MiRNAs as biomarkers for diagnosis of neonatal sepsis: a systematic review and meta-analysis.

BACKGROUND: The relationship between circulating miRNAs and neonatal sepsis and the mechanism of action are still unclear at this time. Therefore, the potential diagnostic role of miRNAs in neonatal sepsis (NS) was studied through meta-analysis. METHOD: Web of Science, Cochrane Library, PubMed, and Embase are retrieved, supplemented by manual search, and the search was conducted to find related studies without time limit until May 2022.The quality of the literature was assessed via QUADAS criteria and meta-analyzed via Stata 11.0 software, including the assessment of specificity, sensitivity, likelihood ratio and diagnostic odds ratio. Then, sensitivity analysis and heterogeneity testing were conducted, and finally, the summary receiver operating characteristics (SROC) curve was drawn. RESULT: This study included 14 articles, including 20 miRNAs and 1597 newborns(control group: 727 and case group: 870). Among them, one article was of low quality, three articles were of high quality, and the rest were of medium quality. According to the results of random effects model analysis, the pooled specificity and sensitivity of miRNA for the diagnosis of NS were 0.83 (95%CI: 0.79-0.87) and 0.76 (95%CI: 0.72-0.80), respectively. And negative likelihood ratio, positive likelihood ratio, and diagnostic odds ratio were 0.29 (95%CI: 0.24-0.34), 4.51 (95%CI: 3.52-5.78), and 15.81 (95%CI: 10.71-23.35), respectively. The area under the SROC curve was 0.86, and there was no evidence publication bias detected in the funnel plot. CONCLUSION: Circulating miRNAs may be very useful in the development of early diagnostic strategies for neonatal sepsis.

The Multi-Component Causes of Late Neonatal Sepsis-Can We Regulate Them?

Elucidating the mechanisms of bacterial translocation is crucial for the prevention and treatment of neonatal sepsis. In the present study, we aimed to evaluate the potential of lactoferrin to inhibit the development of late-onset blood infection in neonates. Our investigation evaluates the role of key stress factors leading to the translocation of intestinal bacteria into the bloodstream and, consequently, the development of life-threatening sepsis. Three stress factors, namely weaning, intraperitoneal administration of Gram-positive cocci and oral intake of Gram-negative rods, were found to act synergistically. We developed a novel model of rat pups sepsis induced by bacterial translocation and observed the inhibition of this process by supplementation of various forms of lactoferrin: iron-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. Additionally, lactoferrin saturated with manganese significantly increases the Lactobacillus bacterial population, which contributes to the fortification of the intestinal barrier and inhibits the translocation phenomenon. The acquired knowledge can be used to limit the development of sepsis in newborns in hospital neonatal intensive care units.

Ten Versus 14 Days of Antibiotic Therapy in Culture-Proven Neonatal Sepsis: A Randomized, Controlled Trial.

OBJECTIVES: To compare the efficacy of 10 d versus 14 d of antibiotic therapy in neonates with culture-positive sepsis. METHODS: Neonates with culture-positive sepsis were randomized to either 10-d or 14-d antibiotic therapy. These neonates were followed up to 28 d after discharge for treatment failure. Primary outcome of the study was treatment failure which was defined as readmission to the NICU within 4 wk of discharge with blood culture growing same organism with similar antibiogram or any readmission with signs of sepsis with negative blood culture. RESULTS: A total of 70 neonates were randomized to receive either 10 d (n = 35) or 14 d (n = 35) of antibiotic therapy. Gram-negative infections were encountered in majority of the neonates. Treatment failure occurred in 1 neonate in 10-d group and none in 14-d group. The duration of hospital stay was significantly less in 10-d group as compared to 14-d group (16 d vs. 23 d, p  <  0.01). CONCLUSIONS: Ten days of antibiotics in neonates with culture-positive sepsis, who have achieved clinical and microbiologic remission at day 7, is noninferior to 14 d of therapy. Larger adequately powered trials will address this issue with certainty.

Zinc Supplementation in Preterm Neonates with Late-Onset Sepsis: Is It Beneficial?

