Research Article: New Approaches to Preventing, Diagnosing, and Treating Neonatal Sepsis

Date Published: March 9, 2010

Publisher: Public Library of Science

Author(s): Karen Edmond, Anita Zaidi

Abstract: Karen Edmond and Anita Zaidi highlight new approaches that could reduce the burden of neonatal sepsis worldwide.

Partial Text: Neonatal sepsis or septicaemia is a clinical syndrome characterized by systemic signs of circulatory compromise (e.g., poor peripheral perfusion, pallor, hypotonia, poor responsiveness) caused by invasion of the bloodstream by bacteria in the first month of life. In the pre-antibiotic era neonatal sepsis was usually fatal. Case fatality rates in antibiotic treated infants now range between 5% and 60% with the highest rates reported from the lowest-income countries [1]. The World Health Organization (WHO) estimates that 1 million deaths per year (10% of all under-five mortality) are due to neonatal sepsis and that 42% of these deaths occur in the first week of life [2]. There are wide disparities in neonatal care between high- and low-income countries. In high-income countries the major concern is the increasing numbers of extremely premature infants with high nosocomial infection rates due to multiresistant organisms in intensive care units. Health facility infections are also a major problem in low-income countries, but the more pressing issues are the high proportion of home deliveries in unclean environments predisposing to sepsis and ensuring that all neonates have access to effective interventions from health care providers in the first days of life2. Indeed, new strategies that can prevent, diagnose, and treat neonates with sepsis are needed in both low- and high-income settings.

Distal risk factors for neonatal sepsis include poverty and poor environmental conditions. Proximate factors include prolonged rupture of membranes, preterm labour, maternal pyrexia, unhygienic intrapartum and postnatal care, low birth weight, and prelacteal feeding of contaminated foods and fluids [3]–[5].

Neonates have a functionally immature immune system. They have extremely low immunoglobulin (Ig) levels except for IgG to specific maternal antigens transferred passively across the placenta during the last trimester of pregnancy [14],[15]. T cell function is relatively unimpaired but complement activity is half that of healthy adults. Neonates have a low neutrophil storage pool, and their existing neutrophils have impaired capacity to migrate from the blood to sites of infection [16].

Neonatal clinical sepsis syndrome identification is difficult as the clinical signs of neonatal septicaemia can be very similar to those of other life-threatening diseases such as necrotising enterocolitis, hyaline membrane disease, and perinatal asphyxia [48],[49]. However, recent studies in middle- and low-income countries have provided seven danger signs which can be used to identify infants with very severe disease including neonatal sepsis (Table 1) [49]. These signs provide high sensitivity and moderate specificity for detecting serious illness in newborns in low-resource settings and have now been incorporated into the new neonatal WHO Integrated Management of Childhood Illness (n-IMCI) guidelines.

As neonatal sepsis can be rapidly fatal if left untreated, highly effective antibiotic therapy must be used and delays in the provision of care must be minimised. Treatment must be effective against the causative pathogen, safe for the newborn, and feasible to deliver reliably in the hospital or community setting.

Newborn sepsis is a major cause of child mortality across the world. Industrialized countries have made remarkable progress in reducing newborn sepsis and sepsis-related mortality by providing access to hygienic skilled delivery for all women, risk-based intrapartum antibiotic prophylaxis, and high-quality intensive care for newborns that need it. Although resource constraints preclude whole-scale adoption of these strategies in developing countries, there are a number of low-cost proven interventions and promising approaches that have the potential to significantly reduce the burden of neonatal sepsis worldwide (Table 2).



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