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Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity

OBJECTIVE Fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans. RESEARCH DESIGN AND METHODS Using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5′ from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ≥5% and a 5–95% range ≥10%, we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort. RESULTS In cohort 1, retinoid X receptor-α (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [β] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and β = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (β = 10% [1–19], P = 0.023, n = 64 and β =12% [4–20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (β = 6% [2–10] and β = 4% [1–7], respectively, both P = 0.002, n = 239). CONCLUSIONS Our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic disease.

Twenty-five year mortality of a community cohort with schizophrenia

BACKGROUND People with schizophrenia have significantly raised mortality but we do not know how these mortality patterns in the UK have changed since the 1990s. AIMS To measure the 25-year mortality of people with schizophrenia with particular focus on changes over time. METHOD Prospective record linkage study of the mortality of a community cohort of 370 people with schizophrenia. RESULTS The cohort had an all-cause standardised mortality ratio of 289 (95% CI 247-337). Most deaths were from the common causes seen in the general population. Unnatural deaths were concentrated in the first 5 years of follow-up. There was an indication that cardiovascular mortality may have increased relative to the general population (P = 0.053) over the course of the study. CONCLUSIONS People with schizophrenia have a mortality risk that is two to three times that of the general population. Most of the extra deaths are from natural causes. The apparent increase in cardiovascular mortality relative to the general population should be of concern to anyone with an interest in mental health.

Mortality of Shipham residents: 40-year follow-up.

The 1939 populations of Shipham, a village in Somerset with high soil-cadmium levels, and a nearby control village have been followed for 40 years. Death certificates were obtained for those who had died, and the mortality rates were compared with those for England and Wales. Small excesses of hypertensive, cerebrovascular, and genitourinary disease were noted in Shipman but not in the control village. These conditions have been associated wih cadmium toxicity, and so it is possible that cadmium had some influence on the disease pattern in Shipham; but if so, the effect was slight. By contrast, fewer deaths than expected from respiratory disease and cancers were observed in both villages. This gave rise to all-cause mortality rates in Shipham and the control village which were similar and well below the national average.

Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children

Summary Background A link between exposure to the air pollutant nitrogen dioxide (NO2) and respiratory disease has been suggested. Viral infections are the major cause of asthma exacerbations. We aimed to assess whether there is a relation between NO2 exposure and the severity of asthma exacerbations caused by proven respiratory viral infections in children. Methods A cohort of 114 asthmatic children aged between 8 and 11 years recorded daily upper and lower respiratory-tract symptoms, peak expiratory flow (PEF), and measured personal NO2 exposures every week for up to 13 months. We took nasal aspirates during reported episodes of upper respiratory-tract illness and tested for infection by common respiratory viruses and atypical bacteria with RT-PCR assays. We used generalised estimating equations to assess the relation between low (<7·5 μg/m3), medium (7·5–14 μg/m3), and high (>14 μg/m3) tertiles of NO2 exposure in the week before or after upper respiratory-tract infection and the severity of asthma exacerbation in the week after the start of an infection. Findings One or more viruses were detected in 78% of reported infection episodes, and the medians of NO2 exposure were 5 (IQR 3·6–6·3), 10 (8·7–12·0), and 21 μg/m3 (16·8–42·9) for low, medium, and high tertiles, respectively. There were significant increases in the severity of lower respiratory-tract symptom scores across the three tertiles (0·6 for all viruses [p=0·05] and >2 for respiratory syncytial virus [p=0·01]) and a reduction in PEF of more than 12 L/min for picornavirus (p=0·04) for high compared with low NO2 exposure before the start of the virus-induced exacerbation. Interpretation High exposure to NO2 in the week before the start of a respiratory viral infection, and at levels within current air quality standards, is associated with an increase in the severity of a resulting asthma exacerbation.

Childhood Socioeconomic Position and Objectively Measured Physical Capability Levels in Adulthood: A Systematic Review and Meta-Analysis

Background Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood. Methods and Findings Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations. Conclusions Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.

