Medical Research Council Lifecourse Epidemiology Unit

Southampton, United Kingdom

Medical Research Council Lifecourse Epidemiology Unit

Southampton, United Kingdom
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News Article | April 25, 2017

These changes, known as epigenetic modifications, control the activity of our genes without changing the actual DNA sequence. One of the main epigenetic modifications is DNA methylation, which plays a key role in embryonic development and the formation of different cell types, regulating when and where genes are switched on. Although DNA methylation was originally thought to be a very stable modification, which once established in early life was then maintained throughout the life span of an individual, there is now growing evidence that the level of DNA methylation can be affected by a range of environmental factors such as parental health, diet and lifestyle. Researchers from the University of Southampton, as part of the EpiGen Global Consortium, analysed the levels of DNA methylation, in umbilical cord tissue of babies born in the Southampton Women's Survey. They compared DNA methylation levels present at birth with the amount of fat tissue in the child at four and six years of age. They found that lower DNA methylation at the CDKN2A gene, which regulates the production of fat cells, was associated with a greater risk of the child developing obesity in later life. Analysis showed that a 10 percent decrease in methylation at the CDKN2A gene was associated with an increase in fat mass of around 220g, at age 4 years. The results, published in EBio Medicine, were replicated in other groups of children and adults, notably the Singapore GUSTO study, the Australian RAINE study and the UK BIOCLAIMS cohort. Lead author Karen Lillycrop said: "This is exciting new evidence that epigenetic changes detectable at birth are linked to a child's health as they grow up. It was very promising to see our initial findings confirmed in so many other cohorts. Not only does it strengthen the body of evidence that shows a mothers health during pregnancy can affect the future health of her child, but it could also allow us to more accurately predict the future risk of obesity. If we can do this, then preventative strategies can be developed in early life to prevent the development of obesity." Professor Keith Godfrey, from the Medical Research Council Lifecourse Epidemiology Unit and the National Institute for Health Research Southampton Biomedical Research Centre and a member of the study team said: "The new findings provide the first direct evidence linking faltering of a baby's growth in the womb with epigenetic modifications that themselves may increase the risk of childhood obesity. The findings are now helping us to trial new nutritional interventions before and during pregnancy to reduce the baby's risk on obesity in childhood and later life, and strengthen the view that effective prevention of childhood obesity has to begin before the baby is born. The new findings may also lead to innovative approaches to the treatment of established obesity in later life." The EpiGen Global Consortium brings together expertise from the Human Development and Health Academic Unit, MRC Lifecourse Epidemiology Unit and Centre for Biological Sciences, University of Southampton; Singapore Institute for Clinical Sciences; National University of Singapore; Auckland UniServices Limited and the Liggins Institute, University of Auckland. The Consortium's aim is to improve human health through the life course by further understanding developmental and environmental processes. The research includes a focus on epigenetics, the biology of understanding how gene function is regulated by environmental factors, such as maternal nutrition, during the very early stages of development. This research was carried out as part of a collaboration with the Nestlé Research Centre, in Lausanne, Switzerland.

PubMed | Agency for Science, Technology and Research Singapore, National University of Singapore, KK Womens and Childrens Hospital KKH, KKH and Medical Research Council Lifecourse Epidemiology Unit
Type: Journal Article | Journal: Birth (Berkeley, Calif.) | Year: 2016

