A longitudinal study of iron status during pregnancy and the risk of gestational diabetes: findings from a prospective, multiracial cohort.
The aim of this study was to prospectively and longitudinally investigate maternal iron status during early to mid-pregnancy, and subsequent risk of gestational diabetes mellitus (GDM), using a comprehensive panel of conventional and novel iron biomarkers.



A case-control study of 107 women with GDM and 214 controls (matched on age, race/ethnicity and gestational week during blood collection) was conducted within the the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort (2009-2013), a prospective and multiracial pregnancy cohort. Plasma hepcidin, ferritin and soluble transferrin receptor (sTfR) were measured and sTfR:ferritin ratio was derived, twice before GDM diagnosis (gestational weeks 10-14 and 15-26) and at weeks 23-31 and 33-39. GDM diagnosis was ascertained from medical records. Adjusted ORs (aORs) for GDM were estimated using conditional logistic regression analysis, adjusting for demographics, prepregnancy BMI and other major risk factors.



Hepcidin concentrations during weeks 15-26 were 16% higher among women with GDM vs controls (median 6.4 vs 5.5 ng/ml; p = 0.02 ), and were positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.61 (1.07, 6.36). Ferritin levels were also positively associated with GDM risk; the aOR (95% CI) for highest vs lowest quartile was 2.43 (1.12, 5.28) at weeks 10-14 and 3.95 (1.38, 11.30) at weeks 15-26. The sTfR:ferritin ratio was inversely related to GDM risk; the aOR (95% CI) for highest vs lowest quartile was 0.33 (0.14, 0.80) at weeks 10-14 and 0.15 (0.05, 0.48) at weeks 15-26.



Our findings suggest that elevated iron stores may be involved in the development of GDM from as early as the first trimester. This raises potential concerns for the recommendation of routine iron supplementation among iron-replete pregnant women.
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, MSC 7004, Bethesda, MD, 20817, USA.
Shristi
S
Rawal
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, MSC 7004, Bethesda, MD, 20817, USA.
Stefanie N
SN
Hinkle
Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA.
Wei
W
Bao
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, MSC 7004, Bethesda, MD, 20817, USA.
Yeyi
Y
Zhu
Office of the Director, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Jagteshwar
J
Grewal
Biostatistics and Bioinformatics Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Paul S
PS
Albert
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA.
Natalie L
NL
Weir
Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA.
Michael Y
MY
Tsai
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, MSC 7004, Bethesda, MD, 20817, USA. zhangcu@mail.nih.gov.
Cuilin
C
Zhang
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016640:Diabetes, Gestational / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D005293:Ferritins / Q000097:blood; D064451:Hepcidins / Q000097:blood; D006801:Humans; D007501:Iron / Q000097:blood; D019190:Iron Overload / Q000097:blood; D008137:Longitudinal Studies; D011247:Pregnancy; D011990:Receptors, Transferrin / Q000378:metabolism; D055815:Young Adult
D064451:Hepcidins; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron
Ferritin; Gestational diabetes mellitus; Hepcidin; Iron overload; Soluble transferrin receptor; sTfR:ferritin ratio