Understanding risk and causal mechanisms for developing obesity in infants and young children: A National Institutes of Health workshop.

Obesity in children remains a major public health problem, with the current prevalence in youth ages 2-19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29-30, 2021, the National Institutes of Health convened a virtual workshop on "Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children." The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi-disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms.

Genome-wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits.

BACKGROUND: The number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta-genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). METHODS: We studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months), and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism-based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models. RESULTS: Early-life vocabulary size was modestly heritable (SNP-h2 = 0.08-0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (rg = -0.74), highlighting developmental heterogeneity. CONCLUSIONS: The genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.

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

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

Study protocol: Generation Victoria (GenV) special care nursery registry.

Introduction: Newborn babies who require admission for specialist care can experience immediate and sometimes lasting impacts. For babies admitted to special care nurseries (SCN), there is no dataset comparable to that of the Australian and New Zealand Neonatal Network (ANZNN), which has helped improve the quality and consistency of neonatal intensive care through standardised data collection. Objectives: We aim to establish a proof-of-concept, Victoria-wide registry of babies admitted to SCN, embedded within the whole-of-Victoria Generation Victoria (GenV) cohort. Methods: This prototype registry is a depth sub-cohort nested within GenV, targeting all babies born in Victoria from Oct-2021 to Oct-2023. Infants admitted to SCN are eligible. The minimum dataset will be harmonised with ANZNN for common constructs but also include SCN-only items, and will cover maternal, antenatal, newborn, respiratory/respiratory support, cardiac, infection, nutrition, feeding, cerebral and other items. As well as the dataset, this protocol outlines the anticipated cohort, timeline for this registry, and how this will serve as a resource for longitudinal research through its integration with the GenV longitudinal cohort and linked datasets. Conclusion: The registry will provide the opportunity to better understand the health and future outcomes of the large and growing cohort of children that require specialist care after birth. The data would generate translatable evidence and could lay the groundwork for a stand-alone ongoing clinical quality registry post-GenV.

Spoken Expressive Vocabulary in 2-Year-Old Children with Hearing Loss: A Community Study.

Through a cross-sectional community study of 2044 children aged 2 years, we (1) examine the impact of hearing loss on early spoken expressive vocabulary outcomes and (2) investigate how early intervention-related factors impact expressive vocabulary outcomes in children with hearing loss predominantly identified through universal newborn hearing screening. We used validated parent/caregiver-reported checklists from two longitudinal cohorts (302 children with unilateral or bilateral hearing loss, 1742 children without hearing loss) representing the same population in Victoria, Australia. The impact of hearing loss and amplification-related factors on vocabulary was estimated using g-computation and multivariable linear regression. Children with versus without hearing loss had poorer expressive vocabulary scores, with mean scores for bilateral loss 0.5 (mild loss) to 0.9 (profound loss) standard deviations lower and for unilateral loss marginally (0.1 to 0.3 standard deviations) lower. For children with hearing loss, early intervention and amplification by 3 months, rather than by 6 months or older, resulted in higher expressive vocabulary scores. Children with hearing loss demonstrated delayed spoken expressive vocabulary despite whole-state systems of early detection and intervention. Our findings align with calls to achieve a 1-2-3 month timeline for early hearing detection and intervention benchmarks for screening, identification, and intervention.

Socioeconomic disadvantage and polygenic risk for high BMI magnify obesity risk across childhood: a longitudinal, population, cohort study.

