Association of serum ferritin concentration in early pregnancy with the risk of subsequent development of gestational diabetes mellitus

Vadla Ruchitha; Supriya Rai

doi:10.18203/2320-1770.ijrcog20263042

Authors

Vadla Ruchitha Department of Obstetrics and Gynecology, K. S. Hegde Medical Academy, NITTE (Deemed to be University), Mangaluru, Karnataka, India
Supriya Rai Department of Obstetrics and Gynecology, K. S. Hegde Medical Academy, NITTE (Deemed to be University), Mangaluru, Karnataka, India https://orcid.org/0009-0003-1371-9727

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20263042

Keywords:

Biomarker, Early pregnancy, Gestational diabetes mellitus, Iron metabolism, Insulin resistance, Serum ferritin

Abstract

Background: Gestational diabetes mellitus (GDM) is among the commonest medical complications of pregnancy and South Asian women are affected at lower body mass indices than Western populations. Serum ferritin reflects body iron stores and is also an acute-phase reactant; iron-catalysed oxidative stress may impair insulin action. We examined whether early-pregnancy ferritin predicts subsequent GDM.

Methods: In this prospective observational study, 111 antenatal women at 12–18 weeks were enrolled consecutively at a tertiary teaching hospital. Fasting serum ferritin was measured by chemiluminescent microparticle immunoassay. Women were followed to 24–28 weeks, when GDM was diagnosed by 75g oral glucose testing using American Diabetes Association criteria. Analysis used Mann–Whitney U and chi-square tests, Spearman correlation, multivariable logistic regression and receiver operating characteristic (ROC) analysis.

Results: GDM developed in 24/111 women (21.6%). Median ferritin was higher in the GDM group (55.35 vs 24.00 ng/mL; p<0.0001). GDM prevalence rose across ferritin quintiles from 8.7% to 77.3% (p<0.0001). Ferritin correlated with glucose challenge values (ρ=0.576; p<0.0001) and independently predicted GDM after adjustment for age, BMI, gravida and haemoglobin (adjusted odds ratio 2.41 per 10 ng/mL; 95% CI 1.68–3.44). Area under the ROC curve was 0.865; a cut-off of 39.9 ng/mL gave 79.2% sensitivity, 92.0% specificity and 94.1% negative predictive value.

Conclusions: Elevated early-pregnancy serum ferritin is independently and gradedly associated with subsequent GDM and discriminates well between affected and unaffected women. Ferritin is inexpensive and already widely measured antenatally and may permit risk stratification well before conventional screening; multicentre validation is required.

References

Leng J, Shao P, Zhang C, Tian H, Zhang F, Zhang S, et al. Prevalence of gestational diabetes mellitus and its risk factors in Chinese pregnant women: a prospective population-based study in Tianjin, China. PLoS One. 2015;10(3):121029.

Zhang C, Rawal S, Chong YS. Risk factors for gestational diabetes: is prevention possible? Diabetologia. 2016;59(7):1385-90.

Chen X, Scholl TO, Stein TP. Association of elevated serum ferritin levels and the risk of gestational diabetes mellitus in pregnant women: the Camden study. Diabetes Care. 2006;29(5):1077-82.

Soheilykhah S, Mojibian M, Jannati Moghadam M. Serum ferritin concentration in early pregnancy and risk of subsequent development of gestational diabetes: a prospective study. Int J Reprod Biomed. 2017;15(3):155-60.

Cheng Y, Li T, He M, Liu J, Wu K, Liu S, et al. The association of elevated serum ferritin concentration in early pregnancy with gestational diabetes mellitus: a prospective observational study. Eur J Clin Nutr. 2020;74(5):741-8.

Bowers KA, Olsen SF, Bao W, Halldorsson TI, Strøm M, Zhang C. Plasma concentrations of ferritin in early pregnancy are associated with risk of gestational diabetes mellitus in women in the Danish National Birth Cohort. J Nutr. 2016;146(9):1756-61.

Rawal S, Hinkle SN, Bao W, Zhu Y, Grewal J, Albert PS, et al. A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort. Diabetologia. 2017;60(2):249-57.

Sun C, Wu QJ, Gao SY, Ma ZM, Liu YS, Zhang JY, et al. Association between the ferritin level and risk of gestational diabetes mellitus: a meta-analysis of observational studies. J Diabetes Investig. 2020;11(3):707-18.

Durrani L, Ejaz S, Tavares LB, Mohyeldin M, Abureesh D, Boorenie M, et al. Correlation between high serum ferritin level and gestational diabetes: a systematic review. Cureus. 2021;13(10):18990.

Guo W, Wang H, Liu Q, Yuan Y, Jing Y, Yang X. Analysis of the correlation of gestational diabetes mellitus and peripheral ferritin with iron levels during early pregnancy. Minerva Endocrinol. 2019;44(1):91-6.

Zhang X, Wu M, Zhong C, Huang L, Zhang Y, Chen R, et al. Association between maternal plasma ferritin concentration, iron supplement use and the risk of gestational diabetes: a prospective cohort study. Am J Clin Nutr. 2021;114(3):1100-6.

Fu S, Li F, Zhou J, Liu Z. The relationship between body iron status, iron intake and gestational diabetes: a systematic review and meta-analysis. Medicine (Baltimore). 2016;95(2):2383.

Khambalia AZ, Aimone A, Nagubandi P, Roberts CL, McElduff A, Morris JM, et al. High maternal iron status, dietary iron intake and iron supplement use in pregnancy and risk of gestational diabetes mellitus: a prospective study and systematic review. Diabet Med. 2016;33(9):1211-21.

Zein S, Rachidi S, Awada S, Osman M, Al-Hajje A, Shami N, et al. High iron level in early pregnancy increased glucose intolerance. J Trace Elem Med Biol. 2015;30:220-5.

Chan KK, Chan BC, Lam KF, Tam S, Lao TT. Iron supplement in pregnancy and development of gestational diabetes — a randomised placebo-controlled trial. BJOG. 2009;116(6):789-97.

Pandey R, Singh U, Solanki V, Mehrotra S. Association of serum ferritin level in early second trimester of pregnancy with development of gestational diabetes mellitus: a prospective observational study. J Obstet Gynaecol India. 2023;73(3):235-41.

Liu L, Yan F, Yan H, Wang Z. Impact of iron supplementation on gestational diabetes mellitus: a literature review. Diabetes Obes Metab. 2023;25(2):342-53.

American Diabetes Association Professional Practice Committee. 15. Management of diabetes in pregnancy: Standards of Care in Diabetes—2024. Diabetes Care. 2024;47(1):282-94.

Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):49-64.

Fisher AL, Nemeth E. Iron homeostasis during pregnancy. Am J Clin Nutr. 2017;106(6):1567-74.