Evaluation of Microbiologic and Hematologic
Parameters and E-Selectin as Early Predictors for
Outcome of Neonatal Sepsis
Maysaa El Sayed Zaki, MD, PhD; Hesham El Sayed, PhD
● Context.—Early diagnosis of neonatal sepsis is manda-
tory. Various markers are used to diagnose the condition.
Objective.—To evaluate the diagnostic value of various
clinical data and hematologic parameters, such as total
leukocyte count, absolute neutrophil count, immature to
total neutrophil ratio, and soluble E-selectin (sE-selectin) in
identification and outcome of neonatal sepsis.
Design.—Newborn infants with a clinical diagnosis of
sepsis in the neonatal intensive care unit at Mansoura Uni-
versity Children’s Hospital during the period between July
2007 and December 2007 were eligible for study. In ad-
dition, 30 healthy neonates were included in the study.
Complete hematologic and microbiologic laboratory inves-
tigations were performed, and serum E-selectin was mea-
sured.
Results.—Plasma sE-selectin levels were significantly
higher (P ⬍ .001) in infected infants (mean [SD], 156.9
[77.0] ng/mL) than in noninfected (mean [SD], 88.8 [47.1]
ng/mL) and healthy infants (mean [SD], 8.67 [3.74] ng/
M orbidity and mortality from neonatal sepsis are ma-
jor health problems. Early warning signs and symp-
toms are often nonspecific and can easily be confused
with those from noninfective causes. Timely diagnosis of
neonatal sepsis is critical because, in this age group, the
illness can progress more rapidly and have a higher mor-
tality rate than in other age groups.1
Microbiologic culture results are usually unavailable
until a minimum of 48 to 72 hours after the specimen
reaches the laboratory; therefore, early identification of in-
fected cases is a major diagnostic problem in newborn in-
fants. Thus, a reliable infection marker or a set of markers
are needed to promptly and accurately identify the in-
fected cases so that treatment can be started without delay.
Equally difficult is the exclusion of infection in infants
with suspected sepsis. Continuation of broad-spectrum
antibiotics for presumptive bacterial infection frequently
Accepted for publication October 23, 2008.
From the Departments of Clinical Pathology (Dr Zaki) and Pediatric
Medicine (Dr El Sayed), Mansoura University, Mansoura, 65, Egypt.
The authors have no relevant financial interest in the products or
companies described in this article.
Reprints: Maysaa El Sayed Zaki, MD, Department of Clinical Pa-
thology, Faculty of Medicine, Mansoura University, Mansoura, 65,
Egypt (e-mail: may㛮s65@hotmail.com).
Arch Pathol Lab Med—Vol 133, August 2009
mL). Infants with gram-negative sepsis had higher sE-selec-
tin levels than did those with gram-positive sepsis (P ⴝ
.04). C-reactive protein was the best laboratory test for
diagnosis of neonatal sepsis, with an overall sensitivity and
specificity of 86% and 97%, respectively. Performing sE-
selectin with C-reactive protein or immature to total ratio
tests increased the specificity, but reduced the sensitivity,
of the tests for the determination of neonatal sepsis. Plas-
ma sE-selectin levels were higher in nonsurvivors than in
survivors (P ⴝ .01) and were higher in those with hemo-
dynamic dysfunction than in those without hemodynamic
dysfunction (P ⬍ .001).
Conclusions.—We conclude that plasma sE-selectin lev-
els are elevated in neonatal sepsis. Significant elevation
was associated with gram-negative sepsis. Plasma sE-selec-
tin had low diagnostic value when used alone or in com-
bination with other tests; however, it can be used as a prog-
nostic indicator for the outcome of neonatal sepsis.
(Arch Pathol Lab Med. 2009;133:1291–1296)
leads to unnecessary treatment and also to emergence of
multiresistant organisms.2,3
Hematologic and biochemical markers, such as imma-
ture to total neutrophil ratio (I/T),4 platelet count,5,6
C-reactive protein (CRP), various cytokines, procalciton-
in,7 and neutrophil CD648 have all been suggested as use-
ful indicators for early identification of infants with sepsis.
