The role of presepsin in predicting neonatal sepsis in cases of preterm premature membrane rupture

Abstract

AimIn this study, our aim was to evaluate the predictive value of presepsin (P-SEP) for neonatal sepsis in pregnant women with preterm premature rupture of the membranes (PPROM).MethodsThe study included 20 pregnant women between the ages of 18 and 40 who presented with PPROM between the 24th and 37th weeks of pregnancy. The control group consisted of a total of 40 pregnant women, confirmed by last menstrual period and early ultrasound examinations, between the 24th and 37th weeks of pregnancy. In our study, samples were collected from both maternal and fetal umbilical cords in the PPROM group and from maternal and fetal cord blood in the control group. Presepsin levels were analyzed in the laboratory using an ELISA kit.ResultsNo statistically significant relationship was found between maternal presepsin, fetal presepsin levels, and clinical data and laboratory assessments of the pregnant women.ConclusionThere is no relationship between presepsin levels and neonatal sepsis.

Keywords

Introduction

Newborn sepsis is a significant cause of morbidity and mortality, particularly in premature infants.¹ The mortality rate can reach up to 70% in very low birth weight infants (birth weight < 1500 g).² Beyond being a life-threatening condition, sepsis can lead to long-term complications in survivors and significantly impair the neurophysiological development of the brain.^3-4 Given that the disease can rapidly progress to septic shock and multiple organ dysfunction syndrome, early diagnosis is crucial for improving survival. Unfortunately, diagnosing sepsis in newborns can be challenging. Blood culture is the gold standard for diagnosing sepsis, but results typically take at least 48-72 hours, and false-negative results cannot be ignored in cases of early-onset sepsis.⁵ While various markers for sepsis have been identified, the quest for the optimal sepsis biomarker is still ongoing. Among these, C-reactive protein (CRP) lacks consistent specificity in distinguishing inflammatory conditions. Procalcitonin (PCT) has the advantage of rising more rapidly and appears to be more specific for bacterial infections.⁶ Presepsin (P-SEP) is a fragment of soluble CD14 subtype (sCD14-ST), released as an acute response from monocytes and macrophages to microbial infection. Clinically, the aim is to identify newborns at high risk for early-onset sepsis before the onset of clinical symptoms and reduce the need for prophylactic antibiotic treatment.⁷ In this study, our goal was to evaluate the predictive value of presepsin for neonatal sepsis in pregnant women with preterm premature rupture of the membranes (PPROM).

Materials and Methods

The study was conducted at Sariyer Hamidiye Etfal Education and Research Hospital and included 20 pregnant women between the ages of 18 and 40 who presented with PPROM between the 24th and 37th weeks of pregnancy during the years 2020-2021. The control group consisted of a total of 40 pregnant women, confirmed by last menstrual period and early ultrasound examinations, between the 24th and 37th weeks of pregnancy. Pregnant women with a history of chronic diseases such as maternal systemic infection, hypertension, diabetes mellitus, or autoimmune diseases, those with clinical chorioamnionitis, those with polyhydramnios detected in ultrasound, multiple pregnancies, uterine malformations, and those with meconium-stained amniotic fluid were excluded from the study.
To determine presepsin levels, 1 mL of blood sample was collected into tubes containing ethylenediaminetetraacetic acid (EDTA). Plasma samples for presepsin were centrifuged at 3000 rpm for 5 minutes and stored at -80°C before analysis. Presepsin was measured using the PATHFAST immunoassay analyzer (Mitsubishi Chemical Medience Co.; Tokyo, Japan), a chemiluminescent enzyme immunoassay for the quantitative measurement of presepsin concentration. Monoclonal and polyclonal antibodies recognizing presepsin were used in the test. Presepsin concentration can be determined within 17 minutes using PATHFAST. In our study, samples were collected from both maternal and fetal umbilical cords in the PPROM group and from maternal and fetal cord blood in the control group. Presepsin analysis was performed using the presepsin ELISA kit in the Special Development Laboratory (Özel Gelişim Laboratuvarı). Diagnosis of neonatal sepsis was based on the Töller Scoring System,⁸ which combines clinical (hypotonia, bradycardia, apnea, respiratory distress, hepatomegaly, poor peripheral circulation, abdominal distension, and changes in skin color) and laboratory (elevated white blood cell count and low platelet count, metabolic acidosis, and immature/total neutrophil ratio) parameters. Each parameter is assigned a score from 0 to 3. If the total score is greater than 10, a clinical sepsis diagnosis is made.
The study was carried out with the permission of Istanbul Health Sciences University Prof. Dr. Cemil Tascioglu Clinical Research Ethics Committee (Date: 2021-10-11, Decision No: 329). All procedures were carried out in accordance with the ethical rules and the principles of the Declaration of Helsinki.Ethical ApprovalEthics Committee approval for the study was obtained. This study was approved by the Ethics Committee of Istanbul Health Sciences University Prof. Dr. Cemil Tascioglu Clinical Research (Date: 11.10.2021, Decision No: 329)Statistical AnalysisStatistical analysis was conducted using SPSS 15.0 for Windows software. Descriptive statistics included counts and percentages for categorical variables, and for numerical variables, means, standard deviations, minimum, maximum, and medians were reported. Group comparisons for proportions were performed using the Chi-square test. Independent group comparisons for numerical variables were conducted using the Student t-test when the assumption of normal distribution was met and the Mann-Whitney U test when it was not met. Relationships between numerical variables were examined using Spearman’s Correlation Analysis due to the non-parametric nature of the data. Associated factors were explored using Linear Regression Analysis. The alpha significance level was set at P<0.05.

