**4. Conclusion**

72 Neonatal Bacterial Infection

predictive value of 0.80.

**3.2. Possible limitations of the use of IG** 

*3.1.3. Reference values for a neonatal study population based on ROC analysis* 

Preliminary data revealed a cut-off value for IG% of 1.3% based on calculations using the Youden's index and a median of 0.05x103/µL (0.05-0.09; 2.5%–97.5% confidence interval) for IG# in our control group of asymptomatic, healthy subjects. According to our data the measurement of IMI# compared to IG# seems to be more favourable as determined by ROC analysis as there seems to be a tendency that the IM# has a higher predictive value than the IG# (Figure 3). Setting a cut off value of 262/µl the measurement of IMI# revealed a positive

White blood cell differential counts are not only influenced by infection. The gestational as well as the infant's age in hours at the time of blood collection, the method of blood sampling and the infant's gender might affect the results as well as the method of delivery, or maternal risk factors like hypertension (Chirico et al., 1999; Christensen et al., 2009; Escobar, 2003; Kayiran et al., 2003; Newman et al., 2010; Schelonka et al., 1995; Schmutz et al., 2008). Even the influence of the sea level on ANC in neonates has been described leading to a wider range of reference values with isolated elevated counts of absolute neutrophil

A prospective longitudinal study observed higher cord blood cortisol levels, as a sensitive marker of intrauterine stress, in infants born by vaginal delivery compared to elective cesarean section in term neonates and a significant positive correlation between total leukocyte and neutrophil counts. After 12 hours of life no differences in the variation of leukocyte counts remained. Although a significant increase of immature neutrophil counts in vaginally delivered infants or after long labour has been previously described (Hasan et al., 1993; Schelonka et al., 1994), no significant differences in the IT-ratio were detected between the two groups (Chirico et al., 1999). In a prospective observational study including 60 preterm infants with a gestational age < 32 weeks prenatal growth retardation has been shown to be an independent factor for significantly lower counts of leukocytes, total neutrophil and immature neutrophil counts in very immature preterm infants immediately after birth when compared with AGA counterparts. It has been assumed that these low numbers of circulating white blood cells might reect the reduced bone marrow reserves (Wirbelauer et al., 2010). As the median granulocyte count in the SGA group was with a count of 1.058/µL near to absolute granulopenia one could consider this as a risk factor for sepsis, as previous studies had reported an association between early onset neutropenia and sepsis (Christensen et al., 2006). But low numbers of inammatory cells could also represent a possible protection mechanism for pulmonary and central-nervous disease by reducing inammatory events postnatally (Wirbelauer et al., 2010). Among extremely low birth weight (ELBW) neonates low neutrophil counts (< 1000/µL) have been observed with a rate of ve times higher than reported in the general NICU population. Most cases were present in the rst days of life and represented a transient phenomenon. SGA or maternal pregnancy induced hypertension were common causes for these alterations, whereas in over

granulocytes but normal IT-ratios in healthy term babies (Lambert et al., 2009).

As clinical signs in preterm and term infants with severe bacterial infection are often nonspecific and scarce, automated detection of IGs and IMI seems to act as a useful adjunctive tool in the diagnosis of neonatal sepsis. Technical development of automated hematology analyzers has led to a precise, fast, accurate, and reproducible determination of IGs. The detection of all immature cells including blasts in a separate channel might be advantageous at an early stage of sepsis, when these cells are released from bone marrow and the peripheral neutrophil count can still be in the normal range.

Although automated determination of IGs is currently carried out in the area of research, evidence exists that this method seems to be worth to be implemented in clinical practice especially as an adjunctive tool in determining early phase of bacterial sepsis. The fact that measurement of this parameter in the course of routine determination of a white blood differential count does not necessitate any additional sample volume, personal effort, or costs, might be a valuable additional argument. Further well designed prospective trials are mandatory to validate the performance characteristics of these new parameters as diagnostic tool in neonatal sepsis. In this context, the availability of an internal quality control and the

development and implementation of external quality assessment schemes to evaluate analytical performance, compare different laboratories and methods as well as the definition of standards represent indispensable conditions for a reasonable use in clinical routine (Briggs, 2009).

The Role of Immature Granulocyte Count

and Immature Myeloid Information in the Diagnosis of Neonatal Sepsis 75

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