Neonatal iron status at birth is independently regulated by fetally derived hepcidin in neonates born to women carrying multiple fetuses

Abstract

Hepcidin is an important regulatory hormone for iron (Fe) homeostasis but little is known on determinants of neonatal hepcidin. To examine the relative importance of maternal versus neonatal hepcidin on neonatal Fe status, Fe status indicators including hemoglobin (Hb), soluble transferrin receptor (sTfR), erythropoietin (EPO), and hepcidin were measured in 63 women carrying multiple fetuses and in their 142 neonates at delivery. The majority of neonates (65%) were born prematurely and had low birth weight (69%). In these pregnancies, 30 neonates were monochorionic, 82 were dichorionic, and 32 were trichorionic. Hepcidin concentrations increased by nearly 3‐fold in neonates across the range of 30–38 weeks of gestation (r2=0.54, p=0.01, n=142). Maternal hepcidin at delivery was positively associated with neonatal hepcidin at birth (r2=0.45, p=0.007, n=118), but maternal hepcidin was not significantly associated with neonatal Hb and EPO. There is a negative but not significant trend between maternal hepcidin and neonatal sTfR (n=118, P=0.06). In contrast, neonatal hepcidin was significantly negatively associated with neonatal Hb (r2=0.76 p<0.0001, n=124), sTfR (r2=0.80, p<0.0001, n=142), and EPO (r2=0.72 p=0.0003, n=137). Significant variability in hepcidin was evident between siblings. As expected, monochorionic neonates had significantly lower intrauterine variability than di/trichorionic neonates in sTfR (p=0.001, n=136) and EPO (p=0.007, n=129). The intrauterine variability of neonatal hepcidin was a significant positive determinant of the intrauterine variability in Hb (r2=0.22, p=0.0004, n=49), sTfR (r2=0.08, p=0.02, n=60), and EPO (r2=0.17, p=0.0007, n=58). These findings suggest that neonates regulate their Fe status independently from their mothers and in relation to their own Fe demands given the variability that was evident between siblings.Support or Funding InformationGrant Funding Source: The Gerber Foundation