Childhood adversity and DNA methylation in two population-based cohorts.

Childhood adversity affects later health, but the underlying molecular mechanisms are unclear. Although there is some evidence from animal models and case-control studies of a role for DNA methylation, evidence from human population-based studies is limited. In two cohorts (mothers from the Avon Longitudinal Study of Parents and Children, ALSPAC, n = 780 and women from the MRC National Survey of Health and Development, NSHD, n = 552), we assessed the association of seven adverse childhood experiences (ACEs: parental physical illness, parental mental illness, parental death, parental separation, suboptimal maternal bonding, childhood illness and child maltreatment) as well as their combination (ACE score) with genome-wide DNA methylation levels measured using the Illumina Infinium HumanMethylation450 BeadChip in peripheral blood at mean age 47 years (ALSPAC) and in buccal cells at age 53 years (NSHD). CpG sites with a genome-wide false discovery rate (FDR) below 0.05 and differentially methylated regions (DMRs) with one-step Sidák correction p-values below 0.05 in each cohort were examined in the other cohort. No individual CpG sites replicated across cohorts. However, nine DMRs replicated across cohorts respectively associated with the ACE score (one region), parental mental illness (two regions), parental physical illness (three regions) and parental death (three regions). These observations indicate that some adverse childhood experiences, notably those related to parental health, may leave imprints on peripheral DNA methylation that persist to mid-life.

Frailty in older-age European migrants: Cross-sectional and longitudinal analyses of the Survey of Health, Aging and Retirement in Europe (SHARE).

Frailty correlates with morbidity and is superior to chronological age in predicting mortality. Frailty of older migrants has important implications for the demands placed on healthcare systems. Examining 95,635 Europeans in the Survey of Health, Aging and Retirement in Europe, we investigated cross-sectional and longitudinal associations between migration and frailty at ages >50 years. We examined whether associations differed by countries' level of healthcare coverage and access for migrants and tested mediation by home-ownership and citizenship. Cross-sectionally, first-generation migrants >50 years old were, on average, 16.4% (95% confidence interval [CI]: 14.6, 18.2%) frailer than non-migrants after confounder-adjustment. This decreased to 12.1% (95% CI: 10.1, 14.1%) after adjustment for citizenship. The strength of association between migrant status and frailty was greater in migrants from low-or-middle-income countries, compared with migrants from high-income countries. Migrants into Northern, Western and Eastern Europe were 37.3% (95% CI: 33.2, 41.5%), 12.2% (95% CI: 10.0, 14.6%) and 5.0% (95% CI: 0.5, 9.6%) frailer than non-migrants, respectively, but migrants into Southern Europe were no frailer than non-migrants. The strength of association between migrant status and frailty was greater in countries with lower healthcare coverage and access for migrants. However, citizenship attenuated this difference. Longitudinally, migrants were frailer than non-migrants at 50 years old and trajectories converged over time until migrants and non-migrants were equally frail by 80-90 years. Our work finds no evidence of the 'healthy migrant effect' outside of Southern Europe in older migrants and suggests that acculturation is a key determinant of migrant health.

DNA methylation from birth to late adolescence and development of multiple-risk behaviours.

BACKGROUND: Risk behaviours in adolescence are linked to poor educational attainment and health and other outcomes in young adulthood. We explored whether there are molecular mechanisms associated with the development, or the result, of multiple risk behaviours (MRBs). METHODS: MRBs (antisocial behaviour and delinquency, traffic-related risk behaviour, risky sexual behaviour, lack of exercise) and their sumscore were characterized based on self-reported questions at age 7 and 17 within the ARIES subsample of the ALSPAC birth cohort, and were linked to DNA methylation at over 485,000 CpG sites at ages 0,7 and 17. Associations were determined for participants with complete data (n = 227-575). RESULTS: There was weak evidence of associations between cumulative MRBs and methylation at cg01783492 and cg16720578 at age 17. DNA methylation at age 17 was associated with risky sexual behaviour (cg22883332), lack of exercise (cg03152353, cg20056908, cg20571116) and substance use (cg02188400, cg13906377). No associations between DNA methylation and individual risk behaviours at age 7 were observed. DNA methylation at age 7 might predispose for traffic-related risk behaviour (cg24683561) and substance use (cg08761410) at age 17. LIMITATIONS: Main limitations are absence of information on directly measured blood cell type proportions and tissue specificity, and a modest sample size. CONCLUSIONS: Cumulative MRB in late adolescence was associated with effects on DNA methylation. More specifically, risky sexual behaviour and sedentary behaviour are associated with changes in DNA methylation, while DNA methylation in childhood may predict later traffic-related risky behaviour. For substance use effects in both temporal directions were observed.

