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Obeagu et al
©IDOSR PUBLICATIONS
International Digital Organization for Scientific Research
IDOSR JOURNAL OF SCIENTIFIC RESEARCH 8(2) 161-166, 2023.
https://doi.org/10.59298/IDOSR/2023/10.2.6013
ISSN: 2550-794X
Neonatal Sepsis: Haematological Perspectives
*
Emmanuel Ifeanyi Obeagu1, Ndakize Benjamin Kigabo2, Getrude Uzoma
Obeagu3, Okechukwu Paul-Chima Ugwu4 and Sophia Kazibwe5
1
Department of Medical Laboratory Science, Kampala International University, Uganda.
Department of Paediatrics and Child Care Health, Kampala International University,
Uganda.
3
School of Nursing Science, Kampala International University, Uganda.
4
Department of Publications and Extension, Kampala International University, Uganda.
5
Department of Public Management, Management Science, Human Resource Management,
Kampala International University, Uganda.
Email: emmanuelobeagu@yahoo.com
2
ABSTRACT
Neonatal sepsis (NS) is a leading cause of neonatal morbidity and mortality and is considered
a global public health challenge. The organisms and pathogens most commonly associated
with neonatal sepsis vary by country. Pathogens range from Gram-positive and Gramnegative bacteria to viruses and fungi, with bacteria being the most commonly identified.
Bacteria most commonly involved include Staphylococcus aureus, coagulase-negative
staphylococci (CONS), Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli,
Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, and Group B
Streptococcus increase, or urine culture is usually delayed for a day or two. A battery of tests,
including C-reactive protein, total leukocyte count, absolute neutrophil count, platelet count,
neutrophil cytoplasmic vacuolization, and polymorphic gastric aspiration cytology, was
performed in neonates with a clinical diagnosis of NS. It's an excellent screening test.
Keywords: Sepsis, neonates, haematological parameters, laboratory diagnosis, clinical
findings
INTRODUCTION
NS, initiation of antibiotic therapy is
Neonatal sepsis is a leading cause of
recommended before diagnostic results
neonatal morbidity and mortality and is
are available. However, some patients with
considered a
global
public
health
bacterial infections may have negative
challenge [1-10]. Symptoms and signs may
blood
cultures
(clinical
infections),
be subtle, varied, and nonspecific. In
requiring other approaches to identify
addition, delays in diagnosis and initiation
infection [12]. Many studies have been
of treatment result in high morbidity and
conducted to develop screening tests or
mortality. 5 million newborns die each
scoring systems that can identify infected
year, mainly in Africa and Asia, of which
infants at initial evaluation and avoid
1.6 million (20%) are due to neonatal
other invasive diagnostic procedures,
sepsis. The incidence of neonatal sepsis in
intravenous antibiotic therapy, motherdeveloped countries ranges from 1 to 10
infant separation, and increased parental
per 1000 live births, whereas it is three
anxiety. Attempts have been made [13].
times higher in Pakistan [12]. Definitive
Current microbiological gold-standard
diagnosis based on blood, CSF, or urine
blood culture screens have low yields in
culture is usually delayed by a day or two.
addition to long turnover times, and
In neonates with clinical manifestations or
collection of small amounts of blood can
epidemiological factors associated with
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Obeagu et al
lead to false-negative results [14].
instead of fixed normal ranges for WBC,
Additional traditional blood, including
ANC, and I/T ratio [16]. Therefore, a rapid
measurement of white blood cell count
and accurate diagnostic test is needed to
(WBC), absolute neutrophil count (ANC),
guide the management of neonates with
immature-to-total neutrophil ratio (I/T),
sepsis.
Detection
of
bacteria
and
and C-reactive protein (CRP) Biologic tests
inflammatory cells on postnatal day 1
may also require serial surveillance with
Gram-stain gastric aspirate cytology (GAC)
low sensitivity and specificity [15]. To
may indicate maternal amnionitis, a risk
better predict sepsis, recent findings
factor for early-onset infection [12].
suggest using age-specific nomograms
Neonatal sepsis
Neonatal sepsis is a blood infection that
In the 1990s, the American Academy of
occurs in infants less than 90 days of age.