BACKGROUND: Across the life course, socioeconomic disadvantage disproportionately afflicts those with genetic predispositions to inflammatory diseases. We describe how socioeconomic disadvantage and polygenic risk for high BMI magnify the risk of obesity across childhood, and using causal analyses, explore the hypothetical impact of intervening on socioeconomic disadvantage to reduce adolescent obesity. METHODS: Data were drawn from a nationally representative Australian birth cohort, with biennial data collection between 2004 and 2018 (research and ethics committee approved). We generated a polygenic risk score for BMI using published genome-wide association studies. We measured early-childhood disadvantage (age 2-3 years) with a neighbourhood census-based measure and a family-level composite of parent income, occupation, and education. We used generalised linear regression (Poisson-log link) to estimate the risk of overweight or obesity (BMI ≥85th percentile) at age 14-15 years for children with early-childhood disadvantage (quintiles 4-5) versus average (quintile 3) and least disadvantage (quintiles 1-2), for those with high and low polygenic risk separately. FINDINGS: For 1607 children (n=796 female, n=811 male; 31% of the original cohort [N=5107]), polygenic risk and disadvantage were both associated with overweight or obesity; effects of disadvantage were more marked as polygenic risk increased. Of children with polygenic risk higher than the median (n=805), 37% of children living in disadvantage at age 2-3 years had an overweight or obese BMI by adolescence, compared with 26% of those with least disadvantage. For genetically vulnerable children, causal analyses indicated that early neighbourhood intervention to lessen disadvantage (to quintile 1-2) would reduce risk of adolescent overweight or obesity by 23% (risk ratio 0·77; 95% CI 0·57-1·04); estimates for improving family environments were similar (0·59; 0·43-0·80). INTERPRETATION: Actions addressing socioeconomic disadvantage could mitigate polygenic risk for developing obesity. This study benefits from population-representative longitudinal data but is limited by sample size. FUNDING: Australian National Health and Medical Research Council.

Greenness modifies the association between ambient air pollution and cognitive function in Australian adolescents, but not in mid-life adults.

Exposure to ambient air pollution has been associated with reduced cognitive function in childhood and later life, with too few mid-life studies to draw conclusions. In contrast, residential greenness has been associated with enhanced cognitive function throughout the lifecourse. Here we examine the extent to which (1) ambient air pollution and residential greenness predict later cognitive function in adolescence and mid-life, and (2) greenness modifies air pollution-cognitive function associations. PARTICIPANTS: 6220 adolescents (51% male) and 2623 mid-life adults (96% mothers) from the Longitudinal Study of Australian Children. MEASURES: Exposures: Annual average particulate matter <2.5 µm (PM2.5), nitrogen dioxide (NO2) and greenness (Normalised Difference Vegetation Index) for residential addresses from validated land-use regression models over a 10-13-year period. OUTCOMES: Cognitive function from CogState tests of attention, working memory and executive function, dichotomised into poorer (worst quartile) versus not poor. ANALYSES: Adjusted mixed-effects generalised linear models with residential greenness assessed as an effect modifier (high vs. low divided at median). The annual mean for PM2.5 and NO2 across exposure windows was 6.3-6.8 µg/m3, and 5.5-7.1 ppb, respectively. For adolescents, an IQR increment of NO2 was associated with 19-24% increased odds of having poorer executive function across all time windows, while associations weren't observed between air pollution and other outcomes. For adults, high NO2 predicted poorer cognitive function across all outcomes, while high PM2.5 predicted poorer attention only. There was little evidence of associations between greenness and cognitive function in adjusted models for both generations. Interactions were found between residential greenness, air pollutants and cognitive function in adolescents, but not adults. The magnitude of effects was similar across generations and exposure windows. Findings highlight the potential benefits of cognitive health associated with the regulation of air pollution and urban planning strategies for increasing green spaces and vegetation.

Association of Polygenic Risk Scores for Hearing Difficulty in Older Adults With Hearing Loss in Mid-Childhood and Midlife: A Population-Based Cross-sectional Study Within the Longitudinal Study of Australian Children.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: 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. Results: 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 243[15.1%] 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. Conclusions and Relevance: 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.

Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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=1.3×10-17) and -0.41 SD for total lipids in medium HDL with SGA (95% CI: -0.56 to -0.25, P=2.6×10-7), 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. CONCLUSIONS: 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.

Using machine-learning methods to identify early-life predictors of 11-year language outcome.