Studies evaluating these parameters as indicators of sepsis
have yielded conflicting results, and satisfactory solutions
remain to be found.
E-selectin is expressed by the endothelium after acti-
vation at sites of acute inflammation and is significant in
migration of neutrophils and some T-cell to the site of in-
jury. It takes part in the first step of the adhesion cascade,
the rolling of leukocytes, leading to the extravasation of
white cells to the sites of inflammation, infection, or dam-
age. The molecule is uniquely displayed only on endothe-
lium and is almost exclusively inducible.9
In human diseases in which unchecked inflammation
contributes to the pathogenesis of disease process, soluble
forms of E-selectin (sE-selectin) are elevated. These eleva-
tions have been interpreted as indicating a role for the
molecules in the pathogenesis of inflammation, as well as
indicating the size of the inflammatory response.10 For this
reason, sE-selectin is considered an early and reliable
marker of immune activation and response. Moreover, sE-
Neonatal Sepsis—Zaki & El Sayed 1291
selectin has been reported to be a reliable marker of in-
fection and sepsis in adults. In infants, soluble E-selectin
responses in neonatal sepsis have been studied to a lesser
extent.11
The aims of this study were (1) to assess microbiologic
and hematologic findings in neonatal sepsis; (2) to deter-
mine whether changes in sE-selectin levels are dependent
on gestational age, onset of sepsis, or the bacterium caus-
ing the sepsis; (3) to establish the diagnostic utility (sen-
sitivity, specificity, predictive values, and likelihood ratio)
of sE-selectin in comparison to commonly used laboratory
markers for sepsis (CRP, I/T ratio, total leukocyte count,
absolute neutrophil count), both individually and in com-
bination, for early diagnosis of neonatal sepsis; and (4) to
test whether sE-selectin levels have any prognostic value
in neonatal sepsis.
MATERIALS AND METHODS
Study Population
Newborn infants with suspected clinical sepsis in the neonatal
intensive care unit at Mansoura University Children’s Hospital
(Mansoura, Egypt) during the period between July 2007 and De-
cember 2007 were eligible for study. Both preterm and full-term
infants were included in the study. Preterm is defined in obstetrics
(American College of Obstetricians and Gynecologists, Washing-
ton, DC) as infants born at 37 weeks of gestation or less. Full-
term is greater than 37 weeks and up to 42 weeks of gestation.
Clinical sepsis was defined as the presence of 3 or more of the
following categories of clinical signs derived from a validated
sepsis score: (1) temperature instability (hypothermia, hyperther-
mia); (2) respiratory (grunting, intercostal retractions, apnea,
tachypnea, cyanosis); (3) cardiovascular (bradycardia, tachycar-
dia, poor perfusion, hypotension); (4) neurologic (hypotonia,
lethargy, seizures); and (5) gastrointestinal (feeding intolerance,
abdominal distension).12 Infants with neonatal asphyxia, meta-
bolic disease, or congenital malformations were excluded. The
infants were recruited into the study at the time of evaluation for
suspected clinical sepsis before the start of antibiotic therapy.
Informed written consent was obtained from the parents of each
infant.
A full laboratory sepsis screen, which included cerebrospinal
fluid analysis and cultures from blood, urine, endotracheal as-
pirate (infants on mechanical ventilation), and indwelling central
lines, was performed. Aerobic bacteria were identified using the
BBL Crystal system (BD, Franklin Lakes, New Jersey). Hemato-
logic and biochemical laboratory parameters, including a com-
plete blood cell, differential white cell, and platelet counts; CRP;
and plasma sE-selectin, were measured at the time of sepsis eval-
uation. Parenteral antibiotics were started immediately after the
samples for the infection screen had been obtained.
Classification of Infants Included in the Study
Three groups were prospectively defined:
● Group 1: The infected group consisted of 58 infants (preterm,
n ⫽ 24 [41%]; full-term, n ⫽ 34 [59%], full-term gestation range,
35–37 weeks) with positive blood culture results.
