**1. Introduction**

It is a daily challenge and the most common clinical practise to rule out possible bacterial infection in the ill neonate and especially in the preterm infant. Approximately half of all newborn infants admitted to the neonatal ward carry a diagnosis of "rule-out sepsis", and diagnosis is often difficult as symptoms and signs of bacterial infection are subtle and nonspecific (1). The incidence of infection is higher in the neonatal period than at any other time of life, and factors that determine this increased susceptibility to bacterial infection include on the one hand the immaturity of the immune system with poor humoral responses to organisms (IgG and A), relatively poor neutrophil responses and complement activity, impaired macrophage function, and relatively poor T cell function, and on the other hand the exposure to microorganism from the maternal genital tract by ascending infections via the amniotic fluid or transplacental haematogenous spread. Additionally peripartum factors like trauma to skin or vessels during parturition or exposure to invasive obstetric procedures as well as portals of colonization and subsequent invasion (umbilicus, mucosal surfaces, eye, skin especially in very preterm infants) contribute to this increased risk for bacterial infection (2). Among extremely low birth weight infants at least 65% had one or more infections during their hospitalization in a National Institute of Child Health and Human Development Neonatal Research Network study including 6093 infants with followup at 18 to 22 months of corrected gestational age. Compared with uninfected infants infected infants were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy (range of significant odds ratios [ORs], 1.4- 1.7), low Bayley Scales of Infant Development II scores on the mental development index (ORs, 1.3-1.6) and psychomotor development index (ORs, 1.5-2.4), and vision impairment (ORs, 1.3-2.2). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome (3). Reasons for the greater susceptibility to infection of preterm infants also include invasive procedures during

© 2013 Resch and Resch, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Resch and Resch, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

their stay at the NICU, prolonged artificial ventilation, intravenous feeding and antibiotic pressures. (2). The incidence is estimated to range from 1 to 5-8.1 per 1000 live births (2,4). The proportion of child deaths that occurs in the neonatal period (38% in the year 2000) is increasing, and the Millennium Development Goal for child survival cannot be met without substantial reductions in neonatal mortality. Every year an estimated 4 million babies die in the first four weeks of life (the neonatal period), and, globally, the main direct causes of neonatal death are estimated to be preterm birth (28%), severe infections (26%), and asphyxia (23%) (5).

Immunoglobulins in the Prevention and Treatment of Neonatal Sepsis 83

correlation with maternal antibody levels in 111 acutely ill infants (10). These data extended earlier observations suggesting the correlation between low levels of type-specific antibody in serum and risk for systemic infection in neonates. Premature infants, compared to fullterm infants, have lower levels of IgG at birth that further decreases during the first few weeks of life (11). The relative deficiency of humoral immunity in premature newborns might contribute to the inverse correlation of birth weight and rate of neonatal sepsis, with an 86-fold increased rate of sepsis in newborns of birth weight 600 to 999 grams compared to newborns of birth weight of more than 2500 grams (11). Ballow et al. (12) measured plasma immunoglobulin concentrations of premature infants of birth weight less than 1500 g longitudinally from birth to 10 months chronological age. During the first week of life plasma IgG levels correlated well with gestational age. At the age of three months mean plasma IgG levels were 60 mg/dl in infants of 25 to 28 weeks gestational age and 104 mg/dl in those of 29 to 32 weeks. Most infants remained hypogammaglobulinaemic at six months with 64% and 62%, respectively, of the infants having plasma IgG levels below 200 mg/dl. Plasma IgM concentrations were low in both groups during the first week of life (7.6 and 9.1 mg/dl, respectively) and rose to 41.8 and 34.7 mg/dl, respectively, by eight to ten months of life. IgA concentrations were comparable for both groups during the first week of life (1.2 and 0.6 mg/dl, respectively). After discharge Ballow et al. (12) followed 43 preterm infants until ten months chronological age and observed a significantly higher incidence of infections compared to 41 term infants (p = 0.04). In another study the level of maternal antibody required to protect neonates against early-onset disease caused by goup-B streptococci (GBS) type Ia was estimated (15). Levels of maternal serum IgG GBS Ia antibodies of 45 neonates with early onset disease case caused by GBS Ia and 319 control subjects (neonates colonized by GBS Ia but without early-onset disease) born at ≥34 weeks gestation were compared. The probability of developing infection declined with increasing maternal levels of IgG GBS Ia antibody (P <.03). Neonates whose mothers had levels of IgG GBS Ia antibody ≥5 mg/mL had an 88% lower risk (95% confidence interval, 7%–98%) of developing type-specific early-onset disease, compared with those whose mothers had

Yang et al. (14) studied the mechanism of bacterial opsonization by intravenous immune globulin (IVIG) complement consumption and polymorphonuclear leukocyte membrane receptor mediated phagocytosis of Staphylococcus epidermidis, Klebsiella pneumoniae, and groups A and B streptococci. IGIV alone did not consume complement and showed no opsonic activity by itself for these organisms. When these bacteria were preopsonized in intravenous immune globulin, significant amounts of complement were consumed (44%- 94%) and the uptake and killing of bacteria occurred. An important finding was the fact that in vitro opsonic activity of IGIV for these organisms was significantly correlated with the amount of complement consumed by the IVIG – opsonised bacteria. The in vivo protective efficacy of IVIG also appeared to be directly associated with its ability to activate and consume complement. The higher the titers of the IVIG preparation are (higher than 200 units:ml) the more opsonic activity has been shown towards slime-producing *S*. *epidermidis* (15). Administered as a prophylactic agent to low-birth weight (lower than 1700 g) preterm neonates immediately after birth revealed significantly higher specific IgG in blood sera

levels <0.5 mg/mL (13).
