Pregnancy Interventions In Mothers Relating to Diabetes In Asian India and Low-income countries (The PRIMORDIAL Study)

Lead Research Organisation: University of Oxford
Department Name: RDM OCDEM


Gestational diabetes (GDM) is associated with significant pregnancy-related complications to the mother and the child and poses a long-term risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Increasing prevalence of obesity, T2D and CVD are major public health concerns in the low- and middle- income countries (LMICs) and will put strain on limited health care resources. For GDM, the incidence is expected to rise across the globe in parallel with increasing adiposity among women. Prevention of GDM will reduce the burden of T2D in the community and has both immediate and life-long benefits on maternal and the child to adult lifespan health.

GDM diagnosis is usually made late in pregnancy and focus is given to women who have already developed GDM. However, a number of established risk factors place a group of women at 'high-risk' for developing GDM. Being overweight or obese prior to, or during pregnancy, excessive weight gain during pregnancy, advancing age at pregnancy, first degree relative with T2D, high blood pressure during pregnancy, previous abortions are all considered 'high-risk' for developing GDM. Therefore, research into factors that are linked to behavioural change and promotion of healthier lifestyle will identify new treatments to prevent GDM.

Recent research from the UK have suggested that initiating lifestyle changes late in pregnancy is unlikely to be helpful in preventing GDM. Therefore, early prevention of GDM has the potential of reducing the risk in both the mother as well as the child. Early screening, optimising maternal nutrition and advocating moderate physical activity beginning from early pregnancy are the mainstays of obstetric management of high-risk mothers. However, the major challenge in implementing lifestyle changes during pregnancy relates to adherence to proposed interventions. Dietary advice on calorie restriction and proposal of set of exercises during pregnancy is usually not successful mainly because poor participant compliance. It is therefore important to understand the socio-cultural barriers and then designing interventions that are suitable, acceptable and cost-effective to improve adherence to any intervention programme.

There are evidences to suggest that any behavioural change in life-style before or during pregnancy has important health implications. Both fermented yoghurt and physical activity have been shown to reduce the risk of diabetes by acting through the gut micro-organisms and also improving the sensitivity of the tissues to insulin. The proposed study will build on these evidences using a gold-standard interventional study design. The project brings together leading researchers in the UK, Indian and Gambian groups to study the effect of lifestyle intervention namely fermented yoghurt and daily walking in women who are high-risk for developing GDM. An overarching objective is to build capacity for improved antenatal care in India and The Gambia. The project will lead to a better understanding how simple lifestyle changes during pregnancy has profound beneficial effects on the maternal and child health, and ultimately to the design of improved interventions for mothers during for pregnancy.

Technical Summary

Given the robust evidence that dietary modification and improved physical activity (PA) reduces T2D risk, such interventions during pregnancy should also reduce the risk of GDM similarly. Studies have shown that dietary changes and PA positively impacts gestational weight gain, maternal metabolic profile and also neonatal outcomes. However, most of the evidence arise from Western populations. The proposed study will be the first investigation to evaluate the effect of fermented yoghurt and PA initiated in early pregnancy and continued to late pregnancy on incidence of GDM in LMICs. We hope to confirm that such realistic and feasible interventions are effective in preventing GDM. We will also examine the effect of such interventions on other pregnancy-related and new born outcomes. This project will build capacity for improved antenatal services in LMICs specifically. The intervention may offer an efficient platform for future research into understanding diet and PA impact on alteration of the gut microbiota of the mother and its effects on child health. If we show that improving a mother's lifestyle during pregnancy using fermented yoghurt and PA reduces the incidence of GDM and improves metabolic health in both mother and the child, with a potential lifelong benefit, our findings will offer a scalable pathway for wide implementation.

Planned Impact

The possibility of changing lifestyle behaviour during pregnancy will influence both immediate and life-long benefits to the mother and the child, which has profound implications that could be of great importance. Lifestyle change is a well-recognized mainstay of management of obesity and GDM and has been elevated to national policy in many countries across the world. By demonstrating that simple interventions during pregnancy can have a lasting impact on mother and child health this will have the prospect of reducing the burden of non-communicable diseases with far-reaching impact. This proposed research will benefit global and national agencies responsible for improving maternal and child health and preventing chronic disease by a) demonstrating the importance of lifestyle changes during pregnancy on health of the mother and offspring and b) identifying the effectiveness of specific nutritional (yoghurt) and PA (walking) interventions on GDM risk reduction. The research will also build capacity for pregnancy-related interventional research in the UK, India and The Gambia. It will foster the competitiveness of UK, Indian and Gambian science and research through the research groups participating in this project which currently lead the world in the field of obesity, diabetes, maternal nutrition and pregnancy-care.
Title PRIMORDIAL clinical trial registrations 
Description The PRIMORDIAL study has started after passing all regulatory and ethical approvals. Clinical trial registration was completed in 2019. The trial is now randomising participants. 
Type Preventative Intervention - Nutrition and Chemoprevention
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2019
Development Status Under active development/distribution
Clinical Trial? Yes
Impact The trial is now randomising participants. 
Description National Gambian TV broadcasting 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact News item describing the landmark PRIMORDIAL trial on QTVNews on Oct 10th 2019 in the Gambia. A 21MB video is available from F Karpe.
Year(s) Of Engagement Activity 2019
Description Participation in a high profile BBC medical program 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interview with me by Dr Michael Mosley in his 3rd series of 'Trust Me, I'm a Doctor', episode one broadcasted Jan 6th 2016 8pm on BBC2. A 10 min interview 45 min into the program on the topic of body fat distribution, which is the area of interest for my BHF funded project grant.
I was then approached to take part in the 5th series (April 2016) in which we helped the Trust Me, I'm a Doctor team to conduct a intervention study to reduce visceral fat content. This was broadcasted in July 2016
Year(s) Of Engagement Activity 2016