Risk Factors Of Neonatal Sepsis In

Trivandrum
rivandrum,
andrum, Kerala
Kerala

NITHIN JAYAN
NITHIN HUMAYOON
NITHA J
Dr.VIJAYAKUMAR
Department Of
Of Community
Medicine,
Govt.
Govt. Medical College
Trivandrum
 DEPARTMENT OF COMMUNITY MEDICINE
Govt.Medical College, Thiruvananthapuram

www.commedtvm.org

CERTIFICATE

Certified that this report by Nitha J, Nithin Humayoon, Nithin Jayan is a record of

bonafide study and research under taken to fulfill the curriculum requirements of graduate

medical education as stipulated by the Medical Council of India, during the year 2008-

2009

Dr.Leela Itty Amma

Professor and Head

Guide

Dr. Vikayakumar

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 ACKNOWLEDGEMENTS

We would like to express our sincere gratitude to Dr. K. Vijayakumar, Professor, Dept. of Community

Medicine, MCH, TVM and Dr. Aneesh for their valuable guidance in this endeavor.

We also thank Dr. Lalitha Kailas, Professor and HOD, Dept. of Paediatrics, SAT Hospital, TVM and

Dr. K.P.Jhansi, Professor and HOD, Dept. of Obstetrics & Gynaecology, SAT Hospital, TVM for
granting us permission to do this survey.

We would like to thank Dr. Sobha, Professor Dept. of Paediatrics, Newborn Chief, SAT Hospital, TVM

for granting us access to the Neonatal Nursery, and for her valuable clinical guidance.

The completion of this work would not have been possible if we had not been lucky enough to get the

support of our colleagues.

Lastly let us thank the almighty for having guided us in the making of this project.

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 Table Of Contents

CONTENTS PAGE

Abstract 5

Sepsis in the newborn

Definition,Epidemiology 7

Etiology 8

Clinical Features 9

Investigation 10

Management 14

Objective, Method, Methodology 18

Results & discussion 19

Conclusion,
Conclusion, Recommendations 37

Questionnaire 40

Resources 41

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 ABSTRACT

Sepsis is the commonest cause of neonatal mortality and is probably responsible for
30-50% of the total neonatal deaths each year in developing countries. 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. Two forms of clinical presentations have been identified.
Early onset sepsis, probably related to perinatal risk factors, usually presents with
respiratory distress and pneumonia within 72 hours of age. Late onset sepsis, related
to hospital acquired infections, usually presents with septicemia and pneumonia after
72 hours of age. Clinical features of sepsis are nonspecific in neonates and a high
index of suspicion is required for the timely diagnosis of sepsis. Although blood culture
is the gold standard for the diagnosis of sepsis, reports are available after 48-72 hours.

A hospital based case control study was conducted with 100 Neonates admitted to
nursery(Inborn & Outborn) S.A.T.Hospital, Trivandrum, with neonatal sepsis and are
RDT Positive as cases and the control being 200 Neonates admitted in the obstetric
ward, S.A.T.Hospital, Trivandrum, along with the mother within a time-period of 3
months from September 5th to December 5th, 2008. The data were collected using a
Semi structured pre-tested questionnaire.

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Univariate analysis was done by odds ratio and chi-square tests. This revealed the
following risk factors:

Perinatal asphyxia

PROM

Endotracheal Intubation

PCOD

Aspiration of amniotic fluid

Age at admission

Low Birth weight

Abortion

PIH

UTI

Prematurity

Rubella

Abruptio Placenta

Breast Feeding and Antenatal Steroid Therapy were found to have a protective role.

Multivariate analysis was done by logistic regression and the following factors
accounted for 33.6 % of the total risk factors predisposing for neonatal sepsis:

Abortion

Age at admission

Birth Weight

Perinatal Asphyxia

PROM

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 Sepsis in the Newborn

DEFINITION

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 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 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 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 features

Non-
Non -specific features
fea 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.
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

Cardiac: Hypotension, poor perfusion, shock

Gastrointestinal: Feed intolerance, vomiting, diarrhea, abdominal distension,
paralytic ileus, necrotizing enterocolitis (NEC).

Hepatic: Hepatomegaly, direct hyperbilirubinemia (especially with UTI)

Renal: Acute renal failure

Hematological: Bleeding, petechiae, purpura,

Skin changes: Multiple pustules, abscess, sclerema, mottling, umbilical redness
and discharge.

