Neonatal GBS diseases occur in two forms: early-onset (within the first 7 days after birth) and late-onset. Most of early-onset disease occurs within 24 hours after birth and are acquired in utero or at birth from GBS- colonized mothers. The development of capsular polysaccharide and protein conjugate vaccines raises the possibility that maternal immunization may become a realistic prevention tool for neonatal GBS in the future. However, an efficacy trial for a GBS vaccine will likely require vaccinating more than 85,000 pregnant women, and there are no standardized assays for measuring anti-capsular polysaccharide antibodies to GBS. Licensure should be considered for vaccines that induce """"""""protective"""""""" levels of type-specific antibody to GBS without the necessity for efficacy trial. The NICHD multi-center study is designed to determine such a protective serum antibody threshold to at least two serotypes. This is a prospective case-control study. At each of the six study centers, cases of early-onset GBS disease (defined as isolation of GBS from a normally sterile body fluid in a newborn whose illness began within 7 days after birth) are identified by active daily surveillance of microbiology laboratories and neonatal intensive care nurseries. Controls are infants who are surface colonized with GBS at birth but do not develop GBS disease. Controls are identified by surface-culturing (throat, anus, umbilicus and ear) a systematic sample of all newborns at each hospital. All cases and controls are born at greater than or equal to 34 weeks gestation (age at which transplacental transfer of antibodies occurs). Maternal sera are obtained shortly before delivery and cord sera are collected from cases and controls. GBS isolates from blood, CSF and surface cultures are collected for serotying. The target for enrollment is 140 cases, 560 heavily colonized controls (>2 sites) and 840 lightly colonized controls (less than or equal to 2 sites). Sera from cases and controls will be assayed using ELISA method for serotype-specific IgG and IgG subclass antibodies to each serotype. During the first 24 months of surveillance, 87 cases, 412 heavily colonized, and 687 lightly colonized newborns were identified. The serotype distribution of the first 67 cases showed that serotypes Ia, III and V accounted for 82% of strains (Ia: 40%, III: 27%, and V: 15%). To determine the best method for measuring specific IgG antibody to GBS polysaccharide, CBER/FDA has compared four different ELISA methods to measure IgG antibody to type III and type Ia, and found that all 4 methods are sensitive, but that an ELISA using methylated human serum albumin comixed with GBS capsular polysaccharide is most specific. Epidemiological data are collected on prospective cases and controls by chart abstraction. In addition, a retrospective case-control study designed to evaluate the effectiveness of intrapartum antibiotic prophylaxis against early-onset GBS disease in neonates was conducted. In this retrospective study, we are comparing 110 early-onset GBS cases with 220 matched controls without GBS disease, all sampled from the same six clinical centers currently participating in the multi center study. Both cases and controls are selected from births between January 1, 1994 to December 31, 1994 to mothers with at least one risk factor to GBS disease, as defined by ACOG guidelines. Early-onset GBS cases, defined as above, are identified by a retrospective microbiology record review and validated by a review of infant's medical record. For each case, two controls, matched by gestational age and birth hospital, are selected via a systematic review of labor and delivery logbooks. Epidemiological data are abstracted from maternal and infant's medical records by chart abstractors who are kept blinded to whether the mothers' newborns were cases and controls. Antibiotic effectiveness will be evaluated by calculating the odds ratio for the comparison of the receipt of intrapartum prophylactic antibiotics in mothers of cases vs. mothers of controls. Analysis of this retrospective study is underway. In an additional assessment of the impact of the published guidelines for intrapartum antibiotic prophylaxis on early-onset GBS, we compared the incidence of early-onset GBS and the prevalence of maternal risk factors of cases collected during this study period with cases of 1992-94 in the same hospitals. Our data showed that the incidence of early-onset GBS decreased from 1.5/1000 live births in 1992-4 to 1.2/1000 in 1995-96, the % of early-onset GBS cases born to mothers with at least one risk factor decreased from 64% to 29%, and the % cases < 37 weeks' gestation (27% vs 13%), % cases born to mothers with fever (29% vs 11%), and to mothers with rupture of membranes >18h before delivery (32% vs 10%) decreased significantly. Analysis of attack rates of early-onset GBS disease in newborns born to mothers with various maternal risk factors and in infants with varying degrees of surface colonization is underway.
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