Hemoglobin A1c in early pregnancy to identify preexisting diabetes mellitus and women at risk of hyperglycemic pregnancy complications

Abstract

BackgroundUnrecognized diabetes during pregnancy could pose serious maternal and neonatal complications. A HbA1c level of ≥ 6.5% was used to diagnose both diabetes in non-pregnant individuals and diabetes in pregnancy (DIP). Since the level of HbA1c could be influenced by maternal physiological changes, the optimal cut-off in early pregnancy to detect women with DIP and associated complications remains unclear. ObjectiveTo evaluate the diagnostic performance of various HbA1c levels, as well as the optimal HbA1c cut-off to identify mothers with DIP diagnosed by the gold standard 75grams oral glucose tolerance test (OGTT) before 24 weeks of gestation. We also compared the pregnancy and neonatal outcomes using the optimal HbA1c cut-off. Study DesignA retrospective cohort study was conducted between 2004 and 2019. Women with at least one risk factor of gestational diabetes (GDM) received OGTT before 24 weeks of gestation. Terminology of hyperglycemia first detected during pregnancy by OGTT was classified as either DIP or GDM following the World Health Organization's recommendation. Women who met the diagnostic criteria of DIP and early onset GDM (i.e., before 24 weeks) and had a paired HbA1c measurement within 4 weeks of their early OGTT were studied. Sensitivity, specificity, positive and negative predictive value (PPV and NPV, respectively) at various HbA1c cut-offs were calculated for the detection of DIP. The optimal HbA1c level was identified from the constructed receiver operating characteristic (ROC) curves. Multivariate binary logistic regression analyses were performed to calculate the unadjusted and adjusted odds ratios for pregnancy complications. ResultThere were 63,111 deliveries and 22,949 underwent OGTT before 24 weeks of gestation. A total of 157 and 3210 women met the diagnostic criteria of DIP and early onset GDM by OGTT respectively. Only 346 subjects had a paired HbA1c and OGTT measurement (82 DIP and 264 early onset GDM). ROC curve identified an optimal HbA1c cut-off of 5.7% to diagnose DIP, with a sensitivity of 64.6%, specificity of 81.1%, PPV of 51.5% and NPV of 88.1%. Either HbA1c cut-off of 5.9% or 6.5% could miss 47.6% or 73.2% women with DIP. In multivariate logistic regression analysis, HbA1c of ≥ 5.7% increased the risk of maternal insulin use (aOR 6.69, 95%CI 3.44-12.99), macrosomia (aOR 7.43, 95%CI 1.90-29.00) and shoulder dystocia (aOR 6.56, 95%CI 1.161-37.032). ConclusionThe optimal HbA1c cut-off to detect DIP diagnosed by OGTT before 24 weeks was 5.7% but this cut-off could not reliably identify DIP owing to the low sensitivity. However, an early HbA1c level of ≥ 5.7% indicated increased risks of pregnancy and neonatal complications.