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

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.

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.

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.