|Year : 2014 | Volume
| Issue : 4 | Page : 254-258
Neonatal sepsis: A risk approach
Vijai Anand Babu Bangi1, S Syamala Devi2
1 Department of Pediatrics, Government Medical College, Ananthapuramu, Andhra Pradesh, India
2 Department of Gynecology, Government Medical College, Ananthapuramu, Andhra Pradesh, India
|Date of Web Publication||10-Dec-2014|
Vijai Anand Babu Bangi
H.No. 49-1-7, Maddur Nagar, Kurnool - 518 002, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: Neonatal sepsis continues to be a major cause of neonatal mortality in India. Incidence of neonatal sepsis in India was 30/1000 live births and is not changed much over the past decade.
Aims and Objectives: The present study was intended to know the incidence and mortality rates of neonatal sepsis among hospital admission, whether there is any change in the risk factors over a decade and to evolve a risk approach in the management of neonatal sepsis.
Patients and Methods: This was a cross-sectional study in a tertiary care teaching hospital. One hundred and twenty neonates with confirmed sepsis were enrolled. Cases were divided into early onset sepsis (EOS) (presenting in the first 72 h) and late onset sepsis (LOS) (presenting after 72 h). Information regarding risk factors was collected by questionnaire. All cases were started on ampicillin and gentamycin later upgraded based on culture and sensitivity. Cases were followed-up to discharge/death and the risk factors associated with fatal sepsis were analyzed using Chi-square test.
Results: During 2003-2004, the incidence of sepsis was 6.04% of total pediatric admissions with EOS and LOS 3.08% and 2.96%. The same in 2013-2014 were 6.03%, 2.57% and 3.44%, respectively. Highly significant risk factors were inadequate antenatal care, assisted vaginal delivery, and premature rupture of membranes, low birth weight and associated complications. Klebsiella, Staphylococcus aureus and Escherichia coli were the most common organisms in both EOS and LOS.
Conclusion: Overall incidence of sepsis and EOS is not changed much but the incidence of LOS has increased from 2.94% to 3.44%.
Keywords: Incidence, neonatal sepsis, risk approach
|How to cite this article:|
Bangi VA, Devi S S. Neonatal sepsis: A risk approach. J NTR Univ Health Sci 2014;3:254-8
| Introduction|| |
Neonatal sepsis continues to be a major cause of neonatal mortality in India. As per National Neonatal Perinatal Database 2002-2003, the incidence of neonatal sepsis in India was 30/1000 live birth. , Some other population-based studies have reported clinical sepsis rates ranging from 49 to 170/1000 live births in rural India.  Incidence is not changed much over the past decade, and the fatality due to sepsis is between 30% and 65%.  The risk factors include lack of antenatal care, unsupervised or poorly supervised home deliveries, unhygienic and unsafe delivery practices and cord care, prematurity, low birth weight, lack of exclusive breast-feeding, and delays in recognition of danger signs in both mother and baby. ,,, Early diagnosis is difficult due to its nonspecific clinical presentation. Yet to treat neonates with antibiotics presumptively on the basis of subtle signs is likely to over treat between 11 and 23 noninfected neonates for everyone neonate with documented infection.  The ideal approach will be identifying high-risk neonates and targeting them for intensive therapy. 
The present study conducted between 2 times periods (epoch-1: 2003-2004 and epoch-2: 2013-2014) was therefore designed to know the changing trends in the incidence of neonatal sepsis, correlate the outcome with clinical and laboratory parameters to find out the risk factors associated with fatal sepsis and develop a risk approach based on the relative importance of identified risk factors.
| Patients and methods|| |
This cross-sectional clinical study was carried out on neonates admitted to the referral neonatal intensive care unit (NICU) of a tertiary care hospital which predominantly serves the poorer strata of the society of three states viz., Andhra Pradesh, Tamil Nadu and Karnataka. Epoch-1 was retrospective (June 2003 to May 2004) while epoch-2 was a prospective (June 2013-May 2014) study. The study was approved by Institutional Review Board.
Neonates with clinically suspected sepsis were divided into early onset sepsis (EOS) (presenting in the first 72 h of life) and late onset sepsis (LOS) (presenting after 72 h). All the cases fulfilling the inclusion criteria formed the basis of this study. Inclusion criteria included presence of one or more of the established clinical features such a fever/hypothermia, poor feeding, reduced activity, respiratory distress/apneic spells, hepatosplenomegaly, abdominal distension, vomiting, diarrhea, seizures, abnormal neonatal reflexes, bulging anterior fontanel, sclerema, signs of either circulatory or respiratory dysfunction (evidenced by tachycardia/bradycardia/capillary refill time of >3 s. and respiratory rate ≥60/chest in drawing and/or grunt respectively) along with ≥2 of the laboratory criteria (total blood leukocyte count <5000/>15000, absolute neutrophil count (ANC) <500 cells/mm 3 or >1500/mm 3 , immature to total neutrophil ratio >0.2, micro erythrocyte sedimentation rate (ESR) >15/1 h, C-reactive protein (CRP) >0.6 μg/ml, positive blood/cerebro spinal fluid/urine.
