First Trimester Glycated Hemoglobin (HBA1C) Level as a Novel Predictor of Gestational Diabetes Mellitus: a Systematic Review and Meta-Analysis

Main Article Content

Ayers Gilberth Ivano Kalaij
Nathaniel Gilbert Dyson
Michael Sugiyanto


Introduction: Gestational diabetes mellitus (GDM) is a severe yet neglected threat to maternal and child health, due to its association with multiple adverse pregnancy outcomes. glycated hemoglobin (HbA1c) level is one of the most promising predictor of GDM in early pregnancy based on several cohort studies done recently.

Purpose of study: This systematic review and meta-analysis aims to evaluate the potency of HbA1c level in first trimester as a novel predictor of GDM.

Methods: This review selects cohort studies found by database searching systematically using previously determined inclusion, such as pregnant woman as the subject, assess Hb1Ac level in the first trimester, and assess odds ratio towards (GDM), and exclusion criteria such as assess outcome at postpartum, not assess GDM outcomes, and studies written in languages other than English or Bahasa Indonesia. This review was arranged based on PRISMA guideline.

Results and Discussion: This review included seven cohort studies with the pooled OR of 4.36 [95%CI: 3.66-5.20]. Quantitative analysis shows that HbA1c level in the first trimester is a significant risk factor of GDM development (p<0.00001). However, heterogeneity analyses revealed substantial heterogeneity are detected in the pooled studies. Therefore, to understand the significance of HbA1c level and the development of GDM, further studies are needed.

Conclusion: This study has proven the potency of first trimester HbA1c level as a novel predictor of gestational diabetes mellitus. Thus, it is necessary to integrate the use of HbA1c level screening as part of antenatal care in the first trimester of pregnancy.

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How to Cite
Kalaij, A. G. I., Dyson, N. G. . and Sugiyanto, M. (2021) “First Trimester Glycated Hemoglobin (HBA1C) Level as a Novel Predictor of Gestational Diabetes Mellitus: a Systematic Review and Meta-Analysis”, Journal of Asian Medical Students’ Association. Kuala Lumpur, Malaysia, 9(1). doi: 10.52629/jamsa.v9i1.260.
Systematic Reviews


American College of Obstetricians and Gynecologists. Gestational Diabetes Mellitus: Practice Bulletin No. 137. Obstet Gynecol. 2013;

Lee KW, Ching SM, Ramachandran V, Yee A, Hoo FK, Chia YC, et al. Prevalence and risk factors of gestational diabetes mellitus in Asia: A systematic review and meta- analysis. BMC Pregnancy Childbirth. 2018;

International Diabetes Federation. IDF Diabetes Atlas, 9th edn. Brussels, Belgium. Atlas de la Diabetes de la FID. 2019.

Buchanan TA, Xiang AH, Page KA. Gestational diabetes mellitus: Risks and management during and after pregnancy. Nat Rev Endocrinol. 2012;

Guariguata L, Linnenkamp U, Beagley J, Whiting DR, Cho NH. Global estimates of the prevalence of hyperglycaemia in pregnancy. Diabetes Res Clin Pract. 2014;

Garrison A. Screening, diagnosis, and management of gestational diabetes mellitus. Am Fam Physician. 2015;

Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020;

Ray JG, Berger H, Lipscombe LL, Sermer M. Gestational prediabetes: A new term for early prevention? Indian Journal of Medical Research. 2010.

Rowan JA, Budden A, Ivanova V, Hughes RC, Sadler LC. Women with an HbA1c of 41-49 mmol/mol (5.9- 6.6%): A higher risk subgroup that may benefit from early pregnancy intervention. Diabet Med. 2016;

Powe CE. Early Pregnancy Biochemical Predictors of Gestational Diabetes Mellitus. Current Diabetes Reports. 2017.

Kansu-Celik H, Ozgu-Erdinc AS, Kisa B, Eldem S, Hancerliogullari N, Engin-Ustun Y. Maternal serum glycated hemoglobin and fasting plasma glucose predicts gestational diabetes at the first trimester in Turkish women with a low-risk pregnancy and its relationship with fetal birth weight; a retrospective cohort study. J Matern Neonatal Med [Internet]. 2019 Aug 12;1–8. Available from: 10.1080/14767058.2019.1651837

Selvin E, Steffes MW, Gregg E, Brancati FL, Coresh J. Performance of A1C for the classification and prediction of diabetes. Diabetes Care. 2011;

Luchini C, Stubbs B, Solmi M, Veronese N. Assessing the quality of studies in meta-analyses: Advantages and limitations of the Newcastle Ottawa Scale. World J Meta-Analysis. 2017;

Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series. Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series. 2008.