Longitudinal study of the associations between change in sedentary behavior and change in adiposity during childhood and adolescence: Gateshead Millennium Study.

BACKGROUND: Sedentary time (ST) has been reported to have a range of negative health effects in adults, however, the evidence for such effects among children and adolescents is sparse. The primary aim of the study was to examine associations between changes in sedentary behavior (time and fragmentation) and changes in adiposity across childhood and adolescence. METHODS: Participants were recruited as part of the Gateshead Millennium Study. Measures were taken at age 7 (n=502), 9 (n=506), 12 (n=420) and 15 years (n=306). Participants wore an ActiGraph GT1M and accelerometer epochs were 'sedentary' when recorded counts were ⩽25 counts per 15 s. ST was calculated and fragmentation (SF) was assessed by calculating the number of sedentary bouts per sedentary hour. Associations of changes in ST and SF with changes in adiposity (body mass index (BMI), and fat mass index (FMI)) were examined using bivariate linear spline models. RESULTS: Increasing ST by 1% per year was associated with an increase in BMI of 0.08 kg m-2 per year (95% CI: 0.06-0.10; P<0.001) and FMI of 0.15 kg m-2 per year (0.11-0.19; P<0.001). Change in SF was associated with BMI and FMI (P<0.001). An increase of 1 bout per sedentary hour per year (that is, sedentary time becoming more fragmented) was associated with an increase in BMI of 0.07 kg m-2 per year (0.06-0.09; P<0.001) and an increase in FMI of 0.14 kg m-2 per year (0.10-0.18; P<0.001) over the 8 years period. However, an increase in SF between 9-12 years was associated with a 0.09 kg m-2 per year decrease in BMI (-0.18-0.00; P=0.046) and 0.11 kg m-2 per year decrease in FMI (-0.22-0.00; P=0.049). CONCLUSIONS: Increased ST and increased SF from 7-15 years were associated with increased adiposity. This is the first study to show age-specific associations between change in objectively measured sedentary behavior and adiposity after adjustment of moderate-to-vigorous-intensity physical activity in children and adolescents. The study suggests that, targeting sedentary behavior for obesity prevention may be most effective during periods in which we see large increases in ST.

Body mass index trajectories from 2 to 18 years - exploring differences between European cohorts.

BACKGROUND: In recent decades, there has been an increase in the prevalence of childhood overweight in most high-income countries. Within northern Europe, prevalence tends to be higher in the UK compared with the Scandinavian countries. We aimed to study differences in body mass index (BMI) trajectories between large cohorts of children from UK and Scandinavian populations. METHODS: We compared BMI trajectories in participants from the English Avon Longitudinal Study of Parents and Children born in 1991-1993 (ALSPAC) (N = 6517), the Northern Finland Birth Cohorts born in 1966 (NFBC1966) (N = 3321) and 1986 (NFBC1986) (N = 4764), and the Danish Aarhus Birth Cohort born in 1990-1992 (ABC) (N = 1920). We used multilevel models to estimate BMI trajectories from 2 to 18 years. We explored whether cohort differences were explained by maternal BMI, height, education or smoking during pregnancy and whether differences were attributable to changes in the degree of skew in the BMI distribution. RESULTS: Differences in mean BMI between the cohorts were small but emerged early and persisted in most cases across childhood. Girls in ALSPAC had a higher BMI than all other cohorts throughout childhood, e.g. compared with the NFBC1986 BMI was 2.2-3.5% higher. For boys, the difference emerging over time (comparing the two NFBC's) exceeded the differences across populations (comparing NFBC1986, ABC and ALSPAC). BMI distribution demonstrated increasing right skew with age. CONCLUSION: Population-level differences between cohorts were small, tended to emerge very early, persisted across childhood, and demonstrated an increase in the right-hand tail of the BMI distribution.

Using Super-Imposition by Translation And Rotation (SITAR) to relate pubertal growth to bone health in later life: the Medical Research Council (MRC) National Survey of Health and Development.

