Hepcidin across pregnancy and its correlation with maternal markers of iron and inflammation, maternal body weight outcomes, and offspring neurodevelopmental outcomes: a systematic review and meta-analysis

Derrick Ssewanyana; Stephane L Borque; Stephen J Lye; Stephen G Matthews

doi:10.1016/j.xagr.2023.100222

Hepcidin across pregnancy and its correlation with maternal markers of iron and inflammation, maternal body weight outcomes, and offspring neurodevelopmental outcomes: a systematic review and meta-analysis

AJOG Glob Rep. 2023 May 11;3(3):100222. doi: 10.1016/j.xagr.2023.100222. eCollection 2023 Aug.

Authors

Derrick Ssewanyana^{1

2

3}, Stephane L Borque⁴, Stephen J Lye^{1

2

3}, Stephen G Matthews^{1

2

3}

Affiliations

¹ Departments of Physiology (Drs Ssewanyana, Lye, and Matthews).
² Medicine (Drs Ssewanyana, Lye, and Matthews), University of Toronto, Toronto, Canada.
³ Alliance for Human Development, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada (Drs Ssewanyana, Lye, and Matthews).
⁴ Department of Anesthesiology and Pain Medicine and Pharmacology, University of Alberta, Edmonton, Canada (Dr Borque).

Abstract

Objective: This study evaluated the correlation between maternal hepcidin and other biomarkers of iron status, markers of inflammation, and maternal body weight during pregnancy, as well as neurodevelopment in the offspring.

Data sources: PubMed, Web of Science, Scopus, and Embase were searched from inception until March 2022.

Study eligibility criteria: Studies conducted among pregnant women without apparent pregnancy complications were included. Eligible studies reported correlation coefficients between maternal hepcidin and any outcomes of maternal biomarkers of iron status or inflammatory load during pregnancy, prenatal maternal body weight, and offspring neurodevelopment. Studies without correlation data were eligible if they quantitatively reported volumes of both maternal hepcidin and any marker of iron status and/or inflammatory load during gestation.

Methods: Pooled correlation coefficients between maternal hepcidin and outcomes of interest were calculated using the Fisher r-to-Z transformation. Both fixed-effects and DerSimonian and Laird random-effects models were used to calculate pooled correlation coefficient. When meta-analysis was not feasible, results were descriptively synthesized.

Results: Forty-six studies with 6624 participants were eligible. Hepcidin was significantly correlated with hemoglobin in the third trimester (r=0.21; 95% confidence interval, 0.1-0.32); ferritin in the first (r=0.31; 95% confidence interval, 0.01-0.61) and third trimester (r=0.35; 95% confidence interval, 0.23-0.48); soluble transferrin receptor in the second trimester (r=-0.27; 95% confidence interval, -0.4 to -0.14); total iron-binding capacity in the second trimester (r=0.37; 95% confidence interval, 0.24-0.50); and serum iron in the third trimester (r=0.11; 95% confidence interval, 0.02-0.19). Hepcidin was significantly correlated with the inflammatory marker interleukin-6 in the third trimester (r=0.26; 95% confidence interval, 0.17-0.34) and C-reactive protein in the second (r=0.16; 95% confidence interval, 0.03-0.30) and third trimester (r=0.28; 95% confidence interval, 0.04-0.52). Four out of 5 studies reported weak-to-moderate positive correlation between hepcidin and body mass index. Hepcidin levels varied across body mass index categories. No single study reported the relationship between maternal hepcidin and neurodevelopment in offspring.

Conclusion: Hepcidin weakly to moderately correlates with biomarkers of iron and inflammation in pregnancy.

Keywords: biomarkers; hepcidin; inflammation; iron metabolism; pregnancy.

Publication types

Review