Do parent-reported early indicators predict later developmental language disorder? A Raine Study investigation.

BACKGROUND: Developmental language disorder (DLD) is one of the most common neurodevelopmental conditions. Due to variable rates of language growth in children under 5 years, the early identification of children with DLD is challenging. Early indicators are often outlined by speech pathology regulatory bodies and other developmental services as evidence to empower caregivers in the early identification of DLD. AIMS: To test the predictive relationship between parent-reported early indicators and the likelihood of children meeting diagnostic criteria for DLD at 10 years of age as determined by standardized assessment measures in a population-based sample. METHODS: Data were leveraged from the prospective Raine Study (n = 1626 second-generation children: n = 104 with DLD; n = 1522 without DLD). These data were transformed into 11 predictor variables that reflect well-established early indicators of DLD from birth to 3 years, including if the child does not smile or interact with others, does not babble, makes only a few sounds, does not understand what others say, says only a few words, says words that are not easily understood, and does not combine words or put words together to make sentences. Family history (mother and father) of speech and language difficulties were also included as variables. Regression analyses were planned to explore the predictive relationship between this set of early indicator variables and likelihood of meeting DLD diagnostic criteria at 10 years. RESULTS: No single parent-reported indicator uniquely accounted for a significant proportion of children with DLD at 10 years of age. Further analyses, including bivariate analyses testing the predictive power of a cumulative risk index of combined predictors (odds ratio (OR) = 0.95, confidence interval (CI) = 0.85-1.09, p = 0.447) and the moderating effect of sex (OR = 0.89, CI = 0.59-1.32, p = 0.563) were also non-significant. CONCLUSIONS: Parent reports of early indicators of DLD are well-intentioned and widely used. However, data from the Raine Study cohort suggest potential retrospective reporting bias in previous studies. We note that missing data for some indicators may have influenced the results. Implications for the impact of using early indicators as evidence to inform early identification of DLD are discussed. WHAT THIS PAPER ADDS: What is already known on the subject DLD is a relatively common childhood condition; however, children with DLD are under-identified and under-served. Individual variability in early childhood makes identification of children at risk of DLD challenging. A range of 'red flags' in communication development are promoted through speech pathology regulatory bodies and developmental services to assist parents to identify if their child should access services. What this paper adds to the existing knowledge No one parent-reported early indicator, family history or a cumulation of indicators predicted DLD at 10 years in the Raine study. Sex (specifically, being male) did not moderate an increased risk of DLD at 10 years in the Raine study. Previous studies reporting on clinical samples may be at risk of retrospective reporting bias. What are the potential or actual clinical implications of this work? The broad dissemination and use of 'red flags' is well-intentioned; however, demonstrating 'red flags' alone may not reliably identify those who are at later risk of DLD. Findings from the literature suggest that parent concern may be complemented with assessment of linguistic behaviours to increase the likelihood of identifying those who at risk of DLD. Approaches to identification and assessment should be considered alongside evaluation of functional impact to inform participation-based interventions.

Advancing Use of DEXA Scans to Quantitatively and Qualitatively Evaluate Lateral Spinal Curves, for Preliminary Identification of Adolescent Idiopathic Scoliosis.

Dual-energy X-ray absorptiometry (DEXA) scan is an emerging screening method for identifying likely adolescent idiopathic scoliosis (AIS). Using DEXA in an unbiased population sample (the Raine Study), we aimed to report the inter-rater reliability and minimal detectable change (MDC95) for scoliosis curve angle measurement, identify likely AIS prevalence, and the concordance between reported AIS diagnosis and DEXA-identified likely AIS. Scoliosis curve angles were measured using the modified Ferguson method on DEXA scans (n = 1238) at age 20 years. For curve angle inter-rater reliability, two examiners measured angles (6-40°) on 41 scans. Likely, AIS was determined with quantitative and qualitative criteria (modified Ferguson angles ≥ 10° and expert review of spinal curves).The inter-rater reliability for scoliosis curve angle measurement was good-excellent (ICC: 0.82; 95% CI: 0.71-0.89; p < 0.001), and MDC95 was 6.2°. The prevalence of likely AIS was 2.1% (26/1238). Diagnosis of AIS was reported despite little or no scoliosis curve (< 3.8°) for 20 participants (1.6%), and diagnosis of AIS was not reported despite scoliosis curve ≥ 10° for 11 participants (0.9%). Results support the use of modified Ferguson method to measure scoliosis curve angles on DEXA. There is potential utility for using a combination of quantitative measurement and qualitative criteria to evaluate DEXA images, to identify likely AIS for reporting prevalence. Without formal school screening, the analysis of DEXA in this population sample suggested that relying on current health professional diagnosis alone could result in 2.5% of this cohort being at risk of false positive diagnosis or delay in necessary management due to non-diagnosis of AIS.