BACKGROUND: To explore associations between pubertal growth and later bone health in a cohort with infrequent measurements, using another cohort with more frequent measurements to support the modelling, data from the Medical Research Council (MRC) National Survey of Health and Development (2-26 years, 4901/30 004 subjects/measurements) and the Avon Longitudinal Study of Parents And Children (ALSPAC) (5-20 years) (10 896/74 120) were related to National Survey of Health and Development (NSHD) bone health outcomes at 60-64 years. METHODS: NSHD data were analysed using Super-Imposition by Translation And Rotation (SITAR) growth curve analysis, either alone or jointly with ALSPAC data. Improved estimation of pubertal growth parameters of size, tempo and velocity was assessed by changes in model fit and correlations with contemporary measures of pubertal timing. Bone outcomes of radius [trabecular volumetric bone mineral density (vBMD) and diaphysis cross-sectional area (CSA)] were regressed on the SITAR parameters, adjusted for current body size. RESULTS: The NSHD SITAR parameters were better estimated in conjunction with ALSPAC, i.e. more strongly correlated with pubertal timing. Trabecular vBMD was associated with early height tempo, whereas diaphysis CSA was related to weight size, early tempo and slow velocity, the bone outcomes being around 15% higher for the better vs worse growth pattern. CONCLUSIONS: By pooling NSHD and ALSPAC data, SITAR more accurately summarized pubertal growth and weight gain in NSHD, and in turn demonstrated notable associations between pubertal timing and later bone outcomes. These associations give insight into the importance of the pubertal period for future skeletal health and osteoporosis risk.

Examining the association between early life social adversity and BMI changes in childhood: a life course trajectory analysis.

BACKGROUND: A number of studies have found associations between multiple aspects of social adversity and obesity in childhood, yet this research has largely been limited to cross-sectional data. OBJECTIVES: This study aimed to address this limitation by using life course trajectory methods to determine whether multiple aspects of social adversity in early childhood are associated with changes in body mass index (BMI) throughout childhood. METHODS: Associations between multiple measures of social adversity from birth to 4 years and subsequent BMI trajectories to age 17 were examined in 7021 children in the Avon Longitudinal Study of Parents and Children. RESULTS: Higher BMI throughout ages 12-17 were observed for children whose parents had separated, were exposed to frequent residential mobility or who experienced moderate or great household financial difficulty in early childhood. After adjustment for confounding variables, associations were attenuated but remained for both moderate (two moves) and high (≥3 moves) residential mobility (mean % difference in BMI at age 17 for children experiencing moderate and high residential mobility before age 4 compared with those experiencing no moves: 2.3; 95% CI: 0.5-4.2; P = 0.015 and 4.2; 95% CI: 1.4-7.0; P = 0.004, respectively). CONCLUSIONS: Associations between BMI and social adversity in childhood are present but largely explained by background socioeconomic position. However, there remain small but important differences between the BMI of children who are exposed to frequent residential mobility in early childhood after adjustment for socioeconomic and other confounders.

Agreement between routine and research measurement of infant height and weight.

UNLABELLED: In many countries, routine data relating to growth of infants are collected as a means of tracking health and illness up to school age. These have potential to be used in research. For health monitoring and research, data should be accurate and reliable. This study aimed to determine the agreement between length/height and weight measurements from routine infant records and researcher-collected data. METHODS: Height/length and weight at ages 6, 12 and 24 months from the longitudinal UK birth cohort (born in Bradford; n=836-1280) were compared with routine data collected by health visitors within 2 months of the research data (n=104-573 for different comparisons). Data were age adjusted and compared using Bland Altman plots. RESULTS: There was agreement between data sources, albeit weaker for height than for weight. Routine data tended to underestimate length/height at 6 months (0.5 cm (95% CI -4.0 to 4.9)) and overestimate it at 12 (-0.3 cm (95% CI -0.5 to 4.0)) and 24 months (0.3 cm (95% CI -4.0 to 3.4)). Routine data slightly overestimated weight at all three ages (range -0.04 kg (95% CI -1.2 to 0.9) to -0.04 (95% CI -0.7 to 0.6)). Limits of agreement were wide, particularly for height. Differences were generally random, although routine data tended to underestimate length in taller infants and underestimate weight in lighter infants. CONCLUSIONS: Routine data can provide an accurate and feasible method of data collection for research, though wide limits of agreement between data sources may be observed. Differences could be due to methodological issues; but may relate to variability in clinical practice. Continued provision of appropriate training and assessment is essential for health professionals responsible for collecting routine data.

The association of birth order with later body mass index and blood pressure: a comparison between prospective cohort studies from the United Kingdom and Brazil.

