One Step or Two Step: Which is the Best Method for GDM Screening?

BACKGROUND AND PURPOSE:

  • The best method for gestational diabetes mellitus (GDM) screening remains controversial
  • One-step approach: 75 g 2 hours OGTT using the IADPSG criteria
    • Recommended by: IADPSG | FIGO | WHO
  • Two-step approach: 50 g 1 hour GCT followed by a 3 hours 100 g OGTT
    • Recommended by: ACOG | ADA
  • Saccone et al. (The Journal of Maternal-Fetal & Neonatal Medicine, 2018) assessed the incidence of maternal and neonatal outcomes comparing one-step vs  two-step approach

METHODS:

  • Systematic review and meta-analysis
  • Data sources
    • Electronic database from inception until June 2018
  • Inclusion criteria
    • RCTs that compared the one-step vs two-step method for screening and diagnosis of GDM
  • Study design
    • Large for gestation age (LGA): Defined as birth weight >90th percentile
    • Meta-analysis was performed using the random effects model
      • Treatment effects calculated as relative risk (RR) with 95% CI
  • Primary outcome
    • Incidence of LGA
  • Multiple secondary outcomes included
    • Maternal complications such as preeclampsia, preterm birth, induction of labor, shoulder dystocia and cesarean delivery
    • Neonatal adverse outcomes, including neonatal hypoglycemia or hyperbilirubinemia and NICU admission  

RESULTS:

  • 4 RCTs were included | Total of 2582 participants | Overall risk of bias was low
  • Control groups (2-step approach) among the 4 studies
    • 2 trials: 50 g 1 hour GCT followed by 100 g 3 hours (OGTT)
    • 1 trial: 50 g 1-hour test before randomization with exclusion if glucose ≥200 mg/dL
    • 3-arm trial with two control groups (considered as 1 control group for this meta-analysis)
      • Two-step 50 g 1 hour followed by 100 g 3 hours OGTT
      • Two-step 50 g 1 hour GCT followed by 75 g 2 hours OGTT
  • Management of diabetes also differed with respect to use of insulin as exclusive first line medication as well as glucose target values  
  • One-step approach was associated with a lower risk of adverse perinatal outcomes, such as
    • LGA (primary outcome): 2.9% vs 6.3%; RR 0.46 (95% CI, 0.25 to 0.83)
    • NICU admission: RR 0.49 (95% CI, 0.29 to 0.84)
    • Neonatal hypoglycemia: RR 0.52 (95% CI, 0.28 to 0.95)
  • The one-step approach was associated with lower mean birth weight
    • Mean difference −112.91 grams (95% CI, −190.48 to −35.33)
  • There was no significant difference in the incidence of GDM
    • One step: 8.3%
    • Two step: 4.4%
    • RR 1.60 (95% CI 0.93 to 2.75)
  • Authors performed a subgroup analysis removing the 3-arm trial (slightly different inclusion criteria, i.e. multiple gestations) and also differences in screening criteria compared to the other studies (Canadian Diabetes Association)
    • Incidence of GDM was increased with removal of this trial (12.6% vs 5.6%; RR 2.20)
  • Subgroup analysis was only performed for GDM incidence and not perinatal outcomes

CONCLUSION:

  • In this meta-analysis, the one-step approach to GDM screening was associated with better perinatal outcomes compared to the two-step approach
  • The authors state that

The argument against the one-step approach has been that it increases the incidence of GDM significantly, without proven improvement in maternal and/or perinatal outcomes
Our meta-analysis of RCTs, however, provides level-1 evidence that the one-step approach significantly improves perinatal outcomes
In particular, we found a 54% reduction in the risk of LGA

Learn More – Primary Sources:

Screening for gestational diabetes mellitus: one step versus two step approach. A meta-analysis of randomized trials

ACOG and SMFM Both Release Guidance on Gestational Diabetes – Insulin vs Metformin for First-Line Therapy?

SUMMARY:

The SMFM released a statement on the use of metformin as a first-line alternative to insulin in women with GDM.  ACOG has also released an update to the major 2017 Practice Bulletin which also addresses this issue and still considers insulin the preferred option to treat women who are not adequately controlled with appropriate nutritional therapy.

