Defining cerebrospinal fluid white blood cell count reference values in neonates and young infants

Abstract

Objective: Cerebrospinal fluid (CSF) white blood cell (WBC) counts for neonates and young infants are usually interpreted on the basis of values reported in reference texts or handbooks; however, current reference texts either present normal CSF parameters without citation or cite studies with significant limitations. The objective of this study was to determine accurate, age-specific reference values for CSF WBC counts in a large population of neonates and young infants.

Methods: This cross-sectional study included patients who were aged < or =56 days and had a lumbar puncture performed in the emergency department from January 1, 2005, to June 30, 2007. Patients were excluded from analysis for conditions that are suspected to cause CSF pleocytosis, including traumatic lumbar puncture, serious bacterial infection, congenital infection, seizure, and presence of a ventricular shunt. Children who tested positive for enterovirus (EV) in the CSF by polymerase chain reaction were also excluded. Two-sample Wilcoxon rank-sum tests were used to compare median CSF WBC values of those who had negative EV testing with those who did not have EV testing.

Results: A total of 380 (36%) of 1064 patients met inclusion criteria; 54% were male, 15% were preterm, and 39% presented during EV season. The median CSF WBC count was significantly higher in infants who were aged < or =28 days (3/microL, 95th percentile: 19/microL) than in infants who were aged 29 to 56 days (2/microL, 95th percentile: 9/microL; P < .001). In both age groups, infants with a negative EV PCR had a higher upper bound of the 95% confidence interval of the mean values compared with infants who did not have EV testing performed.

Conclusions: We determined age-specific CSF WBC reference values in a large cohort of neonates and young infants that can be used to interpret accurately the results of lumbar punctures in this population.

Figure 1

Infants ≤56 days of age presenting to an emergency department with an indication for lumbar puncture and indication for exclusion from the study population.

Figure 2

Figure 2a. Patients ages 0–28 days stratified by CSF EV PCR status and season. Group I represents neonates who tested negative for enterovirus by PCR during all seasons. Group II represents neonates who were not tested for enterovirus, during enterovirus season. Group III represents neonates who were not tested for enterovirus outside of enterovirus season. On each box plot, the box spans the interquartile range (IQR), the horizontal line through the box is the median value, and the whiskers denote outlying values, defined by convention as 1.5 IQRs lower than the first quartile and 1.5 IQRs higher than the third quartile. Dots represent individual patient values that fall beyond 1.5 IQRs. Data from two patients with CSF WBC values of 320/mm³ and 198/mm³ are not shown for clarity of presentation. Figure 2b. Patients ages 29–56 days stratified by CSF EV PCR status and season. Group I represents infants who tested negative for enterovirus by PCR during all seasons. Group II represents infants who were not tested for enterovirus, during enterovirus season. Group III represents infants who were not tested for enterovirus outside of enterovirus season. On each box plot, the box spans the interquartile range (IQR), the horizontal line through the box is the median value, and the whiskers denote outlying values, defined by convention as 1.5 IQRs lower than the first quartile and 1.5 IQRs higher than the third quartile. Dots represent individual patient values that fall beyond 1.5 IQRs. Data from two patients with CSF WBC values of 34/mm³ and 43/mm³ are not shown for clarity of presentation.

Figure 2

Figure 2a. Patients ages 0–28 days stratified by CSF EV PCR status and season. Group I represents neonates who tested negative for enterovirus by PCR during all seasons. Group II represents neonates who were not tested for enterovirus, during enterovirus season. Group III represents neonates who were not tested for enterovirus outside of enterovirus season. On each box plot, the box spans the interquartile range (IQR), the horizontal line through the box is the median value, and the whiskers denote outlying values, defined by convention as 1.5 IQRs lower than the first quartile and 1.5 IQRs higher than the third quartile. Dots represent individual patient values that fall beyond 1.5 IQRs. Data from two patients with CSF WBC values of 320/mm³ and 198/mm³ are not shown for clarity of presentation. Figure 2b. Patients ages 29–56 days stratified by CSF EV PCR status and season. Group I represents infants who tested negative for enterovirus by PCR during all seasons. Group II represents infants who were not tested for enterovirus, during enterovirus season. Group III represents infants who were not tested for enterovirus outside of enterovirus season. On each box plot, the box spans the interquartile range (IQR), the horizontal line through the box is the median value, and the whiskers denote outlying values, defined by convention as 1.5 IQRs lower than the first quartile and 1.5 IQRs higher than the third quartile. Dots represent individual patient values that fall beyond 1.5 IQRs. Data from two patients with CSF WBC values of 34/mm³ and 43/mm³ are not shown for clarity of presentation.