NEONATAL SEPSIS CLINICAL SIGNS
Category: Child Health
Abstract :
History: The risk factors that are associated most highly with neonatal sepsis
include maternal GBS colonization (especially if untreated during labor),
premature rupture of membranes (PROM), preterm rupture of membranes, prolonged
rupture of membranes, prematurity, and chorioamnionitis. Predisposing risk
factors also are associated with neonatal sepsis. They include low Apgar score
(<
History: The risk factors that are associated most highly with neonatal sepsis
include maternal GBS colonization (especially if untreated during labor),
premature rupture of membranes (PROM), preterm rupture of membranes, prolonged
rupture of membranes, prematurity, and chorioamnionitis. Predisposing risk
factors also are associated with neonatal sepsis.
They include low Apgar score
(<6 at 1 or 5 min), maternal fever greater than 101°F (38.4°C), maternal
urinary tract infection, poor prenatal care, poor maternal nutrition, low
socioeconomic status, recurrent abortion, maternal substance abuse, low birth
weight, difficult delivery, birth asphyxia, meconium staining, and congenital
anomalies.
The predisposing risk factors implicated in neonatal sepsis
reflect the stress and illness of the fetus at delivery, as well as the
hazardous uterine environment surrounding the fetus before delivery.
An
awareness of the myriad of risk factors associated with neonatal sepsis prepares
the clinician for early identification and effective treatment, thereby reducing
mortality and morbidity.
• Maternal GBS status
o The most common
etiology of neonatal bacterial sepsis is GBS. Nine serotypes exist, and each is
related to the polysaccharide capsule of the organism. Types I, II, and III are
commonly associated with neonatal GBS infection. The type III strain has been
shown to be most highly associated with CNS involvement in early-onset
infection, whereas type V has been associated with early-onset disease without
CNS involvement.
o The GBS organism colonizes the maternal gastrointestinal
tract and birth canal. Approximately 30% of women have asymptomatic GBS
colonization during pregnancy. GBS is responsible for approximately 50,000
maternal infections per year in women, but only 2 neonates per 1000 live births
are infected. Women with heavy GBS colonization and cultures that are
chronically positive for GBS have the highest risk of perinatal transmission.
Also, heavy colonization at 23-26 weeks of gestation is associated with
prematurity and low birth weight. Colonization at delivery is associated with
neonatal infection. Intrapartal chemoprophylaxis of women with positive cultures
for GBS has been shown to decrease the transmission of the organism to the
neonate during delivery.
• PROM may occur in response to an untreated
infection of the urinary tract or birth canal and is also associated with
previous preterm delivery, uterine bleeding in pregnancy, and heavy cigarette
smoking during pregnancy.
o Rupture of membranes without other complications
for more than 24 hours prior to delivery is associated with a 1% increase in the
incidence of neonatal sepsis; however, when chorioamnionitis accompanies the
rupture of membranes, the incidence of neonatal infection is quadrupled.
o A
recent multicenter study demonstrated that clinical chorioamnionitis and
maternal colonization with GBS are the most important predictors of subsequent
neonatal infection following PROM.
o When membranes have ruptured prematurely
before 37 weeks' gestational age, a longer latent period precedes vaginal
delivery, increasing the likelihood that the infant will be infected. The
relationship between duration of membrane rupture and neonatal infection is
inversely related to gestational age. Therefore, the more premature an infant,
the longer the delay between rupture of membranes and delivery, and higher the
likelihood of neonatal sepsis.
o A study by Seaward et al found that more
than 6 vaginal digital examinations, which may occur as part of the evaluation
for PROM, were associated with neonatal infection even when considered
separately from the presence of chorioamnionitis.
• Prematurity: The
relationship between preterm PROM and neonatal sepsis has already been
described; however, other associations between prematurity and neonatal sepsis
increase the risk for premature infants.
o Preterm infants are more likely to
require invasive procedures, such as umbilical catheterization and
intubation.
o Prematurity is associated with infection from CMV, HSV,
hepatitis B, toxoplasmosis, Mycobacterium tuberculosis, Campylobacter fetus, and
Listeria species.
o Intrauterine growth retardation and low birth weight are
also observed in CMV and toxoplasmosis infections.
o Premature infants have
less immunologic ability to resist infection.
