scholarly journals cfDNA and DNases: New Biomarkers of Sepsis in Preterm Neonates—A Pilot Study

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 192
Author(s):  
Moritz Lenz ◽  
Thomas Maiberger ◽  
Lina Armbrust ◽  
Antonia Kiwit ◽  
Axel Von der Wense ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Dnase I ◽  
Sepsis Group ◽  
Preterm Neonates ◽  
Control Group ◽  
Suspected Sepsis ◽  
Epidemiological Characteristics

Introduction: An early and accurate diagnosis of early onset neonatal sepsis (EONS) and late onset neonatal sepsis (LONS) is essential to improve the outcome of this devastating conditions. Especially, preterm infants are at risk. Reliable biomarkers are rare, clinical decision-making depends on clinical appearance and multiple laboratory findings. Markers of NET formation and NET turnover might improve diagnostic precision. Aim of this study was to evaluate the diagnostic value of NETs in sepsis diagnosis in neonatal preterm infants. Methods: Plasma samples of neonatal preterm infants with suspected sepsis were collected. Blood samples were assayed for markers of NET formation and NET turnover: cfDNA, DNase1, nucleosome, NE, and H3Cit. All clinical findings, values of laboratory markers, and epidemiological characteristics were collected retrospectively. Two subpopulations were created to divide EONS from LONS. EMA sepsis criteria for neonatal sepsis were used to generate a sepsis group (EMA positive) and a control group (EMA negative). Results: A total of 31 preterm neonates with suspected sepsis were included. Out of these, nine patients met the criteria for sepsis according to EMA. Regarding early onset neonatal sepsis (3 EONS vs. 10 controls), cfDNA, DNase I, nucleosome, and CRP were elevated significantly. H3Cit and NE did not show any significant elevations. In the late onset sepsis collective (6 LONS vs. 12 controls), cfDNA, DNase I, and CRP differed significantly compared to control group.

scholarly journals Diagnostic value of urine soluble triggering receptor expressed on myeloid cells (sTREM-1) for late-onset neonatal sepsis in infected preterm neonates

2018 ◽  
Vol 46 (4) ◽  
pp. 1606-1616 ◽  
Author(s):  
Senem Alkan Ozdemir ◽  
Esra Arun Ozer ◽  
Ozkan Ilhan ◽  
Sumer Sutcuoglu ◽  
Mansur Tatlı
Keyword(s):  
Preterm Infants ◽  
Predictive Value ◽  
Late Onset ◽  
Fatal Outcome ◽  
Myeloid Cells ◽  
Diagnostic Value ◽  
Sepsis Group ◽  
Preterm Neonates ◽  
Delivery Mode ◽  
Suspected Sepsis

Objective Sepsis is a complex clinical condition caused by a dysregulated immune response to an infection resulting in a fatal outcome. This study aimed to investigate the value of urine soluble triggering receptor expressed on myeloid cells (sTREM-1) for diagnosing culture-proven sepsis in preterm infants. Methods Preterm neonates were evaluated for late-onset sepsis (LOS). Laboratory investigations were performed. Urine sTREM-1 samples and blood cultures were synchronously collected. Using blood culture results, preterm neonates were divided into the culture-proven group and suspected sepsis group. Results A total of preterm 62 infants were included in the study; 31 had culture-proven sepsis and 31 were suspected as having sepsis. There were no significant differences in gestational age, sex, birth weight, and delivery mode between the groups. Neonates in the culture-proven group had significantly higher urine sTREM-1 levels than did those in the suspected sepsis group. Using a cut-off point for a urine sTREM-1 level of 78.5 pg/mL, the sensitivity was 0.90, specificity was 0.78, positive predictive value was 0.68, and negative predictive value was 0.94. Conclusions The present study highlights the role of urine sTREM-1 levels in LOS. Urine sTREM-1 may be a reliable and sensitive marker in detecting sepsis in preterm infants.

Can Endocan Predict Late-Onset Neonatal Sepsis?