Information regarding maternal (age, literacy, socioeconomic status, parity, antenatal care, prolonged rupture of membranes, predisposing factors such as fever/foul smelling liquor/unclean vaginal examinations and mode of delivery) and neonatal (gestational age, sex, birth weight, intermittent positive pressure ventilation [IPPV], time of onset of symptoms, delay in starting treatment) risk factors was collected by questionnaire and information recorded on a structured proforma.
After obtaining informed consent, all cases were initially started on a combination of ampicillin and gentamycin as per recommended dosage. Antibiotics were subsequently changed if necessary based on culture and sensitivity and response to treatment. Duration of treatment was decided depending upon the site of infection. Supportive therapy included intravenous fluids, warmer care, oxygen, anticonvulsants, phototherapy and blood transfusion depending on the need. Neonates were followed-up to determine the final outcome. Those who died served as cases and those discharged after recovery were taken as controls. The risk factors were analyzed by Chi-square test for the strength of their association with fatal outcome to evolve a "rick approach" to neonatal sepsis. The results were compared to similar data collected retrospectively from case records of 2003-2004 of this institution to know the changing trends in the incidence, causative organisms and risk factors over a decade.
| Results|| |
During 2013-2014, 5220 patients were admitted in pediatric wards. Of these 754 were sick neonates. Sepsis was clinically diagnosed in 315: EOS in 135 and LOS in 180. The incidence of sepsis was 6.03% of the total pediatric admissions. Incidence of EOS and LOS were 2.57% and 3.44%. One hundred and twenty cases of sepsis fulfilled the inclusion criteria and were included in the present study and followed-up. Mortality rate was 46.7%. Male to female ratio was 1.5:1 whereas male to female mortality ratio was 2.5:1. Comparatively, retrospective data of 2003-2004 revealed an overall incidence of 6.04% while that of EOS and LOS was 3.08% and 2.96%. Mortality rate was 48%.
Out of 120 neonates more than half were born to the mother of 20-25 years, one-fourth each to mothers of <20 and >25 years of age. The difference in the mortality rates is not significant. Nearly three-fourths of the babies were born to illiterate mothers and the mortality was significantly more (57.5%) compared with those born to educated mothers (18.2%). A half of the neonates were born to mothers belonging to poor socioeconomic state, and the mortality was significantly high (57.5%) compared with babies of middle-class mothers (25%). Mortality rates in babies born to primipara, second and multipara mothers were almost similar, and difference was not significant. No or inadequate antenatal care was associated with a mortality of 58.6% compared to 15.2% of adequate antenatal care. Premature prolonged rupture of membranes (PPROM) of ≥18 h was definitely associated with high mortality (83.3%). Presence of predisposing factors like maternal fever/fowl smelling liquor/unclean vaginal examinations did not influence the mortality while assisted vaginal delivery was significantly associated with higher mortality [Table 1].
Sixty one babies were preterm and 51 were term. Mortality was significantly high (65.2%) in preterm compared to term (21.6%) babies. Male gender was more associated with fatal outcome (54.8%), but mortality was more significantly seen in low birth weight babies. Mortality was 61.5% in EOS and 35.2% in LOS babies. Delay in initiating treatment from the onset of symptoms if it is ≥12 h is met with highly significant (88.6%) mortality. Refusal of feeds was the most common presenting symptom (90%) followed by poor activity (83.3%), poor cry (81.7%), but the symptoms associated with high mortality were bleeding (100%), shock (100%), hypothermia (90.5%), apneic spells (86.9%) abdominal distention (78.2%), respiratory distress (62.5%), and convulsions (61.5%). Complications like meningitis, disseminated intravascular coagulation (DIC), shock, necrotizing enterocolitis was associated with a mortality of 78.9% [Table 2].
