Abstract
Background: Iron deficiency is the most prevalent nutritional disorder worldwide, especially among
pregnant women and children. Congenital iron deficiency causes several deleterious effects on the
cognitive and motoric development of the infant.
Objective: The objective of this study is to assess the consequences of severe congenital iron
deficiency on the neuron count in the hippocampus and the fatty acid composition of the cerebellum in
male Wistar rats, and to discover whether or not iron supplementation injected during the window of
opportunity, which is equivalent to the 3rd trimester in human development, can restore the
deleterious effects of iron deficiency.
Design: Adult female rats were randomly divided into two groups. The rats assigned for iron
deficiency were exsangiunated and fed an iron depleted diet (<10mg Fe/kg), while the control rats
were fed a commercial diet. The offspring of the iron deficient (ID) dams were designated into two
groups, a treatment group where pups received iron injections (45mg/kg iron isomaltoside 1000) and
a group receiving saline injections, thus remaining ID. The severity of iron deficiency was confirmed by
measuring hematocrit values on postnatal day (P) 8-13, P15-18 and P86-94. A footprint analysis test
was performed on male rats on P85-90 and the rats were euthanized on P86-94, and their brains were
excised for brain iron analysis of the mesencephalon, stereological analysis of the hippocampus and
fatty acid analysis.
Results: The results of the footprint analysis showed significantly increased gait width in ID animals
compared to both control and ID animals receiving iron supplement (ID + im1000). The fatty acid
analysis showed a significant decrease in both docosahexaenoic acid (DHA) and total amount of polyunsaturated
fatty acids (PUFAs) in the ID + im1000 group compared to the control group.
Furthermore, the control group had a higher amount of n-3 fatty acids compared to both the ID and ID
+ im1000 group, and the ID group had a higher amount of n-6 fatty acids compared to the ID + im1000
and control group. The results of stereological counting of the hippocampus showed a larger amount
of neurons in the dentate gyrus (DG) of the ID + im1000 groups compared to the ID group.
Conclusion: The deleterious effects of congenital ID can be reversed to some degree by administering
iron isomaltoside 1000 during the window of opportunity. While motor defects and low hematological
values resulting from congenital ID are reversed completely, the results suggest that the lipid
composition of the cerebellum cannot be fully recovered to that of normal individuals. In addition, the
results suggest that the amount of neurons in the DG can be improved by administering iron in early
life.