2018 ◽  
Vol 14 (03) ◽  
pp. 096-102 ◽  
Author(s):  
Cuneyt Tayman ◽  
Nilufer Okur ◽  
Utku Serkant ◽  
Ufuk Cakir ◽  
Halit Halil ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Neonatal Sepsis ◽  
Late Onset ◽  
Leukocyte Count ◽  
Clinical Findings ◽  
Sepsis Group ◽  
Suspected Sepsis ◽  
Sepsis Diagnosis ◽  
Reactive Protein ◽  
Significant Difference

Objective Endocan, a proteoglycan secreted by endothelial cells, plays a role in the pathogenesis of sepsis. Endocan is an effective diagnostic and prognostic biomarker of sepsis in adult patients. We evaluate the utility of endocan as a new biomarker in the recognition of late-onset neonatal sepsis (LOS) in preterm infants. Methods This study included preterm infants at gestational age ≤ 32 weeks diagnosed with LOS. Sepsis was diagnosed in the presence of three or more clinical findings plus significant elevation of C-reactive protein (CRP) or interleukin 6 (IL-6) levels. Blood samples were obtained to determine leukocyte count, CRP, IL-6, and endocan levels immediately after the sepsis diagnosis and on the 3rd and 7th day after diagnosis. Results A total of 102 preterm infants, 52 with LOS (21 proven, 31 suspected sepsis) and 50 controls, were included in the study. Mean leukocyte count, serum CRP, IL-6, and endocan levels were significantly higher in the LOS group compared with healthy controls (p < 0.001) at enrolment. Serial measurements showed no significant difference in CRP and IL-6 levels between the proven and suspected sepsis groups, while endocan levels were significantly higher at enrolment and on day 7 in the proven sepsis group (p = 0.003 and p = 0.01, respectively). The endocan levels of preterm infants who died were significantly higher at all time points (p < 0.001, p = 0.001, and p = 0.004, respectively). Conclusion Endocan is an effective, reliable, and promising new biomarker for detecting LOS in preterm infants.

scholarly journals Association of inflammatory biomarkers with subsequent clinical course in suspected late onset sepsis in preterm neonates

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Şerife Kurul ◽  
Sinno H. P. Simons ◽  
Christian R. B. Ramakers ◽  
Yolanda B. De Rijke ◽  
René F. Kornelisse ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Gestational Age ◽  
Neonatal Sepsis ◽  
Late Onset ◽  
Medical Center ◽  
Inotropic Support ◽  
Inflammatory Biomarkers ◽  
Preterm Neonates ◽  
Sepsis Severity ◽  
Suspected Sepsis

Abstract Background Sepsis is a major health issue in preterm infants. Biomarkers are used to diagnose and monitor patients with sepsis, but C-reactive protein (CRP) is proven not predictive at onset of late onset neonatal sepsis (LONS) diagnosis. The aim of this study was to evaluate the association of interleukin-6(IL-6), procalcitonin (PCT) and CRP with subsequent sepsis severity and mortality in preterm infants suspected of late onset neonatal sepsis. Methods The study was conducted at the Erasmus University Medical Center–Sophia Children’s Hospital Rotterdam. Patient data from January 2018 until October 2019 were reviewed for all preterm neonates born with a gestational age below 32 weeks with signs and symptoms suggestive of systemic infection, in whom blood was taken for blood culture and for inflammatory biomarkers determinations. Plasma IL-6 and PCT were assessed next to CRP at the moment of suspicion. We assessed the association with 7-day mortality and sepsis severity (neonatal sequential organ failure assessment (nSOFA) score, need for inotropic support, invasive ventilation and thrombocytopenia). Results A total of 480 suspected late onset neonatal sepsis episodes in 208 preterm neonates (gestational age < 32 weeks) were retrospectively analyzed, of which 143 episodes were classified as sepsis (29.8%), with 56 (11.7%) cases of culture negative, 63 (13.1%) cases of gram-positive and 24(5.0%) cases of gram-negative sepsis. A total of 24 (5.0%) sepsis episodes resulted in death within 7 days after suspicion of LONS. Both IL-6 (adjusted hazard ratio (aHR): 2.28; 95% CI 1.64–3.16; p < 0.001) and PCT (aHR: 2.91; 95% CI 1.70–5.00; p < 0.001) levels were associated with 7-day mortality; however, CRP levels were not significantly correlated with 7-day mortality (aHR: 1.16; 95% CI (0.68–2.00; p = 0.56). Log IL-6, log PCT and log CRP levels were all significantly correlated with the need for inotropic support. Conclusions Our findings show that serum IL-6 and PCT levels at moment of suspected late onset neonatal sepsis offer valuable information about sepsis severity and mortality risk in infants born below 32 weeks of gestation. The discriminative value was superior to that of CRP. Determining these biomarkers in suspected sepsis may help identify patients with imminent severe sepsis, who may require more intensive monitoring and therapy.

