Recurrent Group B Streptococcus neonatal invasive infections, France, 2007 -2021.

Recurrence is a rare complication of Group B Streptococcus (GBS) neonatal infections. We conducted a retrospective observational study on GBS neonatal invasive infections in France from 2007 to 2021. 1,527 cases were reported, of which 36 (2.36%) were recurrent. Recurrence mainly concerned preterm (68%) and low birthweight (72%) infants and was associated with the hypervirulent GBS clonal complex 17 (83%, OR 2.86, 95% CI 1.18-6.92). No beta-lactam tolerant strains were identified and bacterial whole genome sequencing could not reveal any specific feature associated with recurrence. Large cohort studies should be undertaken to address the optimal management of these uncommon diseases.

Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Infants Born Extremely Preterm.

OBJECTIVE: The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation. STUDY DESIGN: This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean gestational age: 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47 512 patient-days); of whom, 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5-day antibiotics). RESULTS: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including postmenstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an area under the receiver operator characteristic curve of 0.783. CONCLUSION: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.

Clinical Decision Support for Improved Neonatal Care: The Development of a Machine Learning Model for the Prediction of Late-onset Sepsis and Necrotizing Enterocolitis.

OBJECTIVE: To develop an artificial intelligence-based software system for predicting late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in infants admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: Single-center, retrospective cohort study, conducted in the NICU of the Antwerp University Hospital. Continuous monitoring data of 865 preterm infants born at <32 weeks gestational age, admitted to the NICU in the first week of life, were used to train an XGBoost machine learning (ML) algorithm for LOS and NEC prediction in a cross-validated setup. Afterward, the model's performance was assessed on an independent test set of 148 patients (internal validation). RESULTS: The ML model delivered hourly risk predictions with an overall sensitivity of 69% (142/206) for all LOS/NEC episodes and 81% (67/83) for severe LOS/NEC episodes. The model showed a median time gain of ≤10 hours (IQR, 3.1-21.0 hours), compared with historical clinical diagnosis. On the complete retrospective dataset, the ML model made 721 069 predictions, of which 9805 (1.3%) depicted a LOS/NEC probability of ≥0.15, resulting in a total alarm rate of <1 patient alarm-day per week. The model reached a similar performance on the internal validation set. CONCLUSIONS: Artificial intelligence technology can assist clinicians in the early detection of LOS and NEC in the NICU, which potentially can result in clinical and socioeconomic benefits. Additional studies are required to quantify further the effect of combining artificial and human intelligence on patient outcomes in the NICU.

Gut microbiota in preterm infants with late-onset sepsis and pneumonia: a pilot case-control study.

BACKGROUND: Late-onset sepsis (LOS) and pneumonia are common infectious diseases, with high morbidity and mortality in neonates. This study aimed to investigate the differences in the gut microbiota among preterm infants with LOS, or pneumonia, and full-term infants. Furthermore, this study aimed to determine whether there is a correlation between intestinal pathogenic colonization and LOS. METHODS: In a single-center case‒control study, 16 S rRNA gene sequencing technology was used to compare gut microbiota characteristics and differences among the LOS group, pneumonia group, and control group. RESULTS: Our study revealed that the gut microbiota in the control group was more diverse than that in the LOS group and pneumonia group (P < 0.05). No significant differences in diversity were detected between the LOS and pneumonia groups (P > 0.05). Compared with the control group, the abundances of Akkermansia, Escherichia/Shigella, and Enterococcus increased, while the abundances of Bacteroides and Stenotrophomonas decreased in the LOS and pneumonia groups. The pathogenic bacteria in infants with LOS were consistent with the distribution of the main bacteria in the intestinal microbiota. An increase in Escherichia/Shigella abundance may predict a high risk of LOS occurrence, with an area under the curve (AUC) of 0.773. CONCLUSION: Changes in the gut microbiota composition were associated with an increased risk of LOS and pneumonia. The dominant bacteria in the gut microbiota of the LOS group were found to be associated with the causative pathogen of LOS. Moreover, preterm infants exhibiting an elevated abundance of Escherichia/Shigella may be considered potential candidates for predicting the onset of LOS.

