Gestational hyperglycaemia in Malaysia: early screening and intervention to improve outcomes of pregnancy

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

Abstract

High blood glucose levels in pregnancy or 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 Malaysian 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".

At present, all pregnant women in Malaysia are supposed to be screened for GDM because the population is considered to be high-risk. However, doing OGTTs can be challenging. The test requires pregnant women to come to a laboratory 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 higher body weight and older age. However, selecting women based on these factors can miss up to half of all women with GDM. 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 Malaysian women.

The aims of this study is to find out whether HbA1c 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 all pregnant women with testing only those with risk factors. We will do a trial to see if a drug called metformin can prevent women developing GDM. Metformin is safe in pregnancy.

An accurate HbA1c level 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 level 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 Malaysia. 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, which if untreated, can cause maternal and fetal complications. Diagnosis is made between 24-28 weeks of pregnancy using the oral glucose tolerance test (OGTT). Thus, some harm may have already occurred prior to detection. Universal screening is backed by many guidelines but is not uniformly followed worldwide partly because of doubts about cost-effectiveness. Selective screening may be used based on presence of at least one of the high risk factors (age, BMI, etc.) but can miss up to 50% of women with GDM. In lower middle income countries, the major limitations are difficulty in conducting OGTT, which requires prompt access to laboratory facilities. An alternative to OGTT is screening 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 yet to be determined in Malaysian populations.

The aims of this study are to determine whether HbA1c testing at first antenatal clinic visit can predict the development of GDM and outcomes, whether a baseline HbA1c level can rule out later GDM and whether universal or selective screening is more cost-effective. Cost effectiveness analysis will also be performed to identify what levels of HbA1c should treatments be recommended in Malaysia. Finally, the study will evaluate whether metformin, a drug that is safe in pregnancy, can prevent the development of GDM.

The project will recruit Malaysian women at <= 20 weeks gestation (n=5230). Recruits with HbA1c 5.4-6.4% will be randomised (online) to metformin treatment (50%), or to standard care (50%); both will have OGTT at 28 weeks (being treated if GDM develops). Detailed health 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 morbidity and mortality to women of child-bearing age and their children, especially those living in rural Malaysia and other lower middle income countries (LMICs). Screening and accurate identification of women at risk of GDM is a major challenge to healthcare systems worldwide.

The study will provide data on whether universal or selective screening is more cost-effective, and whether metformin, a drug that is safe in pregnancy, can prevent the development of GDM. Metformin has been shown to reduce the risk of type 2 diabetes mellitus in people with impaired glucose tolerance. In Malaysia, 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. However, screening is currently performed at 24-28 weeks, by which time some harm may already have been done. In this study, we will assess the value of earlier screening using a more convenient test that does not require fasting, and which takes much less time for women.

Beneficiaries from the research will 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 metformin is effective, reduction in the frequency of GDM.

b) Government and non-governmental organisations (NGOs): Current guidelines in Malaysia advocate universal GDM screening, but this was not based on data from Malaysian populations. To date, no cost effective analyses have been performed for universal GDM screening in Malaysia. Our data will help inform government policies and NGOs (e.g. Obstetrical and Gynaecological Society of Malaysia) to provide clear guidelines for screening for GDM.

c) Health care professionals caring for pregnant women: 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 better 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 universal screening of GDM is recommended in Malaysia, which puts significant pressure on the healthcare budget. Better data on identifying women at low risk, could allow concentration of resources on those at higher risk.

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

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

g) Policy makers in other LMICs: Extrapolation beyond Malaysia 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) Research teams: The study will benefit research staff, through exposure to research methods and development of skills, which will not only further their academic careers, but increase research capacity. If successful, we will look to apply for research fellowships from other funds, for staff in training posts in both countries, in order to develop the researchers of the future.