OBJECTIVE: Neonatal sepsis (NS) is a serious neonatal disease. The aim of this study was to detect the role of zinc (Zn) supplementation in preterm neonates with late-onset sepsis (LOS). STUDY DESIGN: A prospective randomized clinical trial study which was done at Tanta University Hospital from August 2016 to March 2018 on 180 preterm neonates with LOS. The studied neonates were divided into two groups: group 1 (90 neonates), which received Zn and antibiotics, and group 2 (90 neonates), which received antibiotics and placebo. In group 1, the neonates received 1.4 mg elemental Zn/kg/d orally for 10 days. Sepsis score, C-reactive protein (CRP), and procalcitonin (PCT) were done for both groups. RESULTS: As regards sepsis score, it showed that before beginning the treatment, there were 85 and 84 neonates who had high probable sepsis (HPS) in intervention and control groups, respectively, and this revealed nonstatistically significant difference (non-SSD) between both groups (p-value is 0.756) and after 10 days of treatment, there were 1 and 4 neonates who had HPS in intervention and control group, respectively, and this revealed SSD between both groups (p-value is 0.045*). As regards CRP and PCT, the results showed that before beginning the treatment, the mean ± standard deviation (SD) of CRP and PCT were 39.4 ± 10.1 mg/L and 5.2 + 1.8 ng/mL, respectively, in intervention group, while it was 39.6 + 9.9 mg/L and 5.1 + 1.9 ng/mL, respectively, in control group and this revealed non-SSD between both groups (p-value is 0.893 and 0.717, respectively) and after 10 days of treatment, the mean ± SD of CRP and PCT were 5.3 ± 1.8 mg/L and 0.39 ± 0.13 ng/mL, respectively, in intervention group and 6.1 + 2 mg/L and 0.61 + 0.22 ng/mL, respectively, in control group and this revealed SSD between both groups (p-value is 0.008* and 0.044*, respectively). CONCLUSION: Zn supplementation in preterm neonates with LOS is beneficial in improving the clinical and laboratory finding. RECOMMENDATION: Zn supplementation for preterm neonates with LOS. KEY POINTS: · NS is a serious neonatal disease.. · Preterm neonates are more liable to infections.. · Zn supplementation in preterm neonates with LOS is beneficial in improving the condition..

Asociación entre la concentración de vitamina D y la sepsis neonatal extrahospitalaria de aparición tardía / Association between vitamin D level and community-acquired late-onset neonatal sepsis

Introducción. El objetivo fue determinar la relación entre la concentración materna e infantil de vitamina D y la sepsis de aparición tardía. Población y métodos. En este estudio se incluyó a los bebés nacidos con ≥ 37 semanas de gestación hospitalizados con diagnóstico de sepsis de aparición tardía. Se comparó la concentración de vitamina D de los niños y sus madres del grupo del estudio y del de referencia. Resultados. El grupo del estudio incluyó a 46 pacientes con sepsis de aparición tardía nacidos a término y el grupo de referencia, 46 pacientes con hiperbilirrubinemia. La suplementación con vitamina D durante el embarazo fue menor en las madres del grupo del estudio que en el de referencia (p = 0,001). La concentración sérica de 25-hidroxivitamina D [25(OH)D] de los niños y las madres del grupo del estudio fue significativamente menor que la del grupo de referencia (p < 0,001). Se observó una correlación positiva entre la 25(OH)D en las madres y los niños de ambos grupos (r: 0,38; p < 0,001). El valor de corte para la 25(OH)D, que determina el riesgo de sepsis neonatal de aparición tardía, se estableció en 15,45 ng/ml (sensibilidad: 91,3 %; especificidad: 71,7 %; área bajo la curva: 0,824; p < 0,001). Conclusiones. La concentración de 25(OH)D fue inferior en los bebés nacidos a término con sepsis de aparición tardía y sus madres en comparación con el grupo de referencia. La correlación entre la concentración sérica de 25(OH)D de los niños y sus madres fue positiva.

