scholarly journals Validity of Serum And Urinary Hepcidin As Biomarkers of Late-Onset Sepsis of Premature Infants

Author(s):  
Hanan Sakr Sherbiny ◽  
Hanaa Mostafa ◽  
Mahmoud Abdel-el Halm ◽  
Amal El Shal ◽  
Naglaa Kamal ◽  
...  

Abstract Background: Sepsis remains one of the leading causes of neonatal morbidity and mortality particularly among premature infants. Blood culture is the “gold standard” for diagnosis of neonatal sepsis but is associated with several pitfalls. Adjunctive diagnostic tests, including biological markers should be used to aid in antibiotic -starting decision in presumed septic preemies until culture results are availableAim of the work: We aim to evaluate the validity of measuring serum hepcidin concentration as diagnostic biomarker for late-onset sepsis in preemies and to quantify its cut-off value that differentiate truly septic from non-septic symptomatic premature infants. In addition, to examine the correlation between serum hepcidin (Hep-S) and urinary hepcidin (Hep-U) and to find out if measuring Hep-U can be used as an alternative safe, non-invasive biomarker for late-onset sepsis diagnosis, without exposure to frequent phlebotomy and its risks.Patients and Methods: The current case-control study included seventy-three (73) cases of clinically and laboratory confirmed late-onset sepsis as "case group" and fifty (50) non-septic premature infants of comparable age and gender as "control group". All participants were evaluated as per unit protocol to rule out sepsis by complete blood count, CRP, blood, urine, CSF and other cultures as indicated, plus different radiologic modalities as needed. Acute serum and urinary hepcidin concentration were evaluated by ELISA for all participants at enrollment "acute sample". After one week of treatment, convalescent samples for serum and urine hepcidin were collected and compared with the acute samples.Results: Statistically significant higher concentration of both serum and urinary hepcidin were recorded among cases as compared with non-septic peers (t=44.2&p=0.0001, t=23.8 &p=0.0001 for serum and urine hepcidin respectively). Similarly, Significant reduction of hepcidin at different body fluids was recoded after one week of treatment as compared with acute samples (paired t =18.1&p=0.001, paired t =14.1&p=0.001 for serum and urine hepcidin respectively). Significant direct correlations were reported between acute serum hepcidin levels and CRP, urinary hepcidin, and total leucocyte count. While significant negative correlation was recorded with platelets count. AUC of serum hepcidin ROC is 0.93, A cut off value of ≥94.8ng/ml of S. hepcidin showed sensitivity (88%), specificity (94%), PPV (95%) and NPV (84%) respectively with accurately diagnosing 90.2% of presenting cases as septic or not. While urinary hepcidin showed slightly less discriminating ability with AUC of 0.87. At cut-off value of ≥ 264 ng/mg of urinary hepcidin/urinary creatinine showed sensitivity (85%), specificity (90%), PPV (92.5%) and NPV (81%) respectively with accurately diagnosing 84.5% of presenting cases as septic or not.Conclusions: Hepcidin concentration in different body fluid can function as promising accurate and rapid surrogate test, with blood culture, that guide empiric antibiotics –starting decision or withholding it safely until the culture results is ready in symptomatic presumed septic preemies. Urinary hepcidin has advantages over serum hepcidin as; it is non-invasive, no hazards of phlebotomy, and less variable throughout the day.

Author(s):  
Adel Hagag ◽  
Mohamed S Elfarargy ◽  
Reham Lyonis ◽  
Ghada M Al-Ashmawy

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.


Author(s):  
Janet Elizabeth Berrington ◽  
William McGuire ◽  
NIcholas David Embleton

Previous studies suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) may reduce late onset sepsis (LOS) and necrotising enterocolitis (NEC), but have been underpowered. The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the United Kingdom (UK), aimed to further address this issue with a well powered double blinded placebo controlled trial of >2200 preterm infants. ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. 316 (29%) of 1093 infants in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group with an adjusted risk ratio of 0·95 (95% CI 0·86–1·04; p=0· 233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungals in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in different trials. Further exploration is being undertaken in the UK NIHR funded Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials (MAGPIE) study, for which results should be available soon.


2015 ◽  
Vol 32 (2) ◽  
pp. 61-65
Author(s):  
Chiranjib Barua ◽  
Md Nurul Anwar ◽  
Md Shahidullah ◽  
Shahadat Hossain ◽  
Sharmila Barua ◽  
...  

