Fetal inflammatory response syndrome predicts early-onset sepsis and cystic periventricular leukomalacia in preterm neonates: A retrospective study.

BACKGROUND: Fetal inflammatory response syndrome (FIRS), the fetal equivalent of chorioamnionitis, is associated with poorer neonatal outcomes. FIRS is diagnosed through placental histology, namely by the identification of funisitis (inflammation of the umbilical cord) and chorionic vasculitis (inflammation of fetal vessels within the chorionic plate). The aim of this study was to identify and evaluate associations between FIRS and neonatal outcomes in preterm neonates. METHODS: We performed a retrospective cohort study at a level III neonatal intensive care unit (NICU), from January 1st 2008 to December 31st 2022, involving all inborn neonates with a gestational age below 30 weeks. We compared preterm neonates based on whether their placental histology described funisitis with chorionic vasculitis (FCV) or not. RESULTS: The study included 113 preterms, 27 (23.9%) of those had FCV and 86 (76.1%) did not. After adjusting to gestational age, prolonged rupture of membranes and preeclampsia, FCV was independently associated with the development of early-onset sepsis (OR = 7.3, p = 0.021) and cystic periventricular leukomalacia (OR = 4.6, p = 0.004). CONCLUSION: The authors identified an association between FIRS and the development of early-onset sepsis and cystic periventricular leukomalacia, highlighting the importance of early detection and management of this condition in order to improve long-term neonatal outcomes.

Epidemiology and Outcomes of Neonatal Sepsis: Experience from a Tertiary Australian NICU.

INTRODUCTION: Neonatal sepsis is associated with significant mortality and morbidity. Low-middle-income countries are disproportionately affected, but late-onset sepsis (LOS) still occurs in up to 20% of infants <28 weeks in high-income countries. Understanding site-specific data is vital to guide management. METHODS: A retrospective cohort study was conducted at King Edward Memorial Hospital (KEMH), Perth. Infants admitted between January 2012 and June 2022 were included. Data were extracted from routine electronic databases. Incidence and aetiology of sepsis were determined and the association of sepsis with neonatal outcomes analysed. RESULTS: During the study period, 23,395 newborns were admitted with a median gestation of 37 weeks and birth weight of 2,800 g. There were 370 sepsis episodes in 350 infants; 102 were early-onset sepsis (EOS) (1.6 per 1,000 live births), predominantly Streptococcus agalactiae (35, 34.3%) and Escherichia coli (27, 26.5%); 268 were LOS (0.9 per 1,000 inpatient days), predominantly coagulase-negative staphylococci (CONS) (156, 57.6%) and E. coli (30, 11.1%). The incidence of LOS declined from 2012 to 2022 (p = 0.002). Infants with EOS had increased brain injury (25.7% vs. 4.1%; p = 0.002) and mortality (18.8% vs. 1.6%; p < 0.001). Those with LOS had increased hospital stay (median 95 vs. 15 days; p < 0.001), mortality (15.3% vs. 1.6%; p = 0.018), necrotising enterocolitis (NEC) (7.4% vs. 0.5%; p < 0.001), and chronic lung disease (CLD) (58.1% vs. 5.9%; p = 0.005). Infants <28 weeks with sepsis were at increased risk of neurodevelopmental impairment compared to those without infection (43.2% vs. 30.9%, p = 0.027). CONCLUSIONS: While we observed a reduction in LOS incidence, sepsis remains associated with higher mortality, and in survivors with longer hospital stay and increased risk of brain injury, NEC, CLD, and neurodevelopmental impairment.

Incidence of Antibiotic Exposure for Suspected and Proven Neonatal Early-Onset Sepsis between 2019 and 2021: A Retrospective, Multicentre Study.

