Serum Soluble ICAM-1, VCAM-1,

L-Selectin, and P-Selectin Levels as Markers

of Infection and their Relation to Clinical
Severity in Neonatal Sepsis
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mez-Lo
pez, M.D., Ph.D.,1
Jose Figueras-Aloy, M.D., Ph.D.,1 Lilian Go
1
Jose-Manuel Rodrguez-Miguelez, M.D., Ph.D.,
M. Dolors. Salvia-Roiges, M.D., Ph.D.,1 Iolanda Jordan-Garca, M.D., Ph.D.,1
Inmaculada Ferrer-Codina, M.D., Ph.D.,2 Xavier Carbonell-Estrany, M.D., Ph.D.,1
and Rafael Jimenez-Gonzalez, M.D., Ph.D.1

ABSTRACT

Adhesion molecules may play a role in the evolution and severity of neonatal
sepsis. The purposes of this study were to determine whether serum soluble intercellular
adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, L-selectin,
and P-selectin levels are useful tools in the diagnosis of proven sepsis in newborn infants,
and whether their levels are related to the clinical severity of the disease. A cohort of
25 consecutive newborns meeting criteria for clinical sepsis, 10 hemoculture-negative
(HC
) and 15 hemoculture-positive (HC ), were prospectively followed and compared with 12 healthy newborns (six  38 weeks of gestational age and six  39 weeks).
Serum soluble (s)ICAM-1, sVCAM-1, sL-selectin, and sP-selectin concentrations were
measured at the time of the septic workup, then followed by up to three determinations in
each newborn every third day. The Score for Neonatal Acute Physiology (SNAP)-II
severity was assessed at the moment of highest clinical severity of the disease. At the
beginning of sepsis, sICAM-1 levels increased in both groups, being higher in
HC sepsis than in HC
; sVCAM-1 only increased slightly in HC sepsis. Soluble
ICAM-1 levels were independently related to group of sepsis, and not to days of life. The
best initial sICAM-1 cutoff level for diagnosing HC neonatal sepsis was 274 mg/L.
The highest sICAM-1 levels were positively correlated with SNAP-II scores. Soluble
L-selectin and sP-selectin did not change. Soluble ICAM-1 levels increased in
HC
and HC sepsis, but concentrations > 274 mg/L suggest HC sepsis. These
levels were related to the clinical severity of the disease. Soluble VCAM-1 levels
increased only slightly in HC sepsis. Soluble L-selectin and sP-selectin did not change.
KEYWORDS: Adhesion molecules, newborn, sepsis, septic shock

Servicio Neonatologa, Institut Clnic de Ginecologia, Obstetrcia i

Neonatologia; 2Agrupacio Sanita`ria Sant Joan de DeuHospital
Clnic, Institut dInvestigacions Biome`diques August Pi i Sunyer
(IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Address for correspondence and reprint requests: Prof. Jose
Figueras-Aloy, Servicio Neonatologa. Hospital Clnic, C/ Sabino de

Arana 1, 08028 Barcelona, Spain.

Am J Perinatol 2007;24:331338. Copyright # 2007 by Thieme
Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001,
USA. Tel: +1(212) 5844662.
Accepted: March 6, 2007. Published online: June 12, 2007.
DOI 10.1055/s-2007-981851. ISSN 0735-1631.

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AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 24, NUMBER 6

he inflammatory response is essential in the

defense against microorganisms in neonatal infections.
Circulating adhesion molecules promote the adherence
of circulating leukocytes to the endothelial cells of the
blood vessel wall. The attached leukocytes migrate
through the endothelial cells to the inflammation site,
attracted by other inflammatory mediators.1 Leukocyte
transmigration starts along the endothelial lining in a
selectin-based interaction intended to reduce the velocity
relative to the blood flow. There are three selectins:
E-selectin, expressed on endothelial cells, P-selectin,
expressed on endothelial cells and platelets, and L-selectin, expressed on leukocytes.2 Soluble (s)L-selectin in the
plasma can reflect immune activation and is increased in
maternal chorioamnionitis and neonatal sepsis.3
Intercellular adhesion molecule (ICAM)-1, a
member of the cell surface immunoglobulin superfamily
of adhesion receptors,2 takes part in lymphocyte-mediated adhesion, cytotoxic T-cell activity, and antigen
presentation.4 ICAM-1 is also a ligand for lymphocyte
function-associated antigen (LFA)-1 and macrophageassociated complex (MAC)-1.5 The soluble form of
vascular cell adhesion molecule (sVCAM)-1 is, like
sICAM-1, a reliable marker of immune activation and
response. Moreover, sVCAM-1 has been reported to be
a potent angiogenic agent.6 High levels of adhesion
molecules have been found in different disease states,
especially inflammation7 and infection.4,811
Serum sICAM-1, sVCAM-1, sL-selectin, and
sP-selectin levels may be useful tools for the diagnosis
of sepsis in newborn infants. The aims of this study were
to evaluate whether adhesion molecule concentrations
increase at the beginning of sepsis and during the days
following and can be used to differentiate hemoculturepositive (HC ) sepsis from hemoculture-negative
(HC
) sepsis and normal newborns, and also to determine whether the degree of alteration of adhesion
molecule concentrations is related to the clinical severity
of the disease.

