Neonatal septicaemia remains a leading cause of neonatal morbidity and mortality, particularly in developing regions like India. It is characterized by a systemic inflammatory response to infection in neonates within the first 28 days of life. Early diagnosis is critical to reducing mortality, yet clinical signs are nonspecific, making laboratory support indispensable [1].

Blood culture remains the gold standard for confirming neonatal sepsis. However, it is limited by delayed turnaround times (48–72 hours), low sensitivity (positive in only 30–40% of suspected cases), and potential for contamination or sampling error [2,3]. These limitations delay targeted therapy and may lead to inappropriate or prolonged empirical antibiotic use.

To overcome these challenges, biomarkers such as C-reactive protein (CRP) have gained attention for their potential in early sepsis diagnosis. CRP is an acute-phase protein synthesized by hepatocytes in response to proinflammatory cytokines like IL-6. It typically rises within 6–8 hours of infection onset, peaks by 24–48 hours, and declines with resolution of inflammation [4]. Its rapid kinetics and wide availability make CRP a useful adjunct in neonatal intensive care units (NICUs), especially in resource-limited settings.

Multiple studies have evaluated CRP’s diagnostic accuracy. Dhanalakshmi and Sivakumar found that CRP was elevated in 37 of 39 culture-positive neonates, suggesting strong correlation between CRP and confirmed sepsis [2]. Hisamuddin et al. reported a CRP sensitivity of 92% and specificity of 80% in blood culture-confirmed cases [3], while Gupta et al. showed diagnostic concordance between CRP positivity and culture results in over 70% of cases [4]. These findings were echoed in older foundational studies like Sabel and Wadsworth's, which established CRP as a valuable early biomarker [5].

Younis et al. found CRP to be a cost-effective and reproducible tool for sepsis screening in high-risk neonates [6], while Reier-Nilsen et al. highlighted the superior turnaround time of CRP compared to molecular diagnostics or conventional cultures [7]. Shoukry et al. further demonstrated that combining CRP with clinical scoring improved early diagnostic accuracy [8]. Likewise, Bhatia et al. advocated CRP as a reliable adjunctive marker to blood culture, particularly in peripheral healthcare setups [9].

This study was undertaken to evaluate the diagnostic utility of CRP relative to blood culture in neonates with suspected septicemia at a tertiary care centre in Rajkot, Gujarat. By quantifying the correlation between CRP and culture outcomes, the aim is to validate CRP’s role as a rapid, accessible screening marker in early sepsis diagnosis.

Aims and Objectives

To evaluate the diagnostic accuracy of C-reactive protein (CRP) in comparison with blood culture in the early identification of neonatal septicemia.

Primary Objective:

• To determine the correlation between CRP positivity and blood culture outcomes in neonates with suspected septicemia.

Secondary Objectives:

• To calculate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CRP in diagnosing neonatal sepsis.
• To evaluate the proportion of CRP-positive neonates who are blood culture-negative, and vice versa, to understand potential discordance.
• To assess the demographic and clinical distribution of suspected sepsis cases by sex, birth weight, and gestational age.

Study Design and Setting

This retrospective, cross-sectional study was conducted in the Department of Paediatrics and Neonatology at a tertiary care centre in Rajkot, Gujarat. The data were collected from the hospital’s medical records over a defined study period involving neonates admitted with suspected septicemia.

Study Population

A total of 118 neonates (≤28 days old) admitted with clinical suspicion of neonatal sepsis were included in the analysis. All enrolled neonates had undergone both CRP testing and blood culture as part of their initial sepsis workup.

Inclusion Criteria:

• Neonates (0–28 days of life) with clinical signs suggestive of septicemia (e.g., lethargy, poor feeding, temperature instability, respiratory distress).
• Availability of both CRP and blood culture reports at admission.

Exclusion Criteria:

• Neonates with incomplete records or missing CRP/blood culture results.
• Neonates with known congenital anomalies or inborn errors of metabolism.

Data Collection and Laboratory Methods

Demographic data including sex, birth weight, and gestational age were extracted from hospital records. CRP was measured using standard immunoturbidimetric methods, with a value ≥6 mg/L considered positive. Blood cultures were processed using automated BACTEC or manual techniques as per hospital protocols. All data were anonymized prior to analysis.

