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

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):  
Siamak Sabour

: I was interested in reading the paper by Hagag A and colleagues that was published in the March 2020 edition of the Infect Disord Drug Targets [1]. 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. The purpose of the authors 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. They carried out a case control study on 40 neonates with suspected high probable late onset neonatal sepsis 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. They reported a 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. First, reproducibility and validity (accuracy) are two different methodological issues of diagnostic studies [2]. Second, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) as well as likelihood ratios [likelihood ratio positive (ranging from 1 to infinity; the higher the LR+, the more accurate the test) and likelihood ratio negative (ranging from 0 to 1; the lower the LR-, the more accurate the test)] are among the estimates to assess validity (accuracy) of a diagnostic test [2-6]. Third, receiver operative characteristic (ROC) curve is usually used to assess diagnostic accuracy (discrimination) of a diagnostic model and has nothing to do with prediction of neonatal sepsis. Finally, logistic regression analyses have nothing to do with prediction studies. For prediction, we need at least two different cohort datasets or at least one cohort dataset, splitting them for development and validation of our model [2,7,8]. They concluded that neonates with high probable sepsis had significantly higher serum cortisol and hepcidin and significantly lower free TT3 and free TT4 compared with healthy neonates. They claimed that higher serum cortisol and hepcidin and lower free TT3 and free TT4 can lead to early diagnosis and subsequently better prognosis. Such conclusion should be supported by the above-mentioned methodological issues. Otherwise, misdiagnosis and mismanagement of the patient may occur.


2020 ◽  
Author(s):  
Mengjiao Kuang ◽  
Suipeng Chen ◽  
Shirui Huang ◽  
Binbin Gong ◽  
Suzhen Lin ◽  
...  

Abstract BackgroundSepsis remains a major cause of neonatal death, but its underlying pathological mechanisms are poorly understood. Methods To characterize the serum cytokine/chemokine profile in neonates with sepsis, we enrolled 40 full-term neonates with sepsis and 19 neonates without infection as controls. Forty cytokines/chemokines in serum were analyzed using the Luminex Bead Immunoassay System. Serum IL-17 was measured using an enzyme-linked immunosorbent assay. ResultsOur results showed that serum IL-6, IL-8, TNF-α, IL-1β, MIF, CXCL13, CXCL1, CXCL2, CXCL5, CXCL6, CXCL16, CCL27, CCL2, CCL8, CCL3, CCL20, CCL23, CCL27, and CX3CL1 levels were significantly increased in neonates with sepsis compared to those in the control group (all p<0.05). The levels of serum CXCL6, CXCL1, IL-6, CXCL10, CXCL11, CCL20, and IL-17 were higher in late-onset sepsis (LOS) than in early-onset sepsis (EOS) (all p<0.05). Conversely, serum IL-16, CXCL16, and CCL22 were lower in LOS than in EOS (all p<0.05). The levels of CX3CL1, CXCL2, CCL8, and TNF-α were all positively correlated with SOFA scores. ConclusionOur findings revealed that excessive pro-inflammatory cytokines might be involved in neonatal sepsis. In addition, chemokines significantly increased the recruitment of immune cells after infection to participate in the anti-infection defense of neonates, but this could lead to damage.


2021 ◽  
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):  
Pramod P. Singhavi

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.


2021 ◽  
pp. 097321792110075
Author(s):  
Rameshwor Yengkhom ◽  
Pradeep Suryawanshi ◽  
Rahul Murugkar ◽  
Bhavya Gupta ◽  
Sujata Deshpande ◽  
...  

