Sepsis is the sixth and eighth common causes of death in newborns and infants, respectively (1). Neonatal sepsis can lead to life-threatening organ dysfunction (2). In countries with the highest neonatal mortalities, infection contributes to approximately half of neonatal deaths, most of which occur shortly after birth (3). The 2016-2017 Global Burden of Disease study estimated that there are about 1,300,000 annual cases of neonatal sepsis worldwide, leading to an alarming figure of about 203,000 deaths solely due to sepsis (4,5). In addition, neonatal sepsis is a leading cause of neonatal mortality in low- or middle-income countries (LMICs), comprising 4.8% of global neonatal deaths. This highlights the alarming gap in neonatal health outcomes worldwide, with many infants suffering due to inadequate healthcare and infection control practices (6,7). Although neonates are vulnerable to sepsis with most deaths occurring in LMICs, data on incidence are often unavailable or unreliable in the geographic locations (8).

Early-onset neonatal sepsis, which occurs within 72 hours of birth, is typically due to the pathogens acquired during the peripartum period (2,9,10). The condition is commonly caused by gram-positive bacteria, such as Streptococcus agalactiae, Escherichia coli, Staphylococcus aureus, Enterococcus spp., and Streptococcus pneumoniae (11). Late-onset neonatal sepsis, which occurs after 72 hours in neonatal intensive care units (NICUs) or after 7 days in full-term neonates, is generally caused by hospital-acquired gram-negative bacteria, such as E. coli, coagulase-negative staphylococci, Klebsiella pneumoniae, and Acinetobacter spp. (3,11-13).

Despite the high burden of neonatal sepsis in emergency departments (EDs), most existing studies have focused on inpatient settings or re-hospitalization rates as signs of morbidity following early neonatal discharge (14,15). There is a gap in signs of neonatal sepsis within EDs. This lack of information restricts our understanding of how neonates with sepsis present in EDs where diagnostic tools are most effective for early intervention to reduce the morbidity and mortality.

The objective of our study was to identify early signs of neonatal sepsis in terms of clinical features, inflammatory biomarkers, multiorgan dysfunction, and birth history to facilitate early recognition and intervention in an ED. Such signs would be highly impactful in LMICs, where the mortality rate is high, and diagnosis is primarily based on clinical features or routine blood works due to the unavailability or unaffordability of resources for neonatal intensive care.

A total of 368 neonates were included in the study, comprising 226 males (61.4%) and 142 females (38.6%; Table 1). Approximately half of the patients were born term or post-term or via cesarean section. The most common presenting symptom was fever (124 [33.7%]), followed by jaundice (77 [20.9%]), vomiting or loose stool (72 [19.6%]), and dyspnea (71 [19.3%]; Figure).

We found that the NJSS or septic shock group had a higher proportion of neonates aged 7 days or younger (P < 0.001; Table 2). At triage, the septic shock group showed the lowest median systolic blood pressure and the highest concentration of CRP. NICU hospitalization was higher in the sepsis and septic shock groups than in the other 2 groups. In-hospital mortality was highest in the septic shock group.

Neonates progressing to sepsis exhibited significant declines in hemoglobin concentration and in platelet count, as well as a rise in blood urea nitrogen concentration (Table 3). In terms of the therapeutic procedures, the septic shock group showed the highest percentages of oxygen therapy, intubation, and transfusion, whereas the NJSS group exhibited the highest percentage of phototherapy. Regarding the antibiotic therapy, the NJSS or suspected sepsis group tended to receive cefotaxime and amikacin more frequently than the other groups. An inverse pattern was observed in the use of vancomycin and meropenem.

BCs were positive in 56 neonates (15.2%), of whom 17 (4.6%) had true positive cultures, most commonly in the septic shock group (27.3%; Table 3). The most commonly isolated bacteria were S. aureus, followed by K. pneumoniae, S. pyogenes, and B. cepacia (Appendix, https://doi.org/10.22470/pemj.2025.01319).

To the authors’ knowledge, this study is the first to explore neonatal sepsis in EDs in LMICs. Karachi is a large and densely populated city with a wide range of healthcare facilities. In resource-limited settings, such as small clinics or secondary hospitals, it may be difficult to meet standardized guidelines of infection control practices or sterilization protocols. As a result, neonates in such an environment might be at higher risk of developing early-onset sepsis due to perinatal exposure to pathogens. This variability in care likely influences some of the trends that we observed in our study.

