Establishing diagnosis of gestational diabetes mellitus: Impact of the hyperglycemia and adverse pregnancy outcome study

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Summary

The diagnosis of gestational diabetes mellitus (GDM) remains controversial, without universal acceptance of a particular set of diagnostic criteria, and, in fact, a lack of consensus as to whether this is an entity worth diagnosis. Some of the debate derives from differences of opinion about what degree of glucose intolerance should be labeled as GDM. Therefore, it is to be expected that there are different viewpoints on how to detect and screen for GDM. It is believed that early diagnosis will result in a significant improvement in perinatal outcome in these patients. In this review, we discuss the current data concerning screening for GDM and new strategies for GDM diagnosis in light of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study.

Introduction

Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. The commonly used definition of GDM (‘carbohydrate intolerance of varying degrees of severity with onset or first recognition during pregnancy’)1 has been accepted for almost the last 30 years. However, methods of ascertainment and diagnostic criteria vary widely. Furthermore, the adverse consequences, benefits of treatment and cost-effectiveness of diagnosis and treatment of GDM remain controversial. The results of several recent studies may lessen some of the controversy. In a 10 year multicenter randomized clinical trial, Crowther et al.2 aimed to determine whether medical nutritional therapy, glucose monitoring, and insulin therapy compared to routine prenatal care reduced the risk of perinatal complications and altered postpartum maternal health status. They found a significant reduction in serious adverse perinatal outcome in the interventional group (1% vs 4%). Other results were higher rates of labor induction, decreased rate of large for gestational age (LGA) infants and decreased rate of shoulder dystopia in the interventional group. The rates of cesarean deliveries and small for gestational age infants were not changed. Moreover, Langer et al.3 in a retrospective study compared pregnancy outcome between GDM pregnant women who were diagnosed after 37 weeks (not treated) with treated GDM women and control non-diabetic pregnant women. A composite adverse outcome of 59% for untreated, 18% for treated, and 11% for non-diabetic subjects was found. A 2–4-fold increase in metabolic complications and macrosomia/LGA was found in the untreated group with no difference between non-diabetics and well-treated subjects. Comparison of maternal size, parity, and disease severity revealed a 2–3-fold higher morbidity rate for the untreated groups compared with the other groups. These studies together with others have reduced concern regarding the identification of GDM. However, there is still debate concerning what is the appropriate screening test (if at all) and what is the most suitable diagnostic test. Initial results from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, initiated in 1999, were recently published.4 The goal was to determine what degree of glucose intolerance short of diabetes conveys a clinically important risk for adverse perinatal outcome. The results showed that the primary outcomes (birthweight >90th percentile for gestational age, umbilical cord-blood serum C-peptide level a proxy for fetal insulin levels), incidence of cesarean delivery, and incidence of neonatal hypoglycemic episodes all increased in direct proportion to higher maternal glucose levels, after an overnight fast and 1 and 2 h after a 75 g glucose load. These associations held with adjustment for potential confounders, including maternal age, body mass index (BMI), and blood pressure.

The data collected in the HAPO study should permit the selection of ‘outcome-based’ criteria for the diagnosis of GDM. However, reaching a consensus on changes in diagnostic criteria and strategies for detection will take some time. Accordingly, the objective of this review is to assess the issues regarding the detection and diagnosis of GDM as they currently apply.

Section snippets

Strategies for detection and diagnosis of GDM

There is no debate about the fact that when overt diabetes mellitus (DM) occurs during pregnancy it is associated with adverse maternal and fetal outcomes. Since early diabetes, especially type 2 DM, is usually asymptomatic, virtually all caregivers are alert to the need to detect and treat this condition. Therefore, they all engage in some form of screening process. Indeed, it has been acknowledged that systematically taking a personal and family medical history represents a form of screening,

Who to screen?

The current prevalence of GDM in the USA ranges from 3% to 14%, depending on the characteristics of the population screened and the diagnostic criteria that are applied.5, 6 In women with defined low risk factors, such as White ethnic origin, age <25 years and BMI <25 kg/m,2 prevalence of gestational diabetes ranges from 1.4% to 2.8%.7, 8, 9 In a recent survey, Getahun et al. have shown that the prevalence rates of GDM increased from 1.9% in 1989–1990 to 4.2% in 2003–2004, a relative increase of

What is the best screening strategy?

Quality evidence comparing the different methods of GDM screening is lacking and often contradictory.14 In a randomized prospective study, Griffin et al. assigned women to one of two groups: universal screening at 26–28 weeks' gestation or women with risk factors for GDM screened at 32 weeks' gestation.21 The results showed an increased prevalence of GDM diagnosed in the universal screening group (2.7% vs 1.45%; P < 0.03) and reaffirmed the poor predictive value of historical risk factors for

What is the recommended GCT threshold?