Gender non-conformity in childhood and adolescence and mental health through to adulthood: a longitudinal cohort study, 1995-2018.

BACKGROUND: Few studies have examined associations between gender non-conformity (GNC) in childhood or adolescence and mental health outcomes later in life. This study examined associations between (1) GNC and mental health over multiple time points in childhood and adolescence, and (2) GNC in childhood and/or adolescence and mental health in adulthood. METHOD: Second generation participants from the Raine Study, a longitudinal cohort from Perth, Western Australia. Data were collected between 1995 and 2018, comprising seven waves: ages 5 (N = 2236), 8 (N = 2140), 10 (N = 2048), 14 (N = 1864), 17 (N = 1726), 22 (N = 1236) and 27 (N = 1190) years. History of GNC, v. absence of this history, was based on responses to item 110 from the Child Behaviour Checklist (CBCL)/Youth Self Report (YSR) ('wishes to be of opposite sex'). The CBCL/YSR were used to measure internalising and externalising symptoms. Items 18 ('deliberate self-harm [DSH] or attempts suicide') and 91 ('talks/thinks about killing self') were used as measures of suicidal ideation (SI) and DSH. For adults, Depression, Anxiety and Stress Subscales and Kessler Psychological Distress Scale assessed mental health. RESULTS: Child and adolescent GNC was associated with elevated internalising and externalising behaviours and increased odds of DSH. A history of GNC was also associated with vulnerability for severe psychological distress in adulthood in some symptom scales. CONCLUSION: GNC over the child and adolescent period is associated with significant emotional and behavioural difficulties, and psychological distress. A history of GNC in childhood and/or adolescence also predicts poorer mental health in adulthood on multiple symptom domains.

Neurodevelopmental outcomes in children after prenatal marijuana exposure.

BACKGROUND: The effect of prenatal marijuana exposure (PME) on child neurodevelopment remains poorly understood. Prior studies have demonstrated inconsistent results. OBJECTIVES: This study evaluated the association between PME and neuropsychological test scores in late childhood and early adulthood, accounting for a wide range of parental characteristics. METHODS: This study evaluated participants from the Raine Study, a cohort of 2868 children born between 1989 and 1992. Children whose mothers provided information on marijuana use during pregnancy were included. The primary outcome was the Clinical Evaluation of Language Fundamentals (CELF) at age 10. Secondary outcomes included the Peabody Picture Vocabulary Test (PPVT), Child Behaviour Checklist (CBCL), McCarron Assessment of Neuromuscular Development (MAND), Coloured Progressive Matrices (CPM), Symbol Digit Modality Test (SDMT) and Autism Spectrum Quotient (AQ) scores. Exposed and unexposed children were matched by propensity score using optimal full matching. Missing covariate data were imputed using multiple imputation. Inverse probability of censoring weighting (IPCW) was used to adjust for missing outcome data. Linear regression within matched sets, adjusted by IPCW, evaluated score differences between exposed and unexposed children. As a secondary analysis, modified Poisson regression, adjusted by match weights and IPCW, evaluated the risk of clinical deficit in each outcome following PME. RESULTS: Of the 2804 children in this cohort, 285 (10.2%) had PME. After optimal full matching and IPCW, exposed children scored similarly on CELF Total (-0.33 points, 95% confidence interval [CI] -4.71, 4.05), Receptive (+0.65 points, 95% CI -4.08, 5.38) or Expressive (-0.53 points, 95% CI -5.07, 4.02). PME was not associated with secondary outcomes or risks of clinical deficit in any neuropsychological assessments. CONCLUSIONS: After adjusting for sociodemographic and clinical covariates, PME was not associated with worse neuropsychological test scores at age 10 or autistic traits at 19-20.

Longitudinal effects of prenatal exposure to plastic-derived chemicals and their metabolites on asthma and lung function from childhood into adulthood.