  • Both the ACOG update and SMFM statement summarize the literature, including recent meta-analyses on the comparison studies between insulin and metformin
    • Data has been conflicting based on whether non-published studies included women with type II diabetes
    • Some studies have demonstrated a higher risk for preterm birth (but lower for gestational hypertension) in the metformin group while other studies have not identified a difference in preterm birth

ACOG

  • Based on current evidence, ACOG states that, consistent with ADA guidance, insulin is the ‘preferred’ approach for GDM for women not sufficiently controlled with diet and exercise
  • In addition, the ACOG update states

Thus, although metformin may be a reasonable alternative approach to treat gestational diabetes, it is important to counsel women about the lack of superiority when compared with insulin, the placental transfer of the drug, and the absence of long-term data in exposed offspring. Additionally, in the aforementioned prospective trials, between 26% and 46% of women who took metformin alone eventually required insulin.

SMFM

  • Upon review of the evidence, SMFM considers metformin to be a “reasonable and safe first-line pharmacologic alternative to insulin”
  • More data is needed to establish long-term safety of oral agents
  • Glyburide has been associated with adverse neonatal events, such as macrosomia and hypoglycemia but SMFM also acknowledges that “the evidence of benefit of one oral agent over the other remains limited”
  • SMFM does acknowledge that their statement conflicts with ACOG, however

…this difference is based on the values placed by different experts and providers on the evidence available in the medical literature and is not meant to represent an exclusive course of management.

KEY POINTS:

Other ACOG Updates

One abnormal values on the 3 hour OGTT

  • In the previous 2017 practice bulletin, while it was clearly stated that diagnosis of GDM is based on 2 abnormal values on the 3 hour OGTT, ACOG seemed to suggest that one abnormal value may be sufficient to make the diagnosis
  • In the updated 2018 version, ACOG has clarified that statement
    • One abnormal glucose level may warrant a higher level of scrutiny, but is not sufficient for diagnosis
    • More studies are required to determine risk of adverse outcomes and who would benefit from making this a diagnostic criteria

Clarification of insulin use and dosage

  • ACOG has clarified the previous practice bulletin and now states that in women who have abnormal postprandial and fasting glucose levels
    • Insulin starting dose is 0.7-1.0 units/kg daily
    • Dosage should be divided and long-acting or intermediate-acting insulin in combination with short-acting insulin should be used
  • Previously, the 2017 documented stated that insulin was ‘first line’ therapy and the updated document now says ‘preferred’
    • ACOG recognizes that clinicians may assess the clinical circumstances and find the use of oral agents to be a better alternative in women (e.g., patient cannot afford insulin or feel administering the drug would be unsafe)

Macrosomia and cesarean section

  • The recommendation that women with GDM should be counseled about the risks/benefits of a scheduled cesarean section if the estimated fetal weight is ≥4,500 g has been moved from ‘limited or inconsistent scientific evidence’ (Level B) to ‘consensus and expert opinion’ (Level C)

Learn More – Primary Sources:

SMFM Statement Pharmacological treatment of gestational diabetes

ACOG Practice Bulletin 190: Gestational Diabetes Mellitus

Updated ACOG Guidance on Gestational Diabetes

SUMMARY:

ACOG released updated guidance on gestational diabetes (GDM), which has become increasingly prevalent worldwide.  Class A1GDM refers to diet-controlled GDM. Class A2GDM refers to the clinical scenario where medications are required. Highlights and changes from the previous practice bulletin include the following:

Screening for GDM – One or Two Step?

  • ACOG (based on NIH consensus panel findings) supports the ‘2 step’ approach (24 – 28 week 1 hour venous glucose measurement following 50g oral glucose solution), followed by a 100g 3 hour oral glucose tolerance test (OGTT) if positive
    • Note: Diagnosis of GDM is based on 2 abnormal values on the 3 hour OGTT
      • ACOG recommends that currently there is insufficient evidence to diagnose GDM based on only one abnormal value
      • Patients with only one elevated value may require additional surveillance
  • 1 step approach (75 g OGTT) on all women will increase the diagnosis of GDM but sufficient prospective studies demonstrating improved outcomes still lacking
  • ACOG does acknowledge that some centers may opt for ‘1 step’ if warranted based on their population
  • ADA considers either 1 step or 2 step (using Coustan Carpenter criteria) to both be valid for GDM diagnosis
  • The USPSTF
    • Recommends screening for gestational diabetes in asymptomatic pregnant persons at ≥24 weeks of gestation or after (B recommendation)
    • Current evidence is insufficient to assess the balance of benefits and harms of screening for gestational diabetes in asymptomatic pregnant persons <24 weeks of gestation (I statement)

Who Should be Screened Early?

