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

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.

Elevated C‐reactive protein in umbilical cord blood: Neonatal case review

“…Although it is difficult to determine a clear management strategy for culture‐negative early onset neonatal sepsis, the current recommendation is that neonates with elevated CRP in umbilical cord blood may not need antimicrobials for >48 h if the blood culture is negative . In the present study and in previous studies, the number of neonates who need antimicrobial treatment for >48 h is small . Another reason why most cases of elevated umbilical cord blood CRP had good prognosis is because the prophylactic use of maternal antimicrobials protected the neonates.…”

“…14,15 In the present study and in previous studies, the number of neonates who need antimicrobial treatment for >48 h is small. [2][3][4][5] Another reason why most cases of elevated umbilical cord blood CRP had good prognosis is because the prophylactic use of maternal antimicrobials protected the neonates. In the present study, however, two neonates with elevated umbilical cord blood CRP and bacteremia had poor prognoses.…”

“…Neonates with elevated CRP in umbilical cord blood are thought to have produced it themselves during the fetal period. Elevated CRP in umbilical cord blood has also been reported to be related to neonatal infection or early onset sepsis . Relying on only CRP level in umbilical cord blood, however, is an inaccurate way to predict early onset neonatal sepsis .…”

“…Elevated CRP in umbilical cord blood has also been reported to be related to neonatal infection or early onset sepsis. 2 Relying on only CRP level in umbilical cord blood, however, is an inaccurate way to predict early onset neonatal sepsis. 3 Although there are some proposals regarding the management of elevated CRP in umbilical cord blood, no universally accepted guideline has been established.…”

Effects of early life NICU stress on the developing gut microbiome

“…Gammaproteobacteria are Gram-negative rod-shaped facultative anaerobes. There are many potentially virulent organisms in this family (e.g., Escherichia, Klebsiella, Serratia, Enterobacter, and Proteus), and many of these are related to common NICU morbidities (Mithal, Palac, Yogev, Ernst, & Mestan, 2017;Patel et al, 2016). Veillonella are Gram-negative commensal obligate anaerobes; however, Veillonella has been implicated in intestinal pathology (Bajer et al, 2017).…”