HbA1c in early pregnancy to identify pre-existing diabetes mellitus and women at risk of hyperglycemic pregnancy complications

Abstract

<h3>BACKGROUND</h3><p>Unrecognized diabetes mellitus during pregnancy could pose serious maternal and neonatal complications. A <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/hemoglobin-a1c" title="Learn more about hemoglobin A1c from ScienceDirect's AI-generated Topic Pages">hemoglobin A1c</a> level of ≥6.5% was used to diagnose both diabetes mellitus in nonpregnant individuals and diabetes in pregnancy. As the hemoglobin A1c level could be influenced by maternal physiological changes, the optimal cutoff in <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/first-trimester-pregnancy" title="Learn more about early pregnancy from ScienceDirect's AI-generated Topic Pages">early pregnancy</a> to detect women with diabetes in pregnancy and associated complications remains unclear.</p><h3>OBJECTIVE</h3><p>This study aimed to evaluate the <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/diagnostic-performance" title="Learn more about diagnostic performance from ScienceDirect's AI-generated Topic Pages">diagnostic performance</a> of various hemoglobin A1c levels and the optimal hemoglobin A1c cutoff to identify mothers with diabetes in pregnancy diagnosed by the gold standard 75 g <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/oral-glucose-tolerance-test" title="Learn more about oral glucose tolerance test from ScienceDirect's AI-generated Topic Pages">oral glucose tolerance test</a> before 24 weeks of gestation. In addition, the pregnancy and neonatal outcomes were compared using the optimal hemoglobin A1c cutoff.</p><h3>STUDY DESIGN</h3><p>A <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/retrospective-cohort-study" title="Learn more about retrospective cohort study from ScienceDirect's AI-generated Topic Pages">retrospective cohort study</a> was conducted between 2004 and 2019. Women with at least 1 risk factor of gestational diabetes mellitus received an oral glucose tolerance test before 24 weeks of gestation. Terminology of <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/hyperglycemia" title="Learn more about hyperglycemia from ScienceDirect's AI-generated Topic Pages">hyperglycemia</a> first detected during pregnancy by oral glucose tolerance test was classified as either diabetes in pregnancy or gestational diabetes mellitus following the World Health Organization's recommendation. Women who met the diagnostic criteria of diabetes in pregnancy and early-onset gestational diabetes mellitus (ie, before 24 weeks of gestation) and had a paired hemoglobin A1c measurement within 4 weeks of their early oral glucose tolerance test were studied. Sensitivity, specificity, and positive and negative predictive values at various hemoglobin A1c cutoffs were calculated for the detection of diabetes in pregnancy. The optimal hemoglobin A1c level was identified from the constructed receiver operating characteristic curves. Multivariate binary <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/logistic-regression-analysis" title="Learn more about logistic regression from ScienceDirect's AI-generated Topic Pages">logistic regression</a> analyses were performed to calculate the unadjusted and adjusted odds ratios for <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/pregnancy-complication" title="Learn more about pregnancy complications from ScienceDirect's AI-generated Topic Pages">pregnancy complications</a>.</p><h3>RESULTS</h3><p>There were 63,111 deliveries, and 22,949 women underwent an oral glucose tolerance test before 24 weeks of gestation. A total of 157 and 3210 women met the diagnostic criteria of diabetes in pregnancy and early-onset gestational diabetes mellitus using an oral glucose tolerance test, respectively. Only 346 participants had a paired hemoglobin A1c and oral glucose tolerance test measurement (82 cases with diabetes in pregnancy and 264 cases with early-onset gestational diabetes mellitus). The receiver operating characteristic curve identified an optimal hemoglobin A1c cutoff of 5.7% to diagnose diabetes in pregnancy, with a sensitivity of 64.6%, specificity of 81.1%, positive predictive value of 51.5%, and negative predictive value of 88.1%. A hemoglobin A1c cutoff of either 5.9% or 6.5% could miss 47.6% or 73.2% of women with diabetes in pregnancy. In <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/multivariate-logistic-regression-analysis" title="Learn more about multivariate logistic regression analysis from ScienceDirect's AI-generated Topic Pages">multivariate logistic regression analysis</a>, a hemoglobin A1c level of ≥5.7% increased the risk of maternal insulin use (adjusted odds ratio, 6.69; 95% confidence interval, 3.44–12.99), <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/macrosomia" title="Learn more about macrosomia from ScienceDirect's AI-generated Topic Pages">macrosomia</a> (adjusted odds ratio, 7.43; 95% confidence interval, 1.90–29.00), and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/shoulder-dystocia" title="Learn more about shoulder dystocia from ScienceDirect's AI-generated Topic Pages">shoulder dystocia</a> (adjusted odds ratio, 6.56; 95% confidence interval, 1.161–37.03).</p><h3>CONCLUSION</h3><p>The optimal hemoglobin A1c cutoff to detect diabetes in pregnancy diagnosed using an oral glucose tolerance test before 24 weeks of gestation was 5.7%, but this cutoff could not reliably identify diabetes in pregnancy owing to the low sensitivity. However, an early hemoglobin A1c level of ≥5.7% indicated increased risks of pregnancy and neonatal complications.</p>