Early-onset neonatal sepsis in the era of widespread intrapartum chemoprophylaxis.

Early-onset sepsis (onset, first week of life) is an important cause of neonatal disease, early death, and adverse neurodevelopmental outcomes. The majority of early-onset infections result from vertical transmission of bacteria from mother to newborn during the intrapartum period. In the early 1900s, group A Streptococcus was the leading cause of neonatal and maternal peripartum infection in the United States. In the 1970s, group B Streptococcus (GBS) emerged as the leading cause of early-onset infection in newborns, resulting in an estimated 7500 cases and more than 1000 deaths annually. Demonstration that intrapartum antibiotic prophylaxis was effective at preventing early-onset GBS infections paved the way for consensus guidelines from the Centers for Disease Control and Prevention, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists, first released in 1996. In 2002, new evidence led to revised guidelines, recommending universal antenatal screening for GBS colonization at 35 to 37 weeks’ gestation and intrapartum prophylaxis with penicillin or ampicillin for colonized women. After implementation of guidelines, the incidence of early-onset GBS infection dropped by 80% from a rate of 1.7/1000 live births in 1993 to 0.34/ 1000 live births in 2004. Although the decline was steepest in the mid-1990s, universal screening guidelines in 2002 led to a 33% further decline by 2004. The overall disease incidence has been below the Healthy People 2010 objective of 0.5 cases per 1000 live births since 1999, but the incidence among black infants remains more than twice that of white infants. It is unknown whether there will be further reduction in disease incidence using current guidelines. The gains from universal screening are close to predicted benefits that led to issuance of the 2002 guidelines. A multistate CDC-sponsored review of labor and delivery records from 2003 and 2004 will shed light on missed opportunities for prevention. With intrapartum prophylaxis, the proportion of women exposed to intrapartum antibiotics has more than doubled. Although -lactam resistance has not been reported for GBS, ampicillin resistance has emerged among Gram-negative pathogens. Thus, is use of intrapartum antibiotics simply replacing GBS sepsis with other potentially more severe causes of neonatal sepsis? To evaluate this question, we turn to 3 sources of evidence: trends in allcause neonatal sepsis during the GBS prevention era, trends in pathogen-specific neonatal sepsis, and evaluations of the association between intrapartum antibiotic exposure and early-onset sepsis risk. Trends in all-cause sepsis are of interest because most neonatal sepsis is not culture-confirmed, and the proportion of infants with “clinical sepsis” may have increased with widespread intrapartum antibiotic use. A recent evaluation of US trends in neonatal sepsisassociated deaths using linked birth and infant death certificate files found a declining rate of sepsis-associated deaths at less than 7 days of age from 1995 through 1998, a period of active GBS prevention. A similar evaluation of trends in neonatal sepsis-associated hospitalizations using national hospital discharge data reported a declining rate of neonatal sepsis-associated hospitalizations from 1990 through 2002. However, whereas the rate among preterm infants declined steadily throughout the 1990s and may reflect other changes in preterm management such as the licenFrom the *National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA; and †Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA. Copyright © 2006 by Lippincott Williams & Wilkins ISSN: 0891-3668/06/2510-0939 DOI: 10.1097/01.inf. 0000239267.42561. 06 CONTENTS Early-Onset Neonatal Sepsis Trends Interferon-Gamma for TB Diagnosis