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Cerebrospinal Fluid Reference Values For Young Infants Undergoing Lumbar Puncture
Cerebrospinal Fluid Reference Values For Young Infants Undergoing Lumbar Puncture
Cerebrospinal Fluid Reference Values For Young Infants Undergoing Lumbar Puncture
OBJECTIVES: To determine age-specific reference values and quantify age-related changes abstract
for cerebrospinal fluid (CSF) white blood cell (WBC) counts and protein and glucose
concentrations in infants ≤60 days of age.
METHODS: This multicenter, cross-sectional study included infants ≤60 days old with CSF
cultures and complete CSF profiles obtained within 24 hours of presentation. Those with
conditions suspected or known to cause abnormal CSF parameters (eg, meningitis) and
those with a hospital length of stay of >72 hours were excluded. Reference standards were
determined for infants ≤28 days of age and 29 to 60 days of age by using the third quartile
+1.5 interquartile range for WBC and protein and the first quartile −1.5 interquartile range
for glucose. CSF parameter centile curves based on age were calculated by using the LMST
method.
RESULTS: A total of 7766 patients were included. CSF WBC counts were higher in infants ≤28
days of age (upper bound: 15 cells/mm3) than in infants 29 to 60 days of age (upper bound:
9 cells/mm3; P < .001). CSF protein concentrations were higher in infants ≤28 days of age
(upper bound: 127 mg/dL) than in infants 29 to 60 days of age (upper bound: 99 mg/dL;
P < .001). CSF glucose concentrations were lower in infants ≤28 days of age (lower bound:
25 mg/dL) than in infants 29 to 60 days of age (lower bound: 27 mg/dL; P < .001).
CONCLUSIONS: The age-specific CSF WBC count, protein concentration, and glucose
concentration reference values identified in this large, multicenter cohort of infants can be
used to interpret the results of lumbar puncture in infants ≤60 days of age.
single-center study of 380 infants, of age. In a single-center study of 60 days of age. These numbers are
Kestenbaum et al6 defined the CSF 596 infants, Byington et al4 presents similar to the upper bound that we
WBC count upper bounds at 15 CSF WBC count upper bounds of defined in our larger, multicenter
cells/mm3 for infants ≤28 days of age 18 cells/mm3 for infants ≤28 days of study (≤28 days: 15 cells/mm3;
and 4 cells/mm3 for those 29 to 56 days age and 9 cells/mm3 for those 29 to 29–60 days: 9 cells/mm3).
For CSF protein concentration, has previously been quantified. Shah negative for enterovirus may have
Byington et al4 defined the upper et al7 found a 6.8% decrease (95% been infected with other viruses.
limits at 131 mg/dL for infants ≤28 confidence interval: 5.4%–8.1%) in CSF To mitigate the potential impact of
days and 106 mg/dL for infants protein concentration for each 1-week this limitation, we excluded infants
29 to 60 days of age, which were increase in age. Our study shows that with observations falling 2 SDs
marginally higher than our upper- the weekly percentage decrease in above or below our sample median.
limit values of 127 mg/dL and 99 median CSF protein concentrations We also repeated analyses in the
mg/dL, respectively. In a single- depends on age, with a higher decrease subset of infants who tested negative
center analysis of 375 infants, Shah during the first few weeks of life. The for enterovirus. Furthermore, the
et al7 defined normative CSF protein provided smoothed centile distribution inadvertent inclusion of infants
concentrations using 95th percentile by age for each CSF parameter can with enterovirus infection (ie, those
values (≤28 days: 115 mg/dL; serve as a reference for evaluating who were not tested) may not
29–56 days: 89 mg/dL). Although WBC counts, protein concentrations, meaningfully influence our findings
we included infants up to 60 days of and glucose concentrations for because up to 41% of young infants
age, our 95th percentile values for infants. Given an infant’s age and CSF with enterovirus infection lack CSF
CSF protein concentration are similar WBC count, one can determine the pleocytosis.39 Second, data on the
(≤28 days: 118 mg/dL; 29–60 days: approximate percentile of the value time of antibiotic administration
91 mg/dL). on the basis of this reference sample. relative to bacterial culture
For example, an infant aged 7 days attainment were not available, which
Compared with the lower limits of
with a WBC count of 5 cells/mm3 might have caused an inadvertent
normal defined by Byington et al4
would be at the median (or the 50th inclusion of infants with pretreated
(≤28 days: 30 mg/dL; 29–60 days:
percentile), but a WBC count of invasive bacterial infection and
30.5 mg/dL), the CSF glucose
20 cells/mm3 would be > 95th negative blood and CSF culture
concentration lower bounds defined
percentile, indicating a potential need results. Furthermore, we could
in our study are marginally more
for further workup and/or referral. not identify children with certain
liberal (≤28 days: 25 mg/dL; 29–60
concomitant invasive bacterial
days: 27 mg/dL).
This study has several limitations. infections (eg, osteomyelitis with
We were further able to model the First, we may have included infants negative blood culture results)
age-related decline in CSF WBC counts with viral meningitis. CSF testing for or congenital infections (eg,
and protein concentrations and the viruses was not routinely performed, cytomegalovirus). We believe that
age-related increase in CSF glucose and data regarding other viral testing these children would likely have
concentrations in the centile estimation or examination findings that are been excluded on the basis of our
by using the LMST method. These age- consistent with viral disease were exclusion of children with a length
related changes have previously been not available. Additionally, higher of stay >3 days. Third, the infants
observed and described, but only the CSF WBC counts may have prompted in this study received LP for a
decline in CSF protein concentrations enteroviral testing, and those testing clinical indication (eg, fever or other
transfer from other sites, and reviewed and revised the manuscript; Drs Nigrovic and Freedman contributed to the study design, supervised data collection
locally and nationally, and reviewed and revised the manuscript; Drs Garro, Balamuth, Mistry, Arms, Ishimine, and Kulik collected data at their sites and reviewed
and revised the manuscript; Dr Neuman helped conceptualize and design the study and reviewed and revised the manuscript; Dr Shah conceptualized and
designed the study, supervised the interpretation of the data, and drafted the initial manuscript; and all authors approved the final manuscript as submitted.
DOI: https://doi.org/10.1542/peds.2017-3405
Accepted for publication Dec 1, 2017
Address correspondence to Joanna Thomson, MD, MPH, Division of Hospital Medicine, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, MLC 9016,
Cincinnati, OH 45208. E-mail: joanna.thomson@cchmc.org
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2018 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: The network data center managed by the Baylor University College of Medicine was supported by the Section on Emergency Medicine of the American
Academy of Pediatrics and the Baylor University College of Medicine. Dr Freedman is supported by the Alberta Children’s Hospital Foundation’s Professorship
in Child Health and Wellness. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data;
preparation, review, or approval of the article; or decision to submit the article for submission.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
*The investigators of the Pediatric Emergency Medicine Collaborative Research Committee (PEM CRC) HSV Study Group collaborated on this manuscript; the
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