BACKGROUND AND OBJECTIVE: Environmental exposure to phthalates and bisphenol A (BPA), chemicals used in the production of plastics, may increase risk for asthma and allergies. However, little is known about the long-term effects of early life exposure to these compounds. We investigated if prenatal exposure to these compounds was associated with asthma, allergy and lung function outcomes from early childhood into adulthood in a cohort study. METHODS: Maternal serum samples collected from 846 pregnant women in the Raine Study were assayed for BPA and phthalate metabolites. The children of these women were followed up at 5, 13 and 22 years where spirometry and respiratory questionnaires were conducted to determine asthma and allergy status. Lung function trajectories were derived from longitudinal spirometry measurements. Multinomial logistic regression and weighted quantile sum regression was used to test associations of individual and chemical mixtures with asthma phenotypes and lung function trajectories. RESULTS: Effects of prenatal BPA and phthalates on asthma phenotypes were seen in male offspring, where BPA was associated with increased risk for persistent asthma, while mono-iso-butyl phthalate and mono-iso-decyl phthalate was associated with increased risk for adult asthma. Prenatal BPA had no effect on lung function trajectories, but prenatal phthalate exposure was associated with improved lung function. CONCLUSION: Prenatal BPA exposure was associated with increased likelihood of persistent asthma in males, while prenatal phthalate exposure was associated with increased likelihood of adult asthma in males. Results suggest that prenatal exposure to prenatal BPA and phthalates affect asthma risk, particularly in males, however lung function was not adversely affected.

Childhood sleep health and epigenetic age acceleration in late adolescence: Cross-sectional and longitudinal analyses.

AIM: Investigate if childhood measures of sleep health are associated with epigenetic age acceleration in late adolescence. METHODS: Parent-reported sleep trajectories from age 5 to 17, self-reported sleep problems at age 17, and six measures of epigenetic age acceleration at age 17 were studied in 1192 young Australians from the Raine Study Gen2. RESULTS: There was no evidence for a relationship between the parent-reported sleep trajectories and epigenetic age acceleration (p ≥ 0.17). There was a positive cross-sectional relationship between self-reported sleep problem score and intrinsic epigenetic age acceleration at age 17 (b = 0.14, p = 0.04), which was attenuated after controlling for depressive symptom score at the same age (b = 0.08, p = 0.34). Follow-up analyses suggested this finding may represent greater overtiredness and intrinsic epigenetic age acceleration in adolescents with higher depressive symptoms. CONCLUSION: There was no evidence for a relationship between self- or parent-reported sleep health and epigenetic age acceleration in late adolescence after adjusting for depressive symptoms. Mental health should be considered as a potential confounding variable in future research on sleep and epigenetic age acceleration, particularly if subjective measures of sleep are used.

Prospective Associations of Sugar-Sweetened Beverage Consumption During Adolescence with Body Composition and Bone Mass at Early Adulthood.

BACKGROUND: Adolescents have a higher consumption of sugar-sweetened beverages (SSBs) than other age groups, but little is known of the impact of SSB intake during adolescence on body composition and bone mass in early adulthood. OBJECTIVES: Associations of SSB intake from 14 to 20 y with fat, lean, and bone mass at 20 y of age were evaluated. METHODS: Study participants were 1137 offspring (562 females) from the Raine Study. Food intake, including SSB consumption in servings/d (1 serving = 250 mL), was estimated using FFQs at 14, 17, and 20 y of age. DXA scanning at 20 y measured whole body fat mass, lean mass, and bone mineral content (BMC). Using latent class growth analysis, 4 SSB intake trajectory classes were identified: consistently low (n = 540, intakes mostly <0.5 serving/d), increasing (n = 65), decreasing (n = 258), and consistently high (n = 274, intakes mostly >1.3 servings/d). RESULTS: Median total SSB intake was 0.8, 0.7, and 0.5 serving/d, and median carbonated SSB intake was 0.3, 0.3, and 0.4 serving/d at 14, 17, and 20 y, respectively. Mean ± SD BMI (in kg/m2) was 23.9 ± 4.2 at 20 y. After adjustment for covariates including sex, demographic, energy intake, and maternal factors, individuals with "consistently high" SSB consumption had significantly higher total body fat mass at 20 y than those with "consistently low" consumption (23.3 ± 0.6 compared with 21.2 ± 0.4 kg, P = 0.004), which remained significant after further adjustment for "Healthy" and "Western" dietary patterns (23.2 ± 0.6 compared with 21.2 ± 0.4 kg, P = 0.011). No significant associations were observed between SSB intake trajectory classes and lean body mass or BMC at 20 y. CONCLUSIONS: In this cohort, consistently higher consumption of SSBs in adolescence and early adulthood are associated with increased fat mass but not with bone mass at 20 y of age.

Applying the 4Ps of social marketing to retain and engage participants in longitudinal cohort studies: generation 2 Raine study participant perspectives.

