorder. Covariates included sex, age, marital status, social support, education, work schedule, body mass index and smoking. RESULTS: Three patterns were derived at each time-point: Grazing (intake spread across the day), Traditional (highest intakes reflected breakfast, lunch and dinner), and Late (skipped/delayed breakfast with higher evening intakes). Compared to those in the lowest third of the respective pattern at baseline and follow-up, during the 5-year follow-up, those in the highest third of the Late pattern at both time-points had a higher prevalence of mood disorder [prevalence ratio (PR) = 2.04; 95% confidence interval (CI) 1.20-3.48], and those in the highest third of the Traditional pattern at both time-points had a lower prevalence of first onset mood disorder (PR = 0.31; 95% CI 0.11-0.87). Participants who experienced a mood disorder during follow-up had a 1.07 higher relative risk of being in a higher Late pattern score category at follow-up than those without mood disorder (95% CI 1.00-1.14). CONCLUSIONS: Non-traditional eating patterns, particularly skipped or delayed breakfast, may be associated with mood disorders.

Determinants of a dietary pattern linked with greater metabolic risk and its tracking during adolescence.

BACKGROUND: Although growing evidence suggests that dietary patterns associated with noncommunicable diseases in adulthood may develop early in life, when these are established, as well as their determinants, remains unclear. METHODS: We examined determinants and tracking of a dietary pattern (DP) associated with metabolic risk and its key food groups among 860 adolescents in the Western Australian Pregnancy (Raine) Cohort study. Food intake was reported using a food frequency questionnaire (FFQ) at 14 and 17 years. Z-scores for an 'energy-dense, high-fat, low-fibre' DP were estimated by applying reduced rank regression at both ages. Tracking was based on the predictive value (PV) of remaining in the DPZ-score or food intake quartile at 14 and 17 years. Early-life exposures included: maternal age; maternal pre-pregnancy body mass index; parent smoking status during pregnancy; and parent socio-economic position (SEP) at 14 and 17 years. Associations between the DPZ-scores, early-life factors and SEP were analysed using regression analysis. RESULTS: Dietary tracking was strongest among boys with high DPZ-scores, high intakes of processed meat, low-fibre bread, crisps and savoury snacks (PV > 1) and the lowest intakes of vegetables, fruit and legumes. Lower maternal education (ß = 0.09, P = 0.002 at 14 years; ß = 0.14, P < 0.001 at 17 years) and lower maternal age at birth (ß = 0.09, P = 0.003 at 14 years; ß = 0.11, P = 0.004 at 17 years) were positively associated with higher DPZ-scores. CONCLUSIONS: An energy-dense, high-fat, low-fibre dietary pattern tracks more strongly among adolescent boys who have high scores for this pattern at 14 years of age. These findings highlight target foods and population subgroups for early interventions aiming to improve dietary behaviours.

Protective benefit of predominant breastfeeding against otitis media may be limited to early childhood: results from a prospective birth cohort study.

OBJECTIVES: To examine the long-term effects of predominant breastfeeding on incidence of otitis media. DESIGN: Prospective birth cohort study. SETTING: The West Australian Pregnancy Cohort (Raine) Study recruited 2900 mothers through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia, between 1989 and 1992. PARTICIPANTS: In total, 2237 children participated in a 6-year cohort follow-up, and a subset of 1344 were given ear and hearing assessments. MAIN OUTCOME MEASURES: OM diagnosis at 6 years of age (diagnosed by low-compliance tympanograms, 0-0.1 mmho). This was compared to OM diagnosed at the 3-year cohort follow-up using parent-report measures. Main exposure measures were duration of predominant breastfeeding (defined as the age other milk was introduced) and duration of partial (any) breastfeeding (defined as the age breastfeeding was stopped). RESULTS: There was a significant, independent association between predominant breastfeeding (OR = 1.33 [1.04, 1.69]; P = 0.02) and OM, and breastfeeding duration (OR = 1.35 [1.08, 1.68]; P = 0.01) with OM at 3 years of age. However, at 6 years of age, this relationship was no longer statistically significant (predominant breastfeeding OR = 0.78 [0.48, 1.06]; P = 0.09; duration of breastfeeding, OR = 1.34 [0.81, 2.23]; P = 0.25). CONCLUSIONS: Our findings are in line with a number of epidemiological studies which show a positive association between breastfeeding and OM in early childhood. However, the long-term follow-up of these children revealed that by 6 years of age, there was no significant influence of breastfeeding on presence of OM. These results suggest that the protective effect of predominant breastfeeding for at least 6 months does not extend to school-age children, where other social and environmental factors may be stronger predictors of OM.

