BACKGROUND AND PURPOSE:

• Hillier et al. (NEJM, 2021) compared the one-step vs two-step approach for GDM screening and diagnosis

METHODS:

• Pragmatic, randomized trial
  • Kaiser Permanente Northwest and Kaiser Permanente Hawaii
• Participants
  • All pregnant women
• Interventions
  • One-step screening (recommended by IADPSG and ADA)
    • Glucose-tolerance test (75 g glucose load) in the fasting state
    • 2-hour OGTT
  • Two-step screening (Carpenter–Coustan approach recommended by ACOG)
    • GCT (50 g glucose load) in the nonfasting state
    • If screen positive: 3 hour fasting diagnostic OGTT
• One step positive result
  • Fasting blood glucose level ≥92 mg per deciliter (5.1 mmol per liter)
  • 1 hour: ≥180 mg per deciliter (10.0 mmol per liter)
  • 2 hour: ≥153 mg per deciliter (8.5 mmol per liter)
• 1 hour GCT
  • GDM diagnosis: Blood glucose level ≥200 mg per deciliter (11.1 mmol per liter)
  • Positive screen: <200 mg per deciliter and ≥130 mg per deciliter (≥7.2 mmol per liter) at Kaiser Permanente Northwest and ≥140 mg per deciliter (≥7.8 mmol per liter) at Kaiser Permanente Hawaii
• 3 hour OGTT
  • ≥2 above threshold: Fasting ≥95 mg per deciliter (≥5.3 mmol per liter) | 1 hour ≥180 mg per deciliter at 1 hour | 2 hour >155 mg per deciliter (≥8.6 mmol per liter) | ≥140 mg per deciliter at 3 hours
• Study design
  • Intention-to-treat
  • Performed at 24 to 28 weeks
  • Consent waived 
• Primary outcomes
  • GDM diagnosis
  • LGA (BW >90^th percentile)
  • Perinatal composite outcome (stillbirth, neonatal death, shoulder dystocia, bone fracture, or any arm or hand nerve palsy related to birth injury)
  • Gestational hypertension or preeclampsia
  • Primary cesarean
• Secondary outcomes
  • Macrosomia (BW >4000 g)
  • SGA (BW ≤10th percentile)
  • Requirement of GDM medication
  • Neonatal: Respiratory distress | Jaundice requiring treatment | Hypoglycemia | Individual components of the composite perinatal outcome

RESULTS:

• 23,792 women underwent randomization
  • Adherence to assigned screening
    • One-step: 66%
    • Two-step: 92%
• GDM diagnoses
  • One-step: 16.5%
  • Two-step: 8.5%
  • Unadjusted relative risk (RR) 1.94 (97.5% CI, 1.79 to 2.11)
• Incidence of other primary outcomes
  • LGA infants
    • One-step: 8.9%
    • Two-step: 9.2%
    • RR 0.95 (97.5% CI, 0.87 to 1.05)
  • Perinatal composite outcome
    • One-step: 3.1%
    • Two-step: 3.0%
    • RR 1.04 (97.5% CI, 0.88 to 1.23)
  • Gestational hypertension or preeclampsia
    • One-step: 3.6%
    • Two-step: 13.5%
    • RR 1.00 (97.5% CI 0.93 to 1.08)
  • Primary cesarean
    • One-step: 24.0%
    • Two-step: 24.6%
    • RR 0.98 (97.5% CI 0.93 to 1.02)
• No change when adjusted for adherence differential

CONCLUSION:

• One-step screening approach led to more gestational diabetes diagnoses than 2-step, but otherwise there were no significant differences in primary outcomes between the groups
• Limitations of this include
  • Black and American Indian women were not well represented
  • Physicians were not blinded to the intervention
  • Two different (although acceptable) GCT thresholds were used
  • Difference in adherence could bias results | Study was extended to ensure sufficient statistical power
• The author of the NEJM editorial concludes

On the basis of the current data, however, the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis

Refocusing attention on interventions in women who are at risk for the development of diabetes is more likely to yield substantive benefits 

Response: Coustan et al. AJOG, 2021

In a Clinical Opinion paper (AJOG, 2021) Coustan et al. respond to ScreenR2GDM conclusions

• Authors acknowledge that the one-step protocol
  • Does require that patient be fasting
  • Will identify 2 to 3 times the number of women with GDM (18 to 20%)
    • However, this is still lower than current US prediabetes rate of 24% (women of reproductive age)
    • Therefore, resources are similar to those required to address prediabetes in nonpregnant individuals
• Concerns regarding the ScreenR2GDM study include
  • Study not sufficiently powered to demonstrate the advantage of one-step testing | Coustan et al., based on data review, determined that relative risk targets of 1.16 for LGA and 1.12 for hypertensive disorders was more in line with previous literature vs the 1.2 relative risk selected by the ScreenR2GDM team
  • 27% of the women were randomized to the one-step protocol but underwent two-step testing
  • 6% of the study cohort had no testing
  • A subset of women assigned to two-step testing did not meet the criteria for GDM but were treated as GDM because of elevated fasting plasma glucose levels | This would reduce adverse outcomes in this group without increasing the number of GDM cases
  • Long term maternal and newborn benefits were not included among the outcomes  

Learn More – Primary Sources:

A Pragmatic, Randomized Clinical Trial of Gestational Diabetes Screening

NEJM Editorial: Gestational Diabetes — On Broadening the Diagnosis

Clinical Opinion (Coustan et al.): One Step or Two Step Testing for Gestational Diabetes: Which Is Best?

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