Summary Preterm birth and infectious diseases are the most common causes of neonatal and early childhood deaths worldwide. The rates of preterm birth have increased over recent decades and currently account for 11% of all births globally. Preterm infants are at significant risk of severe infection in early life and throughout childhood. Bacteraemia and/or inflammation during the neonatal period in preterm infants is associated with adverse outcomes, including death, chronic lung disease and neurodevelopmental impairment. Recent studies suggest that bacteraemia may trigger cerebral injury even without penetration of viable bacteria into the central nervous system. Here we review available evidence that supports the concept of a strong association between bacteraemia, inflammation and cerebral injury in preterm infants, with an emphasis on the underlying biological mechanisms, clinical correlates and translational opportunities.

Neonates, particularly those born prematurely, are exquisitely vulnerable to life-threatening infections. This increased susceptibility to infection is maintained into childhood. Despite the considerable human and economic cost of infection-related neonatal morbidity and mortality, the mechanisms underlying this heightened susceptibility are only partly understood. It is increasingly recognised that innate immune responses are key to the protection against infection early in life, and emerging data suggest that such responses are deficient in the newborn and especially in preterm infants. Here we review the current understanding of the maturation of the innate immune response in human neonates highlighting the clinical relevance and possible avenues for therapeutic intervention.

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SummaryThe functional differentiation of immune cells at early age plays a central role in immune physiology, e.g. for the sufficient eradication of pathogens. However, imbalances in effector cell responses may also have an impact in the pathophysiology of childhood diseases such as atopy and autoimmune disorders. As information on immune cell responses in infancy and early childhood is scarce, we conducted an observational, cross-sectional study in healthy newborns ( n = = = = 18), infants and young children ( n = = = = 54) aged 1-96 months and adult controls ( n = = = = 19) to assess cytokine mRNA and protein expression upon phorbol 12-myristate 13-actate/ionomycin stimulation and LPSinduced IL-12 expression in monocytes. The intracellular expression of interferon (IFN)-γ γ γ γ , tumour necrosis factor (TNF)-α α α α ( R = = = = 0·748, P < < < < 0·0001; R = = = = 0·784, P < < < < 0·0001, respectively) and interleukin (IL)-2 protein expression ( R = = = = 0·384, P = = = = 0·008) was demonstrated to increase progressively with age. While a correlation between IL-4 protein expression and age was noted ( R = = = = 0·342, P = = = = 0·007), the levels of IL-5 and IL-10 protein expression tended to be regulated on an individual basis during infancy and early childhood. An age correlation was also observed for intracellular IL-12 expression ( R = = = = 0·331, P = = = = 0·009) in monocytes. These findings are valuable for further assessment of normal variations and maturation processes in immune cell responses and for the clinical-therapeutic monitoring of immunological status in various childhood diseases.