The role of nutrition in analysis of risk factors and short-term outcomes for late-onset necrotizing enterocolitis among very preterm infants: a nationwide, multicenter study in China.

BACKGROUND: Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. METHOD: Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. RESULTS: Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation. CONCLUSION: Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs. TRIAL REGISTRATION: ChiCTR1900023418 (26/05/2019).

Pre-Sepsis Length of Hospital Stay and Mortality: A Nationwide Multicenter Cohort Study.

BACKGROUND: Prolonged length of hospital stay (LOS) is associated with an increased risk of hospital-acquired conditions and worse outcomes. We conducted a nationwide, multicenter, retrospective cohort study to determine whether prolonged hospitalization before developing sepsis has a negative impact on its prognosis. METHODS: We analyzed data from 19 tertiary referral or university-affiliated hospitals between September 2019 and December 2020. Adult patients with confirmed sepsis during hospitalization were included. In-hospital mortality was the primary outcome. The patients were divided into two groups according to their LOS before the diagnosis of sepsis: early- (< 5 days) and late-onset groups (≥ 5 days). Conditional multivariable logistic regression for propensity score matched-pair analysis was employed to assess the association between late-onset sepsis and the primary outcome. RESULTS: A total of 1,395 patients were included (median age, 68.0 years; women, 36.3%). The early- and late-onset sepsis groups comprised 668 (47.9%) and 727 (52.1%) patients. Propensity score-matched analysis showed an increased risk of in-hospital mortality in the late-onset group (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.69-5.34). The same trend was observed in the entire study population (aOR, 1.85; 95% CI, 1.37-2.50). When patients were divided into LOS quartile groups, an increasing trend of mortality risk was observed in the higher quartiles (P for trend < 0.001). CONCLUSION: Extended LOS before developing sepsis is associated with higher in-hospital mortality. More careful management is required when sepsis occurs in patients hospitalized for ≥ 5 days.

The Potential of Fecal Volatile Organic Compound Analysis for the Early Diagnosis of Late-Onset Sepsis in Preterm Infants: A Narrative Review.

Early diagnosis and treatment of late-onset sepsis (LOS) is crucial for survival, but challenging. Intestinal microbiota and metabolome alterations precede the clinical onset of LOS, and the preterm gut is considered an important source of bacterial pathogens. Fecal volatile organic compounds (VOCs), formed by physiologic and pathophysiologic metabolic processes in the preterm gut, reflect a complex interplay between the human host, the environment, and microbiota. Disease-associated fecal VOCs can be detected with an array of devices with various potential for the development of a point-of-care test (POCT) for preclinical LOS detection. While characteristic VOCs for common LOS pathogens have been described, their VOC profiles often overlap with other pathogens due to similarities in metabolic pathways, hampering the construction of species-specific profiles. Clinical studies have, however, successfully discriminated LOS patients from healthy individuals using fecal VOC analysis with the highest predictive value for Gram-negative pathogens. This review discusses the current advancements in the development of a non-invasive fecal VOC-based POCT for early diagnosis of LOS, which may potentially provide opportunities for early intervention and targeted treatment and could improve clinical neonatal outcomes. Identification of confounding variables impacting VOC synthesis, selection of an optimal detection device, and development of standardized sampling protocols will allow for the development of a novel POCT in the near future.

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OBJECTIVES: To study the predictive value of hemoglobin (Hb) decrease for the occurrence of necrotizing enterocolitis (NEC) in preterm infants with late-onset sepsis (LOS) . METHODS: Clinical data of 93 LOS preterm infants were collected for retrospective analysis, among which 16 infants developed NEC while 77 infants did not. Based on the decrease in Hb levels from the most recent Hb measurement before LOS occurrence to the initial Hb levels during LOS, the infants were divided into three groups: no Hb decrease (n=15), mild Hb decrease (Hb decrease <15 g/L; n=35), and severe Hb decrease (Hb decrease ≥15 g/L; n=43). Multivariate logistic regression analysis was conducted to explore the predictive factors for NEC secondary to LOS, and the value of Hb decrease in predicting NEC secondary to LOS was evaluated through receiver operating characteristic curve analysis. RESULTS: The incidence of NEC in the severe Hb decrease group, mild Hb decrease group, and no Hb decrease group were 26%, 14%, and 0% (P<0.05), respectively. Multivariate logistic regression analysis revealed that a larger Hb decrease was an independent predictive factor for NEC in LOS preterm infants (OR=1.141, 95%CI: 1.061-1.277, P<0.001). Receiver operating characteristic curve analysis showed that the area under the curve for predicting NEC in preterm infants with LOS using Hb decrease (with a cut-off value of 20 g/L) was 0.803, with sensitivity and specificity of 0.69 and 0.78, respectively. CONCLUSIONS: Hb decrease can serve as an indicator for prediction of NEC in preterm infants with LOS.