Risk factors for incident neck and shoulder pain in hospital nurses.

Aim: To assess the incidence and risk factors for neck and shoulder pain in nurses. Methods: A longitudinal study of neck and shoulder pain was carried out in female nurses at two hospitals in England. Personal and occupational risk factors were assessed at baseline. The self reported incidence of symptoms in the neck and shoulder region was ascertained at three-monthly intervals over two years. A Cox regression model was used to estimate hazard ratios (HRs) for incident neck/shoulder pain during follow up in nurses who had been pain free for at least one month at baseline. Results: The baseline response rate was 56%. Of 903 women who were pain free at baseline, 587 (65%) completed at least one follow up while still in the same job. During an average of 13 months, 34% of these (202 women) reported at least one episode of neck/shoulder pain. The strongest predictor of pain in the neck/shoulder was previous history of the symptom (HRs up to 3.3). For physical exposures at work, the highest risks (HRs up to 1.7) were associated with specific patient handling tasks that involved reaching, pushing, and pulling. Nurses who reported low mood or stress at baseline were more likely to develop neck/shoulder pain later (HR 1.5). Workplace psychosocial factors (including job demands, satisfaction, and control) were not associated with incident neck/shoulder symptoms. Conclusions: Neck/shoulder pain is common among hospital nurses, and patient handling tasks that involve reaching and pulling are the most important target for risk reduction strategies.

Women's Dietary Patterns Change Little from Before to During Pregnancy

Principal component analysis (PCA) is a popular method of dietary patterns analysis, but our understanding of its use to describe changes in dietary patterns over time is limited. Using a FFQ, we assessed the diets of 12,572 nonpregnant women aged 20-34 y from Southampton, UK, of whom 2270 and 2649 became pregnant and provided complete dietary data in early and late pregnancy, respectively. Intakes of white bread, breakfast cereals, cakes and biscuits, processed meat, crisps, fruit and fruit juices, sweet spreads, confectionery, hot chocolate drinks, puddings, cream, milk, cheese, full-fat spread, cooking fats and salad oils, red meat, and soft drinks increased in pregnancy. Intakes of rice and pasta, liver and kidney, vegetables, nuts, diet cola, tea and coffee, boiled potatoes, and crackers decreased in pregnancy. PCA at each time point produced 2 consistent dietary patterns, labeled prudent and high-energy. At each time point in pregnancy, and for both the prudent and high-energy patterns, we derived 2 dietary pattern scores for each woman: a natural score, based on the pattern defined at that time point, and an applied score, based on the pattern defined before pregnancy. Applied scores are preferred to natural scores to characterize changes in dietary patterns over time because the scale of measurement remains constant. Using applied scores, there was a very small mean decrease in prudent diet score in pregnancy and a very small mean increase in high-energy diet score in late pregnancy, indicating little overall change in dietary patterns in pregnancy.

Impact of educational attainment on the quality of young women's diets

Objective: New findings, that relate poor foetal growth to long-term outcomes, highlight the need to understand more about the nature of womens diets before and during pregnancy. This study examines the influence of sociodemographic and anthropometric factors on the quality of the diets of young women in the UK.Design: Diet was assessed by an interviewer-administered food frequency questionnaire. A single diet score was calculated for each woman using the first component defined by principal components analysis.Setting: Southampton, UK.Subjects: A total of 6125 non pregnant women aged 20–34 y.Results: The diets of women with low diet scores were characterised by low intakes of fruit and vegetables, wholemeal bread, rice and pasta, yogurt, and breakfast cereals, but high intakes of chips and roast potatoes, sugar, white bread, red, and processed meat and full-fat dairy products. Educational attainment was the most important factor related to the diet score. In all, 55% (95% CI 50–59%) of women with no educational qualifications had scores in the lowest quarter of the distribution, compared with only 3% (95% CI 2–4%) of those who had a degree. Smoking, watching television, lack of strenuous exercise, and living with children were also associated with lower diet scores. After taking these factors into account, no other factor including social class, the deprivation score of the neighbourhood, or receipt of benefits added more than 1% to the variance in the diet score.Conclusions: Poor achievement at school defines a substantial group of women in the UK who may be vulnerable. Many of these women have poor diets that are not simply a result of the level of deprivation in their neighbourhood, or of living at a level of poverty that entitles them to benefits. We suggest that it is a priority to identify and to address the barriers that prevent these women from improving the quality of their diets.Sponsorship: The study was funded by the Dunhill Medical Trust, the University of Southampton and the Medical Research Council.