Kumru P, Arisoy R, Erdogdu E, Demirci O, Kavrut M, Ardıc C, et al. Prediction of gestational diabetes mellitus at first trimester in low-risk pregnancies. Taiwan J Obstet Gynecol. 2016;55(6):815–20.

Higgins JPT GS (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 . The Cochrane Collaboration . 2011.

Chen L, Pocobelli G, Yu O, Shortreed SM, Osmundson SS, Fuller S, et al. Early Pregnancy Hemoglobin A1C and Pregnancy Outcomes: A Population-Based Study. Am J Perinatol. 2019;36(10):1045–53.

Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci. 2018;19(11):1–21.

Egan AM, Dow ML, Vella A. A Review of the Pathophysiology and Management of Diabetes in Pregnancy. Mayo Clin Proc [Internet]. 2020;1–13. Available from: 0.02.019

Hoy AJ, Brandon AE, Turner N, Watt MJ, Bruce CR, Cooney GJ, et al. Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation. Am J Physiol - Endocrinol Metab. 2009;297(1).

Weir GC, Laybutt DR, Kaneto H, Bonner-Weir S, Sharma A. Beta-cell adaptation and decompensation during the progression of diabetes. Diabetes [Internet]. 2001 Feb 1;50(Supplement 1):S154–9. Available from: i/doi/10.2337/diabetes.50.2007.S154

Catalano PM. Trying to understand gestational diabetes. Diabet Med [Internet]. 2014 Mar;31(3):273–81. Available from: 381

Hinkle SN, Tsai MY, Rawal S, Albert PS, Zhang C. HbA1c Measured in the First Trimester of Pregnancy and the Association with Gestational Diabetes. Sci Rep [Internet]. 2018 Dec 16;8(1):12249. Available from: 8-018-30833-8

Arbib N, Shmueli A, Salman L, Krispin E, Toledano Y, Hadar E. First trimester glycated hemoglobin as a predictor of gestational diabetes mellitus. Int J Gynecol Obstet. 2019;145(2):158–63.

Zhang C, Tobias DK, Chavarro JE, Bao W, Wang D, Ley SH, et al. Adherence to healthy lifestyle and risk of gestational diabetes mellitus: prospective cohort study. BMJ [Internet]. 2014 Sep 30;349(1):g5450. Available from: 1136/bmj.g5450

Osmundson S, Zhao B, Kunz L, Wang E, Popat R, Nimbal V, et al. First Trimester Hemoglobin A1c Prediction of Gestational Diabetes. Am J Perinatol [Internet]. 2016 Apr 27;33(10):977–82. Available from: http://www.thieme- 0036-1581055

Mañé L, Flores-Le Roux JA, Benaiges D, Rodríguez M, Marcelo I, Chillarón JJ, et al. Role of first trimester HbA1c as a predictor of adverse obstetric outcomes in a multi-ethnic cohort. J Clin Endocrinol Metab [Internet]. 2016 Nov 23;jc.2016-2581. Available from:


Weissgerber TL, Mudd LM. Preeclampsia and Diabetes. Curr Diab Rep [Internet]. 2015 Mar 3;15(3):9. Available from: 92-015-0579-4

Fong A, Serra AE, Gabby L, Wing DA, Berkowitz KM. Use of hemoglobin A1c as an early predictor of gestational diabetes mellitus. Am J Obstet Gynecol [Internet]. 2014 Dec;211(6):641.e1-641.e7. Available from: e/pii/S0002937814005778

Pezeshki B, Chiti H, Arasteh P, Mazloomzadeh S. Early screening of gestational diabetes mellitus using hemoglobin A1C: Revising current screening guidelines. Casp J Intern Med. 2019;10(1):16–24.

Punnose J, Malhotra RK, Sukhija K, Mathew A, Sharma A, Choudhary N. Glycated haemoglobin in the first trimester: A predictor of gestational diabetes mellitus in pregnant Asian Indian women. Diabetes Res Clin Pract [Internet]. 2020 Jan;159:107953. Available from: e/pii/S0168822719312227

Amaefule CE, Sasitharan A, Kalra P, Iliodromoti S, Huda MSB, Rogozinska E, et al. The accuracy of haemoglobin A1c as a screening and diagnostic test for gestational diabetes: a systematic review and meta-analysis of test accuracy studies. Curr Opin Obstet Gynecol [Internet]. 2020 Oct;32(5):322–34. Available from: O.0000000000000648