(P15-040-20) Erythroferrone Is Associated with Maternal Erythropoietic Drive During Pregnancy

Objectives: Iron (Fe) homeostasis must be tightly regulated during pregnancy to meet both maternal and fetal Fe demands. Several hormones are known to impact Fe homeostasis including hepcidin, erythropoietin and erythroferrone (ERFE).  Few data are available on determinants of ERFE in pregnant women or in their newborns at birth. The objective of this study was to characterize concentrations of ERFE across gestation and evaluate this hormone in relation to other Fe status biomarkers and regulatory hormones in mothers across pregnancy.

Methods: ERFE was measured in serum from pregnant adolescents (n = 166, age 14 - 19) or women carrying multiple fetuses (n = 61, age 20 - 46). ERFE concentrations across gestation (wks 8 – 42.1) were compared to Fe status and nutritional indicators (hemoglobin (Hb), serum ferritin (SF), soluble transferrin receptor (sTfR), total body Fe (TBI), TR-F index (sTfR/log(SF)), folate and vitamin B-12), as well as regulatory hormones (erythropoietin (EPO), hepcidin) and inflammatory markers (IL-6, C-reactive protein (CRP)).

Results: ERFE concentrations increased significantly across pregnancy in women carrying multiple fetuses (p < 0.01), but did not change across pregnancy in the adolescents (p = 0.3). In both populations, 16% (n = 30) of women were anemic at midgestation (MG) and 24% (n = 75) at delivery. ERFE concentrations were significantly increased in anemic women at both MG (p = 0.02) and at delivery (p = 0.02). At MG (median 26 wks), ERFE was significantly positively associated with TfR (p < 0.001) and EPO (p = 0.002). Maternal TfR, IL-6 and serum Fe were the strongest determinants of maternal MG ERFE, and explained 29% of variance in ERFE. At delivery (median 38 wks), ERFE was significantly positively associated with TfR (p < 0.001) and EPO (p < 0.001), which together explained 18% of variance in ERFE at delivery. ERFE was not significantly associated with hepcidin at either MG (p =0.87) or delivery (p =0.52).

Conclusions: ERFE was significantly higher in anemic women across pregnancy and, as expected, was positively associated with indicators of erythropoietic drive. ERFE however, was not significantly associated with hepcidin, possibly because hepcidin is regulated by multiple competing signals. More research is needed to understand the relationship between maternal ERFE and neonatal Fe status at birth.

Funding Sources: Funded by the NIH (NIDDK/NICHD)