scholarly journals Value of Resistin in Early Onset Neonatal Sepsis

2017 ◽  
Vol 07 (01) ◽  
pp. e146-e150
Author(s):  
Abdurrahman Ozdemir ◽  
Yusuf Elgormus
Keyword(s):  
Neonatal Sepsis ◽  
Early Onset ◽  
Neonatal Intensive Care ◽  
Clinical Signs ◽  
Area Under The Curve ◽  
Scoring Systems ◽  
Diagnostic Value ◽  
Sepsis Group ◽  
Control Group ◽  
Reactive Protein

AbstractThe diagnosis of neonatal sepsis is usually difficult because the sign and symptoms are nonspecific. Although C-reactive protein (CRP) and procalcitonin (PCT) are the most commonly used auxiliary tests, they are not reliable enough markers to be used for diagnosis of neonatal sepsis. This study aimed to evaluate the efficacy of resistin in diagnosing early onset neonatal sepsis and to compare its effectiveness to CRP and PCT. This prospective study was performed in the neonatal intensive care unit of Medicine Hospital between June and September 2016. Twenty-nine infants in the sepsis group and 33 infants in the control group were recruited. The Töllner scoring system was used for clinical signs. The hematologic parameters were evaluated using the Manroe and Rodwell scoring systems. The blood samples for CRP, PCT, and resistin were collected at admission (T0), and at 72 hours (T3). Mean plasma resistin level at T0 was 54.20 ± 39.3 ng/mL in the sepsis group and 34.92 ± 6.9 ng/mL in the control group. The sensitivity at T0 for resistin was 76%, and the specificity was 67%. The values of area under the curve (AUC) for CRP, PCT, and resistin were 0.84, 0.66, and 0.72, respectively. We found the diagnostic value of resistin to be lower than CRP, although its plasma levels were elevated. Therefore, we propose that resistin has limited value in diagnosis and follow-up of early-onset neonatal sepsis.

scholarly journals Early-Onset Neonatal Sepsis

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Marija Jovicic ◽  
Marko Folic ◽  
Slobodan Jankovic
Keyword(s):  
Neonatal Sepsis ◽  
Early Onset ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Pediatric Population ◽  
Consensus Conference ◽  
Antibiotic Administration ◽  
Perinatal Medicine ◽  
Suspected Sepsis ◽  
Early Onset Sepsis

Abstract Despite the great progress made in neonatal and perinatal medicine over the last couple of decades, sepsis remains one of the main causes of morbidity and mortality. Sepsis in pediatric population was defined at the Pediatric Sepsis Consensus Conference in 2005. There is still no consensus on the definition of neonatal sepsis. Neonatal sepsis is a sepsis that occurs in the neonatal period. According to the time of occurrence, neonatal sepsis can be of early onset, when it occurs within the first 72 hours of birth and results from vertical transmission, and of late onset, in which the source of infection is found most often in the environment and occurs after the third day of life. The most common causes of early-onset sepsis are Group B Streptococcus (GBS) and E. coli. Risk factors can be mother-related and newborn-related. Clinical symptoms and signs of sepsis are quite unspecific. The dysfunction of different organs may imitate sepsis. On the other hand, infectious and non-infectious factors may exist simultaneously. The start of the antimicrobial therapy in any newborn with suspected sepsis should not be delayed. Pentoxifylline may have potential benefits in preterm newborns with sepsis. The only proven intervention that has been shown to reduce the risk of early-onset neonatal sepsis is intrapartum intravenous antibiotic administration to prevent GBS infection. It is still a great challenge to discontinue antibiotic treatment in non-infected newborns as soon as possible, because any extended antibiotic use may later be associated with other pathological conditions.