Associations of maternal prepregnancy body mass index and gestational weight gain with cardio-metabolic risk factors in adolescent offspring: a prospective cohort study.

OBJECTIVE: To assess the associations of maternal prepregnancy body mass index (BMI) and rates of early-pregnancy, mid-pregnancy and total gestational weight gain with adolescent body fat distribution and cardio-metabolic outcomes. DESIGN: Population-based prospective cohort study. SETTING: Western Australia. POPULATION: Thousand three hundred and ninety-two mothers and their children. METHODS: Maternal prepregnancy weight was assessed by questionnaire. Maternal weights at a mean of 16.5 ± 2.2 SD and 34.1 ± 1.5 SD weeks of gestation were obtained from medical records. Offspring adiposity and cardio-metabolic outcomes were assessed at a median age 17.0 years [95% confidence interval (CI) range: 16.7, 17.7]. MAIN OUTCOME MEASURES: Adolescent BMI, waist circumference (WC), waist-to-hip ratio (WHR), blood pressure, total and HDL-cholesterol, triglycerides, insulin, glucose and HOMA-IR. RESULTS: Higher prepregnancy BMI was associated with higher adolescent BMI, WC, WHR, systolic blood pressure, insulin, glucose and HOMA-IR levels (P-values <0.05). Adjustment for adolescent current BMI attenuated the associations of prepregnancy BMI with adolescent cardio-metabolic outcomes. Higher weight gain in early-pregnancy, but not mid-pregnancy, was associated with higher adolescent BMI, WC and WHR (P-values <0.05), but not with other cardio-metabolic risk factors. Total gestational weight gain was associated with adolescent BMI and WC (P-values <0.05). Higher prepregnancy BMI and early-pregnancy weight gain were associated with increased risks of the high-metabolic risk cluster in adolescents (OR 1.57, 95% CI 1.33, 1.85 and OR 1.23, 95% CI 1.03, 1.47 per SD increase in prepregnancy BMI and early-pregnancy weight gain, respectively). CONCLUSIONS: Higher maternal prepregnancy BMI and early-pregnancy weight gain rate are associated with an adverse adolescent cardio-metabolic profile. These associations are largely mediated by adolescent BMI.

Identification of a dietary pattern associated with greater cardiometabolic risk in adolescence.

BACKGROUND AND AIMS: Energy dense, high fat, low fibre diets may contribute to obesity in young people, however their relationships with other cardiometabolic risk factors are unclear. We examined associations between an 'energy-dense, high-fat and low-fibre' dietary pattern (DP) and cardiometabolic risk factors, and the tracking of this DP in adolescence. METHODS AND RESULTS: Data was sourced from participants in the Western Australian Pregnancy (Raine) Cohort Study. At 14 and 17 y, dietary intake, anthropometric and biochemical data were measured and z-scores for an 'energy dense, high fat and low fibre' DP were estimated using reduced rank regression (RRR). Associations between DP z-scores and cardiometabolic risk factors were examined using regression models. Tracking of DP z-scores was assessed using Pearson's correlation coefficient. A 1 SD unit increase in DP z-score between 14 and 17 y was associated with a 20% greater odds of high metabolic risk (95% CI: 1.01, 1.41) and a 0.04 mmol/L higher fasting glucose in boys (95% CI: 0.01, 0.08); a 28% greater odds of a high-waist circumference (95% CI: 1.00, 1.63) in girls. An increase of 3% and 4% was observed for insulin and HOMA (95% CI: 1%, 7%), respectively, in boys and girls, for every 1 SD increase in DP z-score and independently of BMI. The DP showed moderate tracking between 14 and 17 y of age (r = 0.51 for boys, r = 0.45 for girls). CONCLUSION: An 'energy dense, high fat, low fibre' DP is positively associated with cardiometabolic risk factors and tends to persist throughout adolescence.

