Ethnic specific risk stratification in early pregnancy for identifying mothers at risk of gestational diabetes mellitus in India and Kenya.

High glucose level in Pregnancy or Gestational Diabetes Mellitus (GDM) is one of the most common medical conditions during pregnancy. When undetected, it can cause significant harm for the pregnant women and her offspring. GDM can affect 1-25% of all pregnant women. It depends on the population and where the boundary is drawn between normal and abnormal glucose levels. Certain ethnic minority groups are considered at high-risk for developing GDM, including Indians and Afro-Caribbeans. It is estimated >15% of pregnancies are affected by GDM in India but there are no published data from Kenya.

The immediate risks of untreated GDM are high rates of pre-eclampsia (very high in Africa), higher caesarean section rates and psychological effects such as anxiety and depression. Women who develop GDM have a 7-8 times higher life-time risk of type 2 diabetes (T2D). Similarly, the immediate risks to the children are: being too big or too small, shoulder damage during labour, low glucose levels or jaundice at birth, difficulty in breathing and rarely death (stillbirth). In the long term, the risk of obesity and T2D is also higher.

The diagnosis of GDM is usually made between 24-28 weeks of pregnancy using a glucose drink test called an oral glucose tolerance test (OGTT). Although treatment can improve the outcomes, some of the damage may have already been done to the unborn baby before the detection of GDM. Therefore, screening to detect high glucose level in pregnancy seems beneficial. However, there can be harms as well as benefits in screening programmes. As a recent BMJ article said, "a label of gestational diabetes brings with it an intervention package that includes glucose monitoring, extra clinic visits, more obstetric monitoring with greater likelihood of labour induction, operative delivery and admission of the baby to special care, and finally for the mother a label of high risk for diabetes". We therefore need to try and achieve a balance between identifying women whose blood glucose level is high enough to cause harm and those with glucose level that would not cause harm.

Currently, it is recommended that all pregnant women should be screened for GDM if they belong to a high-risk ethnic population. However, conducting OGTT in rural India and Kenya is challenging, as this test requires pregnant women present themselves to a laboratory facility in a fasting state. In many countries, including the UK, women are selected for OGTT based on the presence of at least one of the high risk factors such as higher body weight, older age and family history of T2D. However, this selection method can miss up to 50% of GDM.

The aim of the study is to develop a risk score in early pregnancy based on a combination of these risk factors that can be collected easily along with a simple finger prick average blood glucose test (called HbA1c). The efficiency of different levels of this combined risk score will be tested against the risk of developing GDM in the later part of pregnancy. Cost-effectiveness analysis will also be conducted to identify at what risk level screening can be recommended in India and Kenya.

An accurate score that can safely exclude women at low risk of developing GDM and will have significant benefits to the pregnant women. They can be reassured. Avoiding the need for OGTT will have significant time and cost benefits. In contrast, if the score identifies them as at high-risk, healthy eating and appropriate life style advice can reduce their risk of developing GDM in later pregnancy. In addition to the direct benefit for the pregnant women and their offspring, the proposed study will also benefit policy makers, governmental and non-governmental organisations both in India and Kenya. The detailed clinical efficiency and health economic evaluations will enable these organisations to allocate the scarce resources to be focused on the high-risk women living in the low and middle-income countries like India and Kenya

Hyperglycaemia in Pregnancy or Gestational Diabetes Mellitus (GDM) is one of the most common obstetric medical conditions which when undetected can cause significant adverse outcomes for the mother and the offspring. Diagnosis is typically made between 24-28 weeks of pregnancy using oral glucose tolerance test (OGTT). Therefore, some damage might have already happened prior to detection. Although universal screening is recommended by many guidelines, this is not uniformly followed across the world, partly because of doubts about cost-effectiveness. Only selective screening is followed based on presence of at least one of the high risk factors (age, BMI, previous history, etc). This strategy can miss up to 50% of GDM. In addition, no data exists in India and Kenya. In low and middle-income countries (LMICs), where majority live in rural settings, the major limitations are difficulty in conducting OGTT, which requires prompt access to laboratory facilities. Combining the clinical and easily analysable biochemical markers (composite risk score) could improve the prediction and if proven, could help to prevent the onset of GDM. Fasting glucose levels (at non-diabetes levels) in early pregnancy could predict future GDM. HbA1c in early pregnancy can be a better marker as it can be done point-of-care and does not require patients to be in a fasting state.

