Early Pregnancy Glycosylated Hemoglobin in Relation to Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes: Evidence from a Multisite Low- and Middle-Income Countries Cohort

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Abstract
Background: Oral glucose tolerance test (OGTT), the gold standard for diagnosing gestational diabetes mellitus (GDM), faces significant implementation challenges, prompting interest in alternative biomarkers, such as glycated hemoglobin (HbA1c), for early detection. This study aimed to assess the association between early pregnancy HbA1c and subsequent GDM and adverse perinatal outcomes in low- and middle-income countries. Methods: We analyzed data from the Pregnancy Risk, Infant Surveillance, and Measurement Alliance - Maternal and Newborn Health (PRISMA-MNH) cohort, which followed pregnant women enrolled before 20 weeks of gestation across five study sites in Kenya, India, Pakistan, and Zambia. We excluded participants with overt diabetes, severe anemia (Hb 2 ) than women without GDM. The AUC for HbA1c alone in predicting GDM was 0.65 (95% confidence interval 0.63–0.67). A single early HbA1c threshold of 5.4%, based on the largest Youden’s index, showed limited predictive performance (sensitivity 46.7%, specificity 75.8%). A two-threshold approach identified rule-out and rule-in cutoffs of 5.0% (sensitivity 80.3%, specificity 35.6%) and 5.5% (sensitivity 34.5%, specificity 83.1%), respectively. In adjusted models, each 0.1% increase in HbA1c was associated with a 12% higher risk (RR 1.12, 95% CI 1.10–1.15) of GDM, while no significant associations were observed for any secondary outcomes. Conclusion: Early pregnancy HbA1c is independently associated with an increased risk of subsequent GDM. However, it demonstrated limited discriminatory ability as a standalone alternative to OGTT for identifying women who would later develop GDM. The identified rule-out threshold may help identify women at low risk of GDM, although the majority would still require OGTT for definitive diagnosis.
Funding Information
  • Gates Foundation (INV-047400)
  • Gates Foundation (INV-057219)
  • Gates Foundation (INV-043092)
  • Gates Foundation (INV-057220)
  • Gates Foundation (INV-016221)
  • Gates Foundation (INV-057222)
  • Gates Foundation (INV-041999)
  • Gates Foundation (INV-060797)
  • Gates Foundation (INV-057223)

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