Unveiling neonatal risk factors, clinical profile and early diagnostic markers of neonatal sepsis in a tertiary care hospital from South India: a cross-sectional study

INTRODUCTION

Neonatal sepsis is a severe systemic infection occurring in the first month of life, primarily affecting infants within the first 72 hours (early-onset sepsis) or later in the neonatal period (late-onset sepsis). It represents a significant global health concern, particularly in developing countries where access to adequate healthcare resources may be limited. The condition can lead to various complications, including septic shock, multi-organ dysfunction, and even death, making prompt recognition and management imperative.¹ The aetiology of neonatal sepsis is diverse, encompassing bacterial, viral, fungal, and occasionally parasitic pathogens. The most common causative agents vary depending on factors such as geographical location, maternal health status, mode of delivery, and the presence of risk factors such as prematurity, low birth weight, prolonged rupture of membranes (PROM), and maternal infections. In resource-limited settings, vertical transmission of pathogens from the mother to the infant during childbirth or through breastfeeding may significantly contribute to the burden of neonatal sepsis.^2-4 The clinical presentation of neonatal sepsis is often nonspecific, posing challenges for timely diagnosis and intervention.

Neonates may manifest symptoms such as lethargy, poor feeding, temperature instability, respiratory distress, tachycardia, and tachypnoea. However, these clinical features can overlap with other neonatal conditions, necessitating a high index of suspicion and the judicious use of diagnostic tools.⁵ Laboratory investigations play a crucial role in the diagnosis of neonatal sepsis, aiming to identify causative pathogens and assess markers of inflammation and organ dysfunction. Blood cultures remain the gold standard for confirming the presence of bloodstream infections, although they may have limitations in sensitivity and turnaround time. Additionally, biomarkers such as CRP, procalcitonin (PCT), and interleukin-6 (IL-6) are commonly utilized to aid in the diagnosis and prognostication of neonatal sepsis.⁶ Effective management of neonatal sepsis hinges on a multifaceted approach that includes empirical antibiotic therapy, supportive care, and targeted interventions based on the identified pathogens and antimicrobial susceptibility patterns.⁷

However, the escalating challenge of antimicrobial resistance underscores the importance of judicious antibiotic use and ongoing surveillance efforts to guide therapeutic decisions and preserve the efficacy of available treatment options. Addressing the epidemiology, risk factors, diagnostic challenges, and management strategies specific to the local context of Vijayapura, Karnataka, South India, is essential for mitigating the burden of neonatal sepsis and improving outcomes for vulnerable infants in the region. Neonatal sepsis remains a significant cause of morbidity and mortality worldwide, particularly in resource-limited settings like Vijayapura. Despite advances in medical care, neonates are vulnerable to infections due to their immature immune systems, predisposing them to severe complications. Understanding the complex interplay of maternal and neonatal risk factors in the causation and outcome of neonatal sepsis is crucial for devising effective preventive and management strategies. Vijayapura, located in South India, is home to a diverse population with unique socio-economic and healthcare challenges. As a tertiary care hospital serving this region, it plays a pivotal role in managing neonatal sepsis cases. However, the epidemiological profile of neonatal sepsis, including the prevalence of risk factors and diagnostic challenges, remains inadequately explored within this context. This cross-sectional study aims to fill this knowledge gap by comprehensively assessing the neonatal risk factors associated with neonatal sepsis in Vijayapura. By identifying these factors, we can better understand the dynamics of sepsis transmission and progression within the local population. Furthermore, this study seeks to evaluate the utility of various laboratory investigations for the early diagnosis of neonatal sepsis, with the goal of improving clinical outcomes through timely intervention. Through this research endeavor, we aspire to contribute valuable insights that inform evidence-based strategies for the prevention, early detection, and management of neonatal sepsis in Vijayapura, and beyond. By addressing the multifaceted aspects of this critical health issue, we aim to enhance neonatal healthcare delivery and reduce the burden of neonatal sepsis on both individuals and the healthcare system. Objectives of the Study was to outline the clinical presentation of community-acquired sepsis in neonates among the study population also to determine neonatal risk factors contributing to the development of neonatal sepsis in the study population, including prematurity, low birth weight (LBW), duration of rupture of membranes and exposure to invasive procedures and to evaluate the correlation of markers of sepsis [C-reactive protein (CRP), white blood cell (WBC), immature to total (IT) ratio and presence of toxic granules in histopathological examination] for the early diagnosis of neonatal sepsis in the study cohort.

