Sepsis and Oxidative Stress in the Newborn: From Pathogenesis to Novel Therapeutic Targets

Table 1

Clinical studies assessing oxidative stress and/or antioxidant defenses in neonatal sepsis.

Subjects	Evaluated markers	Main findings	Ref.
50 newborns: 30 sepsis/20 controls	Serum XO, CPK, SOD, GPx, PO, MDA, uric acid, albumin	Increased XO, CPK, SOD, GPx, MDA, reduced PO, uric acid, albumin in sepsis versus controls	[49]
50 newborns: 30 sepsis/20 controls	Serum TNF-alpha, SOD, GPx	Increased TNF-alpha, SOD, GPx in sepsis versus controls; 5-fold increase of TNF-alpha but no differences in SOD, GPx in septic shock versus nonseptic shock	[50]
128 newborns: 44 sepsis/84 controls	Serum MDA, SOD, GPx, CAT, uric acid, albumin	Increased MDA, SOD, GPx, CAT, reduced uric acid, albumin in sepsis versus controls; Increased MDA, SOD, GPx, CAT, reduced uric acid, albumin in sepsis-related death versus sepsis survivors	[51]
120 preterm newborns: 20 proven EOS/20 clinical EOS/80 controls; Mean GA: 30 wks	Cord blood IL-6, IL-10-TBARS, protein carbonyls	Increased IL-6, IL-10, TBARS, protein carbonyls in proven and clinical sepsis versus controls; Increased TBARS, IL-6 in proven versus clinical sepsis; TBARS and IL-6 best biomarkers for the diagnosis of sepsis (AUC 0.88); TBARS is the only marker independently associated with EOS	[54]
120 preterm newborns	Serum IL-6, IL-10, TBARS, protein carbonyls	IL-6 and TBARS showed mild to moderate correlation with sepsis severity score; No markers predict sepsis-related mortality	[55]
30 term newborns: 20 sepsis/10 controls	Serum MDA + 4-HDA	2-fold increase of MDA + 4-HDA in septic patients versus controls	[63]
52 newborns with LOS: 27 clinical/25 proven LOS; Mean GA: 35 wks	Erythrocyte GPx, TrxR, SOD, CAT, selenium, and glutathione; SePP; plasma lipid peroxidation markers	Increased GPx in clinical sepsis versus controls: Reduced TrxR in proven sepsis versus controls: Increased SOD, CAT, lipid peroxidation, reduced selenium, SePP, glutathione in clinical and proven sepsis versus controls	[64]
70 newborns: 35 LOS/35 controls; Mean GA: 36 wks	Serum PON-1, TOS, TAS, OSI	Increased TAS/TOS/OSI; reduced PON-1 in sepsis pretreatment versus posttreatment.; Increased TAS/TOS/OSI; reduced PON-1 in sepsis pretreatment versus controls	[65]
65 preterm newborns; 31 sepsis/34 controls; Mean GA: 34 wks	Erythrocyte SOD, CAT, GPx, GR	Increased CAT at 60 days following sepsis diagnosis in sepsis versus controls	[68]

XO: xanthine-oxidase; CPK: creatinine phosphokinase; SOD: superoxide dismutase, GPx: glutathione peroxidase, PO: peroxidase; MDA: malondialdehyde; CAT: catalase; BAP: biological antioxidant potentials; TBARS: thiobarbituric acid reactive species; 4-HAD: 4-hydroxylalkenals; TrxR: thioredoxin reductase; PON-1: paraoxonase-1; GR: glutathione reductase; SePP: selenoprotein P; TOS: total oxidant state; TAS: total antioxidant state; OSI: oxidative stress index.