{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:07:18Z","timestamp":1792811238402,"version":"4.5.0"},"reference-count":60,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,10,1]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>To evaluate serial serum C-reactive protein (CRP) levels for diagnosis of neonatal infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting.<\/jats:title><jats:p>A regional intensive care nursery and two community intensive care nurseries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>All neonates treated for suspected bacterial infection were prospectively evaluated using a standardized clinical pathway. Infants were categorized as having proven sepsis (bacteria isolated from blood, cerebrospinal fluid, or urine culture), probable sepsis (clinical and laboratory findings consistent with bacterial infection without a positive culture), or no sepsis (findings not consistent with sepsis), without consideration of CRP levels. Infants whose blood cultures yielded skin flora but who demonstrated no other signs of bacterial infection were not considered to have sepsis. CRP levels were determined at the initial evaluation and on each of the next two mornings. Sensitivity, specificity, predictive values, and likelihood ratios were calculated for the first (CRP #1), second (CRP #2), higher of the second and third (CRP #2 and #3), or highest of all three CRP levels (CRP \u00d7 3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>Sepsis was suspected within the first 3 days after birth in 1002 infants (early-onset) and on 184 occasions in 134 older infants (late-onset). There were 20 early-onset and 53 late-onset episodes of proven sepsis, and 74 early-onset and 12 late-onset episodes of probable sepsis. CRP #1 had sensitivities of 39.4% and 64.6% for proven or probable sepsis and 35.0% and 61.5% for proven sepsis in early-onset and late-onset episodes, respectively. CRP levels on the morning after the initial evaluation (CRP #2) had higher sensitivities (92.9% and 85.0% for proven or probable sepsis and 78.9% and 84.4% for proven sepsis in early-onset and late-onset episodes, respectively), and normal results were associated with lower likelihoods of infection (likelihood ratios for normal results of 0.10 and 0.19 for proven or probable sepsis and 0.27 and 0.21 for proven sepsis, in early-onset and late-onset episodes, respectively). Three serial serum CRP levels had sensitivities of 97.8% and 98.1% for proven or probable sepsis and 88.9% and 97.5% for proven sepsis in early-onset and late-onset episodes, respectively. The negative predictive values for CRP \u00d7 3 were 99.7% and 98.7% for both proven or probable sepsis and for proven sepsis in early-onset and late-onset episodes, respectively. A CRP level obtained at the time of the initial evaluation can be omitted without significant loss of sensitivity or negative predictive value: the sensitivities of CRP #2 and #3 were 97.6% and 94.4% for proven or probable sepsis and 88.9% and 96.4% for proven sepsis in early-onset and late-onset episodes, respectively; negative predictive values were 99.7% both for proven and for proven or probable early-onset sepsis, 97.6% for proven or probable late-onset infection, and 98.8% for proven late-onset infection. Serial normal CRP levels were associated with a markedly reduced likelihood of infection as compared with that in the entire population before testing, with likelihood ratios ranging from 0.03 to 0.16 for the various subgroups. Maximum CRP levels &amp;gt;3 mg\/dL had positive predictive values &amp;gt;20% for proven or probable early-onset infections and for proven or probable and proven late-onset infections, but only those &amp;gt;6 mg\/dL had such a high positive predictive value for proven early-onset sepsis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions.<\/jats:title><jats:p>Serial CRP levels are useful in the diagnostic evaluation of neonates with suspected infection. Two CRP levels &amp;lt;1 mg\/dL obtained 24 hours apart, 8 to 48 hours after presentation, indicate that bacterial infection is unlikely. The sensitivity of a normal CRP at the initial evaluation is not sufficient to justify withholding antibiotic therapy. The positive predictive value of elevated CRP levels is low, especially for culture-proven early-onset infections.<\/jats:p><\/jats:sec>","DOI":"10.1542\/peds.102.4.e41","type":"journal-article","created":{"date-parts":[[2004,8,13]],"date-time":"2004-08-13T23:44:32Z","timestamp":1092440672000},"page":"e41-e41","source":"Crossref","is-referenced-by-count":324,"title":["Serial Serum C-Reactive Protein Levels in the Diagnosis of Neonatal Infection"],"prefix":"10.1542","volume":"102","author":[{"given":"William E.","family":"Benitz","sequence":"first","affiliation":[{"name":"1 From the Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Y.","family":"Han","sequence":"additional","affiliation":[{"name":"1 From the Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashima","family":"Madan","sequence":"additional","affiliation":[{"name":"1 From the Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramela","family":"Ramachandra","sequence":"additional","affiliation":[{"name":"1 From the Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, California."