Alicia Pacala, RN BSN
Prepared for MSN 621 Advanced Pathophysiology (Spring 2006)
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To start Tutorial:
What is Neonatal Sepsis?
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Completing this tutorial will provide the learner with a better
understanding of Neonatal Sepsis:
What will I learn?
What is Neonatal Sepsis?
Neonatal Sepsis is a term
used for a severe infection
in newly born infants.
It can cause death if not recognized and treated properly.
Image used with permission and provided by www.steliz.org/newborn_center.htm
More facts about Neonatal Sepsis
Neonatal Sepsis affects approximately 2 infants per 1000
births with a higher incidence in premature & low birth
weight infants .
There are two types of Neonatal Sepsis:
* This tutorial will focus primarily on Early Onset Sepsis
Causes of Neonatal Sepsis
The primary causes of Neonatal Sepsis are bacteria, such
as Staphylococcus and Group Beta Strep (GBS).
Bacteria may be the cause of neonatal sepsis, but
neonates are more susceptible to these bacteria for two
Immature immune response
What makes a neonate’s immune
Normally an immune system responds
to a pathogen in a specific manner, but
if there are problems with any element
the immune system is unable to
function properly [3&6].
Pathogen enters body
Neutrophils move in
Monocytes kill pathogen
pathogens can enter a neonate’s
body in many ways !
Pathogens can enter through the prenatal, perinatal, and postnatal
Prenatal Maternal Substance Abuse
Premature Rupture of Membranes (>18 Hours)
Perinatal Microbial Colonization at Birth
Vaginal Exam of Mother
Postnatal Invasive Catheters
Exposure to Nosocomial Microorganisms
neutrophils: an important cell in
immunity against pathogens
Neonatal neutrophils are deficient in
their ability to adhere to vessel walls
at site of infection [2&6].
Further release of neutrophils
depletes a neonatal storage
pool because the bone marrow
storage of a neonate is only 20-30%
of the pool in an adult [2&6].
Neonatal neutrophils have a
decreased ability to “deform” &
migrate into tissues [2&6]. Neutrophils
Red Blood Cells
Image provided with permission from
Imagine: Being in a dark tunnel without any direction or a
way out. Finally you see light. You move towards
the light and get out of the tunnel. Well this is like
chemotaxis. The sun is the chemoattractant
attracting you out to the world!!
Neonatal neutrophils have
decreased chemotaxis due to
neutrophils to the site of infection
Neonatal neutrophils therefore
cannot reach the site of infection
because of the chemotaxis
deficiency caused by decreased
Opsonization is the coating of a
pathogen with antibodies that makes
it susceptible to phagocytosis [2&6].
Phagocytosis is the process of cells
(phagocytes) engulfing, ingesting, &
destroying pathogens [2&6].
Neonates have a decreased amount
of opsonins (antibodies that promote
monocytes: another important cell
in the fight against pathogens
Monocytes are a type of White Blood
Cell that ingests pathogens.
Neonates have a sufficient amount of
monocytes and full capability to kill
organisms , but because of a
neonates deficiencies previously
discussed very few monocytes get to
the site of infection.
Image provided with permission and copyrighted by amaxa GmbH at
What makes a neonate’s immune
system susceptible to sepsis?
The immaturity of a neonate’s immune system
makes them MORE SUSCEPTIBLE to sepsis.
Genetic Predisposition to Sepsis
Multiple factors play into a neonate’s response to infection and the
possible development of sepsis. One of these factors is genetics. As
science has moved into recognizing the human genome there have
also been advances with finding genetic contributions to sepsis.
The body’s first response to infection requires recognition of
the presence of a pathogen. After recognition has occurred
the body responds appropriately to resolve the problem
[3&14]. Many polymorphisms have been recognized within
both of these phases and they have been implicated in
influencing the susceptibility to and/or outcome from sepsis
Let’s look further into these two phases to see the effect
polymorphisms have on neonatal sepsis:
Recognition Phase Response Phase
The body’s initial response to infection requires recognition of the
presence of a pathogen .
Polymorphisms in genes coding for proteins involved in the recognition
of pathogens can influence the susceptibility to and/or outcome of
neonatal sepsis .
Let’s look into two of these:
Mannose-Binding Lectine (MBL)
After the initial recognition of a pathogen occurs the
body responds by releasing elevated levels of
proinflammatory cytokines followed by a release of
anti-inflammatory cytokines . This dual release of
opposite cytokines helps the cytokines return to a
baseline level and that enables the start of tissue
repair to start .
It is generally accepted that an imbalance between
proinflammatory and anti-inflammatory cytokines
result in clinical manifestations of sepsis . This
Imbalance is due to polymorphisms in various proteins
involved in the response to pathogens.
Let’s look into two of these :
Tumor Necrosis Factor (TNF) Interleukin 10 (IL-10)
LPS, a major component of bacteria, is a powerful
stimulator of the innate immune response .
LPS elicits it’s response by binding to a cell surface
receptor that is compromised of 3 proteins .
One of these proteins is TLR4.
TLR4 is required for LPS to respond.
When there are polymorphisms in TLR4 there is a
reduced response to LPS and that enhances the
susceptibility to infection!
Mannose-Binding Lectin (MBL)
MBL has two primary immunodefensive roles :
– involved with opsonization
– leads to activation of complement system, independent
Polymorphisms cause deficiencies in MBL level .
This results in decreased levels of MBL. This deficiency
is associated with increased susceptibility to infections!
