Can we delineate brain injury in full-term neonates using serum biomarkers?

OBJECTIVE: Early identification of neonates at risk of neurological impairment is particularly important for the bedside clinician. Clinical value of S100b and neuron-specific enolase in neonates has not been yet established. We investigated their kinetics and possible early clinical utility in neonatal encephalopathy (NE).STUDY DESIGN: 36 full-term neonates (13 with moderate/severe encephalopathy, 11 with mild encephalopathy, 12 controls) were enrolled and studied prospectively. Serum S100b and neuron-specific enolase (NSE) were measured serially on days(d) 1, 3, 9 and 18 of life. Brain MRI and long-term neurodevelopmental outcome were also assessed.RESULT: Neonates with moderate/severe encephalopathy had significantly increased S100b (d1) and NSE levels (d1, d3, d9) compared to controls. Neuron-specific enolase significantly correlated with the degree of encephalopathy, and a cutoff of 38.8 µg/l (d1) accurately predicted moderate/severe encephalopathy. S100b (d1) cutoff points of 1.6 µg/l and 11.4 µg/l prognosticated severe encephalopathy and death/cerebral palsy, respectively. Both biomarkers correlated well with neuroimaging and Bayley-III scores.CONCLUSION: Combined clinical, laboratory, imaging and neurodevelopmental data indicate that serum S100b and NSE can be useful biomarkers for the diagnosis and prognosis of neonatal brain injury, providing useful information to the bedside clinician.

Urine neutrophil gelatinase-associated lipocalin to predict acute kidney injury in preterm neonates. A pilot study.

BACKGROUND: The efficacy of urine neutrophil gelatinase-associated lipocalin (uNGAL) as an early acute kidney injury (AKI) biomarker in preterm neonates was evaluated. METHODS: Thirty-five preterm neonates were prospectively evaluated for serum creatinine (sCre)-documented AKI during the first 14 days of life. Urine samples were collected daily throughout the study period. Of the neonates evaluated, we analyzed 11 who developed AKI (cases) and an equal number of neonates without AKI (controls) matched for gestational and postnatal age (case-control study). uNGAL was measured on the day of AKI occurrence (day 0) and on the 2 days preceding the event (day -1 and day -2, respectively) using an enzyme-linked immunosorbent assay. RESULTS: Cases had significantly higher sCre levels than controls on day 0 (1.21 ± 0.48 vs. 0.83 ± 0.16 mg/dL, p =0.031) but not on days -1 and -2. Similarly, uNGAL levels (ng/mL) were significantly higher in cases than in controls only on day 0 (19.1 ± 3.5 vs. 13.3 ± 7.3, p=0.017) and not on days -1 (18.8 ± 3.4 vs. 16.3 ± 5.9, p=0.118) and -2 (19.3 ± 1.8 vs. 19.4 ± 0.8, p =0.979). The receiver operating characteristic curve analysis showed no significant ability of uNGAL to predict AKI on days -2 and -1. CONCLUSIONS: In this pilot study in preterm neonates, although uNGAL detected sCre-based AKI upon its documentation, it failed to predict its development 1-2 days earlier.

Serum and urine acute kidney injury biomarkers in asphyxiated neonates.

BACKGROUND: We evaluated serum (s) cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) and urine (u) CysC, NGAL and kidney injury molecule-1 (KIM-1) as markers of acute kidney injury (AKI) in asphyxiated neonates. METHODS: AKI biomarkers were measured in 13 asphyxiated neonates born at ≥ 36 weeks gestational age (eight with AKI and five without AKI) and 22 controls. AKI was defined as serum creatinine ≥ 1.5 mg/dl for >24 h or rising values >0.3 mg/dl from day of life (DOL) 1. Biomarkers were measured on DOL 1, 3, and 10. RESULTS: Asphyxiated neonates had significantly higher sCysC on DOL 1 as well as sNGAL and uCysC and uNGAL (standardized to urine creatinine and absolute values) than controls at all time points. Compared to controls, significantly higher sNGAL, uCysC, and uNGAL values were observed in the asphyxia-AKI and asphyxia-no AKI subgroups. Regarding uKIM-1, only the absolute values were significantly higher in asphyxiated neonates (DOL 10). sNGAL, uCyst, and uNGAL had a significant diagnostic performance as predictors AKI on DOL 1. CONCLUSIONS: sNGAL, uCysC, and uNGAL are sensitive, early AKI biomarkers, increasing significantly in asphyxiated neonates even in those not fulfilling AKI criteria. Their measurement on DOL 1 is predictive of post-asphyxia-AKI.

