Amino acid (AA) concentrations are influenced by both exogenous (e.g. diet, lifestyle) and endogenous factors (e.g. genetic, transcriptomic, epigenetic, and metabolomic). Fasting plasma AA profiles ...in adulthood are predictive of diabetes risk over periods of up to 12 years. Data on AA profiles in cross-generational cohorts, including individuals from shared gene-environment settings are scarce, but would allow the identification of the contribution of heritable and environmental factors characterising the levels of circulating AAs. This study aimed to investigate parent-child (familial dyad) concordance, absolute differences between generations- (children versus adults), age- (in adults: 28-71 years), and sex-dependent differences in plasma AA concentrations. Plasma AA concentrations were measured by UHPLC/MS-MS in 1166 children mean (SD) age 11 (0.5) years, 51% female and 1324 of their parents 44 (5.1) years, 87% female. AA concentrations were variably concordant between parents and their children (5-41% of variability explained). Most AA concentrations were higher in adults than children, except for the non-essential AAs arginine, aspartic acid, glutamine, hydroxy-proline, proline, and serine. Male adults and children typically had higher AA concentrations than females. The exceptions were alanine, glutamine, glycine, hydroxy-proline, serine, and threonine in girls; and glycine and serine in women. Age, sex, and shared familial factors are important determinants of plasma AA concentrations.
Common pregnancy and perinatal complications are associated with offspring cardiometabolic risk factors. These complications may influence multiple metabolic traits in the offspring and these ...associations might differ with offspring age.
We used data from eight population-based cohort studies to examine and compare associations of pre-eclampsia (PE), gestational hypertension (GH), gestational diabetes (GD), preterm birth (PTB), small (SGA) and large (LGA) for gestational age (vs. appropriate size for gestational age (AGA)) with up to 167 plasma/serum-based nuclear magnetic resonance-derived metabolic traits encompassing lipids, lipoproteins, fatty acids, amino acids, ketones, glycerides/phospholipids, glycolysis, fluid balance, and inflammation. Confounder-adjusted regression models were used to examine associations (adjusted for maternal education, parity age at pregnancy, ethnicity, pre/early pregnancy body mass index and smoking, and offspring sex and age at metabolic trait assessment), and results were combined using meta-analysis by five age categories representing different periods of the offspring life course: neonates (cord blood), infancy (mean ages: 1.1-1.6 years), childhood (4.2-7.5 years); adolescence (12.0-16.0 years), and adulthood (22.0-67.8 years).
Offspring numbers for each age category/analysis varied from 8925 adults (441 PTB) to 1181 infants (135 GD); 48.4% to 60.0% were females. Pregnancy complications (PE, GH, GD) were each associated with up to three metabolic traits in neonates (P≤0.001) with some evidence of persistence to older ages. PTB and SGA were associated with 32 and 12 metabolic traits in neonates respectively, which included an adjusted standardised mean difference of -0.89 standard deviation (SD) units for albumin with PTB (95% CI: -1.10 to -0.69, P=1.3×10
) and -0.41 SD for total lipids in medium HDL with SGA (95% CI: -0.56 to -0.25, P=2.6×10
), with some evidence of persistence to older ages. LGA was inversely associated with 19 metabolic traits including lower levels of cholesterol, lipoproteins, fatty acids, and amino acids, with associations emerging in adolescence, (e.g. -0.11 SD total fatty acids, 95% CI: -0.18 to -0.05, P=0.0009), and attenuating with older age across adulthood.
These reassuring findings suggest little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits, with most associations only observed for newborns rather than older ages, and for perinatal rather than pregnancy complications.
B vitamers are co-enzymes involved in key physiological processes including energy production, one-carbon, and macronutrient metabolism. Studies profiling B vitamers simultaneously in parent-child ...dyads are scarce. Profiling B vitamers in parent-child dyads enables an insightful determination of gene-environment contributions to their circulating concentrations. We aimed to characterise: (a) parent-child dyad concordance, (b) generation (children versus adults), (c) age (within the adult subgroup (age range 28-71 years)) and (d) sex differences in plasma B vitamer concentrations in the CheckPoint study of Australian children.
