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

Lead Research Organisation: University of Warwick
Department Name: Warwick Medical School

Abstract

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.

Technical Summary

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.

Planned Impact

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.

Publications

10 25 50
 
Description GCRF Fellowship
Amount £2,300 (GBP)
Organisation University of Leicester 
Sector Academic/University
Country United Kingdom
Start 04/2019 
End 07/2019
 
Description Mahidol University Visiting Professorship
Amount ฿70,000 (THB)
Organisation Mahidol University 
Sector Academic/University
Country Thailand
Start 03/2020 
End 09/2020
 
Description GCRF Fellowship University of Leicester application 
Organisation Fujian Agriculture and Forestry University
Country China 
Sector Academic/University 
PI Contribution Conception of research plan for the potential fellow. Transfer of knowledge and skills. Assisting with grant writing. Enhance research capacity. Provide infrastructure and administrative support.
Collaborator Contribution Contribution to the research plan. Transfer of knowledge and skills. Enhance research capacity. Provide infrastructure and administrative support. Contribution to the living costs of the fellow in the UK.
Impact The fellowship has resulted in a systematic review and meta-analysis of 261 studies and 79410 women on the ''Association of maternal lipid profile and gestational diabetes mellitus''. A manuscript has been submitted for publication. In addition, Dr Tan was invited to Fujian Agriculture and Forestry University to give a talk on Gestational Diabetes Mellitus at the 2019 FAFU ''BELT AND ROAD'' FOOD THERAPY AND NUTRACEUTICALS FORUM, 8-10 November 2019, Fuzhou, China.
Start Year 2018
 
Description Phramongkutklao Hospital 
Organisation Phramongkutklao Hospital
Country Thailand 
Sector Hospitals 
PI Contribution 1) Transfer of knowledge and skills. 2) Enhance research capacity.
Collaborator Contribution 1) Provide infrastructure and administrative support to recruit study participants. 2) Medical and nursing staff to facilitate recruitment of study participants.
Impact Recruitment of study participants. No study outputs or outcomes yet.
Start Year 2019
 
Description Royal Society Newton Mobility Grant application 
Organisation Mahidol University
Country Thailand 
Sector Academic/University 
PI Contribution Conception of research plan for the potential fellow. Transfer of knowledge and skills. Assisting with grant writing. Enhance research capacity. Provide infrastructure and administrative support.
Collaborator Contribution Contribution to the research plan. Transfer of knowledge and skills. Enhance research capacity. Provide infrastructure and administrative support.
Impact Negative outcome of grant application.
Start Year 2018
 
Description Siriraj Hospital 
Organisation Mahidol University
Department Siriraj Hospital
Country Thailand 
Sector Hospitals 
PI Contribution 1) Transfer of knowledge and skills. 2) Enhance research capacity.
Collaborator Contribution 1) Provide infrastructure and administrative support to recruit study participants. 2) Medical and nursing staff to facilitate recruitment of study participants.
Impact Recruitment of study participants. No study outputs or outcomes yet.
Start Year 2018
 
Description Songklanagarind Hospital 
Organisation Prince of Songkla University Thailand
Country Thailand 
Sector Academic/University 
PI Contribution 1) Transfer of knowledge and skills. 2) Enhance research capacity.
Collaborator Contribution 1) Provide infrastructure and administrative support to recruit study participants. 2) Medical and nursing staff to facilitate recruitment of study participants.
Impact Recruitment of study participants. No study outputs or outcomes yet.
Start Year 2018
 
Description Sunpasithiprasong Hospital 
Organisation Sappasithiprasong Hospital
Country Thailand 
Sector Hospitals 
PI Contribution 1) Transfer of knowledge and skills. 2) Enhance research capacity.
Collaborator Contribution 1) Provide infrastructure and administrative support to recruit study participants. 2) Medical and nursing staff to facilitate recruitment of study participants.
Impact Recruitment of study participants. No study outputs or outcomes yet.
Start Year 2018
 
Description Thammasat University Hospital 
Organisation Thammasat University Hospital
Country Thailand 
Sector Hospitals 
PI Contribution 1) Transfer of knowledge and skills. 2) Enhance research capacity.
Collaborator Contribution 1) Provide infrastructure and administrative support to recruit study participants. 2) Medical and nursing staff to facilitate recruitment of study participants.
Impact Recruitment of study participants. No study outputs or outcomes yet.
Start Year 2019
 
Description 111 Plan International Collaborative Innovation Symposium of Maternal-Fetal Medicine (2018), Chongqing, China 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact This meeting took place in September 2018. Highlighted the research gaps in gestational diabetes mellitus (GDM) and presented some ideas for research collaboration with Chinese researchers. Discussions and debate on key issues of how to manage GDM. Several positive feedback, including feedback on that it will change their approach to undertaking research and the management of GDM.
Year(s) Of Engagement Activity 2018
 
Description Fujian Agriculture and Forestry University - 2019 FAFU ''BELT AND ROAD'' FOOD THERAPY AND NUTRACEUTICALS FORUM, Fuzhou, China 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact This meeting took place in November 2019. Highlighted the research gaps in gestational diabetes mellitus (GDM) and presented some ideas for research collaboration with Chinese researchers. Professor Tan presented a lecture on 'Gestational Diabetes: Outstanding Issues' unanswered questions in GDM. Discussions and debate on current research on prediction/diagnosis and management of GDM. Several positive feedback, including feedback on that it will change their approach to undertaking research and the management of GDM.
Year(s) Of Engagement Activity 2019
 
Description Meeting at Siriraj Hospital 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Professor Tan (UK PI) met Thai researchers at Siriraj Hospital in Bangkok in November 2018. Professor Tan discussed the research project with lead medical officers, matrons, nurses and study participants. Professor Tan also observed how study participants are engaged, consented for study, data collection and storage at Siriraj Hospital, Bangkok. At Siriraj Hospital, Professor Tan also met corresponding staff involved in recruitment and study participants. Recruitment has started at Siriraj Hospital and Sunpasithiprasong Hospital in Ubon Ratchathani. New research collaborations were established with Mahidol University i.e. Newton Mobility Grant.
Year(s) Of Engagement Activity 2018
 
Description Meeting in Bangkok 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Professor Tan (UK PI), Professor Saravanan and Professor Gill met Thai researchers in Bangkok in June 2018. The UK and Thai researchers discussed the research project, ethical issues, collaboration agreements, communication and risk management plans. They also observed how study participants will be engaged, consented for study, data collection and storage at Siriraj Hospital, Bangkok. At Siriraj Hospital, the UK team also met corresponding staff that will be involved in recruitment and visited labour ward where study participants will give birth.
Year(s) Of Engagement Activity 2018
 
Description Polish Mother's Memorial Hospital - Research Institute Research Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact This meeting took place in March 2019. Highlighted the research gaps in gestational diabetes mellitus (GDM) and presented some ideas for research collaboration with Polish researchers. Professor Tan presented a lecture on unanswered questions in GDM. Discussions and debate on key issues of how to manage GDM. Several positive feedback, including feedback on that it will change their approach to undertaking research and the management of GDM.
Year(s) Of Engagement Activity 2019