Reference: N Engl J Med. 2021 Mar 11;384(10):895-904
The impact of gestational diabetes mellitus (GDM) on perinatal outcomes is well-established, and higher maternal hyperglycemia seems to correspond to worse clinical outcomes. Universal screening for GDM at 24-28 weeks gestation (or earlier if there are additional risk factors) is recommended using one of two clinically accepted methods: a one-step approach that involves a fasting blood glucose and then blood glucose checks at one and two hours after a 75 g glucose challenge, or the two-step method which involves a blood glucose check one hour after a 50 g challenge and a reflex three-hour glucose tolerance test for those who screen positive. Choice of screening method and diagnostic cutoffs are often institution-specific, without strong evidence at this point for a ‘best test.’
To that end, a research group in the Pacific Northwest and Hawaii designed a large trial to assess diagnosis of GDM and four prespecified perinatal outcomes in 23,792 pregnant patients randomized 1:1 to either one- or two-step screening approaches. Providers were made aware of the assigned screening method when they ordered GDM screening at 24-28 weeks gestation. The pragmatic trial design did not allow investigators to strictly enforce adherence to randomization, and there was disproportionate crossover between patients assigned to the one-step (fasting) screening test who received the two-step test (initial nonfasting) instead (66% vs. 92% adherence respectively). This was likely due to the opportunistic screening for non-fasting patients assigned to the one-step test (which requires initial fasting). In response to this discrepancy, additional patients were enrolled until adequate power was achieved for both groups, and an intention-to-treat (ITT) analysis with inverse probability weighting was applied to compensate for nonadherence. Six percent of patients did not undergo any screening for GDM and appeared to have overall worse clinical outcomes.
Of the patients who received any kind of screening for GDM (94%), the diagnosis of GDM was made in 16.5% of patients randomized to one-step screening (fasting) and 8.5% of those randomized to two-step screening (initial nonfasting) (unadjusted relative risk [RR] 1.94, 95% CI 1.79-2.11). There were no differences in any primary clinical outcome including large-for-gestational-age infant, composite perinatal outcome, gestational hypertension or preeclampsia, primary cesarean section, or any secondary clinical outcomes between groups when analyzed with either the preplanned ITT or adjusted ITT with inverse weighting.
If the study question was ‘what is the best test to screen for GDM?’, the answer depends on how you look at these data. Twice as many patients received the diagnosis of GDM with the one-step (fasting) screening method, but without differences in perinatal outcomes. Does that make it a more prognostic test? Or is this really just overdiagnosis? The high crossover rates with the one-step (fasting) approach make this a little less certain, but the size of the trial and the fact that the results were similar across several analyses suggest this likely reflects a true finding despite the potential threat to validity. We must also consider the additional burden on the healthcare system and on patients imposed by a “high-risk” label, especially knowing that patients with the diagnosis of GDM are more likely to have a primary cesarean section without improvements in perinatal outcomes. Given the lack of differences in clinical outcomes and better adherence to the two-step method, maybe we should frame GDM screening the way we frame colorectal cancer screening: the best test is the one the patient is actually willing to do. In this case, the two-step strategy seems like the way to go.
For more information, see the topic Gestational Diabetes Mellitus (GDM) in DynaMed.
DynaMed EBM Focus Editorial Team
This EBM Focus was written by Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency, and Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed.