Estimated Treatment Effects of Tight Glycaemic Targets in Mild Gestational Diabetes Mellitus: A Multiple Cut-Off Regression Discontinuity Study Design

Abstract

Background: We investigated the treatment effects of tight glycaemic targets in a population universally screened according to the International Association of Diabetes and Pregnant Study Groups (IADPSG)/World Health Organisation (WHO) gestational diabetes mellitus (GDM) guidelines. As yet there, have been no randomized control trials evaluating the effectiveness of treatment of mild GDM diagnosed under the IADPSG/WHO diagnostic thresholds. We hypothesize that tight glycaemic control in pregnant women diagnosed with GDM will result in similar clinical outcomes to women just below the diagnostic thresholds. Methods: A multiple cut-off regression discontinuity study design in a retrospective observational cohort undergoing oral glucose tolerance tests (OGTT) (n = 1178). Treatment targets for women with GDM were: fasting capillary blood glucose (CBG) of ≤5.0 mmol/L and the 2-h post-prandial CBG of ≤6.7 mmol/L. Regression discontinuity study designs estimate treatment effects by comparing outcomes between a treated group to a counterfactual group just below the diagnostic thresholds with the assumption that covariates are similar. The counterfactual group was selected based on a composite score based on OGTT plasma glucose categories. Results: Women treated for GDM had lower rates of newborns large for gestational age (LGA), 4.6% versus those just below diagnostic thresholds 12.6%, relative risk 0.37 (95% CI, 0.16-0.85); and reduced caesarean section rates, 32.2% versus 43.0%, relative risk 0.75 (95% CI, 0.56-1.01). This was at the expense of increases in induced deliveries, 61.8% versus 39.3%, relative risk 1.57 (95% CI, 1.18-1.9); notations of neonatal hypoglycaemia, 15.8% versus 5.9%, relative risk 2.66 (95% CI, 1.23-5.73); and high insulin usage 61.1%. The subgroup analysis suggested that treatment of women with GDM with BMI ≥30 kg/m2 drove the reduction in caesarean section rates: 32.9% versus 55.9%, relative risk 0.59 (95%CI, 0.4-0.87). Linear regression interaction term effects between non-GDM and treated GDM were significant for LGA newborns (p = 0.001) and caesarean sections (p = 0.015). Conclusions: Tight glycaemic targets reduced rates of LGA newborns and caesarean sections compared to a counterfactual group just below the diagnostic thresholds albeit at the expense of increased rates of neonatal hypoglycaemia, induced deliveries, and high insulin usage.