A systemic infection that develops during the first 28 days of life, neonatal sepsis continues to be a significant cause of newborn morbidity & mortality worldwide[1]. Nearly one-third of newborn mortality in developing countries attributed to neonatal illnesses, according to the World Health Organization. Improving survival rates requires early diagnosis & timely antibiotic medication beginning[2].

Because clinical indications of newborn sepsis are frequently modest & vague, diagnosing the condition can be challenging. Noninfectious illnesses can be mimicked by symptoms like poor eating, lethargy, respiratory discomfort, temperature instability, & irritability. Although blood culture is regarded as the gold standard for diagnosis, it has a number of drawbacks, such as delayed results, reduced sensitivity because of insufficient sample volume, & previous antibiotic therapy administered to the mother[3].

Due to these constraints, a number of laboratory indicators have been studied for newborn sepsis early diagnosis. Neonatal intensive care units frequently use hematological measures such as total leukocyte count, absolute neutrophil count, immature to total neutrophil ratio, platelet count, & micro-ESR[4]. These parameters are generally accessible, quick, & reasonably priced.

Hepatocytes produce C-reactive protein, an acute-phase reactant, in reaction to inflammatory cytokines. CRP levels peak between 24 & 48 hours after infection, rising within 6 to 8 hours. CRP may be a helpful supplementary measure for newborn sepsis, according to several studies. Nevertheless, when utilized in isolation, no single laboratory test offers adequate sensitivity & specificity[5-6].

Therefore, combining CRP with hematological parameters may improve the diagnostic accuracy for neonatal sepsis. The present study was undertaken to evaluate the diagnostic utility of CRP & hematological parameters in correlation with blood culture for early diagnosis of neonatal sepsis[7].

This prospective observational study was conducted in the Department of Pediatrics & Neonatal Intensive Care Unit of a tertiary care teaching hospital over a period of one year at Mahaveer Institute of Medical Sciences, Bhopal, M.P. Study Population A total of 100 neonates admitted to NICU with clinical suspicion of neonatal sepsis were included in the study. Inclusion Criteria 1. Neonates aged 0–28 days. 2. Presence of one or more clinical features suggestive of sepsis such as: o Fever o Hypothermia o Respiratory distress o Poor feeding o Lethargy o Convulsions o Apnea o Abdominal distension Exclusion Criteria 1. Neonates who received antibiotics before admission. 2. Major congenital malformations. 3. Severe birth asphyxia. 4. Neonates whose parents refused consent. Ethical Consideration Approval was obtained from the Institutional Ethics Committee prior to commencement of the study. Written informed consent was obtained from parents or guardians. Data Collection Detailed maternal & neonatal history was recorded. Clinical examination findings were documented in a structured proforma. Laboratory Investigations Under aseptic precautions, blood samples were collected for: • Blood culture • C-reactive protein • Total leukocyte count • Differential leukocyte count • Absolute neutrophil count • Immature to total neutrophil ratio • Platelet count • Micro-ESR Blood Culture Blood culture was performed before initiation of antibiotic therapy. Growth of pathogenic organisms was considered positive. C-Reactive Protein CRP was measured by latex agglutination method. CRP >6 mg/L was considered positive. Hematological Parameters The following abnormal values were considered suggestive of sepsis: • TLC <5000/mm³ or >25,000/mm³ • ANC below normal for age • I/T ratio >0.2 • Platelet count <150,000/mm³ • Micro-ESR >15 mm in first hour Statistical Analysis Data were entered into Microsoft Excel & analyzed using SPSS software version 24. Quantitative variables were expressed as mean ± standard deviation. Chi-square test & Student’s t-test were applied where appropriate. Sensitivity, specificity, positive predictive value (PPV), & negative predictive value (NPV) were calculated. A p-value <0.05 was considered statistically significant.

Among the 100 neonates included in the study, 42 cases were blood culture positive while 58 cases were culture negative.

Table 1: Demographic Profile of Study Population

The majority of neonates were males (58%) & term babies (54%). Early onset sepsis was more common than late onset sepsis.

Table 2: Comparison of Hematological Parameters Between Culture Positive & Culture Negative Neonates

Elevated I/T ratio & thrombocytopenia showed strong association with blood culture positivity.

Table 3: Correlation of CRP with Blood Culture

CRP positivity was observed in 90.5% of culture-positive neonates & only 20.7% of culture-negative neonates. The association was statistically significant.

Table 4: Diagnostic Accuracy of CRP & Hematological Parameters

CRP demonstrated the highest sensitivity & negative predictive value among all investigated parameters

Neonatal sepsis is still a major health issue, especially in underdeveloped nations where a lack of medical resources causes a delay in identification & treatment. Early recognition of neonatal sepsis is essential because delayed therapy significantly increases mortality & complications[8].

Forty-two percent of probable patients in the current study had positive blood cultures. Previous investigations have shown similar results, with culture positive ranging from 30% to 50%. Low bacterial load, previous maternal antibiotic exposure, or technical constraints of culture techniques could be the cause of the comparatively lower positive rate [9].

In our analysis, males predominated, making about 58% of the cases. This result is in line with earlier research that suggested X-linked immunological variables may make male newborns more vulnerable to infection [10].

