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

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.