Management of suspected early-onset sepsis (EOS) is undergoing continuous evolution aiming to limit antibiotic overtreatment, yet current data on the level of overtreatment are only available for a select number of countries. This study aimed to determine antibiotic initiation and continuation rates for suspected EOS, along with the incidence of culture-proven EOS in The Netherlands. In this retrospective study from 2019 to 2021, data were collected from 15 Dutch hospitals, comprising 13 regional hospitals equipped with Level I-II facilities and 2 academic hospitals equipped with Level IV facilities. Data included birth rates, number of neonates started on antibiotics for suspected EOS, number of neonates that continued treatment beyond 48 h and number of neonates with culture-proven EOS. Additionally, blood culture results were documented. Data were analysed both collectively and separately for regional and academic hospitals. A total of 103,492 live-born neonates were included. In 4755 neonates (4.6%, 95% CI 4.5-4.7), antibiotic therapy was started for suspected EOS, and in 2399 neonates (2.3%, 95% CI 2.2-2.4), antibiotic treatment was continued beyond 48 h. Incidence of culture-proven EOS was 1.1 cases per 1000 live births (0.11%, 95% CI 0.09-0.14). Overall, for each culture-proven EOS case, 40.6 neonates were started on antibiotics and in 21.7 neonates therapy was continued. Large variations in treatment rates were observed across all hospitals, with the number of neonates initiated and continued on antibiotics per culture-proven EOS case varying from 4 to 90 and from 4 to 56, respectively. The high number of antibiotic prescriptions compared to the EOS incidence and wide variety in clinical practice among hospitals in The Netherlands underscore both the need and potential for a novel approach to the management of neonates with suspected EOS.

Exploring factors influencing delayed first antibiotic treatment for suspected early-onset sepsis in preterm newborns: a study before quality improvement initiative.

BACKGROUND: Early-onset sepsis (EOS) is a serious illness that affects preterm newborns, and delayed antibiotic initiation may increase the risk of adverse outcomes. PURPOSE: The objective of this study was to examine the present time of antibiotic administration in preterm infants with suspected EOS and the factors that contribute to delayed antibiotic initiation. METHODS: In this retrospective study in China, a total of 82 early preterm infants with suspected EOS between December 2021 and March 2023 were included. The study utilized a linear regression analytical approach to identify independent factors that contribute to delayed antibiotic administration. RESULTS: The mean gestational age and birth weight of the study population were 29.1 ± 1.4 weeks and 1265.7 ± 176.8 g, respectively. The median time of initial antibiotic administration was 3.8 (3.1-5.0) hours. Linear regression revealed that severe respiratory distress syndrome (RDS) (ß = 0.07, P = 0.013), penicillin skin test (PST) timing (ß = 0.06, P < 0.001) and medical order timing (ß = 0.04, P = 0.017) were significantly associated with the initial timing of antibiotic administration. CONCLUSIONS: There is an evident delay in antibiotic administration in preterm infants with suspected EOS in our unit. Severe RDS, PST postponement and delayed medical orders were found to be associated with the delayed use of antibiotics, which will be helpful for quality improvement efforts in the neonatal intensive care unit (NICU).

Antibiotic Treatment for Well-Appearing Infants Born at ≥35 Weeks' Gestation to Mothers with Chorioamnionitis Before and After Implementation of Neonatal Early-Onset Sepsis Calculator.

