Clinically and epidemiologically, infant group B streptococcal infection can be divided into two distinct syndromes on the basis of age at onset. Early-onset disease appears within the first 6 days of life and historically had an attack rate of 1.3 to 3.7 per 1,000 live births. The incidence, as of 2003, had fallen to 0.32 per 1,000 live births following the 2002 recommendation for universal group B streptococcal culture screening during pregnancy and intrapartum chemoprophylaxis for all culture-positive women. Nearly 90% of early-onset cases and almost all fatal infections occur during the first day of life. Maternal factors increasing risk for early-onset disease are group B streptococcal bacteriuria during pregnancy, preterm delivery, intrapartum fever, prolonged rupture of membranes is greater than or equal to 18 hours, and African-American ethnicity and perhaps age younger than 20 years. Attack rates are related inversely to birth weight, but most neonates (nearly 80%) with early-onset disease are born at 37 or more weeks of gestation.

Late-onset disease, which occurs at 7 through 89 days of age, has an incidence of 0.4 to 1.7 of 1,000 live births. Except for preterm delivery, the obstetric complications commonly accompanying early-onset disease are not factors associated with the later presentation of infant group B streptococcal infection. Very late-onset disease has been described in very low-birth-weight infants who remain hospitalized and susceptible, presumably through acquisition of colonization at mucous membrane sites and by virtue of immature immune status. Another group of infants with very late-onset infection are those with human immunodeficiency virus (HIV) infection. Very late-onset cases may account for up to 20% of infant group B streptococcal cases. Low levels of maternally derived serum IgG antibody directed against group B streptococcal capsular polysaccharide at delivery also increase the risk for invasive disease, no matter the age at onset.

The distribution of serotypes has both epidemiologic and clinical significance. In surveys of large numbers of colonized young adults, children, and neonates, five of the nine defined capsular
serotypes (Ia, Ib, II, III, and V) are dominant. Colonized neonates reflect the serotype of their mothers in all but the rare infant who acquires group B streptococci from nursery personnel or the community. Serotypes Ia, Ib, II, III, and V account for approximately 35%, 10%, 15%, 30%, and 15%, respectively, of the cases of early-onset disease. Serotype III causes some 85% of cases of group B streptococcal meningitis, regardless of age, and 75% of late-onset disease, irrespective of clinical presentation.

The transmission of group B streptococci to the neonate can occur whenever a delivering mother harbors the organism. Exposure may occur by ascending infection through ruptured or (uncommonly) intact amniotic membranes or by aspiration or swallowing of or surface contamination with vaginal fluid as the infant descends through the birth canal. Vertical transmission accounts for asymptomatic infection (or colonization) in approximately 50% of infants born to mothers carrying group B streptococci at delivery. Mothers with “heavy” colonization (more than 10⁵ colony-forming units per milliliter) are more likely to transmit the organism to their infants and to deliver a neonate who develops early-onset group B streptococcal disease. Despite the high rate of transmission and colonization in newborns, overall only 1% to 2% of infants born to colonized mothers who don’t receive intrapartum chemoprophylaxis develop invasive infection. Initial colonization can persist for weeks to months at various mucous membrane sites. Acquisition of the organism by neonates after hospital discharge has been reported to be uncommon, but few studies have addressed this setting for potential transmission.

Genital or gastrointestinal colonization in mothers at delivery provides infant exposure that is the necessary prelude of early-onset group B streptococcal infection. The degree of risk correlates directly with the degree (inoculum) of maternal colonization (heavy or light). A direct relationship between length of membrane rupture before delivery and risk of invasive infant disease also has been documented and, because amniotic fluid readily supports the replication of group B streptococci, the longer the interval, the higher is the inoculum. The invasion of respiratory tract epithelium, pulmonary interstitium, endothelium of the pulmonary vessels, and (finally) bacteremia presumably follow aspiration of infected amniotic fluid or birth canal contents. Several case series document that 35% to 65% of infants are symptomatic at birth, indicating that infection often begins in utero. In late-onset infection, presumably the first step in pathogenesis is the adherence of group B streptococci to the epithelium in the upper respiratory or gastrointestinal tract, resulting in colonization. Surface proteins, such as adhesins, have been implicated, but their role has been incompletely defined. The mechanisms by which organisms replicating at mucosal surfaces invade are not elucidated, but the presence of capsule is crucial to virulence once the organism reaches the bloodstream. Immaturity of a variety of host defense mechanisms undoubtedly contributes to the age-limited susceptibility of neonates and young infants to invasive group B streptococcal infection.

