Screening and Diagnosis of Gestational Diabetes Mellitus

The 1997 World Health Organization (WHO) estimates the prevalence of diabetes in adults, including gestational diabetes mellitus (GDM), will rise more than 120% from 135 million in 1995 to 300 million in 2025. Differences in screening programs and diagnostic criteria make it difficult to compare the prevalence of GDM among various populations.[1]

Screening

Important attributes of any screening test are its sensitivity (the ability of the test to detect true cases) and its specificity (the ability of the test to exclude those without the disease).[2] The purpose of screening, as shown in Figure 1 below, is to identify individuals at high risk for developing the disease and to provide appropriate treatment for individuals who screen positive.

Figure 1. Screening algorithm

At the first prenatal visit, risk assessment for GDM should be determined. Women with high risk of GDM (marked obesity, personal history of GDM, glycosuria, or a strong family history of diabetes) should undergo glucose testing. If the initial screening is negative, they should be retested between 24 and 28 weeks of gestation. Women of average risk should have testing undertaken at 24 to 28 weeks of gestation. Low-risk status requires no glucose testing. This category as identified by the American Diabetes Association (ADA) includes the following characteristics[3]:

• Age <25 years

• Weight normal before pregnancy

• Member of an ethnic group with a low prevalence of GDM

• No known diabetes in first-degree relatives

• No history of abnormal glucose tolerance

• No history of poor obstetric outcome

The purpose of screening is early diagnosis and treatment. Defining the best screening strategy for GDM is complicated due to the lack of a universally accepted "gold standard" for its diagnosis. The 50 g 1-hour oral glucose test (glucose challenge test, GCT) is used to screen for GDM. A glucose threshold value ≥140 mg/dL (7.8 mmol/L) means that GDM is a possibility, and a diagnostic test is indicated, such as the 75-g or 100-g oral glucose tolerance test (OGTT).[4,5]

As per the ADA, a fasting plasma glucose level ≥126 mg/dL (7.0 mmol/L) or a casual plasma glucose level ≥200 mg/dL (11.1 mmol/L) meets the threshold for the diagnosis of diabetes if confirmed on a subsequent day and eliminates the need for any glucose challenge. In the absence of this degree of hyperglycemia, evaluation for GDM in women with average or high-risk characteristics should follow 1 of 2 approaches.[3]

One-step approach

A diagnostic oral glucose tolerance test (OGTT) without prior plasma or serum glucose screening is performed. The 1-step approach may be cost effective in high-risk patients.

Two-step approach

An initial screening is performed by measuring the plasma or serum glucose concentration 1 hour after a GCT, and then a diagnostic OGTT is performed on that subset of women exceeding the glucose threshold value on the GCT. When the 2-step approach is employed, a glucose threshold value ≥140 mg/dL (7.8 mmol/L) identifies approximately 80% of women with GDM, and the yield is further increased to 90% by using a cutoff of ≥130 mg/dL (7.2 mmol/L).[3]

The reliability of the GCT is questionable. In one study, 22% of women who had GDM screening performed on 2 successive days produced different results.[6] Data to support specific timing for screening is also inadequate. Women who develop GDM early in pregnancy are at higher risk for neonatal hypoglycemia and other GDM-related outcomes than women who develop GDM later in pregnancy. Screening earlier in pregnancy detects fewer women with GDM but identifies those at highest risk, thus allowing for earlier intervention. Screening for GDM later in pregnancy detects a larger number of women with GDM, many of whom are at lower risk, but who would be treated for a shorter time.[4]

The ADA recommends screening all women at risk for GDM. The ADA considers women to be at risk for GDM if they are not in the low risk status as mentioned above. A 2001 Practice Bulletin of the American College of Obstetricians and Gynecologists (ACOG) recommends a similar risk-based approach but notes that since only a small percentage of patients meet the criteria for low risk, universal 50-g 1-h GCT screening may be a more practical approach.[4,7]

ACOG recommends universal screening between 24 and 28 weeks of gestation for women of average risk.[8,9] Glucose intolerance increases as gestation advances, in parallel with a rising level of hormones (human placental lactogen, prolactin, cortisol, glucagon, estrogen, and progesterone). This causes decreased glucose tolerance, increased insulin resistance, and increased hepatic production of glucose, with depletion in hepatic glycogen. The gestational age of 24 to 28 weeks is late enough to allow for the developing intolerance, but early enough to allow timely intervention. Screening before 20 weeks has a low yield, and intensive glycemic control initiated after 32 weeks does not improve fetal outcomes. With risk factors, suspicion of pregestational diabetes, or signs and symptoms suggesting hyperglycemia, screening may be performed earlier. In 5% of recurrent GDM cases, recurrence is established before 24 weeks. If a patient has an elevated screening test but a normal diagnostic test before 24 weeks, the diagnostic test needs to be repeated later in pregnancy. These women, compared with women with normal screening, have impaired glucose tolerance and an increased risk of GDM and are at an increased risk of developing preeclampsia.[10]

Many other tests have been proposed for screening. Random glucose determinations or 2-h postprandial determinations have been proposed in order to eliminate the inconvenience of an oral glucose challenge, but these tests proved to have low sensitivity. Glycosylated hemoglobin levels were not found to be helpful, because of low sensitivity and specificity.[10]