Many countries in Asia report low breastfeeding rates and the risk factors for early weaning are not well studied. We assessed the prevalence, duration, and mode of breastfeeding (direct or expressed) among mothers of three Asian ethnic groups.Participants were 1,030 Singaporean women recruited during early pregnancy. Data collected included early breastfeeding experiences, breastfeeding duration, and mode of breastfeeding. Full breastfeeding was defined as the intake of breast milk, with or without water. Cox regression models were used to identify factors associated with discontinuation of any and full breastfeeding. Logistic regression analyses assessed the association of ethnicity with mode of breastfeeding.At 6months postpartum, the prevalence of any breastfeeding was 46 percent for Chinese mothers, 22 percent for Malay mothers, and 41 percent for Indian mothers; prevalence of full breastfeeding was 11, 2, and 5 percent, respectively. More Chinese mothers fed their infants expressed breast milk, instead of directly breastfeeding them, compared with the other two ethnic groups. Duration of any and full breastfeeding were positively associated with breastfeeding a few hours after birth, higher maternal age and education, and negatively associated with irregular breastfeeding frequency and being shown how to breastfeed. Adjusting for maternal education, breastfeeding duration was similar in the three ethnic groups, but ethnicity remained a significant predictor of mode of breastfeeding.The low rates and duration of breastfeeding in this population may be improved with breastfeeding education and support, especially in mothers with lower education. Further work is needed to understand the cultural differences in mode of feeding and its implications for maternal and infant health.

PubMed | Agency for Science, Technology and Research Singapore, KK Womens and Childrens Hospital, National University of Singapore and Medical Research Council Lifecourse Epidemiology Unit
Type: Journal Article | Journal: Archives of women's mental health | Year: 2016

This study aimed to investigate associations of physical activity (PA) and sedentary behavior (SB) with depression and anxiety symptoms during pregnancy among Chinese, Malay, and Indian women.Women answered PA and SB (sitting time and television time) interview questions and self-completed the Edinburgh Postnatal Depression Scale (EPDS) and State-Trait Anxiety Inventory (STAI) questionnaires, at week 26-28 gestation. Sufficient levels of PA (600MET-minutes/week) and higher sitting time (7h/day) were determined. Associations of PA and SB with probable antenatal depression (EPDS-score 15), higher state anxiety (score 42), and higher trait anxiety (score 43) were determined by logistic regression analysis.Among the 1144 pregnant women included in the study, 7.3, 22.5, and 23.6% had probable antenatal depression, higher state anxiety, and higher trait anxiety symptoms, respectively. In the adjusted models, women with sufficient level of PA were less likely to have probable antenatal depression (OR 0.54, 95% CI 0.31-0.94, p=0.030) and higher trait anxiety symptoms (OR 0.68, 95% CI 0.48-0.94, p=0.022). PA was not associated with state anxiety symptoms. SB was not associated with any of the investigated outcomes.Sufficient PA was associated with a reduced likelihood of probable antenatal depression and trait anxiety symptoms. Further investigation of these findings is warranted to determine cause-effect relationships and identify potential preventive strategies.

News Article | October 27, 2016

Vitamin D supplements are less effective at raising vitamin D levels in pregnant women if they deliver their babies in the winter, have low levels of vitamin D early in pregnancy or gain more weight during pregnancy, a new Southampton study has shown. The findings, published the Endocrine Society's Journal of Clinical Endocrinology & Metabolism, showed pregnant women respond differently to vitamin D supplementation depending on their individual attributes. The University of Southampton researchers suggest that supplement levels should be tailored according to individual risk factors. Vitamin D is a hormone that helps the body absorb calcium. It plays a crucial role in bone and muscle health. The skin naturally produces vitamin D after exposure to sunlight but people also obtain smaller amounts of the vitamin through foods, such as milk fortified with vitamin D. Evidence suggests vitamin D deficiency during pregnancy can harm maternal health, fetal development and the child's long-term skeletal health. Professor Nicholas Harvey, of the Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, who led the study with Dr Rebecca Moon, Clinical Research Fellow, comments: "It is important for pregnant women to have sufficient levels of vitamin D for the health of their baby. Our study findings suggest that in order to optimise vitamin D concentrations through pregnancy, the supplemental dose given may need to be tailored to a woman's individual circumstances, such as the anticipated season of delivery." The Maternal Vitamin D Osteoporosis Study (MAVIDOS), is a multi-centre, double-blind, randomised, placebo-controlled trial of vitamin D supplementation in pregnancy. More than 800 pregnant women were recruited and randomised to take either 1000 units (25 micrograms) of vitamin D every day or a matched placebo capsule from 14 week's gestation until delivery of the baby. Analysis showed that participants who received the vitamin D supplement achieved different levels of vitamin D in the blood, even though they received the same dose. Researchers found women who delivered in the summer, who gained less weight during pregnancy and who had higher vitamin D levels early in pregnancy tended to have higher levels of vitamin D in the blood than their counterparts. Women who consistently took the supplement also had higher levels of vitamin D than participants who did not. "Our findings of varied responses to vitamin D supplementation according to individual attributes can be used to tailor approaches to antenatal care," said Professor Cyrus Cooper, Director, and Professor of Rheumatology at the MRC Lifecourse Epidemiology Unit, University of Southampton. "This work forms part of a larger programme of research at the MRC Lifecourse Epidemiology Unit, University of Southampton, addressing the early life determinants of bone development, and will inform novel strategies aimed at improving bone health across future generations." The study was funded by the charity Arthritis Research UK, with further funding support from the MRC, National Institute for Health Research (NIHR) and the Bupa Foundation.

