Neonatal sepsis is very common in very preterm infants, occurring in more than 20% of infants born <30 weeks gestational age, and mortality is twice that of uninfected infants. Sepsis diagnosis remains difficult - clinical signs are non-specific and overlap with other inflammatory conditions. Susceptibility is largely dependent on innate immune development, but the innate defence pathways responsible for recognition and control of neonatal sepsis pathogens are poorly characterised in the newborn. Moreover it is unknown: (i) whether these defence pathways differ in individuals who develop infection, and if such differences can be used to improve timely diagnosis; (ii) if these differences persist beyond infancy and; (iii) how these innate immune pathways are altered by common in utero exposure to infection and inflammation.

Using a range of –omics approaches to study healthy and septic infants of different gestational ages at birth and postnatally, we have begun to map out the ‘in utero’ and postnatal development of critical monocytic, antimicrobial, and pattern recognition receptor (TLR, NLR and other cytosolic pathways) defences. We are currently exploring the postnatal maturation of these pathways, the impact of exposure to chorioamnionitis on their development and the use of novel immunomodulators to treat and prevent neonatal sepsis.