Early Empirical Antibiotics and Adverse Clinical Outcomes in Infants Born Very Preterm: A Population-Based Cohort.

OBJECTIVE: The objective of this study was to evaluate the association between empirical antibiotic therapy in the first postnatal week in uninfected infants born very preterm and the risk of adverse outcomes until discharge. STUDY DESIGN: Population-based, nationwide registry study in Norway including all live-born infants with a gestational age <32 weeks surviving first postnatal week without sepsis, intestinal perforation, or necrotizing enterocolitis (NEC) between 2009 and 2018. Primary outcomes were severe NEC, death after the first postnatal week, and/or a composite outcome of severe morbidity (severe NEC, severe bronchopulmonary dysplasia [BPD], severe retinopathy of prematurity, late-onset sepsis, or cystic periventricular leukomalacia). The association between empirical antibiotics and adverse outcomes was assessed using multivariable logistic regression models, adjusting for known confounders. RESULTS: Of 5296 live-born infants born very preterm, 4932 (93%) were included. Antibiotics were started in first postnatal week in 3790 of 4932 (77%) infants and were associated with higher aOR of death (aOR 9.33; 95% CI: 1.10-79.5, P = .041), severe morbidity (aOR 1.88; 95% CI: 1.16-3.05, P = .01), and severe BPD (aOR 2.17; 95% CI: 1.18-3.98; P = .012), compared with those not exposed. Antibiotics ≥ 5 days were associated with higher odds of severe NEC (aOR 2.27; 95% CI: 1.02-5.06; P = .045). Each additional day of antibiotics was associated with 14% higher aOR of death or severe morbidity and severe BPD. CONCLUSIONS: Early and prolonged antibiotic exposure within the first postnatal week was associated with severe NEC, severe BPD, and death after the first postnatal week.

Prognostic accuracy of Neonatal SOFA score versus SIRS criteria in preterm infants with late-onset sepsis.

Neonatal SOFA score was reported as an accurate predictor of mortality while the prognostic accuracy of SIRS criteria is unknown. The aim was to compare neonatal SOFA and SIRS criteria for the prediction of late onset sepsis-related mortality in preterm newborns. Newborns ≤ 32 weeks with late onset sepsis were retrospectively studied. Neonatal SOFA and SIRS criteria were calculated at onset of sepsis (T0), and after 6 ± 1 (T1), 12 ± 3 (T2) and 24 ± 3 h (T3). Outcome was death during antibiotic treatment for late onset sepsis. We studied 112 newborns with gestational age 26.9 ± 2.3 weeks; 11% met the study outcome. Neonatal SOFA was significantly higher in non-survivors vs. survivors at all time intervals; SIRS criteria were significantly higher in non-survivors vs. survivors at T1, T2 and T3. Neonatal SOFA increased over time in non-survivors (p = 0.003). At T0, the area under receiver operating characteristics curve was significantly higher for neonatal SOFA score than SIRS criteria (0.950 vs. 0.569; p = 0.0002), and the best calculated cut-off for T0 neonatal SOFA score was 4. In multivariate analysis T0 and T1 neonatal SOFA were predictors of late onset sepsis-related mortality (p = 0.048 and p < 0.001).  Conclusion: Neonatal SOFA score showed greater discriminatory capacity for mortality than SIRS criteria and might be helpful to plan management for patients at higher risk of death. What is Known: • Neonatal SOFA score may be an accurate prognostic tool. • No prognostic score has been fully standardized for septic newborns in NICU. What is New: • Neonatal SOFA score outperformed SIRS criteria for the prediction of prognosis in preterm infants with late onset sepsis. • Neonatal SOFA score assessed at onset of sepsis and 6 hrs later is a predictor of mortality.

