Neonatal sepsis is defined as a clinical syndrome of systemic illness accompanied by bacteremia occurring within the first 28 days of life, and it continues to be one of the most significant contributors to neonatal morbidity and mortality worldwide¹. The World Health Organization has estimated that neonatal infections account for a substantial proportion of the nearly four million neonatal deaths that occur globally each year, with the burden disproportionately concentrated in low- and middle-income countries². Despite considerable advances in neonatal intensive care, including improved ventilatory support, antimicrobial therapy, and aseptic protocols, sepsis remains a leading cause of admission to and mortality within neonatal intensive care units (NICUs)³.

Neonatal sepsis is conventionally classified into early-onset sepsis (EOS), occurring within the first 72 hours of life and typically resulting from vertical transmission of organisms from the maternal genital tract, and late-onset sepsis (LOS), occurring after 72 hours and frequently associated with nosocomial or environmental sources within the NICU setting⁴. Several maternal, obstetric, neonatal, and iatrogenic factors have been implicated in the pathogenesis of both forms of sepsis. Maternal risk factors such as premature rupture of membranes, prolonged labor, chorioamnionitis, maternal fever, foul-smelling liquor, and urinary tract infection during pregnancy have consistently been associated with an increased risk of early-onset sepsis⁵, ⁶. Similarly, neonatal factors including prematurity, low birth weight, low Apgar score, and birth asphyxia compromise the immature and relatively immunocompromised neonatal host defense system, predisposing such infants to invasive infection⁷.

Within the NICU environment, invasive procedures performed for life support—such as mechanical ventilation, umbilical vessel catheterization, peripheral and central venous line insertion, and administration of total parenteral nutrition—breach normal mucocutaneous barriers and serve as important portals of entry for nosocomial pathogens, thereby contributing substantially to late-onset sepsis⁸. Prolonged NICU stay further compounds this risk by increasing cumulative exposure to the hospital environment and colonizing flora⁹. Studies from various neonatal units have reported a wide range of incidence rates of neonatal sepsis, varying between 10% and 50% of NICU admissions depending on the population studied, the diagnostic criteria applied, and the level of neonatal care available¹⁰.

The clinical presentation of neonatal sepsis is often nonspecific and may include respiratory distress, lethargy, poor feeding, temperature instability, and apneic spells, making early clinical diagnosis challenging and necessitating a high index of suspicion supported by laboratory parameters such as total leukocyte count, absolute neutrophil count, C-reactive protein, and blood culture¹¹. Blood culture remains the gold standard for confirmatory diagnosis; however, culture positivity rates in many settings range from only 20% to 40%, owing to prior antibiotic exposure, small sample volumes, and fastidious organisms, which further underscores the clinical importance of identifying risk-based predictors that can prompt earlier empirical treatment¹².

Given the substantial contribution of neonatal sepsis to NICU morbidity, mortality, and prolonged hospital stay, and the largely preventable nature of many of its associated risk factors, identification of population-specific predictors is of considerable clinical and public health relevance¹³. Such evidence can guide obstetric and neonatal care practices, inform infection-control policy within NICUs, and support the rational use of empirical antibiotics¹⁴. Against this background, the present study was undertaken to identify the maternal, neonatal, and NICU-related predictors of neonatal sepsis among neonates admitted to a tertiary care NICU, with the aim of generating locally relevant evidence to strengthen preventive and early-intervention strategies¹⁵.

