Neonatal sepsis is a life-threatening condition characterized by systemic signs of infection in the first 28 days of life. It continues to be a major cause of neonatal morbidity and mortality, particularly in low- and middle-income countries (1). Early diagnosis remains a challenge due to the non-specific clinical presentation and the limited reliability of traditional laboratory markers (2). Blood culture, while considered the gold standard for confirming sepsis, is time-consuming and may yield false-negative results, especially when antibiotic therapy is initiated before sample collection (3,4). Hence, there is a growing need for reliable, rapid, and cost-effective biomarkers that can facilitate early diagnosis and monitoring of neonatal sepsis.

C-reactive protein (CRP), an acute-phase reactant synthesized by the liver in response to infection or inflammation, has gained attention as a potential diagnostic marker for neonatal sepsis (5). CRP levels typically rise within 6–8 hours of infection onset and peak at around 48 hours, making it a valuable tool for early detection and follow-up (6). Several studies have demonstrated that serial CRP measurements can improve diagnostic accuracy and assist in guiding the duration of antibiotic therapy in neonates (7,8). However, the interpretation of CRP levels may be influenced by perinatal factors such as birth trauma, maternal fever, or meconium aspiration, necessitating cautious evaluation (9,10).

This study aims to assess the diagnostic utility of CRP in neonates with suspected sepsis, using blood culture as the reference standard, and to determine the sensitivity, specificity, and predictive values of CRP in early detection.

Study Population:

Neonates aged 0–28 days who presented with clinical features suggestive of sepsis, such as poor feeding, lethargy, temperature instability, respiratory distress, or irritability, were included in the study. Neonates with major congenital anomalies, those who had received antibiotics prior to admission, or whose parents declined consent were excluded.

Clinical Evaluation and Grouping:

All neonates underwent a detailed clinical examination and relevant history was recorded. Based on blood culture results, neonates were categorized into two groups:

• Sepsis group: Culture-positive cases
• Non-sepsis group: Culture-negative cases

Sample Collection and CRP Measurement:

Venous blood samples were collected aseptically before the initiation of antibiotics. A minimum of 1 mL blood was sent for culture using standard microbiological techniques. Simultaneously, 1 mL of blood was used to estimate CRP levels using a quantitative immunoturbidimetric assay. CRP measurements were repeated at 24 and 48 hours to assess the trend.

Outcome Measures:

The diagnostic performance of CRP was evaluated by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), using blood culture as the reference standard.

Statistical Analysis:

Data were entered and analyzed using SPSS version 26. Descriptive statistics were used for baseline characteristics. Sensitivity, specificity, PPV, and NPV were calculated using standard 2×2 contingency tables. A p-value of <0.05 was considered statistically significant.

A total of 100 neonates suspected of sepsis were enrolled in the study. Of these, 40 (40%) were confirmed as septic based on positive blood culture results, while 60 (60%) were culture-negative.

Demographic Profile

Among the 100 neonates, 58 were male and 42 were female. The mean birth weight was 2.6 ± 0.4 kg, and the mean gestational age was 37.2 ± 1.8 weeks. There was no statistically significant difference in sex distribution, birth weight, or gestational age between the culture-positive and culture-negative groups (Table 1).

Table 1. Baseline characteristics of study participants

CRP as a Diagnostic Marker

Initial CRP levels (at admission) were elevated (>10 mg/L) in 35 of the 40 culture-positive neonates. Among the 60 culture-negative neonates, elevated CRP was noted in 13 cases. Based on these findings, CRP demonstrated a sensitivity of 87.5%, specificity of 78.3%, PPV of 72.9%, and NPV of 90.6% (Table 2).

Table 2. Diagnostic performance of CRP compared to blood culture

Table 3. Sensitivity, Specificity, and Predictive Values of CRP

CRP levels were significantly higher in the culture-positive group compared to the culture-negative group at admission (mean CRP: 19.6 ± 4.3 mg/L vs. 6.5 ± 3.2 mg/L; p<0.001). Serial CRP measurements at 24 and 48 hours showed declining trends in clinically improving neonates and continued elevation in those with worsening conditions.

Thus, elevated CRP at admission and its dynamic trend over 48 hours were found to be useful indicators in the early diagnosis and management of neonatal sepsis (Table 2, Table 3).

Neonatal sepsis is a critical condition that requires prompt diagnosis and treatment to reduce morbidity and mortality. In this study, we evaluated the diagnostic performance of C-reactive protein (CRP) as an early biomarker of neonatal sepsis and found that CRP had good sensitivity and specificity, supporting its utility as a reliable adjunct to clinical and microbiological findings.

Our results demonstrated a sensitivity of 87.5% and a specificity of 78.3% for CRP, which is consistent with previous literature reporting sensitivities ranging from 70% to 90% and specificities between 60% and 85% (1,2). This diagnostic accuracy highlights the potential of CRP to serve as an early indicator of infection in neonates when blood culture results are pending. Moreover, the high negative predictive value (90.6%) observed in our study reinforces the role of CRP in excluding sepsis when levels are within normal limits (3).

CRP is a well-established acute-phase reactant produced by hepatocytes in response to pro-inflammatory cytokines, particularly interleukin-6 (4). It has been extensively studied for its role in early-onset sepsis (EOS), with several studies suggesting that serial measurements of CRP improve diagnostic precision and assist in determining the duration of antibiotic therapy (5,6). In our study, repeated CRP assessments at 24 and 48 hours provided valuable information on the clinical progression and response to treatment, similar to findings reported by Benitz et al. and Mathai et al. (7,8).

Although blood culture remains the gold standard for diagnosing neonatal sepsis, it has limitations, including delayed results and false negatives due to prior antibiotic administration or inadequate sample volume (9,10). Hence, CRP, due to its rapid kinetics and ease of measurement, serves as a practical and efficient tool in early clinical decision-making (11).

It is noteworthy that elevated CRP levels may not be specific to infection and can also rise due to birth trauma, maternal fever, meconium aspiration, or surgical stress (12,13). Therefore, clinical correlation and consideration of other inflammatory markers such as procalcitonin or interleukins may enhance diagnostic accuracy (14).

Several studies have compared CRP with other biomarkers and found that while CRP alone has limited sensitivity in the very early stages, its combined use with other markers or in serial assessments significantly improves reliability (15).

C-reactive protein is a valuable and accessible biomarker for the early diagnosis of neonatal sepsis. Its high sensitivity and negative predictive value make it especially useful in ruling out infection when used alongside clinical assessment and blood culture. Serial CRP measurements further enhance diagnostic accuracy and assist in monitoring treatment response.

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