White Blood Cell Counts in Neonatal Early-Onset Sepsis

Abstract

To the Editor: We read with interest the article of Murphy and Weiner1 who reported on 100% sensitivity and 100% negative predictive value of 2 normal white blood cell counts (WBC) within 8–12 hours and a negative blood culture at 24 hours for ruling out early-onset sepsis (EOS) in the neonate. A normal WBC count was defined as values between 6000 and 30,000/µL, and an immature to total neutrophil ratio as less than 0.2. The strength of the study was the large number of patients (n = 3213) included that retrospectively was identified by an electronic database during a 10-year period. Data revealed an overall low culture-proven EOS rate of 0.73%. The findings are astonishing by the way that to date no single or combined hematologic index was reported to be sensitive and specific enough to discriminate infected from noninfected symptomatic term and preterm neonates.2 By means of a retrospective cohort analysis of preterm and term neonates admitted to our neonatal intensive care unit between 2004 and 2007, including 737 of a total of 1301 neonates who had at least 1 WBC count determination during the first 72 hours of life, we sought to prove the usefulness of leukocyte counts in the evaluation of EOS. WBC counts were performed in 1–9 times per case (mean 1.65). Median gestational age was 34 weeks and median birth weight was 2137 g, and the number of preterm to term-born infants ratio was 236:501. Culture-proven EOS was diagnosed in 39 neonates (5.3%), and pathogens yielded Group B streptococci in 51%, Ureaplasma urealyticum in 26%, Escherichia coli in 10%, Staphylococcus aureus in 5% and single cases with Enterococci (3%), Chlamydia (3%) and Klebsiella (3%) infections. Defining normal WBC counts as between 9000 and 34,000/µL3 revealed that 39% of cases with culture-proven EOS had abnormal values. By a second approach defining normal WBC counts between 8500 and 21,500/µL calculated using the Youden index (0.29 for optimal cutoff values, sensitivity 64% and specificity 66%) data revealed 59% of cases had abnormal values. Sensitivity of WBC counts decreased when performed at 0–24 hours compared with 48–72 hours of age. The immature to total neutrophil ratio showed sensitivity, specificity, positive predictive and negative predictive values (95% confidence interval) of 14% (5–29), 97% (95–99), 36% (13–65) and 92% (89–94), respectively. Considering that blood cultures often do not reveal positive results before 72 hours of age, low sample volumes obtained in very low birth weight infants result in negative cultures and different rates of false-negative (approximately 20%) and false-positive results have been reported,3 collectively question the reliability of a negative blood culture result after 24 hours. Even when rapid automated blood culture systems were used, 97% and 99% of cultures were positive by 24–36 hours of incubation when only pretherapy (before antibiotic therapy) cultures were evaluated.4 Risk factors associated with clinical symptoms and signs of sepsis seem to be more important in predicting culture-proven EOS than are any adjunct laboratory test.5 Hence, we do not feel confident with the conclusions of Murphy and Weiner1 and would argue not to solely rely on these negative results when the neonate is asymptomatic. Bernhard Resch, MD Division of Neonatology Department of Pediatrics Research Unit for Neonatal Infectious Diseases and Epidemiology Silvia Edlinger, MD Research Unit for Neonatal Infectious Diseases and Epidemiology Wilhelm Müller, MD Division of Neonatology Department of Pediatrics Medical University of Graz Graz, Austria