Investigations
Invest igations
It is important that the supportive and antimicrobial therapy of a neonate with sepsis is
instituted quickly. Hence minimum and rapid investigations should be undertaken.

Blood culture: It is the gold standard for the diagnosis of septicemia and should be
done in all cases of suspected sepsis prior to starting antibiotics. A positive blood
culture and sensitivity of the isolate is the best guide to antimicrobial therapy.
Therefore the procedure for collecting a blood culture should be strictly followed to
avoid contamination. The staff involved should wear sterile gloves prior to the
procedure and prepare a patch of skin approx. 5-cm in diameter over the proposed
veni-puncture site. This area should be cleansed thoroughly with alcohol followed by
povidone-iodine, followed again by alcohol. Application of povidone-iodine should be
done in concentric circles moving outward from the centre. The skin should be allowed
to dry for at least minute before the sample is collected. A one-ml sample of blood
should be adequate for a blood culture bottle containing 5-10 ml of culture media.
Blood cultures should be collected from a fresh veni-puncture site because samples
collected from indwelling lines and catheters are likely to be contaminated. All blood

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cultures should be observed for at least 72 hours before they are reported as sterile. It
is now possible to detect bacterial growth within 12-24 hours by using improved
bacteriological techniques such as BACTEC and BACT/ALERT blood culture systems.
These advanced techniques can detect bacteria at a concentration of 1-2 colony-
forming unit (cfu) per ml.

Septic screen:

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
sepsis screen.
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A practical sepsis screen

Components Abnormal value

Total leukocyte count <5000/mm3

Absolute neutrophil count As per Manroe chart

Immature/total neutrophil >0.2

Micro-ESR > 15 mm in 1st hour

C reactive protein (CRP) >1 mg/dl

Lumbar puncture (LP)

Since clinical features of sepsis and meningitis are non-specific in neonates, it is likely
that meningitis may be present without specific symptomatology along with sepsis.
The incidence of meningitis in neonatal sepsis has varied from 0.3-3% in various
studies and 0.5% according to the NNPD 2000 data. However the morbidity involved
with a delayed or a missed diagnosis of meningitis probably justifies the extra
precaution of performing lumbar punctures in patients suspected of neonatal sepsis. In
situations of early onset sepsis, a lumbar puncture is indicated in the presence of either
a positive blood culture or presence of clinical picture of septicemia. It is probably not
indicated if antibiotics have been started solely due to the presence of risk factors only.
In situations of late onset sepsis, a lumbar puncture should be done in all infants with
signs and symptoms prior to starting antibiotics. The lumbar puncture should be
postponed in a critically sick and hemodynamically unstable baby. However it should
be considered after the clinical condition stabilizes.

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The cerebrospinal fluid characteristics are unique in the newborn period and normal
values have been given in Table.

CSF components Normal range

Cells/mm3 8 (0-30 cells)

PMN (%) 60%

CSF protein (mg/dl) 90 (20-170)

Glucose (mg/dl) 52 (34-119)

CSF/ blood glucose (%) 51 (44-248)

Radiology: A chest x-ray should be considered in the presence of respiratory distress

or apnea. An abdominal x-ray is indicated in the presence of abdominal signs and or
suspicion of necrotizing enterocolitis (NEC). An ultrasound head and CT scan should be
done in all patients diagnosed to have meningitis.

Urine culture: In early onset sepsis, urine cultures have a low yield and are not
indicated. Although a suprapubic bladder puncture sample or bladder catheterization
sample has been recommended in all cases of late onset sepsis, the procedure is
painful and the yield is very poor. We do not recommend a routine urine culture in
babies with sepsis. However, patients at risk for fungal sepsis and very low birth
weight babies with poor weight gain should have a urine examination to exclude
urinary infection.
Urinary tract infection may be diagnosed in presence of one of the following:

>10 WBC/mm in a 10 ml centrifuged sample

>104 organisms /ml in urine obtained by catheterization and

Any organism in urine obtained by suprapubic aspiration
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Management

