Skip to main content Accessibility help

Iron deficiency during pregnancy and lactation modifies the fatty acid composition of the brain of neonatal rats

  • William D. Rees (a1), Susan M. Hay (a1), Helen E. Hayes (a1), Valerie J. Stevens (a1), Lorraine Gambling (a1) and Harry J. McArdle (a1)...


Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam’s milk and neonates’ brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring’s brain and suggests that these effects can be reduced by iron repletion of the dam’s diet at birth.


Corresponding author

Address for correspondence: William D. Rees, Rowett Institute, The University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK. Email:


Hide All
1. Menting, MD, van de Beek, C, Mintjens, S, et al. The link between maternal obesity and offspring neurobehavior: a systematic review of animal experiments. Neurosci Biobehav Rev. 2019; 98, 107121.
2. Lozoff, B, Klein, NK, Nelson, EC, McClish, DK, Manuel, M, Chacon, ME. Behavior of infants with iron-deficiency anemia. Child Dev. 1998; 69(1), 2436.
3. Lozoff, B, Jimenez, F, Hagen, J, Mollen, E, Wolf, AW. Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics. 2000; 105(4), E51.
4. Wachs, TD, Pollitt, E, Cueto, S, Jacoby, E, Creed-Kanashiro, H. Relation of neonatal iron status to individual variability in neonatal temperament. Dev Psychobiol. 2005; 46(2), 141153.
5. Lozoff, B, Beard, J, Connor, J, Barbara, F, Georgieff, M, Schallert, T. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev. 2006; 64(5 Pt 2), S34S43.
6. Doom, JR, Georgieff, MK. Striking while the iron is hot: understanding the biological and neurodevelopmental effects of iron deficiency to optimize intervention in early childhood. Curr Pediatr Rep. 2014; 2(4), 291298.
7. Beard, J. Iron deficiency alters brain development and functioning. J Nutr. 2003; 133(5 Suppl 1), 1468S1472S.
8. Carlson, ES, Stead, JDH, Neal, CR, Petryk, A, Georgieff, MK. Perinatal iron deficiency results in altered developmental expression of genes mediating energy metabolism and neuronal morphogenesis in hippocampus. Hippocampus. 2007; 17(8), 679691.
9. Felt, BT, Beard, JL, Schallert, T, et al. Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats. Behav Brain Res. 2006; 171(2), 261270.
10. Tran, PV, Fretham, SJB, Wobken, J, Miller, BS, Georgieff, MK. Gestational-neonatal iron deficiency suppresses and iron treatment reactivates IGF signaling in developing rat hippocampus. Am J Physiol Endocrinol Metab. 2012; 302(3), E316E324.
11. Beard, JL, Connor, JR. Iron status and neural functioning. Annu Rev Nutr. 2003; 23, 4158.
12. Mennitti, LV, Oliveira, JL, Morais, CA, et al. Type of fatty acids in maternal diets during pregnancy and/or lactation and metabolic consequences of the offspring. J Nutr Biochem. 2015; 26(2), 99111.
13. Gambling, L, Czopek, A, Andersen, HS, et al. Fetal iron status regulates maternal iron metabolism during pregnancy in the rat. Am J Physiol Regul Integr Comp Physiol. 2009; 296(4), R1063R1070.
14. O’Brien, JS, Sampson, EL. Lipid composition of the normal human brain: gray matter, white matter, and myelin. J Lipid Res. 1965; 6(4), 537544.
15. Lien, EL, Richard, C, Hoffman, DR. DHA and ARA addition to infant formula: current status and future research directions. Prostaglandins Leukot Essent Fatty Acids. 2018; 128, 2640.
16. Hay, SM, McArdle, HJ, Hayes, HE, Stevens, VJ, Rees, WD. The effect of iron deficiency on the temporal changes in the expression of genes associated with fat metabolism in the pregnant rat. Physiol Rep. 2016;4(21), e12908.
