Can iron be teratogenic?

Abstract

Several kinds of evidence indicate that elevated iron during the 3-8 week embryonic (organogenesis) period of human gestation may be teratogenic. (1) In the embryonic period, the natural maternal absorption of food iron is 30% below the estimated daily iron loss. (2) As compared with maternal serum, embryonic fetal coelomic fluid contains only one-fourth as much iron but nearly six times the quantity of the iron withholding protein, ferritin. (3) In the embryonic period, intraplacental oxygen pressure is 2-3 times lower than in the subsequent fetal growth period. (4) Iron is a strong inducer of emesis which peaks in the embryonic period. (5) In a murine gestation model, iron was neurotoxic at a sharp peak of 8-9 days. Thus it would be prudent, in human pregnancy, to delay any needed iron supplementation until the embryonic period has been completed.

The reproductive ecology of iron in women

“…Several researchers have suggested low iron during pregnancy is actually an evolved mechanism that benefits maternal–fetal health. Weinberg () suggests that low levels of iron transfer during the first trimester protects the embryo from teratogenic effects of iron on development. His evidence includes the lower concentration of iron in coelemic fluid (the cavity in which the embryo rests) at the end of the embryonic period than during the early fetal period; women's lower absorption of dietary iron during the first trimester than either prepregnancy or later trimesters; and that iron supplementation increases pregnancy sickness during the first trimester.…”

“…His evidence includes the lower concentration of iron in coelemic fluid (the cavity in which the embryo rests) at the end of the embryonic period than during the early fetal period; women's lower absorption of dietary iron during the first trimester than either prepregnancy or later trimesters; and that iron supplementation increases pregnancy sickness during the first trimester. He reports a study of pregnant mice with the effects of iron injections at various days during pregnancy on fetal formation (Kuchta, ; Weinberg, ), finding that iron was teratogenic to mouse fetuses, but only during certain days of development. Specifically, pregnant mice injected with iron had fetal malformations when injected on days 7–9 (peaking on day 8 with 33% of pups malformed), while control mice and mice injected on day 6 had no malformations (Kuchta, ).…”

“…The avoidance of iron‐rich foods such as meat would be especially problematic during later trimesters, when, as the article comments note, the fitness benefits of avoiding iron to prevent infection would have to be significant to outweigh the need for iron during pregnancy (Sellen in Fessler, ). There are consistencies between Fessler's hypothesis and Weinberg's (), in that both argue for avoiding first trimester iron supplementation to iron‐replete pregnant women.…”

Hepcidin and iron species distribution inside the first-trimester human gestational sac

“…The question arises as to the mechanistic role of substances like hepcidin, NTBI and transferrin in supplying and transporting iron to the fetus. Whatever the mechanism, iron homeostasis has to be carefully controlled inside the early gestational sac as any imbalance may result in irreversible damage to fetal tissues (Weinberg, 2010). …”

Health Effects of Metals in Particulate Matter

“…Iron catalyzes the production of hydroxylfree radicals, which destroy cells by lipid peroxidation, enzymes denaturation, carbohydrates depolymerization and ruptures in DNA. Experimental studies in the mouse show that an increase of iron produces histological alterations in the encephalon, as well as spine and ribs malformations [228].…”