NITHIN JAYAN NITHIN JAYAN NITHIN JAYAN NITHIN JAYAN NITHIN HUMAYOON NITHIN HUMAYOON NITHIN HUMAYOON NITHIN HUMAYOON NITHA J NITHA J NITHA J NITHA J Dr.VIJAYAKUMAR .VIJAYAKUMAR .VIJAYAKUMAR .VIJAYAKUMAR Department O Department O Department O Department Of Community ommunity ommunity ommunity Medicine, Medicine, Medicine, Medicine, Govt Govt Govt Govt. Medical Medical Medical Medical College College College College Trivandrum Trivandrum Trivandrum Trivandrum Risk isk isk isk Factors actors actors actors Of Neonatal eonatal eonatal eonatal Sepsis epsis epsis epsis In Triv riv riv rivandrum andrum andrum andrum, K ,K ,K , Kerala erala erala erala
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13489793 Neonatal Sepsis a Study of the Risk Factors
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Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of
infection with or without accompanying bacteremia in the first month of life. It
encompasses various systemic infections of the newborn such as septicemia,
meningitis, pneumonia, arthritis, osteomyelitis, and urinary tract infections. Superficial
infections like conjunctivitis and oral thrush are not usually included under neonatal
sepsis.
EPIDEMIOLOGY
According to recent data from National Neonatal Perinatal Database (NNPD) 2002, the
incidence of neonatal sepsis has been reported to be 30 per 1000 intramural live
births in tertiary care institutions. Septicemia was the commonest clinical category
with an incidence of 23 per 1000 live births. Meningitis was diagnosed in 3 per 1000
live births.
Neonatal sepsis was one of the common causes of neonatal mortality contributing to
19% of all neonatal deaths. Klebsiella pneumoniae was the most frequently isolated
pathogen(32.5%), followed by Staphylococcus aureus (13.6%) among the intramural
live births.
Among extramural babies admitted for neonatal problems, Klebsiella pneumoniae was
the commonest organism (27%), followed by Staphylococcus aureus (15%) and
Pseudomonas (13%).
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ETIOLOGY
Classification of neonatal sepsisClassification of neonatal sepsisClassification of neonatal sepsisClassification of neonatal sepsis
Neonatal sepsis can be divided into two main classes depending on the onset of
symptoms related to sepsis:
Early onset sepsis: Early onset sepsis: Early onset sepsis: Early onset sepsis: Early onset sepsis usually presents within the first 72 hours of life.
In severe cases, the neonate may be symptomatic in utero (fetal tachycardia, poor beat
to beat variability or within a few hours after birth. The source of infection is generally
the maternal genital tract. Clinically, neonates usually present with respiratory distress
and pneumonia. Presence of some perinatal risk factors has been associated with an
increased risk of early onset sepsis. Recommendations from developed countries
suggest that presence of 2 risk factors should be considered an indication for starting
antibiotics.
However the main organism is group B streptococci (GBS) which is not a problem in
our neonatal intensive care units. Hence, their recommendations may not be applicable
to our setting. Since definitive data for our setting is lacking, an empirical approach has
been recommended.
Presence of the following high-risk factors has been associated with an increased risk
of early onset sepsis::::
� Low birth weight (<2500 grams) or preterm baby
� Febrile illness in the mother within 2 weeks prior to delivery.
� Foul smelling and/ or meconium stained liquor amnii.
� Prolonged rupture of membranes >24 hours.
� More than 3 vaginal examinations during labor
� Prolonged and difficult delivery with instrumentation
� Perinatal asphyxia (Apgar score <4 at 1 minute or age) or difficult resuscitation
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Neonates with presence of foul smelling liquor or three of the above mentioned risk
factors should be considered to have early onset sepsis and treated with antibiotics.
Presence of 2 risk factors should be investigated with a septic screen and treated
accordingly.
