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Lumbar Puncture in the Neonate:

Challenges in Decision Making and Interpretation


Lakshmi Srinivasan, MBBS,* Mary C. Harris, MD,* and Samir S. Shah, MD, MSCE

Multiple studies have provided normative ranges for cerebrospinal uid (CSF) parameters
in term and preterm infants and described changes with advancing postnatal age, as well
as in special circumstances, such as traumatic lumbar puncture (LP), previous antibiotic
administration, seizures, and concomitant infections at other sites. Although guidelines
exist for the interpretation of CSF parameters in neonates, there appears to be no single
combination of parameters that conclusively excludes meningitis. It remains important for
clinicians to perform LPs early in the course of illness, ideally before the administration of
antibiotic therapy. This review presents currently available literature on the indications for
LP as well as guidelines for the interpretation of CSF parameters in neonates.
Semin Perinatol 36:445-453 2012 Elsevier Inc. All rights reserved.
KEYWORDS neonate, cerebrospinal uid, lumbar puncture
B
acterial meningitis is a serious infection that occurs more
commonly in neonates than in any other age group, and
is associated with signicant morbidity and mortality.
1-3
The
signs and symptoms of neonatal meningitis are often subtle
and nonspecic, leading to challenges in decision making
regarding when to perform a lumbar puncture (LP). Some
physicians may choose to perform LPs on all neonates who
receive a sepsis workup, but are sometimes forced to defer
the procedure because of cardiorespiratory instability. Oth-
ers may adopt a more selective approach, performing LPs
only on infants with specic symptoms, positive blood cul-
tures, or other concerning ndings.
In addition, interpretation of LP results is fraught with
several issues. A large proportion of neonates receive antibi-
otics before the performance of the LP, decreasing the yield of
the cerebrospinal uid (CSF) culture.
4
Clinicians must then
rely on interpretation of CSF parameters (eg, white blood cell
count [WBC], protein, glucose) rather than culture to deter-
mine whether the neonate has bacterial meningitis. However,
many factors are known to alter normative ranges of these
parameters in neonates, including gestational age, postnatal
age, and traumatic LPs. Several studies of CSF reference
ranges have examined specic subpopulations, such as
healthy neonates, neonates receiving an LP as part of a sepsis
evaluation in the emergency department or in the neonatal
intensive care unit (NICU), or have addressed questions,
such as the effect of increasing postnatal age, and the effect of
a traumatic LP.
In this review, we summarize recent literature regarding
the indications for performance of LPs in neonates and pro-
vide guidelines for the interpretation of CSF parameters in a
variety of common clinical scenarios.
When to Perform
a Lumbar Puncture?
Early-onset sepsis, dened as sepsis occurring within the rst
72 hours of life, occurs in 0.3%-0.4% of neonates. Several
observational studies have examined the incidence of men-
ingitis among neonates evaluated for early-onset sepsis. Vis-
ser and Hall
5
showed that bacterial meningitis was present in
30% of neonates with culture-proven early-onset sepsis and
further demonstrated that 15% of cases of meningitis oc-
curred in the absence of positive blood cultures. In a large
retrospective study of 160,000 neonates born at U.S. army
hospitals from 1988 to 1992, Wiswell and colleagues
6
deter-
mined that the incidence of bacterial meningitis was 0.25 per
1000 live births. If LPs had been performed based on selected
criteria (eg, clinical ndings suggestive of central nervous
system infection) rather than in all neonates with early-onset
sepsis, the diagnosis would have been missed or delayed in
*Department of Pediatrics, The Childrens Hospital of Philadelphia, Phila-
delphia, PA.
Division of Hospital Medicine, Cincinnati Childrens Hospital Medical
Center, Cincinnati, OH.
