Normal Values for Cerebrospinal Fluid in Neonates: A Systematic Review

Abstract

<b><i>Background:</i></b> The diagnosis of neonatal meningitis often rests on microscopic and biochemical findings in the cerebrospinal fluid (CSF). There is ongoing uncertainty about age-related normal values for CSF findings in neonates, and many previous studies have included infants in whom antibiotics were administered before lumbar puncture or in whom viral meningitis was not excluded. <b><i>Methods:</i></b> A systematic search was done using MEDLINE and EMBASE to identify original studies which investigated CSF normal values in either healthy neonates or febrile neonates in whom bacterial and viral meningitis were reliably excluded. <b><i>Results:</i></b> We identified seven studies investigating 270 term and 96 preterm neonates. There were minimal differences between preterm and term neonates in the CSF white blood cell (WBC) count and glucose concentration. In contrast, the CSF neutrophil count and protein concentration were influenced by gestational and chronological age. In the four studies that reported individual patient data, in 95% of cases the CSF WBC count was <12 cells/μL in preterm and <10 cells/μL in term neonates, the neutrophil count was <16 and 8 cells/μL, and the protein concentration was <210 and 110 mg/dL, respectively. <b><i>Conclusion:</i></b> The normal range for CSF parameters in neonates is different to that in older infants, and some parameters are influenced by gestational and chronological age. CSF parameters alone are not sufficiently reliable to exclude meningitis.

Meta-analysis of Cerebrospinal Fluid Cell Count and Biochemistry to Diagnose Meningitis in Infants Aged < 90 Days

“…A recent systematic review and meta-analysis pooled data on studies investigating the normal values of CSF cytochemistry in healthy neonates or febrile neonates where meningitis was excluded. 18 Based on limited individual patient data from four studies, they reported the 95th centiles of CSF WBC and protein as 10 cells/mm 3 and 110 mg/dL, respectively, in term neonates and 12 cells/mm 3 and 210 mg/dL in preterm neonates. Although this reaffirms that CSF cytochemistry levels in neonates differ from older children, diagnostic thresholds for CSF cytochemistry could not be derived from such an analysis in neonates without meningitis.…”

“…blood-brain barrier, the reference ranges of CSF cytochemistry are different in neonates and young infants compared to children and adults 17 . Recently, normative ranges were derived from studies on nearly asymptomatic neonates, but these values cannot be used as thresholds for diagnosing bacterial meningitis in symptomatic neonates 18 . Newer CSF biomarkers have been evaluated in a limited number of studies, but these are not yet ready for introduction in clinical practice [19][20][21][22][23][24] .…”

“…A recent systematic review and meta-analysis pooled data on studies investigating the normal values of CSF cytochemistry in healthy neonates or febrile neonates where meningitis was excluded 18 . Based on limited individual patient data from 4 studies, they reported the 95 th centiles of CSF WBC and protein as 10 cells/mm 3 and 110 mg/dl, respectively, in term neonates and 12 cells/mm 3 and 210 mg/dl in preterm neonates.…”

“…17 Recently, normative ranges were derived from studies on nearly asymptomatic neonates, but these values cannot be used as thresholds for diagnosing bacterial meningitis in symptomatic neonates. 18 Newer CSF biomarkers have been evaluated in a limited number of studies, but these are not yet ready for introduction in clinical practice. [19][20][21][22][23][24] Although many studies on the role of CSF cytochemistry in neonates and young infants have been published, the thresholds used varied widely across the studies.…”

Challenges in Diagnosis and Treatment of Neonatal Ventriculitis: A Case Report and Systematic Review of Difficult-to-Treat Central Nervous System Infection Resistant to Conventional Therapy

“…53 The reference values are 20 to 22 CSF WBCs/μL (neutrophils <2-8 cells/μL), CSF protein <150 mg/dL (preterm neonates) and <100 mg/dL (term neonates), and CSF glucose >30 mg/dL (preterm neonates) and >36 mg/dL (term neonates). 54 However, these recommendations are based on studies that included neonates who had received antibiotics prior to LP or had not reliably excluded viral meningitis. Also, biochemical and/or cytological CSF evaluation or negative cultures may not exclude infection.…”