Study Design and Setting This hospital-based, case–control study was conducted in the Neonatal Intensive Care Unit (NICU) of a tertiary care teaching hospital over a period of one year. The NICU functions as a Level III referral unit, admitting both inborn neonates delivered within the hospital and outborn neonates referred from peripheral centers. Study Population All neonates admitted to the NICU during the study period were screened for eligibility. A total of 300 neonates were enrolled and classified into two groups: Cases comprised 84 neonates who developed clinical sepsis, defined by the presence of at least two clinical signs of sepsis (respiratory distress, lethargy, poor feeding, temperature instability, or apnea) together with at least two abnormal hematological/septic screen parameters, with or without blood culture positivity. Controls comprised 216 neonates admitted to the NICU during the same period for reasons other than sepsis (e.g., prematurity for monitoring, transient tachypnea of the newborn, neonatal jaundice) who did not develop clinical or laboratory evidence of sepsis during their hospital stay. Inclusion and Exclusion Criteria Neonates of either sex, admitted within 28 days of life, whose parents/guardians provided informed consent, were included. Neonates with major congenital malformations incompatible with survival, those with insufficient or incomplete clinical records, and neonates whose parents declined consent were excluded from the study. Data Collection A pre-tested, structured proforma was used to collect data through review of maternal antenatal records, labor and delivery notes, and neonatal case records, supplemented by direct clinical examination of the neonate at admission and during the hospital stay. Variables recorded included: maternal age, parity, antenatal care status, mode of delivery, duration of rupture of membranes, presence of maternal fever, foul-smelling liquor, and urinary tract infection; neonatal gestational age, birth weight, sex, Apgar score at 5 minutes, and place of birth (inborn/outborn); and NICU-related variables including need for mechanical ventilation, umbilical catheterization, total parenteral nutrition, duration of NICU stay, and number of invasive procedures performed. Laboratory Investigations All neonates suspected of sepsis underwent a sepsis screen comprising total leukocyte count, absolute neutrophil count, immature-to-total neutrophil ratio, C-reactive protein, micro-erythrocyte sedimentation rate, and blood culture and sensitivity, performed using standard automated hematology analyzers and the BACTEC/conventional culture method available at the institutional microbiology laboratory. Operational Definitions Low birth weight was defined as birth weight less than 2500 g; prematurity as gestational age less than 37 completed weeks; and premature rupture of membranes as rupture of membranes occurring more than 18 hours before delivery, in accordance with standard accepted definitions used in the relevant period. Statistical Analysis Data were entered into Microsoft Excel and analyzed using SPSS statistical software (version 20.0). Categorical variables were expressed as frequencies and percentages and compared between cases and controls using the chi-square test or Fisher's exact test, as appropriate. Variables found to be significant on univariate analysis (p<0.05) were entered into a multivariate logistic regression model to identify independent predictors of neonatal sepsis, and results were expressed as adjusted odds ratios (AOR) with 95% confidence intervals (CI). A p-value of less than 0.05 was considered statistically significant throughout the analysis. Ethical Considerations The study protocol was approved by the Institutional Ethics Committee, and written informed consent was obtained from the parents/guardians of all enrolled neonates prior to inclusion in the study. Confidentiality of patient information was maintained throughout the study.

Of the 300 neonates admitted to the NICU during the study period, 84 (28.0%) developed clinical sepsis (cases) and 216 (72.0%) did not (controls). The demographic, maternal/obstetric, NICU-procedural, multivariate, and clinical outcome data are presented in Tables 1 through 5 below.

Table 1: Comparison of Neonatal Demographic and Birth Characteristics between Sepsis and Non-Sepsis Groups

Neonates with sepsis had a significantly higher proportion of prematurity (72.6% vs. 38.9%, p<0.001), low birth weight (67.9% vs. 36.6%, p<0.001), outborn status (46.4% vs. 24.1%, p<0.001), and low Apgar score at 5 minutes (33.3% vs. 14.4%, p<0.001) compared with the non-sepsis group. Sex distribution and mode of delivery did not differ significantly between the two groups (p>0.05).

Table 2: Comparison of Maternal and Obstetric Risk Factors between Sepsis and Non-Sepsis Groups

Maternal and obstetric risk factors were significantly more frequent among neonates who developed sepsis. Premature rupture of membranes lasting more than 18 hours was present in 40.5% of cases compared with 13.0% of controls (p<0.001). Maternal fever during labor (25.0% vs. 6.5%, p<0.001), foul-smelling liquor (21.4% vs. 4.2%, p<0.001), maternal urinary tract infection (19.0% vs. 8.8%, p=0.012), multiple per-vaginal examinations (27.4% vs. 11.1%, p=0.001), and lack of antenatal care (36.9% vs. 21.3%, p=0.005) were all significantly associated with neonatal sepsis.

Table 3: Comparison of NICU-Related Procedural and Iatrogenic Factors between Sepsis and Non-Sepsis Groups

Invasive NICU procedures were strongly associated with the development of sepsis. Neonates who required mechanical ventilation (53.6% vs. 17.6%, p<0.001), umbilical catheterization (46.4% vs. 15.3%, p<0.001), or total parenteral nutrition (39.3% vs. 13.4%, p<0.001) had significantly higher rates of sepsis. NICU stay exceeding 7 days (69.0% vs. 28.2%, p<0.001) and exposure to multiple (>2) invasive procedures (48.8% vs. 16.2%, p<0.001) were also significantly more common among septic neonates.

Table 4: Independent Predictors of Neonatal Sepsis on Multivariate Logistic Regression Analysis

On multivariate logistic regression analysis, six variables emerged as independent predictors of neonatal sepsis after adjusting for confounding factors: low birth weight (AOR 3.21, 95% CI 1.74–5.92, p<0.001) was the strongest predictor, followed by premature rupture of membranes >18 hours (AOR 2.87, 95% CI 1.49–5.53, p=0.002), mechanical ventilation (AOR 2.64, 95% CI 1.41–4.95, p=0.002), umbilical catheterization (AOR 2.31, 95% CI 1.22–4.36, p=0.010), maternal fever during labor (AOR 2.18, 95% CI 1.05–4.52, p=0.036), and lack of antenatal care (AOR 1.96, 95% CI 1.08–3.55, p=0.027).