● Group 2: The noninfected group consisted of 32 infants (pre-
term, n ⫽ 14 [44%]; full-term, n ⫽ 18 [56%]) who were initially
thought to be septic but who had negative blood, cerebrospinal,
and urine culture results; negative radiologic evidence of pneu-
monia or necrotizing enterocolitis; and continued improvement
after antibiotic treatment was stopped.
● Group 3: The control group consisted of 30 healthy, newborn
infants (preterm, n ⫽ 12 [40%]; full-term, n ⫽ 18 [60%]).
Blood samples for CRP, sE-selectin, and creatinine were col-
lected from each child and separated within 30 minutes of col-
lection and were stored at ⫺20⬚C until analysis was done, with
1292 Arch Pathol Lab Med—Vol 133, August 2009
the exception of the samples for CRP, which were analyzed im-
mediately.
Other blood samples were obtained for complete blood cell
counts in an automatic cell counter (Abbott Cell-Dyn 1700 he-
matology analyzer, Abbott Laboratories, North Chicago, Illinois),
and differential counts were performed manually on Wright-
stained blood slides.
Plasma CRP concentrations were measured using an immu-
noturbidimetric method (Human Diagnostics, Wiesbaden, Ger-
many) and were quantified with a spectrophotometer. According
to the manufacturer, the detection limits of the assays for CRP
was 0.1 mg/L. Reference values for healthy neonates, using quan-
titative techniques, are less than 1.6 mg/dL during the first 2
days of life and less than 1 mg/dL for the reminder of the neo-
natal period.13
sE-selectin Assay
Plasma concentrations of sE-selectin were determined using a
CD62E enzyme-linked immunosorbent assay kit (Diaclone Re-
search, Besançon, France). This technique uses a monoclonal an-
tibody that is specific for E-selectin, which is precoated onto the
wells of microtiter strips. Standards, samples, and a human con-
trol were placed into the wells, followed by a polyclonal antibody,
conjugated to horseradish peroxidase, which is specific for E-se-
lectin. After removal of the unbound conjugated antibody, sub-
strates for horseradish peroxidase were added, and the product
was quantified at 450 nm, with a correction by subtraction of
background absorbance at 650 nm. A standard curve was plotted
and sE-selectin concentrations were determined by interpolation
from the curve. The sensitivity, intra-assay coefficient of variance,
and interassay coefficient of variance of the assay were ⬍0.5 ng/
mL, 6.4%, and 4.1%, respectively.
Statistical Analysis
Values are presented as means (standard deviation), median
(range), or the number of subjects and proportions. A 1-way anal-
ysis of variance test and an independent-samples Student t test
were used for group comparisons of normally distributed vari-
ables, and the Kruskal-Wallis test and Mann-Whitney U test were
used for comparisons of variables with skewed distribution. The
␹2 test was used to compare proportions.
The receiver-operator characteristic method was used to deter-
mine the best possible cutoff values for the selection of the best
combination of tests for the diagnosis of neonatal sepsis. The
curves were obtained by plotting sensitivity on the y-axis against
the false-positive rate (1-specificity) on the x-axis for all possible
cutoff values of the tests. From this curve, the best or optimal
cutoff value was determined. Significance was considered when
P ⬍ .05. All statistical tests were performed by SPSS for Windows
Release 10.0.1 (SPSS Inc, Chicago, Illinois).
RESULTS
The clinical characteristics of the study groups are sum-
marized in Table 1. There were no significant differences
in gestational age, birth weight, gender, or postnatal age
at blood sampling among the 3 groups. Early sepsis was
associated with ascending infections during delivery, and
late-onset sepsis was developed in the nursery.
Plasma sE-selectin, CRP, and the I/T ratio in the infect-
ed group were significantly increased compared with the
corresponding values in the noninfected and control
groups of infants (P ⬍ .001 for all; Table 2). In contrast,
no significant differences were detected between the non-
infected group and controls for sE-selectin, total leukocyte
count, absolute neutrophil count, or platelet counts (P ⫽
.06).
