Clin Chem Lab Med 2018; aop Letter to the Editor Tania Siahanidou, Alexandra Margeli, Vasiliki Bourika and Ioannis Papassotiriou* Association of fibroblast growth factor 21 plasma levels with neonatal sepsis: preliminary results https://doi.org/10.1515/cclm-2018-0914 Received August 24, 2018; accepted August 27, 2018 Keywords: biomarker; FGF21; infants; infection; neonates; sepsis. To the Editor, Infections are leading causes of morbidity and mortality in neonates and may also have severe long-term conse- quences. As early diagnosis of neonatal sepsis improves prognosis, identification of new or complementary bio- markers is of great importance [1]. Fibroblast growth factor 21 (FGF21), a peptide hormone synthesized by several organs and being a member of the FGF superfamily, has emerged as a key regulator in the metabolism of glucose and lipids [2], but may also play role(s) in inflammation and sepsis. There is scarce evidence showing increased circulating FGF21 levels during experimental sepsis in mice [3], as well as in human adults with sepsis and systemic inflammatory response syndrome (SIRS) [4, 5]. Exogenous FGF21 administration protected animals from the toxicity of lipopolysaccharide (LPS) and sepsis [3] and also reduced the severity of experimental pancreatitis [2]. These findings highlight the potential role of FGF21 as a biomarker and a therapeutic tool in sepsis and inflamma- tion. As the involvement of FGF21 in neonatal infection is not known yet we aimed to explore the clinical value of circulating FGF21 levels as a diagnostic biomarker of neo- natal sepsis. Seventy-seven full-term neonates were studied; of them, 25 neonates (mean ± standard deviation gestational age 38.5 ± 1.1 weeks; postnatal age 18.0 ± 6.0 days; birth- weight 3080 ± 374 g; male/female 17/8) were septic (SIRS plus proven bacterial infection), whereas 52 healthy neo- nates of similar gestational and postnatal age, birthweight and gender distribution made up the control group. Infants with prematurity, congenital malformations, peri- natal asphyxia, previous antibiotic treatment, surgery or age ≤3 days, were excluded. Along with routine hemato- logic and blood chemistry parameters measured using the Siemens-ADVIA 120 whole blood analyzer (Siemens Healthineers, Erlangen, Germany) and Roche Cobas 6000 Clinical Chemistry System (Roche Diagnostics, Basel, Switzerland), respectively, plasma FGF21 levels were determined in all patients on admission and also once in controls using an immunoenzymatic technique (Human FGF21, R&D Systems, Minneapolis, MN, USA). Accord- ing to the manufacturer, the intra-assay coefficients of variation (CVs) ranged from 5.2% to 10.9% and the inter- assay CVs ranged from 2.9% to 3.5% while, as reported, 55 assays were evaluated and the minimum detectable dose of human FGF21 ranged from 1.61 to 8.69 pg/mL. FGF21 values were not normally distributed (Kolmogorov- Smirnov test), thus comparisons between patients and controls were conducted by the Mann-Whitney U-test. Cor- relation (Spearman’s correlation coefficient) and regres- sion analyses following the logarithmic transformation of FGF21 values were used to examine relations among vari- ables of interest. The diagnostic properties of FGF21 levels were assessed by receiver operating characteristic (ROC) analysis. Statistical analyses were performed using the SPSS statistical package (SPSS, version 25.0, Chicago, IL, USA). Levels of statistical significance were set at p ≤ 0.05. The “Aghia Sophia” Children’s Hospital Ethics Committee approved the study and informed parental consent was also obtained. Median (25th–75th) percentiles of plasma FGF21 levels were significantly higher (p < 0.0001) in septic neo- nates (61.5 [24.5–120.4] pg/mL; range 8.4–1171.3 pg/mL) compared to controls (5.9 [2.7–9.6] pg/mL; range 0.4–33.5 pg/mL). In septic neonates, FGF21 levels cor- related significantly with C-reactive protein (CRP) (r s = 0.487, p = 0.01), glucose (r s = 0.446, p = 0.03) and *Corresponding author: Dr. Ioannis Papassotiriou, Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Athens 11527, Greece, Phone/Fax: +30-213-2013171, E-mail: biochem@paidon-agiasofia.gr, ipapassotiriou@gmail.com Tania Siahanidou and Vasiliki Bourika: Neonatal Unit, First Department of Pediatrics, National and Kapodistrian University of Athens, Medical School, Athens, Greece Alexandra Margeli: Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Athens, Greece Brought to you by | University of Sussex Library Authenticated Download Date | 9/25/18 3:47 AM