Supportive: Attention should be given to basic supportive care in a sick child. The
infant should be nursed in a thermo-neutral environment taking care to avoid
hypothermia/ hyperthermia. Oxygen saturation should be maintained in the normal
range and ventilation should be initiated as required. The infant should be regularly
monitored for hypoglycemia/ hyperglycemia. Colloids and inotropes should be used
for maintaining normal tissue perfusion and blood pressure. Enteral feeds should be
avoided till the baby is hemodynamically stable. Packed cells and fresh frozen plasma
should be used appropriately for the management of anemia and bleeding diathesis

Antimicrobial therapy: There cannot be single recommendations for the antibiotic

regimen for neonatal sepsis in all settings. The choice of antibiotics depends on the
prevailing flora responsible for sepsis in the given unit and their antimicrobial
sensitivity.
This write up does not aim to provide a universal recommendation for all settings but
lays down broad guidelines for the providers to make a rational choice of antibiotic
combination. Decision to start antibiotics is based upon clinical features and/ or a
positive septic screen. However duration of antibiotic therapy is dependent upon the
presence of a positive blood culture and meningitis (see table).
Duration of antibiotic therapy in neonatal sepsis

Diagnosis Duration

Meningitis 21 days

Blood culture positive (no meningitis) 14 days

Culture negative but definite clinical sepsis 10-14 days

Culture negative, clinically probable sepsis 7-10 days

screen positive
Culture negative, clinically probable sepsis 5-7 days
Screen negative

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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: 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: 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 & Meningitis

Pneumonia

FIRST LINE Ampicillin or Penicillin and Add Chloramphenicol

Community-acquired or Gentamicin
Resistant strains unlikely
SECOND LINE Hospital- Ampicillin or Cloxacillin and Add Cefotaxime
acquired or Some resistant Gentamicin or Amikacin
strains likely
THIRD LINE Cefotaxime and Same
Hospital-acquired sepsis Amikacin
Resistant strains are most
likely

Reserve antibiotics

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 therapy

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): Non-specific pooled IVIG has not been found to
be useful
Granulocyte-
Granulocyte-Macrophage colony stimulating factor (GM-
(GM-CSF): This mode of
treatment is still experimental.

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OBJECTIVE:

To study the risk factors of neonatal sepsis

METHOD & METHODOLOGY

STUDY SETTING: Neonatal nursery (Inborn & Outborn) S.A.T.Hospital, Trivandrum

STUDY DESIGN: Case-control study

STUDY PERIOD: September 5th to December 5th 2008

STUDY SAMPLE:

CASE: 100 neonates admitted to nursery (Inborn & Outborn) S.A.T.Hospital,
Trivandrum

INCLUSION CRITERIA: Neonates admitted to nursery with neonatal sepsis and
are RDT Positive.

EXCLUSION CRITERIA: Neonates admitted to nursery with life threatening
congential malformation, ambiguous genitalia, metabolic problem.

CONTROL: 200 Neonates admitted in the obstetric ward along with the mother.

STUDY SIZE:

CASE:100 Neonates

CONTROL:200 Neonates

STUDY TOOL:
Semi structured pre-tested questionnaire

ETHICAL CONSIDERATIONS:
Consent was obtained from the concerned authorities and guardians of the neonates.
The guardians who co-operated with us were ensured privacy to the utmost, and were
aware of their freedom to step back from the study at anytime. All details about the
study were conveyed to them.
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 RESULTS AND DISCUSSION
UNIVARIATE ANALYSIS

Important variables which have got a bearing on neonatal sepsis

Factor Odds Ratio 95% CI

Perinatal asphyxia 27.136 3.475-211.927
PROM 14.793 3.268-66.957
Endotracheal 10.474 1.207-90.901
intubation
PCOD 10.474 1.207-90.901
Aspiration(amniotic 7.452 1.519-36.565
fluid)
Age at admission 7.000 4.061-12.065
Low Birthweight 6.047 3.362-10.876
Abortion 5.986 2.639-13.577
PIH 5.706 2.140-15.210
UTI 4.846 1.454-16.150
Prematurity 4.520 2.494-8.191
Rubella 4.191 1.026-17.126
AbruptioPlacenta 3.688 1.053-12.912