Visual function in preterm infants without major retinopathy of prematurity or neurological complications.

OBJECTIVE: Early exposure of preterm infants to visual stimulation could affect the process of visual maturation. The aim of this study was to assess the impact of prematurity on visual function at 15 months post-term. SUBJECTS AND METHODS: Visual function was assessed in 102 preterm (PTI) and 50 full-term infants (FTI) without major cerebral pathology or retinopathy of prematurity (ROP) of grade 2 to 5, at 15 months' corrected age. The visual acuity, refractive status, contrast sensitivity, strabismus, fundus, and neurodevelopment were examined. RESULTS: Impairments of individual visual functions were 2 to 10 times more common in PTI than FTI. However, the difference was significant only for refractive errors (p = 0.007, odds ratio [OR] = 10.5). The incidence of visual deficits was higher in PTI with gestational age less than 32 weeks compared with PTI with higher gestational age (OR = 1.3 to 2.0), but not significantly. Of the PTI, 4.9%, 2.9%, and 10.8% had mild abnormalities on ultrasound scans, neuromotor, and developmental examination, respectively, which were not associated with increased incidence of visual deficits. CONCLUSION: Premature exposure to visual stimulation does not induce visual maturation but it is associated with impairment of certain aspects of visual function even in the absence of major ROP or neurodevelopmental deficits.

The Intertemporal Role of Respiratory Support in Improving Neonatal Outcomes: A Narrative Review.

Defining improvements in healthcare can be challenging due to the need to assess multiple outcomes and measures. In neonates, although progress in respiratory support has been a key factor in improving survival, the same degree of improvement has not been documented in certain outcomes, such as bronchopulmonary dysplasia. By exploring the evolution of neonatal respiratory care over the last 60 years, this review highlights not only the scientific advances that occurred with the application of invasive mechanical ventilation but also the weakness of the existing knowledge. The contributing role of non-invasive ventilation and less-invasive surfactant administration methods as well as of certain pharmacological therapies is also discussed. Moreover, we analyze the cost-benefit of neonatal care-respiratory support and present future challenges and perspectives.

Clara cell secretory protein (CC16) as a peripheral blood biomarker of lung injury in ventilated preterm neonates.

The aim of this study was to assess the serum concentrations of Clara cell secretory protein (CC16) in association with acute and chronic lung injury in mechanically ventilated preterm neonates. Thirty-five preterm neonates (gestational age [GA]

Urine metabolomics in neonates with late-onset sepsis in a case-control study.

Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers.

Bayley-III scales at 12 months of corrected age in preterm infants: Patterns of developmental performance and correlations to environmental and biological influences.

BACKGROUND AND AIMS: Premature infants are at high risk for neurodevelopmental impairment (NDI) even in the absence of known brain complications of prematurity. Evaluation of the effectiveness of therapeutic interventions in association to neurodevelopmental outcome is required to improve or prevent the neurodevelopmental consequences of prematurity. The Bayley-III is currently the most commonly applied measurement tool for assessing early development both in clinical practice and research settings. OBJECTIVE: To evaluate the relationship between known risk factors and early performance on the Bayley Scales of Infant Development-Third Edition at 12 months adjusted age in premature infants. METHODS: Prospective study in a cohort of premature infants with gestational age ≤32 weeks, who underwent comprehensive developmental assessment using the five domains of Bayley Scales, cognitive, language, motor, social emotional and adaptive behavior at 12 months corrected age. Developmental scores were evaluated in relation to environmental influences, therapeutic interventions or practices and complications of prematurity. RESULTS: Composite and Subscale scores for the cognitive, language and motor scales were below the 50th percentile, with no significant differences among them. Scores for the social-emotional and adaptive behavior, which are derived from the parent-report questionnaires, were near the average and significantly higher than the scores derived by the examiners. Multiple regression analyses showed that blood transfusions, apart from severely abnormal head ultrasound, gender, being small for gestational age and duration of invasive mechanical ventilation and oxygen administration were consistently related to neurodevelopmental outcome. CONCLUSIONS: Bayley-III assessments are important for getting early information about development following premature birth. Parents may overestimate children's performance. Neurodevelopmental outcome is related to several environmental, biological or medical conditions associated with prematurity. Adoption of therapeutic strategies targeting known neonatal risk factors could positively affect neurodevelopmental outcome.