Dairy product consumption, dietary nutrient and energy density and associations with obesity in Australian adolescents.

BACKGROUND: Dairy intake is likely to influence dietary energy density (ED) and nutrient density (ND), which are factors representing aspects of dietary quality. Although evidence suggests dairy intake is unlikely to contribute to obesity, intake tends to decrease over adolescence, potentially as a result of concerns around weight gain. We examined associations between dairy intake, ED and ND, and investigated relationships with obesity in adolescents. METHODS: The present study comprised a cross-sectional study of 1613 14-year-olds in the Western Australian Pregnancy Cohort (Raine) Study. Adolescents completed a 212-item food frequency questionnaire. Nutrient Rich Food index 9.3 (NRF9.3) was used to estimate ND. Age-specific body mass index (BMI) and waist-height cut-offs were used to categorise obesity risk. RESULTS: Mean (SD) dairy intake was: 2.62 (1.51) servings daily; ED was 4.53 (0.83) (food and beverage) and 6.28 (1.33) (food only); ND was 373 (109). Dairy intake was inversely associated with ED and positively associated with ND. The odds of being overweight (as assessed by BMI) increased by 1.24 (95% confidence interval = 1.09-1.42) with each 100-point increase in ND, after adjustment for potential confounders and energy intake. ED measures and dairy intake were inversely associated with obesity after adjustment for confounders; associations became nonsignificant after energy adjustment. CONCLUSIONS: The NRF9.3 was originally designed to assess foods, not diets. Further research in other cohorts to determine whether similar findings exist, or investigations into alternate measures of dietary ND, may prove useful. Our findings may be the result of factors such as an excess consumption of refined but fortified foods. Although higher dairy intakes were associated with higher ND, intakes were not associated with higher obesity risk.

A pro-inflammatory diet is associated with long-term depression and anxiety levels but not fatigue in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis is characterised by acute and chronic inflammation in the CNS. Diet may influence inflammation, and therefore MS outcomes. OBJECTIVE: To determine whether the Dietary Inflammatory Index (DII®)) is associated with depression, anxiety, and fatigue in a prospective cohort of people with MS. METHODS: People with a first clinical diagnosis of demyelination were followed over 10 years (n=223). DII and energy-adjusted DII (E-DIITM) scores were calculated from the dietary intake in the preceding 12 months measured by food frequency questionnaire. Depression and anxiety were assessed by the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and fatigue by the Fatigue Severity Scale. RESULTS: A higher E-DII score was associated with higher levels of depression and anxiety five years later (e.g., highest vs lowest E-DII quartile, HADS-D score: ß=2.23, 95%CI=0.98,3.48, p<0.001; HADS-A score: ß=1.90, 95%CI=0.59,3.21, p<0.001). A cumulative E-DII score was associated with depression (p<0.01) and anxiety (p=0.05) at the 10-year review. No associations were seen for fatigue. CONCLUSION: Our findings suggest that, in people with MS, a more pro-inflammatory diet may long-term adverse impact on depression and anxiety, but not fatigue.

Dietary intake in population-based adolescents: support for a relationship between eating disorder symptoms, low fatty acid intake and depressive symptoms.

BACKGROUND: Relatively little is known about the dietary intake and nutritional status of community-based individuals with eating disorders. This research aimed to: (i) describe the dietary intake of population-based adolescents with an eating disorder and (ii) examine associations between eating disorder symptoms, fatty acid intake and depressive symptoms in adolescents with and without an eating disorder. METHODS: Data were drawn from the Western Australian Pregnancy Cohort (Raine) Study, a population-based cohort study that has followed participants from birth to young adulthood. This research utilised self-report data from the 17-year Raine Study assessment. Participants comprised 429 female adolescents who completed comprehensive questionnaire measures on dietary intake, eating disorder symptoms and depressive symptoms. RESULTS: Adolescents with an eating disorder (n = 66) reported a significantly lower intake of total fat, saturated fat, omega-6 fatty acid, starch, vitamin A and vitamin E compared to adolescents without an eating disorder (n = 363). Adolescents with an eating disorder and pronounced depressive symptoms (n = 23) also reported a significantly lower intake of polyunsaturated fat and omega-3 and omega-6 fatty acid than adolescents with an eating disorder but no marked depression (n = 43). In the eating disorder sample but not the control sample, omega-3 and omega-6 fatty acid correlated significantly and negatively with eating disorder symptoms and with depressive symptoms. CONCLUSIONS: Support is provided for a relationship between low omega-3 and omega-6 fatty acid intake and depressive symptoms in adolescents with eating disorders. Research is needed to examine the feasibility and effectiveness of fatty acid supplementation in this high-risk group.

