Neurodevelopmental impairment is a significant complication among survivors of preterm birth. To improve outcomes, reliable biomarkers for early detection of brain injury and prognostic assessment ...are required. Secretoneurin is a promising early biomarker of brain injury in adults and full-term neonates suffering from perinatal asphyxia. Data on preterm infants is currently lacking. The aim of this pilot study was to determine secretoneurin concentrations in preterm infants in the neonatal period, and to assess secretoneurin's potential as a biomarker of preterm brain injury. We included 38 very preterm infants (VPI) born at <32 weeks' gestation in the study. Secretoneurin concentrations were measured in serum samples obtained from the umbilical cord, at 48 hours and 3 weeks of life. Outcome measures included repeated cerebral ultrasonography, magnetic resonance imaging at term-equivalent age, general movements assessment, and neurodevelopmental assessment at a corrected age of 2 years by the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). In comparison to a term-born reference population, VPI had lower secretoneurin serum concentrations in umbilical cord blood and blood collected at 48 hours of life. When measured at 3 weeks of life, concentrations correlated with gestational age at birth. Secretoneurin concentrations did not differ between VPI with an imaging-based diagnosis of brain injury and those without, but when measured in umbilical cord blood and at 3 weeks of life correlated with and were predictive of Bayley-III motor and cognitive scale scores. Secretoneurin levels in VPI differ from term-born neonates. Secretoneurin seems unsuitable as a diagnostic biomarker of preterm brain injury, but bears some prognostic potential and is worthy of further investigation as a blood-based biomarker of preterm brain injury.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Premature birth entails an adverse cardiovascular risk profile, but the underlying mechanisms are insufficiently understood. Here, we employed an unbiased cardiovascular proteomics approach to ...profile former very preterm-born preschoolers.
This observational study investigated differences in plasma concentrations of 79 proteins, including putative cardiovascular biomarkers between very preterm- and term-born children on average 5.5 years old (53.1% male) using multiple-reaction monitoring mass spectrometry.
Very preterm-born (n = 38; median gestational age 29.6 weeks) compared to term-born (n = 26; 40.2 weeks) children featured lower plasma concentrations of platelet factor 4 (PLF4; -61.6%, P < 0.0001), platelet basic protein (CXCL7; -57.8%, P < 0.0001), and hemoglobin subunit beta (-48.3%, P < 0.0001). Results remained virtually unchanged when adjusting for complete blood count parameters, including platelet count. Conversely, whole blood hemoglobin was higher (+7.62%, P < 0.0001) in preterm-born children.
Very preterm birth was associated with decreased markers of platelet activation among preschoolers. These findings are consistent with reduced platelet reactivity persisting from very preterm birth to a preschool age.
Former very preterm-born preschoolers featured reduced levels of platelet activation markers. While lower platelet reactivity in very preterm-born compared to term-born infants in the first days of life was established, it was unknown when, if at all, reactivity normalizes. The current study suggests that platelet hyporeactivity due to very preterm birth persists at least up to a preschool age. "Immaturity of the hemostatic system" may be a persistent sequel of preterm birth, but larger studies are needed to investigate its potential clinical implications.
Cardiovascular disease is the leading cause of death worldwide. Evidence points towards an unfavorable cardiovascular risk profile of former preterm infants in adolescence and adulthood. The aim of ...this study was to determine whether cardiovascular risk predictors are detectable in former very preterm infants at a preschool age. Five- to seven-year-old children born at <32 weeks' gestational age were included in the study. Same-aged children born at term served as controls. Basic data of study participants were collected by means of follow-up databases and standardized questionnaires. At study visit, anthropometric data, blood pressure readings and aortic intima-media thickness were assessed. Blood samples were obtained after an overnight fast. In comparison to children born at term, former preterm infants had higher systolic and diastolic blood pressure readings (odds ratio 95% confidence interval per 1-SD higher blood pressure level 3.2 2.0-5.0, p<0.001 and 1.6 1.1-1.2, p = 0.008), fasting glucose levels (OR 95% CI 5.2 2.7-10.1, p<0.001), homeostasis model assessment index (OR 95% CI 1.6 1.0-2.6, p = 0.036), and cholesterol levels (OR 95% CI 2.1 1.3-3.4, p = 0.002). Systolic prehypertension (23.7% vs. 2.2%; OR 95% CI 13.8 3.1-60.9, p = 0.001), elevated glucose levels (28.6% vs. 5.9%; OR 95% CI 6.4 1.4-28.8, p = 0.016), and hypercholesterolemia (77.4% vs. 52.9%; OR 95% CI 3.0 1.3-7.1, p = 0.010) were significantly more prevalent in the preterm group. As former very preterm infants display an unfavorable cardiovascular risk profile already at a preschool age, implementation of routine cardiovascular follow-up programs might be warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Due to improvements in perinatal care, survival rates of preterm infants have improved during the last decades. However, these infants remain at risk of developing cardiovascular sequelae later in ...life. This study aimed to investigate the cardiac biomarkers and left ventricular systolic function in former preterm infants in comparison with term controls at preschool age.
