Nutrition, developmental epigenetics and lifelong health
Submitting InstitutionUniversity of Southampton
Unit of AssessmentClinical Medicine
Summary Impact TypeSocietal
Research Subject Area(s)
Medical and Health Sciences: Nutrition and Dietetics, Paediatrics and Reproductive Medicine, Public Health and Health Services
Summary of the impact
The University of Southampton's lifecourse cohort studies have led to a
paradigm shift in the medical approach to obesity and non-communicable
diseases. Research linking maternal pre-conception and early years
nutrition with health outcomes for later life has directly influenced
public healthcare policy at international (United Nations), national
(Scientific Advisory Committee on Nutrition) and local (Southampton City)
levels. Dissemination through medical practice and Southampton-designed
public education programmes such as LifeLab means this research
has already led to health benefits for tens of thousands of people,
providing them with the information and tools to help prevent themselves
and their children from succumbing to a non-communicable disease.
While scientists have long known that chromosomes passed from parent to
child form a genetic blueprint for development, they've come to realise
more recently that genes are not a fixed predetermined programme. Instead,
they can be turned on and off by experiences and environment. It is this
science of 'epigenetics', particularly how nutritional influences during
development affect later risk of obesity and chronic non-communicable
diseases (NCDs) that has been the focus of research at the University of
Southampton's Medical Research Council (MRC) Lifecourse Epidemiology Unit
(LEU), led by Professor Cyrus Cooper, LEU Director (joined Southampton
1992), Keith Godfrey, Professor of Epidemiology and Human Development
(joined 1999), Hazel Inskip, Deputy Director LEU (joined 1991), David
Barker, Professor of Clinical Epidemiology (joined 1972) and Mark Hanson,
Director, Institute of Developmental Studies (since 2000).
This research is framed by two ongoing projects: the Hertfordshire
Cohort Study (since 1989) and the Southampton Women's Survey
The Hertfordshire Cohort Study (HCS) comprises 3000 people born
1931-1939. Its principal objective has been to evaluate the relationship
between early growth, genetic influences, adult lifestyle and the risk of
common age-related disorders such as osteoporosis, osteoarthritis,
sarcopenia, type 2 diabetes and cardiovascular disease. Since 1993
researchers focusing on NCDs have undertaken detailed cardiovascular
phenotyping of 1000s of participants during the seventh and eighth decade
of life, and, using historical data (e.g. birthweight, weight at age one
year, method of infant feeding, childhood illnesses) linked these to poor
growth in utero and during infancy [3.1]. Additional key findings
included the insight that elements of the heritable/familial component of
susceptibility to cardiovascular disease, obesity and other NCDs can be
transmitted across generations by non-genomic means [3.2].
The Southampton Women's Survey (SWS) is the only European study
of women and their children for which maternal data and samples were
collected before conception. Between 1998 and 2002, SWS researchers
interviewed 12,583 women aged 20-34 years. Those who became pregnant
afterwards were invited to take part in the pregnancy phase of the survey.
Participants received ultrasound scans at 11, 19 and 34 weeks of
pregnancy, and their babies (3156 between 1998 and 2007) were measured
soon after birth. Offspring were further assessed during home visits at 6,
12, 24 and 36 months. Some attended follow-up clinics to assess bone
density (745 children), heart rate (414 mother/child pairs) and brain
development (269 mother/child pairs) at ages four, six and ten/eleven
years. Dietary information was also collected. Researchers found that
patterns of diet, health behaviours and lifestyle were set before
pregnancy and that maternal pre-pregnancy quality of diet was the
strongest predictor of the quality of her infant's diet, which in turn is
positively associated with later outcomes [3.3], particularly lean
mass [3.4] and cognitive function. Researchers also found that
pre-pregnancy adiposity and excessive weight gain during pregnancy were
associated with increased risk of childhood obesity [3.5].
Epigenetic markers identified from umbilical cord samples were strongly
associated with childhood total and central body fat at age 6 years [3.6].
References to the research
3.1 Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in
utero and early-life conditions on adult health and disease. New
England Journal of Medicine 2008; 359:61-73 [844 cites]
3.2 Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD, Hanson MA.
