Role of HbA1c and 50g GCT in early detection and prediction of gestational diabetes and associated maternal and fetal complications in Thailand

High blood glucose levels in pregnancy called gestational diabetes mellitus (GDM) is one of the most common medical conditions during pregnancy. It can cause harm to the pregnant woman and her child. GDM affects 10-15% of Thai women. More women are being diagnosed with GDM now because a lower level of blood glucose is being used to diagnose GDM.

If not treated, GDM can cause high blood pressure in pregnancy, increased numbers of caesarean deliveries, anxiety and depression. Women who have had GDM have 7-8 times higher life-time risk of type 2 diabetes mellitus (T2DM). There are risks to the children too. They may be too big or too small. If too big, they can have shoulders damaged during the birth. Their blood glucose may fall too low after birth. They may get jaundice soon after birth, or have difficulty in breathing. A very few may die before birth (stillbirth). In the long term, these children are at higher risk of becoming overweight and diabetic.

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 pregnancy outcomes, some of the damage may have already been done to the unborn baby. So screening to detect high glucose levels earlier in pregnancy may be better. However, there can be harms as well as benefits from screening. As a recent British Medical Journal 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".

Some people think that all women should be screened with OGTT has been advocated but that may not be needed. The test requires pregnant women to come to a clinic having not eaten anything for at least 8 hours. In many countries including the UK, women are selected for OGTT based on risk factors such as overweight and older age. However, selecting women based on these factors can miss up to half of all women with GDM.

In Thailand, women at high risk for GDM are supposed to be screened at the first antenatal clinic visit with the 50g Glucose Challenge Test (GCT). But, the rate of screening for GDM in Thailand varies from none at all in rural areas to 78% in cities.

Another blood glucose test done by a simple finger prick (called HbA1c) might do instead. It would be done at the first antenatal clinic visit. The HbA1c is a one-step test and patients do not need to fast. However, the value of HbA1c testing is not yet known in Thai women.

The aims of this study are to find out whether HbA1c and 50g GCT testing at first antenatal clinic visit can predict later GDM and if there is a level that can rule out later GDM. We also want to compare testing of all pregnant women with testing only those with risk factors. We will do a trial to see if diet and lifestyle interventions can prevent women developing GDM.

Accurate HbA1c and 50g GCT levels that can safely rule out GDM in women at low risk would help pregnant women. They can be reassured. Avoiding the need for OGTT would save them time and money. In contrast, if the HbA1c and 50g GCT levels identifies them as at high-risk, healthy eating and lifestyle advice can reduce their risk of getting GDM. In addition to the benefit to mothers and their children, this study will also be useful to people who provide health care in Thailand. They can focus care more on women at high risk. The results could be used by other countries.

Gestational diabetes mellitus (GDM) is one of the commonest maternal medical conditions, and if untreated, can cause maternal and fetal complications. Diagnosis is made between 24-28 weeks of pregnancy using the oral glucose tolerance test (OGTT). However, by then some harm may have occurred. Universal screening is backed by many guidelines but is not uniformly followed. Selective screening based on risk factors (age, BMI, etc.) can miss up to 50% of women with GDM. In lower middle income countries, it may be difficult to do OGTTs, which require access to laboratory facilities.
In Thailand, women at high risk for GDM are supposed to be screened at the first antenatal visit with the 50g Glucose Challenge Test (GCT) but the rate of screening for GDM in Thailand varies from none at all in rural areas to 78% in urban areas.
An alternative is to screen with HbA1c at first antenatal clinic visit. The HbA1c is a one-step test, can be done at point of care and patients do not need to fast. However, the relationship of HbA1c levels in early pregnancy and outcomes of pregnancy (including the development of GDM) is not known in Thai women.
The study aims to determine whether HbA1c and 50g GCT testing at first antenatal clinic visit can predict the development of GDM and outcomes, whether baseline HbA1c and 50g GCT levels can rule out later GDM and whether universal or selective screening is more cost-effective. Cost effectiveness analyses will also be performed to identify what levels of HbA1c and 50g GCT should require treatment in Thailand. Finally, the study will evaluate whether diet/lifestyle interventions, can prevent GDM.
The project will recruit women at <= 20 weeks gestation (n=4264). Those with HbA1c 5.7-6.4% and/or 50g GCT 140-199mg/dL will be randomised to interventions (50%), or to standard care (50%); both will have OGTT at 28 weeks (being treated if GDM develops). Economic analyses will enable policy makers to make informed decisions based on local data.

Gestational diabetes mellitus (GDM) is a major cause of maternal and fetal complications. Screening and accurate identification of women at risk of GDM is a major challenge to healthcare systems worldwide.

This study would provide data on whether universal/selective screening is more cost-effective, which testing strategy is best, and whether diet and lifestyle interventions, can prevent GDM in women at high risk. We know that diet and lifestyle interventions can reduce the risk of type 2 diabetes mellitus in non-pregnant people with impaired glucose tolerance. In Thailand, GDM is one of the leading causes of caesarean sections, which are costly to health care services as well as being a major cause of morbidity to women.

The aim of screening for GDM is to identify women who should be treated to reduce higher than normal blood glucose levels and ensure delivery of a healthy baby. Diagnosis is usually made between 24-28 weeks of pregnancy using the oral glucose tolerance test (OGTT), by then some harm may have occurred. Also, there are women with higher than normal, but not diabetic, blood glucose levels.

In Thailand, women at high risk for GDM are supposed to be screened at the first antenatal visit with the 50g Glucose Challenge Test (GCT) but, the rate of screening for GDM in Thailand varies from none in rural areas to 78% in urban areas.

In this study, we will assess the value of earlier screening using a more convenient test, not requiring fasting, and that takes less time.

Beneficiaries include:

a) Pregnant women and their families: Reduction in anxiety by reassuring them that they are at low risk and unlikely to develop GDM. Reduction in discomfort of doing oral glucose tolerance tests (OGTTs). Further benefits will accrue from cost savings by avoiding unnecessary tests, which in some communities might involve considerable time and costs (travel to clinics for OGTT, cost of OGTTs). If diet and lifestyle interventions are effective, reduction in the frequency of GDM.

b) Government and non-governmental organisations (NGOs): Current Thai guidelines advocate selective GDM screening, but no cost-effective analyses have been undertaken to evaluate universal/selective GDM screening in Thailand. We would provide evidence to enable the Health Intervention and Technology Assessment Program (HITAP) and the Royal Thai College of Obstetricians and Gynaecologists to update clinical guidelines.

c) Health care professionals: Unnecessary testing is avoided for those at low risk and hence resources are focused on those at high risk. By targeting resources and working with women identified as high risk to reduce the risk of developing GDM, this could result in improved job satisfaction and avoid frustration of not being able to avoid the complications of GDM despite treatment.

d) Public health professionals and policy-makers: Currently selective screening of GDM is recommended in Thailand, but the rate of screening for GDM in Thailand is very variable. Better data on identifying women at low risk, could allow concentration of resources on those at higher risk, and improve equity across the country.

e) Private organisations: As significant part of care in Thailand is provided by private hospitals and organisations, our findings will help by informing their policies and practices.

f) Wider public: Increased awareness of 'GDM' can promote lifestyle changes, and will help address the issues of maternal and childhood obesity.

g) Policy makers in other LMICs: Extrapolation beyond Thailand may require conducting further validation studies, but by building on our studies, the time scale of validation studies in other LMICs could be significantly shortened.

h) Areas with high screening rates: Release of resources from unnecessary screening to other forms of health care.