Iron Homeostasis over the First Week of Life: A Prospective Cohort Study in Hospital-Delivered Gambian Neonates

Abstract

Abstract Objectives Full-term newborns elicit an immediate postnatal hypoferremia at birth. We examined whether preterm and low birthweight babies are capable of a similar response. The transience of this innate defence in full-term babies was assessed by measuring iron, inflammatory and haematological parameters over the first postpartum week. Methods We conducted an observational study of 152 babies who were either preterm (>32 to <37weeks gestational age) and/or low birthweight (<2500 g) (PTB/LBW) and 278 term, normal-weight babies (FTB/NBW). Blood was sampled from the umbilical cord and matched venous blood samples were taken from all neonates between 6–24 hours after delivery. Term, normal-weight babies were then randomised to a second blood draw at 25–80 h (V2), 81–136 h (V3) or 137–192 h (V4). We measured haematological, iron and inflammatory markers in all samples. Results PTB/LBW and FTB/NBW babies decreased serum iron 3-fold within 12 h of postpartum life compared to cord blood (7.5 ± 4.5 vs 23.3 ± 7.1 ng/ml, P < 0.001, n = 425). Transferrin saturation showed a similar decline. C-reactive protein levels increased over 10-fold (P < 0.001) and hepcidin levels doubled (P < 0.001). No difference was observed in these responses between study groups. FTB/NBW newborns then steadily increased serum iron (16.5 ± 3.9 µmol/L) and TSAT (36.7 ± 9.2%) by V4 (P for trend <0.0001 for each). Hepcidin (45.2 ± 19.1 ng/ml) increased during this period (P for trend <0.0001), showing only a weak influence on serum iron and TSAT. Inflammatory markers increased from V1 to V4. Conclusions Premature and low birthweight babies mount a rapid postnatal hypoferremia equal to that in term babies. Data suggest that this hepcidin-mediated response is triggered by acute inflammation at birth. This evolved method of protection against septicaemia is transient, with a later increase in serum iron despite very high hepcidin. This indicates hepcidin resistance possibly caused by macrophage iron saturation. Pharmacological prolongation of hypoferremia might offer an ancillary tool in the arsenal against infection, however, it would need to overcome the hepcidin resistance we now report. Funding Sources Bill & Melinda Gates Foundation.