PATIENTS AND METHODS

All the newborns admitted consecutively to the neonatal
intensive care unit (NICU) over 21 months with the
diagnosis of suspected sepsis were enrolled in the study.
Parental informed consent was obtained. The study was
approved by the Neonatology Ethics Committee.

Inclusion Criteria
The diagnosis of suspected sepsis was accepted when a
newborn showed one or more clinical signs of infection
and at least one biological sign. In this case, a hemoculture was drawn and antibiotherapy was started. Clinical
signs of infection were: respiratory distress, apnea, vomiting, abdominal distention, hypothermia or fever, leth-

2007

argy, seizures, purpura, hyperglycemia, or hypotension.

The biological signs included fewer than 5000 leukocytes/mL, immature-to-total neutrophil ratio greater
than 0.20, and/or C-reactive protein more than 40 mg/L.
Hemoculture-positive (HC ) or proven sepsis was
accepted if a positive hemoculture was obtained in a newborn with suspected sepsis. If a newborn presented a
suspected sepsis but the hemoculture was negative, the
diagnosis of hemoculture-negative (HC
) sepsis was
accepted only after excluding intracranial hemorrhage,
drug withdrawal, and cardiac disease; antibiotherapy was
then maintained for at least 7 days.

Exclusion Criteria
Patients with severe congenital anomalies, metabolic
diseases, or chromosomal disorders were excluded.

Groups Analyzed
CONTROL GROUP

Twelve healthy newborns with unconfirmed risk of

perinatal infection (mother colonized by Streptococcus
agalactiae) were considered as controls. Only one extra
blood extraction for determining adhesion molecules was
performed during the first infectious disease workup. For
two of the newborns, the extractions were repeated up to
three times approximately every third day.
STUDY GROUP

Twenty-five patients were identified and enrolled with

the diagnosis of suspected sepsis. At the time of clinical
suspicion of sepsis and when the blood was drawn for
hemoculture, 1 mL was taken to determine adhesion
molecules, and up to three determinations in each newborn were performed approximately every third day.
According to hemoculture results, this group was subdivided into two groups: (1) HC
sepsis (10 patients)
and (2) HC sepsis (15 patients, 3 of whom presented
clinical severity criteria such as death due to the infection,
repeated seizures, disseminated intravascular coagulation
[DIC], or shock, and in need of mechanical ventilation as
support treatment). No meningitis was diagnosed. One
patient died due to the infection (1 of 25, 4%).

Variables Analyzed
Gestational age and birthweight were considered in all
the newborns, as well as C-reactive protein, immatureto-total neutrophil ratio, and Score for Neonatal Acute
Physiology (SNAP)-II.12 This severity score was performed in each newborn when the highest level of
clinical severity was reached. In addition, for each of
the three periods considered in the evolution of the
septic process (initial, middle, and final), the time of

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332

blood extraction to determine adhesion molecule was

recorded.

Serum Soluble ICAM-1, VCAM-1, L-Selectin,

and P-Selectin Determination
Blood (1 mL) was collected in pyrogen-free tubes,
centrifugated immediately after clotting, and nonhemolyzed serum samples were divided into four aliquots
and stored frozen at 408C. Serum levels of adhesion
molecules were measured by commercially available
enzyme-linked immunoadsorbent assays (ELISAs)
(R&D Systems, Minneapolis, MN). The sensitivity
limits were as follows: sL-selectin, 0.3 mg/L; sP-selectin, 0.5 mg/L; sICAM-1, 0.35 mg/L; and sVCAM-1,
2 mg/L.

