Gestational Diabetes: One-Step or Two-Step Screening

No specific approach is used currently but which one is better?

Every year, 2% to 10% of pregnant women are diagnosed with gestational diabetes. Gestational diabetes is a type of diabetes that develops in pregnant women who did not have diabetes before they got pregnant. Some causes or risk factors can lead to developing gestational diabetes like being overweight, low physical activity, race, among others. Having gestational diabetes can bring some complications during pregnancy; the baby can have an increased risk of excessive birth weight, low blood sugar. Also, pregnant women have a higher risk of early labor, develop hypertension or preeclampsia, and have a C-section delivery. Clinicians usually set a screening between 24 and 28 weeks of gestation. There are two acceptable options: one-step screening and two-step screening, but there is no specific way to diagnose gestational diabetes. For these reasons, clinicians are studying and comparing the two screening approaches available.

Researchers compared the one-step screening with the two-step screening to diagnose gestational diabetes during a recent randomized trial. The study took place between 2014 and 2017 in two different centers of Kaiser Permanente. At randomization, all women were assigned to a 1:1 ratio to either the one-step screening or two-step screening at their first prenatal visit. Even though participants were from only two centers, there were 23,792 eligible pregnant women for this study. Providers were notified about randomization when screening was ordered at weeks 24 to 28 of gestation. This study had a few primary endpoints. These endpoints included having a diagnosis of gestational diabetes, large-for-gestational-age infants, a composite measure of perinatal outcome, primary cesarean section, and gestational hypertension or preeclampsia. On the other hand, secondary endpoints included the incidence of macrosomia, small-for-gestational-age infants, neonatal respiratory distress, neonatal jaundice, neonatal hypoglycemia. 

Clinicians defined the two approaches. The one-step and two-step process were defined. The one-step screening consisted of a 2-hour oral glucose tolerance test (OGTT) where the blood glucose was obtained 2 hours after administering a 75 g glucose load in the fasting state. Pregnant women received a diagnosis of gestational diabetes if the fasting blood glucose (FBG) level was at least 92 mg/dL, the timed glucose measurements were at least 180 mg/dL at 1 hour or at least 153 mg/dL at 2 hours. In the two-step screening, the first step consisted of a 1-hour glucose challenge test where the blood glucose was obtained after the oral administration of a 50 g glucose load in the non-fasting state. Pregnant women received a diagnosis of gestational diabetes if the blood glucose level was of at least 200 mg/dL on the challenge test, and no further analyses were made. Those with a positive glucose challenge test with blood glucose level less than 200 mg/dL if the glucose level was ≥140 mg/dL (Kaiser Permanente Northwest) or ≥130 mg/dL (Kaiser Permanente Hawaii), underwent a 3-hour OGTT using 100 g glucose load. Gestational diabetes was diagnosed if they met two out of four criteria. These criteria include having a FBG >95 mg/dL, >180 mg/dL at 1 hour, >155 mg/dL at 2 hours, or >140 mg/dL at 3 hours.

During the analysis, researchers reported a lack of adherence to randomization since a high percentage of women randomly assigned to the one-step process received two-step screening. They modified their protocols to continue with the trial until they reached an adequate sample size in both groups. They evaluated relative risks for each primary endpoint and performed intention-to-treat (ITT) analysis for unadjusted models and adjusted models. Adjusted models count for the diagnosis of gestational diabetes, group-by-diagnosis interactions, and other covariates like excessive gestational weight gain. Also, they performed a sensitivity analysis using 97.5% CI for primary outcomes and 95% CI for secondary outcomes.

Of the 23,792 randomized pregnant women, 94% completed screening, 66% were in the one-screening, while 92% of those were in the two-step process. They reported that women with more than one pregnancy during the trial were assigned to more than one type of screening. Gestational diabetes was diagnosed in 16.5% of pregnant women assigned to the one-step screening process and in 8.5% of those in the two-step screening. (RR:1.94; 97.5% CI:1.79-2.11). Meanwhile, the ITT analyses showed no significant difference between the groups. Results showed large-for-gestational-age infants in 8.9% of women in one-step group and 9.2% of women in two-step group (RR: 0.95; 97.5% CI: 0.87-1.05). Perinatal composite outcomes were present in 3.1% and 3.0% respectively (RR: 1.04; 97.5% CI:0.88-1.23). Gestational hypertension or preeclampsia were present in 13.6% and 13.5% of those women respectively (RR: 1.00; 97.5% CI: 0.93-1.08). Primary cesarean section was performed in 24.0% and 24.6% of women respectively (RR:0.98; 97.5% CI: 0.93-1.02). Researchers reported that after adjustments, there was no significant difference between the groups. The results for the secondary outcomes were similar between the groups. They reported that 42.6% and 45.6% respectively of women diagnosed with gestational diabetes received insulin or hypoglycemic medications.  

Overall, this study showed no significant differences between the one-step and two-step screening processes in maternal and perinatal outcomes among 23,792 participants. They reported lower adherence to the one-step approach, which can be considered a limitation for this study, and researchers in future studies can consider it. Also, they reported as a limitation the fact that the facilities had different thresholds for the glucose challenge test (130 mg/dL and 140 mg/dL). On the other hand, the study had a large sample size and included the entire population from these sites. For future studies, more control on adherence should be made and the idea of the providers being aware of the criteria used for diagnosis.

Practice Pearls:

• There is no specific approach on how to diagnose gestational diabetes in pregnant women.
• The study showed no significant difference in primary and secondary outcomes.
• Future studies must be performed to set the best screening process to diagnose gestational diabetes to reduce complications in pregnancy and at birth.

References:

Hillier, T., et al. A Pragmatic, Randomized Clinical Trial of Gestational Diabetes Screening. N Engl J Med (2021) 384:10. doi:10.1056/NEJMoa2026028. https://www.nejm.org/doi/full/10.1056/NEJMoa2026028

Laura Martínez López, PharmD. Candidate 2021, Lake Erie College of Osteopathic Medicine, College of Pharmacy