METHODS

Place of study

The study was conducted at Al Ameen Medical College, located in Vijayapura, Karnataka, India. This tertiary care hospital serves a diverse population and provides comprehensive healthcare services, including neonatal care.

Study design

This study utilized a cross-sectional design to assess neonatal risk factors associated with neonatal sepsis and to evaluate the performance of laboratory investigations for its early diagnosis.

Sample size

A total of 120 neonates were included in the study cohort. This sample size was determined based on feasibility considerations and the available resources during the study period.

Study period

The study was conducted over a period of 12 months, from December 2022 to November 2023. This time frame was chosen to capture a representative sample of neonates presenting with sepsis within the specified duration.

Inclusion criteria

Neonates admitted to the neonatal intensive care unit (NICU) at Al Ameen Medical College with suspected or confirmed neonatal sepsis. Neonates aged ≤28 days at the time of admission. Written informed consent obtained from parents or legal guardians.

Exclusion criteria

Neonates with congenital anomalies or known immunodeficiency disorders. The investigators themselves have taken interviews of all study subjects. Neonates transferred from other healthcare facilities with a diagnosis of neonatal sepsis.

Data collection

Data collection was performed by trained healthcare professionals using standardized data collection forms. Information was obtained from neonatal medical charts, and laboratory reports. Neonatal variables such as gestational age, birth weight, mode of delivery, clinical presentation, and exposure to invasive procedures were recorded.

Laboratory Investigations: Blood samples were collected from each neonate for analysis, including CRP, WBC counts, IT ratio, and toxic granules examination in histopathological samples were performed. The performance of these laboratory investigations in the early diagnosis of neonatal sepsis was assessed based on established diagnostic criteria and guidelines.

Data analysis

Descriptive statistics were used to summarize demographic characteristics and clinical variables of the study participants. Categorical variables were presented as frequencies and percentages, while continuous variables were summarized using means and standard deviations or medians and interquartile ranges, as appropriate. Associations between neonatal factors and the occurrence of neonatal sepsis were analyzed using appropriate statistical tests, including chi-square tests or Fisher's exact tests for categorical variables and t-tests or Mann-Whitney U tests for continuous variables. Statistical significance was set at p<0.05. the statistical analysis was done using R software version 4.3.2.

Ethical considerations

The study protocol was approved by the Institutional Ethics Committee of Al Ameen Medical College, Vijayapura. Informed consent was obtained from the parents or legal guardians of all participating neonates before enrollment in the study. Confidentiality of patient data was strictly maintained throughout the study period.

RESULTS

Figure 1 presents the distribution of neonatal sepsis cases among different categories within the study cohort. Clinical sepsis was observed in 43% of cases, followed by probable sepsis in 36% of cases, and proven sepsis in 21% of cases. These categories provide insights into the severity and diagnostic certainty of neonatal sepsis cases encountered in the study population.

Table 1 displays the neonatal risk factors for proven sepsis, probable sepsis, and clinical sepsis, with mean values and standard deviations (±1 SD) provided for each variable. It shows that neonates with proven sepsis had a slightly higher mean age, gestational age, and weight on admission compared to those with probable and clinical sepsis. Additionally, the duration of stay was longer for neonates with proven sepsis compared to those with probable and clinical sepsis, indicating potentially more severe cases requiring extended hospitalization.

Figure 2 summarizes the clinical symptoms and signs observed in patients with different categories of sepsis: Proven (n=25), Probable (n=43), and Clinical (n=52), with a total sample size of 120. The most prevalent symptom across all categories is tachypnea, observed in 98.3% of the total patients, with higher proportions in the probable (35.6%) and clinical (43.2%) groups compared to the Proven group (21.2%). Lethargy, refusal to suck, and fever are equally frequent, affecting 65.8% of the total patients.