Results

Mothers with early membrane rupture had a statistically significantly lower gestational age compared to the control group, shorter time until delivery, and a higher rate of normal spontaneous delivery (P=0.048, P=0.020, P=0.004, respectively). The findings are summarized in Table 1.
In pregnant women with early membrane rupture, there was no statistically significant difference in hemoglobin (Hb), hematocrit (Hct), white blood cell count (WBC), C-reactive protein (CRP), and presepsin levels compared to the control group. Similarly, among the babies of the groups described earlier, there was no statistically significant difference in Hb, Hct, WBC, CRP, and presepsin levels. The findings are summarized in Table 2.
Statistically significant relationships were not found between maternal presepsin and infant presepsin levels and the clinical data and laboratory assessments of pregnant women (Table 3). Multivariate Linear Regression Analysis based on variables with P<0.250 in univariate analyses to examine the relationships between maternal and infant presepsin levels, did not identify any significant factors.

Discussion

In our study, there was no relationship found between neonatal sepsis and presepsin levels in preterm mothers with premature rupture of the membranes (PROM) compared to preterm mothers without membrane rupture. Early diagnosis and treatment of sepsis are fundamental for improving survival. Currently, no single biomarker, such as white blood cell count (WBC), procalcitonin (PCT), C-reactive protein (CRP), or interleukin-6 (IL-6), which are widely used in clinical practice, can serve as an ideal biomarker for sepsis.⁹ CD14, a glycoprotein expressed in monocytes and macrophages, serves as a receptor for bacterial lipopolysaccharides (LPS) and plays a role in activating the proinflammatory signaling cascade as part of the innate immune system. CD14 exists in two forms: membrane-bound (mCD14) and soluble (sCD14). Soluble CD14 subtype (sCD14-ST), also known as presepsin, significantly increases during the progression of sepsis cascades.⁹ In a study, C-reactive protein (CRP), one of the other sepsis markers, had limited diagnostic potential in the early stages of sepsis due to delayed hepatic synthesis and the presence of other inducing factors independent of infection. Furthermore, CRP levels at admission were found to be similar in newborns with positive and negative blood cultures suspected of early-onset sepsis.¹⁰ The use of procalcitonin (PCT), one of the most commonly used markers for sepsis, is limited because PCT levels can physiologically rise up to 48 hours after birth.¹¹ While the diagnostic efficiency of these markers may increase when combined, identifying a single early-onset sepsis marker with high sensitivity and positive predictive value (PPV) would benefit clinical practice. Consensus on pediatric sepsis definitions has limited accuracy for term newborns and is not suitable for premature infants. The primary reason is that organ dysfunction, the fundamental diagnostic criterion, is rarely considered in the newborn literature, and it remains unclear how newborns should be screened for organ dysfunction.¹² Previously published data have supported the use of presepsin in the diagnosis of early-onset sepsis and have demonstrated similar or higher diagnostic accuracy compared to other inflammatory markers.¹³ Therefore, incorporating presepsin into clinical practice may help prevent false-positive sepsis diagnoses, limiting newborns’ exposure to antimicrobial drugs, their side effects, and invasive procedures.¹⁴

Limitations

The limitation of this study include limited number of registered newborns, and the quantitative heterogeneity of the studied subgroups could affect the precision of statistical analysis. Secondly, the absence of positive blood culture samples and sepsis in our cohort limits the predictive value of presepsin. Based on our data, we recommend that the performance of presepsin be prospectively investigated in larger cohorts and in heterogeneous groups in the future.

Conclusion

There is no relationship between presepsin levels and neonatal sepsis.

Declarations

References

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