Trends and spatial distribution of neonatal sepsis, Uganda, 2016-2020.

BACKGROUND: In Uganda, sepsis is the third-leading cause of neonatal deaths. Neonatal sepsis can be early-onset sepsis (EOS), which occurs ≤ 7 days postpartum and is usually vertically transmitted from the mother to newborn during the intrapartum period, or late-onset sepsis (LOS), occurring 8-28 days postpartum and largely acquired from the hospital environment or community. We described trends and spatial distribution of neonatal sepsis in Uganda, 2016-2020. METHODS: We conducted a descriptive incidence study using routinely-reported surveillance data on in-patient neonatal sepsis from the District Health Information System version 2 (DHIS2) during 2016-2020. We calculated incidence of EOS, LOS, and total sepsis as cases per 1,000 live births (LB) at district (n = 136), regional (n = 4), and national levels, as well as total sepsis incidence by health facility level. We used logistic regression to evaluate national and regional trends and illustrated spatial distribution using choropleth maps. RESULTS: During 2016-2020, 95,983 neonatal sepsis cases were reported, of which 71,262 (74%) were EOS. Overall neonatal sepsis incidence was 17.4/1,000 LB. EOS increased from 11.7 to 13.4 cases/1,000 LB with an average yearly increase of 3% (p < 0.001); LOS declined from 5.7 to 4.3 cases/1,000 LB with an average yearly decrease of 7% (p < 0.001). Incidence was highest at referral hospitals (68/1,000 LB) and lowest at Health Center IIs (1.3/1,000 LB). Regionally, total sepsis increased in Central (15.5 to 23.0/1,000 LB, p < 0.001) and Northern regions (15.3 to 22.2/1,000 LB, p < 0.001) but decreased in Western (23.7 to 17.0/ 1,000 LB, p < 0.001) and Eastern (15.0 to 8.9/1,000, p < 0.001) regions. CONCLUSION: The high and increasing incidence of EOS in Uganda suggests a major gap in sepsis prevention and quality of care for pregnant women. The heterogenous distribution of neonatal sepsis incidence requires root cause analysis by health authorities in regions with consistently high incidence. Strengthening prevention and treatment interventions in Central and Northern regions, and in the most affected districts, could reduce neonatal sepsis. Employment of strategies which increase uptake of safe newborn care practices and prevent neonatal sepsis, such as community health worker (CHW) home visits for mothers and newborns, could reduce incidence.

Interventions for reducing late-onset sepsis in neonates: an umbrella review.

OBJECTIVES: Neonatal sepsis is one of the leading causes of neonatal deaths in neonatal intensive care units. Hence, it is essential to review the evidence from systematic reviews on interventions for reducing late-onset sepsis (LOS) in neonates. METHODS: PubMed and the Cochrane Central were searched from inception through August 2020 without any language restriction. Cochrane reviews of randomized clinical trials (RCTs) assessing any intervention in the neonatal period and including one or more RCTs reporting LOS. Two authors independently performed screening, data extraction, assessed the quality of evidence using Cochrane Grading of Recommendations Assessment, Development and Evaluation, and assessed the quality of reviews using a measurement tool to assess of multiple systematic reviews 2 tool. RESULTS: A total of 101 high-quality Cochrane reviews involving 612 RCTs and 193,713 neonates, evaluating 141 interventions were included. High-quality evidence showed a reduction in any or culture-proven LOS using antibiotic lock therapy for neonates with central venous catheters (CVC). Moderate-quality evidence showed a decrease in any LOS with antibiotic prophylaxis or vancomycin prophylaxis for neonates with CVC, chlorhexidine for skin or cord care, and kangaroo care for low birth weight babies. Similarly, moderate-quality evidence showed reduced culture-proven LOS with intravenous immunoglobulin prophylaxis for preterm infants and probiotic supplementation for very low birth weight (VLBW) infants. Lastly, moderate-quality evidence showed a reduction in fungal LOS with the use of systemic antifungal prophylaxis in VLBW infants. CONCLUSIONS: The overview summarizes the evidence from the Cochrane reviews assessing interventions for reducing LOS in neonates, and can be utilized by clinicians, researchers, policymakers, and consumers for decision-making and translating evidence into clinical practice.