BACKGROUND: Investigations of participant retention in longitudinal health and medical research, document  strategies that work best but overlook social marketing's capacity to influence participant retention. After applying the social marketing framework: the idea that determining what longitudinal participants 'buy' (product), at what cost (price), in what location (place) and through which communication channels (promotion),  this paper  aims to inform and enhance retention efforts. METHODS: This qualitative study was conducted through in-depth interviews with participants from the Raine Study that began in Western Australia in 1989. The Generation 2 participants, initially enrolled into the Raine Study as babies by their parents (Generation 1), are now young adults invited to attend follow-up studies and tests every few years. Our study defined 'active' participants (n = 17) as those who agreed to attend their 27 year follow-up, and 'inactive' (n = 12) participants as those who had attended neither of the past two follow-ups (22 and 27 years). RESULTS: Raine Study participants experienced core, actual and augmented product benefits. Inactive participants focused on the costs (price) associated with participation, and were more likely to suggest tele-health (place) strategies to overcome barriers to follow-up attendance. Both active and inactive participants found professional processes and friendly staff made the Raine Study environment appealing, suggested that social media (promotion) was underutilised, and offered novel ideas to enhance engagement. CONCLUSIONS: Social marketing can support the development of differentiated strategies addressing the unique needs and wants of active and inactive participants. Sophisticated cohort segmentation can reach participants in a more meaningful way, reinforce the study 'brand' and guard against attrition.

Association between pelvic pain bothersomeness and pain sensitivity: A community-based cross-sectional study of young adult females in the Raine Study.

OBJECTIVE: Pelvic pain has been associated with augmented nociceptive processing, but large studies controlling for multiple potential confounding factors are lacking. This study investigated the association between pelvic pain bothersomeness and pain sensitivity in young adult women, accounting for potential confounding factors. DESIGN: Cross-sectional study. SETTING: Community-dwelling sample. POPULATION: The Raine Study Gen2-22 year follow-up (n = 475). MAIN OUTCOME MEASURES: The experience of bothersomeness related to pelvic pain was determined from a question in the Urogenital Distress Inventory short form. Pain sensitivity was measured using pressure pain and cold pain thresholds. Potential confounding factors included ethnicity, marital status, highest level of education, income, waist-hip ratio, level of activity, sleep quality, smoking, comorbidity history, C-reactive protein level, musculoskeletal pain experience and psychological distress. RESULTS: Three hundred and sixty-two women (76.2%) reported no pelvic pain bothersomeness, 74 (15.6%) reported mild pelvic pain bothersomeness and 39 (8.2%) reported moderate-severe pelvic pain bothersomeness. After adjusting for marital status (and test site), moderate-severe pelvic pain bothersomeness was associated with a lower pressure pain threshold (i.e. greater pressure pain sensitivity) (coefficient -51.46, 95% CI -98.06 to -4.86, p = 0.030). After adjusting for smoking, moderate-severe pelvic pain bothersomeness was also associated with a higher cold pain threshold (i.e. greater cold pain sensitivity) (coefficient 4.35, 95% CI 0.90-7.79, p = 0.014). CONCLUSIONS: This study suggests augmented nociceptive processing as a contributing factor in pelvic pain bothersomeness for some women. Thorough assessment of women who present clinically with pelvic pain should consider pain sensitivity as a potential contributing factor to their presentation.

The impact of parental mental health problems on the educational outcomes of their offspring: Findings from the Raine Study.

OBJECTIVES: There is limited evidence on the impact of parental mental health problems on offspring's educational outcomes. We investigated the impact of maternal anxiety and depressive symptoms, as well as paternal emotional problems on the educational outcomes of their adolescent and young adult offspring. METHODS: We used data from a longitudinal birth cohort recruited between 1989 and 1991 in Australia (the Raine Study). The Depression, Anxiety and Stress Scale was used to assess maternal depressive and anxiety symptoms, and a self-reported question was used to measure paternal mental health problems. Both were assessed when the offspring was aged 10 years. Outcomes included offspring's self-reported education attainment-not completing year 10 at age 17, not attending tertiary education at ages 17 and 22 and primary caregiver's reports of offspring's academic performance at age 17. RESULTS: A total of 1033, 1307 and 1364 parent-offspring pairs were included in the final analysis exploring the association between parental mental health problems and offspring's academic performance at school, completing year 10 and attending tertiary education, respectively. After adjusting for potential confounders, the offspring of mothers with anxiety symptoms were 3.42 times more likely than the offspring of mothers without anxiety symptoms to have poor or below-average academic performance (odds ratio = 3.42; 95% confidence interval = [1.31, 8.92]) and more than 2 times more likely to not attend tertiary education (odds ratio = 2.55; 95% confidence interval = [1.10, 5.5.88]) and not to have completed year 10 (odds ratio = 2.13; 95% confidence interval = [1.04, 4.33]). We found no significant associations between maternal depressive symptoms or paternal emotional problems and offspring educational attainment. CONCLUSION: Maternal anxiety symptoms, but not depression and paternal emotional problems, are associated with poor educational attainment and achievement in adolescent offspring. The findings highlight that efforts to improve the outcomes of offspring of mothers with anxiety could focus on educational attainment.