Epigenetic mechanisms and the mismatch concept of the developmental
origins of health and disease. Pediatr Res 2007; 61:5R-10R. [177
3.3 Robinson S, Marriott L, Poole J, Crozier S, Borland S,
Lawrence W, Law C, Godfrey K, Cooper C, Inskip H, Southampton Women's
Survey Study Group. Dietary patterns in infancy: the importance of
maternal and family influences on feeding practice. Brit J Nutr
3.4 Robinson SM, Marriott LD, Crozier SR, Harvey NC,Gale CR,
Inskip HM, Baird J, Law CM, Godfrey KM, Cooper C, Southampton Women's
Survey Study Group. Variations in infant feeding practice are associated
with body composition in childhood: a prospective cohort study. J Clin
Endocrin Metab 2009; 94:2799-805
3.5 Crozier SR, Inskip HM, Godfrey KM, Cooper C, Harvey NC, Cole
ZA, Robinson SM. Weight gain in pregnancy and childhood body composition:
findings from the Southampton Women's Survey. Am.J Clin Nutr 2010;
3.6 Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC,
McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR, Emerald
BS, Gale CR, Inskip HM, Cooper C, Hanson MA. Epigenetic gene promoter
methylation at birth is associated with child's later adiposity. Diabetes
2011; 60:1528-34. [136 cites] (In Faculty of 1000 top 2% of published
articles in biology and medicine http://f1000.com/13030957)
Key grants awarded:
2010-2014. Inskip H, Robinson S, Godfrey K, Osmond C. Medical Research
Council. MRC Lifecourse Epidemiology Unit, Programme 4: Nutrition,
Development and Lifelong Health: Studies in European Populations.
2012-17. Koletzko B, Poston L, Godfrey KM, et al. European Union (FP7):
EarlyNutrition: Long-term effects of early nutrition on later health,
2012-2017. Jackson A, Godfrey K, Hanson M, Calder P, Cooper C, et al.
National Institute for Health Research. NIHR Southampton Biomedical
Research Centre. £9,677,372
2008-2013. Hanson M, Godfrey K, Cooper C, Inskip H, Deanfield J. British
Heart Foundation. Maternal, infant and childhood determinants of
cardiovascular structure and function. £822,000.
Details of the impact
HCS and SWS research findings have directly resulted in a wide range of
international, national and local policy changes towards the prevention
and control of non-communicable diseases, as well as training and public
education programmes, leading to health benefits for millions of people.
Public policy: Following review by the National Institute for
Health and Care Excellence (NICE), SWS research findings fed directly into
the formation of new public health guidance on nutrition for pregnant and
breastfeeding mothers and children in low-income households (published in
2008, [5.1]) and on weight management before, after and during
pregnancy (published 2010, [5.2]). NICE guidelines are used in the
education and training of health professionals and by pregnant and
breastfeeding mothers to make informed decisions. Government figures show
that there were over 3.9 million children living in low-income households
in 2008/2009; 25-30% of those children were in the first few years of
The Scientific Advisory Committee on Nutrition's (SACN's) policy on early
influences on chronic diseases in later life, published in 2011, similarly
draws heavily on Southampton research. The SACN final report specifically
cites SWS data and findings on the association between longer duration of
breastfeeding and lower fat mass at 4 years, on low maternal vitamin D
status and fetal bone development, and on low income diet and nutrition.
The impact of this research becomes clear in the report's 'Public health
recommendations' which include life-long nutritional interventions linked
to reproductive health and chronic disease prevention, and SACN's specific
recommendation of mandatory fortification of flour with folic acid in the
UK as a measure to prevent pregnancies affected by neural tube defects.
This measure was being considered by health ministers in July 2013 [5.3].
In 2008, Southampton research on the developmental origins of health and
disease informed the World Health Organisation Action Plan for the
prevention of non-communicable diseases [5.4].
In 2009, Hanson met Andrew Lansley, Secretary of State for Health, to
discuss implementation of this plan. Subsequent to that meeting, Lansley
attended a UN General Assembly Summit on NCDs to discuss their rising
incidence, social and economic impact and risk factors (10-12 November
2009). In the public press conference following the summit, Lansley
pointed to the clear links between NCDs and maternal/child health. Poor
nutrition during pregnancy, he told representatives of the international
press, led to higher rates of diabetes and high blood pressure later in
Between 2007-2010, The Food Standards Agency funded Inskip (£434,000) to
undertake SWS data collection and write a comprehensive report on
nutritional influences on body composition, cognitive function development
and respiratory health [5.6].
