Screening for Gestational Diabetes Gestational diabetes mellitus (GDM) is caused by the development of glucose intolerance during pregnancy (National Institutes of Health 2013). In the United States the National Institutes of Health (2013), U.S. Preventive Services Task Force (2008), and the American Diabetes Association (2013) are just a few agencies and organizations who have weighed in on this topic. Elsewhere, the Cochrane Systematic Reviews (Tieu et al. 2010) and the World Health Organization (WHO 2013a) have also published their recommendations. Despite the overwhelming number of recommendations concerning GDM, the best GDM screening protocols, diagnostic methods, and treatment approaches remain controversial.

To better understand recommended best practices for GDM care this proposal will first examine what is known about this disease and then review the evidence-based rationales underlying current recommendations. Particular attention will be paid to the health care challenges facing emerging developed nations, in particular Saudi Arabia.

GDM Epidemiology

The International Diabetes Federation (IDF 2013) estimates that 382 million people globally were suffering from diabetes in 2013, of which nearly half remain undiagnosed. This number is expected to increase to 592 million by 2035, with the vast majority (80%) residing in low- and middle-income countries. The economic burden is estimated to be over half a trillion dollars (U.S.), which represents close to 11% of all healthcare spending on adults.

A recent systematic review estimated the global prevalence of hyperglycemia during pregnancy to be 14.8% (Guariguata et al. 2013). The prevalence rate for North Africa and the Middle East was higher at 17.5%, but the range among all seven IDF regions reached a high of 25.0% for Southeast Asia and a low of 10.4% for the North American Continent. Of these women, close to 16% worldwide were diabetic before pregnancy or undiagnosed.

A recent WHO report (2013b: 13) reported a diabetes prevalence rate of 20% in Saudi Arabia, among the highest in the world. Al-Daghri and colleagues (2011) examined the prevalence of GDM and found 1.4% of women between 18 and 45 and 1.5% of women between 46 and 60 developed the disease during pregnancy. The higher rate among older women is not too surprising given that age is a risk factor for GDM. In addition, an estimated 36.4% of women between 18- and 45-years of age were obese compared to 61.9% for women between 46- and 60-years of age. Obesity also predicts the prevalence of type 2 diabetes among Saudi women, with 9.5% having the disease between the ages of 18 and 45 and 44.1% between 46 and 60-years of age.

GDM Etiology and Risk Factors

Hyperplasia of the pancreatic ?-cells leads to increased insulin production, which is fortunate because pregnancy causes increased insulin resistance after a short period of increased insulin sensitivity (Prutsky et al. 2013). The progressive development of insulin resistance is normal and caused by diabetogenic hormones, such as placental lactogen, estrogen, and prolactin. When insulin production is insufficient to control blood glucose levels, however, GDM develops. There are a number of GDM risk factors that have been identified, including non-European ancestry, overweight, obesity, age, poor diet, sedentary lifestyle, fertility problems, and a family history of diabetes (Zhang et al. 2013).

Adverse Outcomes Associated with GDM

The general view is that GDM should be treated during pregnancy due to the significant risks of adverse outcomes for both mother and child (National Institutes of Health 2013). The short-term adverse outcomes for the mother are gestational hypertension, proteinuria, and preeclampsia, while the long-term consequences include eventual development of type 2 diabetes, metabolic syndrome, and cardiovascular disease. The National Diabetes Education Program (n.d.) in the U.S. estimates that 35 to 60% of women who developed GDM will develop diabetes within 10 to 20 years. The risks to the fetus are hyperinsulinemia, macrosomia, shoulder dystocia, caesarean delivery, respiratory distress syndrome, and the emergence of metabolic problems during the perinatal period (National Institutes of Health 2013). Notably, of the children born during 2013 an estimated 21 million were exposed to maternal hyperglycemia (IDF 2013). Fetuses exposed to GDM are also believed to have an increased risk of developing diabetes later in life (National Diabetes Education Program n.d.).

Screening for and Diagnosing GDM

In 1979 the WHO (2013a: 19-21, 34-40) revised the recommendation that pregnant women be screened for GDM using a 2-hour oral glucose tolerance test (OGTT) after a 75 g glucose challenge. Women with a low-risk of developing diabetes or GDM need not be screened until about 24 to 28 weeks into the pregnancy, but high-risk women should be screened during the first trimester. Other national...