Associations of 12-year sleep behaviour trajectories from childhood to adolescence with myopia and ocular biometry during young adulthood.

PURPOSE: Cross-sectional studies have variably reported that poor sleep quality may be associated with myopia in children. Longitudinal data, collected over the ages when myopia develops and progresses, could provide new insights into the sleep-myopia paradigm. This study tested the hypothesis that 12-year trajectories of sleep behaviour from childhood to adolescence is associated with myopia during young adulthood. METHODS: At the 5-, 8-, 10-, 14- and 17-year follow-ups of the longitudinal Raine Study, which has been following a cohort since their birth in 1989-1992, participants' parents/guardians completed the Child Behaviour Checklist questionnaire (CBCL), which collected information on their child's sleep behaviour and quality. The CBCL includes six questions measuring sleep behaviour, which parents rated as 0 = not true, 1 = somewhat/sometimes true, or 2 = very/often true. Scores were summed at each follow-up to form a composite "sleep behaviour score". Latent Class Growth Analysis (LCGA) was used to classify participants according to their 12-year trajectory of sleep behaviour. At the 20-year follow-up, an eye examination was performed which included cycloplegic autorefraction and axial length measurement. RESULTS: The LCGA identified three clusters of participants based on their trajectory of sleep behaviour: those with minimal' (43.6% of the total Raine Study sample), 'declining' (48.9%), or 'persistent' (7.5%) sleep problems. A total of 1194 participants had ophthalmic data and longitudinal sleep data available for analysis (47.2% female, 85.6% Caucasian). No significant differences were observed in regards to age, sex, ethnicity or ocular parameters between trajectory groups. Unadjusted and fully adjusted analyses demonstrated that sleep problem behaviour was not significantly associated with changes in refractive error, axial length or corneal radius. CONCLUSIONS: Our findings do not support the hypothesis that there is an association between sleep behaviour and myopia. Future longitudinal studies should explore sleep trajectory data pre- and post-myopia diagnosis to confirm our results.

The prevalence of and potential risk factors for Developmental Language Disorder at 10 years in the Raine Study.

AIM: This study sought to determine the prevalence of Developmental Language Disorder (DLD) in Australian school-aged children and associated potential risk factors for DLD at 10 years. METHODS: This study used a cross-sectional design to estimate the prevalence of DLD in Generation 2 of the prospective Raine Study. Participants included 1626 children aged 10 years with available language data. Primary outcomes included variables matching diagnostic criteria for DLD. Associations of other potential prenatal and environmental variables were analysed as secondary outcomes. RESULTS: The prevalence of DLD in this sample was 6.4% (n = 104) at 10 years. This sub-cohort comprised 33.7% (n = 35) with expressive language deficits, 20.2% (n = 21) with receptive language deficits, and 46.2% (n = 48) with receptive-expressive deficits. No significant difference in sex distribution was observed (52.9% male, p = 0.799). Children who were exposed to smoke in utero at 18 weeks gestation were at increased risk of DLD at 10 years (OR = 2.56, CI = 1.23-5.35, p = 0.012). CONCLUSIONS: DLD is a relatively prevalent condition in Australian children, even when assessed in middle childhood years. These findings can inform future research priorities, and public health and educational policy which account for the associations with potential risk factors.

Prenatal exposure to maternal stressful life events and earlier age at menarche: the Raine Study.