BACKGROUND: Previous studies have found greater adiposity and cardiovascular risk in first born children. The causality of this association is not clear. Examining the association in diverse populations may lead to improved insight. METHODS: We examine the association between birth order and body mass index (BMI), systolic and diastolic blood pressure (SBP/DBP) in the 2004 Pelotas cohort from southern Brazil and the Avon Longitudinal Study of Parents and Children (ALSPAC) from Bristol, south-west England, restricting analysis to families with two children in order to remove confounding by family size. RESULTS: No consistent differences in BMI, SBP or DBP were observed comparing first and second born children. Within the Pelotas 2004 cohort, first born females were thinner, with lower SBP and DBP; for example, mean difference in SBP comparing first with second born was -0.979 (95% confidence interval -2.901 to 0.943). In ALSPAC, first born females had higher BMI, SBP and DBP. In both cohorts, associations tended to be in the opposite direction in males, although no statistical evidence for gender interactions was found. CONCLUSIONS: The findings do not support an association between birth order and BMI or blood pressure. Differences to previous studies may be explained by differences in populations and/or confounding by family size in previous studies.

The measurement of household socio-economic position in tuberculosis prevalence surveys: a sensitivity analysis.

OBJECTIVE: To assess the robustness of socio-economic inequalities in tuberculosis (TB) prevalence surveys. DESIGN: Data were drawn from the TB prevalence survey conducted in Lusaka Province, Zambia, in 2005-2006. We compared TB socio-economic inequalities measured through an asset-based index (Index 0) using principal component analysis (PCA) with those observed using three alternative indices: Index 1 and Index 2 accounted respectively for the biases resulting from the inclusion of urban assets and food-related variables in Index 0. Index 3 was built using regression-based analysis instead of PCA to account for the effect of using a different assets weighting strategy. RESULTS: Household socio-economic position (SEP) was significantly associated with prevalent TB, regardless of the index used; however, the magnitude of inequalities did vary across indices. A strong association was found for Index 2, suggesting that the exclusion of food-related variables did not reduce the extent of association between SEP and prevalent TB. The weakest association was found for Index 1, indicating that the exclusion of urban assets did not lead to higher extent of TB inequalities. CONCLUSION: TB socio-economic inequalities seem to be robust to the choice of SEP indicator. The epidemiological meaning of the different extent of TB inequalities is unclear. Further studies are needed to confirm our conclusions.

Identification of a dietary pattern prospectively associated with increased adiposity during childhood and adolescence.

BACKGROUND: Specific dietary risk factors for excess adiposity in young people are poorly understood. However, studies in adults suggest dietary energy density, fat and fibre are critical dietary factors. OBJECTIVE: To examine longitudinal relationships between a dietary pattern (DP) characterised by dietary energy density, % total energy from fat and fibre density and fat mass (FM) in children from 7 to 15 years of age. DESIGN: Subjects were 6772 children from the UK Avon Longitudinal Study of Parents and Children. Dietary intake was assessed using a 3-day food diary at 7, 10 and 13 years of age. An energy-dense, high-fat, low-fibre DP was identified using reduced rank regression and subjects scored for the DP at each age. FM was measured at 11, 13 and 15 years and FM index (FMI) calculated as FM/height((x)). Longitudinal models were adjusted for dietary misreporting, physical activity and maternal factors. RESULTS: DP z-scores at all ages were positively associated with later FMI. A 1 s.d. unit increase in DP z-score was longitudinally associated with an average increase in FMI z-score of 0.04 s.d. units (95% confidence interval (CI), 0.01-0.07). For each 1 s.d. unit increase in DP z-score, the odds of being in the highest quintile for FMI (as a marker of excess adiposity) increased by 13% (95% CI, 1-27%). CONCLUSIONS: Dietary habits during childhood are associated with increased adiposity in adolescence, with specific implications for dietary energy density, fat and fibre intake. Improving diet quality may reduce the risk of obesity in young people.

Are there socioeconomic inequalities in cardiovascular risk factors in childhood, and are they mediated by adiposity? Findings from a prospective cohort study.

