CBC Is Not Reliable for Screening Febrile Infants

Jennifer Garcia

September 11, 2017

Complete blood cell count (CBC) parameters are not sensitive enough to accurately identify invasive bacterial infection (IBI) in febrile infants aged 60 days or younger, a new study shows. Experts suggest it is time to change practice and replace the CBC in the initial workup of these infants.

"While children with IBIs did have higher WBC [white blood cell] counts, ANCs [absolute neutrophil counts], and lower platelet counts, there was not a threshold for these parameters at which IBI could be reliably predicted," write Andrea T. Cruz, MD, MPH, from the Baylor College of Medicine, Houston, Texas, and colleagues. They report their findings in an article published online September 11 in JAMA Pediatrics.

The researchers evaluated prospective observational data from 4313 infants from across 26 emergency departments in the Pediatric Emergency Care Applied Research Network, treated between 2008 and 2013.

They included full-term infants younger than 60 days with temperature 38°C or higher (100.4°F). Infants who were critically ill or premature, were treated with antibiotics within the 4 days before the index visit, or had comorbid medical conditions were excluded. Only infants with blood cultures were included. In addition, only infants with cerebrospinal fluid (CSF) cultures or telephone follow-up within 7 days of the index visit were included in an effort to identify those with bacterial meningitis.

Among the 4313 enrolled infants, 97 (2.2%) had IBIs (bacteremia or bacterial meningitis). With commonly used thresholds, the researchers found CBC parameters to have low sensitivity for correctly identifying which febrile infants have an IBI. For example, WBC count less than 5000 cells/µL identified just 10% of the IBI cases (95% confidence interval [CI], 4% - 16%). Similarly, WBC count of 15,000 cells/µL or greater detected just 27% of cases (95% CI, 18% - 36%), ANC at or above 10,000 cells/µL detected 18% (95% CI, 10% to 25%), and platelet counts below 100 x 103/µL detected 7% (95% CI, 2% - 12%).

"Using widely accepted normal ranges for WBC counts (5000 to 14 900 cells/µL) or an ANC of less than 10 x 103 cells/µL, would have missed 61 (63%) and 80 (82%) of infants with IBIs, respectively," Dr Cruz and colleagues write.

The authors hypothesize that these results may be due to a change in the pathogens that cause IBIs, as modern pathogens may produce less of an inflammatory response. They also postulate that parents in the contemporary era seek care earlier in the course of the infant's illness, potentially before there are inflammatory changes in the CBC.

"Rather than using CBC parameters in isolation, an approach that combines certain CBC parameters (ie, the ANC) with other laboratory tests, such as the urinalysis, procalcitonin, and/or C-reactive protein (when available), may help risk stratify these febrile infants more effectively," Dr Cruz and colleagues write.

"[T]he findings of Cruz et al suggest the time has come for definitive replacement of the total WBC in the initial workup of the febrile infant," write Matthew Mischler, MD, from the University of Illinois College of Medicine, Peoria, and colleagues in an accompanying editorial.

The editorialists note that a strength of the current study was the large sample size, which allowed the authors to confirm the findings of previous, smaller studies in this patient group.

The study findings demonstrate that the chances of correctly identifying an infant with an IBI on the basis of a WBC count above or below current common thresholds is "marginally better than a coin flip," Dr Mischler and colleagues note.

The editorialists agree with the study authors that incorporating new inflammatory markers in screening tests would likely improve diagnostic accuracy in this patient population but note that access and turnaround time for such tests have limited their use.

"In an era where better screening tests exist to identify infants with IBIs, we need to question our continual reliance on a test whose greatest strength may simply be in its ready availability in clinical practice," conclude the study authors.

Funding for this study was provided through grants from the following organizations: the Health Resources and Services Administration, Emergency Services for Children, Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health, Health Resources and Services Administration, Maternal and Child Health Bureau, and Emergency Medical Services for Children Network Development Demonstration Program. The study authors and the editorialists have disclosed no relevant financial relationships.

JAMA Pediatrics. Published online September 11, 2017. AbstractEditorial  

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