Industrial impact: Through the EpiGen Consortium (an international
alliance of six private and public sector epigenetics researchers — one of
which is LEU — established in 2006), SWS research linking perinatal
biological samples to epigenetic measurements has been further
disseminated. So far this has led to more than £10 million in research
collaborations, with Southampton research in metabolic programming
directly leading to three patents for the formulation of nutritional
products for mothers and infants filed in 2007, 2008 and 2009.
Professional practice: Launched in 2010, the Southampton
Initiative for Health (SIH) is a training intervention with Sure Start
Children's Centre (SSCC) staff designed to improve the diets and physical
activity levels of women of childbearing age. Developed with the primary
care trust and based on SWS findings, researchers have trained over 150
SSCC staff in holding 'healthy conversations' with their clients. More
than 500 women have enrolled in the study so far with potential benefits
for their diet and activity levels [5.7]. Sure Start trainees
reported feeling empowered by the training; one said "Very good course...
it has given me a lot to think about when planning my own training and
support in health behaviour change."
Public benefit: In 2008, SWS researchers launched LifeLab —
an innovative educational intervention designed to enable 11-16 year-olds
to learn how diet and lifestyle lay the foundations for a healthier life,
and how their own health is linked to the health of their future children.
So far, more than 1,500 students in Southampton have taken part in the
programme. Feedback indicates that six months after visiting, students had
a greater understanding of the impact of health behaviours in early life
on future health compared with peers. LifeLab students were
significantly more likely to consider pursuing science and healthcare
subjects after their GCSEs. One student said "...there's only so much you
can learn in school... if you actually go there and do it for yourself
it's much better." OFSTED said LifeLab "is making an important
contribution to students' understanding of the need to adopt healthy
lifestyles." LifeLab is now a key part of Southampton City's
public health strategy [5.8].
Public awareness and understanding of the research findings were raised
through a BBC2 Horizon special "The Nine Months That Made You" [5.9]
based on Barker's research, and BBC News coverage (13/2/2009).
Sources to corroborate the impact
5.1 National Institute for Health and Clinical Excellence.
Maternal and child nutrition. NICE public health guidance 11. NICE 2008 http://www.nice.org.uk/nicemedia/live/11943/40097/40097.pdf
5.2 National Institute for Health and Clinical Excellence. Weight
management, before, during and after pregnancy. NICE public health
guidance 27. NICE 2010 http://www.nice.org.uk/nicemedia/live/13056/49926/49926.pdf
5.3 Scientific Advisory Committee on Nutrition. The influence of
maternal, fetal and child nutrition on the development of chronic disease
in later life. Scientific Advisory Committee on Nutrition 2011. http://www.sacn.gov.uk/pdfs/sacn_early_nutrition_final_report_20_6_11.pdf
*n.b* SWS research and findings are specifically mentioned in Sections
404-407 with associated public health recommendations appearing in
Section 8.1, R1-6. See Appendix 2 for details
5.4 World Health Organization, 2008. 2008-2013 Action Plan for the
Global Strategy for the Prevention and Control of Noncommunicable
Diseases. World Health Organization.
5.5 United Nations Political declaration of the High-level Meeting
of the General Assembly on the Prevention and Control of Non-communicable
Diseases (September 2011)
5.6 Inskip H, Godfrey K, Robinson S, Warner J, Calder P, Roberts
G, Lucas J, Jackson A, Cooper C. FSA-N05071. Maternal, infant and
childhood diet: influence on respiratory health and asthma in childhood.
Contractor's final report to the Food Standards Agency 2010 (Confidential
report held by Hazel Inskip and Barbara Thomas)
5.7 Barker M, Lawrence W, Baird J, Jarman M, Black C, Barnard K,
Cradock S, Davies J, Margetts B, Inskip H, Cooper C. The Southampton
Initiative for Health: a complex intervention to improve the diets and
increase the physical activity levels of women and children from
disadvantaged communities. Health Psychol. 2011;16:178-91.
5.8 NHS Southampton City. Health in Southampton 2012. Report from
the Director of Public Health http://www.southamptonhealth.nhs.uk/EasysiteWeb/getresource.axd?AssetID=140605&type=full&servicetype=Attachment
Page 17 refers to LifeLab
5.9 BBC Horizon, August 2011 `The Nine Months That Made You'