Introduction. The objective was to determine the relationship between mother and infant vitamin D levels and late onset sepsis. Population and methods.Infants born ≥37 weeks of gestational age who were hospitalized with the diagnosis of late-onset sepsis were enrolled to this prospective case control study. VitaminD levels of the infants and their mothers in the study and a control group were compared. Results. Fourty six term patients with lateonset sepsis composed the study group, 46 patients with hyperbilirubinemia as the control group. Vitamin D supplementation during pregnancy was lower in mothers of study group compared to the control group (p = 0.001). Serum 25-hydroxyvitamin D levels of infants and mothers in the study group were significantly lower than the control group (p < 0.001). There was a positive correlation between 25-hydroxyvitaminD levels of mothers and infants in both groups (r: 0.38, p < 0.001). The best cut off value of 25-hydroxyvitamin D, which determines the risk of late-onset sepsis in neonates, was detected as 15.45 ng/ml (sensitivity: 91.3 %, specificity: 71.7 %, area under the curve: 0.824, p < 0.001). Conclusions.In this study, 25-hydroxyvitaminD levels were found to be lower in term infants with late-onset sepsis and among their mothers compared to the control group. Positive correlation was found between serum 25(OH)D levels of infants and their mothers. Key words: newborn infant, sepsis,

Assessment of oxidative damage and enzymatic antioxidant system activity on the umbilical cord blood and saliva from preterm newborns with risk factors for early-onset neonatal sepsis.

BACKGROUND: To determine the concentration of the Lipid Peroxidation Marker: Malondialdehyde (MDA), and Antioxidant Markers: Superoxide Dismutase (SOD), Glutathione Peroxidase (GPX), Catalase (CAL) in umbilical cord blood and in unstimulated saliva in the first 24 and 48 hours of life in the PTNB of mothers with and without risk factors for early-onset neonatal sepsis. METHODS: Cross-sectional study with the signing of informed consent by the pregnant women and application of a standard questionnaire classifying the PTNB in Group 1 or 2. RESULTS: Twenty-one PTNB were studied. Regarding gender, birth weight, need for oxygen, use of phototherapy, diagnosis of assumed sepsis, presence of fetal distress, number of pregnancies, type of delivery, use of corticosteroids, premature rupture of membranes, maternal fever, chorioamnionitis, APGAR at the 5th and 10th minute of life. Statistical analysis was performed with the Mann-Whitney test (p = 0.019) on the GPX variable of umbilical cord blood in the group of mothers with risk factors for early-onset neonatal sepsis. There was no statistical difference in the MDA, SOD, and CAT variables of the group with risk factors and in any variable of the group without risk factors. CONCLUSION: There was an increase of the GPX concentration in the blood from the umbilical vein in the group with risk factors for early-onset neonatal sepsis. There was no statistical significance in the comparison of saliva and umbilical cord blood. There was no statistically significant difference in MDA, SOD, CAT.

Assessment of oxidative damage and enzymatic antioxidant system activity on the umbilical cord blood and saliva from preterm newborns with risk factors for early-onset neonatal sepsis

SUMMARY BACKGROUND: To determine the concentration of the Lipid Peroxidation Marker: Malondialdehyde (MDA), and Antioxidant Markers: Superoxide Dismutase (SOD), Glutathione Peroxidase (GPX), Catalase (CAL) in umbilical cord blood and in unstimulated saliva in the first 24 and 48 hours of life in the PTNB of mothers with and without risk factors for early-onset neonatal sepsis. METHODS: Cross-sectional study with the signing of informed consent by the pregnant women and application of a standard questionnaire classifying the PTNB in Group 1 or 2. RESULTS: Twenty-one PTNB were studied. Regarding gender, birth weight, need for oxygen, use of phototherapy, diagnosis of assumed sepsis, presence of fetal distress, number of pregnancies, type of delivery, use of corticosteroids, premature rupture of membranes, maternal fever, chorioamnionitis, APGAR at the 5th and 10th minute of life. Statistical analysis was performed with the Mann-Whitney test (p = 0.019) on the GPX variable of umbilical cord blood in the group of mothers with risk factors for early-onset neonatal sepsis. There was no statistical difference in the MDA, SOD, and CAT variables of the group with risk factors and in any variable of the group without risk factors. CONCLUSION: There was an increase of the GPX concentration in the blood from the umbilical vein in the group with risk factors for early-onset neonatal sepsis. There was no statistical significance in the comparison of saliva and umbilical cord blood. There was no statistically significant difference in MDA, SOD, CAT.