Tumor Necrosis Factor (TNF)
TNF is a proinflammatory cytokine that is responsible
for the initial activation of the inflammatory response
There are several polymorphisms associated with an
increased secretion of TNF resulting in the susceptibility
Interleukin 10 (IL-10)
IL-10 is an anti-inflammatory cytokine produced by
primarily monocytes . IL-10 helps regulate the over
expression of proinflammatory cytokines.
There are three polymorphisms noted that result in an
over expression of IL-10. This over expression is
proposed to induce immunosuppression in bacterial
sepsis and therefore increasing mortality by inhibiting
bacterial clearance .
What effect do polymorphisms
have in Neonatal Sepsis?
They make a neonate more susceptible to sepsis.
They have no apparent effect.
They make a neonate less susceptible to sepsis.
Great answer! You’re correct!
Polymorphisms cause either an over expression or under expression of
proteins and/or genes that have significant roles in the immune
response to infection. This alters their ability to properly function which
makes a neonate more susceptible to sepsis.
Symptoms of Neonatal Sepsis
The symptoms of neonatal sepsis are not concrete and vary
Heart Rate Changes
Difficulty Breathing Temperature Instability
Why are symptoms so broad?
Symptom variability occurs because of the metabolic and inflammatory
processes that occur in neonatal sepsis.
A neonate’s symptoms are rooted in
these two processes.
Let’s look more into these areas: Metabolism
Metabolism in Neonatal Sepsis
Sepsis can alter a neonate’s metabolism .
The Ebb & Flow Metabolic Response  best describes
how a neonate’s metabolism is affected by sepsis.
This is the initial phase and last only 1-3 days. This is how a neonate’s body
initially tries to compensate for losses that occur during sepsis. The body
slows things down in order to let the body recover.
The Ebb Phase consists of several clinical manifestations :
– Decreased energy expenditure
– Decreased cardiac output
– Lowered oxygen consumption
This is the phase that occurs after the initial Ebb Phase. If the body
doesn’t recover it goes into hyperdrive. This is partly due to the
exaggerated inflammatory response (further discussion in inflammatory
process section). This phase leads to much of the mortality and
morbidity related to neonatal sepsis .
The Flow Phase consists of several clinical manifestations :
– Increased energy expenditure
– Increased cardiac output
– High oxygen consumption
What metabolic phase causes a
neonate’s body into “hyperdrive”?
Inflammation in Neonatal Sepsis
It is widely known that sepsis occurs
because of an exaggerated
systemic inflammatory response (SIR) .
Let’s find out how this is true Inflammatory Process
Pathogen enters body
Injury to endothelium
Tissue factors released
Production of thrombin
Increased activity of
Overall, the imbalance among inflammation, over coagulation, and
decreased fibrinolysis are the cause for the majority of deaths in
How is Neonatal Sepsis
There is no definite marker in neonatal sepsis, but there are
determinants of infection.
When a neonate presents with sepsis symptoms a septic work-up
is completed . What is included in a septic work up?
* Complete Blood Count (CBC)
* Blood & Urine cultures
* Lumbar Puncture (LP)
* Chest X-Ray
* Line cultures
Is there a diagnostic marker for
Yeah!!! You are correct!
There is NOT a specific diagnostic marker, only
determinants of infection (labs, x-rays).
Treatments for Neonatal Sepsis
It is of vital importance that treatment is initiated as soon as
sepsis is suspected, especially for those infants at risk.
Broad Spectrum Antibiotics (Ampicillin & Gentamycin) are
the first line of defense against neonatal sepsis .
What are other recommendations/options?
Why is it so important to start
If not treated as soon as sepsis is suspected a neonate is more likely to
die from sepsis and it’s complications.
For this reason it is of vital importance that healthcare workers (nurses
and physicians) notice and act upon even the most subtle changes
in a neonates assessment, particularly those infants at risk (GBS+).
Antibiotics should be initiated after all cultures and lab work is
completed to ensure proper diagnosis.
All neonates will remain on IV antibiotics until blood/urine culture
come back in approximately 2-3 days. Further therapy will depend on
lab work results and the neonate’s response to treatment.
* Every hospital/organization has an antibiotic protocol specific to their site.
Although antibiotic therapy is vital, it is just as important to continue the
overall support of the neonate (i.e. respiratory & cardiac).
Neonatal Sepsis is a severe infection in neonates that has the ability to cause death if not
recognized and treated appropriately. The primary causes of sepsis are pathogens, such
as Staphylococcus and Group Beta Strep [2&6]. These pathogens can enter a neonate’s
body during the prenatal, perinatal, and postnatal period . Although pathogens are the
culprit in sepsis, neonates have factors that make them more susceptible to sepsis. One
of these factors is the immaturity of the neonate’s immune system . The second factor
is related to a possible genetic predisposition that is caused by polymorphisms [3&14]. A
Neonate’s symptoms in sepsis are broad and vary . This is due in part to the
metabolic and inflammatory processes that occur in neonatal sepsis. Because symptoms
are broad and not very concrete, it is of vital importance that the healthcare professional
notice even the most subtle changes in a neonate’s assessment. When sepsis is
suspected a neonate will undergo a septic work up , which includes lab work and x-
rays. After lab work is completed intravenous antibiotics are initiated immediately and will
continue until lab work demonstrates no infection and the neonate shows no further
I hope you have enjoyed your experience and
have learned some new information about
Contact Information: firstname.lastname@example.org
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