Bio-Functionalized Magnetic Nanoparticles for the Immunoassay of C-Reactive Protein and Procalcitonin in Cervicovaginal Secretions of Pregnant Women with Preterm Prelabor Rupture of Membranes to Predict Early-Onset Neonatal Sepsis

Abstract

Purpose Early-onset sepsis is a major cause of neonatal morbidity and mortality. C-reactive protein (CRP) and procalcitonin (PCT) are acute phase reactants related to infection. The aim of this study was to explore the feasibility of measuring CRP and PCT concentrations in cervicovaginal secretions of pregnant women with preterm prelabor rupture of membranes (PPROM) using an immunomagnetic reduction (IMR) assay to predict early-onset neonatal sepsis. Patients and Methods This prospective study was performed at Mackay Memorial Hospital, Taipei, Taiwan from February 2015 to January 2018. Pregnant women with PPROM between 22 and 34 weeks of gestation were recruited. CRP and PCT concentrations in cervicovaginal secretions were measured using an IMR assay. Results Thirty-five cervicovaginal secretion samples were obtained. After excluding two neonatal deaths, early-onset neonatal sepsis was diagnosed in 15 of the 33 surviving neonates. There was no significant relationship between cervicovaginal secretion CRP level and neonatal sepsis; however, cervicovaginal secretion PCT levels were significantly higher in the neonatal sepsis group than in the non-sepsis group (45.99 vs 9.54 ng/mL, P = 0.039). Receiver operating characteristic (ROC) curve analysis revealed a PCT cut-off level of 20.60 ng/mL to predict early-onset sepsis, and the area under the ROC curve was 0.71 (95% confidence interval 0.52 to 0.90, P = 0.039), with sensitivity and specificity of 73.3% and 77.8%, respectively. Conclusion Measuring the concentration of PCT in cervicovaginal secretions with an IMR assay can predict early-onset sepsis in neonates born to mothers with PPROM.

Maternal biomarkers in predicting neonatal sepsis after preterm premature rupture of membranes in preterm infants

“…Proteomic analysis of amniotic fluid is innovative, but this is not yet available in clinical practice. Recently, measuring the concentration of procalcitonin, 10,25 IL‐6 and tumour necrosis factor α 12 in cervicovaginal secretions showed promising results for predicting early‐onset sepsis in neonates born to mothers with pPROM.…”

“…is not yet available in clinical practice. Recently, measuring the concentration of procalcitonin, 10,25 CRP ≥1 mg/dL -A: sensitivity 64.9% specificity 56.0%, PPV 15.8%, NPV 92.6%; B: sensitivity 64.3% specificity 60.3%, PPV 37.7%, NPV 81.9%; CRP ≥2 mg/dL -A: sensitivity 45.5% specificity 74.5%, PPV 18.5%, NPV 91.5%; B: sensitivity 47.0% specificity 79.4%, PPV 46.0%, NPV 80.1%; CRP ≥5 mg/dL -A: sensitivity 24.7% specificity 94.0%, PPV 34.5%, NPV 90.7%; B: sensitivity 17.8% specificity 95.6%, PPV 60.0%, NPV 75.7%; Leukocytes > 16 G/L -A: sensitivity 36.5% specificity 75.1%, PPV 15.3%, NPV 90.6%; B: sensitivity 39.0% specificity 78.5%, PPV 40.1%, NPV 77.8%. Group 1: culture-positive early-onset neonatal sepsis (EONS), group 2: culture-negative EONS, group 3: positive neonatal laboratory biomarkers, group 4: negative neonatal laboratory biomarkers.…”

Nanotechnology Applications in Sepsis: Essential Knowledge for Clinicians

“…Last year, Ang et al published the results of another innovative biosensor, particularly a biofunctionalized magnetic nanoparticle immunoassay of CRP and PCT [ 39 ]. The study evaluated the performance of this system in cervicovaginal secretions of pregnant women with preterm pre-labor rupture of membranes to predict early onset neonatal sepsis.…”

“…The signal is then obtained by measuring the attenuation in oscillation using a series of equations. This diagnostic strategy allowed for extremely low detection limits, ranging from 10 −4 ng/mL and 10 −6 ng/mL in CRP and PCT, respectively [ 39 ]. Additionally, the immunomagnetic assays used were of simple pre-processing and allowed for the evaluation of dozens of samples simultaneously.…”

A Clinician’s Perspective on the Use of Laboratory Markers of Sepsis

“…Не было выявлено значимой связи между уровнем цервиковагинального секрета СРБ и неонатальным сепсисом, однако уровни ПКТ цервиковагинальной секреции оказались значительно выше в группе неонатального сепсиса, чем в группе без сепсиса. Уровень ПКТ 20,60 мкг/л являлся предиктором для прогнозирования сепсиса [7]. Достаточно высокую диагностическую значимость имеют также показатели материнского СРБ (≥12,2 мг/л) для оценки риска развития раннего неонатального сепсиса [8].…”