Chest retractions are more common in the probable group (48.8%) compared to the proven (34.9%) and clinical (16.3%) groups, making up 35.8% of the total. Poor weight gain, incessant crying, weak crying, and abdominal distension are other notable symptoms, with incidences ranging from 19.2% to 28.3%. Less frequent signs include grunting (15.8%), seizures (10.8%), shock (10.0%), bulging fontanelle (4.2%), hypothermia (4.2%), and apnea (2.5%). Table highlights the varied presentation of sepsis symptoms, showing a trend of higher symptom prevalence in the probable and clinical groups compared to the proven group. The analysis of laboratory investigations revealed notable associations with neonatal sepsis across different parameters. WBC counts showed varying distributions among different sepsis categories, with 55.6% of neonates with clinical sepsis having WBC counts <5000, 50.0% of neonates with proven sepsis having WBC counts between 5000-15000, while 57.1% of neonates with probable sepsis had WBC counts greater than 15000, found to be significantly associated with cases of sepsis (p = <0.001). CRP levels above 0.6 mg/dL were significantly associated with both proven and probable sepsis cases (p = <0.001), indicating its potential as a diagnostic marker for neonatal sepsis. Additionally, an IT ratio above 0.2 showed a significant association with neonates diagnosed with sepsis (p = <0.001). Presence of toxic granules in histopathological examination was also found to be significantly associated with sepsis cases (p = <0.001), particularly in neonates with proven sepsis. These findings highlight the importance of various laboratory investigations in the early diagnosis of neonatal sepsis, with CRP levels, IT ratio, and toxic granules demonstrating significant diagnostic value.

*p value<0.05 significant, Chi square test of significance

DISCUSSION

Neonatal sepsis remains a significant cause of morbidity and mortality in newborns, particularly in resource-limited settings such as ours i n Vijayapura, Karnataka. In this study, we aimed to outline the clinical presentation of community-acquired sepsis, to identify neonatal risk factors associated with the occurrence and outcome of neonatal sepsis and to evaluate the correlation of sepsis markers for its early diagnosis. Furthermore, our study highlighted several neonatal risk factors that play a crucial role in the development of sepsis. Prematurity, LBW and PROM were identified as significant risk factors for neonatal sepsis, consistent with previous literature. These findings emphasize the importance of close monitoring and timely intervention in neonates with these risk factors to prevent the onset of sepsis and its associated complications.