• Chorioamnionitis: The
relationship between chorioamnionitis and other risk variables is strong.
Suspect chorioamnionitis in the presence of fetal tachycardia, uterine
tenderness, purulent amniotic fluid, elevated maternal WBC count, and
unexplained maternal temperature above 100.4°F (38°C).
Physical: The
clinical signs of neonatal sepsis are nonspecific and are associated with
characteristics of the causative organism and the body's response to the
invasion. These nonspecific clinical signs of early sepsis syndrome are also
associated with other neonatal diseases, such as Respiratory Distress Syndrome
(RDS), metabolic disorders, intracranial hemorrhage, and a traumatic delivery.
Therefore, diagnose neonatal sepsis by excluding other disease processes,
performing an examination, and testing for more specific indications of neonatal
sepsis.
• Congenital pneumonia and intrauterine infection: Inflammatory
lesions are observed postmortem in the lungs of infants with congenital and
intrauterine pneumonia. This may not be caused by the action of the
microorganisms themselves but may be caused by aspiration of amniotic fluid
containing maternal leukocytes and cellular debris. Tachypnea, irregular
respirations, moderate retracting, apnea, cyanosis, and grunting may be
observed. Neonates with intrauterine pneumonia may also be critically ill at
birth and require high levels of ventilatory support. The chest radiograph may
depict bilateral consolidation or pleural effusions.
• Congenital
pneumonia and intrapartum infection: Neonates who are infected during the birth
process may acquire pneumonia through aspiration of the microorganisms during
the delivery process. The colonization may lead to infection with pulmonary
changes, infiltration, and destruction of bronchopulmonary tissue. This damage
is partly due to the granulocytes' release of prostaglandins and leukotrienes.
Fibrinous exudation into the alveoli leads to inhibition of pulmonary surfactant
function and respiratory failure with an RDS-like presentation. Vascular
congestion, hemorrhage, and necrosis may occur.
o Klebsiella species and
S aureus are especially capable of considerably damaging the lungs, producing
microabscesses and empyema.
o Infectious pneumonia is also characterized
by pneumatoceles within the pulmonary tissue. Coughing, grunting, costal and
sternal retractions, nasal flaring, tachypnea and/or irregular respiration,
rales, decreased breath sounds, and cyanosis may be observed.
o On
radiography, segmental or lobar atelectasis or a diffuse reticulogranular
pattern may exist, much like what is observed in RDS.
o Pleural effusions
may be observed in advanced disease.
• Congenital pneumonia and postnatal
infection: Postnatally acquired pneumonia may occur at any age. Because these
infectious agents exist in the environment, the likely cause depends heavily on
the infant's recent environment. If the infant has remained hospitalized in an
NICU environment, especially with endotracheal intubation and mechanical
ventilation, the organisms may include Staphylococcus or Pseudomonas species.
Additionally, these hospital-acquired organisms frequently demonstrate multiple
antibiotic resistances. Therefore, the choice of antibiotic agents in such cases
requires knowledge of the likely causative organisms and the
antibiotic-resistance patterns of the hospital.
• Cardiac signs: In
overwhelming sepsis, an initial early phase characterized by pulmonary
hypertension, decreased cardiac output, and hypoxemia is postulated to occur.
These cardiopulmonary disturbances may be due to the activity of granulocyte
biochemical mediators, such as hydroxyl radicals and thromboxane B2, an
arachidonic acid metabolite. These biochemical agents have vasoconstrictive
actions that result in pulmonary hypertension when released in pulmonary tissue.
A toxin derived from the polysaccharide capsule of type III Streptococcus has
also been shown to cause pulmonary hypertension. The early phase of pulmonary
hypertension is followed by further progressive decreases in cardiac output with
bradycardia and systemic hypotension. The infant manifests overt shock with
pallor, poor capillary perfusion, and edema. These late signs of shock are
indicative of severe compromise and are highly associated with
mortality.
• Metabolic signs: Hypoglycemia, metabolic acidosis, and
jaundice all are metabolic signs that commonly accompany neonatal sepsis
syndrome. The infant has an increased glucose requirement because of sepsis. The
infant may also have impaired nutrition from a diminished energy intake.
