Hyperglycemia and Adverse Pregnancy Outcome

Abstract & commentary

By John C. Hobbins, MD, Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.

Dr. Hobbins reports no financial relationship to this field of study.

Synopsis: A recent report may put a new spin on screening for gestational diabetes.

Source: International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676-682.

This spring a consensus opinion appears in the journal Diabetes Care, which represented a summary of deliberations of the International Association of Diabetes in Pregnancy Study Groups (IADPSG), a collaboration of 225 experts in the field from 40 countries, who gathered in Pasadena, CA, in June 2008. Since the current screening protocol for gestational diabetes (GDM) is about 40 years old, the group's goal was to make recommendations based on the best up-to-date information.

The screening guidelines that are in place now were based on the likelihood of a pregnant woman eventually becoming overtly diabetic. Instead, the aim of this group was to arrive upon screening guidelines that best correlated with adverse pregnancy outcomes, and they weighed heavily the results from an investigation published in the New England Journal of Medicine in May 2008 — the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study.1 This study included data from 25,500 patients in 15 centers around the world that were accumulated over a 6-year period. Primary outcomes included large-for-gestational (LGA) infants, primary cesarean section, and neonatal hypoglycemia. Secondary outcomes were preterm birth, shoulder dystocia, need for NICA care, neonatal hyperbilirubinemia, and preeclampsia.

The HAPO screening protocol called for a 75 g glucose load to be given to patients at 24-32 weeks gestation, and fasting 1- and 2-hour plasma glucose levels were evaluated (in essence, a 2-hour glucose tolerance test [GTT]). The managing physicians were blinded to the screening results, except in patients with fasting levels > 105 mg/dL and/or 2-hour levels > 200 mg/dL. They were considered to be overt diabetics and, therefore, were excluded from the analysis.

Not surprisingly, the HAPO study results (attaining statistical significant) showed rising odds ratios for the primary and secondary adverse outcomes with increasing glucose levels in the GTT. However, the authors indicated that "there were no obvious thresholds at which risks increased." To the contrary, the IADPSG Consensus Panel used unpublished data from the HAPO study itself, along with information from other studies, to make some important observations and recommendations regarding thresholds.

The group suggests that all patients with a historical predisposition for diabetes be evaluated on their first visit. If the fasting plasma sugars were > 126 mg/dL, a random plasma sugar exceeds 200 mg/dL, or the HbA1C levels were > 6.5%, these patients should be labeled as overt diabetics. If the fasting plasma sugar is > 6.5%, these patients should be labeled as overt diabetics. If the fasting plasma sugar is > 92 mg/dL, but < 126 mg/dL, they should be considered gestational diabetics. If the results are negative, then all patients should have a 75 g oral 2-hour GTT later, at 24-28 weeks, using the screening thresholds noted below. GDM is diagnosed if any of the three thresholds is equaled or exceeded.

Commentary

Although these recommendations will have to pass through a vetting processing by various colleagues and organizations before being officially approved, they are gaining momentum, while being fueled by an alarming increase in obesity and maternal and childhood diabetes.2 The proposed aggressive screening protocol does represent extra effort, but the good news is that very few undiagnosed GDMs will slip through. The bad news is that the total amount of screen positives will be 18% (based on HAPO data).

For years, the concept of screening every patient for gestational diabetes has not been uniformly supported. The detractors have maintained that knowing a patient's glucose status (excluding insulin-requiring diabetics) had not been shown convincingly to affect outcome. Also, labeling a patient as having GDM stigmatized her to a point where she might encounter difficulty in getting insurance coverage (something that should be rectified soon by recent legislation). The proponents say that there has been an explosion of childhood diabetes, perhaps catalyzed by a seeming epidemic of obesity in the United States — 60% of Americans are overweight (BMI 25-30 kg/m2) and 40% are obese (BMI > 30 kg/m2). The HAPO study shows that GDM is associated with adverse outcomes, but, although there are data to suggest that adjustment of management for these patients is cost-effective,3 the remaining doubters may have to be convinced by prospective intervention studies using the new guidelines.

So, in summary, here is what the IADPSG suggests:

  1. With a liberal suspicion for diabetes, appropriate patients should be evaluated at the time of their first visit. As stated above, if the fasting plasma is > 126 mg/dL, a random glucose is > 200 mg/dL, or the HbA1C exceed 6.5%, then the patient will be considered to be an overt diabetic.
  2. If the fasting plasma sugars are 92-126 mg/dL, these patients should be considered to have GDM.
  3. All others should empirically have a 75 g 2-hour GTT at 24-28 weeks using the following thresholds:
    1. Fasting — 92 mg/dL
    2. 1 hour — 180 mg/dL
    3. 2 hour — 153 mg/dL

This means that we substitute the above protocol for the standard 1-hour glucose screen, modify the standard GTT to include a 75 g glucose load, and delete the 3-hour blood draw. Although it is tempting to round off the above thresholds to values that are easier to remember (for example, to use 90 mg/dL instead of 92 mg/dL, and 150 mg/dL instead of 153 mg/dL), the group found that it would diminish the efficacy of the screening strategy. Frankly, it is even more tempting to bag the 2-hour blood draw, since, by itself, it was responsible for only 2% of the screen-positive patients.

It should be pointed out that these guidelines have yet to be endorsed by various official bodies, but, despite the confusion they may generate, it appears that they are on a fast track for approval. I am simply reporting on what is on the horizon, so please do not shoot the messenger.

References

  1. The HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991-2002.
  2. Narayan KM, et al. Effect of BMI on lifetime risk for diabetes in the U.S. Diabetes Care 2007;30:1562-1566.
  3. National Collaborating Centre for Women's and Children's Health. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal Period. London: RCOG Press; 2008.