Suspected sepsis was confirmed in 58 neonates. Of
these, 42 cases (72%) were due to gram-negative organ-
isms, and 16 cases (28%) were due to gram-positive or-
Neonatal Sepsis—Zaki & El Sayed
 Table 1. Clinical Data of Study Population
Infected (n ⴝ 58), Noninfected (n ⴝ 32), Control (n ⴝ 30),
Characteristic Mean (SD) Mean (SD) Mean (SD) P Value
Birth weight (g) 2367 (828) 2435 (846) 2432 (839) .06
Gestational age (wk) 36.3 (3) 36.6 (3) 36.9 (2.6) .06
Male sex, No. (%) 16 (55) 8 (50) 8 (53) .06
Postnatal age (d) 8.7 (4.5) 8.4 (3.6) 8.8 (3.6) .06

Table 2. Laboratory Characteristics of Study Population

Infected (n ⴝ 58), Noninfected (n ⴝ 32), Control (n ⴝ 30),
Laboratory Test Mean (SD) Mean (SD) Mean (SD) P Value
E-selectin (ng/mL) 156.9 (77.0) 88.8 (47.1) 86.7 (37.4) .001
CRP (mg/L), mean (range) 48.0 (0–96) 0.5 (0–48) 0 (0–8) .001
TLC (1000/mL) 13.8 (9.4) 10.5 (5.1) 9.9 (4.5) .07
ANC 6.9 (4.2) 5.2 (2.0) 4.9 (1.9) .10
I/T ratio 0.30 (0.17) 0.12 (0.11) 0.12 (0.12) .001
Platelet count (1000/mL) 220 (80) 235 (80) 242 (83) .10
Abbreviations: ANC, absolute neutrophil count; CRP, C-reactive protein; I/T, immature neutrophil to total leukocytes count; TLC, total leukocytes
count.

Table 3. Causative Organism in 58 Infants With Sepsis

Gram-Positive Sepsis No. (%) Gram-Negative Sepsis No. (%)
Methicillin-sensitive Staphylococcus aureus 6 (10.3) Klebsiella pneumoniae 24 (41.3)
Coagulase-negative staphylococci 4 (6.9) Pseudomonas aeruginosa 8 (13.8)
Methicillin-resistant Staphylococcus aureus 4 (6.9) Escherichia coli 6 (10.3)
Enterococcus faecalis 2 (3.5) Serratia marscens 2 (3.5)
Enterobacter spp 2 (3.5)
Total associations 16 (27.6) 42 (72.4)

Table 4. The Causative Organisms of Sepsis Table 5. Soluble E-Selectin Levels in Relation to
According to Onset Gestational Age, Onset of Sepsis, Gram Stain of the
Organism, and Prognosis
Onset and Organism No. %
Soluble E-Selectin
Early onset sepsis (n ⫽ 18) Clinical and Laboratory Sorting (␮g/mL),
Escherichia coli 6 33.3 of Patients (No.) Mean (SD) P Value
Klebsiella pneumoniae 10 55.6
Coagulase-negative staphylococci 2 11.1 Infected preterm infants (24) 125.0 (43.4) .10
Infected full-term infants (34) 179.4 (88.1)
Late-onset sepsis (n ⫽ 40)
Early onset sepsis (18) 156.6 (74.4) .07
Methicillin-sensitive Late-onset sepsis (40) 170.0 (79.5)
Staphylococcus aureus 6 15
Gram-negative sepsis (42) 174.0 (81.4) .04
Coagulase-negative staphylococci 2 5
Gram-positive sepsis (16) 111.9 (39.5) .03
Enterococcus faecalis 2 5
Klebsiella pneumoniae 14 35 Homodynamic dysfunction (22) 176.0 (79.7)
Pseudomonas aeruginosa 8 20 No homodynamic dysfunction (36) 96.4 (41.7) .01
Serratia marscens 2 5 Nonsurvivors (16) 188.0 (80.7)
Enterobacter spp 2 5 Survivors (42) 110.5 (61.7) .001
Methicillin-resistant Staphylococcus aureus 4 10

pneumoniae and Escherichia coli, whereas gram-positive coc-

ganisms; 18 infants (31%) had early onset sepsis, and 40
infants (69%) had late-onset sepsis.