Metabolic acidosis is due to a conversion to anaerobic metabolism with the
production of lactic acid. When infants are hypothermic or they are not kept in
a neutral thermal environment, efforts to regulate body temperature can cause
metabolic acidosis. Jaundice occurs in response to decreased hepatic
glucuronidation caused by both hepatic dysfunction and increased erythrocyte
destruction.
• Neurologic signs: Meningitis is the common manifestation
of infection of the central nervous system. It is primarily associated with GBS
(36%), E coli (31%), and Listeria species (5-10%) infections, although other
organisms such as S pneumoniae, S aureus, Staphylococcus epidermis, Haemophilus
influenzae, and species of Pseudomonas, Klebsiella, Serratia, Enterobacter, and
Proteus may cause meningitis. Acute and chronic histologic features are
associated with specific organisms.
o Ventriculitis is the initiating
event with inflammation of the ventricular surface. Exudative material usually
appears at the choroid plexus and is external to the plexus. Then, ependymitis
occurs with disruption of the ventricular lining and projections of glial tufts
into the ventricular lumen. Glial bridges may develop by these tufts and cause
obstruction, particularly at the aqueduct of Sylvius. The lateral ventricles may
become multiloculated, which is similar to forming abscesses. Multiloculated
ventricles can isolate organisms in an area, making treatment more difficult.
Meningitis is likely to arise at the choroid plexus and extend via the
ventricles through aqueducts into the arachnoid to affect the cerebral and
cerebellar surfaces. The high glycogen content in the neonatal choroid plexus
provides an excellent medium for the bacteria. Ventricular origination of
meningitis causes significant treatment problems because the areas are
inaccessible. Ventricular obstruction causes an additional problem.
o
Arachnoiditis is the next phase and is the hallmark of meningitis. The arachnoid
is infiltrated with inflammatory cells producing an exudate that is thick over
the base of the brain and more uniform over the rest of the brain. Early in the
infection, the exudate is primarily PMNs, bacteria, and macrophages. Exudate is
prominent around the blood vessels and extends into the brain parenchyma. In the
second and third weeks of infection, the proportion of PMNs decreases; the
dominant cells are histiocytes, macrophages, and some lymphocytes and plasma
cells. Exudate infiltration of cranial roots 3-8 occurs. After this period, the
exudate decreases. Thick strands of collagen form, and arachnoid fibrosis
occurs, which is responsible for obstruction. Hydrocephalus results. Early-onset
GBS meningitis is characterized by much less arachnoiditis than late-onset GBS
meningitis.
o Vasculitis extends the inflammation of the arachnoid and
ventricles to the blood vessels surrounding the brain. Occlusion of the arteries
rarely occurs; however, venous involvement is more severe. Phlebitis may be
accompanied with thrombosis and complete occlusion. Multiple fibrin thrombi are
especially associated with hemorrhagic infarction. This vascular involvement is
apparent within the first days of meningitis and becomes more prominent during
the second and third weeks.
o Cerebral edema may occur during the acute
state of meningitis. The edema may be severe enough to greatly diminish the
ventricular lumen. The cause is unknown, but it is likely related to vasculitis
and the increased permeability of blood vessels. It may also be related to the
cytotoxins of microorganisms. Herniation of edematous supratentorial structures
does not occur in neonates because of the cranium's distensibility.
o
Infarction is a prominent and serious feature of neonatal meningitis. It occurs
in 30% of infants who die. Lesions occur because of multiple venous occlusions,
which are frequently hemorrhagic. The loci of infarcts are most often in the
cerebral cortex and underlying white matter but may also be subependymal within
the deep white matter. Neuronal loss occurs, especially in the cerebral cortex,
and periventricular leukomalacia may subsequently appear in areas of neuronal
cell death.