STUDY QUESTION: Is there an association between prenatal exposure to stressful life events and age at menarche, and does childhood BMI mediate this association? SUMMARY ANSWER: Girls exposed to prenatal stress had a slightly earlier age at menarche, but this association did not show a dose-response effect and was not mediated by childhood offspring BMI. WHAT IS ALREADY KNOWN: Prenatal stress may impact on reproductive function in females including age at menarche, but human data are very limited. High childhood BMI is known to be associated with earlier age at menarche. Only one small study has measured the association between maternal stress and age at menarche and reported that childhood BMI mediated the association between maternal stress and earlier age at menarche. However, neither maternal stress nor age at menarche was prospectively recorded and the study was limited to 31 mother-daughter pairs. STUDY DESIGN, SIZE, DURATION: The Raine Study is a large prospective population-based pregnancy cohort study (n = 1414 mother-daughter pairs) continuously followed from prenatal life through to adolescence. In the present study, we examined the association between exposure to maternal stressful life events during early, late and total gestation and age at menarche in offspring using 753 mother-daughter pairs with complete case information. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mothers prospectively reported stressful life events during pregnancy at 18 and 34 weeks using a standardized 10-point questionnaire. Exact date of menarche was assessed using a purpose-designed questionnaire at 8, 10, 14 and 17 years of age. Complete information on exposure, outcome and confounding variables was obtained from 753 mothers-daughter pairs. Multivariate linear regression complete case analysis was used to examine associations between maternal stressful life event exposure and age at menarche. Potential selection bias was evaluated using multiple imputations (50 datasets). The mediating effects of offspring childhood BMI (ages 5, 8, or 10 years) on these associations were measured in separate sub-analyses. MAIN RESULTS AND ROLE OF CHANCE: Most (580/753, 77%) daughters were exposed to at least one prenatal stressful life event. Exposure to maternal stressful life events during the entire pregnancy was associated with a non-linear earlier age at menarche. Exposure to one event and two or more psychological stressful events was associated with a 3.5 and 1.7-month earlier onset of puberty, respectively when compared to the reference group with no exposure maternal stressful life events. The estimates from multiple imputation with 50 datasets were comparable with complete case analysis confirming the existence of an underlying effect. No separate significant effects were observed for exposure during early or late gestation. The association between prenatal stressful events and age at menarche was not mediated by childhood BMI in the offspring. LIMITATIONS, REASONS FOR CAUTION: Stressful life events may have affected pregnant women in different ways and self-perceived maternal stress severity may have provided a more precise estimate of gestational psychological stress. The observed non-linear U-shape of the association between maternal psychological stress and age at menarche did not reflect a dose-response. This suggests that the first exposure to prenatal stress exerts a greater effect on fetal reproductive development. A potential mechanism is via dramatic initial activation of the hypothalamic-pituitary-adrenal (HPA) axis following the first stressful life event which is greater than that observed following subsequent exposure to two or more maternal stressful life events. Whilst we adjusted for a priori chosen confounders, we cannot exclude residual confounding or confounding by factors we did not include. Maternal age at menarche was not available so the effects of familial history/genetics could not be assessed. There was a large loss due to the number of girls with no information on date of menarche and missing confounder information implying risk of selection bias and multiple imputation analyses did not fully exclude this risk (similar direction but slightly weaker estimate magnitude). WIDER IMPLICATIONS OF THE FINDINGS: Menarche is a sentinel reproductive event and earlier age at menarche carries implications for psychological, social and reproductive health and for long-term risk of common non-communicable diseases. Understanding the factors regulating age at menarche has extensive health implications. This is the first population-based cohort study in humans to demonstrate that prenatal psychological stress might directly modify age at menarche. STUDY FUNDING/COMPETING INTEREST(S): Dr. Bräuner and Trine Koch's salaries were supported by Doctor Sofus Carl Emil Friis and spouse Olga Doris Friis foundation, The Danish Cancer Society (Kræftens Bekæmpelse, RP15468, R204-A12636, Denmark) and The Danish Health Foundation (Helsefonden, F-22181-23, Denmark). Martha Hickey was funded by NHMRC Practitioner Fellowships. The funding bodies played no role in the design, collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Dr. Hart has received personal fees in his function as the Medical Director of Fertility Specialists of Western Australia and received educational sponsorship grants from MSD, Merck-Serono and from Ferring Pharmaceuticals. Dr Hart has also received personal fees from Shareholders in Western IVF outside the submitted work. TRIAL REGISTRATION NUMBER: NA.

Insight into the longitudinal relationship between chronic subclinical inflammation and obesity from adolescence to early adulthood: a dual trajectory analysis.

OBJECTIVES AND DESIGN: This study aimed to understand the longitudinal relationship between C-reactive protein (CRP) and body mass index (BMI) from adolescence to early adulthood. METHODS: CRP and BMI were collected from participants of the Raine Study Gen2 at 14-, 17-, 20- and 22-year follow-ups (n = 1312). A dual trajectory analysis was conducted to assess the association between CRP and BMI trajectories, providing conditional probabilities of membership of CRP trajectory membership given BMI trajectory membership. Best model fit was assessed by systematically fitting two to eight trajectory groups with linear and quadratic terms and comparing models according to the Bayesian Information Criterion statistic. RESULTS: The three CRP trajectories were; "stable-low" (71.0%), "low-to-high" (13.8%) and "stable-high" (15.2%). Participants in a "high-increasing" BMI trajectory had a higher probability of being in the "stable-high" CRP trajectory (60.4% of participants). In contrast, individuals in the "medium-increasing" BMI trajectory did not have a significantly increased probability of being in the "stable-high" CRP trajectory. CONCLUSIONS: These findings support that chronic sub-clinical inflammation is present through adolescence into early adulthood in some individuals. Targeting chronic sub-clinical inflammation though obesity prevention strategies may be important for improving future health outcomes.

