Programme 4 has several collaborations with research groups in low- and middle-income countries LMICs other than India:

  • COHORTS: Five LMIC birth cohorts
  • EMPHASIS: Epigenetic mechanisms linking early life and later health
  • TALENT: Adolescent nutrition
  • NCD-RisC: Global NCD trends
  • INPReP: Guiding policy

The COHORTS collaboration (Consortium of Health-Orientated Research in Transitioning Societies)

Collaborators:

Cesar Victora, Bernardo Horta (Pelotas Birth Cohorts, Brazil); Aryeh Stein, Reynaldo Martorell, Manuel Ramirez (INCAP Nutrition Supplementation Trial Longitudinal Study, Guatemala); Santosh Bhargava, Harshpal Singh Sachdev, New Delhi Birth Cohort, India); Linda Adair, Nanette Lee (Cebu Longitudinal Health and Nutrition Survey, The Philippines); Shane Norris (Birth to Twenty Plus Study, South Africa)

The COHORTS collaboration brings together five prospective LMIC birth cohort studies with adult participants: the 1993 Pelotas Birth Cohort, Brazil; the INCAP Nutrition Supplementation Trial Longitudinal Study, Guatemala; the New Delhi Birth Cohort, India; the Birth to Twenty Plus Study, South Africa; and the Cebu Longitudinal Health and Nutrition Survey, The Philippines. Our previous work together has focussed mainly on weight and height gain during childhood as exposures, and their associations with adult cardiometabolic and human capital outcomes. These analyses benefit from the pooling of data across five cohorts, achieving a sample size of more than 8,000 individuals. These studies have shown that rapid weight gain from mid-childhood onwards is associated with greater adult adiposity, and a higher risk of hypertension and type 2 diabetes. Higher birth weight was associated with a lower risk of childhood stunting, a greater likelihood of completing higher education, and a lower risk of developing adult type 2 diabetes.

We have also shown effects of maternal age at childbirth on later health outcomes. Younger (<19 years) and older (>35 years) maternal age was associated with lower birth weight, gestational age, child nutritional status (weight and height) and schooling, compared with mothers aged 20-24 years. Associations with younger maternal age remained after adjustment for confounding factors. After adjustment, older maternal age remained associated with pre-term birth, but children of older mothers had less 2-year stunting and failure to complete secondary schooling. Offspring of both younger and older mothers had higher adult fasting glucose concentrations.

Legend: Each point represents the amount by which the outcome differs from the value obtained for offspring of mothers aged 20-24 years. These estimates are shown with 95% confidence intervals, and they are obtained by pooling across all five studies. Three of five models are included. Model 1 is adjusted for sex and age. Model 2 is further adjusted for maternal marital status, schooling, wealth, race and urbanicity. Models 3 and 4, in which further adjustment is made for maternal height and breastfeeding duration respectively, are not shown because the results were similar to Model 2. Model 5 is further adjusted for parity. Four p-values are shown: “p lin” is from a test for linear trend in the outcome with mother’s age; “p quad” is from a test for quadratic trend in the outcome with mother’s age; “het lin” is the F-test p-value for heterogeneity in the linear trends in the five studies; “het quad” is the F-test p-value for heterogeneity in the quadratic trends in the five studies. All four p values are derived using maternal age as a continuous variable. HAZ=WHO height for age Z-score. WHZ=WHO weight for height Z-score.

The purpose of the current work in COHORTS (2017-2020) is to further understand the contributions of early-life socio-economic circumstances (SEC) and childhood cognitive potential to adult social and human capital. The study will use existing data, and new measures of adult cognitive, executive and social and emotional function and an array of measures of social and human capital, including schooling attainment, employment history, income, family formation, and mental health. Identical tools are being used wherever possible to increase comparability.

Selected recent COHORTS publications:

  • Richter L, Victora C, Hallal P, Adair L, Bhargava S, Fall C, Martorell R, Lee N, Norris S, Stein A and the COHORTS group (Consortium of Health Orientated Research in Transitioning Societies). Cohort profile. Int J Epidemiol 2012; 41: 621-6. PMID: 21224276
  • Adair LS, Fall CHD, Osmond C, Stein AD, Martorell R, Ramirez-Zea M, Sachdev HPS, Dahly DL, Bas I, Norris S, Micklesfield L, Hallal P, Victora C and the COHORTS group. Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies. Lancet 2013; 382: 525-34. PMID: 23541370
  • Fall CHD, Sachdev HPS, Osmond C, Restrepo-Mendez M-C, Victora C, Martorell R, Stein AD, Sinha S, Tandon N, Adair L, Bas I, Norris S, Richter L and the COHORTS group. Associations between maternal age at childbirth and child and adult outcomes in the offspring; a prospective study in five low-income and middle-income countries. Lancet Global Health 2015; 3: e366-377. PMID: 25999096
  • Fall CH, Osmond C, Haazen DS, Sachdev HS, Victora C, Martorell R, Stein AD, Adair L, Norris S, Richter LM; COHORTS investigators. Disadvantages of having an adolescent mother. Lancet Glob Health. 2016; 4: e787-e788. PMID: 27765286

