Point of Care - Sepsis Study

Early-onset neonatal sepsis is an important cause of illness and death in newborn infants, particularly in preterm infants. Diagnosis can be challenging because the clinical signs and symptoms are often non-specific. Early identification and treatment are important, but commonly used inflammatory markers have limitations. C-reactive protein (CRP), for example, typically begins to increase only several hours after the onset of infection. In addition, conventional laboratory testing may delay the availability of results.

Point-of-care testing may allow inflammatory markers to be measured rapidly using small volumes of blood. This prospective observational pilot study will investigate the use of a point-of-care device for measuring inflammatory markers in preterm infants and compare selected point-of-care measurements with standard laboratory measurements. The study will focus on interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP), and myxovirus resistance protein A (MxA).

The primary objective is to assess the agreement between measurements obtained with the point-of-care device and standard laboratory methods. IL-6 and PCT will be measured in cord blood using both methods, and CRP will be measured in neonatal heel blood using both methods. The study will evaluate the correlation between biomarker concentrations obtained with the point-of-care device and those obtained using standard laboratory methods.

A secondary objective is to investigate very early measurement of IL-6 and PCT in neonatal heel blood during the first 12 hours of life. These measurements will be performed when heel blood is already obtained for routine blood gas analysis. Up to two point-of-care measurements of IL-6 and PCT may be performed during this period. No additional heel prick will be performed if the blood obtained for routine testing is insufficient for the study measurements.

A further objective is to investigate combined measurement of MxA and CRP at the time of routine CRP testing. The study will explore whether MxA, together with CRP, may provide information that could help distinguish bacterial from viral infection in preterm infants.

Participants will be preterm infants born at less than 37+0 weeks of gestation who are admitted to the Division of Neonatology, Department of Pediatrics, Medical University of Graz after birth. Participants will be enrolled prospectively and managed according to standard clinical protocols. There is no randomization and the study does not compare treatment strategies.

Study measurements are scheduled to coincide as closely as possible with routine clinical blood sampling. IL-6 and PCT will be measured in cord blood at birth using the point-of-care device and standard laboratory methods. During the first 12 hours of life, IL-6 and PCT may additionally be measured using the point-of-care device when heel blood is obtained for routine blood gas analysis. After the first 12 hours of life, CRP will be measured using both the point-of-care device and standard laboratory methods, and a combined MxA/CRP point-of-care measurement will be performed. CRP and MxA measurements may be repeated approximately 24 hours after the first routine CRP measurement.

The point-of-care measurements are performed as proof-of-concept measurements and are intended for subsequent analysis. Results obtained with the point-of-care device will not be used for routine clinical decision-making or patient management. Decisions concerning blood cultures, antibiotic treatment, and any additional diagnostic procedures will continue to be based on the infant's clinical presentation and standard clinical protocols.

After the presence or absence of sepsis has been determined according to the predefined study criteria, participants will be classified for analysis. The study will then examine the relationship between the point-of-care biomarker measurements, standard laboratory measurements, and infection status. The pilot study is designed to assess the feasibility of the study procedures and data collection and to obtain preliminary information on measurement accuracy that can be used to refine the design and sample-size calculation of a subsequent larger study.

Approximately 40 preterm infants are expected to be included initially. Because sepsis status is not established at enrollment, eligible infants with suspected infection will be enrolled consecutively until 20 infants who subsequently meet the predefined criteria for sepsis have been identified. The number of participants without sepsis may therefore exceed 20. Enrollment will be stopped if the total number of participants reaches 80, even if fewer than 20 infants with sepsis have been identified.

The overall aim of this pilot study is to determine whether rapid point-of-care measurement of inflammatory biomarkers in small blood volumes is feasible and provides results that are comparable with standard laboratory measurements, and to explore whether very early biomarker measurements and combined MxA/CRP testing may provide useful information for the diagnosis and characterization of infection in preterm infants.

Inclusion criteria

• Preterm neonates born at <37+0 weeks of gestation who are admitted to the Division of Neonatology, Department of Pediatrics, Medical University of Graz after birth.
• Written parental informed consent before birth.

Exclusion criteria

• Term and preterm neonates who are not admitted to the neonatal care unit.
• No point-of-care measurement of IL-6 and PCT in neonatal blood for infants who do not require blood gas analysis within the first 12 hours of life.