Address reprint requests to Samir S. Shah, MD, MSCE, 3333 Burnet Avenue,
ML 9016, Cincinnati Childrens Hospital Medical Center, Cincinnati,
OH 45229. E-mail: Samir.shah@cchmc.org
445 0146-0005/12/$-see front matter 2012 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1053/j.semperi.2012.06.007
Table 1 Studies of CSF Parameters in Term Infants
Study n Age (Days)
CSF WBC (cells/cu.mm) CSF Protein (mg/dL) CSF Glucose (mg/dL)
Median Mean (SD) Upper Limit Median Mean (SD) Upper Limit Median Mean (SD) Lower Limit
Stewart, 1928 10 0-90 23 34* 32 54* 56 42
Widell, 1958 31 0-14 7.5 15* 77 119*
Naidoo, 1968 135 0-1 12 36* 63 240* 51 32
20 7 3 9* 47 65* 55 48
Sarff et al, 1976 87 Most <7 5 8.2 (7.1) 32* 90 170* 52 34
Pappu et al, 1982 46 1-32 LBW: 7; normal
BW: 11
LBW: 28*; normal
BW: 38*
180*
Portnoy and Olson,
1985
64 0-42 3.7 (3.4) 5.2
Bonadio et al, 1992 35 0-28 8.5 11 (10.4) 22 84 (45.1) 46 (10.3)
40 29-56 4.5 7.1 (9.23) 15 59 (25.3) 46 (10.1)
Carraccio et al,
1995
95 0-30 5 6.9 (8) 8.5;
19
67 (32)
Ahmad, 1996 108 0-30 4 7.3 (14) 130*;
11
64.2 (24.2) 51.2 (12.9)
Wong et al, 2000 99 0-60 60 59 (21) 110*;
87

43 0-60 (EV-PCR negative) 62 61 (24)
Garges et al, 2006 9111 0-150 6 90,000*; 15 103 4122*; 142 49 0;
43**
Kestenbaum et al,
2010
142 0-28 3 9.2 (32.1) 6;
12;
19

238 29-56 2 3.1 (5) 3;
6;
9
Shah et al, 2011 52 0-14 78 79 (23) 93;
106;
132

87 15-28 65 69 (20) 85;
95;
100

110 29-42 55 58 (17) 65;
79;
89

126 43-56 50 53 (17) 62;
75;
83

4
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16 of 43 infants with culture-proven bacterial meningitis.
However, a recent large retrospective study reafrmed that in
the current era of maternal Group B Streptococcus (GBS)
prophylaxis, early-onset sepsis was associated with lower
rates of meningitis as compared with late-onset GBS disease.
7
Other recent studies have suggested that in the asymptomatic
infant being evaluated purely because of risk factors, the in-
cidence of bacterial meningitis is very low.
8-10
In line with
these ndings, the most recent American Academy of Pedi-
atrics guidelines for prevention of perinatal GBS disease rec-
ommend a full diagnostic evaluation, including LP in infants
with signs of neonatal sepsis, while advocating more limited
evaluations for infants with risk factors in the absence of
clinical signs of sepsis.
11
In the evaluation of infants for late-onset sepsis occurring
beyond the rst 72 hours of life, there has been similar con-
troversy over whether to routinely perform LPs as part of the
diagnostic evaluation. Some investigators have argued for a
selective approach to the performance of the LP, limiting it to
infants with positive blood cultures and absence of signs
localizing the infection to specic organs.
12
However, there is
considerable evidence that bacterial meningitis in the setting
of late-onset sepsis often occurs without positive blood cul-
tures. In a large retrospective analysis of the Eunice Kennedy
Schriver National Institute of Child Health and Human De-
velopment database, Stoll and colleagues reported that up to
one-third of very low birth-weight infants with culture-
proven bacterial meningitis have negative blood cultures.
2
Similarly, Ansong et al
7
reported that blood cultures were
negative in 9 (20%) of 46 infants with GBS meningitis. Large
retrospective multicenter studies have also found that 30%-
38% of infants with bacterial meningitis had negative blood
cultures.
13,14
These data suggest that it may be prudent to
perform an LP, when possible, in neonates with suspicion of
late-onset sepsis.