Dietary fibre intake and its associations with depressive symptoms in a prospective adolescent cohort.

Depression is a major cause of disability in adolescents. Higher dietary fibre intake has been associated with lower depressive symptoms in adults, but there is a lack of research in adolescents. We examined the association between dietary fibre intake (Commonwealth Scientific and Industrial Research Organisation (CSIRO) FFQ) and depressive symptoms (Beck Depression Inventory for Youth) in adolescents with prospective data from the Raine Study Gen2 14- and 17-year follow-ups (n 1260 and 653). Odds of moderate/extreme (clinically relevant) depressive symptoms by quartile of fibre intake were calculated using mixed-effects logistic regression for all participants, in a paired sample without moderate/extreme depressive symptoms at 14 years and in a sub-sample of participants with available inflammatory data at the ages of 14 and 17 years (n 718 and 547). Odds of moderate/extreme depressive symptoms were lower in the fourth (highest) quartile of overall fibre intake (OR 0·273, 95 % CI 0·09, 0·81) compared with the first (lowest) quartile, adjusting for sex, age, energy intake, adiposity, and family and lifestyle factors. However, further adjustment for dietary patterns attenuated the results. Associations of depressive symptoms with cereal or fruit and vegetable fibre intake were not significant in the final model. Adjustment for inflammation had no effect on OR. The association between a higher dietary fibre intake and lower odds of clinically relevant depressive symptoms may be more reflective of a high-fibre diet with all its accompanying nutrients than of an independent effect of fibre.

Dietary fibre intake and its association with inflammatory markers in adolescents.

A high dietary fibre intake has been associated with improvements in inflammatory conditions in adults. However, little is known on whether associations between dietary fibre and inflammation are evident during adolescence. We examined the relationship between dietary fibre intake measured by FFQ and the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin cross-sectionally in 17-year-olds participating in the Raine Study (n 621). In weighted analysis using tobit and linear regression, and after excluding participants with hs-CRP > 10 mg/l, higher total dietary fibre intake (per 5 g/d) was significantly associated with lower leptin (ß = -0·13, 95 % CI -0·17, -0·09) and adiponectin (ß = -0·28, 95 % CI -0·49, -0·07), but not hs-CRP, in unadjusted analyses. These associations were no longer significant after adjustment for sex, anthropometry and a number of lifestyle factors. However, higher cereal and grain fibre intake was significantly associated with lower leptin (ß = -0·06, 95 % CI -0·10, -0·01) in fully adjusted analysis. Our findings suggest that a higher intake of cereal and grain fibre may contribute to lower leptin in adolescents. This may contribute to reductions in low-grade chronic inflammation and improved health outcomes.

Energy drink intake is associated with insomnia and decreased daytime functioning in young adult females.

OBJECTIVE: To investigate the association between energy drink (ED) use and sleep-related disturbances in a population-based sample of young adults from the Raine Study. DESIGN: Analysis of cross-sectional data obtained from self-administered questionnaires to assess ED use and sleep disturbance (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire (FOSQ-10) and the Pittsburgh Sleep Symptoms Questionnaire-Insomnia (PSSQ-I)). Regression modelling was used to estimate the effect of ED use on sleep disturbances. All models adjusted for various potential confounders. SETTING: Western Australia. PARTICIPANTS: Males and females, aged 22 years, from Raine Study Gen2-22 year follow-up. RESULTS: Of the 1115 participants, 66 % were never/rare users (i.e. once/month to

i-PATHWAY: Development and validation of a prediction model for childhood obesity in an Australian prospective birth cohort.

