CBC Indices and Serum Lactate in Neonatal Sepsis

July 9, 2026 updated by: Faten Samir Malak Nashed, Assiut University

Diagnostic and Prognostic Values of CBC Indices and Serum Lactate in Neonatal Sepsis

Neonatal sepsis is a leading cause of illness and death in Neonatal Intensive Care Units (NICUs). Diagnosing it quickly is challenging because the early signs often overlap with other common newborn health issues. While a blood culture is the most accurate way to confirm an infection, the results can take 48 to 72 hours. This delay highlights the need for faster, more accessible diagnostic tools.

This observational study aims to find quicker ways to diagnose neonatal sepsis and predict its severity using readily available blood tests. Researchers are investigating whether specific details from a standard Complete Blood Count (CBC), such as the variation in red blood cell size (RDW), the average size of platelets (MPV), and the ratio of immature to total white blood cells (I/T ratio), combined with serum lactate levels (a marker of tissue oxygenation and stress) can serve as reliable, early warning signs.

The study will enroll newborns (0 to 28 days old) admitted to the NICU who show clinical signs of a possible infection. Upon admission and before starting any antibiotic treatment, a small blood sample will be drawn to measure these CBC indices and serum lactate, alongside the standard blood culture.

By comparing these rapid blood test results with the final blood culture outcomes and the infants' overall clinical progress in the NICU, the research team hopes to determine if this simple combination of markers can help doctors diagnose sepsis earlier, anticipate the severity of the illness, and make faster, life-saving treatment decisions.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Neonatal sepsis remains one of the most devastating conditions encountered in neonatal intensive care units (NICUs) worldwide. The global population-level incidence of neonatal sepsis is estimated at approximately 2,202 cases per 100,000 live births, with mortality ranging between 11% and 19%. Diagnosis is clinically challenging because signs are nonspecific and overlap with other neonatal conditions. Although blood culture is the gold standard for diagnosis, it has significant limitations, including a 48 to 72-hour delay for results, low sensitivity due to the small blood volumes collected from neonates, and the risk of contamination. Complete blood count (CBC) indices, including the absolute neutrophil count, immature-to-total neutrophil (I/T) ratio, mean platelet volume (MPV), and red cell distribution width (RDW), have attracted interest as accessible screening tools. Furthermore, serum lactate is an established critical prognostic biomarker that reflects tissue hypoperfusion and anaerobic metabolism. This study aims to evaluate the combined diagnostic and prognostic values of these CBC-derived indices and serum lactate in a resource-limited NICU environment.

Upon admission to the NICU, every enrolled neonate will undergo a comprehensive clinical assessment.

Maternal and perinatal history will be extracted from obstetric records, including details such as maternal age, duration of premature rupture of membranes (PROM), intrapartum fever, maternal urinary tract infections, Group B Streptococcus (GBS) status, and mode of delivery.
Continuous physiologic monitoring will record heart rate, respiratory rate, and oxygen saturation.
Core body temperature will be assessed continuously using skin temperature probes.
An attending neonatologist will conduct a physical examination to document clinical signs of sepsis, including feeding intolerance, abdominal distension, lethargy, hypotonia, apnea, chest retractions, cyanosis, and altered capillary refill time.

To prevent pre-analytical errors and sample contamination, a strict aseptic blood sampling protocol will be executed prior to the administration of any empirical antimicrobial therapy.

Skin antisepsis will be performed using a two-step technique with 70% isopropyl alcohol followed by 2% chlorhexidine gluconate, which will be allowed to air-dry completely.
A precise volume of 3.0 to 4.0 mL of peripheral venous blood will be extracted.
The blood will be distributed in a strict order of draw: 1.0 to 2.0 mL for the pediatric aerobic blood culture bottle, 1.0 mL into a gray-top tube containing Sodium Fluoride and Potassium Oxalate to halt glycolysis for lactate testing, and 1.0 mL into a purple-top K2EDTA tube for the CBC.

Laboratory Analytical Methods:

CBC parameters will be analyzed using a fully automated, 5-part differential hematology analyzer utilizing flow cytometry and electrical impedance (Coulter principle). Additionally, a manual peripheral blood smear stained with Leishman's stain will be evaluated under a light microscope by a designated clinical pathologist blinded to the patient's clinical status. The pathologist will evaluate for toxic granulation, Döhle bodies, and cytoplasmic vacuolization, and perform a manual 100-cell differential count to calculate the I/T ratio.
Serum lactate levels will be quantified using a high-throughput automated clinical chemistry analyzer, with photometric measurement at a wavelength of 540 to 550 nm.
Blood cultures will be loaded into an automated, continuous-monitoring microbial detection system. Bottles will be incubated at 37.0°C and continuously agitated, utilizing sensors to detect carbon dioxide produced by actively metabolizing microorganisms. Negative bottles will be incubated for a full 5 days before being finalized.