1166 children (11 ± 0.5 years, 51% female) and 1324 parents (44 ± 5.1 years, 87% female) took part in a biomedical assessment of a population-derived longitudinal cohort study: The Growing Up in Australia's Child Health CheckPoint. B vitamer levels were quantified by UHPLC/MS-MS. B vitamer levels were weakly concordant between parent-child pairs (10-31% of variability explained). All B vitamer concentrations exhibited generation-specificity, except for flavin mononucleotide (FMN). The levels of thiamine, pantothenic acid, and 4-pyridoxic acid were higher in male children, and those of pantothenic acid were higher in male adults compared to their female counterparts.
Family, age, and sex contribute to variations in the concentrations of plasma B vitamers in Australian children and adults.
Equity in healthcare service access and use are national goals and principal indicators of health system performance. Whilst it is important to understand how healthcare costs, socioeconomic position ...(SEP), and children's well-being are associated, limited literature explores how these covary.
To explore the associations between families' SEP and (1) children's health-related quality of life (HRQoL) from 4 to 13 years; and (2) healthcare costs from 0 to 13 years; as well as (3) contributing factors that influence children's HRQoL and healthcare costs.
Data were drawn from the Longitudinal Study of Australian Children (LSAC). We used the parent-reported Pediatric Quality of Life Inventory 4.0 to measure children's HRQoL from 4 to 13 years. Healthcare costs to government from 0 to 13 years were measured using the government administrative data (Medicare) which includes records of both medical and pharmaceutical service utilisation. We used a composite of income, parental education, and occupation to measure SEP. We used linear and mixed effects modelling to explore associations between families' SEP and children's HRQoL or government healthcare costs, including the effects of predictors for these associations. Analyses were weighted and accounted for the survey design.
Compared to children from high SEP families, those from low SEP families had lower HRQoL (from age 6–13 years, p = 0.001) and their families incurred higher government healthcare costs (from birth to 13 years). This association was confirmed using the mixed effects model (p = 0.054). Child special healthcare needs, being a single-parent or having parental stress were related to poorer children's HRQoL and higher government healthcare costs. Living in regional and remote areas was related to lower government healthcare costs.
Up to 13 years of age, children with low SEP used more health services but had lower HRQoL than those from high SEP families. These findings highlight a need to support children from low SEP families to improve their health and wellbeing.
•Between birth and 13 years, disadvantaged children incurred higher government healthcare costs.•Between ages 6 and 13 years disadvantaged children experienced lower HRQoL than advantaged children.•Parental stress and lone parenthood contributed to higher healthcare costs and lower children's HRQoL.•Children with special healthcare needs experienced higher service use and lower HRQoL.•Living in regional and remote areas was associated with lower use of health services.
Although more than 200 genes have been associated with monogenic congenital hearing loss, the polygenic contribution to hearing decline across the life course remains largely unknown.
To examine the ...association of polygenic risk scores (PRSs) for self-reported hearing difficulty among adults (40-69 years) with measured hearing and speech reception abilities in mid-childhood and early midlife.
This was a population-based cross-sectional study nested within the Longitudinal Study of Australian Children that included 1608 children and 1642 adults. Pure tone audiometry, speech reception threshold against noise, and genetic data were evaluated. Linear and logistic regressions of PRSs were conducted for hearing outcomes. Study analysis was performed from March 1 to 31, 2022.
Genotypes were generated from saliva or blood using global single-nucleotide polymorphisms array and PRSs derived from published genome-wide association studies of self-reported hearing difficulty (PRS1) and hearing aid use (PRS2). Hearing outcomes were continuous using the high Fletcher index (mean hearing threshold, 1, 2, and 4 kHz) and speech reception threshold (SRT); and dichotomized for bilateral hearing loss of more than 15 dB HL and abnormal SRT.