The EMPHASIS study (Epigenetic mechanisms linking maternal pre-conceptional micronutrient supplementation with offspring health in India and sub-Saharan Africa

Collaborators:

Andrew Prentice and Matt Silver, MRC The Gambia at the London School of Hygiene and Tropical Medicine; Giriraj Chandak, centre for Cellular and Molecular Biology, Hyderabad, India

This ongoing collaboration (www.emphasisstudy.org) was formed in 2016 to investigate peri-conceptional nutrition interventions and DNA methylation in children as a mechanism linking early life nutrition with later cardiometabolic health and human capital. Data from two intervention studies have been used: the Mumbai Maternal Nutrition Study (SARAS) in Mumbai (link to Mumbai Maternal Nutrition Study Cohort) and the Peri-conceptional Multiple Micronutrient Supple-mentation Trial (PMMST) in The Gambia. The intervention in India was food-based (a daily micronutrient-rich snack made from local foods) and the intervention in The Gambia was a daily multiple micronutrient tablet (UNIMMAP). We have measured epigenome-wide DNA methylation using the 850K Illumina Epic array, and at selected candidate loci not on EPIC. The analysis will be in 3 stages (see EMPHASIS website for analysis plan: 1) associations between the interventions and children’s DNA methylation; 2) associations between methylation and phenotypes (identical outcome measures in SARAS KIDS and PMMST); and 3) mediation analyses to assess the causality of methylation-phenotype associations.

Selected recent EMPHASIS publications:

  • Chandak GR, Silver MJ, Saffari A, Lillycrop KA, Shrestha S, Sahariah SA, Di Gravio C, Goldberg G, Tomar AS, Betts M, Sajjadi S, Acolatse L, James P, Issarapu P, Kumaran K, Potdar RD, Prentice AM, Chopra J, Cooper C, Darboe MK, Gandhi M, Janha R, Jarjou L, Kaur L, Kehoe SH, Ngum M, Nongmaithem SS, Owens S, Prentice A, Priyanka TDS, Sane H, Ward KA, Yadav DK, Yajnik CS, Fall CHD and the EMPHASIS Study Group. Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children’s health in India and Sub-Saharan Africa. BMC Nutrition 2017; 3:81; DOI 10.1186/s40795-017-0200-0. Not Pubmed listed
  • James P, Sajjadi S, Tomar AS, Saffari A, Fall CHD, Prentice AM, Shrestha S, Issarapu P, Yadav DK, Kaur L, Lillycrop K, Silver M, Chandak GR and the EMPHASIS study group. Candidate genes linking maternal nutrient exposure to offspring health via DNA methylation: a review of existing evidence in humans with specific focus on one-carbon metabolism. Int J Epidemiol 2018; 47: 1910-37. PMID: 30137462

The TALENT consortium (Transforming Adolescent Lives Through Nutrition)

Collaborators:

Abraham Haileamlak Mitike, Jimma University, Ethiopia; Julie Jesson, University of Toulouse, France and PAC-CI, Abidjan, Ivory Coast; Landing Jarjou, MRC The Gambia; Sophie Moore, King’s College London; Elizabeth Kimani-Murage, African Population and Health Research Center (APHRC), Nairobi, Kenya; Shane Norris, Witwatersrand University, Johannesburg, South Africa; Sirazul Ameen Sahariah, CSSC, Mumbai, India; Suvarna Patil, Walawalkar Hospital, Dervan, India; Chittaranjan Yajnik, KEM Hospital and Research Centre, Pune, India; GV Krishnaveni, CSI Holdsworth Memorial Hospital, Mysore

Adolescent nutrition is a growing interest in the LEU Programmes 4 and 6, with the recognition that adolescence is a critical life stage for the acquisition of physical and mental capital and behaviour patterns that will influence adolescents’ later life NCD risk and the health of their children. Adolescents now form 25-35% of the population in LMICs but have been relatively neglected in nutrition research, leaving large knowledge gaps about nutritional status in this age group, and the impact of nutrition on growth, achievement of peak physical strength and cognitive capacity. Many adolescents in LMICs experience food insecurity and micronutrient deficiencies, while transition is bringing new causes of malnutrition through energy-dense micronutrient-poor fast foods and barriers to physical exercise.