Study Type

Observational

Enrollment (Estimated)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

The study population will consist of term and preterm neonates, aged 0 to 28 days, who are admitted to the Neonatal Intensive Care Unit (NICU) at the Pediatrics Department of Assiut University Children Hospitals in Assiut, Egypt. Eligible participants must present with two or more clinical signs highly suggestive of sepsis, such as temperature instability, tachycardia or bradycardia, tachypnea, feeding intolerance, lethargy, or altered muscle tone. Neonates with severe congenital anomalies, chromosomal abnormalities, inborn errors of metabolism, severe perinatal asphyxia, or those who have received prior broad-spectrum intravenous antibiotics for more than 24 hours, prior blood transfusions, or require immediate surgical intervention will not be included in the study.

Description

Inclusion Criteria:

Neonates aged 0 to 28 days (term and preterm).
Presence of two or more clinical signs highly suggestive of sepsis (e.g., temperature instability [< 36.5°C or > 37.5°C], tachycardia/bradycardia, tachypnea, feeding intolerance, lethargy, or altered muscle tone).
Informed written consent obtained from the parents or legal guardians.

Exclusion Criteria:

Neonates with severe congenital anomalies or chromosomal abnormalities.
Neonates diagnosed with Inborn Errors of Metabolism (which inherently alter lactate levels).
Neonates with severe perinatal asphyxia or Hypoxic-Ischemic Encephalopathy (HIE), as these conditions cause profound primary lactic acidosis independent of sepsis.
Neonates who received prior broad-spectrum intravenous antibiotics for more than 24 hours prior to admission.
Neonates who have received prior blood transfusions.
Neonates requiring immediate surgical intervention.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Neonates with Suspected Sepsis This cohort includes term and preterm neonates aged 0 to 28 days admitted to the Neonatal Intensive Care Unit (NICU) presenting with two or more clinical signs highly suggestive of sepsis (e.g., temperature instability, tachycardia/bradycardia, tachypnea, feeding intolerance, lethargy, or altered muscle tone). Upon admission and prior to the administration of any empirical antimicrobial therapy, peripheral venous blood samples will be drawn to evaluate Complete Blood Count (CBC) indices, quantify serum lactate levels, and perform a blood culture. As this is an observational study, no experimental interventions or medications will be administered to this group.

Group / Cohort

Neonates with Suspected Sepsis

This cohort includes term and preterm neonates aged 0 to 28 days admitted to the Neonatal Intensive Care Unit (NICU) presenting with two or more clinical signs highly suggestive of sepsis (e.g., temperature instability, tachycardia/bradycardia, tachypnea, feeding intolerance, lethargy, or altered muscle tone). Upon admission and prior to the administration of any empirical antimicrobial therapy, peripheral venous blood samples will be drawn to evaluate Complete Blood Count (CBC) indices, quantify serum lactate levels, and perform a blood culture. As this is an observational study, no experimental interventions or medications will be administered to this group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Accuracy of Immature-to-Total Neutrophil (I/T) Ratio Time Frame: Baseline (Upon admission to the NICU, prior to empirical antimicrobial therapy)	he diagnostic accuracy (including Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and Area Under the ROC Curve) of the initial Immature-to-Total Neutrophil (I/T) ratio in distinguishing between culture-proven sepsis, clinical sepsis, and non-septic neonates.	Baseline (Upon admission to the NICU, prior to empirical antimicrobial therapy)
Diagnostic Accuracy of Mean Platelet Volume (MPV) Time Frame: Baseline (Upon admission to the NICU, prior to empirical antimicrobial therapy)	The diagnostic accuracy (including Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and Area Under the ROC Curve) of the initial Mean Platelet Volume (MPV) in distinguishing between culture-proven sepsis, clinical sepsis, and non-septic neonates.	Baseline (Upon admission to the NICU, prior to empirical antimicrobial therapy)
Diagnostic Accuracy of Red Cell Distribution Width (RDW) Time Frame: Baseline (Upon admission to the NICU, prior to empirical antimicrobial therapy)	The diagnostic accuracy (including Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and Area Under the ROC Curve) of the initial Red Cell Distribution Width (RDW) in distinguishing between culture-proven sepsis, clinical sepsis, and non-septic neonates.	Baseline (Upon admission to the NICU, prior to empirical antimicrobial therapy)
Diagnostic Accuracy of Admission Serum Lactate Levels Time Frame: Baseline (Upon admission to the NICU, prior to empirical antimicrobial therapy)	The diagnostic accuracy (including Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and Area Under the ROC Curve) of initial serum lactate levels in distinguishing between culture-proven sepsis, clinical sepsis, and non-septic neonates.	Baseline (Upon admission to the NICU, prior to empirical antimicrobial therapy)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2026

Primary Completion (Estimated)

August 1, 2027

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

June 17, 2026

First Submitted That Met QC Criteria