Neonatal Sepsis in the Very Low Birth Weight Preterm Infants: Part 1: Review of Patho-physiology

Abstract

Background: Over the last fifty years neonatal care has made tremendous progress; increasing survival, reducing morbidity, developing newer modalities of care and therapy for the very low birth weight (VLBW) and premature infant. However, mortality from neonatal sepsis in this group of infants has remained between 18-20% in the developed world and around 80% in the developing world for last three decades with little sign of decline. There is also clear evidence that VLBW infants who survive infection in the neonatal period are at significantly greater risk of neuro-developmental delay; making sepsis the most important cause of mortality and morbidity in this group of infants today. Objective: The objective of this review is to highlight the reasons for this lack of success in combating neonatal sepsis successfully. These can be attributed to four main reasons; 1) poor host defences, 2) clinician’s inability to diagnose sepsis early and accurately [due to lack of or general availability of highly sensitive and specific markers], 3) clinician’s poor understanding of the ‘process’ i.e. pathophysiology of neonatal sepsis, thus not being able to institute early ‘goal’ directed therapy, and 4) total reliance on killing the pathogen(s) with inadequate attention to correcting the consequences of the inflammatory process itself. This review presents a brief epidemiological background to neonatal infections in the VLBW infants, discusses host defence systems and how immune compromised VLBW infant combats infection by describing the pathophysiological ‘process’ of sepsis in detail. It is our belief that understanding the heterogeneity and complexity of host response and the defence systems is fundamental in formulating management strategies. Conclusion: By discussing patho-physiology, current available diagnostic tests and presenting an evidence based management ‘care bundle’ it is hoped to change clinician's paradigm to use more immune and molecular markers for diagnosis and monitoring of the infection process and in management considering adjunctive therapies that boost host defences. It is recognised that while this review is static i.e. it presents evidence as we understand it today, sepsis is a dynamic process. Our understanding, ability to diagnose and manage neo-natal sepsis is constantly changing and will continue to change and evolve. By presenting this review it is hoped that over a period of time more of our practices would become evidence based and dogma abandoned.