scholarly journals Exploring the Role of Gut Bacteria in Health and Disease in Preterm Neonates

2020 ◽  
Vol 17 (19) ◽  
pp. 6963 ◽  
Author(s):  
Jimmy Kok-Foo Lee ◽  
Loh Teng Hern Tan ◽  
Amutha Ramadas ◽  
Nurul-Syakima Ab Mutalib ◽  
Learn-Han Lee
Keyword(s):  
Preterm Infants ◽  
Gestational Age ◽  
Neonatal Sepsis ◽  
Late Onset ◽  
Bacterial Colonization ◽  
Gut Bacteria ◽  
Preterm Neonates ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Microbial Invasion

The mortality rate of very preterm infants with birth weight <1500 g is as high as 15%. The survivors till discharge have a high incidence of significant morbidity, which includes necrotising enterocolitis (NEC), early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS). More than 25% of preterm births are associated with microbial invasion of amniotic cavity. The preterm gut microbiome subsequently undergoes an early disruption before achieving bacterial maturation. It is postulated that bacterial gut colonisation at birth and postnatal intestinal dysbacteriosis precede the development of NEC and LONS in very preterm infants. In fact, bacterial colonization patterns in preterm infants greatly differ from term infants due to maternal chorioamnionitis, gestational age, delivery method, feeding type, antibiotic exposure and the environment factor in neonatal intensive care unit (NICU). In this regard, this review provides an overview on the gut bacteria in preterm neonates’ meconium and stool. More than 50% of preterm meconium contains bacteria and the proportion increases with lower gestational age. Researchers revealed that the gut bacterial diversity is reduced in preterm infants at risk for LONS and NEC. Nevertheless, the association between gut dysbacteriosis and NEC is inconclusive with regards to relative bacteria abundance and between-sample beta diversity indices. With most studies show a disruption of the Proteobacteria and Firmicutes preceding the NEC. Hence, this review sheds light on whether gut bacteria at birth either alone or in combination with postnatal gut dysbacteriosis are associated with mortality and the morbidity of LONS and NEC in very preterm infants.

scholarly journals The Correlation of Antibacterial Peptides Concentration in Umbilical Cord Blood and Early-Onset Sepsis in Preterm Infants

2021 ◽  
Author(s):  
Jiayu Miao ◽  
Ying Liu ◽  
Zengqing Li ◽  
Zhuxiao Ren ◽  
Zhicheng Zhong ◽  
...  
Keyword(s):  
Cord Blood ◽  
Preterm Infants ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Early Onset ◽  
Sepsis Group ◽  
Control Group ◽  
Early Onset Sepsis ◽  
Prediction Probability

Abstract Background: The role of serum LL37 in systemic inflammation has been confirmed, and the influence of it in umbilical cord blood to early-onset sepsis in preterm infants is currently being investigated.Results: The level of LL37 of sepsis group was higher than those of in control group (362.13±46.71 vs 248.13±83.30 ng/ml), the levels of CRP, WBC and MPV in sepsis group were higher than those of in control group (6.25±4.19 vs 2.89±2.77 mg/L; 17.60±12.35 vs 8.24±3.55×109/L; 11.10±1.11 vs 8.93±0.68 fL), the level of PLT was lower than those of in control group (175.20±38.51 vs 245.75±49.85×109/L) (P < 0.05). The expression of LL37 was negatively correlated with PLT (r = -0.9347, P < 0.0001), and positively correlated with MPV ((r =0.9463 , P < 0.0001), the expression of PLT was negatively correlated with MPV (r = -0.9641, P < 0.0001). The area under curve of LL37 for diagnosis of early-onset sepsis was 0.875, the prediction probability was 0.7, the sensitivity was 90.0% and the specificity was 80.0%.Conclusions：The higher level of LL37 in umbilical cord blood was associated with the development of early-onset sepsis in preterm infants.