Mortality of employees of the United Kingdom Atomic Energy Authority, 1946-1979.

An analysis was conducted of 3373 deaths among 39 546 people employed by the United Kingdom Atomic Energy Authority between 1946 and 1979, the population having been followed up for an average of 16 years. Overall the death rates were below those prevailing in England and Wales but consistent with those expected in a normal workforce. At ages 15-74 years the standardised mortality ratios (SMRs) were 74 for deaths from all causes and 79 for deaths from all cancers. Mortality from only four causes was above the national average--namely, testicular cancer (SMR 153; 10 deaths), leukaemia (SMR 123; 35 deaths), thyroid cancer (SMR 122; three deaths), non-Hodgkins lymphoma (SMR 107; 20 deaths)--but in none was the increase significant at the 5% level. Half of the authoritys employees were recorded as having been monitored for exposure to radiation, their collective recorded exposure being 660 Sv (65 954 rem). Among these prostatic cancer was the only condition with a clearly increased mortality in relation to exposure. Of the 19 men who had a radiation record and died from prostatic cancer at ages 15-74 years, nine had been monitored for several different sources of exposure to radiation. The standardised mortality ratios were 889 (six deaths) in employees monitored for contamination by tritium, 254 (nine deaths) in those monitored for contamination by other radionuclides, and 385 (nine deaths) in those with dosimeter readings totalling more than 50 mSv (5 rem); but the same nine subjects tended to account for each of these significantly raised ratios. Because multiple exposures were common and other relevant information was not available the reason for the increased mortality from prostatic cancer in this population could not be determined and requires further investigation. Excess mortality rates of 2.2 and 12.5 deaths per million person years per 10 mSv (1 rem) were estimated for leukaemia and all cancers, respectively. The confidence limits around these estimates were wide, included zero, and made it unlikely that the International Commission on Radiological Protections cancer risk coefficients were underestimated by more than 15-fold. Thus despite this being the largest British workforce whose mortality has been reported in relation to low level ionising radiation exposure, even larger populations will need to be followed up over longer periods before narrower ranges of risk estimates can be derived.

MULTICENTRE TRIAL OF PHYSIOTHERAPY IN THE MANAGEMENT OF SCIATIC SYMPTOMS

Four treatments for sciatic symptoms--traction, exercises, manipulation, and corset--were assessed in a randomised controlled trial in 322 outpatients. The design was factorial. There were thus sixteen treatment groups, enabling a comparison of combinations of methods as well as of individual methods. Treatment lasted for four weeks. Patients were reviewed at the end of this period and at four and sixteen months after entry to the trial. Progress was measured by the patients account of symptomatic improvement or deterioration and by return to work or normal activities. At four weeks each of the treatments was associated with a small degree of benefit over and above the high rate of spontaneous improvement. For manipulation, the benefit was statistically significant on one of the scales used to measure progress. There was a significant increase in symptomatic improvement with increasing numbers of treatments used in combination. This was complemented by a clear tendency for those who had received fewer types of treatment during the trial to have further treatment in the ensuing three months. There were no beneficial effects of treatment detectable at four or sixteen months. In the short-term, active physiotherapy with several treatments appears to be of value in the outpatient management of patients with sciatic symptoms, but it does not seem to confer any longer-term benefit.