A Pragmatic, Randomized Clinical Trial of Gestational Diabetes Screening

N Engl J Med. 2021 Mar 11;384(10):895-904. doi: 10.1056/NEJMoa2026028.


Background: Gestational diabetes mellitus is common and is associated with an increased risk of adverse maternal and perinatal outcomes. Although experts recommend universal screening for gestational diabetes, consensus is lacking about which of two recommended screening approaches should be used.

Methods: We performed a pragmatic, randomized trial comparing one-step screening (i.e., a glucose-tolerance test in which the blood glucose level was obtained after the oral administration of a 75-g glucose load in the fasting state) with two-step screening (a glucose challenge test in which the blood glucose level was obtained after the oral administration of a 50-g glucose load in the nonfasting state, followed, if positive, by an oral glucose-tolerance test with a 100-g glucose load in the fasting state) in all pregnant women who received care in two health systems. Guidelines for the treatment of gestational diabetes were consistent with the two screening approaches. The primary outcomes were a diagnosis of gestational diabetes, large-for-gestational-age infants, a 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, and primary cesarean section.

Results: A total of 23,792 women underwent randomization; women with more than one pregnancy during the trial could have been assigned to more than one type of screening. A total of 66% of the women in the one-step group and 92% of those in the two-step group adhered to the assigned screening. Gestational diabetes was diagnosed in 16.5% of the women assigned to the one-step approach and in 8.5% of those assigned to the two-step approach (unadjusted relative risk, 1.94; 97.5% confidence interval [CI], 1.79 to 2.11). In intention-to-treat analyses, the respective incidences of the other primary outcomes were as follows: large-for-gestational-age infants, 8.9% and 9.2% (relative risk, 0.95; 97.5% CI, 0.87 to 1.05); perinatal composite outcome, 3.1% and 3.0% (relative risk, 1.04; 97.5% CI, 0.88 to 1.23); gestational hypertension or preeclampsia, 13.6% and 13.5% (relative risk, 1.00; 97.5% CI, 0.93 to 1.08); and primary cesarean section, 24.0% and 24.6% (relative risk, 0.98; 97.5% CI, 0.93 to 1.02). The results were materially unchanged in intention-to-treat analyses with inverse probability weighting to account for differential adherence to the screening approaches.

Conclusions: Despite more diagnoses of gestational diabetes with the one-step approach than with the two-step approach, there were no significant between-group differences in the risks of the primary outcomes relating to perinatal and maternal complications. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ScreenR2GDM ClinicalTrials.gov number, NCT02266758.).

Publication types

  • Comparative Study
  • Multicenter Study
  • Pragmatic Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / diagnosis*
  • Diabetes, Gestational / epidemiology
  • Female
  • Fetal Macrosomia / epidemiology
  • Glucose Tolerance Test / methods*
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / diagnosis*
  • Incidence
  • Mass Screening
  • Pregnancy
  • Pregnancy Outcome


  • Blood Glucose

Associated data

  • ClinicalTrials.gov/NCT02266758