Data Analysis
Due to the small sample in each group, the quantitative
variables are expressed as median and interquartile
range (IQR): percentile 25 to percentile 75. The influences of gestational age and birthweight on sICAM-1,
sVCAM-1, sL-selectin, and sP-selectin concentrations
were studied only in the control group. These adhesion
molecules were also considered in the initial comparison between the control group and the HC
and
HC septic groups. For the sequential data for sICAM-1, sVCAM-1, sL-selectin, and sP-selectin levels, only septic groups were considered. Nonparametric
analyses were used in the group comparison; the
Kruskal-Wallis test was performed for the cross-sectional evaluation, and the Friedman test was performed
for the longitudinal evaluation. When considered appropriate, post hoc comparisons using the MannWhitney U test were also performed. The Spearman
correlation was applied to determine the possible relationship between sICAM-1, sVCAM-1, sL-selectin,
and sP-selectin levels and birthweight and gestational
age in the control group; in the study groups it was used

to evaluate the possible relation between the highest

values of sICAM-1, sVCAM-1, sL-selectin, sP-selectin, C-reactive protein, immature-to-total neutrophil
ratio and SNAP scores. Univariate analysis of variance
was performed to analyze the different influences of
the variable sepsis group (control, HC
septic, or
HC septic) and two covariables (gestational age and
days of life at blood extraction) on the initial sICAM-1
levels. The same was done for sVCAM-1 levels. To
determine whether initial sICAM-1 levels were reliable
early markers of infection in newborns, we compared
HC sepsis newborns and non-HC sepsis newborns (control group and HC
sepsis group), and we
obtained a receiver-operator characteristic (ROC)
curve of sICAM-1 and determined the best cutoff level
(i.e., one with the highest sensitivity and the highest
positive likelihood ratio). Differences were considered
significant if the P value was < 0.05.

RESULTS
Thirty-seven newborns, ranging in age from 1 hour to
32 days (median 24 hours; IQR, 14 to 264 hours), were
studied. The control group included 12 newborns, 6 at
38 weeks gestational age (WGA) or less and 6 at 39
WGA or more. There was no correlation between
sVCAM-1, sL-selectin, sP-selectin, and gestational
age or birthweight. A positive correlation between
sICAM-1 and gestational age was found (r 0.623,
P 0.041), but there was no significant difference between sICAM-1 levels in  38 WGA and  39 WGA
newborns (153 mg/L; IQR, 144 to 156 versus 164 mg/L;
IQR, 158 to 194, respectively).
The bacteria isolated in the 15 newborns with
hemoculture-positive sepsis were: five Staphylococcus
epidermidis, two Enterococcus faecalis, five Streptococcus
agalactiae, two Enterobacter cloacae, and one Klebsiella
oxytoca. The HC sepsis group had lower gestational
age and birthweight than the other groups, although
the differences were not significant (Table 1). However,

Table 1 Characteristics of Newborns Studied

1 Control Group
(n 12)
Gestational age (wk)
Birthweight (g)

38.5 (3740)
3037 (26253835)

2 HC
Sepsis Group
(n 10)
40 (3640)
3365 (28403612)

3 HC Sepsis Group
(n 15)
37 (3239)
2350 (13903120)

P*
NS (0.113)
NS (0.124)

Days of life
Initial blood extraction
Middle blood extraction
Final blood extraction
C-reactive proteiny (mg/L)
Immature-to-total neutrophil ratioy

1 (11)

2.5 (23)

10 (314)

< 0.001 (a)

5.5 (56)

6 (58)

13 (518)

NS (0.185)

9.5 (911)

20 (1024)

NS (0.114)

6 (328)

71 (4087)

61 (50121)

0.015 (0.00.04)

0.106 (0.050.22)

0.041 (0.030.14)

< 0.001 (b)

0.001 (c)

*Kruskal-Wallis test. Post hoc Mann-Whitney U test (P < 0.05) results were: (a) 1 to 2, 1 to 3, 2 to 3; (b) 1 to 2,1 to 3; (c) 1 to 2, 1 to 3.
y
Highest values are shown.
Median (interquartile range [IQR]: percentile 25 to percentile 75).
HC
, hemoculture-negative; HC , hemoculture-positive; NS, not significant.