Background and Objectives: Point of care neonatal ultrasound is a useful tool in evaluation of heart, brain, lungs, and abdomen in neonatal sepsis. The objective of our study was to perform bedside ultrasound screening of heart, brain, lungs, and abdomen in neonates with late onset culture positive sepsis and study the patterns of abnormalities and also their role in change of patient management. Methods: This prospective observational study was conducted at a tertiary level neonatal care unit from March 2017 to May 2018. All neonates with suspected late onset sepsis on the basis of clinical and laboratory findings underwent point of care neonatal ultrasound of heart, brain, lungs, and abdomen. Results: Of 153 suspected and eligible late-onset neonatal sepsis (LONS) cases, 67 (44%) had positive blood culture and were analyzed. Of this 67 neonates, 30 (45%) had abnormal neurosonography, 38 (57%) had abnormal cardiac output, 14 (20%) had abnormal cardiac contractility, 17 (25%) had abnormal pulmonary pressure, 18 (27%) had pulmonary arterial hypertension, 19 (28%) had pneumonia, and 7 (10%) had free fluid in abdomen. Clinical management was changed in 26 (39%) neonates. Conclusion: Bedside point of care neonatal ultrasound is a useful tool in assessment of heart, brain, lungs, and abdomen in a LONS. It could help in making appropriate decisions in the management, and therefore potentially reduce morbidity and mortality.


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.


Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 192
Author(s):  
Moritz Lenz ◽  
Thomas Maiberger ◽  
Lina Armbrust ◽  
Antonia Kiwit ◽  
Axel Von der Wense ◽  
...  

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.


2011 ◽  
Vol 5 (11) ◽  
pp. 799-803 ◽  
Author(s):  
Ruchika Kohli-Kochhar ◽  
Geoffrey Omuse ◽  
Gunturu Revathi

Introduction: Neonatal mortality in developing countries is usually due to an infectious cause.  The gold standard of investigation in developing countries is a positive blood culture.  It is important to know the aetiology of neonatal bloodstream infections so that empiric treatment can be effective.  Methodology: We conducted a retrospective clinical audit over ten years between January 2000 until December 2009, looking at the aetiology of both early and late onset neonatal sepsis.  We analysed data from 152 (23%) patient isolates out of 662 suspected cases of neonatal sepsis.  Results: Our study revealed that Gram-positive organisms were the predominant cause of both early and late onset sepsis; the common isolates were Staphylococcus epidermidis (34%) and Staphylococcus aureus (27%).  There were no isolates of group B Streptococcus.  Candida species was isolated only in patients with late onset sepsis (6.9%).  Bacterial isolates were relatively sensitive to the commonly used first- and second-line empiric antibiotics. Conclusion: Gram-positive organisms remain the major cause of neonatal bloodstream infections in our setup.  The findings of this study will guide clinicians in prescribing the right empiric therapy in cases of suspected neonatal sepsis before the definitive culture results are obtained.


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.


1970 ◽  
Vol 2 ◽  
pp. 28-33
Author(s):  
SM Selimuzzaman ◽  
Noorzahan Begum ◽  
Nadira Islam ◽  
Shelina Begum

The study was designed to observe the effects of surgical stress on serum level of cortisol in patients undergoing surgical treatment and to find out any differences in hormonal response between elective and emergency surgical procedures. A total number of 60 male subjects aged between 18 and 45 years were included in the study. Of them, 20 were healthy control (Group I), 20 underwent elective surgical treatment (Group II) and emergency surgical interventions were applied in rest 20 subjects (Group III). Study Groups were further divided into subgroups A (preoperative samples were collected 1- hour before operation), B (postoperative samples were collected 1-hour after the end of the operation) and C (postoperative samples were collected 24-hours after operation).Serum cortisol level was estimated by invitro-immunolytic test.Statistical analysis was done by paired, unpaired ‘t' test and regression analysis. The preoperative mean serum cortisol concentration in elective surgical cases was almost similar to that of healthy control. On the contrary, in the emergency surgical cases, a significantly increased mean cortisol level were observed (I vs IIIA and IIA vs IIIA; P < 0.05). The serum cortisol concentrations were increased both in elective and emergency surgical cases after operations but the magnitude of rise was more marked in emergency group of patients (IIB vs IIIB; P < 0.05). Therefore, this study reveals that surgical intervention causes increase in serum cortisol which is more marked in emergency procedure. Key Words: Stress; Cortisol; Surgery DOI:10.3329/jbsp.v2i0.981 J Bangladesh Soc Physiol. 2007 Dec;(2): 28-33.


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