Detailed accounts of the organisms are summarized in
Table 3. Klebsiella pneumoniae was the most common or-
ganism (41%) isolated from blood cultures followed by
Pseudomonas aeruginosa (14%), methicillin-sensitive Staphy-
lococcus aureus (10%), Escherichia coli (10%), methicillin-re-
sistant S. aureus (7%), coagulase-negative staphylococci
(7%), Serratia marscens (3%), Enterobacter spp. (3%), and En-
terococcus faecalis (3%). In 32 neonates (noninfected group),
infection was excluded by negative bacterial and fungal
culture findings.
The early onset sepsis was associated with Klebsiella
Arch Pathol Lab Med—Vol 133, August 2009
ci, such as Staphylococcus aureus, was isolated more fre-
quently from late-onset sepsis (Table 4).
In subgroups analyses, neonates with gram-negative
sepsis (n ⫽ 42; 72%) had higher levels of sE-selectin than
did infants with gram-positive sepsis (n ⫽ 16; 28%; P ⫽
.04). Infected preterm infants (n ⫽ 24; 41%) had similar
sE-selectin levels as those of infected full-term infants (n
⫽ 34; 59%; P ⫽ .10). We did not find any significant dif-
ferences for sE-selectin levels when comparing early and
late-onset sepsis subgroups (P ⫽ .07; Table 5).
Higher plasma levels of sE-selectin were found in non-
survivors than in survivors (P ⬍ .001) and in those with
homodynamic dysfunction (defined as a requirement for
Neonatal Sepsis—Zaki & El Sayed 1293
 Table 6. Sensitivity, Specificity, Predictive Values, and Likelihood Ratios of Laboratory Markers in
Early Diagnosis of Neonatal Sepsis
Positive Negative
Sensitivity, Specificity, Predictive Predictive Likelihood Likelihood
Marker Cutoff Value % % Value, % Value, % Positive Negative
CRP 8 mg/L 86 97 96 88 28.7 .11
I/T ratio ⬎0.20 76 87 85 79 5.8 .28
sE-selectin 130 ng/mL 59 87 81 69 4.5 .32
TLC ⬍5 or ⬎20/cm3 48 77 67 62 2.1 .68
ANC ⬍2 or ⬎75/cm3 55 74 67 64 2.1 .61
Platelet count ⬍150/cm3 41 87 50 52 1.1 .99
CRP ⫹ sE-selectin 45 100 100 65 N/A .55
I/T ratio ⫹ CRP 65 100 100 74 N/A .38
I/T ratio ⫹ sE-selectin 55 94 89 69 9.2 .48
Abbreviations: ANC, absolute neutrophil count; CRP, C-reactive protein; I/T, immature neutrophil to total leukocytes count; N/A, data not available;
sE-selectin, soluble E-selectin; TLC, total leukocytes count.

Receiver operating characteristic (ROC)

curves comparing sE-selectin, C-reactive pro-
tein (CRP), and immature to total neutrophil
(I/T) ratio for prediction of neonatal sepsis.

inotropic and vasopressors support) compared with those COMMENT

without homodynamic dysfunction (P ⫽ .01; Table 5).
Table 6 summarizes the sensitivity, specificity, predictive
values, and likelihood ratios of the 5 laboratory markers
and combination of these markers using the different cut-
off values. The receiver operating characteristic curves of
sE-selectin, CRP, and I/T ratio are shown in the Figure.
Comparison of each individual test using the optimal
cutoff values showed that CRP has a higher sensitivity
(86%) and specificity (97%) for detecting neonatal sepsis
than all other laboratory markers.
In contrast, sE-selectin had rather low sensitivity (59%)
and moderate specificity (87%) for detecting infection. The
combination of sE-selectin with either CRP or I/T ratio
and the combination of I/T ratio and CRP slightly im-
proved the specificity and positive predictive value but
significantly lowered the sensitivity and negative predic-
tive value. The areas under the curve were CRP, .89/L
(range, .79–.99/L); I/T ratio, .80 (range, .68–.92); and sE-
selectin, .80 (range, .69–.91).