Statistical Analysis

The diagnostic performance of CRP was evaluated by calculating sensitivity, specificity, PPV, and NPV using blood culture as the gold standard. Chi-square test was used to assess the correlation between CRP and blood culture results. Data analysis was performed using Microsoft Excel and SPSS version 25. A p-value < 0.05 was considered statistically significant.

Demographic and Clinical Profile

A total of 118 neonates were included in the study. Of these, 75 (63.6%) were male and 43 (36.4%) were female. The majority of neonates (82, 69.5%) were born at term, while 36 (30.5%) were preterm. Regarding birth weight distribution, 65 neonates (55.1%) had a birth weight of 2.5 kg or more, and 53 (44.9%) weighed less than 2.5 kg at birth. These baseline characteristics are summarized in Table 1.

Table 1. Neonatal Demographic and Clinical Characteristics

 CRP and Blood Culture Results

Out of the 118 neonates evaluated, 70 (59.3%) tested positive for C-reactive protein (CRP), while 48 (40.7%) were CRP-negative. Blood culture was positive in 31 neonates (26.3%) and negative in 87 (73.7%). These results indicate a higher detection rate for CRP compared to blood culture in suspected neonatal sepsis cases. The diagnostic distribution is presented in Table 2.

Table 2. Distribution of CRP and Blood Culture Results

Diagnostic Accuracy of CRP

The diagnostic accuracy of CRP was assessed using blood culture as the reference standard. Among 31 neonates with culture-confirmed sepsis, 27 were also CRP-positive, yielding a sensitivity of 87.1%. Of the 87 neonates with negative blood culture results, 44 were CRP-negative, corresponding to a specificity of 50.6%. The positive predictive value (PPV) of CRP was 38.6%, while the negative predictive value (NPV) was high at 91.7%. These values suggest that while CRP is sensitive for detecting sepsis, its specificity and PPV are limited, potentially due to false positives in inflammatory but non-septic conditions. Full diagnostic metrics are presented in Table 3.

Table 3. Diagnostic Performance of CRP Compared to Blood Culture

Discordance Analysis

Discordant results between CRP and blood culture were observed in 47 of the 118 neonates (39.8%). Among these, 43 neonates (36.4%) were CRP-positive but had negative blood cultures, suggesting the presence of inflammatory conditions other than culture-confirmed sepsis. Conversely, 4 neonates (3.4%) were CRP-negative yet blood culture-positive, indicating the possibility of early-stage infection or a delayed inflammatory response. These findings highlight the limitations of CRP as a standalone diagnostic marker and underscore the continued importance of blood culture confirmation. Details of the discordant cases are presented in Table 4.

Table 4. Discordant Results between CRP and Blood Culture

Subgroup Analysis

Subgroup analysis based on gestational age and birth weight revealed similar CRP and blood culture positivity rates across groups. Among term neonates (n = 82), 48 (58.5%) were CRP-positive, and 20 (24.4%) had positive blood cultures. In preterm neonates (n = 36), CRP was positive in 22 (61.1%), and blood cultures were positive in 11 (30.6%). CRP positivity was also comparable among neonates with birth weight ≥2.5 kg (58.5%) and <2.5 kg (60.4%). Blood culture positivity was marginally higher in the low birth weight group (24.5%) compared to the higher birth weight group (27.7%). These findings suggest that CRP retains similar diagnostic yield across common neonatal risk strata. Details are shown in Table 5.

Table 5. CRP and Blood Culture Positivity by Neonatal Subgroup

This study evaluated the diagnostic utility of C-reactive protein (CRP) in comparison to blood culture among neonates with clinically suspected septicemia admitted to a tertiary care hospital. The results consistently demonstrated that CRP exhibits high sensitivity and a robust negative predictive value, reinforcing its role as an effective screening biomarker for early identification of neonatal sepsis. However, its relatively lower specificity underscores the need for complementary confirmatory testing in clinical decision-making.