63% of patients had early onset sepsis, which is consistent with the increased prevalence of prenatal & maternal risk factors in poor nations. Lethargy, poor eating, temperature instability, & respiratory distress were common clinical characteristics noted [11].

It is commonly acknowledged that CRP is a significant inflammatory marker in newborn sepsis. 90.5% of culture-positive cases in our study had CRP positivity, with a 79.3% specificity. These results are similar to those of research by Philip & Hewitt & Benitz et al., which showed that CRP had a high sensitivity for newborn sepsis.

A negative CRP result may help rule out sepsis & minimize needless antibiotic exposure, according to the study's high negative predictive value of CRP. However, because hepatic synthesis takes several hours after inflammation begins, CRP levels could stay normal throughout the early stages of illness.

Elevated I/T ratios among hematological markers were statistically significantly associated with culture-positive sepsis. In response to infection, the bone marrow releases more immature neutrophils, which is reflected in the I/T ratio. Our results are consistent with other research that found the I/T ratio to be a trustworthy indicator of newborn infection.

Of the cases who tested positive for culture, 71.4% had thrombocytopenia. This observation may be explained by platelet consumption & destruction during sepsis [12]. In newborns, thrombocytopenia has been linked to serious infection & a bad prognosis.

Neonatal sepsis was also significantly correlated with abnormal TLC & low ANC. Because overwhelming sepsis depletes bone marrow reserves, leukopenia is frequently thought to be more predictive of severe infection than leukocytosis [13].

59.5% of newborns with positive cultures had increased micro-ESR. Micro-ESR is a straightforward bedside diagnostic that might be helpful in environments with limited resources, despite its lack of specificity.

Neonatal sepsis cannot be accurately diagnosed by a single laboratory test. Therefore, improved diagnostic performance is achieved when CRP is combined with hematological markers. Sensitivity & specificity were greatly increased in our study when CRP was combined with thrombocytopenia & a high I/T ratio [14].

The findings of this study support the use of CRP & hematological scoring systems as valuable adjuncts in early diagnosis of neonatal sepsis, especially where blood culture facilities are limited or delayed.

Limitations of the Study

1. Single-center study with relatively small sample size.
2. Serial CRP estimation was not performed.
3. Anaerobic cultures & fungal cultures were not included.
4. Molecular diagnostic techniques were not available.

Despite these limitations, the study provides useful evidence regarding the role of CRP & hematological parameters in neonatal sepsis.

Neonatal sepsis remains a major cause of neonatal morbidity & mortality. Blood culture continues to be the gold standard for diagnosis, but delayed results limit its utility in early management. C-reactive protein demonstrated high sensitivity & negative predictive value in diagnosing neonatal sepsis. Hematological parameters, particularly elevated I/T ratio & thrombocytopenia, were significantly associated with culture-positive sepsis. Combination of CRP with hematological parameters improves diagnostic accuracy & can serve as an effective screening tool for early detection of neonatal sepsis. Early use of these investigations can facilitate prompt treatment & reduce neonatal mortality. Further multicenter studies with larger sample sizes are recommended to validate these findings.

1. Vergnano S, Sharland M, Kazembe P, Mwansambo C, Heath PT. Neonatal sepsis: an international perspective. Arch Dis Child Fetal Neonatal Ed. 2005;90(3):F220-4.
2. Gerdes JS. Diagnosis & management of bacterial infections in the neonate. Pediatr Clin North Am. 2004;51(4):939-59.
3. Philip AG, Hewitt JR. Early diagnosis of neonatal sepsis. Pediatrics. 1980;65(5):1036-41.
4. Benitz WE, Han MY, Madan A, Ramachandra P. Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics. 1998;102(4):E41.
5. Rodwell RL, Leslie AL, Tudehope DI. Early diagnosis of neonatal sepsis using a hematologic scoring system. J Pediatr. 1988;112(5):761-7.
6. Manroe BL, Weinberg AG, Rosenfeld CR, Browne R. The neonatal blood count in health & disease. J Pediatr. 1979;95(1):89-98.
7. Mathers NJ, Pohlandt F. Diagnostic audit of C-reactive protein in neonatal infection. Eur J Pediatr. 1987;146(2):147-51.
8. Da Silva O, Ohlsson A, Kenyon C. Accuracy of leukocyte indices & CRP for diagnosis of neonatal sepsis. Pediatr Infect Dis J. 1995;14(5):362-6.
9. Polin RA. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129(5):1006-15.
10. Sucilathangam G, Amuthavalli K, Velvizhi G, Ashihabegum MA, Jeyamurugan T, Palaniappan N. Early diagnostic markers for neonatal sepsis. J Clin Diagn Res. 2012;6(4):627-31.
11. Sharma A, Kutty CV. Hematological profile in neonatal septicemia. Indian J Pediatr. 1998;65(6):803-8.
12. Chiesa C, Panero A, Osborn JF, Simonetti AF, Pacifico L. Diagnosis of neonatal sepsis: a clinical & laboratory challenge. Clin Chem. 2004;50(2):279-87.
13. Malik GK, Nagpal K, Sharma M, Prasad R. Neonatal sepsis: evaluation of C-reactive protein & hematological parameters. Indian Pediatr. 1991;28(6):693-6.
14. Tollner U. Early diagnosis of septicemia in the newborn. Clinical studies & sepsis score. Eur J Pediatr. 1982;138(4):331-7.