J Med Assoc Thai 2002; 85 (11):1151

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Predictive Values of Serial C-reactive Protein in Neonatal Sepsis
Nuntnarumit P Mail, Pinkaew O , Kitiwanwanich S

Background : Infection is one of the major problems in neonates. The diagnosis of neonatal
septicemia is difficult to establish based on the clinical criteria alone. However, empirical treatment
should not be delayed because of the high mortality. Laboratory tests used to support diagnosis have
shown variable predictive values. C-reactive protein (CRP), an acute phase protein, increases in
inflammatory disorders and tissue injury. Serial CRP have been shown to be more useful than a single
measured CRP in the diagnostic evaluation of neonates with suspected infection.
Objectives : 1. To evaluate the diagnostic accuracy of serial CRP in neonatal sepsis.
2. To compare the diagnostic values between CRP and leukocyte index from
a complete blood count (CBC).
Method : A prospective observational study included newborn infants, aged > 3 days and
diagnosed with clinical sepsis, who were admitted in the newborn intensive care unit and special care
nursery at Ramathibodi Hospital during a 14-months period. Newborn infants who received antibiotics
prior to septic work up were excluded. CRP levels were measured initially at the time of septic
work-up and at 24-48 hours later. Investigations for infection included CBC, blood culture and urine
culture. Radiological study and lumbar puncture were performed if clinically indicated. Based on
clinical and biological data, diagnosis of infants can be categorized into 4 groups as follows; (1)
proven sepsis with positive culture, (2) localized infection with negative culture, (3) probable infection
(clinically consistent with sepsis, negative culture without localized infection), and (4) no infection
(findings not consistent with sepsis and antibiotics were discontinued within 3 days). Diagnosis
was made before the CRP results were known.
Results : Of 76 newborn infants with 90 episodes of clinical sepsis, there were 24 episodes
of proven sepsis, 11 episodes of localized infection with negative culture, 18 episodes of probable
infection and 37 episodes of no infection. Serial CRP had better predictive values than those of CBC.
The sensitivity, specificity, positive predictive value, and negative predictive value of CRP for proven
sepsis and localized infection at cutoff point ≥ 5 mg/L were 100 per cent, 94 per cent, 91.6 per cent
and 100 per cent respectively. False positive CRP were found in post-operative patent ductus arteriosus
ligation, intracerebral hemorrhage, and post resuscitation with chest compression. To improve the
predictive value of CBC, analysis of the receiver operating characteristic (ROC) curve showed that
the predictive value of CBC for sepsis would be enhanced by using abnormal leukocyte index ≥ 2
parameters.
Conclusions : Predictive value of CRP could be enhanced by serial rather than a single
measurement. Serial CRP showed very high predictive values for diagnosis of neonatal sepsis and
were better than those of leukocyte indices of CBC.
Key word : C-reactive Protein, Predictive Value, Neonatal Sepsis

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