Pediatrics (AAP) began to recommend the
Early sepsis occurs in the first week of life.
use of intrapartum antibiotic prophylaxis
Late sepsis occurs after 1 week to 3
(IAP) to prevent perinatal GBS, and in 2002,
months. The organisms and pathogens
the AAP and the American College of
most commonly associated with neonatal
Obstetricians and Gynecologists instituted
sepsis vary by country. Pathogens range
guidelines on the universal screening by
from Gram-positive and Gram-negative
culture of all pregnant women from 35- to
bacteria to viruses and fungi, with bacteria
37-week gestation. Due to the widespread
being the most commonly identified. The
use of prophylactic antibiotics for
most commonly implicated bacteria
neonates,
particularly
intrapartum
include Staphylococcus aureus, coagulase
antibiotic use in mothers with positive
negative
staphylococci
(CONS),
cultures for GBS, the incidence of GBSStreptococcus pneumoniae, Streptococcus
associated neonatal sepsis has declined
pyogenes, Escherichia coli, Klebsiella
significantly, a decrease of 70% in the US
pneumoniae, Pseudomonas aeruginosa,
[19]. During the same period, other
Salmonella
typhi,
and
Group
B
countries such as Canada and Taiwan have
streptococcus (GBS) [17]. Viruses include
recommended the universal use of IAP and
echovirus,
enterovirus,
parechovirus,
have seen a decline in the incidence of
coxsackie virus, adenovirus, parainfluenza
neonatal sepsis secondary to GBS infection
virus, rhinovirus, herpes simplex virus
as well [20]. In countries where IAP is used,
respiratory
syncytial
virus,
and
the most common causative agents of
coronavirus Candida albicans and other
neonatal sepsis are Escherichia coli and
Candida species are the most common
Gram-positive bacteria [21].
fungi associated with neonatal sepsis [18].
Risk Factors
In early-onset neonatal sepsis (EONS),
venous catheters and other invasive
which is usually associated with vertical
medical
devices,
and
prolonged
transmission of pathogens from mother to
hospitalization [24]. Other risk factors
child, the most common pathogens are
include premature rupture of membranes,
group B Streptococcus, Escherichia coli,
amnionitis, meconium aspiration, LBW,
CONS, Haemophilus influenzae, and
VLBW, ELBW, premature birth, >3 vaginal
Listeria monocytogenes [21-22]. ]. In lateexaminations during labor, maternal fever
onset neonatal sepsis (LONS), which is
during labor, or other maternal infections
most commonly associated with iatrogenic
during labor [25]. Among term infants,
or nosocomial infections, the most
males have a higher incidence of sepsis
common pathogens are CONS, followed by
compared with female infants, an
Staphylococcus aureus and Escherichia
association not seen in preterm infants
coli [23]. Risk factors include use of central
[26].
Clinical findings
Given the relatively subtle findings seen
sepsis until more ominous clinical
during clinical examination, neonates are
findings and vital sign abnormalities
at significant risk of delayed detection of
occur. Early-onset individuals may have a
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Obeagu et al
history of fetal distress, including
rhinitis, accessory muscle use, cyanosis,
perinatal fetal tachycardia. Shortly after
and apnea are common in neonatal sepsis.
delivery, other clinical cues such as
Neurological symptoms and signs include
meconium-stained amniotic fluid and low
lethargy, seizures, irregular breathing,
Apgar scores may appear at the initial
high-pitched
crying,
hypotension,
neonatal assessment. Caretakers may
hypoactive deep tendon reflexes, and
report a history of food intolerance,
abnormal
primitive
reflexes.
irritability,
excessive
sleepiness,
or
Gastrointestinal signs include decreased
"looking weird." Vital sign abnormalities
food intake, vomiting, diarrhea, jaundice,
include both hypothermia and fever. Fever
abdominal
distension,
and
is more common in term infants, but
hepatosplenomegaly. Cutaneous findings
premature infants are more likely to
include petechiae, impetigo, cellulitis, and
become hypothermia. Tachycardia or
abscesses. Basal metabolic acidosis due to
bradycardia, signs of poor circulation such
poor perfusion can manifest as tachypnea
as cold or pale extremities, and a rapid,
and shortness of breath in the absence of
lint-like pulse may occur. Respiratory
respiratory infection [27].
symptoms and signs such as moaning,
Diagnostic Testing
As the symptoms and signs of neonatal
(CBC) was performed to determine the total
sepsis are often very subtle and vague, it
and fractional white blood cell (WBC)
is imperative to perform diagnostic testing
counts, the absolute and immature
in any neonate with significant risk factors
neutrophil counts, and the immature and
and concerning signs and symptoms.