Purpose: Our quality improvement study aimed to determine whether application of a neonatal early-onset sepsis calculator (NSC) among well-appearing infants born at ≥35 weeks' gestation to mothers with chorioamnionitis decreases the number of lab evaluations (LEs) and antibiotic treatments (Abxs) without missing early-onset sepsis. Methods: We compared 2 years (January 1, 2019-January 3, 2021) of data from a historical-control group before implementation of the NSC to 1 year (January 4, 2021-December 31, 2021) of data from a calculator group after implementation of the NSC to evaluate whether LE and Abx decreased following implementation of the NSC on January 4, 2021. A P-value of <0.05 was considered statistically significant for the chi-squared test, Fisher's exact test, Student's t-test, and Mann-Whitney U test used for the analyses. Results: In the historical-control group, 94% of infants received LE and Abx. Retrospective application of the NSC in the historical-control group decreased LE from 94% to 21% and Abx from 94% to 13%. In the calculator group, 14% and 5% of infants received LE and Abx, respectively, and none of the blood culture was positive. Median time from birth to antibiotic initiation was significantly longer (14.5 vs 3.8 hours; P=0.0037) with no increase in median length of stay (2.3 vs 2.4 days; P=0.02) after NSC implementation. No significant difference in neonatal intensive care unit admission was identified between groups (4% vs 1%; P=0.15). Conclusions: There was a significant decrease in LE and Abx among well-appearing infants born at ≥35 weeks' gestation to mothers with chorioamnionitis after implementation of the NSC without missing early-onset sepsis. There was no increase in neonatal intensive care unit admission or length of hospital stay in infants who received antibiotics later after they appeared equivocal or clinically ill in the calculator group. Larger prospective studies that include follow ups are needed to confirm that early-onset sepsis is not missed.

Antibiotic use in infants at risk of early-onset sepsis: results from a unicentric retrospective cohort study.

BACKGROUND: Antibiotic use for early-onset sepsis represents a high percentage of antibiotic consumption in the neonatal setting. Measures to assess infants at risk of early-onset sepsis are needed to optimize antibiotic use. Our primary objective was to assess the impact of a departmental guideline on antibiotic use among term infants with suspected EOS not confirmed, in our neonatal unit. METHODS: Retrospective cohort study, to compare antibiotic use in term infants during a baseline period of January to December 2018, and a postintervention period from October 2019, to September 2020, respectively. The primary outcome was antibiotic use measured by days of therapy, the antibiotic spectrum index, the antibiotic use rate, and the length of therapy. RESULTS: We included 71 infants in the baseline period and 66 infants in the postintervention period. Compared to those in the baseline period, there was a significant reduction in overall antibiotic measures in the postintervention period, (P < 0.001). The total days of therapy/1000 patient-days decreased from 63/1000 patient-days during the baseline period to 25.8/1000 patient-days in the postintervention period, representing a relative reduction of 59%. The antibiotic use rate decreased by more than half of the infants, from 3.2% during the baseline period to 1.3% in the postintervention period. CONCLUSIONS: The use of a departmental guideline to assess infants at risk of early-onset sepsis based on their clinical condition and prompt discontinuation of antibiotics, is a simple and low-cost measure that contributed to an important decrease in antibiotic use.

Heart rate and oxygen saturation patterns in very low birth weight infants with early onset sepsis and histologic chorioamnionitis.

BACKGROUND: Chorioamnionitis and early onset sepsis (EOS) in very low birth weight (VLBW,< 1500 g) infants may cause a systemic inflammatory response reflected in patterns of heart rate (HR) and oxygenation measured by pulse oximetry (SpO2). Identification of these patterns might inform decisions about duration of antibiotic therapy after birth. OBJECTIVE: Compare early HR and SpO2 patterns in VLBW infants with or without early onset sepsis (EOS) or histologic chorioamnionitis (HC). STUDY DESIGN: Retrospective study of placental pathology and HR and SpO2 in the first 72 h from birth in relation to EOS status for inborn VLBW NICU patients 2012-2019. RESULT: Among 362 VLBW infants with HR and SpO2 data available, clinical, or culture-positive EOS occurred in 91/362 (25%) and HC in 81/355 (22%). In univariate analysis, EOS was associated with higher mean HR, lower mean SpO2, and less negative skewness of HR in the first 3 days after birth. HC was associated with higher standard deviation and skewness of HR but no difference in SpO2. In multivariable modeling, significant risk factors for EOS were mean HR, gestational age, HC, mean SpO2, and skewness of SpO2. CONCLUSION: HR and SpO2 patterns differ shortly after birth in VLBW infants exposed to HC or with EOS, likely reflecting a systemic inflammatory response.

