Maternal Red Blood Cell Catabolism as a Source of Fetal Iron

Abstract Objectives The developing fetus is reliant on maternal iron (Fe) supply across gestation. Fetal Fe may be obtained from maternal red blood cell (RBC) catabolism, dietary sources or maternal stores. Relative use of these Fe pools has not been explored in humans. The objective of this study was to label the maternal RBC pool in early gestation and evaluate determinants of RBC enrichment across. A second objective was to compare fetal uptake of Fe from RBC catabolism vs recent maternal diet. Methods Fifteen women (age 17–34 y) were dosed with an oral stable ,57Fe isotope during the early second trimester of pregnancy (wk 15 ± 0.7) to label the maternal RBC pool. Enrichment of ,57Fe in maternal RBCs was monitored at regular intervals across pregnancy and in neonatal RBC's at birth. All women ingested an additional stable isotope (,58Fe) in late gestation (wk 34 ± 0.7) to quantify rapid transfer of dietary Fe to the fetus. The net amounts of each isotope in the mother and neonate were calculated using hemoglobin (Hb) concentration, body weight and estimated blood volumes. Hb, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin and erythroferrone (ERFE) were assessed in maternal and cord blood. Results In this population, 25% of women were anemic at delivery (Hb < 11 g/dL), and 36% of the newborns were anemic at birth (wk 39 ± 1.8) (Hb < 13 g/dL). During the third trimester of pregnancy, 25% of women were Fe deficient (SF < 12 mg/L). In the group as a whole, RBC ,57Fe enrichment decreased (b = −0.2, P = 0.06) on average by 2% across the 22 wk study interval (from 13.1% to 9.6%). Of the net amount of ,57Fe released from RBC catabolism, 25.4% [95% CI: 10.0%–64.4%] was transferred to the neonate. Neonatal RBC ,57Fe enrichment was significantly inversely associated with maternal and neonatal SF, which captured 87% of the variance in neonatal RBC ,57Fe enrichment (P < 0.01). Maternal SF was significantly inversely associated with neonatal RBC ,58Fe enrichment from the dietary source in late gestation. Maternal SF captured 55% of the variance in neonatal RBC ,58Fe enrichment (P = 0.01). Conclusions Women with low Fe stores exhibited a greater loss of RBC enrichment across gestation and a higher transfer of Fe from both catabolized RBC's and dietary sources to the fetus. More research on the determinants of placental Fe trafficking of different sources of maternal Fe is needed. Funding Sources Work funded by the NIH/NIDDK.