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 Medical Research Council (MRC) - Thailand Research Fund (TRF)
Amount £370,545 (GBP)
Funding ID MR/R020981/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 04/2018 
End 03/2021
 
Description Role of HbA1c and 50g GCT in early detection and prediction of gestational diabetes and associated maternal and fetal complications in Thailand
Amount £363,666 (GBP)
Funding ID MR/R020981/2 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 05/2018 
End 03/2021
 
Description University of Warwick
Amount £52,836 (GBP)
Organisation University of Warwick 
Sector Academic/University
Country United Kingdom
Start 01/2017 
End 12/2019
 
Description CRC Malaysia 
Organisation Queen Elizabeth Hospital (Malaysia)
Department Clinical Research Centre
Country Malaysia 
Sector Hospitals 
PI Contribution Enhance research capacity.
Collaborator Contribution Provide infrastructure and administrative support to recruit study participants.
Impact Recruitment of study participants. No study outputs or outcomes yet.
Start Year 2017
 
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 No outputs or outcomes yet from the fellowship.
Start Year 2017
 
Description HSA 
Organisation Hospital Sultanah Aminah, Johor Bahru
Country Malaysia 
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 2017
 
Description Monash University Malaysia 
Organisation Monash University Malaysia
PI Contribution Because of this study, Dr Tan was invited to meet a delegation to the University of Warwick in 2017, led by Professor Andrew Walker, President and Pro Vice-Chancellor of Monash Malaysia to discuss research, specifically on diabstes, in Malaysia. Dr Tan has had initial discussions on possible research projects, which could potentially enhance the research capacity of Monash University Malaysia.
Collaborator Contribution Monash University Malaysia has verbally pledged pump-priming funds (amount yet to be determined) for research to be undertaken in 2018.
Impact No study outputs or outcomes yet.
Start Year 2017
 
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 Awaiting outcome of grant application.
Start Year 2017
 
Description Universiti Malaya and UMMC 
Organisation University Malaya Medical Centre
Department Department of Obstetrics and Gynaecology
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 2017
 
Description Universiti Malaya and UMMC 
Organisation University of Malaya
Country Malaysia 
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 2017
 
Description Universiti Sains Malaysia 
Organisation Hospital University Sains Malaysia
Country Malaysia 
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 2017
 
Description Universiti Sains Malaysia 
Organisation University of Science Malaysia
Country Malaysia 
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 2017
 
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 Meeting at UMMC 
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 Because of the on-going late disbursement of research funds from the Akademi Sains Malaysia, recruitment rate was significantly affected.
The strategies to mitigate this issue following Professor Tan's visit in June 2018 did increase recruitment rates but this still fell short of targets.
As of the 26/11/2018, recruitment of study participants stood at 3803 i.e. 72.7% of our target recruitment of 5230.
At this meeting, a plan of action to apply to the MRC and Akademi Sains Malaysia for an extension was agreed upon.
The MRC has granted an extension to 31 December 2019.
Year(s) Of Engagement Activity 2018
 
Description National Diabetes in Pregnancy (DiP) Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was organised by Prof P Saravanan, in collaboration with Diabetes UK and national DiP interest group. More than 350 professional participants attended. Highlighted the research Gaps in Gestational Diabetes and presented the preliminary results. Discussions and debate on key issue of how to manage GDM. Several positive feedback, including feedback on that it will change their practice
Year(s) Of Engagement Activity 2018
 
Description PPI and stakeholder meeting - University of Warwick 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact 47 people (researchers, GPs, PPI representatives) attended the meeting which was help at University of Warwick. Emerging data from the UK GDM cohort was discussed alongside with the STRiDE study's rationale, plan and implementation and proposed rationale and plan for MAGIC in Malaysia
Year(s) Of Engagement Activity 2016
 
