A Cluster Randomized Noninferiority Field Trial of Gestational Diabetes Mellitus Screening

Abstract

Context Although it is well-acknowledged that gestational diabetes mellitus (GDM) is associated with the increased risks of adverse pregnancy outcomes, the optimal strategy for screening and diagnosis of GDM are still a matter of debate. Objective This study was conducted to demonstrate the non-inferiority of less strict GDM-screening criteria compared to the strict International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria with respect to maternal and neonatal outcomes. Methods A cluster randomized non-inferiority field-trial was conducted on 35528 pregnant women; they were scheduled to have two phases of GDM-screening, based on five different pre-specified protocols including fasting plasma glucose in the first trimester with threshold of 5.1 mmol/L (92 mg/dL) (protocols A, D) or 5.6 mmol/L (100 mg/dL) (protocols B, C, E) and either a one-step (GDM is defined if one of the plasma glucose values is exceeded ( protocol A and C) or two or more exceeded values are needed (protocol B)) or two-step approach (protocol D, E) in the second trimester. Guidelines for treatment of GDM were consistent with all protocols. Primary outcomes of the study were the prevalence of macrosomia and primary cesarean-section (C-S). The null hypothesis that less strict protocols are inferior to protocol A (IADPSG) was tested with a non-inferiority margin effect (OR) of 1.7. Results The percentages of pregnant women diagnosed with GDM and assigned to protocols A, B, C, D and E were 21.9%, 10.5%, 12.1%, 19.4%, and 8.1%, respectively. Intention to treat (ITT) analyses satisfying the non-inferiority of the less strict protocols of B, C, D and E compared to protocol A. However, non-inferiority was not shown for primary C-section comparing protocol E vs A. The ORs (95% CI) for macrosomia and C-S were: B (1.01(0.95-1.08); 0.85(0.56- 1.28), C (1.03, (0.73-1.47); 1.16, (0.88-1.51)), D (0.89(0.68-1.17); 0.94, (0.61-1.44)) and E (1.05, (0.65-1.69); 1.33, (0.82-2.00)) versus A. There were no statistically significant differences in the adjusted odds of adverse pregnancy outcomes in the two-step compared to one-step screening approaches, considering multiplicity adjustment. Conclusions The IADPSG GDM-definition significantly increased the prevalence of GDM diagnosis. However, the less strict approaches were not inferior to other criteria in terms of adverse maternal and neonatal outcomes.

One-step versus two-step screening for diagnosis of gestational diabetes mellitus in Iranian population: A randomized community trial

“…One of the important strengths of our study is the generalizability of findings due to its characteristics, including its design as a community-based trial, large sample size, the geographic distribution of the regions involved, and using similar laboratory protocols. In addition, the adherence to each protocol in our study was high ( 25 ), which could increase the validity of our findings.…”

“…In addition, the Iranian Ministry of Health and Medical Education (MoHME) approved the study protocol, and pre-specified GDM modalities were made available to all those provinces as mandatory guidelines. Detailed methods have been described elsewhere ( 24 , 25 ). Briefly, a total of 35,613 pregnant women in the first trimester of pregnancy from five different geographic regions of Iran were recruited.…”

“…Finally, five different protocols were randomly allocated to each provincial center. Also, in the cluster of other cities, four other cities in each province were randomly allocated to the rest of the protocols ( Supplementary Table 1 ) ( 24 , 25 ). Along with routine prenatal standard care, all participants underwent two phases of GDM screening in the first and second trimester of pregnancy, based on fasting plasma glucose (FPS) levels in the first and either a One-step or a Two-step screening method in second trimester of pregnancy.…”

“…It should be noted that we excluded all those pregnant women who assigned to the protocol B in original study ( 25 ), since it was not a standard One-step approach and there was no corresponding group in the Two-step screening approach. Data on protocol B are presented in Supplementary Tables 2 , 3 .…”

Various screening and diagnosis approaches for gestational diabetes mellitus and adverse pregnancy outcomes: a secondary analysis of a randomized non-inferiority field trial

“…This is a secondary analysis of a randomized community non-inferiority trial among pregnant women in the GULF Study. Detailed methods and results of the main trial have been reported previously 23 24. Briefly, this study was conducted to determine non-inferiority of less strict GDM screening criteria compared with the stringent IADPSG criteria with respect to maternal and neonatal outcomes, in which 35 430 pregnant women in the first trimester of pregnancy, aged 18 years and over from five different geographic regions of Iran participated.…”