A Study Of Early Onset Neonatal Sepsis With Special Reference To Sepsis Screening Parameters In A Tertiary Care Centre Of Rural India
K Swarnkar, M Swarnkar
early onset neonatal septicemia, maternal risk factor, rural india, sepsis screen parameter
K Swarnkar, M Swarnkar. A Study Of Early Onset Neonatal Sepsis With Special Reference To Sepsis Screening Parameters In A Tertiary Care Centre Of Rural India. The Internet Journal of Infectious Diseases. 2012 Volume 10 Number 1.
Almost 99% of the estimated 4 million annual neonatal deaths occur in developing country(1, 2). Although post-neonatal mortality rates have declined substantially, in large part due to successful child survival interventions, deaths in the neonatal period have been largely unaddressed as a global health concern and account for 40% of all deaths in children under 5(2, 3). Despite the current increased efforts, much more needs to be accomplished to reduce neonatal mortality rates from levels as high as 40 to 60 per 1000 live births, and to achieve the Millennium Development Goal for child survival(2, 3). Sepsis is the commonest cause of neonatal mortality; it is responsible for about 30-50% of the total neonatal deaths in developing countries(4, 5). It is estimated that up to 20% of neonates develop sepsis and approximately 1% die of sepsis related causes(5). The incidence of neonatal sepsis according to the data from National Neonatal Perinatal Database (NNPD, 2002-03) is 30 per 1000 live births. The database comprising 18 tertiary care neonatal units across India found sepsis to be one of the commonest causes of neonatal mortality contributing to 19% of all neonatal deaths(6). Septicemia was the commonest clinical category with an incidence of 23 per 1000 live births while the incidence of meningitis was reported to be 3 per 1000 live births. Infection is the primary cause of mortality in 18.6% of intramural neonates in which
Material and methods
This study was conducted at Acharya Vinoba Bhave Rural Hospital, Sawangi (M), Wardha, for a period of two years, from 1 st July 2008 to 30 th Jun 2010. Neonates who were clinically suspected to have bacterial infections within the first 48 hours of life, based on the risk factors and/or clinical features, were subjected to various hematological screening parameters and blood cultures. Neonates developing symptoms after 48 hours of life and blood cultures which grew fungi were excluded. The investigations done were Blood culture, Buffy coat smear examination, C-Reactive protein (CRP) test, micro-Erythrocyte sedimentation rate (micro-ESR) estimation, Total leucocyte (WBC) count, Absolute neutrophil count (ANC), and Immature (band cells) count / Total neutrophil count ratio [I/T ratio]. The blood cultures were processed and the isolates identified by standard microbiological procedures.(11, 12) Cultures were reported as negative when they did not yield any growth at the end of 7 days. Buffy coat smear examination was done according to the technique described by Brooks and associates.(13) The CRP test was done by the rapid slide latex agglutination method using the diagnostic kit for the in-vitro detection of CRP in human serum supplied commercially by Span Diagnostics Ltd. The test was carried out as per the instructions described in the kit. Micro-ESR estimation was done by using commercially available (Greiner Bioone) standard heparinised micro-hematocrit capillary tubes. Blood was collected in the capillary tubes provided in the kit, from a heel prick of the neonate after disinfecting the area. One end of the tube was sealed with plasticin and the tubes were fixed vertically in an ESR stand. The rate of erythrocyte sedimentation was measured in millimeters at the end of one hour. The total leukocyte count, differential count, ANC, I/T ratio and the Platelet count calculated as per standard hematological methods.(14)
The cut off values for the positive rapid screening tests in this study were as follows(10, 15):
All the findings were recorded and comparisons drawn between blood culture results and the sepsis screen tests. Data was analyzed using the SPSS software for Windows version 11 (Statistical Presentation System Software, SPSS Inc,1999, NewYork) and categorical tables, Chi-square values, probability coefficients, sensitivity, specificity, positive predictive values and negative predictive values of the three diagnostic methods derived and the results correlated. Conclusions were drawn from the tabulated results. A
Ethical consideration- The ethical committee of Jawahar lal Nehru medical college sawangi wardha had approved the study protocol.