Evaluation of systemic inflammatory indices in the diagnosis of early onset neonatal sepsis in very low birth weight infants.

BACKGROUND: Previously, not six systemic inflammatory indices were evaluated in the diagnosis of early onset sepsis (EOS) in very low birth weight (VLBW, <1500g) premature infants. OBJECTIVES: We evaluated the effectiveness of systemic inflammatory indices in the diagnosis of EOS in VLBW infants. METHODS: Premature infants with birth weight <1500 g were included in the study. Six systemic inflammatory indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI) were compared in patients with EOS (treatment group) and without EOS (control group). RESULTS: Of 917 infants enrolled, 204 infants were in the EOS group and 713 infants comprised the control group. NLR, MLR and SIRI values were significantly higher in the EOS group than in the control group (p < 0.001). The AUC value of SIRI for the predictivity of EOS was 0.803. CONCLUSIONS: The SIRI can be used together with other parameters as both an easily accessible and the reliable systemic inflammatory indices in the diagnosis of EOS in VLBW preterm infants.

Diagnostic value of maternal, cord blood and neonatal biomarkers for early-onset sepsis: a systematic review and meta-analysis.

BACKGROUND: An accurate diagnosis of early-onset sepsis (EOS) is challenging because of subtle symptoms and the lack of a good diagnostic tool, resulting in considerable antibiotic overtreatment. A biomarker, discriminating between infected and non-infected newborns at an early stage of the disease, could improve EOS prediction. Numerous biomarkers have been tested, but have never been compared directly. OBJECTIVES: We aimed to provide a comprehensive overview of early biomarkers and their diagnostic value in maternal samples, umbilical cord blood, and neonatal serum. DATA SOURCES: PubMed-Medline, EMBASE, The Cochrane Library, and Web of Science were searched up to 1 March 2023, without restrictions on publication date, population, or language. STUDY ELIGIBILITY CRITERIA: Articles describing the diagnostic value of at least one biomarker in the detection of EOS in neonates, independent of gestational age, were included. ASSESSMENT OF RISK OF BIAS: The QUADAS-2 tool was used to assess study quality. METHODS OF DATA SYNTHESIS: Three independent researchers assessed the articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was performed with all manuscripts describing diagnostic accuracy using a random-effects model. RESULTS: Of 2296 identified articles, 171 reports were included in the systematic review and 69 in the meta-analysis. Literature showed mixed and inconsistent evidence for most biomarkers and sample types, because of a lack of a uniform EOS case definition, small sample sizes, and large heterogeneity between studies. Interesting markers were procalcitonin (pooled sensitivity 79%, 95% CI 71-84%; specificity 91%, 95% CI 83-96%, n = 11) and interleukin (IL)-6 (pooled sensitivity 83%, 95% CI 71-90%; specificity 87%, 95% CI 78-93%, n = 8) in umbilical cord blood and presepsin (pooled sensitivity 82%, 95% CI 62-93%; specificity 86%, 95% CI 73-93%, n = 3) and serum amyloid A (pooled sensitivity 92%, 95% CI 75-98%; specificity 96%, 95% CI 78-99%, n = 4) in neonatal serum. Studies on the combination of biomarkers were scarce. CONCLUSIONS: A biomarker stand-alone test is currently not reliable for direct antibiotic stewardship in newborns, although several biomarkers show promising initial results. Further research into biomarker combinations could lead to an improved EOS diagnosis, reduce antibiotic overtreatment, and prevent associated health-related problems.

Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants.