The clinical presentation of community-acquired sepsis in neonates admitted to our hospital's extramural ward reveals a diverse range of symptoms. Tachypnoea was the most prevalent symptom, affecting 98.3% of the patients, with higher proportions in the probable (35.6%) and clinical (43.2%) groups compared to the Proven group (21.2%). Additionally, lethargy, refusal to suck, and fever were equally common, each affecting 65.8% of the total patients. Chest retractions were notably more frequent in the Probable group (48.8%) compared to the Proven (34.9%) and Clinical (16.3%) groups. Other significant symptoms included poor weight gain (28.3%), incessant crying (23.3%), weak crying (19.2%), and abdominal distension (19.2%). Less common signs were grunting (15.8%), seizures (10.8%), shock (10.0%), bulging fontanelle (4.2%), hypothermia (4.2%), and apnea (2.5%). These findings are consistent with those reported in a study from Ethiopia by Melkamu Berhane et.al. Which also highlighted tachypnea and lethargy were predominant symptoms in neonatal sepsis. The varied presentation emphasizes the complexity of diagnosing and managing sepsis in neonates, necessitating vigilant monitoring and a comprehensive clinical approach. Laboratory investigations play a vital role in the early diagnosis of neonatal sepsis, allowing for timely initiation of appropriate treatment. Our study evaluated the markers of sepsis. Elevated CRP levels (>0.6 mg/dl) demonstrated a significant association with proven and probable sepsis cases, highlighting its utility as a diagnostic marker for neonatal sepsis. Similarly, an WBC counts, IT ratio above 0.2 and the presence of toxic granules were found to be significantly associated with sepsis cases, further supporting their diagnostic value in identifying neonates at risk of sepsis. Our findings align with previous studies that have identified neonatal risk factors as significant contributors to the occurrence and outcome of neonatal sepsis. For instance, a study found that PROM exceeding 18 hours was associated with an increased risk of neonatal sepsis, consistent with our findings.⁸ Similarly, a systematic review from India. reported that prematurity and LBW were important risk factors for the development of neonatal sepsis, corroborating our observations. These consistent findings across multiple studies underscore the importance of neonatal risk factor assessment in identifying neonates at risk of sepsis and implementing targeted interventions to prevent its occurrence.⁹ Furthermore, our study contributes to the growing body of evidence supporting the diagnostic value of laboratory investigations in the early diagnosis of neonatal sepsis. A meta-analysis by Lee et al (2020) demonstrated that elevated CRP levels were associated with an increased risk of neonatal sepsis, consistent with our findings.¹⁰ Additionally, several studies have reported the utility of IT ratio and toxic granule examination as valuable diagnostic markers for neonatal sepsis (Gupta et al 2017 Patel et al 2018). Our study adds to this evidence base by reaffirming the diagnostic significance of these laboratory markers in the context of neonatal sepsis in a resource-limited setting like Vijayapura, Karnataka, South India.

Limitations

Despite these findings, our study has several limitations. The sample size was relatively small, limiting the generalizability of our results. Additionally, our study was conducted in a single tertiary care hospital, which may not be representative of the broader population. Future studies with larger sample sizes and multicenter designs are warranted to validate our findings and further elucidate the role of neonatal risk factors in the development of neonatal sepsis. Overall, our study highlights the importance of neonatal risk factor assessment and laboratory investigations in the early diagnosis and management of neonatal sepsis. Early identification and intervention in high-risk neonates, coupled with appropriate antimicrobial therapy guided by laboratory markers, are essential for improving outcomes and reducing the burden of neonatal sepsis in resource-limited settings.

CONCLUSION

Neonatal sepsis remains a significant healthcare challenge, particularly in resource-limited settings like Vijayapura, Karnataka, South India. Through our study, we identified common clinical presentations and several neonatal risk factors associated with the occurrence and outcome of neonatal sepsis. Neonatal risk factors including prematurity, LBW, and prolonged duration of rupture of membranes were also identified as important contributors to the development of sepsis. Furthermore, laboratory investigations such as WBC counts, CRP levels, IT ratio, and presence of toxic granules demonstrated significant diagnostic value in the early identification of neonatal sepsis.

Recommendations

Based on our findings, we recommend the following strategies for the prevention and management of neonatal sepsis: Implementing measures to improve neonatal care, particularly in preterm and low birth weight infants, is essential for preventing neonatal sepsis. This includes promoting breastfeeding, minimizing invasive procedures, and ensuring timely administration of appropriate antibiotics when indicated. Incorporating routine laboratory investigations, including CRP levels, IT ratio, and toxic granule examination, into neonatal care protocols can aid in the early diagnosis and management of neonatal sepsis. Healthcare providers should be trained to recognize and interpret these laboratory markers to facilitate timely intervention. Conducting multicentre studies with larger sample sizes to validate our findings and further elucidate the role of neonatal risk factors in the development of neonatal sepsis. Collaborative efforts involving multiple healthcare facilities can provide valuable insights into the epidemiology and management of neonatal sepsis on a broader scale. By implementing these recommendations, we can improve the early detection and management of neonatal sepsis, ultimately reducing its burden on neonatal health outcomes in resource-limited settings.

ACKNOWLEDGEMENTS

Authors would like to thank all the teaching and non-teaching staff and postgraduate residents of department of paediatrics, Al Ameen Medical College, Vijayapura for their cooperation and support throughout the period of study.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

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