1294 Arch Pathol Lab Med—Vol 133, August 2009
Early diagnosis of neonatal sepsis is difficult because
the clinical signs are neither uniform nor specific. How-
ever, empirical treatment should not be delayed because
of the high mortality. The inability to adequately exclude
the diagnosis of neonatal sepsis can result in unnecessary
and prolonged exposure to antibiotics. Laboratory tests
used to support diagnosis have shown varied predictive
values.
The data presented here demonstrated several impor-
tant findings relating to the altered functional status fol-
lowing neonatal sepsis. Infected newborn infants had
higher plasma sE-selectin levels compared with nonin-
fected and control infants. This confirms previous reports
indicating elevated sE-selectin in infected adults14 and
neonates.11
Unlike Austgulen et al,15 we have found that levels of
sE-selectin in infected preterm infants were not statisti-
cally different from those in infected term infants. The
Neonatal Sepsis—Zaki & El Sayed
divergent results may be due to differences in the criteria
that were used to classify newborn infants as infected and
the postnatal age of neonates at sampling. Other investi-
gators reported increased levels of sE-selectin in prema-
ture infants with sepsis16 and with persistent inflamma-
tion of chronic lung disease.17 These findings indicate that
the shedding of sE-selectin molecules is a component of
the immune system and infection-induced immune re-
sponse that develops early in gestation.
In the patients in our study, sE-selectin levels were high-
er in patients with gram-negative sepsis than in those with
gram-positive sepsis, suggesting that the endothelium was
more intensely activated in gram-negative than in gram-
positive infections. Moreover, gram-negative bacilli was
isolated mainly from early onset sepsis. The mechanisms
by which the concentrations of soluble adhesion molecules
increase in the plasma during infection with gram-nega-
tive bacilli includes interaction of endotoxin through mem-
brane-specific endotoxin receptors, such as L-selectin and
CD13/CD14, which cause increased production of adhe-
sions molecules like E-selectin. Increased amounts of sE-
selectin in blood may be due to endothelial injury rather
than to mere activation. However, numerous studies have
demonstrated that-E-selectin is shed from cultured endo-
thelial cells that are activated but have no evidence of in-
jury or detachment.18
There is evidence that sE-selectin, as well as other ad-
hesion molecules, remains active once it is shed and can
influence subsequent adhesion in several ways. E-selectin
upregulates neutrophil CD1 1b and the ligand for ICAM1,
the intracellular adhesion molecule 1 gene, enhancing firm
leukocyte attachment and transendothelial migration. Be-
cause recombinant E-selectin can inhibit leukocyte adhe-
sion to endothelium in vitro, it is likely that circulating
E-selectin limits E-selectin–mediated rolling of activated
leukocytes via competitive binding of cell bound ligands,
thus down-regulating the inflammatory response.11
In our study, the cutoff value for sE-selectin in diagnosis
of neonatal sepsis was found to be 130 ng/mL, which is
lower than that reported in previous studies. A 150-ng/
mL cutoff value for sE-selectin in detection of sepsis in
full-term neonates had a sensitivity of 79% and a specific-
ity of 61%.11 On the other hand, a cutoff value for sE-
selectin of 174 ng/mL for detection of late-onset sepsis in
very low birth weight infants gave a sensitivity of 64%
and a specificity of 89% when samples were taken from
infants during the first 24 hours of suspected clinical sep-
sis.
Considering the high mortality and potential morbidity
associated with neonatal sepsis, diagnostic tests with high
sensitivity and negative predictive value are most desir-
able because all infants with sepsis have to be identified.
The lack of reliable clinical signs and laboratory tests often
results in anticipatory antimicrobial treatment. To mini-
mize the unnecessary use of antibiotics in false-positive
cases, tests need to have a reasonably high specificity and
good positive predictive value.
We found that sE-selectin had a low diagnostic sensitiv-
ity and specificity. Measuring CRP had the best sensitivity
(86%) and specificity (97%) for the diagnosis of infection.