Normative Ranges
for CSF Parameters
Exclusion of the diagnosis of bacterial meningitis requires
comparison against established normative ranges of CSF pa-
rameters. However, development of these reference ranges in
neonates is complicated by a number of factors. Ethically, it is
not appropriate to obtain CSF samples from neonates with-
out indication, as the LP is an invasive procedure and in-
formed consent, or even assent, is not possible. Therefore,
normative ranges are dened using patients with indications
for LP, and this selection bias may inuence the normative
values that are obtained. However, this approach is clinically
sensible as we are often more interested in differentiating
infants with serious illness from those with benign and self-
limiting conditions, rather than from healthy patients. Other
challenges to the development of reference ranges relate to
the wide range of values seen in neonates, leading to consid-
erable overlap between normal and abnormal, as well as the
changes that occur with differing gestational and postnatal
ages. T
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Lumbar puncture in the neonate 447
The earliest studies examining normative CSF parameters
were limited by small sample sizes and poorly dened inclu-
sion and exclusion criteria. Several did not clearly mention
culture results or whether the LPs were traumatic.
15-19
More
recent studies have evaluated larger populations of neonates
in the NICU or in the emergency department to establish
normative ranges.
13,14,20-24
Studies from the emergency de-
partment have typically examined CSF parameters in neo-
nates undergoing LP as part of a standard evaluation of fever.
In several recent studies, the results of enterovirus polymer-
ase chain reaction (PCR) testing have been included to im-
prove the stringency of inclusion criteria.
20-22,25,26
Tables 1 and 2 provide reference data for CSF parameters
in term and preterm neonates from several studies. The de-
tails and specic limitations of each are characterized in Table
3. Many of the older studies presented data as means and
standard deviations, which may not be the best method to
represent skewed data, such as CSF parameters.
18,19,27
Fur-
ther, these data are not as useful as values that represent the
upper limit of normal, which can help guide clinicians in
their diagnostic decision making. More recent studies have
attempted to dene values representing the upper limit of
normal, such as 90th or 95th percentile values.
20,21,25
An-
other statistically sound method involves applying a stan-
dardized approach to identifying outliers that is less likely to
be affected by small sample sizes. Calculation of 1.5 times the
interquartile range added to the upper interquartile range
(which is equivalent to the 92nd percentile of a logarithmic
distribution) is deemed especially useful for data with outli-
ers.
22,24,28
Garges and colleagues
13
performed one of the largest ret-
rospective studies of CSF parameters to date, using data from
9000 infants. This study revealed that 10% of neonates
with bacterial meningitis had 3 CSF WBC per cu.mm and
also showed that CSF glucose and protein values overlapped
greatly between infants with and without meningitis. No
combination of CSF parameter cut-off values appeared to
provide optimal sensitivity and specicity. For example, a
CSF WBC 21 cells per cu.mm had a sensitivity of 79% and
a specicity of 81%, whereas a CSF protein value of 120
mg/dL had a sensitivity and specicity of 76% and 63%,
respectively.
Some studies have paid special emphasis to the diagnostic
ability of CSF parameters in pretermand/or lowbirth-weight
infants, in whom CSF WBC and protein are often thought to
be higher than in terminfants (Table 2). Among 4632 infants
34 weeks gestation, Smith et al
14
demonstrated that using
traditional cut-off values, such as a CSF WBC 25 cells per
cu.mm, CSF protein 170 mg/dL, and CSF glucose 24
mg/dL, would only identify 26% of preterm infants with
bacterial meningitis. Mhanna et al
29
provided reference
ranges by week of gestational age; however, the number of
infants in each gestational age group was small. Most re-
cently, Srinivasan et al
24
provide a comparison of reference
ranges for CSF parameters from term and preterm infants in
the NICU setting. Most studies in preterm infants consis-
tently showthat CSF protein is higher in pretermversus term
infants. However, contrary to popular belief, CSF WBC
ranges do not seem to be signicantly different between pre-
term and term infants. CSF glucose is also similar across
gestational ages.
