Positivity thresholds of HbA1c assay as a screening test for diabetes mellitus in the first trimester in high-risk populations

Objective: Both gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) are associated with increased risks of preeclampsia, macrosomia, shoulder dystocia, and irreversible brachial plexus injury (BPI). Compared to the conventional second trimester oral glucose tolerance test (OGTT), screening with the HbA1c assay in the first trimester with a diagnostic second trimester OGTT has been shown to diagnose more cases of T2DM and GDM earlier. Our study examined the effect of treatment based on varied positivity thresholds in high-risk pregnancies. Study design: A decision analysis model was created using TreeAge 2016 software to compare the outcomes of screening with an HbA1C in the first trimester verses no first trimester screening, with positivity thresholds ranging from 5.9 to 6.4%. Outcomes examined included neonatal mortality, preeclampsia, preterm delivery, cerebral palsy, macrosomia, permanent BPI, cost, and quality adjusted life years (QALYs) of the mother and neonate. Probabilities, utilities, and costs were derived from the literature, and a cost-effectiveness threshold was set at $100,000/QALY. Univariate analyses were used to investigate the impact of screening positivity. Results: First trimester screening was not cost-effective with an incremental cost effectiveness ratio of 5.87 when compared to screening with a positivity threshold of 6.4%. In a theoretical cohort of one million pregnancies, a screening threshold of 5.9% was the most cost-effective strategy. This strategy resulted in 2.999 million more QALYs, one less neonatal death, 346 fewer cases of preeclampsia, 66 less preterm deliveries, one less instance of cerebral palsy, and 615 fewer cases of macrosomia with nine less PBI cases. The 5.9% threshold provided an overall cost savings of $29.72 million. Conclusions: Screening for diabetes in high risk pregnancies with the HbA1c assay in the first trimester is not cost effective compared to no screening; however, if screening is preformed, 5.9% should be used as the positivity threshold for diagnosis and treatment. Brief rationale: With the increasing prevalence of diabetes mellitus among high-risk women in the USA, screening during pregnancy has become more important than ever. As a laboratory test, the HbA1c is relatively simple to obtain clinically, inexpensive, and its use has been well documented in the diagnosis and management of diabetes. However, there is limited data on its use in pregnancy and in particular during the first trimester. We sought to characterize the cost-effectiveness of screening with an HbA1c assay at various positivity thresholds for gestational diabetes mellitus and pre-existing type 2 diabetes in high-risk pregnancies in the first trimester. We found that this screening strategy is not cost-effective compared to no HbA1c in the first trimester and traditional oral glucose tolerance testing in the late second trimester. However, if screening is preformed, a positivity threshold of 5.9% should be used as the positivity threshold for diagnosis and treatment as it is associated with the best outcomes.