RESUMEN
OBJECTIVES: Thermostability is one of the pre-requisites for the reliability of analytes in clinical practice and biomedical research. Although presepsin represents a promising new biomarker for the early diagnosis of sepsis in newborns, data on its stability under different storage conditions are lacking. We aimed to investigate presepsin thermostability in blood, urine and saliva samples after thawing at 4 predetermined monitoring time-points in a cohort of preterm and term infants. METHODS: We conducted an observational study, where each case served as its own control, in 24 preterm and term infants. Blood, urine and saliva samples were stored at -80⯰C for 18 months, and presepsin measured in different biological fluids at thawing (T0), 24 (T1), 48 (T2) and at 72 (T3) hours after thawing. RESULTS: No significant differences (p>0.05, for all) in presepsin levels were observed at T0-T3 in the different biological fluids. Furthermore, no differences at T0-T3 were observed in presepsin levels between blood and saliva fluids, whilst urine levels were significantly higher (p<0.05, for all) than blood and saliva at T0-T3. CONCLUSIONS: Results on presepsin pre-analytical thermo-stability in different biological fluids after long-term refrigeration support the reliability of this biomarker in the diagnosis and monitoring of perinatal sepsis.
Asunto(s)
Líquidos Corporales , Sepsis , Lactante , Femenino , Embarazo , Humanos , Recién Nacido , Temperatura , Reproducibilidad de los Resultados , Sepsis/diagnóstico , Biomarcadores , Receptores de Lipopolisacáridos , Fragmentos de Péptidos , Proteína C-ReactivaRESUMEN
OBJECTIVES: Early sepsis detection and diagnosis still constitutes an open issue since the accuracy of standard-of care parameters is biased by a series of perinatal factors including hypoxia. Therefore, we aimed at investigating the effect of fetal chronic hypoxia insult on urine levels of a promising new marker of sepsis, namely presepsin (P-SEP). METHODS: We conducted a prospective case-control study in 22 cases of early-intrauterine growth restriction (E-IUGR) compared with 22 small-for-gestational-age (SGA) newborns and 66 healthy controls. P-SEP urine samples were collected over the first 72â¯h from birth. Blood culture and C-reactive protein (CRP) blood levels were measured in E-IUGR and SGA infants. Perinatal standard monitoring parameters and main outcomes were also recorded. RESULTS: No significant urinary P-SEP differences (p>0.05, for all) were observed among studied groups. Moreover, no significant correlations (p>0.05, for both) between urinary P-SEP and blood CRP levels in both E-IUGR and SGA groups (R=0.08; R=0.07, respectively) were observed. CONCLUSIONS: The present results showing the lack of influence of fetal chronic hypoxia on urinary P-SEP levels offer additional data to hypothesize the possible use of urinary P-SEP measurement in neonates in daily clinical practice. Further multicenter prospective data are needed, including infants with early-onset sepsis.
Asunto(s)
Receptores de Lipopolisacáridos , Fragmentos de Péptidos , Humanos , Recién Nacido , Femenino , Estudios de Casos y Controles , Estudios Prospectivos , Fragmentos de Péptidos/orina , Fragmentos de Péptidos/sangre , Masculino , Embarazo , Hipoxia Fetal/orina , Hipoxia Fetal/diagnóstico , Hipoxia Fetal/sangre , Proteína C-Reactiva/análisis , Biomarcadores/orina , Biomarcadores/sangre , Recién Nacido Pequeño para la Edad Gestacional , Retardo del Crecimiento Fetal/orina , Retardo del Crecimiento Fetal/diagnóstico , Retardo del Crecimiento Fetal/sangre , Sepsis/orina , Sepsis/diagnóstico , Sepsis/sangreRESUMEN
OBJECTIVES: Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. METHODS: We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. RESULTS: S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78⯵g/L achieved a sensitivity/specificity of 63 and 84â¯%, positive/negative predictive values of 83 and 64â¯%. CONCLUSIONS: The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE.
