Inflammatory Mediators in Umbilical Plasma from Neonates Who Develop Early-Onset Sepsis

Abstract

Objectives: To study whether early-onset neonatal sepsis is associated with a prenatal immune response with elevated umbilical plasma levels of inflammatory mediators, and to study whether mediator levels may be helpful in identifying infected neonates. Setting: Nested case-control study. Methods: Cord blood was sampled from 7,073 consecutively delivered neonates. After review of the medical records, neonates suspected to suffer from infection were classified as infected (n = 52) or noninfected but sick controls (n = 33). We also included a group of healthy controls (n = 99). Umbilical plasma levels of tumour necrosis factor-α (TNFα), interleukin (IL)-1β, IL-6, IL-8, soluble TNF receptors (p55 and p75), IL-1 receptor antagonist (IL-1RA) and C-reactive protein were measured by immunoassays. Results: Infected neonates had higher levels of TNFα, IL-1β, IL-6, IL-8, p55, p75 and IL-1RA than healthy controls (all p < 0.01). Among preterm infants (GA <37 weeks), those with infection (n = 11) had higher levels of IL-1β, IL-6, IL-8, p55 and p75 than noninfected sick controls (n = 13) (all p < 0.05), but among term infants, the infected did not differ from the noninfected sick controls. Receiver operator characteristic plots showed that IL-1β, IL-6 and IL-8 identified preterm infected neonates accurately. Conclusions: Early-onset neonatal sepsis is associated with a prenatal immune response with increased TNFα, IL-1β, IL-6, IL-8, p55, p75 and IL-1RA levels in umbilical plasma. Among neonates who present symptoms suggestive of infection, cytokine levels may be helpful in identifying preterm, but not term infected individuals.

Toward Resolving the Challenges of Sepsis Diagnosis

“…Furthermore, published values are generally Ͻ100 ng/L during sepsis in studies of both adults (30,(55)(56)(57)(58) and neonates (59 -63 ), which is well below peak concentrations found during experimental endotoxemia (54 ). Difficulties in using TNF␣ for sepsis diagnosis arise from the central role this cytokine plays in the inflammatory response, its short-term concentration in response to bacterial challenge, its short half-life of 17 min (64 ), and from excessive concentrations of soluble receptors p55 (sTNF-RI) and p75 (sTNF-RII) during sepsis (55,58,60 ).…”

“…Studies involving neonates revealed similar diagnostic ambiguity, although ROC analyses demonstrated substantially higher mean specificity. The lower cutoff range stipulated in neonatal studies is indicative of the lower production of CRP in septic and healthy neonates, as is clearly reflected in values of 1-77 mg/L for septic and 0.1-6 mg/L for healthy neonates (21,27,28,59,60,62,68,72,89,90 ). Although the diagnostic usefulness is superior in neonates than in adults, application of CRP for diagnostic purposes is best left until 24 h after birth.…”

Genetic Variants of TNF-α, IL-1β, IL-4 Receptor α-Chain, IL-6 and IL-10 Genes Are Not Risk Factors for Sepsis in Low-Birth-Weight Infants

“…Infection, sepsis: Clinical signs and symptoms of infection were divided into six categories according to Dollner et al [19]: (1) pallor and icterus; (2) lethargy, apnea, bradycardia, irritability and seizures; (3) tachypnea and dyspnea; (4) hypotension, tachycardia and compromised microcirculation; (5) vomiting and abdominal dystension; (6) fever and temperature instability.…”

Secretory phospholipase A2 in newborn infants with sepsis

“…Infants in the suspected infection group had a sterile blood culture in the presence of clinical symptoms of infection (for example, apnea, temperature instability, feeding intolerance). 13 Controls were infants without clinical signs of infection.…”