Iron deficiency remains a global problem that is even more problematic during pregnancy, as it contributes to many health challenges for the mother and developing fetus.  Oral supplements are commonly used with the most frequent intervention composed of ferrous iron salts.  However, there are gastrointestinal side effects that lead to compliance issues and there is a potential for oxidative damage to maternal organs and the placenta upon the rapid absorption of iron.  Newer versions of oral iron supplementation are under development and include nanoparticles containing iron hydroxide adipate tartrate (IHAT).  The safety and efficacy of IHAT supplementation has not been demonstrated during pregnancy, which was the focus of a study conducted by Helman and colleagues.  They report their results in the March 2022 issue of The Journal of Nutrition.

Female mice consuming an iron-deficient or control diet for 2 weeks before mating served as models in which to evaluate the effectiveness and safety of oral IHAT administration.  The mice were gavaged with water (negative control), or with 10 mg iron/kg body weight as ferrous sulfate (positive control), or IHAT starting on embryonic day 4.5.  On embryonic day 18.5, iron and hematological parameters, gene expression and oxidative stress markers in the duodenum and placenta, and hepatic hepcidin were measured in the dams, as well as fetal iron.

Both iron supplements were effective at increasing maternal hemoglobin and hepatic iron, and total fetal iron, and there were no changes in oxidative stress markers induced by the supplements in the iron-deficient mice.  However, in iron-replete mice, placental expression of heme oxidase 1 was elevated in those receiving ferrous sulfate relative to those receiving IHAT.  These results led the authors to conclude that IHAT was safe and effective at alleviating iron deficiency in this mouse model, suggesting it may be useful in the treatment of iron deficiency during human pregnancy.

In an editorial, Collins articulated the importance of this step taken by Helman and colleagues to identify safe and effective iron supplementation approaches in order to reduce anemia during pregnancy.  However, he does point out the doses used were much greater than those used in humans, which could have altered iron absorption kinetics.  In order to combat the reduction in fetal copper occurring with the supplements, Collins suggests IHAT supplements should also include copper in order to avoid potential fetal complications resulting from both iron and copper deficiencies.  Collins concludes that IHAT may be a potentially superior treatment regimen to treat anemia during pregnancy.


Sheridan L Helman, Sarah J Wilkins, Daniel R McKeating, Anthony V Perkins, James S M Cuffe, Gunter Hartel, Nuno Faria, Jonathan J Powell, Gregory J Anderson, David M Frazer, A Novel Ferritin-Core Analog Is a Safe and Effective Alternative to Oral Ferrous Iron for Treating Iron Deficiency during Pregnancy in Mice, The Journal of Nutrition, Volume 152, Issue 3, March 2022, Pages 714–722,

James F Collins, A Synthetic Ferritin Core Analog Functions as a Next-Generation Iron Supplement, The Journal of Nutrition, Volume 152, Issue 3, March 2022, Pages 651–652,

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