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AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 24, NUMBER 6

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Table 2 Adhesion Molecules Concentrations During the Septicemic Process

Control Group (1)

HC
Sepsis Group (2)

HC Sepsis Group (3)

P*

sICAM-1 (mg/L)
Initial

(11)y 156 (150194)**

(10)y 242 (226331)**

(14)y 394 (342600)**

< 0.001 (a)

Middle

(2)y 214 (126302)**

(10)y 271 (221371)**

(15)y 418 (326646)**

0.008 (b)

Final

(1)y 274**

(8)y 278 (213366)**

(10)y 458 (323568)**

NS (0.146)

sVCAM-1 (mg/L)
Initial

(12)y 856 (742960)**

(10)y 768 (629861)**

(14)y 1153 (7261307)**

0.027 (c)

Middle

(2)y 895 (6961095)**

(10)y 887 (7251040)**

(15)y 1094 (8091354)**

NS (0.111)

(1)y 1005**

(8)y 897 (7781069)**

(10)y 1072 (9311279)**

NS (0.235)

Final
sL-selectin (mg/L)
Initial

(12)y 580 (523717)**

(10)y 637 (553696)**

(14)y 681 (541757)**

NS (0.580)

Middle

(2)y 419 (338500)**

(10)y 746 (647812)**

(15)y 700 (586806)**

NS (0.096)

Final

(1)y 434**

(8)y 808 (665856)**

(10)y 790 (6281076)**

NS (0.235)
NS (0.791)

sP-selectin (mg/L)
Initial

(9)y 272 (152288)**

(7)y 224 (168318)**

(9)y 244 (170324)**

Middle

(2)y 300 (237364)**

(8)y 187 (141238)**

(10)y 289 (187316)**

NS (0.126)

Final

(1)y 338**

(7)y 458 (160562)**

(7)y 268 (240344)**

NS (0.842)

*Kruskal-Wallis test. Post hoc Mann-Whitney U test (P < 0.05) results were: (a) 1 to 2, 1 to 3, 2 to 3; (b) 1 to 3, 2 to 3; (c) 2 to 3.
y
Number of cases.
**Median (interquartile range [IQR]: percentile 25 to percentile 75).
The Friedman test was not significant except for sL-selectin in the HC
sepsis group (P 0.010).
HC
, hemoculture-negative; HC , hemoculture-positive; sICAM, soluble intercellular adhesion molecule; sVCAM, soluble vascular cell
adhesion molecule; s, soluble; NS, not significant.

the HC sepsis groups blood samples were obtained

later than from the other groups (Table 1), the difference being significant only in the first sample.
C-reactive protein and immature-to-total neutrophil
ratio were high in both the HC
and HC sepsis
groups, although the differences were not significant
(Table 1).

When we analyzed sICAM-1 levels in the initial

period, significant differences appeared between control
and HC
sepsis or HC sepsis (Table 2). Newborns
with HC sepsis had higher sICAM-1 concentrations
in the initial and middle periods than the HC
septic
and control group newborns (Table 2 and Fig. 1). The
same analysis applied to sVCAM-1 concentrations

Figure 1 sICAM-1 concentrations (median,

values) in newborns studied, differentiating
between HC sepsis, HC
sepsis and control groups. sICAM, soluble intercellular adhesion molecule; HC , hemoculture-positive;
HC
, hemoculture-negative.

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334

Figure 2 Correlation between sICAM-1

concentrations and SNAP-II scores. sICAM,
soluble intercellular adhesion molecule; HC ,
hemoculture-positive; HC
, hemoculture-negative; SNAP, Score for Neonatal Acute Physiology.

showed significant differences in the initial period between HC sepsis and HC
sepsis (Table 2). The
highest value of sICAM-1 correlated positively with
the highest value of sVCAM-1 (r 0.625; P < 0.001).
There were no significant differences in sL-selectin and
sP-selectin either at the beginning or during the sepsis
period (Table 2).
SNAP-II scores correlated positively with the
highest value of sICAM-1 concentrations in each septicemic newborn (r 0.537, P 0.006) (Fig. 2), but not
with the highest value of sVCAM-1. Bacteria were
similar (P 0.637) in the subgroup with a high
SNAP-II score (16 to 105; 3 Gram-positive bacteria
and 1 Gram-negative bacteria) and in the subgroup with
a low SNAP-II score (0 to 5, 9 Gram-positive bacteria
and 2 Gram-negative bacteria). The highest value of
C-reactive protein in each septicemic newborn correlated positively with the highest value of the immatureto-total neutrophil ratio (n 25; r 0.590, P 0.002).
There was also a correlation between the value of
C-reactive protein in each septicemic newborn and the
value of the immature-to-total neutrophil ratio in the
first blood sample when sepsis was suspected (n 25,
r 0.523, P 0.007). However, these values did
not correlate with the concentrations of sICAM-1,
sVCAM-1, or SNAP-II scores.
Univariate analysis of variance of sICAM-1 levels
related to the variable sepsis group being considered with

