Clinical Early-onset Neonatal Sepsis Research Articles

Potential of Molecular Culture in Early Onset Neonatal Sepsis Diagnosis: A Proof of Principle Study.

Delay in the time-to-positivity of a peripheral blood culture (PBC), the gold standard for early onset neonatal sepsis (EOS) diagnosis, has resulted in excessive use of antibiotics. In this study, we evaluate the potential of the rapid Molecular Culture (MC) assay for quick EOS diagnosis. In the first part of this study, known positive and spiked blood samples were used to assess the performance of MC. In the in vivo clinical study, the second part of this study, all infants receiving antibiotics for suspicion of EOS were included. At initial EOS suspicion, a blood sample was collected for PBC and MC. MC was able to detect bacteria present in the spiked samples even when the bacterial load was low. In the clinical study, MC was positive in one infant with clinical EOS (Enterococcus faecalis) that was not detected by PBC. Additionally, MC was positive in two infants without clinical sepsis (Streptococcus mitis and multiple species), referred to as contamination. The other 37 samples were negative both by MC and PBC. MC seems to be able to detect bacteria even when the bacterial load is low. The majority of MC and PBC results were comparable and the risk for contamination and false positive MC results seems to be limited. Since MC can generate results within 4 h following sampling compared with 36-72 h in PBC, MC may have the potential to replace conventional PBC in EOS diagnostics in order to guide clinicians on when to discontinue antibiotic therapy several hours after birth.

Can Presepsin Be Valuable in Reducing Unnecessary Antibiotic Exposure after Birth?

Due to a lack of rapid, accurate diagnostic tools for early-onset neonatal sepsis (EOS) at the initial suspicion, infants are often unnecessarily given antibiotics directly after birth. We aimed to determine the diagnostic accuracy of presepsin for EOS before antibiotic initiation and to investigate whether presepsin can be used to guide clinicians' decisions on whether to start antibiotics. In this multicenter prospective observational cohort study, all infants who started on antibiotics for EOS suspicion were consecutively included. Presepsin concentrations were determined in blood samples collected at the initial EOS suspicion (t = 0). In addition to this, samples were collected at 3, 6, 12 and 24 h after the initial EOS suspicion and from the umbilical cord directly after birth. The diagnostic accuracy of presepsin was calculated. A total of 333 infants were included, of whom 169 were born preterm. We included 65 term and 15 preterm EOS cases. At the initial EOS suspicion, the area under the curve (AUC) was 0.60 (95% confidence interval (CI) 0.50-0.70) in the term-born infants compared to 0.84 (95% CI 0.73-0.95) in the preterm infants. A cut-off value of 645 pg/mL resulted in a sensitivity of 100% and a specificity of 54% in the preterm infants. The presepsin concentrations in cord blood and at other time points did not differ significantly from the concentrations at the initial EOS suspicion. Presepsin is a biomarker with an acceptable diagnostic accuracy for EOS (culture-proven and clinical EOS) in preterm infants and might be of value in reducing antibiotic exposure after birth when appended to current EOS guidelines. However, the small number of EOS cases prevents us from drawing firm conclusions. Further research should be performed to evaluate whether appending a presepsin-guided step to current EOS guidelines leads to a safe decrease in antibiotic overtreatment and antibiotic-related morbidity.

COVID-19 Infection in Parturients: Comparative Neonatal and Maternal Outcomes in a Single-Institute Regional Hospital in Thailand

