Infants less than or equal to 56 days of age were eligible for inclusion if they had a lumbar puncture performed as part of their emergency department evaluation between January 1, 2005 and June 30, 2007. Children in this age range were selected as they routinely undergo lumbar puncture when presenting with fever at our institution.28 (link), 29 (link) Patients undergoing lumbar puncture in the emergency department were identified using two different data sources to ensure accurate identification of all eligible infants: 1.) Emergency department computerized order entry records identified all infants with cerebrospinal fluid testing (including CSF gram stain, culture, cell count, glucose or protein) performed during the study period, and 2.) Clinical Virology Laboratory records identified all infants in whom CSF herpes simplex virus or enterovirus PCR testing was performed. Medical records of infants identified by these two sources were reviewed to determine study eligibility.
Figure 1 outlines major exclusion criteria used to derive the reference group. Patients were excluded sequentially if the lumbar puncture was traumatic or a condition known or suspected to cause CSF pleocytosis was present. In a traumatic lumbar puncture, the presence of red blood cells in the CSF alters WBC counts, and adjustment formulas cannot reliably approximate the actual values.30 (link)–33 (link) Conditions known or suspected to cause CSF pleocytosis include stroke, hydrocephalus, seizure on presentation, ventricular shunt or previous intracranial infection, congenital infection, herpes simplex virus meningoencephalitis, and bacterial meningitis.34 (link)–36 (link) Patients with serious bacterial illness including bacteremia, urinary tract infection, osteomyelitis, septic arthritis, pneumonia and bacterial gastroenteritis were also excluded as studies have identified CSF pleocytosis with non-central nervous system infections.36 (link)–38 (link) Infants may have met more than one of the exclusion criteria.
The remaining infants were divided based on whether or not testing for enterovirus was performed in the CSF by polymerase chain reaction and, if performed, whether the test result was positive or negative. Details of our approach to enterovirus PCR testing have been published previously.39 (link) As viral meningitis can cause CSF pleocytosis, patients with a positive CSF enterovirus PCR were excluded from the reference group.40 (link), 41 (link) While previous studies have examined preterm infants separately from term infants, CSF WBC counts are influenced by postnatal rather than postgestational age.42 (link) Our primary analysis, therefore, combined preterm and term infants into a single group.
The remaining infants were divided based on whether or not testing for enterovirus was performed in the CSF by polymerase chain reaction and, if performed, whether the test result was positive or negative. Details of our approach to enterovirus PCR testing have been published previously.39 (link) As viral meningitis can cause CSF pleocytosis, patients with a positive CSF enterovirus PCR were excluded from the reference group.40 (link), 41 (link) While previous studies have examined preterm infants separately from term infants, CSF WBC counts are influenced by postnatal rather than postgestational age.42 (link) Our primary analysis, therefore, combined preterm and term infants into a single group.