Higher dietary quality is prospectively associated with lower MRI FLAIR lesion volume, but not with hazard of relapse, change in disability or black hole volume in people with Multiple Sclerosis.

BACKGROUND: The influence of diet quality on multiple sclerosis (MS) progression or inflammatory activity is not well understood. METHODS: Study participants with MS from the AusLong cohort, were followed annually (10 years, n = 223 post-onset). At baseline, 5 and 10-year reviews, indices of dietary quality - the Australian Recommended Food Score (ARFS) and Diet Quality Tracker (DQT) - were calculated from self-reported dietary intake data of the preceding 12 months (Food Frequency Questionnaire, Dietary Questionnaire for Epidemiological Studies v2). Associations were examined between measures of dietary quality with measures of MS progression and inflammatory activity hazard of relapse, annualised disability progression (Expanded Disability Status Scale, EDSS) and Magnetic Resonance Imaging (MRI) outcomes. MRI outcomes included fluid-attenuated inversion recovery (FLAIR, T2 MRI) lesion volume and black hole volume (T1 MRI) in the juxtacortical, periventricular, and infratentorial regions of the brain, as well as total calculated from the sum of the three regions. RESULTS: A higher diet quality (at least with the ARFS) was associated with lower FLAIR lesion volume in the periventricular region only (highest vs lowest quartile: ß=-1.89,95%CI=-3.64, -0.13, p = 0.04, periventricular FLAIR region median (IQR) for 5-year review: 4.41 (6.06) and 10-year review: 4.68 (7.27)). Associations with black hole lesion volume, hazard of relapse, and annualised EDSS progression, lacked in significance and/or dose-dependency. CONCLUSION: We found evidence that diet quality may have a role in modulating one aspect of MS inflammatory activity (periventricular MRI FLAIR lesion volume), but not other MRI and clinical outcome measures.

Differential DNA methylation of steatosis and non-alcoholic fatty liver disease in adolescence.

BACKGROUND AND AIMS: Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. APPROACH AND RESULTS: We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10-3). CONCLUSIONS: We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.

The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood.

BACKGROUND: Dietary changes may epigenetically modify fetal gene expression during critical periods of development to potentially influence disease susceptibility. This study examined whether maternal and/or fetal folate status in pregnancy is associated with infant allergic outcomes. METHODS: Pregnant women (n=628) were recruited in the last trimester of pregnancy. Folate status determined by both food frequency questionnaires and folate levels in maternal and cord blood serum was examined in relation to infant allergic outcomes at 1 year of age (n=484). RESULTS: Infants who developed allergic disease (namely eczema) did not show any differences in cord blood or maternal folate levels compared with children without disease. Although maternal folate intake from foods was also not different, folate derived from supplements was higher (P=0.017) in children with subsequent eczema. Furthermore, infants exposed to >500 µg folic acid/day as a supplement in utero were more likely to develop eczema than those taking <200 µg/day (OR [odds ratio] =1.85; 95% CI 1.14-3.02; P=0.013), remaining significant after adjustment for maternal allergy and other confounders. There was a nonlinear relationship between cord blood folate and sensitization, with folate levels <50 nmol/l (OR=3.02; 95% CI 1.16-7.87; P=0.024) and >75 nmol/l (OR=3.59; 95% CI 1.40-9.20; P=0.008) associated with greater sensitization risk than levels between 50 and 75 nmol/l. CONCLUSION: Fetal levels between 50 and 75 nmol/l appeared optimal for minimizing sensitization. While folate taken as a supplement in higher doses during the third trimester was associated with eczema, there was no effect on other allergic outcomes including sensitization. Further studies are needed to determine the significance of this.