ACOG has adopted the NIDDK / ADA guidance on screening for diabetes and prediabetes which takes in to account not only previous pregnancy history but also risk factors associated with type 2 diabetes. Consider early screening in pregnancy if:

Patient is overweight with BMI of 25 (23 in Asian Americans), and one of the following

  • Physical inactivity
  • Known impaired glucose metabolism
  • Previous pregnancy history of:
    • GDM
    • Macrosomia (≥ 4000 g)
    • Stillbirth
  • Hypertension (140/90 mm Hg or being treated for hypertension)
  • HDL cholesterol ≤ 35 mg/dl (0.90 mmol/L)
  • Fasting triglyceride ≥ 250 mg/dL (2.82 mmol/L)
  • PCOS,  acanthosis nigricans, nonalcoholic steatohepatitis, morbid obesity and other conditions associated with insulin resistance
  • Hgb A1C ≥ 5.7%, impaired glucose tolerance or impaired fasting glucose | If A1C>6.5%, diagnosis of pregestational diabetes is met and GCT/GTT not needed
  • Cardiovascular disease
  • Family history of diabetes – 1st degree relative (parent or sibling)
  • Ethnicity of African American, American Indian, Asian American, Hispanic, Latina, or Pacific Islander

(more…)

Practical obstetrics info for your women's healthcare practice

What Is The ‘One-Step’ GDM Screening Approach?

CLINICAL ACTIONS:

There is no debate that all pregnant women should be screened for Gestational Diabetes Mellitus (GDM) between 24 and 28 weeks. However, there are two different approaches to screening for GDM. ACOG currently prefers the traditional ‘two-step’ approach, using an initial screen that, if positive, requires an additional confirmatory test. Alternatively, there is the option of the International Association of Diabetes and Pregnancy Study Groups that recommend a ‘one-step’ approach as follows

  • Perform a 75 g oral glucose tolerance test on all women, after an overnight fast, not previously found to have overt diabetes or GMD earlier in pregnancy
  • Diagnose GDM when one or more of the following plasma glucose values are exceeded
    • Fasting ≥ 92 mg/dL (5.1 mmol/l)
    • 1-hour ≥ 180 mg/dL (10.0 mmol/l)
    • 2-hour ≥ 153 mg/dL (8.5 mmol/l)
  • Early screening for overt diabetes in women at high risk for type 2 diabetes is recommended by this professional group at the first prenatal visit to allow for early detection and management for complications such as fetal anomalies and potential microvascular disease in the mother
    • If fasting plasma glucose is ≥92 mg/dL (≥5.1 mmol/l) but < 126 mg/dL (7.0 mmol/l) diagnose GDM
    • Overt diabetes as per standard cut-offs

SYNOPSIS:

Unfortunately, with the obesity epidemic and more sedentary lifestyles, GDM is increasing as well, and being observed in younger age groups. Complications are significant, including birth trauma to both mother and child. Treatment including diet, increased exercise and if necessary medications can be effective, if GDM is identified in time to implement these changes to achieve best results.

KEY POINTS:

  • ACOG and consensus panel convened by the NIH do not recommend the ‘one-step’ approach, but rather the ‘two-step’ approach
    • Centers can adopt ‘one-step approach’ if more clinically applicable for a particular population
  • The ‘one-step’ screening approach will result in increased diagnosis of GDM
  • The controversy relates to whether with the increased costs and resources necessitated by the ‘one-step’ approach will result in improved outcomes
  • Targeting obesity and improved nutrition can also address macrosomia risks
  • The ADA recognizes ‘2 step’ Carpenter and Coustan approach or ‘1 step’ approach (see Related ObG Topics below) to both be valid for GDM diagnosis

Learn More – Primary Sources:

International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy

NIDDK– Test Criteria for Prediabetes, Diabetes, and Gestational Diabetes

ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus

ADA Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020