The most recent WHO recommendations suggest that clinicians distinguish between GDM and 'diabetes first diagnosed during pregnancy' (diabetes in pregnancy, DIP), because DIP patients typically suffer from a more severe manifestation of the disease. This distinction is important in part because treatment strategies can differ.
DIP is defined by a fasting plasma glucose ? 126 mg/dl, plasma glucose ? 200 mg/dl 2 hours after a 75 g oral glucose challenge, and/or random plasma glucose ? 200 mg/dl if diabetes symptoms are evident (WHOa 2013: 34-40). Common symptoms associated with diabetes are excessive thirst, weight loss, and frequent urination. This recommendation is not evidence-based, since the cut off points were defined by studies evaluating non-pregnant adults only.

The WHO (2013a: 34-40) defines GDM as either fasting plasma glucose between 92 and 125 mg/dl, plasma glucose ? 180 mg/dl 1 hour after a 75 g oral glucose challenge, or plasma glucose between 153 and 199 mg/dl 2 hours after a 75 g oral glucose challenge. The WHO admits that these cut offs are somewhat arbitrary, since the risks associated with different degrees of hyperglycemia severity have not been determined. The strongest evidence supporting these diagnostic criteria came from a limited number of studies examining the relationship between neonatal outcomes and maternal blood glucose data obtained during gestation.

An important consideration for clinicians is when these tests are conducted, because fasting plasma glucose in non-obese pregnant women will decline until the end of the first trimester by 9 mg/dl in addition to an increased risk of false positives (WHOa, 2013: 34-40). However, above normal fasting plasma glucose during the first trimester, which is below the cutoffs for a DIP or GDM diagnosis, is still considered a risk factor for later development of GDM. The WHO recommends a diagnosis of GDM during the first trimester if fasting plasma glucose is ? 92 mg/dl.

The scientific and clinical evidence supporting the use of these screening methods remains weak. Prutsky and colleagues (2013) conducted a systematic review and meta-analysis of the research literature published prior to May 2011 and could not find a single randomized controlled study examining the relationship between screening methods and feto-maternal outcomes. The studies they did review primarily relied on plasma glucose 1 hour after a 50 g oral glucose challenge with a cutoff of 140 mg/dl, but with such a low cutoff only 11% of women diagnosed with GDM ever developed this condition. There is thus a clear need for studies evaluating the efficacy of these screening methods relative to feto-maternal outcomes.

Treatment of GDM

The first-line treatment approach for women diagnosed with GDM, according to the American College of Obstetricians and Gynecologists (2013: 409-410), is nutrition therapy to reduce hyperglycemia, prevent ketosis, and weight management. The recommended calorie distribution is 33 to 40% carbohydrates, 20% protein, and 40% fat. When possible, a low-glycemic index diet should be combined with regular, moderate exercise. Should diet modification and exercise fail to normalize plasma glucose levels then GDM should be treated pharmacologically. The primary recommended drug therapy is insulin, because it does not cross the placenta and achieves tight control over blood glucose levels. The initial dose ranges between 0.7 and 1.0 units/kg/d, divided evenly between several administrations during the day.

GDM Screening in Practice

OGTT, in its various forms, is the most widely-recognized laboratory screening method for GDM (Hanna et al. 2008). Screening for risk factors is also a critical method for identifying which patients need to be screened during the first trimester; however in countries which have not implemented national recommendations, such as the United Kingdom, the screening methods being utilized by clinicians can vary widely. A recent survey in the UK has found that routine screening was performed in 52% of the antenatal clinics who responded to a survey, while the others relied on a two-step protocol involving an evaluation of risk factors before conducting an OGTT (Hanna et al. 2008). The reasons given for not performing universal OGTT screening included no national recommendation, low GDM risk, and organizational obstacles.

In terms of screening methods, respondents to the survey predominantly relied on glycosuria (54%) and/or random plasma glucose (52%) for a first screen (Hanna et al. 2008). The second most common first screen was risk factors (34%), followed by fasting plasma glucose (27%). The cutoff values for fasting glucose used by respondents varied from 5.5 to 7.8 mmol/L. The secondary screening method used was 2-hour OGTT with a 75 g glucose challenge, but…