Asunto(s)
Asfixia Neonatal , Hipotermia Inducida , Subunidad beta de la Proteína de Unión al Calcio S100 , Convulsiones , Humanos , Subunidad beta de la Proteína de Unión al Calcio S100/orina , Convulsiones/orina , Convulsiones/diagnóstico , Convulsiones/tratamiento farmacológico , Masculino , Recién Nacido , Femenino , Estudios de Casos y Controles , Estudios Prospectivos , Asfixia Neonatal/orina , Asfixia Neonatal/terapia , Asfixia Neonatal/complicaciones , Curva ROC , Hipoxia-Isquemia Encefálica/orina , Hipoxia-Isquemia Encefálica/terapia , Hipoxia-Isquemia Encefálica/diagnóstico , Fenobarbital/uso terapéutico , Lactante , Biomarcadores/orinaRESUMEN
AIM: To investigate the effects of caffeine loading/maintenance administration on near-infrared spectroscopy cerebral, kidney and splanchnic patterns in preterm infants. METHODS: We conducted a multicentre case-control prospective study in 40 preterm infants (gestational age 29 ± 2 weeks) where each case acted as its own control. A caffeine loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg after 24 h were administered intravenously. Near infrared spectroscopy monitoring parameters were monitored 30 min before, 30 min during and 180 min after caffeine therapy administration. RESULTS: A significant increase (p < 0.05) in splanchnic regional oxygenation and tissue function and a decrease (p < 0.05) in cerebral tissue function after loading dose was shown. A preferential hemodynamic redistribution from cerebral to splanchnic bloodstream was also observed. After caffeine maintenance dose regional oxygenation did not change in the monitored districts, while tissue function increased in kidney and splanchnic bloodstream. CONCLUSION: Different caffeine administration modalities affect cerebral/systemic oxygenation status, tissue function and hemodynamic pattern in preterm infants. Future studies correlating near infrared spectroscopy parameters and caffeine therapy are needed to determine the short/long-term effect of caffeine in preterm infants.
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Cafeína , Recien Nacido Prematuro , Recién Nacido , Humanos , Lactante , Cafeína/farmacología , Espectroscopía Infrarroja Corta , Estudios Prospectivos , Edad Gestacional , OxígenoRESUMEN
Perinatal sepsis constitutes a medical emergency and is still one of the major causes of mortality and morbidity. The possibility of an early diagnosis of sepsis is still debated and controversial. In particular, clinical symptoms can be hidden by the association of sepsis with other perinatal diseases and/or by therapeutic strategies performed. In this context, there is evidence that the accuracy of standard of care diagnostic parameters (i.e. blood culture, C-reactive protein, procalcitonin) can be biased by additional confounding factors (gestational age, birth-weight, acute-chronic hypoxia). Therefore, the inclusion in clinical daily practice of new biomarkers of sepsis is of utmost importance. Of a panel of biomarkers, Presepsin (P-SEP) plays an important role in the development and response of the immune system and as an early marker of sepsis both in adult and pediatric patients. Therefore, in the present review we aim to offer an overview of the role of P-SEP in the early detection of perinatal sepsis as a trustworthy marker according to actual statements of official international institutions. Future perspectives regard the possibility of a longitudinal non-invasive biological fluids P-SEP assessment thus limiting the sample stress in high risk newborns.
