Inequalities in energy drink consumption among UK adolescents: a mixed-methods study.

OBJECTIVE: To examine energy drink consumption among adolescents in the United Kingdom (UK) and associations with deprivation and dietary inequalities. DESIGN: Quantitative dietary and demographic data from the National Diet and Nutrition Survey (NDNS) repeated cross-sectional survey were analysed using logistic regression models. Qualitative data from semi-structured interviews were analysed using inductive thematic analysis. SETTING: UK. PARTICIPANTS: Quantitative data: nationally representative sample of 2587 adolescents aged 11-18 years. Qualitative data: 20 parents, 9 teachers, and 28 adolescents from Hampshire, UK. RESULTS: NDNS data showed adolescents' consumption of energy drinks was associated with poorer dietary quality (OR 0.46 per SD; 95% CI 0.37, 0.58; p<0.001). Adolescents from more deprived areas and lower income households were more likely to consume energy drinks than those in more affluent areas and households (OR 1.40; 95%CI 1.16, 1.69; p<0.001; OR 0.98 per £1000; 95%CI, 0.96, 0.99; p<0.001 respectively). Between 2008 and 2016, energy drink consumption among adolescents living in the most deprived areas increased, but decreased among those living in the most affluent neighbourhoods (p=0.04). Qualitative data identified three themes. First, many adolescents drink energy drinks because of their friends and because the unbranded drinks are cheap. Second, energy drink consumption clusters with other unhealthy eating behaviours and adolescents don't know why energy drinks are unhealthy. Third, adolescents believe voluntary bans in retail outlets and schools do not work. CONCLUSIONS: This study supports the introduction of age-dependent legal restrictions on the sale of energy drinks which may help curb existing socio-economic disparities in adolescents' energy drink intake.

Determining individual trajectories of joint space loss: improved statistical methods for monitoring knee osteoarthritis disease progression.

OBJECTIVES: Knee osteoarthritis (KOA) progression is frequently monitored by calculating the change in knee joint space width (JSW) measurements. Such differences are small and sensitive to measurement error. We aimed to assess the utility of two alternative statistical modelling methods for monitoring KOA. MATERIAL AND METHODS: We used JSW on radiographs from both the control arm of the Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA), a 3-year multicentre, double-blind, placebo-controlled phase three trial, and the Osteoarthritis Initiative (OAI), an open-access longitudinal dataset from the USA comprising participants followed over 8 years. Individual estimates of annualised change obtained from frequentist linear mixed effect (LME) and Bayesian hierarchical modelling, were compared with annualised crude change, and the association of these parameters with change in WOMAC pain was examined. RESULTS: Mean annualised JSW changes were comparable for all estimates, a reduction of around 0.14 mm/y in SEKOIA and 0.08 mm/y in OAI. The standard deviation (SD) of change estimates was lower with LME and Bayesian modelling than crude change (SEKOIA SD = 0.12, 0.12 and 0.21 respectively; OAI SD = 0.08, 0.08 and 0.11 respectively). Estimates from LME and Bayesian modelling were statistically significant predictors of change in pain in SEKOIA (LME P-value = 0.04, Bayes P-value = 0.04), while crude change did not predict change in pain (P-value = 0.10). CONCLUSIONS: Implementation of LME or Bayesian modelling in clinical trials and epidemiological studies, would reduce sample sizes by enabling all study participants to be included in analysis regardless of incomplete follow up, and precision of change estimates would improve. They provide increased power to detect associations with other measures.

Improving pregnant women's diet and physical activity behaviours: the emergent role of health identity.

BACKGROUND: Women who gain too much weight in pregnancy are at increased risk of disease and of having children with increased risk. Interventions to improve health behaviours are usually designed for a general population of pregnant women, and trial outcomes show an average impact that does not represent the differences between individuals. To inform the development of future interventions, this study explored the factors that influenced women's diet and physical activity during pregnancy and aimed to identify the needs of these women with regards to lifestyle support. METHODS: Women who completed a trial of vitamin D supplementation and nurse support in pregnancy were invited to take part in an interview. Seventeen women were interviewed about their lifestyles during pregnancy, the support they had, and the support they wanted. Interview transcripts were coded thematically and analysed to understand the factors that influenced the diets and physical activity levels of these women and their engagement with resources that could provide support. RESULTS: Women identified barriers to eating well or being physically active, and pregnancy-specific issues like nausea and pain were common. Women's interest in maintaining a healthy lifestyle and their engagement with lifestyle support was related to the extent to which they self-identified as healthy people. Health-disengaged women were disinterested in talking about their lifestyles while health-focused women did not feel that they needed extra support. Women between these ends of the 'health identity' spectrum were interested in improving their health, and were able to identify barriers as well as sources of support. CONCLUSIONS: Lifestyle interventions in pregnancy should be adapted to meet the needs of individuals with different health identities, and encouraging a change in health identity may be one way of supporting sustained change in health behaviours.

Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Breech presentation is associated with lower bone mass and area: findings from the Southampton Women's Survey.

We compared bone outcomes in children with breech and cephalic presentation at delivery. Neonatal whole-body bone mineral content (BMC) and area were lower in children with breech presentation. At 4 years, no differences in whole-body or spine measures were found, but hip BMC and area were lower after breech presentation. INTRODUCTION: Breech presentation is associated with altered joint shape and hip dysplasias, but effects on bone mineral content (BMC), area (BA) and density (BMD) are unknown. METHODS: In the prospective Southampton Women's Survey mother-offspring cohort, whole-body bone outcomes were measured using dual-energy X-ray absorptiometry (DXA) in 1430 offspring, as neonates (mean age 6 days, n = 965, 39 with a breech presentation at birth) and/or at age 4.1 years (n = 999, 39 breech). Hip and spine bone outcomes were also measured at age 4 years. RESULTS: Neonates with breech presentation had 4.2 g lower whole-body BMC (95% CI -7.4 to - 0.9 g, P = 0.012) and 5.9 cm2 lower BA (- 10.8 to - 1.0 cm2, P = 0.019), but BMD was similar between groups (mean difference - 0.007, - 0.016 to 0.002 g/cm2, P = 0.146) adjusting for sex, maternal smoking, gestational diabetes, mode of delivery, social class, parity, ethnicity, age at scan, birthweight, gestational age and crown-heel length. There were no associations between breech presentation and whole-body outcomes at age 4 years, but, in similarly adjusted models, regional DXA (not available in infants) showed that breech presentation was associated with lower hip BMC (- 0.51, - 0.98 to - 0.04 g, P = 0.034) and BA (- 0.67, - 1.28 to - 0.07 cm2, P = 0.03) but not with BMD (- 0.009, - 0.029 to 0.012 g, P = 0.408), or spine outcomes. CONCLUSIONS: These results suggest that breech presentation is associated with lower neonatal whole-body BMC and BA, which may relate to altered prenatal loading in babies occupying a breech position; these differences did not persist into later childhood. Modest differences in 4-year hip BMC and BA require further investigation.

Modifiable risk factors of maternal postpartum weight retention: an analysis of their combined impact and potential opportunities for prevention.

BACKGROUND/OBJECTIVES: Pregnancy triggers a physiological change in weight status. Postpartum weight retention in the childbearing years can substantially alter a woman's weight gain trajectory, with several potential contributing factors identified. Most research has relied on women's recall of pre-pregnancy weight during pregnancy or later, and not considered risk factors in combination. Using measured pre-pregnancy weight, this study aimed to examine the associations of maternal postpartum weight retention with parity, pre-pregnancy BMI, excessive gestational weight gain (GWG), maternal serum vitamin D concentration and dietary Glycaemic Index in early and late pregnancy, and breastfeeding duration, including analysis of the combined impact of potentially modifiable risk factors. SUBJECTS/METHODS: Prospective cohort study of 12 583 non-pregnant women aged 20-34 years in Southampton (UK) who were assessed prior to pregnancy, with those who subsequently became pregnant followed up in early and late gestation, and after delivery (n=2559 in the final sample). Linear regression models examined potential predictors of weight retention in adjusted individual and multivariate analyses, and as a risk factor score. RESULTS: Compared with pre-pregnancy weight, 73% of women retained some weight at 6 months postpartum (mean (s.d.): 3.5 (6.2) kg). In the adjusted multivariate model, women who were primiparous, had a lower pre-pregnancy BMI, excessive GWG, a lower early pregnancy vitamin D concentration and breastfed for <6 months had greater weight retention 6 months postpartum (P<0.05 for all variables). For each additional modifiable risk factor (excessive GWG, low vitamin D concentration in early pregnancy and short breastfeeding duration; scale 0-3), women retained an additional 2.49 kg (95% CI: 2.16, 2.82; P<0.001). CONCLUSIONS: Having a greater number of modifiable risk factors was associated with greater weight retention 6 months postpartum. Initiatives supporting women to target these risk factors in the years prior to, during and after pregnancy could impact on their weight gain trajectory and later risk of adverse weight-related outcomes.