The combination of sE-selectin with either CRP or I/T ra-
tio slightly improved the specificity but adversely affected
the sensitivity of these tests, so it cannot be used as a
diagnostic marker of neonatal sepsis. Furthermore, the
likelihood ratio and receiver operating characteristic curve
Arch Pathol Lab Med—Vol 133, August 2009
analysis demonstrated the higher diagnostic value of CRP
and I/T ratio compared with sE-selectin as markers for
sepsis.
C-reactive protein has been thoroughly studied as a di-
agnostic tool in neonatal sepsis and also as an indicator
of response to therapy.19,20 The sensitivity of CRP in initial
determinations for the detection of early onset neonatal
infection has been reported to vary from 35% to 65%, in-
creasing to 94% to 97% by the time of the third determi-
nation. The specificity of CRP varied in initial determi-
nation from 92% to 96% and decreased to 76% to 86% for
the third measurement.21
Our data support the view of some authors that the leu-
kocyte count had little value in differentiating between in-
fected and noninfected neonates.22 Although the specific-
ity of the I/T ratio has been questioned, in our study, we
demonstrated low sensitivities and poor positive predic-
tive values of the I/T ratio and total leukocyte count in
identifying the small number of initially asymptomatic at-
risk newborns who progressed to clinical sepsis. These
results were similar to the results reported by Ottolini et
al.23
We have found that plasma sE-selectin levels were high-
er in nonsurvivors and in those with homodynamic dys-
function. A striking positive relationship among sE-selec-
tin level and concomitant homodynamic dysfunction and
multiple organ failure was reported in adults with sep-
sis.14
Because the intensity of E-selectin expression and shed-
ding appears to correlate with organ hypoperfusion and
dysfunction, inactivation of cell-bound E-selectin might be
expected to ameliorate these problems. In a preliminary
study, administration of a murine monoclonal antibody to
E-selectin to patients with septic shock was well tolerated
and associated with dose-related improvement in oxygen-
ation and trends for faster resolution of organ failure.24
We conclude that plasma sE-selectin levels were elevated
in neonatal sepsis. Plasma sE-selectin had low diagnostic
value when used alone or in combination with other tests.
However, it can be used as a prognostic indicator in neo-
natal sepsis and can be used as clue in predicting that the
causative bacteria in blood culture is gram-negative bac-
teria.
References
1. Gredes JS. Clinicopathologic approach to the diagnosis of neonatal sepsis.
Clin Perinatol. 1991;18(2):361–381.
2. Kocbas E, Sarikeioglu A, Aksaray N, Seydaoglu G, Seyhun Y, Yaman A. Role
of procalcitonin, C-reactive protein, interleukin-6, interleukin-8, and tumor-ne-
crosis factor- alpha in the diagnosis of neonatal sepsis. Turk J Pediatr. 2007;49(1):
7–20.
3. Sinha A, Yokoe D, Platt R. Epidemiology of neonatal infections: experience
during and after hospitalization. Pediatr Infect Dis J. 2003;22(3):244–251.
4. Krediet T, Gerards L, Fleer A, van Stekelenburg G. The predictive value of
C-reactive protein and I/T-ratio in neonatal infection. J Perinat Med. 1992;20(6):
479–485.
5. Berger C, Uhelinger J, Ghelfi D, Blau N, Fanconi S. Comparison of C-re-
active protein and white blood cell count with differential in neonates at risk for
septicemia. Eur J Pediatr. 1995;154(2):138–144.
6. Reyes CS, Garcia-Munoz F, Reyes D, Gonzalez G, Dominguez C, Dome-
nech E. Role of cytokines (interleukin-1 beta, 6, 8, tumor necrosis factor-alpha,
and soluble receptor of interleukin-2) and C-reactive protein in the diagnosis of
neonatal sepsis. Acta Pediatr. 2003;92(2):221–227.
7. Berner R, Tuksen B, Clad A, Forster J, Brandis M. Elevated gene expression
of interleukin-8 in cord blood as a sensitive marker for neonatal infection. Eur J
Pediatr. 2000;159(3):205–210.