scholarly journals Clinical Profile of Neonatal Sepsis With Reference to Antibiotic Resistance

2018 ◽  
Vol 5 (1) ◽  
pp. 3460-3464
Author(s):  
Dr. Gargi Pathak ◽  
Dr. Anuya Chauhan ◽  
Dr. Sruthi Nair
Keyword(s):  
Antibiotic Resistance ◽  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Abdominal Distension ◽  
Preterm Neonates ◽  
Total Blood ◽  
Civil Hospital ◽  
Late Onset Sepsis ◽  
Early Onset Sepsis

Introduction : Neonatal sepsis continues to be a major cause of morbidity and mortality in neonates. It is 30 per 1000 live births in India. The prevalence is more in preterm neonates. Objectives To describe the clinical and bacteriological spectrum in early onset sepsis and late onset sepsis. To describe the antibiotic resistance profile of bacteria causing early and late onset sepsis. To compare the risk factors and bacteriological spectrum in early onset and late onset sepsis. Setting:  NICU of civil hospital Ahmedabad Study period: June 2016 to December 2016 Design: retrospective cohort study Methods:  all neonate admitted in NICU of civil hospital Ahmedabad during the abovementioned period were assessed. Inclusion criteria: presence of one or more of established clinical features like , (fever/hypothermia, poor feeding, poor activity, respiratory distress/apneic spells, hepatospleenomegaly, vomitting, abdominal distension, seizures, signs of either respiratory or circulatory dysfunction evidenced by tachycardia/bradycardia, capillary refill time>3 seconds,, respiratory rate>60/minute, chest indrawing and/or grunting)along with >_2 of the following laboratory criteria(total blood leukocyte count<5000 or>15000, absolute neutrophil count(ANC)<500 cells/mm3or >1500 cells/mm3,C reactive protein (CRP)>0.6microgram/ml, positive blood culture). Information assessed in a proforma. Cases were divided into early onset sepsis(EOS) (presenting in the first 72 hours) and late onset sepsis(LOS) (presenting after 72 hours). All cases were started on antibiotics and upgraded or stopped based on culture and sensitivity. Cases were followed to discharge/death.

NEONATAL SEPSIS AND IDENTIFICATION OF RISK FACTORS: STUDY IN AVBRH HOSPITAL SAWANGI

2019 ◽  
Vol 3 (6) ◽  
Author(s):  
Pramod P. Singhavi
Keyword(s):  
Risk Factors ◽  
Neonatal Sepsis ◽  
Early Onset ◽  
Late Onset ◽  
Signs And Symptoms ◽  
Premature Rupture ◽  
Maternal Risk ◽  
Late Onset Sepsis ◽  
Early Onset Sepsis ◽  
Meconium Stained Amniotic Fluid

Introduction: India has the highest incidence of clinical sepsis i.e.17,000/ 1,00,000 live births. In Neonatal sepsis septicaemia, pneumonia, meningitis, osteomyelitis, arthritis and urinary tract infections can be included. Mortality in the neonatal period each year account for 41% (3.6 million) of all deaths in children under 5 years and most of these deaths occur in low income countries and about one million of these deaths are due to infectious causes including neonatal sepsis, meningitis, and pneumonia. In early onset neonatal sepsis (EOS) Clinical features are non-specific and are inefficient for identifying neonates with early-onset sepsis. Culture results take up to 48 hours and may give false-positive or low-yield results because of the antenatal antibiotic exposure. Reviews of risk factors has been used globally to guide the development of management guidelines for neonatal sepsis, and it is similarly recommended that such evidence be used to inform guideline development for management of neonatal sepsis. Material and Methods: This study was carried out using institution based cross section study . The total number neonates admitted in the hospital in given study period was 644, of which 234 were diagnosed for neonatal sepsis by the treating pediatrician based on the signs and symptoms during admission. The data was collected: Sociodemographic characteristics; maternal information; and neonatal information for neonatal sepsis like neonatal age on admission, sex, gestational age, birth weight, crying immediately at birth, and resuscitation at birth. Results: Out of 644 neonates admitted 234 (36.34%) were diagnosed for neonatal sepsis by the paediatrician based on the signs and symptoms during admission. Of the 234 neonates, 189 (80.77%) infants were in the age range of 0 to 7 days (Early onset sepsis) while 45 (19.23%) were aged between 8 and 28 days (Late onset sepsis). Male to female ratio in our study was 53.8% and 46% respectively. Out of total 126 male neonates 91(72.2%) were having early onset sepsis while 35 (27.8%) were late onset type. Out of total 108 female neonates 89(82.4%) were having early onset sepsis while 19 (17.6%) were late onset type. Maternal risk factors were identified in 103(57.2%) of early onset sepsis cases while in late onset sepsis cases were 11(20.4%). Foul smelling liquor in early onset sepsis and in late onset sepsis was 10(5.56%) and 2 (3.70%) respectively. In early onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 21(11.67%), 19 (10.56%), 20(11.11%) and 33 (18.33%) cases respectively. In late onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 2 (3.70%), 1(1.85%), 3 (5.56%) and 3 (5.56%) cases respectively. Conclusion: Maternal risk identification may help in the early identification and empirical antibiotic treatment in neonatal sepsis and thus mortality and morbidity can be reduced.