AIM: To develop and validate a model (i-PATHWAY) to predict childhood (age 8-9 years) overweight/obesity from infancy (age 12 months) using an Australian prospective birth cohort. METHODS: The Transparent Reporting of a multivariable Prediction model for individual Prognosis or Diagnosis (TRIPOD) checklist was followed. Participants were n = 1947 children (aged 8-9 years) from the Raine Study Gen2 - an Australian prospective birth cohort - who had complete anthropometric measurement data available at follow up. The primary outcome was childhood overweight or obesity (age 8-9 years), defined by age- and gender-specific cut-offs. Multiple imputation was performed to handle missing data. Predictors were selected using 2000 unique backward stepwise logistic regression models. Predictive performance was assessed via: calibration, discrimination and decision-threshold analysis. Internal validation of i-PATHWAY was conducted using bootstrapping (1000 repetitions) to adjust for optimism and improve reliability. A clinical model was developed to support relevance to practice. RESULTS: At age 8-9 years, 18.9% (n = 367) of children were classified with overweight or obesity. i-PATHWAY predictors included: weight change (0-1 year); maternal pre-pregnancy body mass index (BMI); paternal BMI; maternal smoking during pregnancy; premature birth; infant sleep patterns; and sex. After validation, predictive accuracy was acceptable: calibration slope = 0.956 (0.952-0.960), intercept = -0.052 (-0.063, -0.048), area under the curve = 0.737 (0.736-0.738), optimised sensitivity = 0.703(0.568-0.790), optimised specificity = 0.646 (0.571-0.986). The clinical model retained acceptable predictive accuracy without paternal BMI. CONCLUSIONS: i-PATHWAY is a simple, valid and clinically relevant prediction model for childhood overweight/obesity. After further validation, this model can influence state and national health policy for overweight/obesity screening in the early years.

Informing retention in longitudinal cohort studies through a social marketing lens: Raine Study Generation 2 participants' perspectives on benefits and barriers to participation.

BACKGROUND: Longitudinal cohort studies have made significant contributions to medical discoveries and provide the impetus for health interventions which reduce the risk of disease. Establishing and maintaining these cohorts is challenging and costly. While some attrition is unavoidable, maintaining a sufficient number of participants ensures that results remain representative and free from bias. Numerous studies have investigated ways to reduce attrition but few studies have sought to understand the experience of participants, and none have examined this through a social marketing framework. This first paper in a two part-series describes participants' experiences according to: benefits, barriers, motivators and influencers. The second paper uses this understanding to address issues relating to the 4Ps (product, price, place, promotion) of social marketing. METHODS: Participants were recruited from the Raine Study, a pregnancy cohort study that has been running in Western Australia since 1989. Qualitative interviews were conducted with 29 active and inactive participants from the Generation 2 cohort, who were originally enrolled in the Raine Study at birth by their parents (Generation 1). 'Active' participants (n = 17) were defined as those who agreed to attend their 27 year follow-up, while 'inactive' (n = 12) participants were defined as those who had not attended either of the past two follow-ups (at 22 and 27 years). RESULTS: There were considerable differences between active and inactive participants, with active participants perceiving far more personal and collective benefits from their participation. Inactive participants described being constrained by structural barriers around work and life, whereas active participants were able to overcome them to attend follow-ups. Inactive participants also described the value of extrinsic incentives which might motivate their attendance, and active participants described the role of their parents as significant influencers in their propensity to remain in the study. CONCLUSIONS: This paper provides rich descriptions of what participation in a long-running study means to participants. Use of a social marketing framework ensured that participants were constructed as 'human consumers' who are influenced by individual and broader social systems. Understanding participants in this way means that differentiated strategies can be tailored to enhance retention.

Estimated intake and major food sources of flavonoids among Australian adolescents.

PURPOSE: The consumption of dietary flavonoids from plant-based foods has been related to the prevention of multiple chronic diseases. However, intake data from adolescents are lacking. We aimed to characterise the intake and major sources of dietary flavonoids among Australian adolescents and investigate changes during adolescence. METHODS: The Raine Study Gen 2 participants completed a 212-item food frequency questionnaire at age 14 years and 17 years, with repeated measures for n = 883. Items were assigned a content for six flavonoid subclasses using the Phenol-Explorer database, which were summed for total flavonoid intake. Daily intakes and sources of flavonoids and flavonoid-subclasses were determined, and change assessed between 14 and 17 years, for males and females. RESULTS: Major food sources of flavonoids and each subclass were similar at 14 and 17 years, with fruit juice the major contributor to total flavonoid intake at both time points (providing 44% and 38%, respectively). Citrus flavanones (predominantly hesperitin) were the major subclass at 14 years, while tea flavan-3-ols were a major subclass (predominantly procyanidin dimers) at 17 years. The mean intake of total flavonoids at 14 years was 210 ± 133 mg/day, reducing by 5% (10 mg/day) by 17 years. Females consumed a more flavonoid-dense diet compared to males (104.5 ± 71.5 mg/1000 kcal vs 80.4 ± 50.3 mg/1000 kcal per day; p < 0.001). CONCLUSION: This study provides a comprehensive estimation of flavonoid intake and their major food sources in a sample of Australian adolescents, which may be useful in the development of practical dietary recommendations.