RESUMO OBJETIVOS: Determinar a concentração do marcador de peroxidação lipídica: Malondialdeído (MDA) e dos marcadores antioxidantes: Superóxido Dismutase (SOD), Glutationa Peroxidase (GPX), Catalase (CAL) no sangue do cordão umbilical e na saliva não estimulada nas primeiras 24 e 48 horas de vida nos RNPT de mães com e sem fatores de risco para sepse neonatal precoce. METODOLOGIA: Estudo transversal com a assinatura do termo de consentimento livre esclarecido pela gestante e aplicação de um questionário padrão classificando o RNPT no Grupo 1 ou 2. RESULTADOS: Foram estudados 21 RNPT. Quanto ao gênero, peso ao nascimento, necessidade de oxigênio, uso de fototerapia, diagnóstico de sepse presumida, presença de sofrimento fetal, número de gestações, tipo de parto, uso de corticoide, rotura prematura de membranas, a presença de febre materna, a presença de corioamnionite, Apgar no 50 e 100 minuto de vida, a análise estatística foi feita com o teste de Mann-Whitney (p=0,019) na váriável GPX do sangue do cordão umbilical no grupo das mães com fatores de risco para sepse neonatal precoce. Não houve diferença estatística nas outras variáveis MDA, SOD, CAT do grupo com fatores de risco e em nenhuma variável do grupo sem fatores de risco. CONCLUSÃO: O aumento de duas vezes a concentração da GPX no sangue da veia umbilical dos RNPT do grupo das mães com fatores de risco para sepse neonatal precoce. Sem significância estatística na comparação entre a saliva e o sangue do cordão umbilical. Não houve diferença estatisticamente significante nas variáveis MDA, SOD e CAT.

Re-exploring the value of surveillance cultures in predicting pathogens of late onset neonatal sepsis in a tertiary care hospital in southern Sri Lanka.

OBJECTIVE: To identify the validity of surveillance cultures in predicting causative organism(s) of late onset neonatal sepsis. RESULTS: Prospective analytical study was conducted from January to April 2011 at the Neonatal Intensive Care Unit, Teaching Hospital, Karapitiya, Galle, Sri Lanka. Fifty neonates were screened on admission and weekly thereafter for colonization with potential pathogens. On suspicion of infection, relevant samples were cultured and tested for antibiotic sensitivity. There were 55 episodes of clinically suspected infections including 33 nosocomial infections. One-third (17/55) of all clinically suspected infections were culture positive. Out of 55, only 33 episodes were clinically suspected nosocomial infections. Clinically suspected nosocomial infection rate was 50/1000 patient-days. Culture proven nosocomial infection rate was 13.61/1000 patient-days. Coliforms were the commonest clinical isolate (76%) and 2/3 of them produced extended spectrum ß lactamase. More than 80% of the isolates causing late onset sepsis were sensitive to carbapenems and aminoglycosides. Sensitivity, specificity, positive predictive value and negative predictive value of surveillance cultures were 77.8, 37.5, 31.8 and 81.8%, respectively. Surveillance samples can be used to predict pathogens of late-onset sepsis. Broad-spectrum antibiotics (carbapenems, aminoglycosides) are recommended as empirical therapy for late-onset neonatal sepsis.

A Quantitative, Risk-Based Approach to the Management of Neonatal Early-Onset Sepsis.