Diagnostic value of assessment of Serum Cortisol, Hepcidin and Thyroid Hormone Levels in Neonates with Late Onset Sepsis

2020 ◽  
Vol 20 ◽  
Author(s):  
Adel Hagag ◽  
Mohamed S Elfarargy ◽  
Reham Lyonis ◽  
Ghada M Al-Ashmawy
Keyword(s):  
Thyroid Hormones ◽  
Antibiotic Therapy ◽  
Neonatal Sepsis ◽  
Late Onset ◽  
Serum Cortisol ◽  
Control Group ◽  
Serum Free ◽  
Group I ◽  
Late Onset Sepsis ◽  
Serum Hepcidin

Background: Neonatal sepsis is a clinical syndrome characterized by symptoms and signs of infection in the first twenty eight days of life. Serum thyroid, cortisol and hepcidin are affected by neonatal sepsis. Aim of the work: The aim of this study was to assess the predictive value of serum thyroid hormones including free triiodothyronine (free TT3) and free tetraiodothyronine (free TT4), serum cortisol and hepcidin levels through comparison of their concentrations between normal neonates and neonates with high probable late onset sepsis. Patients and Methods: This case control study was carried out on 40 neonates with suspected high probable late onset neonatal sepsis based on clinical and laboratory finding who were admitted to NICU of Pediatric Department, Tanta University, Egypt in the period from April 2017 to May 2019 (group I) and 40 healthy neonates matched in age and sex as a control group (group II). For patients and controls; blood culture, highly sensitive C‑reactive protein (H-s CRP), serum hepcidin, serum cortisol and thyroid hormones levels including free TT3 and free TT4 were assessed. Results: There were no significant differences between studied groups as regard weight, gestational age, sex and mode of delivery. H-s CRP, serum cortisol and hepcidin were significantly higher in group I than group II while serum free TT3 and free TT4 were significantly lower in group I compared with controls. There was significantly lower H-s CRP, serum hepcidin and cortisol and significantly higher serum free TT3 and free TT4 in group I after antibiotic therapy compared to the same group before treatment while there were no significant differences between group I after antibiotic therapy and control group as regard the same parameters. There were significant positive correlation between H-s CRP and serum hepcidin and cortisol in group I while there was significant negative correlation between H-s CRP and free TT3 and free TT4. ROC curve of specificity and sensitivity of H-s CRP, serum hepcidin, cortisol, free TT3 and free TT4 in prediction of neonatal sepsis shows that serum hepcidin had the highest sensitivity and specificity with 95% and 90% respectively followed by serum cortisol, H-s CRP, free TT3 and lastly free TT4. Conclusion and recommendations: Neonates with high probable sepsis had significantly higher serum cortisol and hepcidin and significantly lower free TT3 and free TT4 compared with healthy neonates. These findings may arouse our attention about the use of these markers in diagnosis of in neonatal sepsis which can lead to early treatment and subsequently better prognosis.

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