three categories (control group, HC
septic group, and

HC septic group) and two covariables (gestational age
and days of life at blood extraction) showed that the
model was valid (R2 0.585, P < 0.001) and that the
only independent significant factor was the sepsis group
being considered (P 0.002). The covariable days of life
at blood extraction did not reach statistical significance
(P 0.836). A similar analysis performed on sVCAM-1
levels showed that the model was not as good as the
previous one (R2 0.414, P < 0.001) and that the most
significant factor was, again, the sepsis group being
considered (P 0.023).
According to our sICAM-1 determinations at
the beginning of the neonatal sepsis, a cutoff level of
274 mg/L predicted HC neonatal sepsis with sensitivity of 100%, specificity of 85.7% (confidence interval
[CI] 95%: 70.7 to 100%), positive predictive value of
82.3%, negative predictive value of 100%, accuracy of
91.4%, and positive likelihood ratio of 7.0 (CI 95%:
2.45 to 19.95). Area under the curve was 0.939
(P < 0.001) (Fig. 3).

DISCUSSION
Accurate new markers of neonatal sepsis are needed.
Early appropriate diagnosis of sepsis will help to ensure
that newborns treated with antibiotics are only those
with clinical symptoms and truly suspicious biological

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AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 24, NUMBER 6

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Figure 3 ROC curve of sICAM-1 levels and HC sepsis.

sICAM, soluble intercellular adhesion molecule; HC , hemoculture-positive; HC
, hemoculture-negative; SNAP, Score
for Neonatal Acute Physiology; ROC, receiver-operator characteristic.

parameters. The 25 patients from our study group had

suspected sepsis. When hemoculture was positive, sepsis
was accepted as proven. If hemoculture was negative,
other conditions were ruled out and antibiotherapy was
maintained for at least 7 days because the attending
physician considered that the syndrome was probably
due to sepsis. A SNAP-II score was determined when
the septic process reached the highest severity.12
Our study and control groups were small and
cannot be considered completely homogeneous in terms
of gestational age and birthweight, especially at the time
of the first blood extraction. However, soluble adhesion
molecule levels were not influenced by birthweight, and
we found no significant differences between  38 WGA
and  39 WGA infants in the control group. Studying
168 noninfected newborns, Austgulen and colleagues4
also found no relation between sICAM-1 and sVCAM1 and gestational age. However, in a study of 28 newborns > 38 WGA and 15 newborns between 35 and 38
WGA, Phocas and colleagues13 found a reduction of
sICAM-1 levels in > 38 WGA infants, although the
difference was small. Increasing postnatal age in newborns has a positive effect on sICAM-1 and sVCAM-1
values from days 1 to 5 and then to day 30 of life7,13,14
The most likely reason for the increase in sICAM-1

and sVCAM-1 after birth is the change from a relatively

hypoxic intrauterine environment to the more oxygenrich extrauterine environment. Moreover, there is an
immature or deficient antioxidant defense mechanism,15
which leads to relative enhanced lipid peroxidation
and oxidative stress,16 resulting in a proinflammatory
state. This physiological increase is especially noted in
sICAM-1. Malamitsi-Puchner and colleagues17 reported that in healthy neonates serum levels of sVCAM-1
and sL-selectin did not change during early neonatal life.
In our study, at the beginning of neonatal sepsis,
sICAM-1 increased in both the HC
and HC sepsis
groups, although its levels in HC sepsis were higher.
High sICAM-1 has been considered a good marker of
infection in newborns.4,10,11,18,19 Later, sICAM-1 and
sVCAM-1 increased with age in control and sepsis
groups. This finding is difficult to interpret because the
cases were older than the controls at the time of the first
blood sample. However, we believe that the initial
sICAM-1 and sVCAM-1 increases in our HC septisepticemic newborns were due to the inflammatory
process and not to the time of blood sampling. Univariate
analysis of variance of sICAM-1 levels showed that the
only independent significant factor was the sepsis group
being considered (control group, HC
septic group, or