The demographic and clinical profile of our cohort was representative of a typical NICU population in a developing country, with a slight male predominance (63.6%) and a majority of term neonates (69.5%). Notably, CRP positivity was seen in 59.3% of cases, whereas only 26.3% had blood culture-confirmed sepsis, consistent with global reports highlighting CRP’s broader inflammatory response spectrum. Ohlin et al. also observed higher CRP detection rates than culture yields, emphasizing its early responsiveness to systemic inflammation [10].

Diagnostic performance metrics in our study underscore CRP’s clinical utility. With a sensitivity of 87.1% and a negative predictive value (NPV) of 91.7%, CRP appears particularly reliable for ruling out sepsis. This aligns with findings from Hisamuddin et al., who reported similarly high sensitivity and NPV for CRP in a Pakistani neonatal cohort [11]. The specificity in our study (50.6%) was lower, likely due to CRP elevation in non-infectious inflammatory conditions, a limitation previously noted by Gupta et al. in comparable settings [12].

The discordance analysis further contextualizes CRP’s strengths and limitations. While 36.4% of neonates were CRP-positive but culture-negative, this may reflect either false-positive CRP elevation or false-negative blood culture results due to sample volume or prior antibiotic exposure. On the other hand, 3.4% of neonates were CRP-negative despite a positive culture—an important reminder of the potential for early sepsis without inflammatory marker elevation. Dhanalakshmi and Sivakumar highlighted similar discordant findings in early-stage infections [13].

Subgroup analysis revealed consistent CRP and culture positivity rates across gestational and birth weight strata, reinforcing CRP’s diagnostic stability across vulnerable neonatal subpopulations. Preterm neonates had slightly higher culture positivity (30.6%) compared to term infants (24.4%), as expected given their immature immune response. Bhatia et al. similarly observed higher CRP positivity among low birth weight neonates but noted its preserved diagnostic yield across strata [14].

Two complementary figures provided further clarity. Figure 1 visually contrasted the positivity rates of CRP and blood culture, reaffirming CRP’s broader detection reach. Figure 2, which mapped true and false diagnostic classifications, highlighted the predominance of CRP false positives, reinforcing the need for confirmatory testing when CRP is used as a standalone screen.

Overall, our findings strongly support CRP as a reliable, rapid, and accessible biomarker for early detection and risk stratification in neonatal sepsis. However, it should be interpreted in the context of clinical findings and, where available, culture confirmation. As Shoukry et al. and Sabel and Wadsworth noted decades apart, CRP performs best as part of a multi-modal diagnostic strategy [15,16].

Limitations

This study had several limitations. First, it was conducted at a single tertiary care center, which may limit the generalizability of results. Second, blood culture as the reference standard is known to have suboptimal sensitivity, particularly in neonates where sample volume is limited. Third, we did not stratify CRP values by temporal kinetics (e.g., serial CRP), which may provide additional diagnostic insight. Lastly, potential prior antibiotic exposure could have influenced culture results in some cases, leading to possible underestimation of true sepsis rates.

CRP demonstrated high sensitivity and negative predictive value in detecting neonatal septicemia, supporting its role as a frontline screening tool in resource-limited settings. However, its limited specificity underscores the need for confirmatory testing and clinical correlation. Used in conjunction with blood culture and clinical judgment, CRP can aid in early risk stratification and timely management of neonatal sepsis.

