50 Years Ago in The Journal of Pediatrics: Early Onset Sepsis, Progress in Incidence, but Little in Diagnostics, Treatment, or Outcome

Sarah S. Long

doi:10.1016/j.jpeds.2019.10.003

Overall JC, Jr. Neonatal Bacterial Meningitis: Analysis of Predisposing Factors and Outcome Compared with Matched Control Subjects J Pediatr 1970;76:499-511 and Fulginiti VA. Bacterial Infections in the Newborn Infants (Editorial). J Pediatr 1970;76:646-8 Overall reports a multicenter collaborative prospective study under the leadership of the Perinatal Research Branch of the National Institutes of Health.1 Begun in 1959, 54 535 live births were identified prospectively to determine the incidence, risks, clinical manifestations, mortality, and 7-year neurologic sequelae of bacterial meningitis occurring in the first 28 days of life. Controls matched by institution and birth weight were entered 2:1 for the 25 cases of meningitis and both groups were followed similarly. Remarkably, placentas were universally examined grossly and microscopically. The incidence of neonatal bacterial meningitis was 0.46 per 1000 live births. Cases, compared with controls, were substantially more likely to have low birth weight, complications of labor and delivery, eg, maternal infection such as urinary tract infection and especially chorioamnionitis, and signs of fetal distress. Clinical manifestations in the neonate were nonspecific. Most cases were due to coliform bacteria. Overall fatality was 60% and was associated with low birth weight (88%), severe neurologic abnormalities (but not seizures) acutely, and low peripheral white blood cell count. Long-term neurologic sequelae occurred in 50% of survivors. Data and analysis from this study led to the “truths” about neonatal infection that were widely held for the next 4 decades and on which tenants of management were based. Since then much has changed—emergence of group B Streptococcus and then its prevention of early-onset disease by intrapartum antibiotic prophylaxis, as well as aggressive changes in obstetrical care that drastically reduced the risks of fetal distress. Much has not changed—the lack of highly predictive clinical or laboratory markers of infection, and management and morbidity of neonatal meningitis should it occur. Modern studies generally replicative of Overall's show poor predictive value of chorioamnionitis for early-onset infection in infants born near term and challenge algorithmic reflexive use of antibiotics.2 Editorialist Vincent A. Fulginiti presciently identified the provider's dilemma of urgent administration of an antibiotic to an infected infant while avoiding use in an uninfected infant.3 He also highlighted the contribution that only can be made by such a large prospective comprehensive study. This reader also was struck by the ambitious undertaking of this decade-long study across 14 institutions and >45 000 births, all before electronic records. Dr Overall went on to have a lengthy and important career in infectious diseases, and Dr Fluginiti was a visionary leader in pediatric education, research, and bioethics.

50 Years Ago in The Journal of Pediatrics: Early Onset Sepsis, Progress in Incidence, but Little in Diagnostics, Treatment, or Outcome

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50 Years Ago in The Journal of Pediatrics: Early Onset Sepsis, Progress in Incidence, but Little in Diagnostics, Treatment, or Outcome

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