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336

HC septic group), whereas days of life at blood sampling and gestational age did not show any statistical
significance.
DAlquen and colleagues20 recently found that
cord blood serum concentrations of sICAM-1 were
higher in a group with chorioamnionitis and funisitis
when compared with a group with only chorioamnionitis
or controls, probably due to the higher inflammatory
response when funisitis is present. However, cord serum
sICAM-1 determinations have no diagnostic relevance
in neonatal infection.21,22
Whalen and colleagues19 reported that, in children with sepsis-induced multiple organ failure, plasma
sICAM-1 concentrations independently predicted number of organ failures, development of more than three
organ failures, and mortality. Xanthou and colleagues10
reported that sICAM-1 rose in the peripheral blood of
both asphyxiated and infected neonates in the first 5 days
of life; sICAM-1 levels were higher in severe cases. In
addition, increased C-reactive protein levels were found
in perinatally infected but not perinatally asphyxiated
neonates. In our study, throughout the sepsis period,
only sICAM-1 remained significantly higher in infants
with HC sepsis. In addition, the highest values of
sICAM-1 correlated positively with the SNAP-II severity score system in septic newborns. Austgulen and
colleagues,4 who studied 24 infected newborns and 168
noninfected newborns, proposed an sICAM-1 cutoff of
250 mg/L (sensitivity of 80% and specificity of 61%),
whereas Hansen and colleagues,23 who studied 45 infected newborns and 45 noninfected newborns, raised
the cutoff to 300 mg/L. Our data suggest that the best
initial cutoff would be 274 mg/L, with no false-negatives
and a very low rate of false-positives. Edgar and colleagues24 studied 46 newborns and reported that a low
level of serum sICAM-1 might help exclude infection.
Our results support this suggestion because the negative
predictive value of 100% that we obtained means that all
the newborns with sICAM-1 concentrations below 274
mg/L will not be affected by HC sepsis.
In relation to C-reactive protein, a recognized
marker of neonatal infections, Apostolou and colleagues25 studied 20 infected newborns (10 full-term
and 10 preterm) and 20 noninfected newborns (10 fullterm and 10 preterm). They demonstrated that increased
sICAM-1 levels could be detected early in both fullterm and premature neonates with sepsis, while Creactive protein levels were concurrently within the
normal range. Hansen and colleagues23 showed that
for identification of infection in newborns less than
5 days old, sICAM-1 and C-reactive protein in combination are better primary markers than C-reactive protein alone. We could not demonstrate a relation between
C-reactive protein levels or immature-to-total neutrophil ratio and sICAM-1 and sVCAM-1 concentrations,
probably because adhesion molecules increased earlier.

In our study, sVCAM-1 concentrations only increased at the beginning of the sepsis and in the
HC sepsis group. Whalen and colleagues19 also reported an increase in sVCAM-1 on the first day of sepsis,
whereas Austgulen and colleagues4 found no increase in
either full-term or preterm septic newborns. These differences are probably due to the small increase in sVCAM-1,
and therefore justify analyzing sICAM-1 first.
According to our data, sL-selectin and sP-selectin
did not change either at the beginning or, indeed, at any
time during the sepsis period. Kourtis and colleagues3
reported slightly higher levels of sL-selectin in early
neonatal sepsis (median 1331 versus 1149 mg/L;
P 0.026). The selectins are the first adhesion molecules
to increase, with a very quick return to normal values.
Very early blood samples are needed to detect any
change.
Assessments of sICAM-1 levels in newborn infants without perinatal asphyxia or after 5 days of life
may provide further evidence of enhanced inflammatory
responses. The results of adhesion molecule expression
were not available to the treating clinician during the
management of the infant. A high sICAM-1 value
(> 274 mg/L) would mean probable HC sepsis
(82.3% of positive predictive value) and therefore antibiotherapy would be justified. If the sICAM-1 value is
low (< 274 mg/L), the probability of not having
HC sepsis is 100%, and, in case of good clinical
evolution, antibiotics could be withdrawn or not started.
However, the final decision will depend on blood culture
results and evolution of clinical signs and biological
markers (C-reactive protein, immature-to-total neutrophil ratio). Soluble ICAM-1 may not be a good indicator
of favorable evolution because during the HC sepsis
the values may even increase (Fig. 1). Further studies to
determine the biological significance of soluble adhesion
molecule levels in newborns and whether their assessments can be used as a tool to guide clinical care are
warranted.
In conclusion, sICAM-1 determination seems to
be a good indicator of neonatal sepsis, especially of
HC sepsis, and its severity. Soluble VCAM-1 concentrations only increase slightly in HC sepsis, and
sL-selectin and sP-selectin do not change.

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