Inflammation IndicesSepsisNCT07635264
Late-Onset Neonatal Sepsis: A Case-Control Study
An observational study of Inflammation Indices and Late Onset Neonatal Sepsis, run by Mersin University at 1 site in Turkey (Türkiye).
Trial summary
The diagnosis of late-onset sepsis in term neonates has been studied less than that of early-onset sepsis. Procalcitonin (PCT) and C-reactive protein (CRP) are commonly used biomarkers in the diagnosis of sepsis. However, their diagnostic advantage for late-onset sepsis (GNS) is debatable. Read more about this study
- Who is it for?
- Ages 3 to 28 daysHealthy volunteers can take part
- Conditions the study is for
- Inflammation Indices, Late Onset Neonatal Sepsis
- What is being tested?
- serum biomarker
- How many people
- 128 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Jul 2020to 1 Jul 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 28 days
- All sexes
- Healthy volunteers accepted
- Child
Study population: The study was conducted with two groups: term patients (38-42 weeks' gestation) and controls. The control group was selected to match the sepsis group as closely as possible (at a 1:1 ratio) in terms of demographic characteristics, and taking gestational age into account
Who may be able to join
- Term newborn
- Late-onset neonatal sepsis
Who cannot join
- Preterm newborn
- Major congenital anomaly
- Congenital metabolic disease
- Hemolytic anemia
- Hematological diseases
- Congenital leukemia
Show all 13Show fewer
- Dyserythropoietic anemia
- Early-onset neonatal sepsis
- Control group
- Neonatal jaundice (indirect hyperbilirubinemia)
- Transient neonatal tachypnea
- Early neonatal sepsis
- Exclusion criteria Perinatal asphyxia, Meconium aspiration syndrome Polycythemia İntraventricular hemoragy Pneumothorax Hemolytic Anemia
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Traditional Biomarkers and Novel Inflammatory Indices in the Diagnosis of Late-Onset Neonatal Sepsis: A Case-Control Study
The diagnosis of late-onset sepsis in term neonates has been studied less than that of early-onset sepsis. Procalcitonin (PCT) and C-reactive protein (CRP) are commonly used biomarkers in the diagnosis of sepsis. However, their diagnostic advantage for late-onset sepsis (GNS) is debatable. Rapid and accurate diagnosis of late-onset infection in newborn infants remains a significant goal in clinical practice worldwide. Therefore, the accuracy of diagnostic tests needs to be improved. This study aimed to evaluate the effectiveness of serum biomarkers in the diagnosis and treatment monitoring of late neonatal sepsis (LOS) in term neonates.
Read the detailed description
Early diagnosis and detection of LOS are challenging due to its often nonspecific symptoms and the limited diagnostic efficacy of commonly used biomarkers. Therefore, a combined evaluation of clinical and laboratory findings is necessary. While initial assessment often includes nonspecific tests such as complete blood count and inflammatory markers, the most important test is a blood culture of at least 1 mL of blood before antibiotic administration.Although acute phase reactants such as C-reactive protein (CRP), procalcitonin (PCT), and various interleukins are used to support the diagnosis of sepsis in newborns, they are also elevated by other non-infectious inflammatory causes (fetal hypoxia, birth stress, RDS, MAS, IVH, surgery, and pneumothorax). Serum CRP could be a useful biomarker for LOS in newborn infants if it can be demonstrated to have acceptable levels of accuracy. Currently, the role of serum CRP in diagnostic algorithms for late-onset infection is largely varied in the absence of robust evidence to inform the development of guidelines or protocols. Further studies have shown that the immature/total neutrophil ratio and absolute neutrophil values are poor predictors of LOS. Due to age-specific, gestational age-dependent, and neonatal physiological changes in the early postpartum period, there is no consensus on the threshold value of serum PCT levels in bacterial infection.Common laboratory markers of infection, such as white blood cell count (WBC), immature neutrophil/total neutrophil ratio (IT ratio), hematological tests (thrombocytopenia), and acute phase reactants (CRP, PCT), do not have sufficient specificity and sensitivity to detect all infected newborns.Literature analysis has shown that, despite extensive research, the diagnosis and antibiotic treatment of neonatal sepsis cannot currently be determined based on a single biomarker. However, instead of searching for new biomarkers, testing combinations of two or more of the currently available biomarkers seems easier and more productive. The literature has focused primarily on the diagnosis of LOS in preterm neonates. Our current study differs from previous studies in that it evaluates the systemic inflammation aggregate index (SIAI) and systemic inflammation index (SII) values serially, in addition to classical biomarkers. Our aim is to identify a practical combination of commonly used laboratory tests that can evaluate the diagnosis and monitoring of term LOS when suspected.