18,21,24,29,30
There has been interest in dening the effect of postnatal
age on CSF parameters. Bonadio et al
31
showed that the 90th
percentile value for CSF WBC in the rst 4 weeks of life was
22 WBC per cu.mm, which declined to 15 WBC per cu.mm
between 4 and 8 weeks of life. These ndings have also been
borne out by Kestenbaum et al
21
(95th percentile value at
0-28 days: 19 WBCper cu.mm, at 29-56 days: 9 per cu.mm).
However, Ahmed et al and Srinivasan et al did not nd a
declining trend for CSF WBC with increasing postnatal age,
which may be because of differences in relative sample sizes
at the different postnatal ages, or other characteristics of the
population studied.
24,25
In contrast, every study that has ex-
amined the trend of CSF protein with increasing postnatal
age has noted a decline over time. Shah et al
20
quantied this
as a 6.8%decrease for every additional postnatal week of life.
This decline is thought to be related to increasing maturity of
the bloodbrain barrier or possibly because of changing
amounts of growth factors and other proteins intrinsic to the
CSF. Except for Byington et al, most studies have shown that
CSF glucose does not change signicantly with postnatal age
for the rst weeks to months of life.
Studies have examined other predictive factors related to
CSF WBC, including the proportion of polymorphonuclear
leukocytes in CSF, elevated CSF absolute neutrophil counts,
and the presence of immature neutrophils (bands) in
CSF.
25,32,33
None of these parameters have been shown to be
consistently useful in the diagnosis of bacterial meningitis.
Various investigators have developed clinical prediction rules
incorporating cut-off points for CSF parameters, such as the
bacterial meningitis score, that aid in the diagnosis of pedi-
atric bacterial meningitis.
34-36
However, these studies were
conducted on pediatric subjects who presented to emergency
departments, included very small numbers of neonates, and
were not validated specically in the neonatal population. As
demonstrated by Garges et al,
13
it is difcult to identify a
similar prediction rule in neonates that would help to reliably
exclude bacterial meningitis.
Effect of Traumatic
LPs on Interpretation
of CSF Parameters
Traumatic LPs occur very frequently in neonates, with stud-
ies showing rates of 30%-46%, depending on how the con-
dition was dened.
37-39
A common clinical dilemma involves
the interpretation of the CSF WBCcount froma traumatic LP
and whether to apply a correction factor for the contami-
nation with blood. Suggested approaches to correct the CSF
WBC include using the ratio of 500 or 1000 red blood cell
count (RBC) to 1 WBC, using the ratio of peripheral RBC:
WBC, and/or calculating an observed-to-predicted ratio for
CSF WBC.
40
A large retrospective study of an administrative database
evaluated 6000 neonates, of whom2519 had traumatic LPs
448 L. Srinivasan, M.C. Harris, and S.S. Shah
Table 2 Studies of CSF Parameters in Preterm/VLBW infants
Study n
Age
(Days)
GA/Birth
Weight
CSF WBC (cells/cu.mm) CSF Protein (mg/dL) CSF Glucose (mg/dL)
Median Mean
Upper
Limit Median Mean
Upper
Limit Median Mean
Lower
Limit
Sarff et al, 1976 30 Most <7 6 9 (8.2) 29* 115 150* 50 24
Rodriguez et al,
1990
43 0-84 <1500 g, <33 wks 5 44* 142 370* 6 29
Smith et al, 2008 4632 0-257 <34 wks 6 16 130 172 49 40
Mhanna et al,
2008
243 1-85 25-34 wks 50.4 (23.1) 11
25 wks 14 23* 128 180*
26 wks 4 7* 139 196*
27 wks 7 30* 180 270*
28 wks 7 8* 126 189*
29 wks 8 12* 152 210*
30 wks 8 22* 128 173*
31 wks 6 21* 154 225*
32 wks 5 15* 155 229*
33 wks 13 20* 126 152*
34 wks 8 10* 115 162*
Kestenbaum et al,
2010
57 0-28 <37 wks 3 19
29-56 2 7
Srinivasan et al,
2012
148 0-180 <37 wks 3 6;
16;
14**
104 131;
203;
209**
49 42;
33;
12
Ellipses indicate the value was not reported by study authors.