No properly conducted randomized controlled trial has examined the benefit of universal or selective screening for GDM, compared with no screening. Even if screening and treatment are effective, the benefits of widespread screening as a means for preventing birth trauma due to macrosomia are likely to be very small. Modeling done for the US Preventive Services Task Force (USPSTF), which assumed that treatment with insulin would reduce the risk of mothers with GDM having an infant with macrosomia by 75%, calculated that nearly 7,000 women at high risk and 9,000 women at average risk would need to be screened to prevent one case of brachial plexus injury. Although serious, 80% of these injuries resolve within the first year.[4]

Cost and cost effectiveness of screening

There is absence of adequate evidence to determine whether selective or universal screening is effective in improving health outcomes. Reliable estimates of the costs of GDM for women who are not screened are also not available.[4] In one study, based on reported prevalence data (5% for GDM and 0.1% for neural tube defects), the authors calculated that 10,000 women need to be screened for gestational diabetes to prevent 50 cases of fetal macrosomia, and possibly 6 cases of shoulder dystocia, whereas only approximately 600 women need to be screened with maternal serum α-fetoprotein in order to detect one case of neural tube defect.[10] In another study, conducted in a developing country to determine the screening methods for GDM suited for the local population, the authors recommended universal screening where the prevalence was high. In developing countries where the health service can be stretched to the limit, universal screening is less expensive and can lead to long-term savings.[11]

Diagnosis

The 100-g 3-h OGTT (oral glucose tolerance test) is used to diagnose GDM. The diagnostic criteria were developed for their ability to identify mothers at risk for developing diabetes. Expert groups have proposed different criteria for diagnosis based on the 3-h OGTT. The test also helps identify women with an increased risk of fetal macrosomia and caesarean delivery.[1]

Diagnostic criteria for the 100-g OGTT are derived from the original work of O' Sullivan and Mahan, modified by Carpenter and Coustan, and are shown in Table 1.[12] Alternatively, the diagnosis can be made using a 75-g glucose load, but the 75-g test is not as well validated for detection of at-risk infants or mothers as the 100-g OGTT.[3]

Table 1. ADA criteria for the diagnosis of GDM with a 100-g glucose load[12]

The cutoff values for the 3-h OGTT represent still another source of controversy.

The Fourth International Workshop-Conference on Gestational Diabetes in 1997, as well as ADA, adopted the Carpenter and Coustan criteria. ACOG uses either the Carpenter and Coustan criteria or the National Diabetes Data Group. At least 2 abnormal values out of 4 on a 3-h OGTT are necessary for the diagnosis of GDM.[10] The Fourth International Workshop-Conference on Gestational Diabetes recommended the 75-g OGTT as an alternative to the 100-g OGTT. The 75-g OGTT is preferred by the WHO, many European countries, and Japan. The cutoff values recommended by WHO are 126 mg/dL for fasting, and 150 mg/dL for 2 hours.[10]

Cost analysis of diagnosis

No randomized trials have been done to determine if the diagnosis and treatment of GDM would reduce the outcome costs compared with those without GDM or compared with a group with untreated GDM. Obesity is a potential confounder in the literature on health care costs for women with GDM. The prevalence of macrosomia and caesarean delivery is higher in obese mothers, as are postoperative complications. The average cost of hospital care is also higher for these patients.[13]

References

1. Ben-Haroush A, Yogev Y, Hod M. Epidemiology of gestational diabetes mellitus and its association with type 2 diabetes. Diabet Med. 2004;21:103-113.
2. Diabetes in America. 2nd edition. National Diabetes Data Group. National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases. 1995;NIH Publication No. 95-1468.
3. ADA. Standards of medical care in diabetes-2006. Diabetes Care. 2006;29(suppl 1):S4-S42. 
4. US Preventive Services Task Force. Screening for gestational diabetes mellitus: recommendations and rationale. Obstet Gynecol. 2003;101:393-395.
5. Hoffman L, Nolan C, Wilson D, Oats JJN, Davis Simmons. Gestational Diabetes Mellitus Guidelines. The Australian Diabetes in Pregnancy Society. MJA 1998;169:93-97. Available at: http:www.mja.com.au/public/issues/jul20/hoffman/hoffman.html. Accessed January 25, 2005. 
6. Harlass FE, Brady K, Read JA. Reproducibility of the oral glucose tolerance test in pregnancy. Am J Obstet Gynecol. 1991;164:564-568.
7. American College of Obstetricians and Gynecologists Practice Bulletin. Clinical management guidelines for obstetrician gynecologists. Number 30, September 2001. Obstet Gynecol. 2001;98:525-538.
8. Hicks P. Gestational diabetes in primary care. Medscape Women's Health. 2000;5:2. Available at: http://www.medscape.com/viewarticle/408910. Accessed on January 25, 2005.
9. American College of Obstetricians and Gynecologists. Diabetes and Pregnancy [Technical Bulletin No. 200]. Washington, DC; December 1994.
10. Vidaeff AC, Yeomans ER, Ramin SM. Gestational diabetes: a field of controversy. Obstet Gynecol Surv. 2003;58:759-69.
11. Larijani B, Hossein-nezhad A, Rizvi SW, Munir S, Vassigh AR. Cost analysis of different screening strategies for gestational diabetes mellitus. Endocr Pract. 2003;9:504-509.
12. ADA. Standards of medical care in diabetes. Diabetes Care. 2006;29(suppl 1):S7.
13. Galtier-Dereure F, Boegner C, Bringer J. Obesity and pregnancy: complications and cost. Am J Clin Nutr. 2000;71(suppl 5):1242S-1248S.