total neutrophil count ratios. Must be
There are various multivariate predictive
evaluated. Absolute leukocytosis has a low
scoring systems based on retrospective
susceptibility to neonatal sepsis, but is
studies that may be used to predict the
useful for clinical decision-making when
need for antibiotics and extensive
there is mild to moderate clinical
laboratory evaluation of a neonate versus
suspicion of sepsis. Interestingly, a low
observation for concerning signs and
WBC count, a low absolute neutrophil
symptoms. One such example is the EONS
count (ANC),
and
a
neutrophil-tocalculator based on a large retrospective
prematurity ratio (I/T) greater than or
population study performed in the US to
equal to 0.2 were highly predictive of
support clinicians in the decision to start
infection. has been shown [31]. Dividing
antibiotics in neonates suspected of
the I/T by the total neutrophil count to
having sepsis [28]. The newborn's prior
obtain the I/T ratio has been shown to
probability of EONS obtained from
provide improved specificity and area
maternal
risk
factors
such
as
under the curve over I/T and ANC alone in
chorioamnionitis and premature rupture
diagnosing EONS [32].The I/T2 ratio
of membranes is combined with findings
accounts for both elevated immature
based on the clinical examination, creating
neutrophils and the neutropenia that is of
a scoring system that can determine the
concern in the setting of sepsis. ANC, I/T,
need for antibiotics and level of
and I/T2 sensitivity, specificity, odds
monitoring required This scoring system
ratio, and area under the curve were
has been shown to reduce the proportion
highest at 4 hours postpartum compared
of
newborns
undergoing
extensive
to previous [33]. Therefore, placental
laboratory evaluation and administration
culture results should not be used as a
of antibiotics without any adverse effects
reason for antibiotic therapy. Urinary tract
[29]. The number needed to treat (NNT) for
infections are rare within the first 72 hours
the high-risk group requiring antibiotics
of life. Therefore, urine cultures are
determined by this scoring system was
performed only when assessing LONS [28].
still 118, highlighting the challenges
Neonates with evidence of EONS or LONS
involved in coming up with better
should undergo routine lumbar puncture
diagnostic tools in picking up EONS at an
(LP). Approximately 23% of neonates with
early stage [30]. A complete blood count
culture-positive bacteremia also develop
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Obeagu et al
meningitis [28]. Acute-phase reactants
phase reactants such as procalcitonin, IL-6
such
as
C-reactive
protein
(CRP),
and IL-8 can improve diagnostic accuracy
procalcitonin, interleukin (IL-6 and IL-8)
[33]. Procalcitonin (PCT) is more specific
levels,
presepsin,
haptoglobin,
and
than CRP against bacterial infection and
neutrophil CD64 are potential biomarkers
increases faster than CRP in response to
for neonatal sepsis. being investigated.
infection. In normal-weight infants, PCT
CRP may not be elevated during the early
levels above 0.5 ng/mL are associated with
stages of infection because it takes time to
nosocomial infections, and in VLBW
synthesize in the liver and eventually
infants levels above 2.4 ng/mL should
appears in the blood. Serial measurement
prompt antibiotic therapy [33].
of CRP in combination with other acute
CONCLUSION
neonatal sepsis. A battery of tests,
Although the incidence of neonatal sepsis
including
C-reactive
protein,
total
has declined in some parts of the world, it
leukocyte count, absolute neutrophil
remains a significant problem worldwide.
count,
platelet
count,
neutrophil
Tests for the identification and diagnosis
cytoplasmic
vacuolization,
and
of neonatal sepsis continue to be
polymorphic gastric aspiration cytology,
developed, and new test techniques are
was performed in neonates with a clinical
still
being tested.
Monitoring and
diagnosis of NS. It's an excellent screening
management of risk factors and IAPs
test. These tests are readily available,
remain important in preventing and
inexpensive, reliable and sensitive in
controlling infection in this vulnerable
detecting neonatal sepsis. Combining the
population. Treatment includes prompt
three tests increases the sensitivity and
administration
of
antibiotics
and
negative predictive value of these tests to
supportive care in an appropriate hospital
nearly 100%.
setting. Continuous vigilance is essential
in the diagnosis and management of
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Emmanuel Ifeanyi Obeagu, Ndakize Benjamin Kigabo, Getrude Uzoma Obeagu,
Okechukwu Paul-Chima Ugwu and Sophia Kazibwe (2023). Neonatal Sepsis:
Haematological Perspectives.IDOSR Journal of Scientific Research, 8(2) 161-166.
https://doi.org/10.59298/IDOSR/2023/10.2.6013
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