Early Pregnancy Glycosylated Hemoglobin in Relation to Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes: Evidence from a Multisite Low- and Middle-Income Countries Cohort
- 1Department of Community Medicine, Christian Medical College, Vellore, India
Abstract
BackgroundOral 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.
MethodsWe 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 <7.0 g/dl), multiple gestations, or pregnancies that ended before 24 weeks of gestation. HbA1c was measured at enrollment. The primary outcome was GDM, diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria based on OGTT performed after 24 weeks of gestation. Secondary outcomes included hypertensive disorder of pregnancy, emergent Cesarean section, preterm birth, large for gestational age, and stillbirth after 28 weeks. We used AUC and ROC analyses to evaluate predictive performance and single- and two-threshold approaches to identify optimal cutoffs for predicting GDM. We used modified Poisson regression with robust standard errors to assess associations between early HbA1c and outcomes, and meta-analysis to pool site-specific estimates.
ResultsAmong 10,918 pregnancies, GDM prevalence was 6.4%. Women with GDM were older (28.0{+/-}5.4 versus 26.0{+/-}5.3 years) and had higher BMI at enrollment (25.0{+/-}5.8 versus 22.9{+/-}5.0 kg/m2) 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 Youdens 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.
ConclusionEarly 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.
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BibTeX
@misc{yang2026early,
title = {{Early Pregnancy Glycosylated Hemoglobin in Relation to Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes: Evidence from a Multisite Low- and Middle-Income Countries Cohort}},
author = {W.-C. Yang and S. Sunil Joseph and B. Vijayalekshmi and B. L. Freeman and M. I. Nisar and Q. Pan and S. J. Benjamin and J. A. G and N. Sharma and S. Mazumder and Z. Hoodbhoy and V. Akelo and F. Aweyo and E. R. Smith and C. N. Mores and E. M. Oakley and M. B. Spelke and H. Mwape and S. Mukuka and M. P. Kasaro and A. G. Cherian},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.23.26362980},
url = {https://www.medrxiv.org/content/10.64898/2026.09.23.26362980v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Early Pregnancy Glycosylated Hemoglobin in Relation to Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes: Evidence from a Multisite Low- and Middle-Income Countries Cohort
AU - W.-C. Yang
AU - S. Sunil Joseph
AU - B. Vijayalekshmi
AU - B. L. Freeman
AU - M. I. Nisar
AU - Q. Pan
AU - S. J. Benjamin
AU - J. A. G
AU - N. Sharma
AU - S. Mazumder
AU - Z. Hoodbhoy
AU - V. Akelo
AU - F. Aweyo
AU - E. R. Smith
AU - C. N. Mores
AU - E. M. Oakley
AU - M. B. Spelke
AU - H. Mwape
AU - S. Mukuka
AU - M. P. Kasaro
AU - A. G. Cherian
PY - 2026
DA - 2026/09/23
PB - medRxiv
DO - 10.64898/2026.09.23.26362980
UR - https://www.medrxiv.org/content/10.64898/2026.09.23.26362980v1
AB - BackgroundOral 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. MethodsWe 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 <7.0 g/dl), multiple gestations, or pregnancies that ended before 24 weeks of gestation. HbA1c was measured at enrollment. The primary outcome was GDM, diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria based on OGTT performed after 24 weeks of gestation. Secondary outcomes included hypertensive disorder of pregnancy, emergent Cesarean section, preterm birth, large for gestational age, and stillbirth after 28 weeks. We used AUC and ROC analyses to evaluate predictive performance and single- and two-threshold approaches to identify optimal cutoffs for predicting GDM. We used modified Poisson regression with robust standard errors to assess associations between early HbA1c and outcomes, and meta-analysis to pool site-specific estimates. ResultsAmong 10,918 pregnancies, GDM prevalence was 6.4%. Women with GDM were older (28.0{+/-}5.4 versus 26.0{+/-}5.3 years) and had higher BMI at enrollment (25.0{+/-}5.8 versus 22.9{+/-}5.0 kg/m2) 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 Youdens 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. ConclusionEarly 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.
ER -