Cheung Ka Wang, Au Tiffany Sin-Tung, Lee Chi-Ho, Ng Vivian Wai Yan, Wong Felix Chi-Kin, Chow Wing-Sun, Hui Pui Wah, Seto Mimi Tin Yan
Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China (Dr Cheung, Ms Au, Dr Ng, Dr Hui, and Dr Seto).
Department of Medicine, Queen Mary Hospital, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China (Dr Lee and Dr Chow).
AJOG Glob Rep. 2024 Jan 19;4(1):100315. doi: 10.1016/j.xagr.2024.100315. eCollection 2024 Feb.
Unrecognized diabetes mellitus during pregnancy could pose serious maternal and neonatal complications. A hemoglobin A1c 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 early pregnancy to detect women with diabetes in pregnancy and associated complications remains unclear.
This study aimed to evaluate the diagnostic performance 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 oral glucose tolerance test before 24 weeks of gestation. In addition, the pregnancy and neonatal outcomes were compared using the optimal hemoglobin A1c cutoff.
A retrospective cohort study 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 hyperglycemia 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 logistic regression analyses were performed to calculate the unadjusted and adjusted odds ratios for pregnancy complications.
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 multivariate logistic regression analysis, 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), macrosomia (adjusted odds ratio, 7.43; 95% confidence interval, 1.90-29.00), and shoulder dystocia (adjusted odds ratio, 6.56; 95% confidence interval, 1.161-37.03).
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.
孕期未被识别的糖尿病可能会引发严重的母婴并发症。血红蛋白A1c水平≥6.5%被用于诊断非孕期个体的糖尿病以及孕期糖尿病。由于血红蛋白A1c水平可能受到母体生理变化的影响，因此孕早期用于检测孕期糖尿病女性及其相关并发症的最佳临界值仍不明确。
本研究旨在评估不同血红蛋白A1c水平的诊断效能，以及确定在妊娠24周前通过金标准75克口服葡萄糖耐量试验诊断孕期糖尿病母亲的最佳血红蛋白A1c临界值。此外，使用最佳血红蛋白A1c临界值比较妊娠和新生儿结局。
进行了一项2004年至2019年的回顾性队列研究。具有至少1项妊娠期糖尿病危险因素的女性在妊娠24周前接受口服葡萄糖耐量试验。孕期首次通过口服葡萄糖耐量试验检测出的高血糖术语按照世界卫生组织的建议分类为孕期糖尿病或妊娠期糖尿病。对符合孕期糖尿病和早发型妊娠期糖尿病（即妊娠24周前）诊断标准且在早期口服葡萄糖耐量试验后4周内进行了配对血红蛋白A1c测量的女性进行研究。计算了不同血红蛋白A1c临界值下检测孕期糖尿病的敏感性、特异性、阳性预测值和阴性预测值。从构建的受试者工作特征曲线中确定最佳血红蛋白A1c水平。进行多变量二元逻辑回归分析以计算妊娠并发症的未调整和调整后的比值比。
共有63111例分娩，22949名女性在妊娠24周前接受了口服葡萄糖耐量试验。分别有157名和3210名女性通过口服葡萄糖耐量试验符合孕期糖尿病和早发型妊娠期糖尿病的诊断标准。只有346名参与者进行了配对血红蛋白A1c和口服葡萄糖耐量试验测量（82例孕期糖尿病和264例早发型妊娠期糖尿病）。受试者工作特征曲线确定诊断孕期糖尿病的最佳血红蛋白A1c临界值为5.7%，敏感性为64.6%，特异性为81.1%，阳性预测值为51.5%，阴性预测值为88.1%。血红蛋白A1c临界值为5.9%或6.5%时，会漏诊47.6%或73.2%的孕期糖尿病女性。在多变量逻辑回归分析中，血红蛋白A1c水平≥5.7%会增加母体使用胰岛素的风险（调整后的比值比为6.69；95%置信区间为3.44 - 12.99）、巨大儿风险（调整后的比值比为7.43；95%置信区间为1.90 - 29.00）和肩难产风险（调整后的比值比为6.56；95%置信区间为1.161 - 37.03）。
在妊娠24周前通过口服葡萄糖耐量试验诊断孕期糖尿病的最佳血红蛋白A1c临界值为5.7%，但由于敏感性较低，该临界值不能可靠地识别孕期糖尿病。然而，早期血红蛋白A1c水平≥5.7%表明妊娠和新生儿并发症风险增加。