Associations between diet quality and depression, anxiety, and fatigue in multiple sclerosis.

BACKGROUND: Many people with multiple sclerosis (MS) modify their dietary intake post diagnosis, but there is little evidence that dietary modifications influence MS outcomes. METHODS: People with a first clinical diagnosis of central nervous system demyelination were followed annually for 10 years. Depression, anxiety, and fatigue were assessed at the 5-and 10-year reviews using the Hospital Anxiety and Depression Scale and Fatigue Severity Scale, respectively. Dietary intake in the preceding 12 months was assessed at baseline, and 5-and 10-year reviews using a food frequency questionnaire. We used the Australian Recommended Food Score (ARFS) and the Diet Quality Tracker (DQT) to assess diet quality. RESULTS: A higher diet quality in the previous 12 months using the ARFS score, but not the DQT, was associated with lower levels of depression (e.g., highest vs lowest quartile: ß=-1.35,95%CI=-2.44,-0.26,p=0.01), but neither score was associated with anxiety or fatigue. After assessing diet quality prospectively with outcomes five years later, we found that higher ARFS score, but not DQT score, was associated with lower levels of subsequent anxiety and depression (highest vs lowest quartile; Anxiety: ß=-1.61,95%CI=-2.76,-0.46,p=0.01, Depression: ß=-1.25,95%CI=-2.44,-0.07,p=0.04), but not fatigue. No associations were observed between diet quality and subsequent change in depression and anxiety over five years, although an association was observed between diet quality and change in fatigue (e.g., highest vs lowest DQT quartile: ß=-1.06,95%CI=-1.92,-0.21,p=0.02). When examining the cumulative effect of diet quality across the study period with our 10-year outcomes, only the cumulative DQT score was associated with depression but not anxiety or fatigue. CONCLUSION: We found significant inverse associations between diet quality and depression and anxiety, but the effect sizes were modest and there was a lack of consistency between the two diet quality measures (ARFS and DQT). A diet measure that correlates with diet quality might underlie our observed associations.

Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors.

Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs (Bonferroni corrected p < 1.06E-07) associated with body mass index (BMI), 10 with waist circumference (WC) and 9 with subcutaneous fat thickness. DmCpGs within Ras Association (RalGDS/AF-6), Pleckstrin Homology Domains 1 (RAPH1), Musashi RNA-Binding Protein 2 (MSI2), and solute carrier family 25 member 10 (SLC25A10) are associated with both BMI and WC. Validation by pyrosequencing confirmed these associations and showed that MSI2 , SLC25A10 , and RAPH1 methylation was positively associated with serum leptin. These were  also associated with the early environment; MSI2 methylation (ß = 0.81, p = 0.0004) was associated with pregnancy maternal smoking, SLC25A10 (CpG2 ß = 0.12, p = 0.002) with pre- and early pregnancy BMI, and RAPH1 (ß = -1.49, p = 0.036) with gestational weight gain. Adjusting for perinatal factors, methylation of the dmCpGs within MSI2, RAPH1, and SLC25A10 independently predicted BMI, accounting for 24% of variance. MSI2 methylation was additionally associated with BMI over time (17 years old ß = 0.026, p = 0.0025; 20 years old ß = 0.027, p = 0.0029) and between generations (mother ß = 0.044, p = 7.5e-04). Overall findings suggest that DNA methylation in MSI2, RAPH1, and SLC25A10 in blood may be robust markers, mediating through early life factors.

Milk-derived or recombinant transforming growth factor-beta has effects on immunological outcomes: a review of evidence from animal experimental studies.

