What is the role of serum lab studies in the workup of neonates with suspected sepsis due to chorioamnionitis?

Updated: May 08, 2018
  • Author: Fayez M Bany-Mohammed, MD; Chief Editor: Ted Rosenkrantz, MD  more...
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Answer

WBC profiles (leukopenia [< 5000/µL], leukocytosis [>30,000/µL], a markedly diminished absolute neutrophil count [ANC] [0.3-0.4]) are commonly used screening tests for the septic neonate. Note that the immature-to-total neutrophil ratio of 0.3-0.4 is higher than the previous value of 0.2 reported in the classic studies of Manroe (1977 and 1979). [182, 183] Clinical pathologists have been less accepting of the immature-to-total neutrophil ratio as a diagnostic aid in neonatal sepsis, [184]  and studies have reexamined the WBC counts and the leukocyte profiles present in extremely preterm infants [185] and at high altitude. [186] Other diagnostic tests (eg, inflammatory factors, adhesion molecules, cytokines, neutrophil surface antigens, even bacterial DNA) may be superior alternatives to this test. To date, these markers of neonatal inflammation/infection have not replaced leukocyte counts as diagnostic methods.

WBC profiles and kinetics are influenced by the genetic make-up of the patient, the gestational age, maternal noninfectious disorders such as pregnancy-induced hypertension (PIH), medications administered to the mother, fetal disease, and other factors. Reference range WBC counts in the neonate do not exclude infection, and serial studies of WBC indices at approximately 6- to 12-hour intervals may be more useful in detecting sepsis. [187] A continued assessment of WBC kinetics offers more information regarding decision making. For example, a physician should be particularly concerned with a falling total WBC count, a declining absolute mature neutrophil count, and a rising immature-to-total neutrophil ratio. These findings, taken together, indicate depletion in the bone marrow–related storage pool of neutrophils. [188]

The predictive accuracy of WBC indices for the diagnosis of the EOS is poor. Likewise, the accuracy of CRP determinations to predict neonatal infections shortly after birth is low. However, a negative CRP (especially if done serially, 12-24 hours apart) is a reason to stop antibiotic therapy after 48 hours. [189, 10]

Akin to maternal diagnostic studies for infection, levels of A1PI complex and cytokines (eg, IL-1 and IL-6; in particular, IL-1 receptor antagonist), as well as the detection of bacterial products in neonatal blood, have not gained widespread use as markers of neonatal sepsis. However, these effectors of inflammation may prove to have better predictive accuracy than WBC tests or the CRP level. Procalcitonin level may have better sensitivity, specificity, and positive and negative predictive value than CRP in the diagnosis of early-onset neonatal sepsis and is increasingly being used. [9, 10] Cell-surface markers of inflammation on leukocytes remain under investigation as potential markers to detect EOS. [190, 191, 192]  Serum amyloid A levels appear to be have high sensitivity at the onset of symptoms and 2 days after, although existing data show a variable positive predictive value with a high negative predictive value. [10]

Molecular methods that use real-time PCR and DNA sequencing for amplification and detection of 16S rRNA of pathogenic bacteria in neonatal blood have created enormous interest because a rapid diagnosis is possible. [193, 194, 195]  However, despite showing that 16S rRNA PCR increased the sensitivity in detecting bacterial DNA in newborns with signs of sepsis and allowing shortening of antibiotic courses, a report concluded that uncertainty about the bacterial cause of sepsis was not reduced by this test, and that blood culture remains currently irreplaceable. [196] As technology advances, caregivers should pay close attention to this rapidly advancing field.


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