o Meningitis due to early-onset neonatal sepsis usually
occurs within 24-48 hours and is dominated by nonneural signs. Neurologic signs
may include stupor and irritability. Overt signs of meningitis occur in only 30%
of cases. Even culture-proven meningitis may not demonstrate white cell changes
in the CSF. Meningitis due to late-onset disease is more likely to demonstrate
neurologic signs (80-90%). Impairment of consciousness (ie, stupor with or
without irritability), coma, seizures, bulging anterior fontanel, extensor
rigidity, focal cerebral signs, cranial nerve signs, and nuchal rigidity
occur.
o The CSF findings in infectious neonatal meningitis are an
elevated WBC count (predominately PMNs), an elevated protein level, a decreased
CSF glucose concentration, and positive cultures. The decrease in CSF glucose
concentration does not necessarily reflect serum hypoglycemia. Glucose
concentration abnormalities are more severe in late-onset disease and with
gram-negative organisms. The CSF WBC count is within the reference range in 29%
of GBS meningitis infections; in gram-negative meningitis, it is within the
reference range in only 4%. Reference range CSF protein and glucose
concentrations are found in about 50% of patients with GBS meningitis; however,
in gram-negative infections, reference range CSF protein and glucose
concentrations are found in only 15-20%.
o Temperature instability is
observed with neonatal sepsis and meningitis, either in response to pyrogens
secreted by the bacterial organisms or from sympathetic nervous system
instability. The neonate is most likely to be hypothermic. The infant is also
floppy, lethargic, and disinterested in feeding. Signs of neurologic
hyperactivity are more likely when late-onset meningitis occurs.
•
Hematologic signs
o The platelet count in the healthy newborn is rarely less
than 100,000 per mm3 in the first 10 days of life. Thrombocytopenia with counts
less than 100,000 may occur in neonatal sepsis in response to the cellular
products of the microorganisms. These cellular products cause platelet clumping
and adherence leading to platelet destruction. Thrombocytopenia is generally
observed after sepsis has been diagnosed and usually lasts 1 week, though it can
last as long as 3 weeks. Only 10-60% of infants with sepsis have
thrombocytopenia. Because of the appearance of newly formed platelets, mean
platelet volume (MPV) and platelet distribution width (PDW) are shown to be
significantly higher in neonatal sepsis after 3 days. Because of the myriad of
causes of thrombocytopenia and its late appearance in neonatal sepsis, the
presence of thrombocytopenia does not aid the diagnosis of neonatal
sepsis.
o WBC counts and ratios are more sensitive for determining sepsis
than platelet counts, although normal WBC counts may be observed in as many as
50% of cases of culture-proven sepsis. Infants who are not infected may also
demonstrate abnormal WBC counts related to the stress of delivery. A
differential may be of more use in diagnosing sepsis. Total neutrophil count
(PMNs and immature forms) is slightly more sensitive in determining sepsis than
total leukocyte count (percent lymphocyte + monocyte/PMNs + bands). Abnormal
neutrophil counts, taken at the time of symptom onset, are only observed in two
thirds of infants; therefore, the neutrophil count does not provide adequate
confirmation of sepsis. Neutropenia is observed with maternal hypertension,
severe perinatal asphyxia, and periventricular or intraventricular hemorrhage. o
Neutrophil ratios have been more useful in diagnosing or excluding neonatal
sepsis; the immature-to-total (I/T) ratio is the most sensitive. All immature
neutrophil forms are counted, and the maximum acceptable ratio for excluding
sepsis during the first 24 hours is 0.16. In most newborns, the ratio falls to
0.12 within 60 hours of life. The sensitivity of the I/T ratio has ranged from
60-90%, and elevations may be observed with other physiological events;
therefore, when diagnosing sepsis, the elevated I/T ratio should be used in
combination with other signs.
• Gastrointestinal signs: The gut can be
colonized by organisms in utero or at delivery by swallowing infected amniotic
fluid. The immunologic defenses of the gut are not mature, especially in the
preterm infant. Lymphocytes proliferate in the gut in response to mitogen
stimulation; however, this proliferation is not fully effective in responding to
a microorganism because antibody formation and cytokine formation is immature
until approximately 46 weeks. Necrotizing enterocolitis (NEC) has been
associated with the presence of a number of species of bacteria in the immature
gut, and bacterial overgrowth of these organisms in the neonatal lumen is a
component of the multifactorial pathophysiology of NEC.
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