Important variables which have got a protective role on neonatal sepsis

Factor Odds Ratio 95% CI

Breast Feed 0.860 0.795-0.931
AntenatalSteroidTherapy 0.940 0.895-0.988

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 1) PERINATAL ASPHYXIA

Perinatal asphyxia was found to lower and compromise the immunological profile of
the newborn. Both cellular and humoral immunity were found to be affected. The T-
cell function was affected more than the B-cell function, i.e. cellular immunity was
affected more than the humoral immunity. The CD4/CD8 ratio was reversed in
asphyxiated newborns, implying a deficient immune status.Perinatal asphyxia is caused
by a decreased supply of oxygen to the fetus or newborn. It can happen in the
antepartum period, during labor, or at the time of birth. When it occurs, it results in an
inadequate exchange of respiratory gases and impaired tissue perfusion. Various
systemic functions of the newborn suffering from birth asphyxia have been evaluated
and have been found to be deranged

Our study revealed that perinatal asphyxia is a risk factor of neonatal sepsis with an
odds ratio of 27.136
Cross tabulation :Status v/s Perinatal asphyxia

Perinatal asphyxia

Status
Yes No Total

Case 12 88 100

Control 1 199 200

Total 13 287 300

Pearson Chi-Square: 21.268(df=1)

p value:0.000

Odds Ratio: 27.136

95% Confidence Interval: 3.475-211.927

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 2) PROM

“Prolonged leaking and premature rupture of membranes is considered as a major

risk factor for sepsis because of the danger of ascending infection”

Our study revealed that PROM is a risk factor of neonatal sepsis with an odds ratio of
14.793

Crosstabulation :Status v/s PROM

PROM

Status
Yes No Total

Case 13 87 100

Control 2 198 200

Total 15 285 300

Pearson Chi-Square: 20.211 (df=1)

p value:0.000

Odds Ratio: 14.793

95% Confidence Interval: 3.268-66.957

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 3) ENDOTRACHEAL INTUBATION

Endotracheal intubation provides a major portal of entry for colonization and infection
with potential pathogens.(late onset association)

By Univariate analysis we found endotracheal intubation is a risk factor for neonatal

sepsis with an odds ratio of 10.474

Crosstabulation :Status v/s Endotracheal

intubation

Endotracheal
intubation

Status Yes No Total

Case 5 95 100

Control 1 199 200

Total 6 294 300

Pearson Chi-Square: 6.888(df=1)

p value:0.009

Odds Ratio:10.474

95% Confidence Interval: 1.207-90.901

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 4) PCOD

Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with

many characteristic features, including hyperandrogenaemia, insulin resistance and
obesity which may have significant implications for pregnancy outcomes and long-
term health of the woman.

In our study PCOD was found to be a significant risk factor of neonatal sepsis with an
odds ratio of 10.474

Crosstabulation :Status v/s PCOD

PCOD

Status
Yes No Total

Case 5 95 100

Control 1 199 200

Total 6 294 300

Pearson Chi-Square: 6.888(df=1)

p value:0.009

Odds Ratio:10.474

95% Confidence Interval: 1.207-90.901

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 5) ASPIRATION

“Congenital pneumonia is a usual manifestation of neonatal sepsis. This is due to

aspiration of infected amniotic fluid. Autopsy findings (Naeye et al , 1971) reveal the
presence of poly morpho nuclear leucocytes in the alveoli, often mixed with squamous
cells and vernix, suggesting aspiration of infected amniotic fluid. In a large proportion
no bacterial pathogens could be isolated. It has hence been proposed that these
pathological changes result from hypoxia and aspiration of maternal inflammatory
cells rather than active infection”

In our study aspiration of amniotic fluid was found to be a significant risk factor of
neonatal sepsis with an odds ratio of 7.452

Crosstabulation :Status v/s Aspiration(amniotic fluid)

Aspiration(amniotic fluid)

Status
1 2 Total

Case 7 93 100

Control 2 198 200

Total 9 291 300

Pearson Chi-Square:8.247(df=1)

p value:0.004

Odds Ratio:7.452

95% Confidence Interval: 1.519-36.565

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 6) AGE AT ADMISSION

“Eighty-five percent of newborns with early-onset infection present within 24 hours,

5% present at 24-48 hours, and a smaller percentage of patients present between 48
hours and 6 days of life.

Early onset sepsis syndrome is associated with acquisition of microorganisms from the
mother”

In our study, age at admission was found to be significant with an odds ratio of 7.000

Neonates below the age of 72 hours were considered as belonging to the risk group.
The study supported this assumption.