- Conditions
- Inflammation Indices, Late Onset Neonatal Sepsis
- Being tested
- serum biomarker
- Keywords
- late onset sepsis, biomarkers, CRP, PCT, inflammation indices, term newborn
- Medical subject headings
- Neonatal Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
serum biomarkerDiagnostic test
that of diagnosis of sepsis, and on the third and seventh days after the commencement of antibiotic therapy. SII was calculated using the formula (neutrophils×platelets)/lymphocytes, and SIAI using neutrophils×monocytes×platelets / lymphocytes
| Study group | Role | What they receive |
|---|---|---|
| Patient group 1 control group 2 | The control group was selected to match the sepsis group as closely as possible (at a 1:1 ratio) in terms of demographic characteristics and taking gestational age into account Receives: Diagnostic Test: serum biomarker | |
| control group and patient group | Neonates born before the 38th week of pregnancy, with major congenital anomaly or congenital metabolic disease, babies born to substance-dependent mothers, with hemolytic anemia or other hematological diseases (such as congenital leukemia, dyserythropoetic anemia, or severe hemolytic diseases), and babies diagnosed with immunodeficiency, with early-onset sepsis, with histories of surgery, or with deficient laboratory data were excluded. All babies diagnosed with LOS and meeting none of the exclusion criteria were enrolled and constituted the LOS cohort. In case of more than one LOS episode, only the first was included in the analysis.
Babies with neonatal jaundice (indirect hyperbillurubinemia) of non-hemolytic causes that resolved with phototherapy alone, with transient neonatal tachypnea resolving within the first 24 hours and with no sepsis attack, and infants with non-infectious causes admitted to the NICU were included in the control group. Exclusion criteria for the control gr Receives: Diagnostic Test: serum biomarker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary outcome measure
Immature granulocyte (IG) percentage, the neutrophil/lymphocyte ratio (NLR), CRP, PCT, SIAI, and SII values were recorded from retrospective file data on the first day, that of diagnosis of sepsis, and on the third and seventh days after the commencement of antibiotic therapy. SII was calculated using the formula (neutrophils×platelets)/lymphocytes, and SIAI using neutrophils×monocytes×platelets / lymphocytes.
Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. This study aimed to evaluate the diagnostic performance of commonly used and novel inflammatory biomarkers, both individually and in combination, focusing on their temporal dynamics.
The performance of diagnostic biomarkers (CRP, PCT, IG, SII, and SIAI) was evaluated using receiver operating characteristic (ROC) curve analysis. For each biomarker, the area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were planned to be c
Measured: From July 2020 to July 2024
practical and effective biomarker combination consisting of widely available laboratory tests capable of being used in the diagnosis and monitoring of LOS in term neonates.
Term late onset sepsis diagnosis
Measured: From July 2020 to July 2024
Diagnostic efficacy of biomarkers in late neonatal sepsis
LOS was defined as onset of sepsis symptoms after the 72nd hour (third day). LOS resulted in respiratory symptoms (apnea, tachypnea, desaturation, and increasing mechanical ventilator support requirements), hemodynamic symptoms (bradycardia, skin color changes, decreased peripheral perfusion, hypotension and cardiovascular impairment, and inotropic therapy requirements), metabolic abnormalities (hypoglycemia, hyperglycemia, or metabolic acidosis abnormalities), body temperature irregularities (hypo or hyperthermia), feeding intolerance, and neurological symptoms (hypotonia, poor sucking, and low neurological activity) . Sepsis was evaluated using complete blood count, CRP, PCT, and blood culture. In line with our routine clinical protocol, specimens were collected from neonates with sepsis before the initiation of antibiotic therapy.