8. Ng PC, Cheng SH, Chui KM, et al. Diagnosis of late onset neonatal sepsis
with cytokines, adhesion molecule, and C-reactive protein in preterm very low
birth weight infants. Arch Dis Child Fetal Neonatal Ed. 1997;77(3):F221–F227.
9. Springer TA. Adhesion receptors of the immune system. Nature. 1990;
346(6283):425–434.
10. Endo S, Inada K, Yamada Y, et al. Levels of soluble adhesion molecules
Neonatal Sepsis—Zaki & El Sayed 1295
and cytokines in patients with septic multiple organ failure. J Inflamm. 1996;
46(4):212–219.
11. Reinhart K, Bayer O, Brunkhorst F, Meisner M. Markers of endothelial
damage in organ dysfunction and sepsis. Crit Care Med. 2002;30(5)(suppl):S302–
S312.
12. Tollner U. Early diagnosis of septicaemia in the newborn: clinical studies
and sepsis score. Eur J Pediatr. 1982;138(4):331–337.
13. Da Silva O, Hammerberg O. Diagnostic value of leukocyte indices in late
neonatal sepsis. Pediatr Infect Dis J. 1994;13(5):409–410.
14. Carraway MS, Welty-Wolf KE, Kantrow SP, et al. Antibody to E- and l-se-
lectin does not prevent lung injury or mortality in septic baboons. Am J Respir
Crit Care Med. 1998;157(3, pt 1):938–949.
15. Austgulen R, Arntzen KJ, Haereid PE, Aag S, Dollner H. Infections in neo-
nates delivered at term are associated with increased serum levels of ICAM-1 and
E-selectin. Acta Pediatr. 1997;86(3):274–280.
16. Dollner H, Vatten L, Austgulen R. Early diagnostic markers for neonatal
sepsis: comparing C-reactive protein, interleukin-6, soluble tumor necrosis factor
receptors and soluble adhesion molecules. J Clin Epidemiol. 2001;54(12):11251–
11257.
17. Peakman M, Senaldi G, Liossis G, Gamsu HR, Vergani D. Complement
activation in neonatal infection. Arch Dis Child. 1992;67(7):802–807.
1296 Arch Pathol Lab Med—Vol 133, August 2009
18. Newman W, Beall DB, Carson CW. et al. Soluble E-selectin is found in
supernatants of activated endothelial cells and is elevated in the serum of patients
with septic shock. J Immunol. 1993;150(2):633–654.
19. Hatherill M, Tibby SM, Sykes K, Turner C, Murdoch IA. Diagnostic markers
of infection: comparison of procalcitonin with C reactive protein and leukocyte
count. Arch Dis Child. 1999;81:417–421.
20. Manucha V, Rusia U, Sikka M, Faridi MM, Madan N. Utility of hemato-
logical parameters and C-reactive protein in the detection of neonatal sepsis. J
Pediatr Child Health. 2002;38(5):459–564.
21. Ramsay PL, Smith EO, Hegemier S, Welty S. Early clinical markers for the
development of bronchopulmonary dysplasia: soluble E-selectin and ICAM-1. Pe-
diatrics. 1998;102(4):927–932.
22. Nuntnarumit P, Pinkaew 0, Kitiwanwanich S. Predictive values of serial
C-reactive protein in neonatal sepsis. J Med Assoc Thai. 2002;85(suppl 4):S1151–
S1158.
23. Ottolini MC, Lundgren K, Mirkinson LJ, Cason S, Ottolini MG. Utility of
complete blood count and blood culture screening to diagnose neonatal sepsis
in the asymptomatic at risk newborn. Pediatr Infect Dis J. 2003;22(5):430–434.
24. Ridings PC, Windsor ACJ, Jutila MA, et al. A dual-binding antibody to E-
and l-selectin attenuates sepsis-induced lung injury. Am J Respir Crit Care Med.
1995;152(1):247–253.
Neonatal Sepsis—Zaki & El Sayed