Clinical profile of infants with late onset sepsis admitted in a North East Indian tertiary care center: insights into the uncharted.

OBJECTIVES: To assess the clinical profile of infants with late onset sepsis admitted in a tertiary care hospital in North-East India. METHODS: Prospective observational study was carried out in Department of Paediatrics, Regional Institute of Medical Sciences hospital during a period of 2 years (September 2019-August 2021). RESULTS: A total of 109 patients were included in the study, of which 80 were community-acquired and 29 infants were hospital-acquired cases of late onset sepsis (LOS). The major risk factors were low socioeconomic status, prematurity, low birth weight, a history of intervention (mechanical ventilation, umbilical venous catheter, total parenteral nutrition, resuscitation) and lack of exclusive breastfeeding. The most common presenting features were decreased feeding, lethargy and respiratory distress. Blood cultures were positive in 33% of patients. Klebsiella was the most common hospital-acquired pathogen while Escherichia coli was the most common isolate in community-acquired cases. Thrombocytopenia was the most common complication. The in-hospital mortality rate was 13.7%. CONCLUSION: Low socioeconomic status, low birth weight, prematurity, invasive interventions and lack of exclusive breastfeeding are the major risk factors of LOS. The clinical signs and symptoms are varied and subtle. The mean C-reactive protein in the hospital-acquired group was significantly higher as compared to the community-acquired group. There is substantial morbidity and mortality, resulting in an increased toll on resources, therefore, an aggressive preventive and treatment approach is recommended for late onset sepsis.

Can We Estimate Late-Onset Sepsis by Serial Methemoglobin Levels? An Observational Study in Preterm Neonates.

Objective: To assess serial methemoglobin (MetHb) levels in preterm infants as a possible diagnostic method for late-onset sepsis (LOS). Methods: Preterm infants were assigned into two groups: those with culture-proven LOS and controls. Serial MetHb levels were measured. Results: The MetHb values of the LOS group were found to be significantly increased (p < 0.001). The cutoff value for the detection of LOS was calculated as MetHb > 1.75%, optimized for a sensitivity of 81.9% and specificity of 90%. After antimicrobial therapy, MetHb values were found to decrease significantly (p < 0.001). MetHb had an AUC of 0.810 for mortality using the calculated cutoff of >2% (p < 0.005). Conclusions: MetHb levels increase at the onset of LOS and decrease following treatment. MetHb can be added to other sepsis biomarkers as a rapid infectious process indicator for preterm neonates. MetHb > 2% is associated with LOS mortality.

Mean Platelet Volume and Mean Platelet Volume/Platelet Count Ratio Are Predictors of Late-Onset Sepsis in Preterm Infants: A Case-Control Study.

Objective: Our aim was to assess mean platelet volume (MPV) and mean platelet volume to platelet count ratio (MPR) in the setting of late-onset sepsis (LOS) and their association with the type of bacteria causing LOS. Study design: The MPV and MPR levels were obtained at the onset of LOS and then assessed in intra/inter group analyses in preterm infants. Results: Overall, 136 preterm infants were enrolled. The MPV and MPR levels were higher during a LOS event (P < 0.001). A MPV cutoff of >9.2 was related with a sensitivity of 63% and a specificity of 73% for predicting LOS (P < 0.001). A MPR cutoff of >0.15 was related with a sensitivity of 88% and a specificity of 63% for predicting gram negative LOS (P < 0.001). Conclusion: Elevated MPV values and MPR ratios may be helpful in assessing LOS.