GA, gestational age; IQR, interquartile range.
*Upper limit of range; lower limit of range; 75th percentile; 25th percentile; 95th percentile; **upper IQR 1.5 IQR; 5th percentile; lower IQR 1.5 IQR.
L
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4
4
9
Table 3 Key Points From Studies of CSF Parameters
Study Comments
Stewart, 1928 Healthy children; did not mention exclusion criteria.
Widell, 1958 Normal children; did not mention traumatic taps as exclusion; CSF WBC higher in rst 3 mo than later.
Naidoo, 1968 Did not mention culture results or traumatic taps.
Sarff et al,
1976
Excluded infants with syphilis, bacterial, or viral meningitis, grossly bloody CSF; found no change in CSF
WBC with postnatal age; included 30 preterm infants.
Pappu et al,
1982
Excluded infants with CSF RBC >500 cells cu.mm; did not comment on gestational age, just used birth-
weight categories.
Portnoy and
Olson,
1985
Excluded positive bacterial or viral CSF cultures; did not specify traumatic LPs; showed that subjects
with seizures did not have higher CSF WBC.
Rodriguez et
al. 1990
Included infants 24-33 wks GA, <1500 g; excluded positive CSF cultures, intraventricular hemorrhage.
Bonadio et al,
1992
Excluded traumatic LPs (>1000 RBC), antibiotics before LP, positive gram stain or bacterial or viral
culture of CSF, positive blood or urine cultures, seizures.
Carraccio et
al, 1995
Excluded traumatic LPs (>1000 RBC), positive bacterial or viral CSF culture, clinical diagnosis of
encephalitis or partially treated meningitis or aseptic meningitis (CSF WBC> 40); CSF WBC lower in
children with seizures.
Ahmad, 1996 Excluded traumatic LPs (>1000 RBC), antibiotics before LP, positive blood, CSF, urine cultures, positive
CSF viral culture, positive CSF enterovirus PCR; no signicant difference between each week of
postnatal age for total CSF WBC, ANC or glucose; protein higher in rst 2 wks, decreasing beyond the
second week.
Wong et al,
2000
Excluded premature infants, traumatic LPs (gross blood or >200 RBC), acute or chronic neurologic or
systemic disease, including infections; used CSF pleocytosis to dene meningitis, thus excluding
infants with higher CSF WBC even in the absence of positive CSF cultures; tested EV-PCR on all
eligible subjects, presented 2 sets of reference ranges based on whether EV-PCR results were used.
Garges et al,
2006
Included infants >34 wks GA; excluded ventricular shunt/tap, likely contaminants; performed subanalysis
with CSF RBC >100 excluded; no combination of parameters could successfully rule out meningitis;
commonly used CSF WBC cut-off of 21 would miss 12.6% cases; limitations: missing data; lack of
information on antibiotic exposure.
Smith et al,
2008
Included only infants <34 wks GA; excluded ventricular shunts, likely contaminants, viral meningitis;
performed subanalysis with CSF RBC >100; if all Harriet lane values abnormal (CSF WBC >25,
glucose <24, protein >170), only 26% sensitivity; limitations: missing data; lack of information on
antibiotic exposure; did not mention inuence of postnatal age.
Mhanna et al,
2008
Included only VLBW infants 25-34 wks GA; excluded major congenital anomaly, intraventricular
hemorrhage, RBC >1000, meningitis, sepsis, repeat LPs; numbers in each gestational age group were
small; CSF WBC and protein did not change with advancing GA, but decreased with advancing
postnatal age; no correlations between CSF glucose and gestational age or postnatal age.