The evasion of host defenses is critical to the survival and replication of group B streptococci in vivo. When compared to immune effector mechanisms in adults and older infants, neonates (especially preterm infants) are developmentally deficient. Group B streptococci elaborate surface molecules, including capsule, which inhibit host defenses. Pulmonary alveolar macrophages and monocytes [but not polymorphonuclear leukocytes (PMNLs)] are recruited into the alveoli of infants with early-onset infection, but the capsular polysaccharide attenuates this response. This decreased ability to recruit host cells effectively correlates with diminished pulmonary clearance. Once bacteremia ensues, the capsule of the organism, which is necessary for virulence in animal models of lethal bacteremia, inhibits deposition of complement proteins and phagocytosis by PMNLs. In the absence of a sufficient quantity of type-specific antibodies directed against the capsular polysaccharide or of complement, phagocytosis of group B streptococci by PMNLs is minimal.

The role of surface receptors and functional abnormalities in neonatal PMNLs appear important in the pathogenesis and outcome of invasive infection. The development of profound neutropenia in fulminant early-onset sepsis is known to relate to an exhaustion of neutrophil reserves in the bone marrow, and this development occurs rapidly in some infants.

Type-specific immunity also is important in considering the pathogenesis of group B streptococcal infections. One of the earliest observations was that neonates at greatest risk for infection with type III strains were those with low levels of maternally derived type-specific serum antibody to the type III capsular polysaccharide. In vitro assays of the functional capacity of this type III–specific group B streptococcal antibody indicate that opsonization, ingestion by PMNLs, and killing of type III group B streptococci require a sufficient amount of type III–specific IgG and complement. Similar observations have been reported for serotypes Ia, Ib, II, and V. The relative deficiency of type-specific group B streptococcal antibodies in cord sera may be related either to very low levels in sera of women of childbearing age (documented in 80% to 90% in most studies) or to failure of placental transport of available maternal antibodies caused by placental abnormalities, delivery before 34 weeks’ gestation, or both.

Although the pathogenesis of late-onset group B streptococcal infection is not as well understood, type III strains appear to be uniquely virulent for the healthy term infant older than 6 days. As in those with early-onset infection, infants with late-onset disease exhibit low levels of type-specific antibody in their sera, as do their mothers. The common association of upper respiratory infection with late-onset group B streptococcal meningitis leads to speculation that alteration of the respiratory epithelium by a viral agent favors invasion of epithelium and subsequent bacteremia. Type III strains, the most frequent cause of late-onset disease, elaborate high levels of type-specific polysaccharide into the blood as they multiply, and this contributes to their virulence. The relationship between the terminal sialic acid determinant to the tertiary structure of the type III polysaccharide also allows these organisms to escape several host immune-effector mechanisms.

Presumably, group B streptococci are capable of entering the blood–brain barrier through complex evasive maneuvers. Interactions between type-specific antibodies and serum complement components are important to the opsonization and phagocytosis of type III group B streptococcus and, presumably, bloodstream clearance, but little is known about host–pathogen interactions in the cerebrospinal fluid.

Inflammatory mediators play a major role in the pathogenesis of group B streptococcal sepsis. Once invasive infection is established, ongoing replication and degradation of organisms can instigate host inflammatory responses that may be deleterious. Neonates recovering from group B streptococcal disease have circulating immune complexes that may contribute to end-organ damage. These immune complexes also elicit inflammatory mediators, such as leukotriene B₄ and interleukin-6 (IL-6). Group B streptococcal cell wall components, particularly peptidoglycan, elicit tumor necrosis factor-alpha (TNF-α), IL-1, IL-6, and granulocyte colony-stimulating factor. TNF-α is found in the acute serum of up to 50% of infants with group B streptococcal sepsis. In animal models of lethal sepsis, pretreatment with either pentoxifylline, which blocks TNF-α, or a monoclonal antibody to TNF-α modestly improves outcome. If pentoxifylline and indomethacin (a blocker of eicosanoid production) are combined in a piglet model of sepsis, however, hypoxemia and pulmonary hypertension are reduced significantly. This suggests that TNF-α and eicosanoids, including thromboxane A₂ and prostaglandin I₂, have a synergistic effect in sepsis caused by group B streptococcus. In the same model, IL-1 receptor antagonist ameliorates systemic hypotension and prolongs survival. Additional data will be required to characterize fully the inflammatory mechanisms that dictate the clinical consequences of group B streptococcal disease in neonates and young infants.

The pathologic findings in infants with fatal group B streptococcal infection depend on age at onset and clinical syndrome. Histologic findings of congenital pneumonia and atypical hyaline membranes containing these bacteria are characteristic of infants with early-onset group B streptococcal sepsis with pulmonary involvement. In early-onset meningitis, evidence of meningeal inflammation is present in a few infants. Perivascular inflammation with small-vessel thrombosis and parenchymal hemorrhage is found frequently. Some premature infants surviving group B streptococcal sepsis complicated by hypotension develop periventricular leukomalacia, indicating infarction of the white matter around the lateral ventricles. Older infants with fatal group B streptococcal meningitis usually have purulent leptomeningitis and a large number of organisms in the CSF.