Late onset sepsis: Late onset sepsis: Late onset sepsis: Late onset sepsis: Late onset sepsis usually presents after 72 hours of age. The source
of infection is either nosocomial or community-acquired and neonates usually present
with septicemia, pneumonia or meningitis. Various factors that predispose to an
increased risk of nosocomial sepsis include NICU admissions, low birth weight,
prematurity, invasive procedures, parenteral fluid therapy, ventilation and use of stock
solutions. Factors that may increase risk of community-acquired late onset sepsis
include poor hygiene, poor cord care, bottle-feeding and prelacteal feeds. Breast-
feeding, on the other hand, prevents infection in neonates.
Clinical featuresClinical featuresClinical featuresClinical features
NonNonNonNon----specific feaspecific feaspecific feaspecific features of sepsis: tures of sepsis: tures of sepsis: tures of sepsis: The earliest signs of sepsis are often subtle and non
specific and need a high index of suspicion for early diagnosis.
Babies with sepsis may present with one or more of the following symptoms and signs
(a) Hypothermia or fever (former is more common in low birth weight babies)
(b) Lethargy, poor cry, refusal to suck
(c) Poor perfusion, prolonged capillary refill time
(d) Hypotonia, absent neonatal reflexes
(e) Bradycardia; tachycardia
(f) Respiratory distress, apnea and gasping respiration
(g) Hypoglycemia, hyperglycemia
(h) Metabolic acidosis
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Specific features related to various systems.Specific features related to various systems.Specific features related to various systems.Specific features related to various systems. Central nervous system (CNS): Bulging anterior fontanelle, blank look, high-pitched cry,
excess irritability, not arousable, comatose, seizures, neck retraction. Presence of these
features should raise a clinical suspicion of meningitis
All newborns suspected to have neonatal sepsis should have a septic screen to
corroborate the diagnosis of sepsis. However, if there is a strong clinical suspicion of
sepsis, the decision to start antibiotics need not be conditional to a sepsis screen.
Presence of any factor in neonates at risk of early onset sepsis should have a septic
screen to decide antibiotic therapy. The various components of the septic screen
include total leukocyte count, absolute neutrophil count, immature to total neutrophil
ratio, micro-erythrocyte sedimentation rate and C reactive protein. The absolute
neutrophil count varies considerably in the immediate neonatal period and normal
reference ranges are available in Manroe’s charts. The lower limit for normal total neutrophil counts in the newborn begins at 1800/cmm, rises to 7200/cmm at 12 hours of age and then declines and persists at 1800/cmm after 72 hours of age. The ratio of immature to total neutrophils (I/T ratio) is 0.16 at birth and declines to a peak value of 0.12 after 72 hours of age. Presence of two abnormal parameters in a screen
is associated with a sensitivity of 93-100%, specificity of 83%, positive and negative
predictive values of 27% and 100% respectively in detecting sepsis. Hence, if two
parameters are abnormal, it should be considered as a positive septic screen and it is
reasonable to start antibiotic therapy. If a septic screen is negative in the presence of
strong clinical suspicion, it should be repeated within 12 hours. If the screen is still
negative, sepsis can be excluded with reasonable certainty.
For early onset sepsis, documentation of polymorphs in the neonatal gastric aspirate at
birth serves as a marker of chorioamnionitis and it may be taken as one parameter of
Indications for starting antibiotics: Indications for starting antibiotics: Indications for starting antibiotics: Indications for starting antibiotics:
The indications for starting antibiotics in neonates at risk of early onset sepsis include
the following:
� presence of three risk factors for early onset sepsis
� presence of foul smelling liquor
� presence of 2 antenatal risk factor(s) with a positive septic screen and
� strong clinical suspicion of sepsis.
The indications for starting antibiotics in late onset sepsis include
� positive septic screen and/ or
� strong clinical suspicion of sepsis.
Prophylactic antibiotics: Prophylactic antibiotics: Prophylactic antibiotics: Prophylactic antibiotics: We do not recommend the use of prophylactic antibiotics for
single exchange transfusions. An exchange transfusion conducted under strict asepsis
(single use catheter, sterile gloves, removal of catheter after the procedure) does not
increase the risk of sepsis and does not merit antibiotics. However a messy exchange
or 3 exchange transfusions should be treated with prophylactic antibiotics. In our unit,
ventilated neonates are treated with prophylactic antibiotics for 5-7 days.