Maternal stress and psychological distress preconception: association with offspring atopic eczema at age 12 months.

BACKGROUND: Perinatal maternal stress and low mood have been linked to offspring atopic eczema. OBJECTIVES: To examine the relation of maternal stress/mood with atopic eczema in the offspring, focusing particularly on stress/psychological distress preconception. METHODS: At recruitment in the UK Southampton Women's Survey, preconception maternal reports of perceived stress in daily living and the effect of stress on health were recorded; in a subsample, psychological distress was assessed (12-item General Health Questionnaire). Infants were followed up at ages 6 (n = 2956) and 12 (n = 2872) months and atopic eczema ascertained (based on UK Working Party Criteria for the Definition of Atopic Dermatitis). At 6 months post-partum, mothers were asked if they had experienced symptoms of low mood since childbirth and completed the Edinburgh Postnatal Depression Scale. RESULTS: Preconception perceived stress affecting health [OR 1.21 (95% CI 1.08-1.35), P = 0.001] and stress in daily living [OR 1.16 (1.03-1.30), P = 0.014] were associated with an increased risk of offspring atopic eczema at age 12 months but not at 6 months, robust to adjustment for potentially confounding variables. Findings were similar for maternal psychological distress preconception. Low maternal mood between delivery and 6 months post-partum was associated with an increased risk of infantile atopic eczema at age 12 months, but no significant association between post-natal mood and atopic eczema was seen after taking account of preconception stress. CONCLUSION AND CLINICAL RELEVANCE: Our data provide novel evidence linking maternal stress at preconception to atopic eczema risk, supporting a developmental contribution to the aetiology of atopic eczema and pointing to potentially modifiable influences.

DNA methylation of Th2 lineage determination genes at birth is associated with allergic outcomes in childhood.

BACKGROUND: There is now increasing evidence that asthma and atopy originate in part in utero, with disease risk being associated with the altered epigenetic regulation of genes. OBJECTIVE AND METHODS: To determine the relationship between variations in DNA methylation at birth and the development of allergic disease, we examined the methylation status of CpG loci within the promoter regions of Th1/2 lineage commitment genes (GATA3, IL-4, IL-4R, STAT4 and TBET) in umbilical cord DNA at birth in a cohort of infants from the Southampton Women's Survey (n = 696) who were later assessed for asthma, atopic eczema and atopy. RESULTS: We found that higher methylation of GATA3 CpGs -2211/-2209 at birth was associated with a reduced risk of asthma at ages 3 (median ratio [median methylation in asthma group/median methylation in non-asthma group] = 0.74, P = .006) and 6-7 (median ratio 0.90, P = .048) years. Furthermore, we demonstrated that the GATA3 CpG loci associated with later risk of asthma lie within a NF-κB binding site and that methylation here blocks transcription factor binding to the GATA3 promoter in the human Jurkat T-cell line. Associations between umbilical cord methylation of CpG loci within IL-4R with atopic eczema at 12 months (median ratio 1.02, P = .028), and TBET with atopy (median ratio 0.98, P = .017) at 6-7 years of age were also observed. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings provide further evidence of a developmental contribution to the risk of later allergic disorders and suggest that involvement of epigenetic mechanisms in childhood asthma is already demonstrable at birth.

The relationship between maternal self-efficacy, compliance and outcome in a trial of vitamin D supplementation in pregnancy.