To reiterate, screening is a test performed on asymptomatic patients in order to identify those at risk for developing a disease. Coustan et al.23 studied 6000 women using a 50 g oral GCT, and an abnormal threshold designated as 130 mg/dL. Twenty-three percent of his study population required a 3 h OGTT. Lowering the threshold from 140 to 130 mg/dL resulted in an 11% increase in test sensitivity. However, there was a significant increase in the rate of women requiring OGTT. Studies have

What is the best screening test?

Since the pioneer study by O'Sullivan et al.,12 a 50 g GCT has became the most common screening test.15 Perucchini et al.27 suggested the use of a fasting glucose value to screen for gestational diabetes. They compared the 50 g challenge test with fasting plasma from the OGTT using the Carpenter–Coustan criteria on each subject regardless of the screening results. They proposed that a 126 mg/dL screening value is the best threshold for the challenge test resulting in a sensitivity of 81% and

Potential harms of screening

There are two potential domains of harms of screening for, and treatment of, gestational diabetes: the psychological and the physical. The primary adverse effects associated with screening would be the psychological effect of screening on the mother with gestational diabetes, and potentially on the mother who does not have gestational diabetes but has the added time, cost, physical discomfort, and psychological burden of screening and confirmatory diagnostic testing. A review of the literature

Pregnancy outcome associated with abnormal screening value

It has been suggested that even minor degrees of increased glucose intolerance during pregnancy in women without GDM are related in a continuous and graded pattern with significantly increased incidence of macrosomia, cesarean section, pre-eclampsia, and increased need for neonatal intensive care unit admission, as well as greater length of maternal and neonatal hospital stay.32, 33, 34, 35, 36 In a prospective study of >6000 women, Yogev et al. found a gradual increase in the rate of

Diagnosis of GDM

Diagnostic tests differ from screening tests in that they are applied to patients with positive screening results and/or symptomatic populations. The ideal diagnostic test for gestational diabetes has not yet been developed. There are limitations of the OGTT that include test duration, time of performance (morning only after nocturnal fast), patient discomfort, especially during the first trimester with potential nausea and vomiting as well as the supraphysiological glucose load unrelated to

Reproducibility of the OGTT

The main deficiency of the OGTT is the lack of reproducibility. In non-pregnant individuals, repetition of the test showed a mean difference of 26 mg/dL at 1 h and 20 mg/dL at 2 h levels.38 Harlass et al.7 found a significant variability in the OGTT results especially when the glucose values were in the upper normal range. This resulted in upgraded reclassification of many patients from non-diabetic to diabetic. Therefore, they recommended that borderline OGTT results be repeated. Espinosa de los

100 vs 75g glucose OGTT

There is no consensus on the glucose load concentration that should be used for the glucose test. Several clinical studies have attempted to test whether the 75 g load (recommended by the World Health Organization and by the American Diabetes Association) is more convenient and provides greater accuracy than the 100 g load, whereas others have suggested that some GDM women will not be identified with the lower load. A report by Mello et al.41 suggested that more women meet the diagnostic

One abnormal value in the OGTT: the predictive value for a GDM diagnosis

Despite repeated reports of the association between one abnormal value on the OGTT results and adverse outcome in pregnancy, the use of one abnormal value for the diagnosis of GDM remains controversial.

If we accept the idea that glucose is a continuous measure, it may then reflect a continuum of glucose abnormality. Currently, there is paucity of information related to the degree of abnormality (i.e. the number of abnormal test values), threshold criteria, and pregnancy outcome. There is a need

Is there a difference between NDDG and Carpenter–Coustan criteria?

The multiple criteria have resulted in different rates of prevalence even within the same geographic and demographic catchments. As a rule of thumb, the lower the thresholds, the higher the prevalence. A clinical evaluation of the two sets of criteria in 103 patients found that 10 of 39 (26%) patients whose glucose tolerance tests were abnormal by the Carpenter–Coustan criterion but not by the NDDG criterion required insulin during pregnancy.56 This is a substantial number compared with the

Association of maternal glycemia with perinatal outcome: additive role of the HAPO study

Due to the aforementioned uncertainty concerning the appropriate threshold for GDM diagnosis, and the fact that no consensus exists regarding different screening and diagnosis tools, the need for a comprehensive study has risen. There is a consensus that overt DM, whether or not accompanied by symptoms or signs of metabolic decompensation, is associated with a significant risk of adverse pregnancy outcome. However, there is controversy over the risk of adverse outcome associated with degrees of

Summary

Although recent studies, both randomized and retrospective,*2, *3 have shown that not treating GDM is associated with poor pregnancy outcome, there is still no consensus on screening method or on establishing globally applicable threshold criteria.

A recent survey47 reported that routine screening for GDM is common practice and is used by 96% of obstetricians in the USA; 95.2% used a 50 g GCT. Furthermore, in 1987, only 83.8% of ACOG members used universal screening and this increased to 96% in

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