The TALENT consortium (http://generic.wordpress.soton.ac.uk/adolescentnutrition/ ), led by Caroline Fall and Mary Barker, along with others from the LEU and University of Southampton (Polly Hardy-Johnson, Susan Weller, Sarah Kehoe, Kate Ward) in partnership with investigators from India, Ethiopia, Ivory Coast, The Gambia, Kenya and South Africa was set up in 2018.

We have held three workshops, in India, South Africa and Southampton to train teams from all the centres in qualitative research methods. Qualitative data were then collected from young (10-12y) and older (15-17y) adolescents and their parents to explore what young people think about diet, nutrition and activity and their influence on health; how important these are to them; what drives their eating and activity habits; and what might engage them in changing these.

Data from 51 focus groups in 8 centres are still being processed but have yielded several insights. Adolescents from even the poorest settings were well-informed about the importance of diet and physical activity for health, and wanted better health (eg. more energy, physical strength and longer life) but admitted that other considerations (taste, peer and social media influence) made them eat unhealthily and do too little exercise, a major source of conflict with parents. Adolescents’ diet and exercise habits were influenced by their environment and community; factors included income, religion, culture, gender, and availability and safety of outside spaces.

We concluded that interventions to improve adolescent diet and physical activity in these settings would need to be complex in design, context-specific, co-created with adolescents, and address adolescent needs for autonomy and recognition. In future work together we aim to fill knowledge gaps about adolescent nutritional status in LMICs (and its impact on health) and develop such interventions to improve diet, nutrition and physical activity in this age group.

NCD Risk Factor Collaboration (NCD-RisC)

Collaborators:

NCD-RisC is led by a large group of investigators from Imperial College London (Bin Zhou, Majid Ezzati, James Bentham, Mariachiara Di Cesare, Honor Bixby, James E Bennett); Harvard TH Chan School of Public Health (Yuan Lu, Kaveh Hajifathalian, Goodarz Danaei); WHO (Melanie Cowan, Gretchen Stevens, Leanne Riley); and others, along with multiple data contributors globally.

Programme 4 contributes New Delhi Birth Cohort data to NCD-RisC (www.ncdrisc.org), which analyses NCD trends among >19 million people in >180 countries. NCD-RisC has produced a series of high-impact papers documenting the rise of obesity, hypertension and diabetes, with the most rapid increases occurring in LMICs, over the past 30 years.

Selected recent publications from the NCD-RisC group:

  • NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: pooled analysis of 751 population-based measurement studies with over 4.4 million participants. Lancet 2016; 387: 1513-30. PMID: 27061677
  • NCD Risk Factor Collaboration (NCD-RisC). A century of trends in adult human height. E-life 2016; 5. pii: e13410. doi: 10.7554/eLife.13410. PMID: 27458798
  • NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1,479 population-based measurement studies with 19.1 million participants. Lancet 2017;7;389:37-55. PMID: 27863813
  • NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body mass index, underweight, overweight and obesity from 1975 to 2016: a pooled analysis of 2,416 population-based measurement studies with 128.9 million children, adolescents and adults. Lancet 2017; 390: 2627-42. PMID: 29029897

INPReP (Improved Nutrition, Preconception, Pregnancy and Post-delivery)

Collaborators:

Marie-Louise Newell, NIHR Southampton Biomedical Research Centre and Global Health Research Institute, University of Southampton; Shane Norris, Karen Hofman, Witwatersrand University, Johannesburg, S Africa; Engelbert Nonterah, Navrongo Health Research Centre, Ghana; Hermann Sorgho, Institut de Recherche en Sciences de la Sante, Nanoro, Burkina Faso.

The INPreP (Improved Nutrition, Preconception, Pregnancy and Post-delivery) study is led by Prof Marie-Louise Newell, with major contributions from LEU staff Kate Ward and Sarah Kehoe. Over the next three years it aims to establish a framework for optimising nutrition before, during and after pregnancy (‘1000 DaysPlus’) in sub-Saharan Africa and develop and pilot nutritional interventions that tackle both aspects of the double burden of malnutrition and are feasible within policy frameworks and health systems. An in-depth review of nutrition policies in South Africa, Burkina Faso and Ghana will be carried out and there will be engagement with multi-sector stakeholders around pre-conception, pregnancy and post-natal care, to understand needs and priorities, barriers and opportunities. An economic modelling exercise will be conducted, to understand the costs and benefits of investment in 1000 DaysPlus nutrition, and to formulate an economic case for investment. The study will identify existing evidence-based nutrition interventions that could be embedded in policy, reproductive health services, programmes and clinics, and identify novel interventions. The latter activity will be supported by public and stakeholder engagement tool an adapted ‘CHAT’ tool (Choosing Health Plans All Together). Finally, the study will develop protocols and pilot these novel interventions.