BACKGROUND: Language is foundational for neurodevelopment and quality of life, but an estimated 10% of children have a language disorder at age 5. Many children shift between classifications of typical and low language if assessed at multiple times in the early years, making it difficult to identify which children will have persisting difficulties and benefit most from support. This study aims to identify a parsimonious set of preschool indicators that predict language outcomes in late childhood, using data from the population-based Early Language in Victoria Study (n = 839). METHODS: Parents completed surveys about their children at ages 8, 12, 24, and 36 months. At 11 years, children were assessed using the Clinical Evaluation of Language Fundamentals 4th Edition (CELF-4). We used random forests to identify which of the 1990 parent-reported questions best predict children's 11-year language outcome (CELF-4 score ≤81 representing low language) and used SuperLearner to estimate the accuracy of the constrained sets of questions. RESULTS: At 24 months, seven predictors relating to vocabulary, symbolic play, pragmatics and behavior yielded 73% sensitivity (95% CI: 57, 85) and 77% specificity (95% CI: 74, 80) for predicting low language at 11 years. [Corrections made on 5 May 2023, after first online publication: In the preceding sentence 'motor skills' has been corrected to 'behavior' in this version.] At 36 months, 7 predictors relating to morphosyntax, vocabulary, parent-child interactions, and parental stress yielded 75% sensitivity (95% CI: 58, 88) and 85% specificity (95% CI: 81, 87). Measures at 8 and 12 months yielded unsatisfactory accuracy. CONCLUSIONS: We identified two short sets of questions that predict language outcomes at age 11 with fair accuracy. Future research should seek to replicate results in a separate cohort.

Improving Cohort-Hospital Matching Accuracy through Standardization and Validation of Participant Identifiable Information.

Linking very large, consented birth cohorts to birthing hospitals clinical data could elucidate the lifecourse outcomes of health care and exposures during the pregnancy, birth and newborn periods. Unfortunately, cohort personally identifiable information (PII) often does not include unique identifier numbers, presenting matching challenges. To develop optimized cohort matching to birthing hospital clinical records, this pilot drew on a one-year (December 2020-December 2021) cohort for a single Australian birthing hospital participating in the whole-of-state Generation Victoria (GenV) study. For 1819 consented mother-baby pairs and 58 additional babies (whose mothers were not themselves participating), we tested the accuracy and effort of various approaches to matching. We selected demographic variables drawn from names, DOB, sex, telephone, address (and birth order for multiple births). After variable standardization and validation, accuracy rose from 10% to 99% using a deterministic-rule-based approach in 10 steps. Using cohort-specific modifications of the Australian Statistical Linkage Key (SLK-581), it took only 3 steps to reach 97% (SLK-5881) and 98% (SLK-5881.1) accuracy. We conclude that our SLK-5881 process could safely and efficiently achieve high accuracy at the population level for future birth cohort-birth hospital matching in the absence of unique identifier numbers.

Fat-Soluble Vitamers: Parent-Child Concordance and Population Epidemiology in the Longitudinal Study of Australian Children.

Fat-soluble vitamers (FSV) are a class of diverse organic substances important in a wide range of biological processes, including immune function, vision, bone health, and coagulation. Profiling FSV in parents and children enables insights into gene-environment contributions to their circulating levels, but no studies have reported on the population epidemiology of FSV in these groups as of yet. In this study, we report distributions of FSV, their parent-child concordance and variation by key characteristics for 2490 children (aged 11-12 years) and adults (aged 28-71 years) in the Child Health CheckPoint of the Longitudinal Study of Australian Children. Ten A, D, E and K vitamers were quantified using a novel automated LC-MS/MS method. All three K vitamers (i.e., K1, MK-4, MK-7) and 1-α-25(OH)2D3 were below the instrument detection limit and were removed from the present analysis. We observed a strong vitamer-specific parent-child concordance for the six quantifiable A, D and E FSVs. FSV concentrations all varied by age, BMI, and sex. We provide the first cross-sectional population values for multiple FSV. Future studies could examine relative genetic vs. environmental determinants of FSV, how FSV values change longitudinally, and how they contribute to future health and disease.