Kajantie E.,Finnish National Institute for Health and Welfare | Kajantie E.,University of Helsinki | Osmond C.,Medical Research Council Lifecourse Epidemiology Unit | Osmond C.,University of Southampton | And 8 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - The association between low birth weight and type 2 diabetes is well established. We studied whether preterm birth carries a similar risk. RESEARCH DESIGN AND METHODS - The Helsinki Birth Cohort includes 13,345 men and women born between 1934 and 1944. Of them, 12,813 had adequate data on length of gestation, which we linked with data on special reimbursement for diabetes medication. RESULTS - Of the subjects, 5.1% had received special reimbursement after age 40. In subjects born before 35 weeks of gestation, the odds ratio for diabetes was 1.68 (95% CI 1.06-2.65) compared with that in those born at term. After adjustment for birth weight relative to length of gestation, the odds ratio was 1.59 (1.00-2.52). CONCLUSIONS - Preterm birth before 35 weeks of gestation is associated with an increased risk of type 2 diabetes in adult life. The risk is independent of that associated with slow fetal growth. © 2010 by the American Diabetes Association.

Duncan E.L.,University of Queensland | Danoy P.,University of Queensland | Kemp J.P.,University of Bristol | Leo P.J.,University of Queensland | And 53 more authors.
PLoS Genetics | Year: 2011

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. © 2011 Duncan et al.

van Sluijs E.M.F.,Medical Research Council Epidemiology Unit | van Sluijs E.M.F.,Center for Diet and Activity Research | McMinn A.M.,Medical Research Council Epidemiology Unit | McMinn A.M.,Center for Diet and Activity Research | And 8 more authors.
PLoS ONE | Year: 2013

Background:Correlates of physical activity (PA) are hypothesized to be context and behaviour specific, but there is limited evidence of this in young children. The aim of the current study is to investigate associations between personal, social and environmental factors and objectively measured light and moderate-to-vigorous PA (LPA and MVPA, respectively) in four-year-old children.Methods:Cross-sectional data were used from the Southampton Women's Survey, a UK population-based longitudinal study. Four-year old children (n = 487, 47.0% male) had valid PA data assessed using accelerometry (Actiheart) and exposure data collected with a validated maternal questionnaire (including data on child personality, family demographics, maternal behaviour, rules and restrictions, and perceived local environment). Linear regression modelling was used to analyse associations with LPA and MVPA separately, interactions with sex were explored.Results:LPA minutes were greater in children whose mothers reported more PA (vs. inactive: regression coefficient±standard error: 6.70±2.94 minutes), and without other children in the neighbourhood to play with (-6.33±2.44). MVPA minutes were greater in children with older siblings (vs. none: 5.81±2.80) and those whose mothers used active transport for short trips (vs. inactive: 6.24±2.95). Children accumulated more MVPA in spring (vs. winter: 9.50±4.03) and, in boys only, less MVPA with availability of other children in the neighbourhood (-3.98±1.70).Discussion:Young children's LPA and MVPA have differing associations with a number of social and environmental variables. Interventions targeting PA promotion in young children outside of formal care settings should consider including intensity specific factors. © 2013 van Sluijs et al.