In a randomised controlled trial of vitamin D during pregnancy, we demonstrated that women with lower self-efficacy were more likely to experience practical problems with taking the trial medication and that this was associated with lower compliance and achieved 25(OH)-vitamin D concentrations. INTRODUCTION: The relationship between self-efficacy (the belief that one can carry out a behaviour), compliance with study protocol and outcome was explored within a randomised, double-blind, placebo-controlled trial of vitamin D supplementation in pregnancy. METHODS: In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial, women with circulating plasma 25(OH)-vitamin D of 25-100 nmol/l in early pregnancy were randomised to either 1000 IU cholecalciferol/day or matched placebo from 14 weeks until delivery. Circulating 25(OH)-vitamin D concentrations were assessed at 14 and 34 weeks' gestation. A sequential sub-sample completed Schwarzer's General Self-Efficacy Scale at 14 and 34 weeks and the Problematic Experiences of Therapy Scale at 34 weeks. Women were interviewed about their experiences of the trial and interview transcripts analysed thematically. RESULTS: In 203 women, those with higher self-efficacy were less likely to experience practical problems taking the study medication (odds ratio (OR) 0.81 (95 % confidence interval (CI) 0.69-0.95), p = 0.01). Over half reported practical problems associated with poorer compliance with the protocol requiring women to take the medication daily. Compliance in women who experienced practical problems was 94 % compared with 98 % for those with no problems (p < 0.001). Poorer compliance was also associated with lower concentrations of 25(OH)-D in late pregnancy in the treatment group (ß = 0.54 nmol/l (95 % CI 0.18-0.89), p = 0.003). Thematic analysis suggested common difficulties were remembering to take the medication every day and swallowing the large capsules. CONCLUSIONS: These findings suggest that differences in self-efficacy influence trial outcomes. Such information may help clinicians anticipate responses to routine vitamin D supplementation in pregnancy and identify those who may need more support to comply. TRIAL REGISTRATION: ISRCTN82927713, registered 11/04/2008.

Higher maternal serum concentrations of nicotinamide and related metabolites in late pregnancy are associated with a lower risk of offspring atopic eczema at age 12 months.

BACKGROUND: Evidence that atopic eczema partly originates in utero is increasing, with some studies linking the risk of developing the condition with aspects of maternal diet during pregnancy. Nicotinamide, a naturally occurring nutrient that is maintained through the dietary intakes of vitamin B3 and tryptophan, has been used in the treatment of some skin conditions including atopic eczema. OBJECTIVE: To examine the relation of maternal serum concentrations of nicotinamide and related tryptophan metabolites to the risk of atopic eczema in the offspring. METHODS: Within the UK Southampton Women Survey, infantile atopic eczema at ages 6 and 12 months was ascertained (modified UK Working Party Criteria for the Definition of Atopic Dermatitis). Maternal serum levels of kynurenine, kynurenic acid, anthranilic acid, tryptophan, nicotinamide and N1-methylnicotinamide were measured in late pregnancy by mass spectrometry (n = 497) and related to the odds ratio of infantile atopic eczema. RESULTS: Maternal nicotinamide and related metabolite concentrations were not associated with offspring atopic eczema at age 6 months. Higher concentrations of nicotinamide and anthranilic acid were, however, associated with a lower risk of eczema at age 12 months (odds ratios 0.69, 95% CI 0.53-0.91/SD change, P = 0.007 and 0.63, 0.48-0.83, P = 0.001, respectively). The associations were robust to adjustment for potentially confounding variables. CONCLUSION AND CLINICAL RELEVANCE: This is the first study linking maternal serum concentrations of nicotinamide and related metabolites to the risk of atopic eczema in the offspring. The findings point to potentially modifiable maternal influences on this complex and highly prevalent condition.

Greater access to fast-food outlets is associated with poorer bone health in young children.

SUMMARY: A healthy diet positively influences childhood bone health, but how the food environment relates to bone development is unknown. Greater neighbourhood access to fast-food outlets was associated with lower bone mass among infants, while greater access to healthy speciality stores was associated with higher bone mass at 4 years. INTRODUCTION: Identifying factors that contribute to optimal childhood bone development could help pinpoint strategies to improve long-term bone health. A healthy diet positively influences bone health from before birth and during childhood. This study addressed a gap in the literature by examining the relationship between residential neighbourhood food environment and bone mass in infants and children. METHODS: One thousand one hundred and seven children participating in the Southampton Women's Survey, UK, underwent measurement of bone mineral density (BMD) and bone mineral content (BMC) at birth and 4 and/or 6 years by dual-energy X-ray absorptiometry (DXA). Cross-sectional observational data describing food outlets within the boundary of each participant's neighbourhood were used to derive three measures of the food environment: the counts of fast-food outlets, healthy speciality stores and supermarkets. RESULTS: Neighbourhood exposure to fast-food outlets was associated with lower BMD in infancy (ß = -0.23 (z-score): 95% CI -0.38, -0.08) and lower BMC after adjustment for bone area and confounding variables (ß = -0.17 (z-score): 95% CI -0.32, -0.02). Increasing neighbourhood exposure to healthy speciality stores was associated with higher BMD at 4 and 6 years (ß = 0.16(z-score): 95% CI 0.00, 0.32 and ß = 0.13(z-score): 95% CI -0.01, 0.26 respectively). The relationship with BMC after adjustment for bone area and confounding variables was statistically significant at 4 years, but not at 6 years. CONCLUSIONS: The neighbourhood food environment that pregnant mothers and young children are exposed may affect bone development during early childhood. If confirmed in future studies, action to reduce access to fast-food outlets could have benefits for childhood development and long-term bone health.

