Prenatal iron exposure and childhood type 1 diabetes

Ketil Størdal*, Harry J. McArdle, Helen Hayes, German Tapia, Marte K. Viken, Nicolai A. Lund-Blix, Margaretha Haugen, Geir Joner, Torild Skrivarhaug, Karl Mårild, Pål R. Njølstad, Merete Eggesbø, Siddhartha Mandal, Christian M. Page, Stephanie J. London, Benedicte A. Lie, Lars C. Stene

*Corresponding author for this work

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Abstract

Iron overload due to environmental or genetic causes have been associated diabetes. We hypothesized that prenatal iron exposure is associated with higher risk of childhood type 1 diabetes. In the Norwegian Mother and Child cohort study (n = 94,209 pregnancies, n = 373 developed type 1 diabetes) the incidence of type 1 diabetes was higher in children exposed to maternal iron supplementation than unexposed (36.8/100,000/year compared to 28.6/100,000/year, adjusted hazard ratio 1.33, 95%CI: 1.06-1.67). Cord plasma biomarkers of high iron status were non-significantly associated with higher risk of type 1 diabetes (ferritin OR = 1.05 [95%CI: 0.99-1.13] per 50 mg/L increase; soluble transferrin receptor: OR = 0.91 [95%CI: 0.81-1.01] per 0.5 mg/L increase). Maternal but not fetal HFE genotypes causing high/intermediate iron stores were associated with offspring diabetes (odds ratio: 1.45, 95%CI: 1.04, 2.02). Maternal anaemia or non-iron dietary supplements did not significantly predict type 1 diabetes. Perinatal iron exposures were not associated with cord blood DNA genome-wide methylation, but fetal HFE genotype was associated with differential fetal methylation near HFE. Maternal cytokines in mid-pregnancy of the pro-inflammatory M1 pathway differed by maternal iron supplements and HFE genotype. Our results suggest that exposure to iron during pregnancy may be a risk factor for type 1 diabetes in the offspring.

Original languageEnglish
Article number9067
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 13 Jun 2018

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    Størdal, K., McArdle, H. J., Hayes, H., Tapia, G., Viken, M. K., Lund-Blix, N. A., Haugen, M., Joner, G., Skrivarhaug, T., Mårild, K., Njølstad, P. R., Eggesbø, M., Mandal, S., Page, C. M., London, S. J., Lie, B. A., & Stene, L. C. (2018). Prenatal iron exposure and childhood type 1 diabetes. Scientific Reports, 8, [9067]. https://doi.org/10.1038/s41598-018-27391-4