The effect of adverse and positive experiences on inflammatory markers in Australian and UK children.

Background: The relationship between childhood adversity and inflammation is well-established. Examination of positive experiences can provide a more complete understanding of intervention opportunities. We investigated associations of adverse and positive experiences, and their intersection, with inflammation in children and adolescents. Methods: Data sources: Longitudinal Study of Australian Children (LSAC; N = 1237) and Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3488). Exposures: Adverse and positive experiences assessed repeatedly (LSAC: 0-11 years; ALSPAC: 0-15 years). Outcomes: Inflammation quantified by high sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA) (LSAC: 11-12 years; ALSPAC: 15.5 years). Analyses: Linear regression on the log-transformed outcomes estimated the relative difference in inflammatory markers with adverse/positive experiences, adjusting for socio-demographics and concurrent positive/adverse experiences, respectively. Results: Most associations were in the expected direction but differed in magnitude by exposure, outcome and cohort. Across both cohorts, adverse experiences were associated with up to 7.3% higher hsCRP (95% CI: -18.6%, 33.2%) and up to 2.0% higher GlycA (95% CI: 0.5%, 3.5%); while positive experiences were associated with up to 22.1% lower hsCRP (95% CI: -49.0%, 4.7%) and 1.3% lower GlycA (95% CI: -2.7%, 0.2%). In LSAC, the beneficial effect of positive experiences on inflammation was more pronounced among those with fewer concurrent adverse experiences. Conclusion: Across two cohorts, we found small but directionally consistent associations between adverse experiences and higher inflammation, and positive experiences and lower inflammation, particularly for GlycA. Future research should give further consideration to positive experiences to complement the current focus on adversity and inform the design and evaluation of early life interventions.

Your best day: An interactive app to translate how time reallocations within a 24-hour day are associated with health measures.

Reallocations of time between daily activities such as sleep, sedentary behavior and physical activity are differentially associated with markers of physical, mental and social health. An individual's most desirable allocation of time may differ depending on which outcomes they value most, with these outcomes potentially competing with each other for reallocations. We aimed to develop an interactive app that translates how self-selected time reallocations are associated with multiple health measures. We used data from the Australian Child Health CheckPoint study (n = 1685, 48% female, 11-12 y), with time spent in daily activities derived from a validated 24-h recall instrument, %body fat from bioelectric impedance, psychosocial health from the Pediatric Quality of Life Inventory and academic performance (writing) from national standardized tests. We created a user-interface to the compositional isotemporal substitution model with interactive sliders that can be manipulated to self-select time reallocations between activities. The time-use composition was significantly associated with body fat percentage (F = 2.66, P < .001), psychosocial health (F = 4.02, P < .001), and academic performance (F = 2.76, P < .001). Dragging the sliders on the app shows how self-selected time reallocations are associated with the health measures. For example, reallocating 60 minutes from screen time to physical activity was associated with -0.8 [95% CI -1.0 to -0.5] %body fat, +1.9 [1.4 to 2.5] psychosocial score and +4.5 [1.8 to 7.2] academic performance. Our app allows the health associations of time reallocations to be compared against each other. Interactive interfaces provide flexibility in selecting which time reallocations to investigate, and may transform how research findings are disseminated.

Multi-omics analysis from archival neonatal dried blood spots: limitations and opportunities.

Newborn screening (NBS) programs operate in many countries, processing millions of dried bloodspot (DBS) samples annually. In addition to early identification of various adverse health outcomes, these samples have considerable potential as a resource for population-based research that could address key questions related to child health. The feasibility of archival DBS samples for emerging targeted and untargeted multi-omics analysis has not been previously explored in the literature. This review aims to critically evaluate the latest advances to identify opportunities and challenges of applying omics analyses to NBS cards in a research setting. Medline, Embase and PubMed databases were searched to identify studies utilizing DBS for genomic, proteomic and metabolomic assays. A total of 800 records were identified after removing duplicates, of which 23 records were included in this review. These papers consisted of one combined genomic/metabolomic, four genomic, three epigenomic, four proteomic and 11 metabolomic studies. Together they demonstrate that the increasing sensitivity of multi-omic analytical techniques makes the broad use of NBS samples achievable for large cohort studies. Maintaining the pre-analytical integrity of the DBS sample through storage at temperatures below -20 °C will enable this important resource to be fully realized in a research capacity.