Kestenbaum
et al, 2010
Excluded traumatic LPs, stroke, hydrocephalus, seizures, VP shunt, systemic and intracranial infections,
including HSV and EV; 57 (15%) patients were preterm; 80% had fever at presentation; no difference in
CSF WBC in neonates with and without fever; 11.3% received antibiotics before LP; subjects with
negative EV-PCR testing had higher CSF WBC than subjects without testing; no statistically signicant
differences between term and preterm neonates.
Shah, 2011 Excluded traumatic LPs, serious bacterial infections (meningitis, UTI, bacteremia, pneumonia,
osteomyelitis, septic arthritis), congenital syphilis, EV, HSV, seizures, VP shunt, abnormal CNS
imaging, elevated serum bilirubin; 57 patients were preterm.
Byington,
2011
Excluded antibiotic exposure, oral polio vaccine, positive CSF, blood or urine cultures, EV, HSV, CSF
RBC >1000, outliers; CSF WBC and protein higher in rst month than later; CSF glucose lower in rst
month than later.
Chadwick et
al, 2011
Three cohorts of infants were combined (one cohort did not have CSF protein or glucose values);
excluded positive CSF, urine or blood cultures, positive CSF viral culture or PCR, VP shunt, recent
neurosurgery, antibiotic exposure, <36 wks gestation, seizures, presumptive bacterial infection, CSF
RBC >1000, CSF WBC >100; CSF WBC and protein decreased with increasing age; no change in
CSF glucose with age.
Srinivasan et
al, 2012
Excluded CSF culture positive, or unknown, positive CSF viral PCR (HSV/EV), VP shunts, seizures,
bacteremia, CSF RBC >500; 72% patients were on antibiotics before LP; comments on lack of
clinically relevant effect of antibiotic exposure on CSF parameters; 148 were preterm; CSF WBC and
glucose did not decline with increasing postnatal age, whereas CSF protein did.
EV, enterovirus; EV-PCR, enterovirus polymerase chain reaction; PCR, polymerase chain reaction; HSV, herpes simplex virus; VLBW, very low
birth weight; VP shunt, ventriculoperitoneal shunt; ANC, absolute neutrophil counts; CSF, cerebrospinal uid; LPs, lumbar puncture; UTI,
urinary tract infections.
450 L. Srinivasan, M.C. Harris, and S.S. Shah
(dened as CSF RBC 500 per cu.mm).
37
The study used
both unadjusted and adjusted CSF WBC counts to predict
bacterial meningitis; adjustments were performed using a
variety of the methods listed previously. On comparison of
areas under the receiver operator characteristic curves for
unadjusted and adjusted values, there were no signicant
differences noted. The study further noted that any improve-
ment in specicity or positive predictive value with the use of
adjusted CSF WBC occurred at the cost of sensitivity, thus
potentially leading to missed diagnoses of meningitis. This
conclusion is similar to that of previous studies of traumatic
taps in pediatric subjects that have also questioned the valid-
ity of the various correction factor approaches.
41
A recent
prospective study of 496 infants, 131 of whomhad traumatic
LPs (dened as CSF RBC1000 per cu.mm) demonstrated
that CSF WBC increased by 1 cell for every 3300 RBCs/
cu.mm.
42
This suggests that the use of the 500:1 rule would
overestimate the correction factor because of contamination
by blood. Therefore, it appears that adjustment of CSF WBC
in traumatic LPs does not improve the diagnosis of neonatal
bacterial meningitis. CSF protein may also be elevated in the
presence of blood contamination from a traumatic LP. Hines
and colleagues
43
evaluated 1241 LPs in infants 56 days old
and found that CSF protein rose by 1.9 mg/dL for every
additional 1000 RBC/cu.mm. This nding persisted when
the analysis was limited to infants 28 days old. However,
the sample excluded infants with extremely high CSF RBC
(150,000 per cu.mm), and therefore, these results should
not be extrapolated to situations where the CSF is grossly
bloody.
Other Factors That Could
Inuence Interpretation
of CSF Parameters
Effect of Antibiotic
Pretreatment on CSF Parameters
Antibiotic treatment before the LP is a common occur-
rence.