Crosstabulation :Status v/s age at admission

age at admission

Status
Yes No Total

Case 75 25 100

Control 60 140 200

Total 135 165 300

Pearson Chi-Square:54.545(df=1)

p value:0.000

Odds Ratio:7.000

95% Confidence Interval: 4.061-12.065

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 7) LOW BIRTH WEIGHT

“Neonates are deficient in humoral and cellular immunity; they produce

immunoglobulins at a lower rate than adults (3). Transplacental maternal antibodies
mediate humoral immunity primarily, hence very low birthweight (VLBW) premature
infants are less likely to receive as many immunoglobulins as term infants. T–cell
function is also less efficient in neonates (4). Complement function and phagocytic
function inclusive of phagocytosis, phagocyte migration and toxin production are also
deficient

The incidence of sepsis and its complications are therefore greater in VLBW infants
and extremely premature babies

Onset of infection within the first six days of life is thought to be primarily due to
vertical transmission from mother-to-infant, while onset of infection at seven days of
life or greater is more likely to be acquired through horizontal transmission. By virtue
of the length of time VLBW infants may spend in the hospital setting, they are at
prolonged risk for acquiring infection, particularly nosocomial infections. The
identification of strategies to reduce infection in these infants will result in decreased
mortality and morbidity.

It can also be hypothesized that by virtue of the length of time VLBW infants spend on
the neo-natal unit the organisms causing infection will be predominantly nosocomial in
origin.”

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With an odds ratio of 6.047, our study supports the hypothesis that low birth weight is a risk
factor for neonatal sepsis.

(In our study, neonates weighing below 2.5kg have been grouped as Low Birth Weight babies)

Crosstabulation :Status v/s Low Birthweight

Low Birthweight

Status
Yes No Total

Case 44 56 100

Control 23 177 200

Total 67 233 300

Pearson Chi-Square value:40.596(df=1)

p value:0.000

Odds Ratio: 6.047

95% Confidence Interval: 3.362-10.876

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 8) ABORTION

It was recently suggested that a previous abortion increases the risk of intrapartum
infection in a following pregnancy. A case-control study of neonatal sepsis was
conducted using the Washington State Birth Registry. Cases of sepsis were selected
among singleton live births during the period 1984-90, and compared with a control
group for the occurrence of spontaneous or induced abortion in previous pregnancies.
According to this study induced abortion is associated with an increased risk of
neonatal sepsis in a subsequent pregnancy, but the association between spontaneous
abortion and sepsis is small and non-significant. The authors suggest that the
procedures involved in a therapeutic abortion might produce a latent, sub-clinical
infection that persists until the next pregnancy, and is then transmitted to the
newborn. In our study, abortion was found to be significant with an odds ratio of 5.986

Crosstabulation :Status v/s abortion

Abortion

Status
Yes No Total

Case 22 78 100

Control 9 191 200

Total 31 269 300

Pearson Chi-Square value:22.035(df=1)

p value:0.000

Odds Ratio: 5.986

95% Confidence Interval: 2.639-13.577

Page | 28
 9) PIH

Utero placental insufficiency is the underlying pathology of Pregnancy Induced

Hypertension(PIH) which usually leads to low birth weight babies. Low birth weight is
a condition that predisposes to neonatal sepsis.

Our study proves that PIH is a risk factor of neonatal sepsis with an odds ratio of
5.706

Crosstabulation: Status v/s PIH

PIH

Status
Yes No Total

Case 15 85 100

Control 6 194 200

Total 21 279 300

Pearson Chi-Square: 14.747(df=1)

p value:0.000

Odds Ratio: 5.706

95% Confidence Interval: 2.140-15.210

Page | 29
 10) UTI

Transplacental infection or an ascending infection from the cervix may be caused by

organisms that colonize in the mother's genitourinary tract, with acquisition of the
microbe by passage through a colonized birth canal at delivery.

With an odds ratio of 7.880, our study supports the hypothesis that low birth weight is
a risk factor for neonatal sepsis

Crosstabulation :Status v/s UTI

UTI

Status
Yes No Total

Case 9 91 100

Control 4 196 200

Total 13 287 300

Pearson Chi-Square:7.880(df=1)

p value:0.005

Odds Ratio:4.846

95% Confidence Interval: 1.454-16.150

Page | 30
 11) PREMATURITY

Premature infants have an increased susceptibility to sepsis and subtle nonspecific

initial presentations; therefore, they require much vigilance so that sepsis can be
effectively identified and treated.

