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Indian Pediatr 2011;48: 471-473 |
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Prognostic Value of Plasma Pro-Adrenomedullin
and Antithrombin Levels in Neonatal Sepsis |
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Adel A Hagag , Heba S Elmahdy and Aml A Ezzat*
From the Departments of Pediatrics and *Clinical
Pathology, Faculty of Medicine, Tanta University, Egypt.
Correspondence to: Dr Heba Said Elmahdy, Department of
Pediatrics, Faculty of Medicine, Tanta University, Egypt.
Email: [email protected]
Received: July 30, 2010;
Initial review: August 26, 2010;
Accepted: October 28, 2010.
Published online: 2011 February, 28.
PII: S09747559INPE1000149-2
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Abstract
The aim of this study was to clarify the prognostic
value of serum pro-Adrenomedullin level (pro-ADM) and Anti thrombin
level in neonatal sepsis. 40 term neonates with sepsis
were enrolled in this study including 20 cases with mild sepsis and 20
cases with severe sepsis. Twenty healthy matched neonates served as a
control group. Serum levels of Pro ADM and Antithrombin were measured in
all patients and the control group. Serum Pro ADM level was higher in
neonates with sepsis than control group, higher in severe than mild
sepsis, and was higher in non survivors. Antithrombin concentrations
were lower in sepsis cases than control, lower in severe than mild
sepsis, and lower in non-survivors.
Key words: Antithrombin, Neonate, Pro-adrenomedullin,
Prognosis, Sepsis.
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N
eonatal sepsis is a significant cause of morbidity and mortality
in neonates [1]. Quantification of adrenomedullin (ADM) could be helpful
in diagnosis, monitoring of sepsis and in the prognosis. Unfortunately,
reliable measurement of ADM is almost impossible, as it is rapidly cleared
from the circulation [2]. Recently, the more stable midregional fragment
of pro-adrenomedullin, which directly reflects levels of the rapidly
degraded active peptide ADM, has been detected in plasma of patients with
septic shock [3]. Antithrombin is a potent inhibitor of thrombin-mediated
vascular injury in the microcirculation during severe sepsis [4]. The aim
of this study was to find out prognostic value of serum ADM and
Antithrombin level in neonatal sepsis.
Methods
Forty term neonates with sepsis were eligible
for the study including 20 cases with manifestations of mild sepsis and 20
cases with severe sepsis. All were admitted to NICU, Tanta University
Hospital. Twenty healthy neonates of matched gestational age and
birthweight served as control group. This work was done with the approval
of Research Committee, Tanta University Hospital. For all cases and
controls, complete blood picture, C-reactive protein (EMIT; Merck
Diagnostica, Zurich, Switzerland) and blood and urine cultures were
obtained. CSF analysis and cultures, and plain X-ray chest were
done in septic neonates only. Serum pro-ADM concentration: Blood
samples were obtained before starting antibiotic therapy, separated into
plasma and frozen to –70ºC. Measurements were done in a blinded manner as
a batch analysis. Pro-ADM was detected in EDTA plasma of all patients
using a new sandwich immunoassay (B.R.A.H.M.S. Sevadil
LIA; B.R.A.H.M.S., AG, Hennigsdorf/Berlin, Germany), [5]. Serum
antithrombin concentration: Determination was done by using a
functional activity assay. The residual enzyme was measured by a
clotting-based assay or by using chromogenic peptide substrates [6].
Results
The three study groups are compared for their
demographic and clinical characteristics in Table I. Serum Pro ADM were
significantly higher in neonates with mild and severe sepsis versus
control (P<0.05). Serum ADM were significantly higher in neonates
with severe versus mild sepsis (P<0.05). Serum antithrombin levels
were significantly lower in neonates with mild, severe sepsis versus
control (P<0.05) Also serum Antithrombin levels were significantly
lower in neonates with severe versus mild sepsis (P<0.05). (Table
I). Serum pro-ADM levels were significantly higher in neonates who
did not survive (P<0.05). Serum antithrombin levels were
significantly lower in neonates who died. (Table II). There
was significant negative correlation between the plasma ADM levels and
survival rate in sepsis cases [r = 0.67, P<0.05]. There was
significant positive correlation between the plasma Antithrombin levels
and survival in neonatal sepsis [r =1, P<0.01].