4,24,44
In a study of 128 pediatric subjects with proven
or probable bacterial meningitis, Kanegaye
4
demonstrated
that CSF sterilization occurs as quickly as 2-4 hours after
initiation of antibiotic therapy. The low yield of CSF cultures
in the face of antibiotic pretreatment leads clinicians to rely
on interpretation of CSF parameters to diagnose meningitis.
However, few studies have attempted to quantify the impact
of antibiotic therapy on CSF parameters. In a large emer-
gency department study of pediatric bacterial meningitis
(proven and probable), 35% of children had received antibi-
otic pretreatment. In subjects exposed to antibiotics for up to
24 hours, CSF WBC values remained elevated without sig-
nicant alteration. CSF protein values decreased over this
period but still remained higher than normative values,
whereas CSF glucose values showed rapid normalization, as
early as 4 hours after initiation of antibiotic therapy.
44
How-
ever, this study did not include neonates. In a recent study of
termand preterminfants in the NICUwithout bacterial men-
ingitis, antibiotic exposed and unexposed infants did not
have clinically relevant differences in CSF parameters, and
there were no associations between CSF parameters and in-
creasing number of days of antibiotic exposure.
24
Effect of Seizures on CSF Parameters
Portnoy and Olson
27
found no signicant difference in CSF
WBC values in infants with and without seizures, whereas
Carraccio et al
45
actually noted CSF WBC to be lower in
infants with seizures. Although the number of studies is
small, it would not appear that seizures are an important
cause of CSF pleocytosis.
Other Systemic Infections
Adler-Shohet et al
46
examined the relationship between uri-
nary tract infections (UTIs) and aseptic meningitis. Among
260 infants 6 months with a UTI who had an LP, 31 infants
(11.9%) had aseptic meningitis (dened by an elevated CSF
WBC count but negative CSF culture), whereas only one had
bacterial meningitis. Only 3 of the infants with aseptic men-
ingitis had received antibiotics before the LP. The authors
hypothesized that systemic inammation or bacterial anti-
gens released fromthe UTI may lead to a sterile pleocytosis.
46
In a more recent study, Shah and colleagues showed that
when traumatic LPs were excluded, and data were collected
fromperiods of lowenteroviral prevalence, there was a much
lower occurrence of CSF pleocytosis in infants with UTI.
These data suggest that CSF pleocytosis reported in associa-
tion with UTI in previous studies may have been attributable
to traumatic LPs or concomitant viral meningitis.
47
Viral Meningitis
As mentioned earlier, recent studies of CSF parameters have
examined results of viral testing to exclude cases of enterovi-
ral meningitis. However, studies have demonstrated that en-
teroviral meningitis is often associated with a lack of CSF
pleocytosis, especially in the youngest, most immature in-
fants.
48
Relying on the results of CSF parameters to make
decisions regarding viral testing may lead to missed diagno-
ses. Therefore, it is prudent to have a low threshold for en-
terovirus PCR and other viral testing when there is suspicion
for viral illness, irrespective of the presence or absence of
elevations of CSF parameters.
Conclusions
CSF parameters are useful adjuncts for the diagnosis of neo-
natal bacterial meningitis. However, despite a large number
of studies on the topic, there is no clinical prediction rule
with optimal sensitivity and specicity in this age group ow-
ing to the wide ranges of CSF parameters and the overlap in
values between infected and uninfected neonates. Newer
broad-range bacterial identication techniques, such as 16S
PCR tests, could potentially add to or improve on the sensi-
tivity of the CSF culture in the diagnosis of bacterial menin-
gitis. However, until such tests become standardized and
incorporated as part of clinical practice, it remains important
Lumbar puncture in the neonate 451
for clinicians to performLPs at the time of suspicion for sepsis
and meningitis, and when clinically feasible, before the initi-
ation of antibiotics. This practice should improve the diag-
nostic yield of the CSF culture, and thus minimize prolonged
antibiotic courses in patients with equivocal CSF results.
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