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Enfermedades del Recién Nacido , Sepsis , Adulto , Biomarcadores , Proteína C-Reactiva/análisis , Niño , Femenino , Humanos , Recién Nacido , Receptores de Lipopolisacáridos , Fragmentos de Péptidos , Embarazo , Polipéptido alfa Relacionado con Calcitonina , Sepsis/diagnósticoRESUMEN
The early detection of perinatal brain damage in preterm and term newborns (i.e. intraventricular hemorrhage, periventricular leukomalacia and perinatal asphyxia) still constitute an unsolved issue. To date, despite technological improvement in standard perinatal monitoring procedures, decreasing the incidence of perinatal mortality, the perinatal morbidity pattern has a flat trend. Against this background, the measurement of brain constituents could be particularly useful in the early detection of cases at risk for short-/long-term brain injury. On this scenario, the main European and US international health-care institutions promoted perinatal clinical and experimental neuroprotection research projects aimed at validating and including a panel of biomarkers in the clinical guidelines. Although this is a promising attempt, there are several limitations that do not allow biomarkers to be included in standard monitoring procedures. The main limitations are: (i) the heterogeneity of neurological complications in the perinatal period, (ii) the small cohort sizes, (iii) the lack of multicenter investigations, (iv) the different techniques for neurobiomarkers assessment, (iv) the lack of consensus for the validation of assays in biological fluids such as urine and saliva, and (v), the lack of reference curves according to measurement technique and biological fluid. In the present review we offer an up-to-date overview of the most promising developments in the use of biomarkers in the perinatal period such as calcium binding proteins (S100B protein), vasoactive agents (adrenomedullin), brain biomarkers (activin A, neuron specific enolase, glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase-L1) and oxidative stress markers.
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Biomarcadores/líquido cefalorraquídeo , Lesiones Encefálicas/diagnóstico , Biomarcadores/sangre , Biomarcadores/orina , Femenino , Proteína Ácida Fibrilar de la Glía/sangre , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Proteína Ácida Fibrilar de la Glía/orina , Humanos , Atención Perinatal , Embarazo , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/líquido cefalorraquídeo , Subunidad beta de la Proteína de Unión al Calcio S100/orina , Saliva/metabolismo , Ubiquitina Tiolesterasa/sangre , Ubiquitina Tiolesterasa/líquido cefalorraquídeo , Ubiquitina Tiolesterasa/orinaRESUMEN
AIM: Near-infrared spectroscopy (NIRS) has been proposed to provide reliable information concerning brain oximetry and tissue activation level in the perinatal period. We aimed to investigate whether NIRS brain patterns in healthy preterm (PT) and term (T) infants were gender- and gestational age (GA)-dependent. METHODS: We conducted an observational study in 74 newborns, from consecutive singleton pregnancies, of whom 37 were born at term (male: n = 19 female: n = 18) and 37 (male: n = 18 female: n = 19) were PT. Cerebral oximetry (crSO2 ) and fractional tissue oxygen extraction (cFTOE), were recorded on the 5th day from birth. RESULTS: crSO2 was significantly higher and cFTOE lower (p < 0.001, for both) in the PT female than male group. At term, crSO2 was significantly higher and cFTOE lower (p < 0.001, for both) in males. crSO2 (male: R = 0.84, p < 0.001; female: R = 0.74, p < 0.001) and cFTOE (male: R = 0.72, p < 0.001; female: R = 0.72, p < 0.001) in male and female groups correlated positively with GA at recording. CONCLUSION: Different brain oximetry between males and females in PT a T infants, may suggest that in the perinatal period brain development is gender- and time-dependent. Data support the use of NIRS as a feasible tool for non-invasive cerebral monitoring.
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Encéfalo/metabolismo , Oximetría , Factores de Edad , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Factores Sexuales , Espectroscopía Infrarroja Corta , Nacimiento a TérminoRESUMEN
AIM: The effects of different milk and, or, administration regimens on cerebro-splanchnic perfusion are still a matter of debate. We investigated the effects of the bolus administration of breast milk or formula on cerebro-splanchnic oximetry, function and perfusion, assessed by near-infrared spectroscopy (NIRS). METHODS: This observational study of 30 infants fed with breast (n = 15) or formula (n = 15) milk, and matched for gestational age and birth weight, was carried out in the neonatal intensive care unit of the C Arrigo Children's Hospital, Alessandria, Italy, a tertiary-level referral centre, from October 2015 to December 2016. NIRS monitoring parameters, such as cerebral and splanchnic oximetry, fraction of tissue oxygen extraction and the cerebral-splanchnic ratio, were recorded before, during and after feeding. RESULTS: Breast milk led to a significant increase in cerebro-splanchnic oximetry and tissue oxygen extraction (p < 0.001) during and after feeding, and the cerebro-splanchnic perfusion ratio was significantly higher (p < 0.001) in the breast than formula group. CONCLUSION: Our study results suggest that breast milk was better tolerated than formula, requiring lower energy expenditure and lower cerebro-splanchnic haemodynamic redistribution. The findings could prompt investigations using NIRS as a promising noninvasive tool for cerebral and splanchnic longitudinal monitoring during neonatal feeding.
