**2. Pathophysiology of neonatal sepsis**

The immune system of the neonate is immature in both humoral and cell mediated defense with prematurity further increasing the physiological inadequacies of the immune system. Sepsis spreads easily to the various organ systems in the neonates and thus, often presents as a multiorgan dysfunctions syndrome. Infection initiates a complex immune process, which includes antigen detection, T-cell activation and proliferation, and release of cytokines. Cytokines are low molecular mass proteins, which mediate cell growth, inflammation, immunity, differentiation, migration and repair. They regulate the amplitude and the duration of the inflammatory response and include interleukins-6 and -8, interferons-γ, colony-stimulating factors, tumour necrosis factor-α and others. However in the setting of overwhelming sepsis as a result to the microbial insult, these cytokines give rise to what is described as the systemic inflammatory response syndrome, where the much of the damage paradoxically results from the host defences (e.g. cytokines) analogous to a chain reaction themselves. The neutrophil functions: adhesion, diapedesis, phagocytosis and degranulation are also of prime importance in the host defence mechanisms against bacterial and fungal pathogens. The proteolytic enzymes released by the neutrophils are also damaging to the host tissue. Thus, immunoglobulins and neutrophils are responsible for both host defence and damage in the setting of overwhelming neonatal sepsis (6).

In 2005, definitions for paediatric infection, systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and organ dysfunction were published that included term neonates of 0 to 7 days and newborns of 1 to 4 weeks of age (7). But one has to question why there are no criteria for the definition of sepsis and septic shock in preterm infants? The challenge of diagnosis of sepsis in the preterm infants is strongly associated with the immaturity of organ systems and transitional physiology. Suggested modifications of these definitions have recently been published (8) but still have to be proven in clinical trials (9).
