The health and economic burden of non-communicable diseases (NCDs) such as diabetes and cardiovascular disease is increasing rapidly worldwide, and falls disproportionally on low- and middle-income countries (LMICs) where almost 75% of the global deaths from NCDs occur. Current preventive strategies to reduce the burden of diabetes and cardiovascular disease focus on lifestyle improvement in middle-aged individuals with pre-existing disease or risk factors. While these measures can improve the outlook for those individuals, they do little to prevent the disease in future generations. Research, including that from our group in India, has shown that poor maternal nutrition has an adverse impact on fetal growth and development, leading to an increased susceptibility to diabetes and cardiovascular disease in adult life. Therefore, optimising maternal nutrition, and fetal growth and development, by intervening before and during pregnancy, offers a paradigm shift in thinking about the prevention of NCDs.

We have previously demonstrated a strong role for maternal micronutrient deficiency in fetal growth and risk factors for type 2 diabetes in their children. Based on our findings, we embarked on two maternal nutritional supplementation trials. Previous intervention studies of maternal supplementation started in mid-pregnancy and would have missed the processes that occur around conception and early-gestation. We therefore decided to start the intervention pre-conceptionally to influence these processes.

Project SARAS

The Mumbai Maternal Nutrition Project (Project SARAS) (add link to the Mumbai Maternal Nutrition Project) was a community-based randomised controlled trial among women who lived in the urban slums of Mumbai. The main aim was to test whether improving the micronutrient quality of their diet before conception, and throughout pregnancy, improved birth weight and the long-term health of their children. The intervention was a daily snack made from micronutrient-rich foods (green leafy vegetables, fruit and milk) starting pre-conceptionally and continuing until delivery (Figure). Control snacks were made from low micronutrient vegetables. Of the 6513 women who were recruited, 2291 became pregnant and 1962 delivered live singleton newborns. Mothers who received the supplements for >3 months before conception had babies whose birthweight was higher by 48 g (p=0.05) compared to controls. The supplement had a stronger effect if the mother had a BMI >18.5 kg/m2 (Figure). The prevalence of low birth weight was reduced in the treatment group (34% vs 41%, p=0.03), as was the prevalence of gestational diabetes mellitus (GDM) (7% v 12%; p=0.008).

The children (Project SARAS KIDS) were subsequently followed up at age 5-8 years for body composition (DXA), cardiometabolic risk markers and cognitive function. We completed the follow-up in 2018 in 1276 children (67% of survivors); the results are currently being analysed.

Selected recent publications from Project SARAS:

  • Potdar RD, Sahariah SA, Gandhi M, Kehoe SH, Brown N, Sane H, Dayama M, Jha S, Lawande A, Coakley PJ, Marley-Zagar E, Chopra H, Shivshankaran D, Chheda-Gala P, Muley-Lotankar P, Subbulakshmi G, Wills AK, Cox VA, Taskar V, Barker DJP, Jackson AA, Margetts BM, Fall CHD. Improving women’s diet quality pre-conceptionally and during gestation: effects on birth weight and prevalence of LBW; a randomized controlled efficacy trial in India (Mumbai Maternal Nutrition Project). Am J Clin Nutr 2014; 100: 1257-68. PMID: 25332324
  • Kehoe S, Chopra H, Sahariah SA, Bhat DS, Munshi R, Young S, Brown N, Tarwande D, Gandhi M, Margetts BM, Potdar R, Fall CHD. Effects of a food-based intervention on markers of micronutrient status in low-income Indian women. Br J Nutr 2015; 113: 813-21. PMID: 25677713
  • Sahariah SA, Potdar RD, Gandhi M, Kehoe SH, Brown N, Sane H, Coakley PJ, Marley-Zagar E, Chopra H, Shivshankaran D, Cox VA, Jackson AA, Margetts BM, Fall CHD. A daily snack containing green leafy vegetables, fruit and milk before and during pregnancy prevented gestational diabetes in a randomized controlled trial in Mumbai, India. J Nutr 2016; 146: 1453S-60S. PMID: 27281802
  • 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
  • Lawande A, Di Gravio C, Potdar RD, Sahariah SA, Gandhi M, Chopra H, Sane H, Kehoe SH, Marley-Zagar E, Margetts BM, Jackson AA, Fall CHD. Effect of a micronutrient-rich snack taken pre-conceptionally and throughout pregnancy on ultrasound measures of fetal growth: the Mumbai Maternal Nutrition Project (MMNP). Matern Child Nutr 2018; doi: 10.1111/mcn.12441. PMID: 28251804
  • Chopra HV, Kehoe SH, Sahariah SA, Sane HN, Cox VA, Tarwade DV, Margetts BM, Potdar RD, Fall CHD, Joshi SR. Effect of a daily snack containing green leafy vegetables on women’s fatty acid status – a randomized controlled trial in Mumbai, India. Asia Pacific J Clin Nutr 2018; 27: 804-817. PMID: 30045425