Early Antibiotic Exposure and Adverse Outcomes in Very Preterm Infants at Low Risk of Early-Onset Sepsis: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors for early-onset sepsis (EOS). STUDY DESIGN: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of EOS (ie, born after preterm labor or preterm premature rupture of membranes or from a mother who had clinical chorioamnionitis or had received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotic therapy started at day 0 or day 1 of life, irrespective of the duration and type of antibiotics. We compared treated and untreated patients using inverse probability of treatment weighting based on estimated propensity scores. RESULTS: Among 648 very preterm infants at low risk of EOS, 173 (26.2%) had received early antibiotic treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR, 1.04; 95% CI, 0.72-1.50); however, it was associated with higher odds of severe cerebral lesions (OR, 2.71; 95% CI, 1.25-5.86) and moderate-severe bronchopulmonary dysplasia (BPD) (OR, 2.30; 95% CI, 1.21-4.38). CONCLUSIONS: Early empirical antibiotic therapy administrated in very preterm infants at low risk of EOS was associated with a higher risk of severe cerebral lesions and moderate-severe BPD.

Multivariable Predictive Models of Death or Neurodevelopmental Impairment Among Extremely Low Birth Weight Infants Using Heart Rate Characteristics.

OBJECTIVE: We hypothesized that a cumulative heart rate characteristics (HRC) index in real-time throughout the neonatal intensive care unit (NICU) hospitalization, alone or combined with birth demographics and clinical characteristics, can predict a composite outcome of death or neurodevelopmental impairment (NDI). STUDY DESIGN: We performed a retrospective analysis using data from extremely low birth weight infants who were monitored for HRC during neonatal intensive care. Surviving infants were assessed for NDI at 18-22 months of age. Multivariable predictive modeling of subsequent death or NDI using logistic regression, cross-validation with repeats, and step-wise feature elimination was performed each postnatal day through day 60. RESULTS: Among the 598 study participants, infants with the composite outcome of death or moderate-to-severe NDI had higher mean HRC scores during their stay in the NICU (3.1 ± 1.8 vs 1.3 ± 0.8; P < .001). Predictive models for subsequent death or NDI were consistently higher when the cumulative mean HRC score was included as a predictor variable. A parsimonious model including birth weight, sex, ventilatory status, and cumulative mean HRC score had a cross-validated receiver-operator characteristic curve as high as 0.84 on days 4, 5, 6, and 8 and as low as 0.78 on days 50-52 and 56-58 to predict subsequent death or NDI. CONCLUSIONS: In extremely low birth weight infants, higher mean HRC scores throughout their stay in the NICU were associated with a higher risk of the composite outcome of death or NDI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00307333.

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study.

The threshold to initiate empiric antibiotics for suspicion of early-onset sepsis (EOS) is low in preterm infants. Antibiotics' effects on short-term outcomes have recently been debated. We aimed at exploring the extent of early empiric antibiotic exposure (EEAE) in preterm infants and the association between the duration of EEAE with necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) within different EEAE groups. EEAE practice for suspicion of EOS was evaluated in all included infants (gestational age < 30 weeks) born in 9 centers in the Netherlands and Belgium between Oct. 2014 and Jan. 2019. EEAE association with NEC and LOS development was analyzed by multivariate regression. After excluding 56 EOS cases, 1259 infants were included. A total of 1122 infants (89.1%) were exposed to empirical antibiotics for the suspicion of EOS of whom 802 (63.7%) had short (≤ 72 h) and 320 (25.4%) prolonged EEAE (> 72 h). Infants with EEAE ≤ 72 h had a lower incidence of NEC compared to both infants without EEAE (adjusted odds ratio (aOR) 0.39; 95% confidence interval (CI) [0.19-0.80]; p = 0.01) and with prolonged EEAE (> 72 h) (aOR [95%CI]: 0.58 [0.35-0.96]; p = 0.03). With every additional day of EEAE, LOS incidence decreased (aOR [95%CI]: 0.90 [0.85-0.97]; p = 0.003). CONCLUSION: Almost 90% of preterm infants who have negative blood culture results in the first 72 h of life are exposed to EEAE under suspicion of EOS. One-fourth has prolonged EEAE. Duration of EEAE was differently associated with NEC and LOS incidence. The effects of antibiotics, and potentially induced microbial dysbiosis related to development of NEC and LOS, should further be explored. WHAT IS KNOWN: • Preterm infants often receive antibiotics empirically directly after birth for suspicion of early-onset sepsis. • The effects of the duration of early empirical antibiotic exposure on the risk for necrotizing enterocolitis and late-onset sepsis are debated. WHAT IS NEW: • Almost 90% of preterm infants with a gestational age below 30 weeks are exposed to antibiotics empirically after birth despite negative culture results. In a quarter of these culture-negative infants, empirical antibiotics are prolonged. • A short course of empirical antibiotics (≤72h) is associated with decreased odds for necrotizing enterocolitis compared to both prolonged (>72h) or no empirical antibiotics after birth. Furthermore, every additional day of empirical antibiotic exposure is associated with decreased risk for late-onset sepsis in the first month of life.