Choice of antibiotics: Choice of antibiotics: Choice of antibiotics: Choice of antibiotics: Empirical antibiotic therapy should be unit specific and
determined by the prevalent spectrum of etiological agents and their antibiotic
sensitivity pattern. Antibiotics once started should be modified according to the culture
sensitivity reports. Guidelines for empirical antibiotic therapy have been provided in
Table.
The empirical choice of antibiotics is dependent upon the probable source of origin of
infection. For infections that are likely to be community-acquired and where resistant
strains are unlikely; a combination of ampicillin or penicillin with gentamicin may be a
good choice for first line therapy. Chloramphenicol may be added to treat meningitis
acquired from the community. For infections that are acquired during hospital stay,
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resistant pathogens are likely and a combination of ampicillin or cloxacillin with
gentamicin or amikacin may be instituted. Cefotaxime or Ceftriaxone should be added
for treatment of meningitis where resistant strains are likely. In nurseries where this
combination is ineffective due to the presence of multiple resistant strains of Klebsiella
and other gram-negative bacilli, a combination of a third generation cephalosporin
(cefotaxime or ceftizoxime) with amikacin may be appropriate Clinical situation
Septicemia & Pneumonia
Meningitis
FIRST LINE Community-acquired or Resistant strains unlikely
Ampicillin or Penicillin and Gentamicin
Add Chloramphenicol
SECOND LINE Hospital-acquired or Some resistant strains likely
Ampicillin or Cloxacillin and Gentamicin or Amikacin
Add Cefotaxime
THIRD LINE Hospital-acquired sepsis Resistant strains are most likely
Third generation cephalosporins including cefotaxime, ceftriaxone and ceftazidime
have excellent antimicrobial activity against gram negative organisms (including
klebsiella) and have very good CSF penetration. Ceftazidime is particularly effective
against pseudomonas infections. These antibiotics are an excellent choice for the
treatment of nosocomial infections and meningitis. Newer antibiotics like aztreonam
and imepenem are also now available in the market. Aztreonam has excellent activity
against gram-negative organisms and imepenem is effective against most bacterial
pathogens except methicillin resistant Staphylococcus aureus (MRSA) and
Enterococcus.
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The empirical use of the last two antibiotics is best avoided and should be reserved for
situations where sensitivity of the isolate justifies its use. Ciprofloxacillin is another
antibiotic with excellent activity against gram-negative organisms although it does not
have very good CSF penetration. Hence ciprofloxacillin may be used for the treatment
of resistant gram-negative bacteremia after excluding meningitis. A combination of
piperacillin or ceftazidime with amikacin should be considered if pseudomonas sepsis
is suspected. Penicillin resistant Staphylococcus aureus should be treated with
cloxacillin, nafcillin or methicillin. Addition of an aminoglycoside is useful in therapy
against Staphylococcus. Methicillin resistant Staphylococcus aureus (MRSA) should be
treated with a combination of either ciprofloxacillin or vancomycin with amikacin. For
sepsis due to Enterococcus, a combination of ampicillin and gentamicin is a good
choice for initial therapy. Vancomycin should be used for the treatment of
Enterococcus resistant to the first line of therapy.
Adjunctive therapyAdjunctive therapyAdjunctive therapyAdjunctive therapy Exchange transfusion (ET): Exchange transfusion (ET): Exchange transfusion (ET): Exchange transfusion (ET): Sadana et al have evaluated the role of a single double
volume exchange transfusion in septic neonates with sclerema and demonstrated a
50% reduction in sepsis related mortality in the treated group. We perform double-
volume exchange transfusion with cross-matched fresh whole blood as adjunctive
therapy in septic neonates with sclerema.
Intravenous Immunoglobulin (IVIG): Intravenous Immunoglobulin (IVIG): Intravenous Immunoglobulin (IVIG): Intravenous Immunoglobulin (IVIG): Non-specific pooled IVIG has not been found to
“Concern about the effect of corticosteroids in the presence of intrauterine infection
stems mainly from the fear that the immunosuppressive effects of corti-costeroids
could dampen the immunologic host response to infection by worsening the damaging
effects of bacteria and their toxins on the nervous tissue. Our findings do not support
such an adverse effect; in fact, the opposite is tthe opposite is tthe opposite is tthe opposite is truerueruerue.”