17. Cusick, SE, Georgieff, MK, Rao, R. Approaches for Reducing the Risk of Early-Life Iron Deficiency-Induced Brain Dysfunction in Children. Nutrients. 2018;10(2), E227.
18. Williams, RB, Mills, CF. The experimental production of zinc deficiency in the rat. Br J Nutr. 1970; 24(04), 9891003.
19. Lenartowicz, M, Kennedy, C, Hayes, H, McArdle, H. Transcriptional regulation of copper metabolism genes in the liver of fetal and neonatal control and iron-deficient rats. BioMetals. 2015; 28(1), 51–9.
20. Bowen, RA, Clandinin, MT. Maternal dietary 22: 6n-3 is more effective than 18: 3n-3 in increasing the 22 : 6n-3 content in phospholipids of glial cells from neonatal rat brain. Br J Nutr. 2005; 93(5), 601611.
21. Gambling, L, Andersen, HS, Czopek, A, Wojciak, R, Krejpcio, Z, McArdle, HJ. Effect of timing of iron supplementation on maternal and neonatal growth and iron status of iron-deficient pregnant rats. J Physiol. 2004; 561(Pt 1), 195203.
22. Woodman, AG, Care, AS, Mansour, Y, et al. Modest and severe maternal iron deficiency in pregnancy are associated with fetal anaemia and organ-specific hypoxia in rats. Sci Rep. 2017; 7, 46573.
23. Semple, BD, Blomgren, K, Gimlin, K, Ferriero, DM, Noble-Haeusslein, LJ. Brain development in rodents and humans: identifying benchmarks of maturation and vulnerability to injury across species. Prog Neurobiol. 2013; 106–107, 116.
24. Herrera, E. Metabolic adaptations in pregnancy and their implications for the availability of substrates to the fetus. Eur J Clin Nutr. 2000; 54(Suppl 1), S47S51.
25. O’Connor, DL, Picciano, MF, Sherman, AR. Impact of maternal iron deficiency on quality and quantity of milk ingested by neonatal rats. Br J Nutr. 1988; 60(3), 477485.
26. Rao, GA, Manix, M, Larkin, EC. Reduction of essential fatty acid deficiency in rat fed a low iron fat free diet. Lipids. 1980; 15(1), 5560.
27. Larkin, EC, Jarratt, BA, Ananda Rao, G. Reduction of relative levels of nervonic to lignoceric acid in the brain of rat pups due to iron deficiency. Nutr Res. 1986; 6(3), 309317.
28. Bichi, E, Toral, PG, Hervás, G, et al. Inhibition of Δ9-desaturase activity with sterculic acid: effect on the endogenous synthesis of cis-9 18:1 and cis-9, trans-11 18:2 in dairy sheep. J Dairy Sci. 2012; 95(9), 52425252.
29. Rao, GA, Crane, RT, Larkin, EC. Reduction of hepatic stearoyl-CoA desaturase activity in rats fed iron-deficient diets. Lipids. 1983; 18(8), 573575.
30. Cunnane, SC, McAdoo, KR. Iron intake influences essential fatty acid and lipid composition of rat plasma and erythrocytes. J Nutr. 1987;117(9), 15141519.
31. Beard, JL, Unger, EL, Bianco, LE, Paul, T, Rundle, SE, Jones, BC. Early postnatal iron repletion overcomes lasting effects of gestational iron deficiency in rats. J Nutr. 2007; 137(5), 11761182.
32. Tran, PV, Kennedy, BC, Pisansky, MT, et al. Prenatal choline supplementation diminishes early-life iron deficiency–induced reprogramming of molecular networks associated with behavioral abnormalities in the adult rat hippocampus. J Nutr. 2016; 146(3), 484493.
33. Kennedy, BC, Tran, PV, Kohli, M, Maertens, JJ, Gewirtz, JC, Georgieff, MK. Beneficial effects of postnatal choline supplementation on long-term neurocognitive deficit resulting from fetal-neonatal iron deficiency. Behav Brain Res. 2018; 336, 4043.


Iron deficiency during pregnancy and lactation modifies the fatty acid composition of the brain of neonatal rats

  • William D. Rees (a1), Susan M. Hay (a1), Helen E. Hayes (a1), Valerie J. Stevens (a1), Lorraine Gambling (a1) and Harry J. McArdle (a1)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed