13489793 neonatal sepsis a study of the risk factors

NITHIN JAYANNITHIN JAYANNITHIN JAYANNITHIN JAYAN

NITHIN HUMAYOONNITHIN HUMAYOONNITHIN HUMAYOONNITHIN HUMAYOON

NITHA JNITHA JNITHA JNITHA J

DDDDrrrr.VIJAYAKUMAR.VIJAYAKUMAR.VIJAYAKUMAR.VIJAYAKUMAR

DepartmentODepartmentODepartmentODepartmentOffff CCCCommunityommunityommunityommunity

Medicine,Medicine,Medicine,Medicine,

GovtGovtGovtGovt.... MedicalMedicalMedicalMedical CollegeCollegeCollegeCollege

TrivandrumTrivandrumTrivandrumTrivandrum

RRRRiskiskiskiskFFFFactorsactorsactorsactorsOOOOffffNNNNeonataleonataleonataleonatalSSSSepsisepsisepsisepsisIIIInnnnTTTTrivrivrivrivandrumandrumandrumandrum,K,K,K,Keralaeralaeralaerala

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DEPARTMENT OF COMMUNITY MEDICINE

Govt.Medical College, Thiruvananthapuram

www.commedtvm.org

CERTIFICATECERTIFICATECERTIFICATECERTIFICATE

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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ACKNOWLEDGEMENTSACKNOWLEDGEMENTSACKNOWLEDGEMENTSACKNOWLEDGEMENTS

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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TTTTableableableableOOOOffffCCCContentsontentsontentsontents

CONTENTSCONTENTSCONTENTSCONTENTS PAGEPAGEPAGEPAGE

AbstractAbstractAbstractAbstract 5

Sepsis in the newbornSepsis in the newbornSepsis in the newbornSepsis in the newborn

Definition,EpidemiologyDefinition,EpidemiologyDefinition,EpidemiologyDefinition,Epidemiology 7

EtiologyEtiologyEtiologyEtiology 8

Clinical FeaturesClinical FeaturesClinical FeaturesClinical Features 9

InvestigationInvestigationInvestigationInvestigation 10

ManagementManagementManagementManagement 14

Objective, Method, MethodologyObjective, Method, MethodologyObjective, Method, MethodologyObjective, Method, Methodology 18

Results & discussionResults & discussionResults & discussionResults & discussion 19

ConcluConcluConcluConclusion, Recommendationssion, Recommendationssion, Recommendationssion, Recommendations 37

QuestionnaireQuestionnaireQuestionnaireQuestionnaire 40

ResourcesResourcesResourcesResources 41

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ABSTRACTABSTRACTABSTRACTABSTRACT

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 analysisUnivariate analysisUnivariate analysisUnivariate 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 analysisMultivariate analysisMultivariate analysisMultivariate 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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SepsisintheNewbornSepsisintheNewbornSepsisintheNewbornSepsisintheNewborn 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 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

� 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.

InvestInvestInvestInvestigationsigationsigationsigations

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: Blood culture: Blood culture: 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:Septic screen:Septic screen: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)Lumbar puncture (LP)Lumbar puncture (LP)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: Radiology: Radiology: 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: Urine culture: Urine culture: 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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ManagementManagementManagementManagement

SupportiveSupportiveSupportiveSupportive: : : : 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: Antimicrobial therapy: Antimicrobial therapy: 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 screen positive

7-10 days

Culture negative, clinically probable sepsis Screen negative

5-7 days

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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

Cefotaxime and Amikacin

Same

Reserve antibiotics Reserve antibiotics Reserve antibiotics 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 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

be useful

GranulocyteGranulocyteGranulocyteGranulocyte----Macrophage colony stimulating factor (GMMacrophage colony stimulating factor (GMMacrophage colony stimulating factor (GMMacrophage colony stimulating factor (GM----CSF): CSF): CSF): 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 CONSIDERATIONSETHICAL CONSIDERATIONSETHICAL CONSIDERATIONSETHICAL 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

intubation

10.474 1.207-90.901

PCOD 10.474 1.207-90.901

Aspiration(amniotic

fluid)

7.452 1.519-36.565

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)1)1)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


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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


p value:0.009

Odds Ratio:10.474


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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


p value:0.009

Odds Ratio:10.474


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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


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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


p value:0.000

Odds Ratio:7.000


Page | 26

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.”

Page | 27

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


Page | 28

8)8)8)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


p value:0.000

Odds Ratio: 5.986


Page | 29

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


p value:0.000

Odds Ratio: 5.706


Page | 30

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


p value:0.005

Odds Ratio:4.846


Page | 31

11)11)11)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


p value:0.000

Odds Ratio:4.520


Page | 32

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


Page | 33

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


p value:0.030

Odds Ratio:3.688


Page | 34

Important variables which have got a protective role on neonatal sepsis

1)1)1)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


p value:0.000

Odds Ratio:0.860

95% Confidence Interval: .795-.931

Page | 35

2)2)2)2) ANTENATALANTENATALANTENATALANTENATAL STEROIDSTEROIDSTEROIDSTEROID THERAPYTHERAPYTHERAPYTHERAPY

“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


p value:0.000

Odds Ratio: 0.940


Page | 36

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

Page | 37

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.

Page | 38

� 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.

� Seek regular prenatal carSeek regular prenatal carSeek regular prenatal carSeek regular prenatal careeee � Eat healthy foodsEat healthy foodsEat healthy foodsEat healthy foods � Manage chronic conditionsManage chronic conditionsManage chronic conditionsManage chronic conditions.... such as diabetes and high blood pressure

� 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

with your cervix or placenta.

� Limit stressLimit stressLimit stressLimit stress

Page | 39

� 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).

� Intestinal infection (necrotizing enterocolitis).

� Death.

Page | 40

QUESTIONNAIREQUESTIONNAIREQUESTIONNAIREQUESTIONNAIRE

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 | 41

RESOURESOURESOURESOURCESRCESRCESRCES

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 | 42

13489793 neonatal sepsis a study of the risk factors

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