Identified factors from milk have been shown to improve health outcomes. One specific factor, transforming growth factor-Beta (TGF)-ß, has been identified previously as having the potential to impact on immunological outcomes in the newborn offspring. The primary objective of this review was to examine the published studies that have considered TGF-ß in association with immunological outcomes of experimental models. We hypothesized that oral administration of TGF-ß (through human milk, cow's milk, infant formula) or recombinant TGF-ß delivered via gavage, may down-regulate immune activation in newborn offspring. Animal experimental studies were identified through MEDLINE, CAB Abstracts, Biological Abstracts and Scopus. Selection criteria included well-described animal populations, sample and study design, source of TGF-ß, age and immunological outcomes measured and effect size. The findings were summarized temporally in tabular format, giving an overall measure of effect based on the literature available since 1994. Animal experimental studies (n=13) were included in the review to determine an association between maternal TGF-ß and immunological outcomes. Overall 92% of these studies (12/13) showed a positive association with TGF-ß1 or TGF-ß2, demonstrating protection against immunologically related outcomes in early life in an animal model. TGF-ß is important in developing and maintaining appropriate immune responses in the offspring. TGF-ß delivered orally to neonatal animals provides protection against adverse immunological outcomes, corroborating and supporting findings from human studies. Animal studies provide important clues to the pathogenesis and therapeutics of immune activation and allergy in early childhood. TGF-ßs are important growth factors involved in maintaining homeostasis in the intestine, regulating inflammation and allergy development and promoting oral tolerance in infants. Thus, taken as a whole, these and our other findings suggest that this cytokine in milk may influence the development of immunological outcomes in offspring.

The effectiveness of health promotion materials and activities on breastfeeding outcomes.

AIM: To determine the effect of mothers receiving health promotion material and education antenatally and/or postnatally on breastfeeding outcomes in Perth, Western Australia. METHODS: A 12-month longitudinal study was conducted in two public maternity hospitals in Perth, Western Australia, between 2002 and 2003. Data were collected on a consecutive sample 587 mothers. RESULTS: The results showed that mothers who received an individual consultation or were involved in a discussion on breastfeeding antenatally with hospital staff were approximately 55% less likely to cease fully breastfeeding (HR 0.44; 95% CI 0.24-0.88) before 6 months, and 50% less likely to cease any breastfeeding before 12 months postnatally (HR 0.51; 95% CI 0.28-0.92). In the postnatal period, mothers who received instruction on positioning and attachment of the infant to the breast while in hospital were approximately 30% less likely to cease fully breastfeeding before 6 months (HR 0.66; 95% CI 0.45-0.99). CONCLUSION: The results of this study suggest a positive association between receiving individualized breastfeeding information in both the antenatal and postnatal period, and breastfeeding outcomes.

Associations of dietary patterns with bone density and fractures in adults: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Although nutrition is important to bone health, the impact of different dietary patterns on bone density and fracture is unclear. The aim of this study was to synthesise conflicting evidence from observational studies to determine associations of empirically derived dietary patterns with bone density and fracture in healthy adults. METHOD: A systematic review (PROSPERO CRD42017071676) with meta-analysis where possible (for hip fracture) and otherwise with best-evidence synthesis. RESULTS: Twenty-one studies were included in the best-evidence synthesis and four in the meta-analysis. Meta-analysis demonstrated a protective association between 'healthy' pattern score and hip fracture (risk ratio 0.73; 95% confidence interval: 0.56, 0.96; I2 = 95%) for highest compared to lowest 'healthy' pattern score category. In best-evidence synthesis, there was conflicting evidence for associations of both pattern scores with bone density at all sites and total fractures and for 'Western' score and hip fracture. No study reported detrimental effects of 'healthy' patterns, or beneficial effects of 'Western' patterns. DISCUSSION: The results suggest that general practitioners promoting a 'healthy' dietary pattern is, at worst, unlikely to be detrimental for bone health and, at best, may reduce hip fracture.

Body mass index, adiposity rebound and early feeding in a longitudinal cohort (Raine Study).

OBJECTIVE: This study examined the influence of type and duration of infant feeding on adiposity rebound and the tracking of body mass index (BMI) from birth to 14 years of age. METHODS: A sample of 1330 individuals over eight follows-ups was drawn from the Western Australian Pregnancy Cohort (Raine) Study. Trajectories of BMI from birth to adolescence using linear mixed model analysis investigated the influence of age at which breastfeeding was stopped and the age at which other milk was introduced (binomial 4-month cutoff point). A subsample of linear mixed model-predicted BMI was used to determine BMI and age at nadir for early infant feeding groups. RESULTS: Chi-square analysis between early feeding and weight status (normal weight, overweight and obese) groups found a significant difference between thee age at which breastfeeding was stopped (P<0.001) and the age at which other milk was introduced (P=0.011), with a higher proportion of overweight and obese in the < or = 4-month group, even after controlling for maternal education. Using the linear mixed model, the BMI determined was higher over time for the group that was breastfed for < or = 4 months (P=0.015), with a significant interaction effect with the group in which other milk was introduced at < or = 4 months (P=0.011). Using predicted BMI from the linear mixed model, significant differences for nadirs of adiposity rebound between early feeding groups were found (P<0.005). CONCLUSIONS: Early infant feeding was important in the timing of, and BMI at, adiposity rebound. The relationship between infant feeding and BMI remained up to the age of 14 years. Although confounding factors cannot be excluded, these findings support the importance of exclusive breastfeeding for longer than 4 months as a protective behaviour against the development of adolescent obesity.

