Cord Blood Acute Phase Reactants Predict Early Onset Neonatal Sepsis in Preterm Infants.

Leena B Mithal,Ram Yogev,Linda M Ernst,Karen K Mestan,Hannah L Palac,Zheng-Liang Ma

doi:10.1371/journal.pone.0168677

Abstract

BackgroundEarly onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection.MethodsIn this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results.ResultscEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p<0.01). SAA, CRP, and Hp were elevated in cEOS but not in PS (p<0.01) and had AUCs of 99%, 96%, and 95% respectively in predicting cEOS. Regression analysis revealed robust associations of SAA, CRP, and Hp with EOS after adjustment for covariates. Procalcitonin, fibrinogen, α-2-macroglobulin and tissue plasminogen activator were not significantly different across groups. Placental acute inflammation was associated with APR elevation and was present in all cEOS, 9 PS, and 17 control infants.ConclusionThis study shows that certain APRs are elevated in cord blood of premature infants with EOS of intrauterine origin. SAA, CRP, and Hp at birth have potential diagnostic utility for risk stratification and identification of infants with EOS.

Highlights

Despite advances in maternal screening and antibiotic prophylaxis, early onset sepsis (EOS) remains a major problem and causes infant morbidity and mortality
C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in confirmed EOS (cEOS) compared to controls (p
This study shows that certain acute phase reactant (APR) are elevated in cord blood of premature infants with EOS of intrauterine origin

Summary

Introduction

Despite advances in maternal screening and antibiotic prophylaxis, early onset sepsis (EOS) remains a major problem and causes infant morbidity and mortality. Blood culture is the current gold standard for diagnosis of sepsis but the result is delayed and has a low sensitivity in neonates due to maternal antibiotic treatment, small specimen volumes, and low-grade bacteremia [8, 9]. Broad-spectrum empiric antimicrobial treatment despite negative cultures is common in the preterm population causing serious adverse consequences including disrupted gastrointestinal and mucosal colonization, necrotizing enterocolitis, invasive fungal infections, and antibiotic resistance [11,12,13]. Onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection

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