BACKGROUND: There are wide variations in antibiotic use in neonatal intensive care units (NICUs). Limited data are available on antimicrobial stewardship (AS) programs and long-term maintenance of AS interventions in preterm very-low-birth-weight (VLBW) infants. METHODS: We extended a single-centre observational study carried out in an Italian NICU. Three periods were compared: I. "baseline" (2011-2012), II. "intervention" (2016-2017), and III. "maintenance" (2020-2021). Intensive training of medical and nursing staff on AS occurred between periods I and II. AS protocols and algorithms were maintained and implemented between periods II and III. RESULTS: There were 111, 119, and 100 VLBW infants in periods I, II, and III, respectively. In the "intervention period", there was a reduction in antibiotic use, reported as days of antibiotic therapy per 1000 patient days (215 vs. 302, p < 0.01). In the "maintenance period", the number of culture-proven sepsis increased. Nevertheless, antibiotic exposure of uninfected VLBW infants was lower, while no sepsis-related deaths occurred. Our restriction was mostly directed at shortening antibiotic regimens with a policy of 48 h rule-out sepsis (median days of early empiric antibiotics: 6 vs. 3 vs. 2 in periods I, II, and III, respectively, p < 0.001). Moreover, antibiotics administered for so-called culture-negative sepsis were reduced (22% vs. 11% vs. 6%, p = 0.002), especially in infants with a birth weight between 1000 and 1499 g. CONCLUSIONS: AS is feasible in preterm VLBW infants, and antibiotic use can be safely reduced. AS interventions, namely, the shortening of antibiotic courses in uninfected infants, can be sustained over time with periodic clinical audits and daily discussion of antimicrobial therapies among staff members.

An Overview of Antibiotic Therapy for Early- and Late-Onset Neonatal Sepsis: Current Strategies and Future Prospects.

Neonatal sepsis is a clinical syndrome mainly associated with a bacterial infection leading to severe clinical manifestations that could be associated with fatal sequalae. According to the time of onset, neonatal sepsis is categorized as early- (EOS) or late-onset sepsis (LOS). Despite blood culture being the gold standard for diagnosis, it has several limitations, and early diagnosis is not immediate. Consequently, most infants who start empirical antimicrobial therapy do not have an underlying infection. Despite stewardship programs partially reduced this negative trend, in neonatology, antibiotic overuse still persists, and it is associated with several relevant problems, the first of which is the increase in antimicrobial resistance (AMR). Starting with these considerations, we performed a narrative review to summarize the main findings and the future prospects regarding antibiotics use to treat neonatal sepsis. Because of the impact on morbidity and mortality that EOS and LOS entail, it is essential to start an effective and prompt treatment as soon as possible. The use of targeted antibiotics is peremptory as soon as the pathogen in the culture is detected. Although prompt therapy is essential, it should be better assessed whether, when and how to treat neonates with antibiotics, even those at higher risk. Considering that we are certainly in the worrying era defined as the "post-antibiotic era", it is still essential and urgent to define novel strategies for the development of antibacterial compounds with new targets or mechanisms of action. A future strategy could also be to perform well-designed studies to develop innovative algorithms for improving the etiological diagnosis of infection, allowing for more personalized use of the antibiotics to treat EOS and LOS.

Early-onset neonatal sepsis: Effectiveness of classification based on ante- and intrapartum risk factors and clinical monitoring.

INTRODUCTION: In 2017, the French public health authority HAS published new guidelines for the management of newborns at risk of early bacterial neonatal infection. These guidelines were based on ante- and intrapartum risk factors and clinical monitoring. In January 2021, we implemented a new protocol based on these guidelines in our tertiary maternity unit. OBJECTIVES: To assess the impact of the protocol implemented on neonates' antibiotic prescriptions. METHOD: An "old protocol" group comprising newborns hospitalized between July 1, 2020 and December 31, 2020, was compared to a "new protocol" group formed between January 14, 2021 and July 13, 2021. Data were collected on infectious risk factors, antibiotic prescriptions, and emergency room visits within 2 weeks for an infection or suspected infection. RESULTS: The "old protocol" population comprised 1565 children and the "new protocol" population 1513. Antibiotic therapy was prescribed for 29 newborns (1.85 %) in the old protocol group versus 15 (0.99 %) in the new one (p = 0.05). The median duration was 5 days and 2 days respectively (p = 0.08). With the new protocol, newborns in category B were about 20 times more likely (p = 0.01), and those in category C about 54 times more likely (p = 0.005) to have an infection than those classified in categories N or A. CONCLUSION: This study demonstrates that clinical monitoring criteria enable reduced use and duration of antibiotic therapy and are reliable.