Dietary glycaemic carbohydrate in relation to the metabolic syndrome in adolescents: comparison of different metabolic syndrome definitions.

AIMS: High dietary glycaemic carbohydrate, as measured by the dietary glycaemic index and glycaemic load has been associated with increased risk of the metabolic syndrome in adults, but limited research exists for younger populations. We aimed to evaluate associations between dietary glycaemic carbohydrate and insulin resistance or the prevalence of the metabolic syndrome defined by three different criteria in a population-based adolescent cohort. METHODS: Diet was assessed using 3 day food records in 769 adolescents aged 13-15 years participating in the Western Australian Pregnancy Cohort (Raine) Study. The metabolic syndrome was identified using age-specific adolescent definitions from the International Diabetes Federation, the National Cholesterol Education Program Adult Treatment Panel III and a population-derived 'high-risk' metabolic cluster algorithm. Presence of a high waist circumference was mandatory only in the International Diabetes Federation definition. Insulin resistance was measured using homeostasis model assessment (HOMA-IR). RESULTS: The prevalence of the metabolic syndrome as defined by the International Diabetes Federation and the Adult Treatment Panel III was 3.6 and 4.0%, respectively; 25.9% of subjects were classified into the high-risk cluster. Significantly increased odds of International Diabetes Federation-defined metabolic syndrome were independently associated with a 20 unit glycaemic load increase (odds ratio 2.18; 95% confidence interval 1.26-3.78) and a 30 g carbohydrate increase (odds ratio 3.86; 95% confidence interval 1.80-8.28). No significant associations were observed when using the Adult Treatment Panel III, or the cluster-defined metabolic syndrome, or with HOMA-IR. CONCLUSIONS: This study supports the concept that high dietary glycaemic carbohydrate is associated with a higher prevalence of the metabolic syndrome in adolescents. However, relationships vary according to the definition of the metabolic syndrome used, with waist circumference a potentially relevant factor.

Low-moderate prenatal alcohol exposure and risk to child behavioural development: a prospective cohort study.

OBJECTIVE: To examine the association of fetal alcohol exposure during pregnancy with child and adolescent behavioural development. DESIGN: The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnancies (1989-91) and the 14-year follow up was conducted between 2003 and 2006. SETTING: Tertiary obstetric hospital in Perth, Western Australia. POPULATION: The women in the study provided data at 18 and 34 weeks of gestation on weekly alcohol intake: no drinking, occasional drinking (up to one standard drink per week), light drinking (2-6 standard drinks per week), moderate drinking (7-10 standard drinks per week), and heavy drinking (11 or more standard drinks per week). Methods Longitudinal regression models were used to analyse the effect of prenatal alcohol exposure on Child Behaviour Checklist (CBCL) scores over 14 years, assessed by continuous z-scores and clinical cutoff points, after adjusting for confounders. MAIN OUTCOME MEASURE: Their children were followed up at ages 2, 5, 8, 10 and 14 years. The CBCL was used to measure child behaviour. RESULTS: Light drinking and moderate drinking in the first 3 months of pregnancy were associated with child CBCL z-scores indicative of positive behaviour over 14 years after adjusting for maternal and sociodemographic characteristics. These changes in z-score indicated a clinically meaningful reduction in total, internalising and externalising behavioural problems across the 14 years of follow up. CONCLUSIONS: Our findings do not implicate light-moderate consumption of alcohol in pregnancy as a risk factor in the epidemiology of child behavioural problems.