Study of the hematological scoring system and C-reactive protein (CRP) in determining Neonatal sepsis

Study of the hematological scoring system and C-reactive protein (CRP) in determining Neonatal sepsis Ramesh Godbole C.1*, Ramdas Joshi S.2, Jaison J.3 DOI: https://doi.org/10.17511/jopm.2020.i02.11 1* Chandrahas Ramesh Godbole, Associate Professor, Department of Pathology, MIMER Medical College, Talegaon, Maharashtra, India. 2 Sneha Ramdas Joshi, Professor and Head of Department, Department of Pathology, MIMER Medical College, Talegaon, Maharashtra, India. 3 Janice Jaison, Associate Professor, Department of Pathology, MIMER Medical College, Talegaon, Maharashtra, India.


Introduction
Neonatal sepsis is defined as an aggressive bacterial infection occurring in the first 4 weeks of life. The incidence of neonatal sepsis varies from 11-24.5 /1000 live births in India [1]. The clinical pointer of sepsis in new-born infants is usually non-specific.
Because of the high morbidity and mortality which is related to neonatal sepsis [2,3,4], antibiotic therapy is started soon after the commencement of the symptoms before the diagnosis is long-established by blood culture.
The use of effective antimicrobial therapy has evidently reduced neonatal mortality. However, there is a need for a rapid test that can identify  Under complete aseptic conditions, 0.5-1 ml of the blood sample was obtained. Sepsis workup involved complete blood counts along with hematological score (Rodwell's) and microbial culture. Uncorrected WBC count, platelet count was measured using 5 part fully automated analyzer.
Neutrophils were classified as band forms when there was no nuclear segmentation or when the width of the nucleus at any constriction was not less than one-third the widths at its widest portion.
Band forms together with less mature cell forms were classified as immature Polymorphonuclear The HSS assigns a score of one for each of the seven criteria found to be significantly associated with sepsis with one exception. An abnormal total PMN count is assigned a score of 2 instead of 1 as shown in the [ Table 1]. Sensitivity, specificity, positive and negative predictive values will be evaluated for each of the seven criteria of HSS.
Blood Culture and CRP estimation were done as per the standard protocol.

Results
In the current study, blood culture was positive in 10 cases (25%), out of which 6 (60%) were Grampositive and 4 (40%) were Gram-negative, whereas 30 cases were found to be negative for blood culture. If the bacteriological profile of the culture is assumed to be the standard outcome, 10 cases are labeled as the definitive sepsis cases.
Klebsiella Pneumonia, Pseudomonas, Enterococcus, Staphylococcus aureus,and E. coli were the infections observed in the positive culture (Table 2).  The commonest age in the cases was 6-10 days and ≤5 days in both the positive and negative culture cases. 6 (60%) of positive culture cases were under 6-10 days while 13 (43.3%) of cases were ≤ 5 days (Table 4). Based on Rodwell's scoring system, neonates could be classified as sepsis to be unlikely Score Interpretation ≤ 2 Sepsis is unlikely in 4 cases, possible in 11 cases and very likely in 25 cases (Table 5 and Table 6).   The current study showed 10 neonates with positive culture, of which all of them had a HSS of ≥6 (Table   7). The sensitivity, specificity, PPV and NPV of HSS with cut-off score of 6 in predicting sepsis was 33.3%, 56.6%, 62.5%, 100%.
Band cell is described as a PMN in which the nucleus is indented by more than one-half, but in which, the isthmus between the lobes is wide enough to reveal two distinct margins with nuclear material in between.

Fig-1: Leucocytosis with degenerative changes and band forms.
Toxic granulations represent the cytoplasmic alterations in peripheral blood neutrophils in response to bacterial infection and have been found to be of greater use in differentiating localized from generalized infection or the development of complications (Figure 2).

Discussion
Neonatal sepsis is a serious and potentially lifethreatening condition. In developing countries like India, neonatal sepsis is the major cause of morbidity and mortality in new-born. Risk is increased very much again because of noninstitutional delivery and poor postnatal follow-up. However early diagnosis and treatment are vital for a favorable outcome. Early diagnosis is a difficult task and based mainly on clinical suspicion. No doubt, blood culture is still the gold standard but because of its non-availability in most peripheral setups, high cost, more chances of contamination and delayed results, a need for more convenient, cost-effective test protocol whose results are consistently associated with poor prognosis. These findings were in comparison with other studies [29][30][31][32]. The higher the score, the greater was the likelihood of sepsis. A score ≤2 suggests that sepsis was unlikely.
Protein sepsis markers, such as CRP, should be used in concert with clinical signs and findings to make the diagnosis of neonatal sepsis and formulate a plan for management [33,34]. CRP has been used to monitor response to infection and to assist in ruling out an infection. Most of these studies have been done in children, term, or near-term neonates using the lower CRP level cutoffs of <8 mg/dL or <10 mg/dL [35]. The Committee of Fetus and Newborn of the American Academy of Pediatrics (AAP) in their statement on infants with suspected or proven sepsis have expressed agreement in the utility of inflammatory biomarkers [36]. Although other biomarkers such as PCT may also be used, CRP has been described as a later but more specific marker of infection The major limitations of the present study were the small size of the subjects. A similar study with a large sample size might be able to provide a more comprehensive outcome on the role of HSS and CRP in neonatal sepsis.

Conclusion
HSS is a simple, quick, cost-effective tool that can be used as a screening test for early diagnosis of neonatal sepsis. It may aid the clinicians in identifying sepsis and to institute proper antibiotic therapy. Unnecessary exposure of infants to antibiotic therapy can thus be avoided. A hematological score can be obtained by a complete blood count and examination of a peripheral blood smear, thus permitting an objective assessment of hematological changes that occur in a neonate suspected of sepsis. Similarly, it would be fair to say that the estimation of CRP in the diagnosis of neonatal sepsis have emerged and evolve rapidly over the last few years. Combining the estimation of CRP with HSS appears to provide a far more effective tool to be used as a screening method for neonatal sepsis.
What does the study add to the existing knowledge?
The current study aims to highlight the significant role and association between HSS and CRP in the diagnosis of neonatal sepsis. C-reactive protein values correlate well with HSS in predicting sepsis.
However, C-reactive protein along with HSS does promise to establish a more effective tool to be used in the screening of neonatal sepsis.
Godbole CR et al: Study of the hematological scoring system and C-reactive Tropical Journal of Pathology and Microbiology 2020;6(2)