Among the sepsis screen parameters high mortality was associated with leucopenia (84.6), neutropenia (78.3%), culture positivity (62.5%) and Gram-negative isolates (78.6%). Commonest organisms isolated were Klebsiella (31.2%) followed by Escherichia coli (18.7%), Staphylococcus aureus (18.7%) and coagulase negative staphylococci (16.7%). Less frequently isolated organisms were streptococci, Pseudomonas and enterococci. However, highest mortality was seen with Pseudomonas (100%) and least with enterococci (0%). Association of risk factors and the mortality rates revealed similar findings in the retrospective data collected during 2003-2004.
| Discussion|| |
Our study was one of the few studies comparing the incidence and mortality rates of neonatal sepsis between two different time periods (June 2003-May 2004 and June 2013-May 2014) of a decade apart. This study was also intended to know changing trends in the risk factors associated with fatal sepsis and to evolve a risk approach in the management of neonatal sepsis. It was found that the overall incidences of sepsis (6.04 and 6.03%) and mortality rates (48% and 46.7%) were not changed much, but the incidence of EOS decreased from 3.08% to 2.57% and LOS increased from 2.96% to 3.44% of total pediatric admissions. In a similar study from North India  reported an increase in the incidence of LOS from 12 to 16.5/1000 live births. There was marked difference in the mortality rates of EOS and LOS (61.5%, 35.5% and 58.5%, 41.5%). The difference was statistically significant in both the groups (0.0041 and 0.0043). Higher mortality in EOS was due to acute fulminate multi-system involvement especially in low birth weight neonates. Similar incidence was reported in earlier studies, ,, while some other studies observed higher mortality among LOS.  The later finding could be due to different time interval (≥7 days compared to ≥72 h) as demarcation between EOS and LOS.
Prior studies have identified maternal risk factors such as age, literacy, socioeconomic status, parity, antenatal care, PPROM, predisposing factors like maternal fever/foul smelling liquor and mode of delivery. , In our study, maternal risk factors significantly associated with fatal outcome were: Illiteracy (0.0001), poor socioeconomic status (0.0008), inadequate antenatal care (<0.0001), premature rupture of membranes (0.0273), assisted vaginal delivery (0.0236). Babies of poor, illiterate mother have a higher incidence of sepsis because they are usually of low birth weight, delivered premature thus diminishing their immunity and predisposing them to infection. There is also delay in appreciating and seeking treatment. Besides, most deliveries in these families are conducted at home under improper aseptic conditions.  Adequate antenatal cares is crucial for a favorable outcome of pregnancy. Lack of adequate antenatal care associated with home deliveries without aseptic precautions, conducted by untrained dais are the preconditions for sepsis. Studies have reported 3 times higher mortality in babies with inadequate antenatal care compared to those with adequate antenatal care.  Instrument assisted deliveries had higher mortality as shown in a number of other studies due to increasing chance of infection. ,
Neonatal risk factors significantly associated with higher mortality were gestational age (0.0001), gender (0.0261), birth weight (0.0001), IPPV (0.0329), time of onset of symptoms (0.0043), delay in starting treatment (0.0001) and presence of complications (0.0001). Gestational age and neonatal mortality were inversely related. Preterm babies need NICU admission and are subjected to invasive procedures and mechanical ventilation which increases the risk of infection. Increased incidences of sepsis and its mortality were noticed among male infants in our study as reported by authors of other studies.  Once again as observed in other studies neonates who had IPPV demonstrated high risk of infection and significant fatality.  The time gap of >12 h from the onset of symptoms and starting of treatment and consequent complications like DIC/multi organ dysfunction syndrome leads to higher mortality. 
Though CRP was the most sensitive test (80%) followed by m-ESR (73.3%) and I/T ratio of >0.2 (55%) there was no correlation between the positivity of these tests and mortality. total leukocyte count/ANC was found to be least sensitive tests. However, high mortality was noticed in cases with neutropenia and leucopenia as was noticed in different studies.  The organisms isolated from EOS and LOS were similar with the commonest isolate being Klebsiella followed by E. coli, S. aureus and coagulase-negative staphylococci. Enterobacter infection was associated with least mortality while highest mortality was seen in Pseudomonas infection.
In our study, risk factors associated with fatal outcome were identified, and a score was given to each risk factor based on probability of association and the strength of association. Summation of clinical and laboratory scores of 6 or more was indicative of definite sepsis and needs aggressive treatment without waiting for culture reports based on the experience of local organisms and their antibiotic sensitivity pattern. It is better than previous scoring systems of proposed by other authors. ,, As it is based on probability and strength of association [Table 3].
| Conclusion|| |
Our experience of a decade of sepsis in South India has confirmed following things through present study:
- Incidence and mortality of sepsis has not changed much.
- Though EOS has shown slight downward trend, incidence of LOS is on increase.
- Both the EOS and LOS were caused by similar organisms and there is no change in the causative organisms and associated maternal and neonatal risk factors.
- To improve survival rate, better approach suggested is a risk approach with early initiation of appropriate antibiotics and aggressive supportive care based on local sensitivity pattern and fatal risk factors.
| Acknowledgements|| |
We are deeply indebted to neonates and their patents and we profusely thank them for their extreme cooperation.
| References|| |
Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and management of sepsis on neonatal mortality: Field trial in rural India. Lancet 1999;354:1955-61.