Table 5: Clinical Presentation and Outcome among Neonates with Sepsis (n=84)

Respiratory distress was the most common clinical manifestation among septic neonates (61.9%), followed by poor feeding/feed intolerance (56.0%), lethargy/hypotonia (46.4%), temperature instability (41.7%), and apnea/bradycardia spells (25.0%). Blood culture positivity was documented in 34.5% of cases. The overall case fatality rate among neonates with sepsis was 16.7% (14 of 84 cases).

The present study found an overall incidence of neonatal sepsis of 28% among NICU admissions, a figure that falls within the wide range of 10% to 50% reported across various neonatal units globally, reflecting differences in case definitions, levels of neonatal care, and the proportion of high-risk and referred neonates admitted to individual units10. Low birth weight emerged as the strongest independent predictor of neonatal sepsis in this study (AOR 3.21), a finding consistent with multiple previous studies that have identified prematurity and low birth weight as key determinants of neonatal infection, attributable to the relative immaturity of cellular and humoral immune mechanisms, reduced transplacental transfer of maternal immunoglobulins, and increased need for invasive supportive care in this vulnerable population7, 16. Premature rupture of membranes for more than 18 hours was the second strongest predictor identified, corroborating earlier reports that have consistently linked prolonged rupture of membranes with ascending bacterial colonization of the amniotic cavity and subsequent early-onset neonatal sepsis5. Similarly, maternal fever during labor, considered a clinical marker of chorioamnionitis, was significantly associated with neonatal sepsis in the present study, a relationship that has been well documented in earlier obstetric and neonatal literature, given that intrauterine infection exposes the fetus directly to maternal inflammatory mediators and potential pathogens before birth6, 17. The strong association observed between invasive NICU procedures—particularly mechanical ventilation and umbilical catheterization—and late-onset sepsis in this study aligns with previous observations that indwelling devices compromise the integrity of natural mucocutaneous barriers, providing a direct conduit for nosocomial organisms, and that the risk of infection increases proportionately with both the number and the duration of invasive interventions8, 9. This underscores the importance of strict aseptic technique, judicious and time-limited use of invasive devices, and adherence to evidence-based bundles for the prevention of catheter- and ventilator-associated infections within the NICU setting18. Lack of antenatal care was also identified as an independent predictor in this study, reflecting findings from earlier community- and hospital-based studies that have shown that inadequate antenatal screening and management of maternal infections, anemia, and other risk conditions translate into a higher burden of adverse neonatal outcomes, including sepsis19. This finding has important public health implications, suggesting that strengthening antenatal care coverage and quality, including screening and treatment of genitourinary infections during pregnancy, may serve as an effective upstream strategy for reducing neonatal sepsis incidence13. The clinical presentation observed in this study—respiratory distress, poor feeding, lethargy, and temperature instability being the predominant features—is consistent with the well-recognized nonspecific nature of neonatal sepsis symptomatology described in earlier literature, reinforcing the need for a high index of clinical suspicion supported by septic screening parameters, given that reliance on clinical features alone may delay diagnosis and treatment11. The blood culture positivity rate of 34.5% observed in this study is comparable to rates reported in other studies from similar settings and may be attributable to factors such as prior maternal or neonatal antibiotic exposure, small sample volume relative to adult standards, and the fastidious growth requirements of certain causative organisms12. The case fatality rate of 16.7% observed among septic neonates in this study is in keeping with mortality rates reported from comparable tertiary neonatal units in resource-limited settings, and highlights the continued contribution of sepsis to preventable neonatal mortality despite the availability of modern intensive care support3, 14. This study has certain limitations that warrant consideration, including its single-center design, which may limit the generalizability of findings to other settings with differing patient populations and resource availability; reliance on clinical sepsis criteria for a majority of cases owing to the relatively low blood culture positivity rate; and the retrospective ascertainment of certain maternal variables from hospital records, which may be subject to documentation bias. Despite these limitations, the consistency of the present findings with the existing body of literature lends credibility to the identified predictors and supports their relevance for clinical practice in similar tertiary care settings.

This study identifies low birth weight, premature rupture of membranes exceeding 18 hours, mechanical ventilation, umbilical catheterization, maternal fever during labor, and lack of antenatal care as significant independent predictors of neonatal sepsis among NICU admissions. The majority of these risk factors are potentially preventable or modifiable through strengthened antenatal care services, prompt and judicious obstetric intervention in cases of prolonged rupture of membranes or intrapartum fever, and strict adherence to aseptic protocols during invasive NICU procedures. Early identification of neonates with these risk factors, combined with a high index of clinical suspicion and timely initiation of empirical antimicrobial therapy guided by sepsis screening, may help reduce the substantial morbidity and mortality attributable to neonatal sepsis. These findings support the need for targeted antenatal screening programs, NICU infection-control bundles, and continued surveillance of sepsis predictors to inform unit-specific preventive strategies.

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