COVID-19 pandemic in the neonatal intensive care unit: any effect on late-onset sepsis and necrotizing enterocolitis?

The study was aimed at describing potential indirect effects of pandemic-related measures on very-low-birthweight infants in four Italian NICUs. No overall change in late-onset sepsis (LOS) and necrotizing enterocolitis was documented. However, in the NICU where baseline LOS rate was high, a significant reduction in LOS incidence was recorded. Conclusion: COVID-19-related implementation of NICU hygiene policies is likely to reduce the occurrence of LOS in high-risk settings. What is Known: • COVID-19 pandemic has disrupted routine care in Neonatal Intensive Care Units (NICUs), mostly by tightening infection control measures and restricting parental presence in the NICU. • Beyond the described psychological impact of COVID-19 related measures on healthcare workers and NICU families, their consequences in terms of preterm infants' clinical outcomes have not been described in detail yet. What is New: • Strengthened infection-control measures do not seem to have an overall influence on the incidence of necrotising enterocolitis and late-onset sepsis in very-low-birth-weight infants. • However, the implementation of these measures appears to reduce the occurrence of late-onset sepsis in settings where the baseline incidence of the disease is high.

Neonatal Sequential Organ Failure Assessment as a late-onset sepsis mortality predictor in very low birth weight newborns: a Brazilian cohort study.

Death is a frequent occurrence in late-onset neonatal sepsis (LOS). We aimed to evaluate if the Neonatal Sequential Organ Failure Assessment (nSOFA) is associated with mortality due to LOS in very low birth weight (VLBW) infants. This is a single-center Brazilian cohort study including VLBW infants admitted between 2006 and 2020 who were diagnosed with LOS caused by Staphylococcus aureus, Enterococcus sp or Gram-negative bacteria. The primary outcome was mortality associated with sepsis. Two groups of patients-survivors and non-survivors-were compared regarding descriptive maternal and neonatal variables and the nSOFA score, evaluated at nine moments, from 48 hours before the diagnosis of sepsis to 48 hours later (T-48, T-24, T-12, T-6, T0, T+6, T+12, T+24, T+48). Diagnostic accuracy was expressed as the area under the curve (AUC). Among the 1574 VLBW infants hospitalized in the period, 114 episodes of culture-confirmed LOS occurred. There were 21 sepsis-related deaths (18.4%), mostly from Gram-negative bacteria and Enterococcus sp. There were no statistically significant differences between the groups regarding maternal and neonatal variables. Median nSOFA was significantly higher in the non-survivor group at all time points (range 2 to 13 versus 1 to 3). In the logistic regression analysis, each increment of one point in the score significantly increases the risk of death in eight of the nine moments, but no difference was found in T-24. Time T-6 had the best accuracy (88.1%).   Conclusion: The nSOFA score was significantly associated with the risk of death from LOS in VLBW infants. What is Known: • The neonatal sepsis may result in organ dysfunction and death, and it is important to find indicators that could identify this clinical progression. • The nSOFA score was proposed in 2020 to predict mortality from LOS, but since it is recent and still in the research phase, further studies are important to improve it before being widely used in clinical practice. What is New: • We showed a significative association between higher nSOFA scores and mortality. Our results corroborate the validity and the importance of the nSOFA score and highlight its high NPV.