The study included children aged 5-7 years old born below 32 weeks of gestational age. The control group consisted of same-age children born at term. Basic data of study participants were collected using questionnaires and follow-up databases. During the study visit, we recorded anthropometric data and blood pressure readings, determined high-sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentrations, and calculated fractional shortening (FS) and left ventricular mass (LVM).
Term-born (
= 25; median gestational age, 40.1 weeks) compared with preterm-born infants (
= 80; median gestational age 29.6 weeks) showed no significant differences in the median concentration of hs-cTnT median, 3.5 (IQR 3.5; 3.5) vs. 3.5 (3.5; 3.5) ng/L,
= 0.328 and the median concentration of NT-pro-BNP median, 91.0 (IQR 40.8; 150.3) vs. 87.5 (50.1; 189.5) ng/L,
= 0.087. FS and LVM/LVMI were not significantly different between the two groups.
At preschool age, we observed no significant differences in cardiac biomarkers and left ventricular systolic function in preterm infants. Further studies are warranted to explore the potential of cardiac biomarkers as a prognostic tool for subclinical cardiac alterations after preterm birth.
Background. The current literature suggests that neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections generally have a mild course. Data on how in utero exposure to ...maternal infection affects neonatal health outcomes are limited, but there is evidence that neurological damage to the fetus and thromboembolic events may occur. Case Presentation. We describe the case of a late preterm infant, who presented with striatal lacunar infarction in the neonatal period, born to a mother with active peripartum SARS-CoV-2 infection. Diagnostic workup did not identify risk factors apart from the maternal SARS-CoV-2 infection. Repeated reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 using oropharyngeal swab specimens of the patient were negative. IgG, but not IgM antibodies against spike protein S1 receptor-binding domain (S1RBD) epitope were detectable in umbilical cord blood and neonatal serum collected at 48 hours of life. Anti-SARS-CoV-2 total antibody titers against nucleocapsid protein in umbilical cord blood were negative. Conclusions. Bearing in mind a possible association of in utero exposure to SARS-CoV-2 and neonatal thromboembolic events, neonatologists should be aware of these complications even in well-appearing preterm infants.
Background Little is known about plasma apolipoprotein profiles in very preterm-born and term-born preschool children compared with the adult population. This is of particular interest because ...apolipoprotein composition might contribute to cardiometabolic outcome in later life. Methods and Results Children aged 5 to 7 years born at term or with <32 weeks of gestation were included. Apolipoprotein concentrations were measured in plasma collected after an overnight fast using multiple-reaction monitoring-based mass spectrometry. Twelve apolipoproteins were measured in 26 former term and 38 former very preterm infants. Key findings were confirmed by assessing apolipoprotein levels using antibody-based assays. Comparing children born term and preterm, apolipoprotein A-I, A- IV , C- II , and C- III were significantly higher in the latter group. Term-born children showed plasma levels of apolipoprotein C- II and C- III quantitatively similar to the adult range (Bruneck study). Hierarchical clustering analyses suggested that a higher proportion of apolipoprotein C- III and C- II reside on high-density lipoprotein particles in children than in adults given the marked correlations of apolipoprotein C- III and C- II with high-density lipoprotein cholesterol and apolipoprotein A-I in children but not adults. High-density lipoprotein cholesterol concentrations were similar in children and adults but the pattern of high-density lipoprotein cholesterol-associated apolipoproteins was different (lower apolipoprotein A-I and C-I but higher A- II , A- IV , and M). Conclusions Our study defines apolipoprotein profiles in preschoolers and reports potential effects of prematurity. Further large-scale studies are required to provide evidence whether this apolipoprotein signature of prematurity, including high apolipoprotein C- II and C- III levels, might translate into adverse cardiometabolic outcome in later life.
Aim
LISA is a promising method in improving preterm outcome. The aim of this study was to assess whether the INSURE (intubation‐surfactant extubation) technique or LISA (less invasive surfactant ...administration) procedure for surfactant administration is associated with more pain‐relieving interventions after the intervention in preterm infants.
Methods
Preterm infants born at <32 weeks gestational age admitted to the Neonatal Intensive Care Unit of Innsbruck University hospital between Jan 2012 and June 2017 subjected to INSURE or LISA were included in the study, which was performed as a retrospective analysis of routinely collected data. Pain assessments were made bedside using the Bernese Pain Scale for Neonates.