Among the 3574 live birth during study period 189 episodes of Neonatal sepsis occurred, the incidence being 52.88/1000 livebirth. EOS occurred in 72 neonates with an incidence of 20.15/1000 live birth constituting 38% of overall neonatal sepsis. Male constitute 42 (58%) and females were 30(42%), ratio being 1.4:1.among the infant with EOS, 64(88.8%) were LBW, 26(36%) were VLBW and 63(87.5%) were Pre-term. The incidence of EOS in various categories of babies as shown in table.1 is significantly higher in preterm and LBW infants. Culture proven sepsis occurred in 37 cases constituting 51.38% of overall EOS. Among the culture positive cases, septicemia was more common among male neonates, seen in 22(59.5%) of the cases compared to female neonates 15(40.5%).
Among a total of 292 neonates with underlying potential neonatal risk factor for sepsis 20.9% developed sepsis, while in those without risk factor EOS occurred in only 11 cases (0.32%) (p=.0000). Among the various high risk group of infants such as VLBW, Pre-term and SGA, the incidence of sepsis was negligible if maternal risk factor were absent(.67-4%) but in those cases where risk factor were present the incidence varied from 0.31-38.46%.
As shown in table -2a that 20% mother with PROM and 30% with foul smelling liquor has infant with EOS (p<.001) compared to those without these risk factors. There was no significant association of maternal diabetes, multiple pregnancy and meconium staining of liquor with EOS(table-2b).Asphyxiated infants were more likely to have EOS(p<.0001).
The co-morbidities seen among infant with EOS were pneumonia in 68%, necrotizing enterocolitis in 15.3.% and meningitis in 8.3%,culture positivity had no significant influence on rate of occurrence of various co-morbidities except for pneumonia which was more common in culture negative than culture positive cases(76%vs33.3,p<.001).
The majority of blood culture isolates i.e. out of 37 culture positive cases, 21(56.75%) were Gram negative and klebsiella pneumoniae being commonest in 18(48.6%), followed by E.coli 5(13.5%),Gram positive organism isolated in 16(43%) of cases commonest organism being staphylococcus aureaus in 14(38%) followed by staphylococcus epidermidis in 2(5.4%) cases.
Of 37 culture positive cases CRP (89.2%), Buffy coat smear (86.4%) and I/T ratio ≥.2 (81%) were the most common positive single test.
A positive Buffy coat smear study was the single best reliable septic screen test to diagnose sepsis and positive predictive value and specificity was high when two or more sepsis screen were combined. 14 neonates with EOS died with case fatality rate of 19.4% while among culture positive cases 6 died, the mortality rate being 16.2%.
An overall incidence of neonatal sepsis of 52.88/1000 LB in the present study is comparable to other studies studies.(16, 17) The incidence of culture proven EOS of 10.35/1000 LB is comparable to 9.8/1000 LB and 8.6/1000 reported from South and North India.(18, 19) Male constitute 42(58%) and females were 30(42%), ratio being 1.4:1, these results are comparable with the observations made by other authors.(16, 20) The male preponderance in neonatal septicemia may be linked to the X- linked immunoregulatory gene factor contributing to the host's susceptibility to infections in males.(21)
An accurate and timely diagnosis of early onset neonatal sepsis remains challenging to the clinician and the laboratory. A test with a rapid turnaround time, with 100% sensitivity which allows accurate diagnosis and appropriate antimicrobial treatment, is desirable. A reasonable specificity is also required to allow the antibiotics to be safely withheld in noninfected infants. Recently, measures of acute phase proteins, cytokines, cell surface antigens, and bacterial genomes have been used alone or in combination to improve the diagnosis of neonatal sepsis.(36) The value of the sepsis screen is more for excluding the diagnosis of neonatal septicemia which can be done reasonably if two screens 12-24 hours apart are negative. In a neonate who is stable otherwise or suspected of sepsis because of maternal risk factors, it is desirable to await results of sepsis screen before initiation of antibiotics. Since symptoms suggestive of sepsis may be caused by a variety of other illnesses, confirmation of sepsis by the sepsis screen tests may help in avoiding unnecessary antibiotic therapy.(15) Blood culture is still the “Gold standard” for the diagnosis of septicemia in neonates and should be done in all cases of suspected septicemia. In view of the changing spectrum of the causative agents of neonatal septicemia and their antibiotic susceptibility patterns from time to time and from one hospital to another, a positive blood culture and the antibiotic susceptibility testing of the isolates are the best guide in choosing the appropriate antimicrobial therapy in treating neonatal septicemia.