By Univariate analysis we found that antenatal steroid therapy is a protective factor
with odds ratio of 0.940
Crosstabulation :StatusV/S
AntenatalSteroidTherapy
AntenatalSteroidTherapy
Status Yes No Total
Case 6 94 100
Control 0 200 200
Total 6 294 300
Pearson Chi-Square value:12.245(df=1)
p value:0.000
Odds Ratio: 0.940
95% Confidence Interval: 0.895-0.988
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MULTIVARIATE ANALYSIS
The variables of our study were subjected to multivariate analysis by binary logistic
regression. It was found that the following factors accounted for 33.6% of the total risk
factors predisposing to neonatal sepsis
� Abortion
� Age at admission
� Birth Weight
� Perinatal Asphyxia
� PROM
Logistic regression of significant factors
VARIABLES B Sig Exp(B)
Abortion 1.056 .038 2.873
Age at admission 1.722 .000 5.597
Birth Weight 1.729 .000 5.633
Perinatal Asphyxia 2.538 .019 12.657
PROM 2.182 .015 8.861
SUMMARY OF VALUES
-2 Log
likelihood
Cox & Snell R
Square
Nagelkerke R
Square
267.911 .336 .439
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CONCLUSIONS AND CONCLUSIONS AND CONCLUSIONS AND CONCLUSIONS AND RECOMMENDATIONSRECOMMENDATIONSRECOMMENDATIONSRECOMMENDATIONS
� Perinatal asphyxiaPerinatal asphyxiaPerinatal asphyxiaPerinatal asphyxia is caused by a decreased supply of oxygen to the foetus or
newborn.
It can happen in the antepartum period, during labour, or at the time of birth. In
suspected cases adequate oxygen therapy to the mother can prevent
antepartum foetal hypoxia. Every labour should be conducted under an ideal
setup by trained persons avoiding unwanted delays. This is because;
prolongation of labour exposes the neonate to the risk of developing hypoxia.
� In case of suspected cases of PROMPROMPROMPROM (which is a strong risk factor of neonatal
sepsis) avoid cervical examination since it decreases latency and increases
chances of ascending infection. Early induction and delivery of the baby must be
done in those cases.
� Endotracheal intubation and aspiratiEndotracheal intubation and aspiratiEndotracheal intubation and aspiratiEndotracheal intubation and aspiration of amniotic fluidon of amniotic fluidon of amniotic fluidon of amniotic fluid are risk factors, the
possible explanation being that these factors create a new portal of entry of
infected pathogenic materials.
� PCODPCODPCODPCOD, a risk factor of neonatal sepsis can be controlled efficiently by primordial
intervention. Factors like Chronic stress, nutrient deficiencies, and excess consumption of animal foods (high in arachidonic acid) which contribute to the development of PCOD are to be controlled.
� Neonates (below 72 hours of age) are more vulnerable to developing neonatal
sepsis. Hence greater care must be provided during the early hours. � Early onset sepsis syndromeEarly onset sepsis syndromeEarly onset sepsis syndromeEarly onset sepsis syndrome is associated with acquisition of microorganisms from
the mother (in conditions like Rubella, UTI). Regular anti-natal checkups are to be advocated since these facilitate early diagnosis and hence effective management of
these infectious conditions.
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� The source of infection is either nosocomial or community-acquired in late onset late onset late onset late onset sepsissepsissepsissepsis hence:
� All persons taking care of the baby should strictly follow hand washinhand washinhand washinhand washing policiesg policiesg policiesg policies before
touching any baby. It is preferable to use bar soaps rather than liquid soapsbar soaps rather than liquid soapsbar soaps rather than liquid soapsbar soaps rather than liquid soaps as the
latter tend to harbour organisms after storage.
� The nursery environment should be clean and drynursery environment should be clean and drynursery environment should be clean and drynursery environment should be clean and dry with 24 hour water supply and
electricity. There should be adequate ventilation and lightingventilation and lightingventilation and lightingventilation and lighting. The nursery
temperature should be maintained between 30temperature should be maintained between 30temperature should be maintained between 30temperature should be maintained between 30++++2°C2°C2°C2°C. Overcrowding should be Overcrowding should be Overcrowding should be Overcrowding should be avoided. avoided. avoided. avoided.