The overall objective of the proposed project is to develop a composite risk score to predict GDM in early pregnancy using a combination of easily identifiable risk factors such as age, BMI, family history of Type 2 Diabetes along with HbA1c in Indians and Kenyans. The project will recruit pregnant women in early pregnancy from South India (n=3400) and Western Kenya (n=4000). Contribution of individual risk factors as well as the composite risk score on the risk of developing GDM will be assessed. Detailed health economic analyses will enable policy makers to make informed decision based on local data.

Adverse pregnancy outcomes are still major causes of morbidity and mortality to women and their offspring, especially those living in rural India and other LMICs such as Kenya. GDM contributes to these adverse outcomes significantly. Screening and accurate identification of women at risk of GDM is a major challenge for public health professionals, policy makers, health care professionals and non-governmental and social care organisations who are involved in improving the health status of women during pregnancy. Our proposed research, if proven, has the potential to safely exclude women at low-risk of GDM.

Benefits from the proposed research will include:
a) Pregnant women and their families: Reduction in level of anxiety by reassuring them that they are at low risk and unlikely to develop GDM. Reduction in discomfort of doing OGTTs. Further benefits will accrue from cost savings by avoiding unnecessary investigations, which in some communities might involve considerable time and costs (travel to clinics for OGTT, cost of OGTTs and related tests). If they are identified as moderate to high-risk early in the pregnancy, healthy eating and active lifestyle advice can reduce their risk of developing GDM in later pregnancy. This, however, needs to be tested in subsequent prospective studies.

b) Health care professionals (diabetologists, obstetricians, midwives and others) directly involved in the care of pregnant women: Unnecessary testing is avoided for those at low risk and hence resources are focused on those at high risk. Target the resources and work with women identified at high risk to reduce the risk of developing GDM. This could result in better job satisfaction and avoid frustration of not being able to avoid the complications of GDM despite treatment.

c) Public health professionals: Clear guidance and algorithms for identifying and reassuring women at low risk, allowing concentration of resources on those at higher risk.

d) Social care, non-governmental and charitable organisations: Currently universal guidelines are recommended in India and no clear guidelines exist in Kenya. It is neither followed nor affordable due to resources and lack of local data. Our findings will provide vital data for policy makers to redefine these guidelines based on local data. Clear risk stratification would enable better allocation of scarce resources in rural India and Kenya. In addition, the study would also provide data that could, with caution, be extrapolated to other LMICs.

e) Private organisations: As significant part of the care in these countries is provided by many private hospitals and organisations, our findings will help these third sector organisations.

f) Wider public: Knowledge of 'GDM' can be predicted and prevented could result in positive view and reduce the stigma, especially in India, Kenya and other LMICs

g) Policy makers in other LMICs: The study will be adequately powered to make clear guidelines for screening GDM in the populations studied. Extrapolation beyond India and Kenya may require conducting further validation studies, in the respective populations, but by building on our risk stratification studies, the time scale of validation studies in other populations living in other LMICs could be significantly shortened.

h) Research teams: The study will also benefit the cohort of research and other staff in each country, through exposure to research methods and development of skills which will not only further their academic careers, but also help them to secure careers in other employment sectors.

i) UK and Indian governments: We would also develop a link with NICE International, which might help develop the UK's track record of conducting key research studies that change medical practice across the world. Similarly, DBT's track record on funding landmark studies will be further strengthened.