Our findings noted that most of the patients were 7 days or younger, consistent with the existing literature. Neonates at this age are more susceptible to neonatal sepsis, possibly due to perinatal exposure, unsterilized instrumentation, or immature immunity, relative to older neonates (2,15). AlGhamdi et al. (16) found that neonates frequently present to EDs, with the majority being under 2 weeks of age. In LMICs, most infections during the first week of life were related to environmental causes, such as unhygienic delivery practices (17). This is due to an immature immunity in the neonates, increasing susceptibility to infection (18).

We found that approximately half of the neonates with sepsis underwent cesarean sections. A possible association between the sepsis and cesarean delivery could be either due to unsterilized instruments or no exposure to vaginal flora, predisposing the neonates to pathogenic bacterial infection (19). In addition, the prolonged hospital stays at birth, which is associated with cesarean section, could also contribute development of sepsis (20).

In addition, gestational age at birth was also a risk factor. Our findings also showed that the preterm-born neonates had a higher susceptibility to sepsis, similar to what has been found in previous studies (21). A Ghanaian study found that delayed or insufficient breastfeeding could also lead to neonatal infections (22). This possible association was not analyzed in our study.

Our findings of high CRP concentration and thrombocytopenia were indicative of sepsis, consistent with an Indian study on the platelet count indices in neonatal sepsis (23). A high creatinine indicates deteriorating renal function and signaling progression towards sepsis (24). While BC remains the gold standard, we found CRP to be particularly useful for diagnosis. However, given its low sensitivity, the biomarker should be combined with other biomarkers, such as interleukins or cluster of differentiation 64, for diagnostic performance. For diagnostic purposes, Delanghe and Speeckaert (25) developed the ApoSAA score and found it to be highly sensitive for identifying neonatal sepsis. However, there is still a gap in the current literature on infection signs for neonatal sepsis in EDs, as most research has focused on inpatient care.

We found that contamination was a common issue in neonatal BC collection. Hashemizadeh et al. (26) found that contaminants accounted for 8.5% of samples for neonatal BCs. Contamination could be attributed to differences in sampling techniques, as shown by the fact that 26 Canadian NICUs where BC was performed for diagnosis of neonatal sepsis showed a significant practice variation in such techniques (27). Therefore, the best approach would be standardization of sampling techniques for BC, as well as using true positivity for diagnosis. The true positivity would help optimize antibiotic therapy. A study done at a Moroccan tertiary hospital found that true bacteremia cases showed a significantly different clinical course, based on whether appropriate antibiotics were given (28).

Limitations of this study include the retrospective study design, along with brief medical histories recorded during stay in the ED, limiting our ability to gather data on maternal history, antenatal history, reasons for caesarian sections, or Apgar scores. Furthermore, as a single-center study, it may not fully represent the diversity of patient populations or clinical practices across LMICs. This limitation identifies the need for multicenter research across EDs in LMICs to better understand the broader implications and trends in this topic.

To summarize, our study findings based on clinical and laboratory variables may help diagnose neonatal sepsis early on and assess its deterioration. Neonates in the first week of life, particularly those born preterm, were at a higher risk, reflected in triage vital signs and inflammatory biomarkers. With respect to deterioration, progression to septic shock was associated with worsening values of hemoglobin, platelet count, CRP, and blood urea nitrogen. BC has been proven to be a low-yield diagnostic test due to false positivity. In this context, we found that true positive BC contributes to more accurate diagnosis and more appropriate empirical antibiotic therapy. With respect to other therapeutic plans for neonatal sepsis in EDs, neonates diagnosed under the neonatal sepsis umbrella required ventilation, phototherapy, or transfusions. Inability to diagnose can lead to the use of inappropriate antibiotics or clinical deterioration, worsening morbidity and mortality, and a burden on resource-limited EDs in LMICs. Therefore, more research is needed to identify an affordable biomarker that can potentially help diagnose neonatal sepsis early on. We believe that this study will help reduce morbidity and mortality by contributing to earlier diagnosis and treatment in LMICs.