Measured: Baseline and 3, 7-day serum biomarker
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2026
- Study start1 Jul 2020
- Primary completion1 Jul 2024
- Study completion1 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammation IndicesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mersin University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aysen Orman, Mersin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07635264
- Sponsor's protocol ID
- Mersin University Neonatology
- Acronym
- Sepsis
- Status last verified
- Jun 2026
- First submitted
- 21 Apr 2026
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Special sensitive population
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Traditional Biomarkers and Novel Inflammatory Indices in the Diagnosis of Late-Onset Neonatal Sepsis: A Case-Control Study
- ClinicalTrials.gov ID
- NCT07635264
- Acronym / sponsor ID
- Sepsis / Mersin University Neonatology
- Conditions
- Inflammation Indices, Late Onset Neonatal Sepsis
- Keywords
- late onset sepsis, biomarkers, CRP, PCT, inflammation indices, term newborn
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- Mersin UniversityUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 1 Jul 2024 (actual)
- Study completion
- 1 Jul 2025 (actual)
- First posted
- 9 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The diagnosis of late-onset sepsis in term neonates has been studied less than that of early-onset sepsis. Procalcitonin (PCT) and C-reactive protein (CRP) are commonly used biomarkers in the diagnosis of sepsis. However, their diagnostic advantage for late-onset sepsis (GNS) is debatable. Rapid and accurate diagnosis of late-onset infection in newborn infants remains a significant goal in clinical practice worldwide. Therefore, the accuracy of diagnostic tests needs to be improved. This study aimed to evaluate the effectiveness of serum biomarkers in the diagnosis and treatment monitoring of late neonatal sepsis (LOS) in term neonates.
Detailed description
Early diagnosis and detection of LOS are challenging due to its often nonspecific symptoms and the limited diagnostic efficacy of commonly used biomarkers. Therefore, a combined evaluation of clinical and laboratory findings is necessary. While initial assessment often includes nonspecific tests such as complete blood count and inflammatory markers, the most important test is a blood culture of at least 1 mL of blood before antibiotic administration.Although acute phase reactants such as C-reactive protein (CRP), procalcitonin (PCT), and various interleukins are used to support the diagnosis of sepsis in newborns, they are also elevated by other non-infectious inflammatory causes (fetal hypoxia, birth stress, RDS, MAS, IVH, surgery, and pneumothorax). Serum CRP could be a useful biomarker for LOS in newborn infants if it can be demonstrated to have acceptable levels of accuracy. Currently, the role of serum CRP in diagnostic algorithms for late-onset infection is largely varied in the absence of robust evidence to inform the development of guidelines or protocols. Further studies have shown that the immature/total neutrophil ratio and absolute neutrophil values are poor predictors of LOS. Due to age-specific, gestational age-dependent, and neonatal physiological changes in the early postpartum period, there is no consensus on the threshold value of serum PCT levels in bacterial infection.Common laboratory markers of infection, such as white blood cell count (WBC), immature neutrophil/total neutrophil ratio (IT ratio), hematological tests (thrombocytopenia), and acute phase reactants (CRP, PCT), do not have sufficient specificity and sensitivity to detect all infected newborns.Literature analysis has shown that, despite extensive research, the diagnosis and antibiotic treatment of neonatal sepsis cannot currently be determined based on a single biomarker. However, instead of searching for new biomarkers, testing combinations of two or more of the currently available biomarkers seems easier and more productive. The literature has focused primarily on the diagnosis of LOS in preterm neonates. Our current study differs from previous studies in that it evaluates the systemic inflammation aggregate index (SIAI) and systemic inflammation index (SII) values serially, in addition to classical biomarkers. Our aim is to identify a practical combination of commonly used laboratory tests that can evaluate the diagnosis and monitoring of term LOS when suspected.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patient group 1 control group 2 | – | Diagnostic Test: serum biomarkerThe control group was selected to match the sepsis group as closely as possible (at a 1:1 ratio) in terms of demographic characteristics and taking gestational age into account |