Neonatal septicemia is a clinical syndrome of systemic illness accompanied by bacteremia occuring in the first 28 days of life. Neonatal septicemia is one of the major causes of neonatal death in developing countries. Early diagnosis and treatment can prevent neonatal mortality and morbidity. The present study includes: 1) usefulness of CRP (C-reactive protein), Total Leucocyte Count, Platelet Count and Blood Culture in early diagnosis of Neonatal Sepsis, 2) significance of serial CRP in diagnosis of neonatal sepsis. 3) the prognostic value of CRP in neonatal sepsis. This is a prospective study done in neonatal ward, Chittagong Medical College Hospital and carried out from January 2008 to January 2011. Sample size was 300. One hundred fifty neonates with suspected sepsis as cases and 150 healthy babies as control were enrolled in this study. Seventy two percent of cases neonates were preterm and low birth weight. Common risk factors for neonatal septicemia which were identified in this study; preterm (72%), low birth weight (72%), premature rupture membrane (60%), chorioamnionitis (26%) and maternal urinary tract infection (16%) . Out of 150 cases of suspected neonatal sepsis total 80.7%% had raised CRP, in initial sample 70.39% were CRP positive and in 2nd sample additional 9.31% case were CRP positive . In control group 91% were CRP negative. CRP was positive in 100% of culture proven sepsis. Sensitivity of CRP was 80.67% and specificity of CRP was 76.44%. Leucocytosis was observed in 7% of cases and leucopenia was found in 11% of cases. In 82 % cases leucocyte count was found normal. In control group, 95% had normal leucocyte count and 5% had leucocytosis but no leucopenia. Sensitivity of leucocyte count was 18% and specificity was 20.68%. Thrombocytopenia was found in 28% of case group. Out of 150 cases only 15.33% yielded growth of organisms in blood culture. Klebsiella was the most common pathogen isolated which was followed by E.coli and Strph. aureus. Sensitivity of blood culture was 15.33% and specificity was 100% Therefore serial CRP can be taken as alternative method for diagnosis of neonatal sepsis specially in developing countries where blood culture is not readily available.J Bangladesh Coll Phys Surg 2014; 32: 61-65


Author(s):  
Sagori Mukhopadhyay ◽  
Karen M Puopolo ◽  
Nellie I Hansen ◽  
Scott A Lorch ◽  
Sara B DeMauro ◽  
...  

ObjectiveDetermine risk of death or neurodevelopmental impairment (NDI) in infants with late-onset sepsis (LOS) versus late-onset, antibiotic-treated, blood culture-negative conditions (LOCNC).DesignRetrospective cohort study.Setting24 neonatal centres.PatientsInfants born 1/1/2006–31/12/2014, at 22–26 weeks gestation, with birth weight 401–1000 g and surviving >7 days were included. Infants with early-onset sepsis, necrotising enterocolitis, intestinal perforation or both LOS and LOCNC were excluded.ExposuresLOS and LOCNC were defined as antibiotic administration for ≥5 days with and without a positive blood/cerebrospinal fluid culture, respectively. Infants with these diagnoses were also compared with infants with neither condition.OutcomesDeath or NDI was assessed at 18–26 months corrected age follow-up. Modified Poisson regression models were used to estimate relative risks adjusting for covariates occurring ≤7 days of age.ResultsOf 7354 eligible infants, 3940 met inclusion criteria: 786 (20%) with LOS, 1601 (41%) with LOCNC and 1553 (39%) with neither. Infants with LOS had higher adjusted relative risk (95% CI) for death/NDI (1.14 (1.05 to 1.25)) and death before follow-up (1.71 (1.44 to 2.03)) than those with LOCNC. Among survivors, risk for NDI did not differ between the two groups (0.99 (0.86 to 1.13)) but was higher for LOCNC infants (1.17 (1.04 to 1.31)) compared with unaffected infants.ConclusionsInfants with LOS had higher risk of death, but not NDI, compared with infants with LOCNC. Surviving infants with LOCNC had higher risk of NDI compared with unaffected infants. Improving outcomes for infants with LOCNC requires study of the underlying conditions and the potential impact of antibiotic exposure.


PEDIATRICS ◽  
1987 ◽  
Vol 79 (4) ◽  
pp. 489-500 ◽  
Author(s):  
Dale L. Phelps ◽  
Arthur L. Rosenbaum ◽  
Sherwin J. lsenberg ◽  
Rosemary D. Leake ◽  
Frederick J. Dorey