BACKGROUND: Socioeconomic gradients in adiposity were not present during childhood for previous generations, but have emerged in contemporary children. It is unknown whether this translates to socioeconomic gradients in associated cardiovascular risk factors in children, with consequent implications for inequalities in coronary heart disease (CHD) and diabetes when these children reach adulthood. METHODS: Using data from 7772 participants aged 10-years from the Avon Longitudinal Study of Parents and Children, we examined the association between maternal education and a large number of cardiovascular risk factors (cholesterol, triglycerides, high-density lipoprotein, apolipoprotein, adiponectin, leptin, C-reactive protein (CRP), interleukin-6 (IL-6) and systolic and diastolic blood pressure), and examined whether inequalities were mediated by adiposity, measured by dual energy X-ray absorptiometry (DXA)-assessed total fat mass. RESULTS: There were socioeconomic differences in a number of the cardiovascular risk factors (apolipoprotein B, systolic and diastolic blood pressure, CRP, leptin and IL-6). Inequalities were greater in girls than boys. Inequalities in CRP and leptin were completely mediated by adiposity. Inequalities in other cardiovascular risk factors were partially mediated by adiposity. CONCLUSION: This study showed important socioeconomic inequalities in adiposity and associated cardiovascular risk factors in a contemporary UK population of 10-year-old children. Differences between contemporary children and previous generations in the socioeconomic patterning of cardiovascular risk factors suggest future adults may have greater inequalities in diabetes and CHD than current adults. These findings highlight the importance of interventions aimed at preventing obesity in childhood, particularly among those of lower socioeconomic position.

Accuracy of height and weight data from child health records.

BACKGROUND: There is limited knowledge of the accuracy of height and weight measurements from child health records, despite widespread use for research and clinical care. We assess the accuracy of such measurements, using research measurements as the gold standard. METHODS: We compare height/length and weight measurements from clinics of the Avon Longitudinal Study of Parents and Children with routinely collected child health records within 2 months of the clinic date at age 4 (n = 345), 8 (n = 1051), 12 (n = 139), 18 (n = 649), 25 (n = 183), and 43 months (n = 123). To adjust for age differences at measurement, growth data were converted into standard deviation scores using the UK 1990 growth reference. RESULTS: Mean weight standard deviation score (SDS) differences were < or =0.08, with mean predicted differences < or =0.1 kg (eg, mean predicted difference at 8 months -0.011 kg, 95% level of agreement -0.64 to 0.62 kg). Mean height SDS differences were < or =0.45, with mean predicted differences < or =0.9 cm (eg, mean predicted difference at 8 months -0.59 cm, 95% level of agreement -3.84 to 2.66 cm). There was indication of lower accuracy at 4 months old (mean predicted height difference at 4 months -0.91 cm, 95% level of agreement -4.61 to 2.79 cm), but this decreased when the age difference between measurements was reduced. Routine measurements slightly overestimated heights of tall children and underestimated those of short children, but otherwise differences were not associated with sex, social class, birth weight, birth length, or maternal anthropometry. CONCLUSION: Routinely collected child health record height/length and weight data are compatible with no systematic bias, at least in children over 8 months old, supporting their use in clinical practice and research.

Is the wealth index a proxy for consumption expenditure? A systematic review.

BACKGROUND: Many epidemiological studies require a measure of socioeconomic position. The monetary measure preferred by economists is consumption expenditure; the wealth index has been proposed as a reliable, simple alternative to expenditure and is extensively used. METHODS: A systematic review was conducted of the agreement between wealth indices and consumption expenditure, summarising the agreement and exploring factors affecting agreement. RESULTS: Seventeen studies using 36 datasets met the inclusion criteria. Of these, 22 demonstrated weak agreement, 10 moderate agreement, and four strong agreement. There was some evidence that agreement is higher: in middle-income settings; in urban areas; for wealth indices with a greater number of indicators; and for wealth indices including a wider range of indicators. CONCLUSIONS: The wealth index is mostly a poor proxy for consumption expenditure.

Risk factors for injuries in young children in four developing countries: the Young Lives Study.

OBJECTIVE: To assess the occurrence of child injury in four developing country settings and to explore potential risk factors for injury. METHODS: Injury occurrence was studied in cohorts of 2000 children of age 6-17 months at enrolment, in each of Ethiopia, Peru, Vietnam and India (Andhra Pradesh). Generalized estimating equation models were used to explore potential risk factors for child injury. RESULTS: Occurrence of child injury was high in all countries. Caregiver depression emerged as a consistent risk factor for all types of injury measured (burns, serious falls, broken bones and near-fatal injury) across all countries. Other risk factors also showed consistent associations, including long-term child health problems, region of residence and the regular care of the child by a non-household member. CONCLUSIONS: This report provides further evidence of the importance of childhood injury in developing countries and emphasizes the importance of including infants in injury research and prevention strategies. It provides strong evidence of an association between caregiver mental health and child injury risk and contributes to the limited knowledge base on risk factors for child injury in developing countries.