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[1998,10,1]]},"reference":[{"key":"2021121010195278700_B1","first-page":"1","article-title":"Prevention of perinatal group B streptococcal disease: a public health perspective.","volume":"45","author":"Centers for Disease Control and Prevention","year":"1996","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2021121010195278700_B2","first-page":"33","article-title":"Changes in the pattern of neonatal septicemia and meningitis.","volume":"112","author":"McCracken","year":"1966","journal-title":"Am J Dis Child"},{"key":"2021121010195278700_B3","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/S0031-3955(16)31911-3","article-title":"Septicemia of the newborn.","volume":"13","author":"Gluck","year":"1966","journal-title":"Pediatr Clin North Am"},{"key":"2021121010195278700_B4","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1177\/000992288102000602","article-title":"Study of the usefulness of clinical and hematologic findings in the diagnosis of neonatal bacterial infections.","volume":"20","author":"Spector","year":"1981","journal-title":"Clin Pediatr (Phila)"},{"key":"2021121010195278700_B5","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/0029-7844(95)00402-5","article-title":"Risk factors for neonatal sepsis.","volume":"87","author":"Yancey","year":"1996","journal-title":"Obstet Gynecol"},{"key":"2021121010195278700_B6","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1056\/NEJM197706022962206","article-title":"Patterns of use of antibiotics in two newborn nurseries.","volume":"296","author":"Hammerschlag","year":"1977","journal-title":"N Engl J Med"},{"key":"2021121010195278700_B7","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1542\/peds.65.5.1036","article-title":"Early diagnosis of neonatal sepsis.","volume":"65","author":"Philip","year":"1980","journal-title":"Pediatrics"},{"key":"2021121010195278700_B8","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1097\/00006454-198705000-00005","article-title":"Sepsis screen in neonates with evaluation of plasma fibronectin.","volume":"6","author":"Gerdes","year":"1987","journal-title":"Pediatr Infect Dis J"},{"key":"2021121010195278700_B9","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1542\/peds.92.3.431","article-title":"Significance of serial C-reactive protein responses in neonatal infection and other disorders.","volume":"92","author":"Pourcyrous","year":"1993","journal-title":"Pediatrics"},{"key":"2021121010195278700_B10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0022-3476(79)80096-7","article-title":"The neonatal blood count in health and disease. 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Protease inhibitors, complement factors, and C-reactive protein.","volume":"14","author":"Daniels","year":"1974","journal-title":"J Trauma"},{"key":"2021121010195278700_B45","first-page":"334","article-title":"C-reactive protein in management of children's burns.","volume":"19","author":"Pruchniewski","year":"1987","journal-title":"Ann Clin Res"},{"key":"2021121010195278700_B46","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1177\/000992288402300703","article-title":"Serum levels of C-reactive protein in neonatal respiratory distress syndrome.","volume":"23","author":"Dyck","year":"1984","journal-title":"Clin Pediatr (Phila)"},{"key":"2021121010195278700_B47","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1111\/j.1651-2227.1986.tb10337.x","article-title":"Acute phase proteins in neonatal necrotizing enterocolitis.","volume":"75","author":"Philip","year":"1986","journal-title":"Acta Paediatr Scand"},{"key":"2021121010195278700_B48","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1111\/j.1651-2227.1987.tb17265.x","article-title":"Serum acute phase reactants in necrotizing enterocolitis.","volume":"76","author":"Isaacs","year":"1987","journal-title":"Acta Paediatr Scand"},{"key":"2021121010195278700_B49","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1651-2227.1994.tb13243.x","article-title":"Risk factors and severity indices in necrotizing enterocolitis.","volume":"396","author":"Schober","year":"1994","journal-title":"Acta Paediatr Suppl"},{"key":"2021121010195278700_B50","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/BF02469494","article-title":"Serum acute phase reactants in pediatric patients; 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