The Pune Maternal Nutrition Study (PMNS) (add link to the Pune Maternal Nutrition Study) is a birth cohort set up in six villages near the city of Pune in 1993. When the cohort members reached late adolescence, in collaboration with Chittaranjan Yajnik, we enrolled them in a community-based randomised controlled trial of vitamin B12 supplementation (Pune Rural Intervention in Young Adolescents; PRIYA). Those with B12 concentrations <100 pmol/l were excluded from the trial and treated. The remainder (N=557) were randomised into three arms to receive supplements pre-conceptionally for at least 5 years or until their first delivery (Figure): 1) B12 alone (2μg/day), 2) B12 2μg + multiple micronutrients + 5g protein, and 3) standard care. The main hypothesis is that vitamin B12 supplementation of adolescent girls improves their offspring birth weight and B12 status, newborn and childhood body composition (reduced adiposity and increased lean mass), and reduces future diabetes. We plan long-term cardiometabolic and neurocognitive follow-up of the children. Biospecimens, including placenta, maternal and cord blood, newborn buccal swabs and microbiota are being collected. We intend to study the molecular changes between the intervention groups to develop a better understanding of the mechanisms of fetal programming.

The trial is ongoing; we expect to achieve the target sample (180-200 deliveries) by 2020. As of date, ~175 have become pregnant and ~130 have delivered.

Selected recent publications from the PRIYA Trial:

  • Kumaran K, Yajnik P, Lubree H, Joglekar C, Bhat D, Katre P, Joshi S, Ladkat R, Fall CHD, Yajnik CS. The Pune Rural Intervention in Young Adolescents (PRIYA) study: design and methods. BMC Nutrition 2017; 3: 41. doi: 10.1186/s40795-017-0143-5. Not Pubmed listed

HeLTI-India Trial

We are moving on from single nutritional interventions to complex interventions in order to address multiple dimensions affecting long-term health. Our group is involved in the Healthy Life Trajectories Initiative (HeLTI), developed in partnership with national funders from Canada, India, China and South Africa and in collaboration with the World Health Organization. There are four separate but harmonized intervention studies implemented in Mysore, Shanghai, Johannesburg and three provinces in Canada. The HeLTI-India study will deliver an integrated package of interventions starting pre-pregnancy and at appropriate points during pregnancy, infancy and childhood. The goal is to reduce childhood adiposity, and improve child health and neurodevelopment. It is a community-based randomised trial set in rural Mysore, South India with three arms (pre-conception, pregnancy and controls) (Figure). Women of reproductive age will receive a multi-faceted intervention delivered by community health workers comprising of: a) multiple micronutrients; b) a group parenting program to address maternal depression and improve child development; c) hygiene and infection prevention measures; and d) reduction of environmental pollution exposure. Interventions will be underpinned by a lifestyle behavior change strategy.

The study will track a host of intermediate and process outcomes, as well as the efficacy, cost-effectiveness, and acceptability of the intervention package, compared with standard care. The study will also report on the relative costs and benefits of commencing the intervention in early pregnancy compared with the preconception period.

At present we are undertaking formative work in 3 representative villages. We will engage with community leaders, women’s self-help groups, and local community health workers. Objectives will be to understand perceptions about pregnancy and aspirations for children, and discuss existing mother-child care provision and the acceptability of our proposed intervention package. Through survey work and group discussions we will obtain information on socioeconomic circumstances, diet, environmental toxin exposure, water and sanitation facilities, and hygiene practices, to inform the development of engagement materials for the main study.