Importance: Current algorithms for management of neonatal early-onset sepsis (EOS) result in medical intervention for large numbers of uninfected infants. We developed multivariable prediction models for estimating the risk of EOS among late preterm and term infants based on objective data available at birth and the newborn's clinical status. Objectives: To examine the effect of neonatal EOS risk prediction models on sepsis evaluations and antibiotic use and assess their safety in a large integrated health care system. Design, Setting, and Participants: The study cohort includes 204 485 infants born at 35 weeks' gestation or later at a Kaiser Permanente Northern California hospital from January 1, 2010, through December 31, 2015. The study compared 3 periods when EOS management was based on (1) national recommended guidelines (baseline period [January 1, 2010, through November 31, 2012]), (2) multivariable estimates of sepsis risk at birth (learning period [December 1, 2012, through June 30, 2014]), and (3) the multivariable risk estimate combined with the infant's clinical condition in the first 24 hours after birth (EOS calculator period [July 1, 2014, through December 31, 2015]). Main Outcomes and Measures: The primary outcome was antibiotic administration in the first 24 hours. Secondary outcomes included blood culture use, antibiotic administration between 24 and 72 hours, clinical outcomes, and readmissions for EOS. Results: The study cohort included 204 485 infants born at 35 weeks' gestation or later: 95 343 in the baseline period (mean [SD] age, 39.4 [1.3] weeks; 46 651 male [51.0%]; 37 007 white, non-Hispanic [38.8%]), 52 881 in the learning period (mean [SD] age, 39.3 [1.3] weeks; 27 067 male [51.2%]; 20 175 white, non-Hispanic [38.2%]), and 56 261 in the EOS calculator period (mean [SD] age, 39.4 [1.3] weeks; 28 575 male [50.8%]; 20 484 white, non-Hispanic [36.4%]). In a comparison of the baseline period with the EOS calculator period, blood culture use decreased from 14.5% to 4.9% (adjusted difference, -7.7%; 95% CI, -13.1% to -2.4%). Empirical antibiotic administration in the first 24 hours decreased from 5.0% to 2.6% (adjusted difference, -1.8; 95% CI, -2.4% to -1.3%). No increase in antibiotic use occurred between 24 and 72 hours after birth; use decreased from 0.5% to 0.4% (adjusted difference, 0.0%; 95% CI, -0.1% to 0.2%). The incidence of culture-confirmed EOS was similar during the 3 periods (0.03% in the baseline period, 0.03% in the learning period, and 0.02% in the EOS calculator period). Readmissions for EOS (within 7 days of birth) were rare in all periods (5.2 per 100 000 births in the baseline period, 1.9 per 100 000 births in the learning period, and 5.3 per 100 000 births in the EOS calculator period) and did not differ statistically (P = .70). Incidence of adverse clinical outcomes, including need for inotropes, mechanical ventilation, meningitis, and death, was unchanged after introduction of the EOS calculator. Conclusions and Relevance: Clinical care algorithms based on individual infant estimates of EOS risk derived from a multivariable risk prediction model reduced the proportion of newborns undergoing laboratory testing and receiving empirical antibiotic treatment without apparent adverse effects.

Syndrome Evaluation System (SES) versus Blood Culture (BACTEC) in the Diagnosis and Management of Neonatal Sepsis--A Randomized Controlled Trial.

OBJECTIVE: To compare the clinical outcome of a multiplex polymerase chain reaction (PCR) based molecular diagnostic method -- Syndrome Evaluation System (SES) directed treatment strategy vs. standard of care (blood culture) directed treatment strategy for neonatal sepsis. METHODS: This randomized controlled trial (RCT) included 385 neonates with sepsis who were randomized into two groups -- SES and control (BACTEC). Both tests were performed for all the neonates. However, in the SES group, the results of SES test were revealed to the treating clinicians, while in the control group, SES results were withheld. Two ml of blood was drawn from each baby. One aliquot was sent for blood culture, whereas the remaining aliquot was sent for SES. Babies were then administered empirical IV antibiotics and given supportive care. Further antibiotic changes, if required were done in SES and control groups based on their respective reports. The microbiological profile, immediate outcome, duration of hospital stay, number of antibiotics used and readmission within a month in both groups were compared. RESULTS: SES was better than BACTEC in identifying the causative organism in both the groups (68 % vs. 18 % in SES group and 72 % vs. 18 % in control group). SES had 100 % concordance with blood culture by BACTEC. Detection of bacteria and fungi were four and ten-fold higher respectively with SES when compared to BACTEC culture. Microbiological diagnosis was rapid with SES compared to BACTEC (7 h vs. 72 h). Treatment based on SES resulted in significantly less mortality (3 % vs. 18 %). Readmission rate, duration of hospital stay and change in antibiotics were also significantly less in SES group. CONCLUSIONS: This new molecular based diagnostic system (SES) helps in rapid and accurate diagnosis of neonatal sepsis and reduces mortality and morbidity in affected neonates.