| control group and patient group | – | Diagnostic Test: serum biomarkerNeonates born before the 38th week of pregnancy, with major congenital anomaly or congenital metabolic disease, babies born to substance-dependent mothers, with hemolytic anemia or other hematological diseases (such as congenital leukemia, dyserythropoetic anemia, or severe hemolytic diseases), and babies diagnosed with immunodeficiency, with early-onset sepsis, with histories of surgery, or with deficient laboratory data were excluded. All babies diagnosed with LOS and meeting none of the exclusion criteria were enrolled and constituted the LOS cohort. In case of more than one LOS episode, only the first was included in the analysis. Babies with neonatal jaundice (indirect hyperbillurubinemia) of non-hemolytic causes that resolved with phototherapy alone, with transient neonatal tachypnea resolving within the first 24 hours and with no sepsis attack, and infants with non-infectious causes admitted to the NICU were included in the control group. Exclusion criteria for the control gr |
Who may qualify
- Ages
- 3 to 28 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- The study was conducted with two groups: term patients (38-42 weeks' gestation) and controls. The control group was selected to match the sepsis group as closely as possible (at a 1:1 ratio) in terms of demographic characteristics, and taking gestational age into account
Key inclusion criteria (2 listed)
- Term newborn
- Late-onset neonatal sepsis
Key exclusion criteria (13 listed)
- Preterm newborn
- Major congenital anomaly
- Congenital metabolic disease
- Hemolytic anemia
- Hematological diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| serum biomarkerthat of diagnosis of sepsis, and on the third and seventh days after the commencement of antibiotic therapy. SII was calculated using the formula (neutrophils×platelets)/lymphocytes, and SIAI using neutrophils×monocytes×platelets / lymphocytes | Diagnostic test | Patient group 1 control group 2, control group and patient group |
Primary outcome
Primary outcome measure
Time frame: From July 2020 to July 2024
Immature granulocyte (IG) percentage, the neutrophil/lymphocyte ratio (NLR), CRP, PCT, SIAI, and SII values were recorded from retrospective file data on the first day, that of diagnosis of sepsis, and on the third and seventh days after the commencement of antibiotic therapy. SII was calculated using the formula (neutrophils×platelets)/lymphocytes, and SIAI using neutrophils×monocytes×platelets / lymphocytes. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. This study aimed to evaluate the diagnostic performance of commonly used and novel inflammatory biomarkers, both individually and in combination, focusing on their temporal dynamics. The performance of diagnostic biomarkers (CRP, PCT, IG, SII, and SIAI) was evaluated using receiver operating characteristic (ROC) curve analysis. For each biomarker, the area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were planned to be c
practical and effective biomarker combination consisting of widely available laboratory tests capable of being used in the diagnosis and monitoring of LOS in term neonates.
Time frame: From July 2020 to July 2024
Term late onset sepsis diagnosis
Diagnostic efficacy of biomarkers in late neonatal sepsis
Time frame: Baseline and 3, 7-day serum biomarker
LOS was defined as onset of sepsis symptoms after the 72nd hour (third day). LOS resulted in respiratory symptoms (apnea, tachypnea, desaturation, and increasing mechanical ventilator support requirements), hemodynamic symptoms (bradycardia, skin color changes, decreased peripheral perfusion, hypotension and cardiovascular impairment, and inotropic therapy requirements), metabolic abnormalities (hypoglycemia, hyperglycemia, or metabolic acidosis abnormalities), body temperature irregularities (hypo or hyperthermia), feeding intolerance, and neurological symptoms (hypotonia, poor sucking, and low neurological activity) . Sepsis was evaluated using complete blood count, CRP, PCT, and blood culture. In line with our routine clinical protocol, specimens were collected from neonates with sepsis before the initiation of antibiotic therapy.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2026.
- Individual participant dataSharing planned: No. Special sensitive population
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammation Indices and Late Onset Neonatal Sepsis, run by Mersin University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary outcome measure (time frame: From July 2020 to July 2024). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2026.