Risk Factors Of Neonatal Sepsis In rivandrum Kerala andrum, Trivandrum, Kerala

NITHIN JAYAN NITHIN HUMAYOON NITHA J Dr.VIJAYAKUMAR

Of Department 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 20082009

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

Abstract Sepsis in the newborn
Definition,Epidemiology Etiology

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5

7 8 9 10 14 18 19 37 40 41

Clinical Features Investigation Management Objective, Method, Methodology Results & discussion Conclusion, Conclusion, Recommendations Questionnaire Resources

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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. Breastfeeding, on the other hand, prevents infection in neonates. Clinical features

Non-specific features of sepsis: The earliest signs of sepsis are often subtle and non Non fea tures
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 colonyforming 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 Manroes 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 Total leukocyte count Absolute neutrophil count Immature/total neutrophil Micro-ESR C reactive protein (CRP) Abnormal value <5000/mm3 As per Manroe chart >0.2 > 15 mm in 1st hour >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 Cells/mm3 PMN (%) CSF protein (mg/dl) Glucose (mg/dl) CSF/ blood glucose (%)

Normal range 8 (0-30 cells) 60% 90 (20-170) 52 (34-119) 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 Meningitis Blood culture positive (no meningitis) Culture negative but definite clinical sepsis Culture negative, clinically probable sepsis screen positive Culture negative, clinically probable sepsis Screen negative

Duration 21 days 14 days 10-14 days 7-10 days 5-7 days

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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 & Pneumonia Ampicillin or Penicillin and Gentamicin Ampicillin or Cloxacillin and Gentamicin or Amikacin Cefotaxime and Amikacin Meningitis

FIRST LINE Community-acquired or Resistant strains unlikely SECOND LINE Hospitalacquired or Some resistant strains likely THIRD LINE Hospital-acquired sepsis Resistant strains are most likely

Add Chloramphenicol

Add Cefotaxime

Same

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 doublevolume 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(GMGranulocyte-Macrophage colony stimulating factor (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 Perinatal asphyxia PROM Endotracheal intubation PCOD Aspiration(amniotic fluid) Age at admission Low Birthweight Abortion PIH UTI Prematurity Rubella AbruptioPlacenta

Odds Ratio 27.136 14.793 10.474 10.474 7.452 7.000 6.047 5.986 5.706 4.846 4.520 4.191 3.688

95% CI 3.475-211.927 3.268-66.957 1.207-90.901 1.207-90.901 1.519-36.565 4.061-12.065 3.362-10.876 2.639-13.577 2.140-15.210 1.454-16.150 2.494-8.191 1.026-17.126 1.053-12.912

Important variables which have got a protective role on neonatal sepsis

Factor Odds Ratio Breast Feed 0.860 AntenatalSteroidTherapy 0.940

95% CI 0.795-0.931 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 Tcell 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 12 1 13 No 88 199 287 Total 100 200 300

Case Control Total

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 13 2 15 No 87 198 285 Total 100 200 300

Case Control Total

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
Case Control Total

Yes 5 1 6

No 95 199 294

Total 100 200 300

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 longterm 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 5 1 6 No 95 199 294 Total 100 200 300

Case Control Total

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 7 2 9 2 93 198 291 Total 100 200 300

Case Control Total

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 75 60 135 No 25 140 165 Total 100 200 300

Case Control Total

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. Tcell 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 44 23 67 No 56 177 233 Total 100 200 300

Case Control Total

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 22 9 31 No 78 191 269 Total 100 200 300

Case Control Total

Pearson Chi-Square value:22.035(df=1) p value:0.000 Odds Ratio: 5.986 95% Confidence Interval: 2.639-13.577
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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 15 6 21 No 85 194 279 Total 100 200 300

Case Control Total

Pearson Chi-Square: 14.747(df=1) p value:0.000 Odds Ratio: 5.706 95% Confidence Interval: 2.140-15.210

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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 9 4 13 No 91 196 287 Total 100 200 300

Case Control Total

Pearson Chi-Square:7.880(df=1) p value:0.005 Odds Ratio:4.846 95% Confidence Interval: 1.454-16.150

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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 37 23 60

No 63 177 240

Total 100 200 300

Case Control Total

Pearson Chi-Square: 27.094(df=1) p value:0.000 Odds Ratio:4.520 95% Confidence Interval: 2.494-8.191
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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 6 3 9 No 94 197 291 Total 100 200 300

Case Control Total

Pearson Chi-Square: 4.639 (df=1) p value:0.031 Odds Ratio: 4.191 95% Confidence Interval: 1.026-17.126

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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 7 4 11 No 93 196 289 Total 100 200 300

Case Control Total

Pearson Chi-Square: 4.718(df=1) p value:0.030 Odds Ratio:3.688 95% Confidence Interval: 1.053-12.912
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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 86 200 286 No 14 0 14 Total 100 200 300

Case Control Total

Pearson Chi-Square: 29.371(df=1) p value:0.000 Odds Ratio:0.860 95% Confidence Interval: .795-.931

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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 6 0 6 No 94 200 294 Total 100 200 300

Case Control Total

Pearson Chi-Square value:12.245(df=1) p value:0.000 Odds Ratio: 0.940 95% Confidence Interval: 0.895-0.988

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MULTIVARIATE ANALYSIS

The variables of our study were subjected to multivariate analysis by binary logistic regression. It was found that the following factors accounted for 33.6% of the total risk factors predisposing to neonatal sepsis Abortion Age at admission Birth Weight Perinatal Asphyxia PROM

Logistic regression of significant factors VARIABLES

Abortion Age at admission Birth Weight Perinatal Asphyxia PROM

B
1.056 1.722 1.729 2.538 2.182

Sig
.038 .000 .000 .019 .015

Exp(B)
2.873 5.597 5.633 12.657 8.861

SUMMARY OF VALUES
-2 Log likelihood 267.911 Cox & Snell R Square .336 Nagelkerke R Square .439

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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 of amniotic fluid are risk factors, the aspiration
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.

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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 policies before washing 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+2C. Overcrowding should be 30+ avoided.

All procedures should be performed after wearing mask and gloves. Unnecessary

invasive interventions such as needle pricks and setting up of intravenous lines and 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 contribute to low birth weight babies. These factors need to be resolved. dependency
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

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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.

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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:

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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.e1404.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

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