Included in the study were 1608 children (mean SD age, 11.5 0.5 years; 812 50.5% male children; 1365 84.9% European and 24315.1% non-European) and 1642 adults (mean SD age, 43.7 5.1 years; 1442 87.8% female adults; 1430 87.1% European and 212 12.9% non-European individuals). In adults, both PRS1 and PRS2 were associated with hearing thresholds. For each SD increment in PRS1 and PRS2, hearing thresholds were 0.4 (95% CI, 0-0.8) decibel hearing level (dB HL) and 0.9 (95% CI, 0.5-1.2) dB HL higher on the high Fletcher index, respectively. Each SD increment in PRS increased the odds of adult hearing loss of more than 15 dB HL by 10% to 30% (OR for PRS1, 1.1; 95% CI, 1.0-1.3; OR for PRS2, 1.3; 95% CI, 1.1-1.5). Similar but attenuated patterns were noted in children (OR for PRS1, 1.1; 95% CI, 0.8-1.2; OR for PRS2, 1.2; 95% CI, 1.0-1.5). Both PRSs showed minimal evidence of associations with speech reception thresholds or abnormal SRT in children or adults.
This population-based cross-sectional study of PRSs for self-reported hearing difficulty among adults found an association with hearing ability in mid-childhood. This adds to the evidence that age-related hearing loss begins as early as the first decade of life and that polygenic inheritance may play a role together with other environmental risk factors.
Obesity is characterized by heightened inflammation, and both phenotypes are associated with hearing loss. We aimed to determine if inflammation mediates the associations between obesity and hearing ...ability in mid-childhood and mid-life.
Participants: 1165 11- to 12-year-old children and 1316 parents in the population-based cross-sectional Child Health CheckPoint within the Longitudinal Study of Australian Children. Adiposity measures: Body mass index (BMI) classified as normal, overweight and obesity; waist-to-height ratio (WHtR) classified as <0.5 and ≥0.5; fat mass index. Inflammatory biomarkers: Serum glycoprotein A (GlycA); high-sensitivity C-reactive protein (hsCRP). Audiometry: Composite high Fletcher Index (mean threshold of 1, 2, 4 kHz) in the better ear.
Causal mediation analysis decomposed a 'total effect' (obesity on hearing status) into 'indirect' effect via a mediator (eg GlycA, hsCRP) and 'direct' effect via other pathways, adjusting for age, sex and socioeconomic position.
Compared to adults with BMI within the normal range, those with obesity had hearing thresholds 1.9 dB HL (95% CI 1.0-2.8) higher on the high Fletcher Index; 40% of the total effect was mediated via GlycA (indirect effect: 0.8 dB HL, 95% CI 0.1-1.4). Children with obesity had hearing thresholds 1.3 dB HL (95% CI 0.2-2.5) higher than those with normal BMI, of which 67% (indirect effect: 0.9 dB HL, 95% CI 0.4-1.4) was mediated via GlycA. Similar mediation effects were noted using other adiposity measures. Similar but less marked mediation effects were observed when hsCRP was used as the inflammatory biomarker (6-23% in adults and 23-33% in children).
Inflammation may play an important mediating role in the modest hearing reductions associated with obesity, particularly in children. These findings offer insights into possible mechanisms and early prevention strategies for hearing loss.
Abstract
Study Objectives
To examine longitudinal, bidirectional associations among behavioral sleep problems, internalizing and externalizing symptoms, and domains of health-related quality of life ...(HRQoL) from early childhood to adolescence in a population sample of Australian children.
Method
Data were drawn from the Longitudinal Study of Australian Children, a national prospective cohort study with 4983 children participating in the Kindergarten cohort. Data were collected when children were aged 4–5, 6–7, 8–9, 10–11, and 12–13 years. At each study wave, the primary parent (97% mothers) reported on behavioral child sleep problems, internalizing and externalizing symptoms, and HRQoL domains (psychosocial and physical). Cross-lagged structural equation models were used to evaluate bidirectional associations.
Results
At nearly every age, behavioral sleep problems were associated with worse subsequent psychosocial and physical HRQoL. Despite bidirectional associations between mental health and HRQoL at many waves, HRQoL domains more strongly predicted later internalizing symptoms, while externalizing symptoms more strongly predicted later HRQoL. Many of the bidirectional associations among sleep, mental health, and HRQoL were found earlier in childhood.