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Cerebro/fisiología , Fórmulas Infantiles , Recién Nacido/fisiología , Leche Humana , Espectroscopía Infrarroja Corta , Vísceras/fisiología , Análisis de Varianza , Cerebro/irrigación sanguínea , Edad Gestacional , Hemodinámica , Humanos , Oximetría , Oxígeno/metabolismo , Circulación EsplácnicaRESUMEN
Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case-control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at -80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes' degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP.
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Receptores de Lipopolisacáridos , Leche Humana , Fragmentos de Péptidos , Humanos , Leche Humana/química , Femenino , Estudios Prospectivos , Recién Nacido , Estudios de Casos y Controles , Masculino , Fragmentos de Péptidos/análisis , Receptores de Lipopolisacáridos/metabolismo , Recien Nacido Prematuro , Adulto , Biomarcadores/análisis , Parto Obstétrico , Factores Sexuales , EmbarazoRESUMEN
BACKGROUND: Near Infrared Spectroscopy (NIRS) has been proposed as a useful, noninvasive monitoring technique providing reliable information about central nervous system (CNS) oximetry and function. Recently, brain damage has been reconsidered as a dynamic process evolving over the weeks of gestation. We therefore investigated NIRS cerebral pattern differences between healthy late preterm infants (LPTo) and very preterm infants becoming late preterm (LPT). METHODS: We conducted an observational study in 40 healthy late preterm infants, matched for gestational age at monitoring, of whom 20 where LPTo and 20 LPT. Clinical, diagnostic and laboratory monitoring procedures and cerebral oximetry (crSO2) and function (cFTOE) were recorded on admission into the study. RESULTS: No significant differences (p > .05, for all) were found between groups regarding clinical, diagnostic or laboratory parameters. Higher crSO2 and lower cFTOE (p < .001, for both) were found in the LPTo group. CONCLUSIONS: Our results, showing impaired oximetry and function of CNS in LPT, offer additional support to NIRS parameters as a useful tool for longitudinal CNS monitoring of very preterm infants becoming LPT. Future studies correlating NIRS variables and long-term neurological outcome in LPT are needed to elucidate the concept of dynamic brain damage pathogenesis.
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Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Edad Gestacional , Recien Nacido Prematuro/fisiología , Adulto , Peso al Nacer , Encefalopatías/diagnóstico por imagen , Encefalopatías/fisiopatología , Femenino , Rotura Prematura de Membranas Fetales , Humanos , Recién Nacido , Enfermedades del Prematuro/diagnóstico por imagen , Enfermedades del Prematuro/fisiopatología , Cuidado Intensivo Neonatal , Masculino , Oximetría , Preeclampsia , Embarazo , Síndrome de Dificultad Respiratoria del Recién Nacido , Espectroscopía Infrarroja CortaRESUMEN
Perinatal asphyxia and its complication, hypoxic-ischemic encephalopathy, are still among the major causes of perinatal mortality and morbidity. Despite accurate standard postnatal monitoring procedures, the post-insult period is crucial because at a time when radiologic pictures are still silent, brain damage may already be at a subclinical stage. Against this background, the measurement of quantitative parameters, such as constituents of nervous tissue, that are able to detect subclinical lesions at a stage when routine brain monitoring procedures are still silent, could be particularly useful. Therefore, in the present review we report the potentials and limitations of biomarkers in predicting outcome in neonates complicated by perinatal asphyxia.