Objective: Chonburi province is ranked fourth in Thailand in terms of COVID-19 cases. The objective was to compare neonatal and maternal outcomes among pregnant women with and without COVID-19 infection delivered in Chonburi hospital. Materials and Methods: The present study was a retrospective matched cohort study that included all pregnant women who delivered between January 1 and August 31, 2021, at Chonburi Hospital, Thailand. The exposure group comprised women with a current or previous positive COVID-19 PCR test, while the comparators were the PCR negative group. The matching ratio was 1:4, based on gestational and maternal age, parity, and the closest delivery date. Clinical data were obtained from medical records. Results: Forty-six pregnant women had a positive COVID-19 PCR, 24 (52.17%) were Thai and 22 (47.83%) were of other ethnicities. Most (60.87%) were asymptomatic or required no medical assistance. Three (6.52%) had severe pneumonia and required respiratory support. Neither maternal death nor vertical transmission was detected. Compared with 184 COVID-19-negative pregnant women, no significant differences in low APGAR score of less than 7, and preeclampsia in the 46 COVID-19-positive pregnant women were observed. However, COVID-19-positive pregnant women showed an increased rate of neonatal respiratory distress (RD) (relative risk [RR] 2.55; 95% confidence interval [CI] 1.04 to 6.21] and clinical early-onset neonatal sepsis (RR 3.60; 1.55 to 8.36). Additionally, a higher cesarean section rate was observed in the COVID-19 positive group (RR 1.45, 1.11 to 1.85). Conclusion: There were no significant differences in neonates with APGAR of less than 7 between the cohort of 46 pregnant women who tested positive for COVID-19 and those who tested negative. However, a higher rate of cesarean delivery, presumed early-onset neonatal septicemia, and RD in the COVID-19 positive group were noted and should be monitored. Keywords: COVID-19; Pregnancy; Neonatal outcome; Birth asphyxia

Meconium microbiota predicts clinical early-onset neonatal sepsis in preterm neonates

Background Early-onset neonatal sepsis (EONS) remains one of the leading causes of morbidity and mortality related to premature birth, and its diagnosis remains difficult. Our goal was to evaluate the intestinal microbiota of the first meconium of preterm newborns and ascertain whether it is associated with clinical EONS. Methods In a controlled, prospective cohort study, samples of the first meconium of premature infants with a gestational age (GA) ≤32 weeks was obtained at Hospital de Clínicas de Porto Alegre and DNA was isolated from the samples. 16S rDNA based microbiota composition of preterm infants with a clinical diagnosis of EONS was compared to that of a control group. Results 40 (48%) premature infants with clinical diagnosis of EONS and 44 (52%) without EONS were included in the analysis. The most abundant phylum detected in both groups, Proteobacteria, was more prevalent in the sepsis group (p = .034). 14% of variance among bacterial communities (p = .001) correlated with EONS. The genera most strongly associated with EONS were Paenibacillus, Caulobacter, Dialister, Akkermansia, Phenylobacterium, Propionibacterium, Ruminococcus, Bradyrhizobium, and Alloprevotella. A single genus, Flavobacterium, was most strongly associated with the control group. Conclusion These findings suggest that the first-meconium microbiota is different in preterm neonates with and without clinical EONS.

Serum zinc level and prognosis of neonatal sepsis

Background The prognosis of neonatal sepsis can be influenced by various risk factors, one of which is a deficiency of zinc micronutrient substances.
 Objective To assess for a potential association between serum zinc level and prognosis of infants with early-onset neonatal sepsis (EONS).
 Methods This prospective cohort study was done in neonates with clinical EONS from September 2017 until December 2018. Serum zinc level was measured on the first day of diagnosis and prognosis was assessed on the fourth day. The association between serum zinc levels and prognosis of EONS was analyzed by Chi-square test and logistic regression with adjustment for confounding variables.
 Results A total of 70 subjects were divided into two groups based on their serum zinc levels. A cut-off point of 75 ug/dL was used based on area under the curve (sensitivity 91.2% and specificity 93.7%), with accuracy 97.8% (95%CI 0.943 to 1.000; P=0.0001). Subjects with lowzinc level had a 16.8 times greater risk compared to subjects with high serum zinc (RR=16.81; 95% CI 4.35 to 65.02; P <0.0001). Multivariate analysis revealed that subjects with low serum zinc levels had 203.7 times greater risk of worsening than subjects who had a higher serum zinc level (RR 203.72; 95% CI 26.79 to 1549.17; P <0.0001). Covariates such as male sex, low gestational age (<37 weeks), low birth weight (<2,500 grams), asphyxia, Caesarean section delivery, and the presence of comorbidities did not have significant associations with outcomes of EONS (P >0.05).
 Conclusion Serum zinc level is associated with prognosis of early onset neonatal sepsis, with a cut-off of 75 μg/dL. The high level of serum zinc associates with a better prognosis.

