Effects of maternal iron and zinc deficiency and supplementation on neonatal iron and zinc status, iron uptake, and intestinal iron and zinc transporter expression in a rat model

Iron (Fe) and zinc (Zn) deficiencies are common during pregnancy. While pregnant women are routinely supplemented with Fe, Zn supplementation is also often recommended. However, the effects of maternal Fe and Zn deficiency and supplementation during pregnancy on infant Fe and Zn status at weaning are largely unknown. In particular, there are no reports on how maternal supplementations during pregnancy regulate proteins involved in postnatal Fe absorption in the offspring. We developed a rat model to evaluate effects of maternal Fe and Zn deficiency and supplementation during pregnancy on pup Fe and Zn status and regulation of hepcidin and proteins involved in Fe and Zn homeostasis in pup intestine postnatally. We found that maternal Fe deficiency decreased pup body weight at weaning and that maternal Zn deficiency compromised pup Zn status. Maternal Fe supplementation during pregnancy increased pup body weight and that increase depended on adequate maternal Zn status or co-supplementation with Zn. Zn supplementation on the other hand increases pup body weight only when Zn status is low. However, Zn supplementation decreased pup body weight in Zn adequate dams. Hepcidin, the hepatic regulator of intestinal Fe absorption, was recently identified and its expression parallels liver Fe concentration. When dams were simultaneously deficient in both Fe and Zn, Fe supplementation during pregnancy increased pup liver Fe concentration, thereby increasing hepatic hepcidin expression. Zn supplementation increased pup intestinal ferritin expression suggesting intracellular trapping of Fe. In pups from Fe and Zn adequate dams, Zn supplementation increased pup liver Fe concentration. In Fe deficient but Zn adequate dams, Fe supplementation increased Fe status of the pups and thereby hepcidin expression and Zn supplementation increased liver Fe concentration but decreased hemoglobin levels. Maternal Fe and Zn deficiency should be corrected to ensure proper Fe and Zn status of pups. However, given the negative effects of maternal Zn supplementation when dams had adequate Zn status, and the current lack of reliable indicators of Zn status, we conclude that, though Zn supplementation during pregnancy could be an option, it should recommended with caution.