Early procalcitonin assays may reduce antibiotic exposure in premature newborn infants.

AIM: The diagnosis of early-onset neonatal sepsis (EOS) remains difficult. The main aim was to study the effect of a new algorithm for EOS, which includes the level of procalcitonin in umbilical cord blood, on the exposure to antibiotic therapy of premature newborn infants. METHODS: This was a monocentric, observational and retrospective study with before-and-after design. The duration and dose of antibiotic therapy provided as well as the morbidity and mortality were compared in two groups, one included 01 May 2015-30 November 2015 when procalcitonin was not used, and one after the change 01 November 2016-30 May 2017 when procalcitonin was used in a hospital setting in Nice, France. RESULTS: Sixty newborn infants were included in the before group and 54 in the after group. Antibiotic therapy was stopped after 24 h for 18 newborn infants in the after group and four in the before group, and after 48 h for 26 newborn infants in the after group and 10 in the before group. CONCLUSION: The implementation of a new decision-making algorithm including early procalcitonin assay of premature newborn infants significantly reduced exposure to antibiotics without modifying mortality or morbidity.

Does perinatal management have the potential to reduce the risk of intraventricular hemorrhage in preterm infants?

Background: Intraventricular hemorrhage (IVH) is an important cause of neurodevelopmental impairment in preterm infants. A number of risk factors for IVH have already been proposed; however, some controversies regarding optimal perinatal management persist. This study aimed to identify perinatal and neonatal attributes associated with IVH in a representative population of preterm infants. Methods: Perinatal data on 1,279 very preterm infants (<32 weeks of gestation) admitted to a tertiary neonatal intensive care unit were analyzed. The records were assessed using univariate analysis and logistic regression model to evaluate the risk factors for any and high-grade IVH (grade III-IV according to the classification by Papile) within the first week after birth. Results: The incidence of any IVH was 14.3% (183/1,279); the rate of low-grade (I-II) and high-grade (III-IV) IVH was 9.0% (115/1,279) and 5.3% (68/1,279), respectively. Univariate analysis revealed multiple factors significantly associated with intraventricular hemorrhage: lower gestational age and birth weight, absence of antenatal steroids, vaginal delivery, low Apgar score at 5 min, delivery room intubation, surfactant administration, high frequency oscillation, pulmonary hypertension, pulmonary hemorrhage, tension pneumothorax, persistent ductus arteriosus, hypotension and early onset sepsis. Logistic regression confirmed lower gestational age, vaginal delivery, ductus arteriosus and early onset sepsis to be independent predictors for any IVH. Pulmonary hemorrhage, tension pneumothorax and early onset sepsis were independent risk factors for high-grade IVH. Complete course of antenatal steroids was associated with a lower risk for any (odds ratio 0.58, 95% confidence interval 0.39-0.85; P = .006) and for high-grade intraventricular hemorrhage (odds ratio 0.36, 95% confidence interval 0.20-0.65; P < .001). Conclusion: The use of antenatal steroids and mode of delivery are crucial in the prevention of IVH; however, our study did not confirm the protective effect of placental transfusion. Severe respiratory insufficiency and circulatory instability remain to be powerful contributors to the development of IVH. Early detection and management of perinatal infection may also help to reduce the rate of brain injury and improve neurodevelopment in high-risk newborns.

Application of Advanced Molecular Methods to Study Early-Onset Neonatal Sepsis.

Early-onset sepsis (EOS) is a global health issue, considered one of the primary causes of neonatal mortality. Diagnosis of EOS is challenging because its clinical signs are nonspecific, and blood culture, which is the current gold-standard diagnostic tool, has low sensitivity. Commonly used biomarkers for sepsis diagnosis, including C-reactive protein, procalcitonin, and interleukin-6, lack specificity for infection. Due to the disadvantages of blood culture and other common biomarkers, ongoing efforts are directed towards identifying innovative molecular approaches to diagnose neonates at risk of sepsis. This review aims to gather knowledge and recent research on these emerging molecular methods. PCR-based techniques and unrestricted techniques based on 16S rRNA sequencing and 16S-23S rRNA gene interspace region sequencing offer several advantages. Despite their potential, these approaches are not able to replace blood cultures due to several limitations; however, they may prove valuable as complementary tests in neonatal sepsis diagnosis. Several microRNAs have been evaluated and have been proposed as diagnostic biomarkers in EOS. T2 magnetic resonance and bioinformatic analysis have proposed potential biomarkers of neonatal sepsis, though further studies are essential to validate these findings.

Effect of Serial Clinical Observation Complemented by Point-of-Care Blood Culture Volume Verification on Antibiotic Exposure in Newborns.

Objective. This study evaluated the effects of serial clinical observation strategy complemented by point-of-care verification of blood culture volume in managing term and near-term newborns at risk for early-onset sepsis. Methods. We used a "before-and-after" approach. Infants born at ≥35 0/7 weeks' gestation were eligible. Our strategy was based on serial clinical observation complemented with point-of-care verification of blood culture volume. Two separate 12-month periods were analyzed. The number of infants exposed to antibiotics started during the first 3 days of life was compared before and after introducing the strategy. Results. During the post-intervention period, 0.6% of infants received antibiotic therapy, compared to 4.1% during the pre-intervention period (P < .001; relative risk [RR]: 0.15; 95% CI: 0.08-0.28). Conclusion. Serial clinical observation complemented with verification of blood culture volume might reduce antibiotic utilization in newborns in the early postnatal period.

Investigating the Association between Serum and Hematological Biomarkers and Neonatal Sepsis in Newborns with Premature Rupture of Membranes: A Retrospective Study.

(1) Background: Neonatal early-onset sepsis (EOS) is associated with important mortality and morbidity. The aims of this study were to evaluate the association between serum and hematological biomarkers with early onset neonatal sepsis in a cohort of patients with prolonged rupture of membranes (PROM) and to calculate their diagnostic accuracy. (2) Methods: A retrospective cohort study was conducted on 1355 newborns with PROM admitted between January 2017 and March 2020, who were divided into two groups: group A, with PROM ≥ 18 h, and group B, with ROM < 18 h. Both groups were further split into subgroups: proven sepsis, presumed sepsis, and no sepsis. Descriptive statistics, analysis of variance (ANOVA) and a Random Effects Generalized Least Squares (GLS) regression were used to evaluate the data. (3) Results: The statistically significant predictors of neonatal sepsis were the high white blood cell count from the first (p = 0.005) and third day (p = 0.028), and high C-reactive protein (CRP) values from the first day (p = 0.004). Procalcitonin (area under the curve-AUC = 0.78) and CRP (AUC = 0.76) measured on the first day had the best predictive performance for early-onset neonatal sepsis. (4) Conclusions: Our results outline the feasibility of using procalcitonin and CRP measured on the first day taken individually in order to increase the detection rate of early-onset neonatal sepsis, in the absence of positive blood culture.

Umbilical cord blood hematological parameters in predicting early onset neonatal sepsis (EOS) - a prospective cohort study.

