Academic Corner: Diabetes during pregnancy

More than half a million women die in connection with pregnancy or childbirth every year (1).  The main reason quoted is lack of access to basic health care. Hence the solution to the problem is to create better access to care.

But what is better access to care? Is it improved health infrastructure? Is it more funding? Is it better education and awareness? Should maternal care involve some attention to non-communicable diseases (NCDs) and their risk factors such as obesity, diabetes and hypertension given their earlier onset and rising burden during the reproductive age group? The list is inexhaustible and resources scarce. How should health systems prioritise needs and different agendas?

Safe motherhood and healthy children is a universal wish - but not a given in many

developing countries.

The World Diabetes Foundation’s area of expertise is diabetes and two of our main focus areas are prevention of diabetes and gestational diabetes. Both have relevance to improved maternal health care services. From a pilot project on gestational diabetes in India dating back to 2004, a wealth of experience on women and diabetes was obtained. The first major finding was a surprisingly high prevalence of impaired glucose intolerance (IGT) and gestational diabetes (GDM) among pregnant women. The second finding was that in the majority of cases, the condition could be controlled with lifestyle changes and diet alone. The third finding documented that once diabetes is under control, clear improvements in maternal and child health were seen (read more about the India project). And the last and most important lesson was that awareness, education and screening for diabetes during pregnancy can be easily incorporated within the existing maternal and child health programs with minimal additional costs. Based on the good experience from India, the World Diabetes Foundation has been promoting the inclusion of screening for gestational diabetes at least in the high risk group in the developing world as an important contributor for improving maternal health care.

What is gestational diabetes?

Now, first let us look at what is gestational diabetes and why it is relevant for improving maternal health in development countries. There are two forms of diabetes seen during pregnancy. One form is called pre-gestational diabetes; here the woman has existing known diabetes before she becomes pregnant. The other form occurs in women who did not have diabetes before the pregnancy and who will only experience it during pregnancy. This is called gestational diabetes. Our focus here is on gestational diabetes, because often times the condition goes unnoticed and major improvements in maternal and foetal outcome can be made if it is detected and properly managed.

According to World Health Organization (WHO) standards, gestational diabetes is diagnosed by means of a standard OGTT (Oral Glucose Tolerance Test) conducted at 24-28 weeks of gestation after an overnight fast. If the fasting sample is >=6.1 mmol/L (or 126 mg/dL) and/or if at two hours, following a glucose drink containing 75 gms glucose, the plasma glucose level is >=7.8 mmol/L (or 140 mg/dL) the pregnant woman is diagnosed with gestational diabetes. The test is simple, cheap and requires easily available equipment. In between normality and diabetes the intermediate conditions named Impaired Glucose Tolerance (IGT) and Impaired Fasting Glycaemia (IFG) occur.

It should be mentioned that different screening methods and diagnostic criteria are used worldwide to diagnose gestational diabetes, which adds to the confusion about prevalence rates. There is an urgent need to come up with internationally accepted uniform and simple criteria. Several studies have found that some ethnic groups are more prone to develop gestational diabetes than others and based on these studies, risk assessment scores to facilitate screening have been developed.

Gestational diabetes entails risks for mother as well as for child, and contributes substantially to maternal and child morbidity and mortality. The risks connected to gestational diabetes are summarised in the below table :

(figure 1) Gestational diabetes causes risks to both child (foetal risks) and mother
(maternal risks).

Furthermore, both mother as well as child has a high risk developing diabetes later in life if appropriate preventive actions are not taken (2). Offspring of women with uncontrolled diabetes during pregnancy are at 4  to 10 times higher risk of developing diabetes in adult life compared to offspring of non-diabetic pregnancy. This is referred to as foetal programming, and indicates that the metabolic and nutritional environment in the womb is an important determinant of future adult diseases. 

70 million women at risk

Worldwide, it is estimated that 70 million women in the reproductive age have diabetes or impaired glucose tolerance which puts them at risk of hyperglycemia (high blood sugar) during pregnancy(3). The prevalence rates of GDM vary from between 3% to 15%, a variation that reflects variable risks related to ethnicity, lifestyle and environment. But it also reflects a general lack of screening and variable diagnostic methods and criteria. “People are simply not looking for it and awareness about gestational diabetes is generally low,” says Dr. Anil Kapur, Managing Director of the World Diabetes Foundation. He is convinced that the reported numbers are low and that many more cases would be found if people started looking.

“The prevalence rates for gestational diabetes should have a close link to the rates of diabetes and impaired glucose tolerance in the female population aged 20 to 40 years. Because of the increasingly earlier onset of obesity, IGT and diabetes, young females of reproductive age are affected, and as a consequence more pregnancies are complicated by hyperglycemia or diabetes, but sadly many of them are missed and cause severe consequences,“ he says.

(Figure 2) Estimates of diabetes and IGT in women aged 20-39 years.
Data based on the IDF Diabetes Atlas, 3rd edition.

While the conclusion is that rise in obesity, unhealthy lifestyles and diabetes will also lead to a rise in gestational diabetes, non-communicable diseases such as diabetes are getting very little attention on the development and public health agenda in developing countries and amongst international development organisations and scant, if any, in the arena of maternal health. “It is scary that we have not dealt with diabetes in pregnancy, considering the increase in diabetes worldwide,” says Dr. Manuel Carballo currently Director of the International Centre for Migration and Health and with a long trajectory of working with maternal health in development settings. “Gestational diabetes is simply not understood at all – nor is the concept of women coming into pregnancy with diabetes,” he argues.