In our study, Prematurity was found to be a significant risk factor with an odds ratio of
4.520

Crosstabulation :Status v/s Prematurity

Prematurity

Status
Yes No Total

Case 37 63 100

Control 23 177 200

Total 60 240 300

Pearson Chi-Square: 27.094(df=1)

p value:0.000

Odds Ratio:4.520

95% Confidence Interval: 2.494-8.191

Page | 31
 12) RUBELLA

“Early in gestation, the virus is thought to establish a chronic intrauterine infection.

Its effects include endothelial damage to blood vessels, direct cytolysis of cells, and
disruption of cellular mitosis.”

In our RUBELLA was found to be a significant risk factor of neonatal sepsis with an
odds ratio of 4.191

Crosstabulation :Status v/s Rubella

Rubella

Status
Yes No Total

Case 6 94 100

Control 3 197 200

Total 9 291 300

Pearson Chi-Square: 4.639 (df=1)

p value:0.031

Odds Ratio: 4.191

95% Confidence Interval: 1.026-17.126

Page | 32
 13) ABRUPTIOPLACENTA

“Early amnion rupture may cause abortion or stillbirth, craniofacial clefts, and
cerebral, body wall and limb/skeletal defects. The risk of chorioamnionitis is also
increased, with serious consequences to the fetus and neonate”

In our study, abruptioplacenta was found to be significant with an odds ratio of 3.688

Crosstabulation :Status v/s AbruptioPlacenta

AbruptioPlacenta

Status
Yes No Total

Case 7 93 100

Control 4 196 200

Total 11 289 300

Pearson Chi-Square: 4.718(df=1)

p value:0.030

Odds Ratio:3.688

95% Confidence Interval: 1.053-12.912

Page | 33
 Important variables which have got a protective role on neonatal sepsis

1) BREAST FEEDING

Protection against neonatal sepsis by breast feeding was investigated in a developing

community. A case-control study was carried out with 42 cases from a hospital and
270 controls, matched for age and socioeconomic conditions from the community.
Exclusive breast feeding was extremely rare, most babies being partially breast fed and
a few being given formula feed or animal milk. A highly significant odds ratio of 18
was obtained, showing that even partial breast feeding protects against neonatal sepsis
in such a population. By Univariate analysis it was found that breast feeding was
protective against neonatal sepsis with an odds ratio of 0.860

Crosstabulation :Status v/s BreastFeeding

BreastFeeding

Status
Yes No Total

Case 86 14 100

Control 200 0 200

Total 286 14 300

Pearson Chi-Square: 29.371(df=1)

p value:0.000

Odds Ratio:0.860

95% Confidence Interval: .795-.931

Page | 34
 2) ANTENATAL STEROID THERAPY

“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 true
true.”

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

Page | 35
 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 Cox & Snell R Nagelkerke R

likelihood Square Square

267.911 .336 .439

Page | 36
 CONCLUSIONS AND RECOMMENDATIONS

 Perinatal 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 PROM (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 aspiration

aspiration of amniotic fluid are risk factors, the
possible explanation being that these factors create a new portal of entry of
infected pathogenic materials.

 PCOD , 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 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.

Page | 37
 The source of infection is either nosocomial or community-acquired in late onset
sepsis hence:
 All persons taking care of the baby should strictly follow hand washing
washing policies before
touching any baby. It is preferable to use bar soaps rather than liquid soaps as the
latter tend to harbour organisms after storage.
 The nursery environment should be clean and dry with 24 hour water supply and
electricity. There should be adequate ventilation and lighting. The nursery
temperature should be maintained between 30+
30+2°C. Overcrowding should be
avoided.
 All procedures should be performed after wearing mask and gloves. Unnecessary
invasive interventions such as needle pricks and
and setting up of intravenous lines
should be kept to the barest minimum. There should be no compromise in the use of
disposables. Stock solutions for rinsing should be avoided.
 Every baby must have separate thermometer and stethoscope and all barrier
nursing measures must be followed.