OBJECTIVES: In low and middle income countries, there is a need for affordable and accurate biomarkers to identify neonates at risk of early onset neonatal sepsis (EOS). Cord blood hematological parameters if reliable and accurate for the detection of EOS are cost effective and can reduce the need for repeated venipuncture in the neonate. METHODS: In this prospective cohort study, the umbilical cord parameters of newborns with gestational age >34 weeks were collected. These neonates were followed up for 72 h and septic screen was employed in those babies who had risk factors or developed clinical features of sepsis. The cord blood parameters of the normal newborn and those who had sepsis were analyzed. RESULTS: A total of 513 neonates were enrolled for the study, 32 required septic screening of whom 13 neonates were found to meet the criteria for sepsis: either blood culture positive or sepsis screen positive with clinical features. Cord blood parameters were analyzed using independent t test. Red cell distribution width (RDW) and band cells were statistically significant (p 0.007 and 0.009 respectively) between the septic and normal neonates. Increased RDW had a sensitivity of 61.54 %, specificity of 54.60 %. Increased band cells with a cut off of >15 cells had a sensitivity of 7.7 % with specificity of 100 % with higher numbers in septic neonates. Increased RDW and band cells in combination had sensitivity of 61.54 % and specificity of 54.6 %. CONCLUSIONS: RDW and band cell can be potential markers of EOS in cord blood but require further study in a larger population.

Neonatal early-onset sepsis calculator: Impact on antibiotic use in a level II neonatal unit in Western Australia.

BACKGROUND: Overuse of empirical intravenous antibiotics in neonates in high-income countries (HICs) is well documented. The Kaiser Permanente neonatal early-onset sepsis (EOS) calculator is an evidence-based sepsis risk assessment tool that has demonstrated potential to reduce antibiotic usage in this population. The incidence of early-onset sepsis in most HICs is 0.4-0.8 per 1000 live births. The objective was to evaluate the calculator's impact on antibiotic rates and length of stay in a regional level II Special Care Nursery. METHODS: A single-centre retrospective cohort study compared antibiotic administration rates in the first 72 h in neonates ≥35 weeks gestation born during two 6-month periods in 2019 (pre-EOS calculator) and 2021 (post-EOS calculator). Electronic and paper case records were accessed to capture data. Continuous data were summarised using mean and standard deviation, and categorical data were summarized using frequency distributions. There were 951 (2019) and 1129 (2021) infants born during the study periods. RESULTS: Following implementation of the calculator, antibiotic exposure decreased from 13.7% to 4.7% of all neonates without reported negative outcomes. Mean length of stay for neonates born across the two periods decreased from 2.38 to 2.13 days. Indications for antibiotic use shifted more towards clinical condition and away from obstetric risk factors. There were no culture-proven cases of sepsis or readmissions with EOS in either period. CONCLUSION: Implementation of the EOS calculator significantly reduced exposure to antibiotics, without adverse outcomes.

Association Between Hypoglycemia and the Occurrence of Early Onset Sepsis in Premature Infants.

BACKGROUND: We examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU). METHODS: We included infants discharged from 358 NICUs between 1997 and 2020 with gestational age <34 weeks, ≥1 culture collected in the first 3 days of life, and ≥1 serum glucose value recorded on the day of or day prior to culture collection. We used multivariable logistic regression and inverse probability weighting (IPW) and constructed models for three definitions of hypoglycemia: American Academy of Pediatrics (AAP), Pediatric Endocrine Society, and a definition based on neurodevelopmental studies. We performed subgroup analysis in EOS episodes caused by Gram-negative and Gram-positive organisms. RESULTS: Of the 62,178 infants and 64,559 cultures that met study inclusion criteria, 739 (1%) cultures were positive. The median (25th, 75th percentile) glucose value was 75 mg/dL (50, 106) on the day of or day prior to a positive culture versus 70 mg/dL (50, 95) on the day of or day prior to a negative culture. We found that hypoglycemia was not associated with the occurrence of EOS for all organisms and Gram-positive organisms, whereas there was a small but significant association between the lower AAP glucose cutoff value and EOS due to Gram-negative organisms (logistic regression: risk difference [RD] 0.24% [95% CI, 0.01-0.47]; IPW: RD 0.22% [95% CI, 0.00-0.43]). CONCLUSIONS: Hypoglycemia may be an early marker of EOS, particularly in episodes caused by Gram-negative organisms and when using a stricter definition of hypoglycemia.