Age at introduction of solid foods and feeding difficulties in childhood: findings from the Southampton Women's Survey.

This study aimed to determine whether age at introduction of solid foods was associated with feeding difficulties at 3 years of age. The present study was carried out using data from the Southampton Women's Survey (SWS). Women enrolled in the SWS who subsequently became pregnant were followed-up during pregnancy and postpartum, and the offspring have been studied through childhood. Maternal socio-demographic and anthropometric data and child anthropometric and feeding data were collected through interviews and self-administered questionnaires. When the children were 3 years of age, mothers/carers rated six potential child feeding difficulty questions on a four-point Likert scale, including one general question and five specific feeding difficulty questions. Age at introduction of solids as a predictor of feeding difficulties was examined in 2389 mother-child pairs, adjusting for child (age last breast fed, sex, gestation) and maternal characteristics (parity, pre-pregnancy BMI, age, education, employment, parenting difficulties, diet quality). The majority of mothers/carers (61 %) reported some feeding difficulties (general feeding difficulty question) at 3 years of age, specifically with their child eating enough food (61 %), eating the right food (66 %) and being choosy with food (74 %). Children who were introduced to solids ≥6 months had a lower risk of feeding difficulties (RR 0·73; 95 % CI 0·59, 0·91, P=0·004) than children who were introduced to solids between 4 and 6 months. No other significant associations were found. There were few associations between feeding difficulties in relation to age at introduction of solid foods. However, general feeding difficulties were less common among infants introduced to solid foods ≥6 months of age.

Diet quality across early childhood and adiposity at 6 years: the Southampton Women's Survey.

BACKGROUND: Poor diet quality in early childhood is inconsistently linked to obesity risk. Understanding may be limited by the use of cross-sectional data and the use of body mass index (BMI) to define adiposity in childhood. OBJECTIVE: The objective of this study is to examine the effects of continued exposure to diets of varying quality across early childhood in relation to adiposity at 6 years. METHODS: One thousand and eighteen children from a prospective UK birth cohort were studied. Diet was assessed using food frequency questionnaires when the children were aged 6 and 12 months, and 3 and 6 years; diet quality was determined according to scores for a principal component analysis-defined dietary pattern at each age (characterized by frequent consumption of fruits, vegetables and fish). At each age, children were allocated a value of 0/1/2 according to third of the distribution (bottom/middle/top) their diet quality score was in; values were summed to calculate an overall diet quality index (DQI) for early childhood (range 0-8). Obesity outcomes considered at 6 years were dual-energy X-ray absorptiometry-assessed fat mass and BMI. RESULTS: One hundred and seven (11%) children had a DQI=0, indicating a consistently low diet quality, 339 (33%) had a DQI=1-3, 378 (37%) had a DQI=4-6 and 194 (19%) had a DQI=7-8. There was a strong association between lower DQI and higher fat mass z-score at 6 years that was robust to adjustment for confounders (fat mass s.d. per 1-unit DQI increase: ß=-0.05 (95% confidence interval (CI): -0.09, -0.01), P=0.01). In comparison with children who had the highest diet quality (DQI=7-8), this amounted to a difference in fat mass of 14% (95% CI: 2%, 28%) at 6 years for children with the poorest diets (DQI=0). In contrast, no independent associations were observed between DQI and BMI. CONCLUSIONS: Continued exposure to diets of low quality across early childhood is linked to adiposity at the age of 6 years.

Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey.

Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampton Women's Survey, and gene expression was analysed using quantitative real-time PCR. Gene expression data were normalised to the geometric mean of three housekeeping genes, and related to maternal factors and childhood body composition. Maternal serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal 25(OH)D and VDBP levels were positively associated with placental expression of specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP concentrations were correlated with the expression of specific placental amino acid transporters, and thus may be involved in the regulation of amino acid transfer to the fetus. The positive correlation of VDBP levels and placental transporter expression suggests that delivery of vitamin D to the placenta may be important. This exploratory study identifies placental amino acid transporters which may be altered in response to modifiable maternal factors and provides a basis for further studies.

Does maternal long chain polyunsaturated fatty acid status in pregnancy influence the bone health of children? The Southampton Women's Survey.

UNLABELLED: In this large, population-based, prospective, mother-offspring cohort study, maternal long chain polyunsaturated fatty acid (LCPUFA) status during pregnancy was found to be positively associated with bone mass in the offspring at age 4 years. The findings suggest that variation in intrauterine exposure to n-3 and n-6 LCPUFAs may have potential consequences for skeletal development. INTRODUCTION: Maternal diet in pregnancy has been linked to childhood bone mass, but the mechanisms and nutrients involved are uncertain. Long-chain polyunsaturated fatty acids (LCPUFAs) have been shown to affect bone metabolism, but the relationship between maternal fatty acid status and bone mass in the offspring remains unknown. METHODS: We evaluated the association between maternal LCPUFA status in late pregnancy (34 weeks gestation) and bone density in their children at age 4 years within 727 mother-child pairs taking part in the Southampton Women's Survey. RESULTS: Concentrations of the n-3 LCPUFA component of maternal plasma phosphatidylcholine were positively associated with a number of bone mineral measures at the age of 4 years; these associations persisted after adjustment for maternal body build, walking speed and infant feeding. Relationships were most evident for eicosapentaenoic acid (r = 0.09, p = 0.02 for whole body areal bone mineral density [aBMD] and r = 0.1, p = 0.008 for lumbar spine aBMD) and for docosapentaenoic acid (r = 0.09, p = 0.02 for whole body aBMD and r = 0.12, p = 0.002 for lumbar spine aBMD). CONCLUSIONS: These findings suggest that variation in early exposure to n-3 and n-6 LCPUFA may have potential consequences for bone development and that the effects appear to persist into early childhood.

Physical activity, calcium intake and childhood bone mineral: a population-based cross-sectional study.

UNLABELLED: In a free-living cohort of 4-year old children, mean daily time in moderate-vigorous physical activity and daily calcium intake at 3 years, were positively related to hip bone size and density. Relationships between physical activity and bone indices were stronger when calcium intake was above compared with below median (966 mg/day). INTRODUCTION: We examined the cross-sectional relationships between childhood physical activity, dietary calcium intake and bone size and density. METHODS: Children aged 4 years were recruited from the Southampton Women's Survey. They underwent measurement of bone mass by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart, Cambridge Neurotechnology Ltd, Cambridge, UK) for seven continuous days. RESULTS: Four hundred twenty-two children (212 boys) participated. In a cross-sectional analysis, after adjusting for gender, daily mean time(minutes per day) spent in moderate to very vigorous activity (MVPA) was positively related to hip BA (R(2) = 3%, p < 0.001), BMC (R(2) = 4%, p < 0.001), aBMD (R (2) = 3%, p = 0.001) and estimated vBMD (R(2) = 2%, p = 0.01), but not height (r (s) = 0.04, p = 0.42) or weight (r(s) = 0.01, p = 0.76). Mean daily calcium intake (assessed at 3 years old) positively predicted bone indices in those with a calcium intake below the median (966 mg/day), but there was a much attenuated relationship in those above this. These associations persisted after inclusion of total energy, protein and phosphorus in multivariate models. The relationships between MVPA and bone indices were stronger in children with calcium intakes above the median. Thus, for aBMD, the variance explained by MVPA when daily calcium intake was below the median was 2% (p = 0.1) and above median was 6% (p = 0.001). CONCLUSIONS: These results support the notion that adequate calcium intake may be required for optimal action of physical activity on bone development and that improving levels of physical activity and calcium intake in childhood may help to optimise accrual of bone mass.

Using cohort studies in lifecourse epidemiology.

The UK Medical Research Council (MRC) Population Health Sciences Research Network is a network of MRC research units and centres that aims to bring together and add value to existing MRC investment in public health, health services and epidemiological research. This symposium held in August 2011 at the World Congress of Epidemiology, Edinburgh, discussed a range of topics including methodology and analytical issues based on a number of examples of cohort studies within the context of lifecourse epidemiology.