Pre-gestational and gestational diabetes contribute substantially to “high-risk” pregnancies and, in some countries, may already be the leading cause of maternal morbidity and mortality due to worsening of vascular complications, greater risk of pregnancy induced hypertension (PIH), preeclampsia, hydroamnios as well as poor pregnancy outcomes such as spontaneous abortions, still births, congenital anomalies, macrosomia (large for gestational age), shoulder dystocia, need for caesarean delivery, instrumental deliveries, and long-term complications to the offspring.

The hidden link between diabetes and maternal mortality

“When asked why women die, the classic response is that there is no midwife or clean delivery,” says Dr. Carballo. “However, if one looks more closely at why women die, the reason is much more medical. Women die of haemorrhage, rupture, obstructed labour or infection,” he says. “All factors enhanced or worsened by an underlying diabetic state,” adds Dr. Anil Kapur. 
 
In a 2006 WHO study on the causes of maternal death, an analysis of 35,197 maternal deaths in developing countries was conducted. The conclusion was that haemorrhage and hypertensive disorders are major contributors to maternal deaths in developing countries. In Africa, 34% of all maternal deaths were caused by haemorrhage; in Asia the percentage was 31%. In Latin America and the Caribbean, hypertensive disorders were responsible for the most deaths (26%)(4). The next apparent question to ask is whether some of these ruptures (and hypertensive disorders) might have been caused by big babies born to mothers with undetected gestational diabetes.

The link between diabetes, macrosomia and maternal mortality

Pregnancy associated with diabetes carries a high risk of perinatal morbidity and mortality. One well-known complication is the big baby syndrome (macrosomia) which causes shoulder dystocia and related birth injuries for both mother and the newborn. Babies born with a birth weight above 3,500 g are defined as macrosomic - a condition which is associated with higher weight in childhood and higher rates of obesity in adulthood. In a study of 249 cases of macrosomia in Nigeria (5), an elevated rate of postpartum haemorrhage was found. More alarmingly, the maternal mortality rate for mothers of large infants was two times higher than in the control group (1,667 per 100,000 live births as compared to 800 per 100,000).  

This is not to say that all macrosomic babies are born of mothers with diabetes. But there is probably a connection. A 12-year follow-up study by Nickel et al. found that 60% of women giving birth to macrosomic babies developed diabetes later in life. This means that six out of ten mothers may have had gestational diabetes or hyperglycemia during pregnancy, but they were never diagnosed (6). 

A costly strategy not to screen

The potential scope and consequences of gestational diabetes on maternal and perinatal morbidity and mortality are well known; greater attention and awareness of the issue will help further enhance and improve maternal and child health services. “But the icing on the cake is the fact this focus helps identify women at high risk of future diabetes while offering an opportunity for primary prevention of diabetes in the same women. At the same time, good metabolic control during pregnancy will help prevent several non-communicable diseases including diabetes in the offspring. Very rarely in medical care such an opportunity arises where a short term targeted intervention of a few months will produce a three pronged long-term and inter generational benefit,” says Dr. Anil Kapur. 

But in order to accomplish this, a diagnosis must first be made and once that is done, the pregnant woman must be informed about how to keep her diabetes under control. In other words, she has to learn how to control her blood sugar.

Projects in Cuba and India both suggest that the majority of women diagnosed with gestational diabetes managed to control their blood sugar with lifestyle modifications (diet and physical activity) alone and only a minority needed treatment with insulin. This is no less than excellent news! – Not only for the women who get a safer pregnancy and healthier offspring, but also for health economists. In developing countries, women are the most vulnerable segment of society, and seen from a cost-benefit perspective, focusing on gestational diabetes will be highly rewarding for the poorly resourced health systems.
 
The benefits of screening and detecting diabetes during pregnancy are far-reaching. “Not screening for diabetes during pregnancy – especially in women at high risk - is both a dangerous and a potentially costly strategy,” says Dr. Anil Kapur and points to the below figure to illustrate his point. “While the burden of diabetes grows, there is no global recommendation on women, gender equality and health specifically mentioning diabetes. Recommendations do call for action on non-communicable diseases, including research on the causes and consequences, and measures to ensure that women receive full information about options and access to services available. There is an urgent need to address the issue of diabetes in this context,” he concludes.

(Figure 3) The three-pronged relevance of diabetes and pregnancy for public health.

Through supporting gestational diabetes projects in developing countries, the World Diabetes Foundation will continue to create awareness about the necessity of screening for gestational diabetes in order to improve maternal and child health. At the same time, we will work determinedly with national and international organisations to ensure that the issue of gestational diabetes gets the place it deserves on the global health agenda.

Factsheet: Diabetes holds key to maternal health
Film about gestational diabetes in India: Breaking the chain

 

References: (1) Of the estimated total of 536 000 maternal deaths worldwide in 2005, developing countries accounted
for 99% (533 000) of these deaths. WHO, UNICEF, UNFPA and The World Bank, 2007; (2) “Offspring of women with GDM have a 4 to 8 fold increased risk of developing diabetes.” Clausen TD et al. “High prevalence of type 2 diabetes and pre-diabetes in offspring of women with GDM or type 1 diabetes.”, Diabetes Care, February 2008. Dana Dabelea et al. "Association of Intrauterine Exposure to Maternal Diabetes and Obesity With Type 2 Diabetes in Youth." Diabetes Care, July 2008; (3) IDF Diabetes Atlas, 3rd edition; (4) Khan et al. “WHO analysis of causes of maternal death: a systematic review.” The Lancet, April 2006; (5) Kamanu et al. “Fetal Macrosomia in African women: a study of 249 cases”. Archives of Gynecology and Obstetrics, June 2009; (6) Nickel I, Hagacad WP, Wease WH (1966) "Glucose tolerance and excessively large infant. A twelve year follow-up study". Am J Obstet Gynecol 94:62.