Table I
Demographic Data of Studied Cases
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Patient information |
Mild sepsis |
Severe sepsis |
Control |
P value |
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n= 20 |
n= 20 |
n= 20 |
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Gestational age (wk) |
38.85±0.88 |
38.75±0.97 |
38.9±0.64 |
0.84 |
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Birth weight (kg) |
3.175± 0.28 |
3.24± 0.25 |
3.26± 0.24 |
0.78 |
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Total leucocyte count |
9 ±3 ×103 |
10 ±4×103 |
8 ±2×103 |
0.14 |
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ANC |
2973±739 |
2835±822 |
3345±719 |
0.1 |
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Immature/total ratio |
0.35±0.1 |
0.4 ±0.1 |
0.15 ± 0.01 |
0.29 |
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Platelet count§ |
140±20×103 |
110 ±20×103 |
290 ±20x103 |
0.0001 |
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Serum Pro-ADM |
0.086±0.96 |
3. 94 ±1.78 |
8.98±2.91 |
0.05*$ |
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Serum Anti-thrombin |
28.89±2.60 |
16.57±1.64 |
11.29±1.43 |
0.05*$ |
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§There
were statistically significant differences in platelet count between
septic neonates and control group (P<0.05); *mild cases versus
control, $mild cases versus severe, õ severe cases versus control, ‡
P value < 0.05; ANC (absolute neutrophil count) |
Table II
Comparison Between Pro Adm, Antithrombin And Crp In Neonates With Sepsis
Who Survived And Who Did Not Survive
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Parameters |
Survived |
Non survived |
P |
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cases (n=32) |
cases (n= 8) |
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| Pro-ADM (nmol/L) |
5.22 ± 2.24 |
11.40 ± 3.09 |
<0.05 |
| CRP (mg/L) |
73.09 ± 22.71 |
78.37 ± 15.23 |
>0.05 |
| Antithrombin
(mg/dL) |
14.97 ± 2.46 |
9.75 ± 0.87 |
<0.05 |
Discussion
In this study we found a significant increase in pro-ADM
in the plasma of septic patients as compared with controls. This was in
agreement with previous studies [7,8], but in contrast to
Christ-Crain, et al. [9] who found the circulating levels of
ADM only modestly elevated and not significantly different between
patients with SIRS and those with sepsis, prohibiting its use as a
diagnostic tool. In contrast, they found that circulating levels of pro
ADM vary to a much greater extent between health and disease with
significantly higher levels in patients with sepsis who did not survive
than in survivors and concluded that pro ADM can be used as predictor of
outcome in sepsis.
In this study, initial Antithrombin levels were
significantly lower in neonates with mild and severe sepsis versus
control, significantly lower in neonates with severe versus mild sepsis
and significantly lower in non survivor in contrast to survivor cases.
These results were in agreement with [10] who found that newborns with
lower AT levels initially, had a higher rate of developing DIC and death.
Similar results were obtained by [11] in adult sepsis. Many
previous adult studies have reported that initial AT levels of patients
with sepsis who developed septic shock and DIC are an indicator of
prognosis and cases with very low AT levels have a higher mortality rate;
moreover, significantly lower initial AT levels in patients who did not
survive compared to the survivors [12].
Contibutors: All authors contributed to concept,
design, conduct and writing of the study.
Funding: None.
Competing interests: None stated.
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What This Study Adds?
• Both Pro-ADM and AT levels can be useful
markers in predicting clinical outcome in neonatal sepsis.
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