1. Ohlin, A., Björkqvist, M., & Montgomery, S. M. (2010). Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis. Acta Paediatrica, 99(3), 402–406. https://doi.org/10.1111/j.1651-2227.2010.01913.x
2. Dhanalakshmi, V., & Sivakumar, E. S. (2015). Comparative study in early neonates with septicemia by blood culture, staining techniques and C–reactive protein (CRP). Journal of Clinical and Diagnostic Research, 9(4), DC12–DC14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413066/
3. Hisamuddin, E., Hisam, A., & Wahid, S. (2015). Validity of C-reactive protein (CRP) for diagnosis of neonatal sepsis. Pakistan Journal of Medical Sciences, 31(3), 527–531. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485264/
4. Gupta, A., Rajput, D., Sodani, S., & Mutha, A. (2021). Comparison of CRP with blood culture in the diagnosis of neonatal septicaemia. Journal of Clinical Neonatology. https://www.academia.edu/download/95416034/12893.pdf
5. Sabel, K. G., & Wadsworth, C. H. (1979). C-reactive protein (CRP) in early diagnosis of neonatal septicemia. Acta Paediatrica Scandinavica, 68(6), 825–831. https://doi.org/10.1111/j.1651-2227.1979.tb08219.x
6. Younis, S., Sheikh, M. A., & Raza, A. A. (2014). Diagnostic accuracy of C-reactive protein in neonatal sepsis. Journal of Biomedical Management, 1(1). https://corescholar.libraries.wright.edu/jbm/vol1/iss1/1/
7. Reier-Nilsen, T., Farstad, T., Nakstad, B., & Lauvrak, V. (2009). Comparison of broad range 16S rDNA PCR and conventional blood culture for diagnosis of sepsis in the newborn: a case-control study. BMC Pediatrics, 9(5). https://link.springer.com/article/10.1186/1471-2431-9-5
8. Shoukry, L. R., Mohamed, A. N., & Sharaf, A. E. A. (2021). Diagnostic markers for early detection of neonatal sepsis. Journal of Scientific Research in Medical and Biological Sciences, 2(3), 40–49. https://doi.org/10.47631/jsrmbs.v2i3.319
9. Bhatia, S., Verma, C. R., Tomar, B. S., & Natani, B. S. (2016). Correlation of CRP and Blood Culture in evaluation of Neonatal Sepsis. International Journal of Biomedical and Advance Research, 7(12), 663–670. https://www.ijbamr.com/assets/images/issues/pdf/December%202016%20663-670.pdf.pdf
10. Ohlin, A., Björkqvist, M., & Montgomery, S. M. (2010). Clinical signs and CRP values associated with blood culture results in neonates evaluated for suspected sepsis. Acta Paediatrica, 99(3), 402–406. https://doi.org/10.1111/j.1651-2227.2010.01913.x
11. Hisamuddin, E., Hisam, A., & Wahid, S. (2015). Validity of C-reactive protein (CRP) for diagnosis of neonatal sepsis. Pakistan Journal of Medical Sciences, 31(3), 527–531. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485264/
12. Gupta, A., Rajput, D., Sodani, S., & Mutha, A. (2021). Comparison of CRP with blood culture in the diagnosis of neonatal septicaemia. Journal of Clinical Neonatology. https://www.academia.edu/download/95416034/12893.pdf
13. Dhanalakshmi, V., & Sivakumar, E. S. (2015). Comparative study in early neonates with septicemia by blood culture, staining techniques and C–reactive protein (CRP). Journal of Clinical and Diagnostic Research, 9(4), DC12–DC14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413066/
14. Bhatia, S., Verma, C. R., Tomar, B. S., & Natani, B. S. (2016). Correlation of CRP and Blood Culture in evaluation of Neonatal Sepsis. International Journal of Biomedical and Advance Research, 7(12), 663–670. https://www.ijbamr.com/assets/images/issues/pdf/December%202016%20663-670.pdf.pdf
15. Shoukry, L. R., Mohamed, A. N., & Sharaf, A. E. A. (2021). Diagnostic markers for early detection of neonatal sepsis. Journal of Scientific Research in Medical and Biological Sciences, 2(3), 40–49. https://doi.org/10.47631/jsrmbs.v2i3.319
16. Sabel, K. G., & Wadsworth, C. H. (1979). C-reactive protein (CRP) in early diagnosis of neonatal septicemia. Acta Paediatrica Scandinavica, 68(6), 825–831. https://doi.org/10.1111/j.1651-2227.1979.tb08219.x
17. Younis, S., Sheikh, M. A., & Raza, A. A. (2014). Diagnostic accuracy of C-reactive protein in neonatal sepsis. Journal of Biomedical Management, 1(1). https://corescholar.libraries.wright.edu/jbm/vol1/iss1/1/

  Reier-Nilsen, T., Farstad, T., Nakstad, B., & Lauvrak, V. (2009). Comparison of broad range 16S rDNA PCR and conventional blood culture for diagnosis of sepsis in the newborn: a case-control study. BMC Pediatrics, 9(5). https://doi.org/10.1186/1471-2431-9-5