 Low birth weight (less than 2.5 kg) babies and preterm babies (born before 37
or 38 weeks of gestation) are at significant risk of developing sepsis.
 Low pre pregnancy weight, maternal age, smoking, drinking, and drug
dependency
dependency contribute to low birth weight babies. These factors need to be resolved.
Adequate nutrition during the period of pregnancy is to be ensured.

 Studies prove the utility of the following points in preventing pre term babies.

Seek regular prenatal care
care

Eat healthy foods

Manage chronic conditions. such as diabetes and high blood pressure

Avoid risky substances. Smoking may trigger preterm labor. Alcohol and
recreational drugs are off-limits, too

Sex may be off-limits in certain complications, such as vaginal bleeding or problems

with your cervix or placenta.

Limit stress

Page | 38

Gum 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 placenta .

 As per the Medical Termination of Pregnancy Act, 1971, ‘failure of

contraceptive method in a married woman’ is an indication for abortion . 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 breastfeeding up to 6 months of age and

survival of infants throughout the first year of life. “The younger the infant
and the longer the breastfeeding, the greater the estimated benefits in
terms of death averted”
averted”

 Corticosteroids 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).

 Intestinal infection (necrotizing enterocolitis).
 Death.

Page | 39
 QUESTIONNAIRE

1) Status: Case/Control
2) Age of mother:
3) Socio economic status: APL/BPL
4) Gender of child: Male/Female
5) Rapid Diagnostic Test: Positive/ Negative
6) CRP:
7) Micro ESR
8) ANC
9) Inborn nursery/ Outborn nursery
10) Age in days at the time of admission:≤3 days / >3days
11) Place of delivery: SAT/PRIVATE/OTHER Government.Inst.
12) Mode of delivery: Caesarian/ Vaginal
13) If Caesarian: emergency/elective
14) If vaginal: Normal/ Assisted
15) PROM: Yes/ No
16) DIAGNOSED MATERNAL D/S: UTI: Yes/No
17) DIAGNOSED MATERNAL D/S: GDM: Yes/No
18) DIAGNOSED MATERNAL D/S: STD: Yes/No
19) DIAGNOSED MATERNAL D/S: PIH: Yes/No
20) Gestational age: PRETERM OR NEARTERM/ TERM
21) Birth weight: <2.49kg/≥2.5kg
22) Breast feed: Yes/No
23) Aspiration of amniotic fluid: Yes/No
24) Endotracheal Intubation: Yes/No
25) Perinatal asphyxia: Yes/No
26) Culture: Positive/Negative/Not available
27) IF Culture positive which organism:
28) Duration of nursery stay:

Page | 40
 RESOURCES
RESOURCES
Neonatal consequences of placental and membrane dysfunction: Reproduction, Fertility and
Development 3(4) 431 – 437

Indian Journal of Paediatrics volume: 75, March 2008

AntenatalSteroidTherapy : American Journal of Obstetrics & Gynecology 2008;199:404.e1-

404.e5

“Immunological Profile in Asphyxiated Newborns” by Vani Bhatt, MD, FAAP,National Institute

of Immunology

Infectious Disease in Pregnancy and the Newborn Infant by Gwendolyn L. Gilber,Published by

Informa Health Care, 1991

Department of Social and Preventive Paediatrics, King Edward Medical College, Lahore,
Pakistan.

West Indian Medical Journal, vol.55 no.3 Mona June 2006

Neonatal Sepsis,Author: Ann L Anderson-Berry, MD, Assistant Professor of Pediatrics, Joint

Division of Newborn Medicine, Creighton University, University of Nebraska Medical Center

Fetal and neonatal secrets by Richard Alan Polin, Alan R. Spitzer

PCOD: Published by Oxford University Press on behalf of the European Society of Human
Reproduction and Embryology.

PROM: Department of Paediatrics and Adolescent Medicine, BP Koirala Institute of Health

Sciences, Dharan, Nepal. Kathmandu University Medical Journal (2006), Vol. 4, No. 2, Issue 14,
187-191

The Merck Manuals, EIGHTEENTH EDITION

Sepsis in the Newborn: Rajiv Aggarwal, Nupur Sarkar, Ashok K Deorari, Vinod K Paul
Division of Neonatology, Department of Paediatrics
All India Institute of Medical Sciences
Ansari Nagar, New Delhi –110029

Page | 41
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