Can adult polygenic scores improve prediction of body mass index in childhood?

BACKGROUND/OBJECTIVES: Modelling genetic pre-disposition may identify children at risk of obesity. However, most polygenic scores (PGSs) have been derived in adults, and lack validation during childhood. This study compared the utility of existing large-scale adult-derived PGSs to predict common anthropometric traits (body mass index (BMI), waist circumference, and body fat) in children and adults, and examined whether childhood BMI prediction could be improved by combining PGSs and non-genetic factors (maternal and earlier child BMI). SUBJECTS/METHODS: Participants (n = 1365 children, and n = 2094 adults made up of their parents) were drawn from the Longitudinal Study of Australian Children. Children were weighed and measured every two years from 0-1 to 12-13 years, and adults were measured or self-reported measurements were obtained concurrently (average analysed). Participants were genotyped from blood or oral samples, and PGSs were derived based on published genome-wide association studies. We used linear regression to compare the relative utility of these PGSs to predict their respective traits at different ages. RESULTS: BMI PGSs explained up to 12% of child BMI z-score variance in 10-13 year olds, compared with up to 15% in adults. PGSs for waist circumference and body fat explained less variance (up to 8%). An interaction between BMI PGSs and puberty (p = 0.001-0.002) suggests the effect of some variants may differ across the life course. Individual BMI measures across childhood predicted 10-60% of the variance in BMI at 12-13 years, and maternal BMI and BMI PGS each added 1-9% above this. CONCLUSION: Adult-derived PGSs for BMI, particularly those derived by modelling between-variant interactions, may be useful for predicting BMI during adolescence with similar accuracy to that obtained in adulthood. The level of precision presented here to predict BMI during childhood may be relevant to public health, but is likely to be less useful for individual clinical purposes.

The role of Australian clinical quality registries in pregnancy care: A scoping review.

BACKGROUND: Pregnancy represents a time of increased morbidity and mortality for women and their infants. Clinical quality registries (CQRs) collect, analyse and report key healthcare quality indicators for patient cohorts to improve patient care. There are limited data regarding existing CQRs in pregnancy. This scoping review aimed to: (1) identify Australian CQRs specific to pregnancy care and describe their general characteristics; and (2) outline their aims and measured outcomes METHODS: The scoping review was undertaken according to Joanna Briggs Institute guidelines. CQRs were identified using a systematic approach from publications (Ovid MEDLINE, PubMed, Google Scholar), peer consultation, the Australian register of clinical registries and web searches. Details surrounding general characteristics, aims and outcomes were collated. RESULTS: We identified two primary sources of information about pregnancy care. (1) Six CQRs are specific to pregnancy (Australia and New Zealand twin-twin transfusion syndrome registry, Australian Pregnancy Register for women with epilepsy and those taking anti-epileptic drugs, National Register of Antipsychotic Medication in Pregnancy, Australasian Maternity Outcomes Surveillance System, Neonatal Alloimmune Thrombocytopaenia Registry and the Diabetes in Pregnancy clinical register). (2) Fourteen observational cohort studies were facilitated by non-pregnancy-specific CQRs where a subsection of patients underwent pregnancy. CONCLUSIONS: Australian CQRs currently report varied information regarding some selected conditions during pregnancy and offer therapeutic and epidemiological insight into their care. Further research into their effectiveness is warranted. We note the lack of a CQR spanning the common problems of pregnancy in general, where significant health, service and economic gains are possible.