National Neonatology Forum NNPD Network. National Neonatal-Perinatal Database: Report for 2002-2003. New Delhi: National Neonatology Forum NNPD Network; 2005.
Thaver D, Zaidi AK. Burden of neonatal infections in developing countries: A review of evidence from community-based studies. Pediatr Infect Dis J 2009;28:S3-9.
Mathur NB. Neonatal sepsis. Indian Pediatr 1996;33:663-74.
Lawn JE, Cousens S, Zupan J, Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: When? Where? Why? Lancet 2005;365:891-900.
Stoll BJ. The global impact of neonatal infection. Clin Perinatol 1997;24:1-21.
Osrin D, Tumbahangphe KM, Shrestha D, Mesko N, Shrestha BP, Manandhar MK, et al
. Cross sectional, community based study of care of newborn infants in Nepal. BMJ 2002;325:1063.
Barnett S, Azad K, Barua S, Mridha M, Abrar M, Rego A, et al
. Maternal and newborn-care practices during pregnancy, childbirth, and the postnatal period: A comparison in three rural districts in Bangladesh. J Health Popul Nutr 2006;24:394-402.
Mathur NB, Khalil A, Sarkar R, Puri RK. Mortality in neonatal septicemia with involvement of mother in management. Indian Pediatr 1991;28:1259-63.
Mathur NB, Singh A, Sharma VK, Satyanarayana L. Evaluation of risk factors for fatal neonatal sepsis. Indian Pediatr 1996;33:817-22.
Sundaram V, Kumar P, Dutta S, Mukhopadhyay K, Ray P, Gautam V, et al
. Blood culture confirmed bacterial sepsis in neonates in a North Indian tertiary care center: Changes over the last decade. Jpn J Infect Dis 2009;62:46-50.
Karthikeyan G, Premkumar K. Neonatal sepsis: Staphylococcus aureus
as the predominant pathogen. Indian J Pediatr 2001;68:715-7.
Gandhi S, Ranjan KP, Ranjan N, Sapre N, Masani M. Incidence of neonatal sepsis in tertiary care hospital: An overview. Int J Med Sci Public Health 2013;2:548-52.
Tallur SS, Kasturi AV, Nadgir SD, Krishna BV. Clinico-bacteriological study of neonatal septicemia in Hubli. Indian J Pediatr 2000;67:169-74.
Lawn JE, Wilczynska-Ketende K, Cousens SN. Estimating the causes of 4 million neonatal deaths in the year 2000. Int J Epidemiol 2006;35:706-18.
Auriti C, Ronchetti MP, Pezzotti P, Marrocco G, Quondamcarlo A, Seganti G, et al.
Determinants of nosocomial infection in 6 neonatal intensive care units: An Italian multicenter prospective cohort study. Infect Control Hosp Epidemiol 2010;31:926-33.
Mehrotra N, Kumar A, Chansoria M, Kaul KK. Neonatal sepsis: Correlation of maternal and neonatal factors to positive bacterial cultures. Indian Pediatr 1985;22:275-80.
Ravikumara M, Bhat BV. Early neonatal mortality in an intramural birth cohort at a tertiary care hospital. Indian J Pediatr 1996;63:785-9.
Maguire GC, Nordin J, Myers MG, Koontz FP, Hierholzer W, Nassif E. Infections acquired by young infants. Am J Dis Child 1981;135:693-8.
Raghavan M, Mondal GP, Bhat BV, Srinivasan S. Perinatal risk factors in neonatal infections. Indian J Pediatr 1992;59:335-40.
Chandna A, Nagaraj RM, Srinivas M, Shyamala S. Rapid diagnostic tests in neonatal septicemia. Indian J Pediatr 1988;55:947-53.
Mondal GP, Raghavan M, Bhat BV, Srinivasan S. Neonatal septicaemia among inborn and outborn babies in a referral hospital. Indian J Pediatr 1991;58:529-33.
Bhutta ZA. Enterobacter
sepsis in the newborn - a growing problem in Karachi. J Hosp Infect 1996;34:211-6.
Chan DK, Hol LY. Usefulness of CRP in the diagnosis of neonatal sepsis. Singapore Med J 1997;38:252-5.
Bhakoo ON. Neonatal bacterial infections at Chandigarh: A decade of experience. Indian J Pediatr 1980;47:419-24.
Dalvi R, Rao S, Rangnekar J, Fernandez A. Exchange transfusions in neonatal sepsis. Indian Pediatr 1991;28:39-43.
Fernandez A. Neonatal infections. In: Fernandez A, editor. Manual of Neonatal Care. 1 st
ed. New Delhi: Churchill Livingstone; 1993. p. 152-8.
[Table 1], [Table 2], [Table 3]
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