Iron and Infection: Neonatal Iron Transition

Neonates, particularly those born preterm (PTB) and low birthweight (LBW), are especially susceptible to bacterial infections that cause an estimated 225,000 deaths annually. Iron is a vital substrate for the most common organisms causing septicaemia. Full-term babies elicit an immediate post-natal hypoferremia assumed to have evolved as an innate defence. This thesis aimed to test whether preterm and low birthweight newborns are capable of a similar response. A longitudinal observational study was conducted in 430 hospital-delivered Gambian babies. Demographic, anthropometric and haematological data were collected from 152 babies who were either PTB (between ≥32-<37 weeks gestational age) and/or LBW (<2500g) (PTB/LBW) and 278 full-term, normal-weight babies (FTB/NBW). Blood was sampled from the umbilical cord and matched venous blood samples from all neonates between 6-24 hours after delivery. An additional matched venous blood sample was taken from all full-term, normal birth weight newborns between 24-192 hours of life. In both FTB/NBW and PTB/LBW neonates, serum iron decreased 3-fold compared to umbilical blood concentrations within 12h of delivery (23·3±0·35 vs 7·5±0·22 ng/ml, P<0.001, n=425). Hepcidin levels doubled (27·0±0·96 vs 52·9±1·63 ng/ml, P<0·001, n=425). In FTB/NBW neonates, a steady increase in serum iron and TSAT follows (to 16.5±3.9μmol/L and 36.7±9.2% respectively by 136-192hrs postdelivery), even in the presence of relatively high serum hepcidin levels (45.2±19.1ng/ml) suggestive of hepcidin resistance possibly caused by iron saturation of macrophages. Our findings confirm that a very rapid hypoferremia occurs in the early hours of post-natal life with evidence that it is mediated by an increase in hepcidin. The strength and consistency of this effect in all neonates indicates that it may have evolved as an innate immune response designed to protect newborns from bacterial septicaemia.