To test the efficacy and safety of vitamin E in preventing retinopathy of prematurity, 287 infants with birth weights of less than 1.5 kg or gestational ages of less than 33 weeks were enrolled within 24 hours of birth in a randomized, double-masked trial of IV, followed by oral, placebo v tocopherol (adjusted to plasma levels of 3 to 3.5 mg/dL). In the 196 infants completing ophthalmic follow-up, tocopherol did not prevent retinopathy of prematurity of any stage (28% placebo treated v 26% tocopherol treated) or moderately severe retinopathy of prematurity (8% placebo treated v 11% tocopherol treated). Cicatricial sequelae were not significantly different (1/97 placebo treated v 3/99 tocopherol treated), with one placebo-treated infant and one tocopherol-treated infant having retinal detachments. Among all 232 infants examined, those treated with tocopherol had more retinal hemorrhage than placebo-treated infants (8/121 placebo treated v 16/111 tocopherol treated), and retinal hemorrhage correlated positively (P &lt; .01) with plasma levels of tocopherol after the first 2 weeks of age. Prospective monitoring of morbidity including late-onset sepsis, necrotizing enterocolitis, etc revealed no differences between groups except that grades 3 and 4 intraventricular hemorrhage occurred more frequently in infants weighing less than 1 kg at birth who had received tocopherol (14/42, 33%) v those who had received placebo (4/43, 9%) (P &lt; .02). Our data do not support the use of tocopherol for prophylaxis against retinopathy of prematurity in premature infants and suggest that IV tocopherol treatment starting on day 1 may increase the incidence of hemorrhagic complications of prematurity, particularly in infants with birth weights of less than 1 kg.


2021 ◽  
Author(s):  
Gabriele Varisco ◽  
Deedee Kommers ◽  
Xi Long ◽  
Zhuozhao Zhan ◽  
Marina M. Nano ◽  
...  

2019 ◽  
Vol 39 (3) ◽  
pp. 155-161
Author(s):  
Amit Kumar Das ◽  
Deepak Mishra ◽  
Nitu Kumari Jha ◽  
Rakesh Mishra ◽  
Soniya Jha

Introduction: Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or without accompanying bacteremia in the first month of life.  It is responsible for about 30-50% of the total neonatal deaths in developing countries.  Neonatal sepsis can be divided into two sub-types depending upon whether the onset of symptoms within the first 72 hours of life (Early Onset Neonatal Sepsis) or after 72 hours of life (Late Onset Neonatal Sepsis ).  Meningitis is an important complication of late onset neonatal sepsis. Method: This was hospital based prospective observational study conducted among the neonates admitted with diagnosis of late onset neonatal sepsis in Neonatal Intermediate Care Unit (NIMCU) and Neonatal Intensive Care Unit (NICU) of Kanti Children’s Hospital from July 2016 to June 2017. The objective of this study was to evaluate the importance of performing LP in neonates with LONS. Results: 16.8% neonates with late onset neonatal sepsis were found to have meningitis. Among the neonates with meningitis CRP was positive 57.2% and negative in 42.8 %.  Among the cases with abnormal CSF findings, blood culture was sterile in 85% cases and organism was isolated 15% cases. In 88.8% cases with positive blood culture, no meningitis was detected. Lumbar puncture was traumatic in 1 neonate (0.8%) in first attempt. Apart from this no other complication of performing lumbar puncture was noted. Conclusion: Lumbar puncture and CSF examination is mandatory in all cases with late-onset sepsis.


BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e023044 ◽  
Author(s):  
Andrew Martin ◽  
Alpana Ghadge ◽  
Paolo Manzoni ◽  
Kei Lui ◽  
Rebecca Brown ◽  
...  

IntroductionVery-low birthweight (VLBW, <1500 g) infants comprise about 1%–1.4% of all births in high-income countries. Every year, about 3000 VLBW babies in Australia and New Zealand receive intensive care. Many die or else survive with severe brain injury, retinopathy, late-onset sepsis or necrotising enterocolitis (NEC), each of which carries substantial risk of disability.Methods and analysisThis trial tests whether adding bovine lactoferrin (bLF) to feeds in VLBW infants improves (1) survival to hospital discharge free from brain injury, late-onset sepsis, NEC and treated retinopathy of prematurity (primary composite end point); (2) each component of the primary composite end point and (3) time to reach full enteral feeds, number of blood transfusions, chronic lung disease and length of hospital stay. It includes a cost-effectiveness analysis of bLF in improving survival free from major morbidity, and evaluates the effect of bLF on survival and developmental outcomes at 24 to 36 months corrected gestational age.This is a multicentre, two-arm, randomised trial comparing the treatment group receiving bLF added to breast milk or formula milk daily (up to 250 mg/kg/day bLF) versus the control group receiving no bLF supplementation. The intervention is administered until 34 completed weeks corrected gestation or for 2 weeks, whichever is longer, or until discharge home, if earlier. The target sample size of 1500 participants yields 85% power, at the two-sided 5% level significance, to detect a difference in proportions meeting the primary outcome assuming the true probability is 74% in controls and 80.5% in the bLF group.Ethics and disseminationThis protocol was approved by Northern Sydney Local Human Research Ethics Committee in January 2017 (Version 2.0, Reference 1003-118M) and other relevant ethics committees. The findings of the trial will be disseminated through peer-reviewed journals and conference presentations.Trial registration numberACTRN12611000247976; Pre-results.


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