Serum zinc level and prognosis of neonatal sepsis

Background The prognosis of neonatal sepsis can be influenced by various risk factors, one of which is a deficiency of zinc micronutrient substances.
 Objective To assess for a potential association between serum zinc level and prognosis of infants with early-onset neonatal sepsis (EONS).
 Methods This prospective cohort study was done in neonates with clinical EONS from September 2017 until December 2018. Serum zinc level was measured on the first day of diagnosis and prognosis was assessed on the fourth day. The association between serum zinc levels and prognosis of EONS was analyzed by Chi-square test and logistic regression with adjustment for confounding variables.
 Results A total of 70 subjects were divided into two groups based on their serum zinc levels. A cut-off point of 75 ug/dL was used based on area under the curve (sensitivity 91.2% and specificity 93.7%), with accuracy 97.8% (95%CI 0.943 to 1.000; P=0.0001). Subjects with lowzinc level had a 16.8 times greater risk compared to subjects with high serum zinc (RR=16.81; 95% CI 4.35 to 65.02; P <0.0001). Multivariate analysis revealed that subjects with low serum zinc levels had 203.7 times greater risk of worsening than subjects who had a higher serum zinc level (RR 203.72; 95% CI 26.79 to 1549.17; P <0.0001). Covariates such as male sex, low gestational age (<37 weeks), low birth weight (<2,500 grams), asphyxia, Caesarean section delivery, and the presence of comorbidities did not have significant associations with outcomes of EONS (P >0.05).
 Conclusion Serum zinc level is associated with prognosis of early onset neonatal sepsis, with a cut-off of 75 μg/dL. The high level of serum zinc associates with a better prognosis.

Association between Tumor Necrosis Factor-α Promoter -308 G/A Polymorphism and Early Onset Sepsis in Preterm Infants.

Early-onset neonatal sepsis (EOS) is diagnosed during the first 7 days of neonatal life and is the major cause of morbidity and mortality among preterm infants. Genetic predisposition may have an impact on EOS susceptibility and outcome. The aim of our study was to explore the association between TNF-α -308 G/A or IL-6 -174 G/C gene polymorphism and the susceptibility and outcome of EOS in preterm infants. The study included 471 preterm infants: 282 with EOS (151 with culture proven sepsis and 131 with clinical sepsis) and 189 without infection (control group). TNF-α -308 G/A and IL-6 -174 G/C were genotyped using Real-time RCR method. We observed significantly higher frequency of A allele of TNF-α -308 G/A polymorphism in blood culture proven EOS (p = 0.017) or clinical EOS (p = 0.025) compared with the control group. Logistic regression confirmed significant association between TNF-α -308 GA+AA genotypes and development of culture proven EOS (B = -0.718, p = 0.013) or clinical EOS (B = -0.602, p = 0.027). No significant differences in IL6 -174G/C alleles or genotypes distribution have been observed between culture proven EOS group, clinical EOS group and the control group. An association between TNF-α -308 G/A or IL-6 -174 G/C genotypes and EOS lethal outcome was not observed (p = 0.652 and p = 0.384, respectively). According to our analysis of large cohort of preterm infants with clearly defined EOS groups, the TNF-α -308 A allele may be a risk factor for the EOS occurrence.

TNF-α and Interleukin-6 Levels in Clinical Early Onset Neonatal Sepsis Toward Acute Liver Injury

TNF-α and IL-6 level have an important role in acute liver injury during early onset neonatal sepsis. This study aims to investigate the correlation of TNF-α and IL-6 levels in neonates with clinical early onset neonatal sepsis toward the occurrence of acute liver injury 44 neonates with clinical early onset neonatal sepsis based on SIRS criteria and Rodwell hematologic scored ≥3 were included in this study. Acute liver injury is defined as elevated of AST, ALT, or AST: ALT ratio <1. TNF-α and IL-6 levels were measured using ELISA methods. This study showed that TNF-α correlated significantly with AST level (p<0,001, r=0,570), ALT level (p<0,001, r=0,554), and AST: ALT ratio (p<0,001, r=0,652). This study also showed that IL-6 correlated significantly with AST level (p<0,001, r=0,523), ALT level (p<0,001, r=0,482), AST: ALT ratio (p<0,001, r=0,603). Regression test using backward methods showed that TNF-α influence acute liver injury (indicated by AST, ALT, and AST: ALT ratio) more than IL-6. We concluded that TNF-α and IL-6 level in clinical early onset neonatal sepsis correlated with acute liver injury, whereas early onset neonatal sepsis was correlated with acute liver injury.Keywords: Acute liver injury, clinical early neonatal sepsis, IL-6 level, TNF-α level