DNA methylation signatures in cord blood associated with birthweight are enriched for dmCpGs previously associated with maternal hypertension or pre-eclampsia, smoking and folic acid intake.

Many epidemiological studies have linked low birthweight to an increased risk of non-communicable diseases (NCDs) in later life, with epigenetic proceseses suggested as an underlying mechanism. Here, we sought to identify neonatal methylation changes associated with birthweight, at the individual CpG and genomic regional level, and whether the birthweight-associated methylation signatures were associated with specific maternal factors. Using the Illumina Human Methylation EPIC array, we assessed DNA methylation in the cord blood of 557 and 483 infants from the UK Pregnancies Better Eating and Activity Trial and Southampton Women's Survey, respectively. Adjusting for gestational age and other covariates, an epigenome-wide association study identified 2911 (FDR≤0.05) and 236 (Bonferroni corrected p ≤ 6.45×10-8) differentially methylated CpGs (dmCpGs), and 1230 differentially methylated regions (DMRs) (Stouffer ≤0.05) associated with birthweight. The top birthweight-associated dmCpG was located within the Homeobox Telomere-Binding Protein 1 (HMBOX1) gene with a 195 g (95%CI: -241, -149 g) decrease in birthweight per 10% increase in methylation, while the top DMR was located within the promoter of corticotropin-releasing hormone-binding protein (CRHBP). Furthermore, the birthweight-related dmCpGs were enriched for dmCpGs previously associated with gestational hypertension/pre-eclampsia (14.51%, p = 1.37×10-255), maternal smoking (7.71%, p = 1.50 x 10-57) and maternal plasma folate levels during pregnancy (0.33%, p = 0.029). The identification of birthweight-associated methylation markers, particularly those connected to specific pregnancy complications and exposures, may provide insights into the developmental pathways that affect birthweight and suggest surrogate markers to identify adverse prenatal exposures for stratifying for individuals at risk of later NCDs.

Differential relationships between parent-child DXA and pQCT bone measures: Results from the Southampton Women's Survey.

AIM: To investigate the associations between indices of bone health in childhood and corresponding parental measures. METHODS: The Southampton Women's Survey characterised 12,583 non-pregnant women aged 20-34 years; 3158 subsequently had singleton live births. In a subset, dual-energy X-ray absorptiometry (DXA) measurements of bone area (BA), bone mineral content (BMC) and areal bone mineral density (aBMD) lumbar spine and total hip were obtained in the parent/offspring (aged 8-9 years) trios. Another subset of children (aged 6-7 years), and their parents, had peripheral quantitative computed tomography (pQCT; 4% and 38% tibia) measures. Using multivariable linear regression we examined relationships between mother/father and offspring, adjusting for parental age, habitual walking speed and education; offspring age and sex; and the corresponding bone measure in the other parent (ß-coefficients (95%CI) unit/unit for each bone measure). RESULTS: Data were available for 260 trios with DXA and 99 with pQCT. There were positive associations for BA, BMC and aBMD between either parent and offspring. Mother-child associations were of greater magnitude than father-child; for example, mother-child aBMD (ß = 0.26 g·cm-2/g·cm-2 (0.21,0.32)) and father-child aBMD (ß = 0.16 g·cm-2/g·cm-2 (0.11,0.21)), P-difference in ß = 0.007. In the subset with pQCT there was a positive association for mother-offspring 4% tibial total area (ß = 0.33 mm2/mm2 (0.17,0.48)), but little evidence of a father-offspring association (ß = -0.06 mm2/mm2 (-0.17,0.06)). In contrast offspring 38% cortical density was more strongly associated with this measure in fathers (ß = 0.48 mg·cm-3/mg·cm-3 (0.15,0.82)) than mothers (ß = 0.27 mg·cm-3/mg·cm-3 (-0.03,0.56)). In general mother-father differences were attenuated by adjustment for height. CONCLUSIONS: Whilst offspring bone measures are independently associated with those of either parent, the magnitude of the association is often greater for maternal than paternal relationships. These findings are consistent with an in utero influence on offspring growth but might also reflect genetic and/or epigenetic parent of origin effects. SUMMARY: In an established parent-offspring cohort, associations between parent and offspring bone indices were generally greater in magnitude for mother-offspring than father-offspring relationships.