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Background: Guidelines issued in 1996 in the United States recommend either screening of pregnant women for group B streptococcal colonization by means of cultures (screening approach) or assessing clinical risk factors (risk-based approach) to identify candidates for intrapartum antibiotic prophylaxis. Methods: In a multistate retrospective cohort study, we compared the effectiveness of the screening and risk-based approaches in preventing early-onset group B streptococcal disease (in infants less than seven days old). We studied a stratified random sample of the 629,912 live births in 1998 and 1999 in eight geographical areas where there was active surveillance for group B streptococcal infection, including all births in which the neonate had early-onset disease. Women with no documented culture for group B streptococcus were considered to have been cared for according to the risk-based approach. Results: We studied 5144 births, including 312 in which the newborn had early-onset group B streptococcal disease. Antenatal screening was documented for 52 percent of the mothers. The risk of early-onset disease was significantly lower among the infants of screened women than among those in the risk-based group (adjusted relative risk, 0.46; 95 percent confidence interval, 0.36 to 0.60). Because women whose providers had no strategy for prophylaxis may have been misclassified in the risk-based group, we excluded all women with risk factors and adequate time for prophylaxis who did not receive antibiotics. The adjusted relative risk of early-onset disease associated with the screening approach in this secondary analysis was similar — 0.48 (95 percent confidence interval, 0.37 to 0.63). Conclusions: Routine screening for group B streptococcus during pregnancy prevents more cases of early-onset disease than the risk-based approach. Recommendations that endorse both strategies as equivalent warrant reconsideration. (N Engl J Med 2002;347:233-9.) [ABSTRACT FROM AUTHOR]