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
 
Description Visit HSA 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Study participants or study members
Results and Impact Dr Tan (UK PI), accompanied by Professor Omar (Malaysian PI) visited Hospital Sultanah Aminah (teaching hospital of Monash University Malaysia) and peripheral recruitment clinics in Johor Bahru. The Johor Bahru lead is Dr Jeganathan. Dr Tan met and discussed the research project with lead medical officers, matrons, nurses, research assistants (comprising of fresh medical graduates awaiting housemanship posting) and study participants. Dr Tan observed how study participants are engaged, consented for study, data collection and storage. At Hospital Sultanah Aminah, Dr Tan also met corresponding staff involved in recruitment, met study participants, and visited labour ward where study participants will give birth. In addition, Dr Tan observed how data at the time of delivery is linked to the National Obstetric Registry. Recruitment on-going and accelerating. Dr Tan, Professor Omar and Dr Jeganathan discussed ways to increase efficiency of recruitment as well as the opening of an additional recruitment site at Tampoi peripheral clinic. Dr Tan engaged directly with research assistants in teaching and clarifying queries from research assistants. Dr Tan was also able to meet and participate in the teaching of postgraduate and undergraduate students of Monash University Malaysia on the subject of gestational diabetes mellitus.
Year(s) Of Engagement Activity 2018
 
Description Visit HUSM 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Study participants or study members
Results and Impact Dr Tan (UK PI), accompanied by Professor Omar (Malaysian PI) visited Hospital Universiti Sains Malaysia and peripheral recruitment clinics in Kota Bahru. The Kota Bahru lead is Dr Ismail. Dr Tan met and discussed the research project with lead medical officers, matrons, nurses, research assistants (comprising of fresh medical graduates awaiting housemanship posting) and study participants. Dr Tan observed how study participants are engaged, consented for study, data collection and storage. At Hospital Universiti Sains Malaysia, Dr Tan also met corresponding staff involved in recruitment, met study participants, and visited labour ward where study participants will give birth. Recruitment on-going and accelerating. Dr Tan was informed that Dr Amir, consultant obstetrician at Hospital Universiti Sains Malaysia has started a sabbatical, the purpose of which is to contribute further and to help drive recruitment to the study in Kelantan. Dr Tan, Professor Omar, Dr Ismail and Dr Amir discussed ways to increase efficiency of recruitment as well as the opening of an additional recruitment site at Bachok peripheral clinic. Dr Tan engaged directly with research assistants in teaching and clarifying queries from research assistants. Dr Tan was also able to meet and participate in the teaching of postgraduate and undergraduate students at Hospital Universiti Sains Malaysia on the subject of gestational diabetes mellitus.
Year(s) Of Engagement Activity 2018
 
Description Visit UMMC 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Study participants or study members
Results and Impact Dr Tan (UK PI) visited University Malaya Medical Centre (UMMC) in Kuala Lumpur. The UMMC recruitment site is led by Professor Omar (Malaysian PI) assisted by Professor PC Tan. Dr Tan met and discussed the research project with lead medical officers, matrons, nurses, research assistants (comprising of fresh medical graduates awaiting housemanship posting) and study participants. Dr Tan observed how study participants are engaged, consented for study, data collection and storage. At UMMC, Dr Tan also met corresponding staff involved in recruitment, met study participants, and visited labour ward where study participants will give birth. Recruitment on-going and accelerating at UMMC. Dr Tan, Professor Omar and Professor PC Tan discussed ways to increase efficiency of recruitment. Dr Tan engaged directly with research assistants in teaching and clarifying queries from research assistants. Dr Tan was also able to meet and participate in the teaching of postgraduate and undergraduate students on the subject of gestational diabetes mellitus.
Year(s) Of Engagement Activity 2018
 
Description Visit to UMMC 
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) visited University Malaya Medical Centre (UMMC) in Kuala Lumpur in June 2018. The UMMC recruitment site is led by Professor Omar (Malaysian PI) assisted by Professor PC Tan. Professor Tan met and discussed the research project with lead medical officers, matrons, nurses, research assistants (comprising of fresh medical graduates awaiting housemanship posting) and study participants. Recruitment was threatened by the late disbursement of funds from the Akademi Sains Malaysia and this delay was further compounded by the political unrest in Malaysia attributed to an unprecedented change in Malaysian politics wherein the opposition parties for the first time since Malaysia's independence in 1957 won the 2018 Malaysian general election. Strategies were discussed and a plan of action agreed to mitigate this problem.
Year(s) Of Engagement Activity 2018