� All procedures should be performed after wearing mask and glovesmask and glovesmask and glovesmask and gloves. Unnecessary Unnecessary Unnecessary Unnecessary invasive interventions such as needle pricks ainvasive interventions such as needle pricks ainvasive interventions such as needle pricks ainvasive interventions such as needle pricks and setting up of intravenous lines nd setting up of intravenous lines nd setting up of intravenous lines nd setting up of intravenous lines should be kept to the barest minimum.should be kept to the barest minimum.should be kept to the barest minimum.should be kept to the barest minimum. There should be no compromise in the use of
disposablesdisposablesdisposablesdisposables. Stock solutions for rinsing should be avoided.
� Every baby must have separate thermometer and stethoscopeEvery baby must have separate thermometer and stethoscopeEvery baby must have separate thermometer and stethoscopeEvery baby must have separate thermometer and stethoscope and all barrier
nursing measures must be followed.
� Low birth weightLow birth weightLow birth weightLow birth weight (less than 2.5 kg) babies and preterm babiespreterm babiespreterm babiespreterm babies (born before 37
or 38 weeks of gestation) are at significant risk of developing sepsis. � Low pre pregnancy weight, maternal age, smoking, drinking, andLow pre pregnancy weight, maternal age, smoking, drinking, andLow pre pregnancy weight, maternal age, smoking, drinking, andLow pre pregnancy weight, maternal age, smoking, drinking, and drug drug drug drug
depedepedepedependencyndencyndencyndency contribute to low birth weight babies.contribute to low birth weight babies.contribute to low birth weight babies.contribute to low birth weight babies. These factors need to be resolved.
Adequate nutritionnutritionnutritionnutrition during the period of pregnancy is to be ensured.
� Studies prove the utility of the following points in preventing pre term babiespre term babiespre term babiespre term babies.
� Avoid risky substancesAvoid risky substancesAvoid risky substancesAvoid risky substances.... SmokingSmokingSmokingSmoking may trigger preterm labor. Alcohol and Alcohol and Alcohol and Alcohol and
recreational drugsrecreational drugsrecreational drugsrecreational drugs are off-limits, too
� SexSexSexSex may be off-limits in certain complications, such as vaginal bleeding or problems
� Gum disease may be associated with preterm birthGum disease may be associated with preterm birthGum disease may be associated with preterm birthGum disease may be associated with preterm birth.... Regular visits to the dentist are
hence advocated.
� Regular anti natal checkups and adequate anti natal care can effectively tackle
the ill outcomes of risk factors like PIH and abruptio placentaPIH and abruptio placentaPIH and abruptio placentaPIH and abruptio placenta.
� As per the Medical Termination of Pregnancy Act, 1971, ‘failure of contraceptive method in a married woman’ is an indication for abortionabortionabortionabortion. But
this clause is being widely misused. The procedures involved in an abortion might produce a latent, sub-clinical infection that persists until the next pregnancy, and is then transmitted to the newborn. Hence therapeutic and eugenic abortions need to be encouraged.
� Our study emphasises the protective role of breast feed and anti natal steroid
therapy in neonatal sepsis.
� There is an association between breastfeedingbreastfeedingbreastfeedingbreastfeeding up to 6 months of age and
survival of infants throughout the first year of life. “The younger the infant The younger the infant The younger the infant The younger the infant and the longer the breastfeeding, theand the longer the breastfeeding, theand the longer the breastfeeding, theand the longer the breastfeeding, the greater the estimated benefits in greater the estimated benefits in greater the estimated benefits in greater the estimated benefits in terms of death avertedterms of death avertedterms of death avertedterms of death averted””””
� CorticosteroidsCorticosteroidsCorticosteroidsCorticosteroids like betamethasone and dexamethasone cause an immature
fetus's lungs to produce surfactant aid in lung maturation and resolution of
respiratory distress syndrome.
The added advantages being: Reduced incidence of
� Bleeding in the brain (intraventricular hemorrhage).