Conclusions
Behavioral sleep problems may forecast later HRQoL psychosocial and physical impairments. Attending to both sleep problems and HRQoL could prevent the progression of internalizing conditions, while a focus on externalizing concerns could prevent the worsening of these symptoms, sleep problems, and HRQoL, particularly during the transition to school.
Students define academic competence across two axes: developing skills and understanding (mastery) versus comparisons with peers (performance), and achieving goals (approach) versus avoiding failure ...(avoidance). We aimed to examine the longitudinal association between achievement goals and adolescent depressive symptoms.
We analysed data from the Kindergarten (recruited at age 4–5 years; born between March, 1999, and February, 2000; recruited from March, 2004 to November, 2004) and Baby (recruited at age 0–1 years; born between March, 2003, and February, 2004; recruited from March, 2004 to January, 2005) cohorts of the Longitudinal Study of Australian Children. Participants were identified through the Medicare enrolment database and sampled using a randomised selection stratified by postcode to represent the Australian population. Achievement goals were measured at age 12–13 years with the Achievement Goal Questionnaire (ranges from 1 to 7 on each of the four subscales), and depressive symptoms with the Short Mood and Feelings Questionnaire (score ranges from 0 to 26, with higher scores indicating more severe symptoms) at ages 14–15 years (both cohorts) and 16–17 years (Kindergarten cohort only). Analyses were linear multilevel and traditional regressions, with confounder adjustment, for participants with available data on the exposures, confounders, and outcome.
We included 3200 participants (1585 female and 1615 male) from the Kindergarten cohort and 2671 participants (1310 female and 1361 male) from the Baby cohort. A 1-point increase in mastery-approach goals was associated with decreased depressive symptom severity score (Kindergarten, –0·33 95% CI –0·52 to –0·15; Baby, –0·29 –0·54 to –0·03), while a 1-point increase in mastery-avoidance goals was associated with increased depressive symptom severity score (Kindergarten, 0·35 95% CI 0·21 to 0·48; Baby, 0·44 0·25 to 0·64). A 1-point increase in performance-avoidance goals was associated with increased depressive symptom severity score in the Kindergarten cohort but not the Baby cohort (Kindergarten, 0·26 95% CI 0·11 to 0·41; Baby, –0·04 –0·27 to 0·19). We found little evidence of an association between depressive symptom severity and performance-approach goals.
Depressive symptoms in adolescents were associated with their achievement goals, which could be targetable risk factors for future trials to investigate whether school-based interventions that aim to enhance factors consistent with mastery goals (ie, learning skills and understanding the subject, rather than assessing competence in comparison to peers) could prevent depression in adolescents.
Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society.
Introduction
Studying parent‐child pair health provides the opportunity to identify risk factors and opportunities for oral health prevention and intervention focusing on the family context. The aim ...of this study was to describe the oral health of children aged 11‐12 years and their parents in a national sample of parent‐child dyads in Australia.
Methods
The Child Health CheckPoint is a study of 11 to 12‐year‐old children and one parent nested within the Longitudinal Study of Australian Children, a nationally representative cohort study. In 2015‐16, the study collected two‐dimensional photographic intra‐oral images and was scored using visual assessments of the teeth, oral hygiene and malocclusion.
Results
Of the 1874 CheckPoint families, 1396 biological parent‐child pairs had at least one oral health measure recorded. Over two‐thirds of children had moderate to severe gingival inflammation (69.7%, 95%CI 64.7‐74.9). Parents had a lower proportion of poor oral hygiene (2.1%, 95% CI 1.4‐3.0) than children (13.0%, 95% CI 11.3‐14.9). High concordance was seen in the Modified Gingival Index correlation coefficient 0.49 (95%CI 0.44‐0.53).
Conclusion
The high concordance in gingival health between child‐parent pairs supports the familial and behavioural links established in previous studies. Children had poorer oral hygiene but fewer visible dental caries lesions than their parents. As dental caries is a chronic and cumulative disease, preventive interventions targeting children's oral hygiene are needed.
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