Simmonds S.J.,Medical Research Council Lifecourse Epidemiology Unit | Syddall H.E.,Medical Research Council Lifecourse Epidemiology Unit | Westbury L.D.,Medical Research Council Lifecourse Epidemiology Unit | Dodds R.M.,Medical Research Council Lifecourse Epidemiology Unit | And 6 more authors.
Age and Ageing | Year: 2015

Background: lower grip strength on admission to hospital is known to be associated with longer stay, but the link between customary grip and risk of future admission is less clear.Objective: to compare grip strength with subsequent risk of hospital admission among community-dwelling older people in a UK setting.Design: cohort study with linked administrative data.Setting: Hertfordshire, UK.Subjects: a total of 2,997 community-dwelling men and women aged 59-73 years at baseline.Methods: the Hertfordshire Cohort Study (HCS) participants completed a baseline assessment between 1998 and 2004, during which grip strength was measured. Hospital Episode Statistics and mortality data to March 2010 were linked with the HCS database. Statistical models were used to investigate the association of grip strength with subsequent elective, emergency and long-stay hospitalisation and readmission.Results: there was a statistically significant negative association between grip strength and all classes of admission in women [unadjusted hazard ratio per standard deviation (SD) decrease in grip strength for: any admission/death 1.10 (95% CI: 1.06, 1.14), elective admission/death 1.09 (95% CI: 1.05, 1.13), emergency admission/death 1.21 (95% CI: 1.13, 1.31), long-stay admission/death 1.22 (95% CI: 1.13, 1.32) and unadjusted relative risk per SD decrease in grip strength for 30-day readmission/death 1.30 (95% CI: 1.19, 1.43)]. These associations remained significant after adjustment for potential confounding factors (age, height, weight for height, smoking, alcohol, social class). In men, unadjusted rates for emergency admission/death, long-stay admission/death and readmission/death were significantly associated with grip strength; associations that similarly withstood adjustment.Conclusion: this study provides the first evidence that grip strength among community-dwelling men and women in the UK is associated with risk of hospital admission over the following decade. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

PubMed | National Health Research Institute, University of Southern Denmark, University of Southampton, UK National Institute for Medical Research and Medical Research Council Lifecourse Epidemiology Unit
Type: Journal Article | Journal: The American journal of clinical nutrition | Year: 2016

Studies in older adults and animals have suggested contrasting relations between bone health and different vitamin A compounds. To our knowledge, the associations between maternal vitamin A status and offspring bone development have not previously been elucidated.We examined the associations between maternal serum retinol and -carotene concentrations during late pregnancy and offspring bone mineralization assessed at birth with the use of dual-energy X-ray absorptiometry.In the Southampton Womens Survey mother-offspring birth cohort, maternal health, lifestyle, and diet were assessed prepregnancy and at 11 and 34 wk of gestation. In late pregnancy, maternal serum retinol and -carotene concentrations were measured. Offspring total body bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were measured within 2 wk after birth.In total, 520 and 446 mother-offspring pairs had measurements of maternal serum retinol and -carotene, respectively. Higher maternal serum retinol in late pregnancy was associated with lower offspring total body BMC ( = -0.10 SD/SD; 95% CI: -0.19, -0.02; P = 0.020) and BA ( = -0.12 SD/SD; 95% CI: -0.20, -0.03; P = 0.009) but not BMD. Conversely, higher maternal serum -carotene concentrations in late pregnancy were associated with greater total body BMC ( = 0.12 SD/SD; 95% CI: 0.02, 0.21; P = 0.016) and BA ( = 0.12 SD/SD; 95% CI: 0.03, 0.22; P = 0.010) but not BMD.Maternal serum retinol and -carotene concentrations had differing associations with offspring bone size and growth at birth: retinol was negatively associated with these measurements, whereas -carotene was positively associated. These findings highlight the need for further investigation of the effects of maternal retinol and carotenoid status on offspring bone development.

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