Results
During the study period 15 preterm infants (median gestational age 30.7 weeks; range: 25.9‐32.0 weeks) were subjected to INSURE technique and 59 (median gestational age 29.4 weeks; range: 25.1‐31.4 weeks) to LISA. Infants subjected to LISA showed a higher need for nonpharmacological pain‐relieving interventions in the first three days of life.
Conclusion
LISA procedure compared to INSURE technique was associated with a higher need for pain‐relieving interventions in the first three days of life. Prospective randomized controlled trials are needed to optimize this less invasive method for surfactant application with special focus on pain in neonates.
Preterm birth is associated with long-term cardiovascular morbidity and mortality. In adults, fibroblast growth factor-23 (FGF-23), α-Klotho, and secretoneurin have all garnered attention as ...cardiovascular biomarkers, but their utility in pediatric populations has not yet been ascertained. The aim of this pilot study was to evaluate these novel cardiovascular biomarkers and their association with indicators of cardiovascular impairment in the highly vulnerable population of former very preterm infants.
Five- to seven-year-old children born at < 32 weeks' gestation were eligible for the study. Healthy same-aged children born at term served as controls. Biomarkers were quantified in fasting blood samples, and echocardiographic measurements including assessment of aortic elastic properties were obtained.
We included 26 former very preterm infants and 21 term-born children in the study. At kindergarten age, former very preterm infants exhibited significantly higher plasma concentrations of biologically active intact FGF-23 (iFGF-23; mean 43.2 pg/mL vs. 29.1 pg/mL, p = 0.003) and secretoneurin (median 93.8 pmol/L vs. 70.5 pmol/L, p = 0.046). iFGF-23 inversely correlated with distensibility of the descending aorta.
In preterm-born children, iFGF-23 and secretoneurin both offer prospects as valuable cardiovascular biomarkers, potentially allowing for risk stratification and timely implementation of preventive measures.
Former very preterm infants have increased plasma concentrations of the novel cardiovascular biomarkers intact fibroblast growth factor-23 (iFGF-23) and secretoneurin at kindergarten age. Increases in iFGF-23 concentrations are associated with decreased distensibility of the descending aorta even at this early age. Monitoring of cardiovascular risk factors is essential in individuals with a history of preterm birth. Both iFGF-23 and secretoneurin hold promise as clinically valuable biomarkers for risk stratification, enabling the implementation of early preventive measures.
Excitotoxicity plays an important role in the pathogenesis of developing brain injury. The neuropeptide secretoneurin (SN) has neuroprotective potential. The aim of this study was to investigate SN ...plasma concentrations following excitotoxicity and to evaluate the effect of SN as therapeutic strategy in excitotoxic newborn brain injury. Baseline SN plasma concentrations were established in healthy animals. To evaluate the effect of an excitotoxic insult on SN levels, mice pups were subjected to an intracranial injection of ibotenic acid and SN plasma concentrations were measured thereafter. To assess SN's neuroprotective potential, a subgroup of animals was randomly assigned to the following groups: i) “single treatment”: vehicle 1× phosphate-buffered saline (PBS), SN 0.25 μg/g body weight (bw), SN 2.5 μg/g bw or SN 12.5 μg/g bw in a single dose 1 h after insult; ii) “acute repetitive treatment”: vehicle 1× PBS or SN 0.25 μg/g bw every 24 h starting 1 h after insult; iii) “delayed repetitive treatment”: vehicle 1× PBS or SN 0.25 μg/g bw every 24 h starting 60 h after insult. Animals subjected to excitotoxic injury showed significantly lower SN plasma concentrations 6 and 120 h after insult in comparison to healthy controls. Administration of SN did not positively affect lesion size, apoptotic cell death, microglial cell activation or cell proliferation. To conclude, endogenous SN plasma levels are lower in newborn mice subjected to an excitotoxic insult than in healthy controls. Supplementation with SN in various treatment regimens is not neuroprotective in the experimental animal model of excitotoxic newborn brain injury.
•Secretoneurin (SN) is a neuropeptide with neuroprotective potential.•Experimental excitotoxic newborn brain injury alters endogenous SN plasma levels.•Administration of SN does not protect against excitotoxic injury in newborn mice.
Aim
Measures to detect and monitor brain injury in preterm infants are amplitude‐integrated electroencephalography (aEEG) and magnetic resonance imaging (MRI). To investigate the association between ...aEEG and MRI in a large cohort of preterm infants. Five hundred and twenty‐three preterm infants were included in the study.
Methods
AEEG was interpreted for the total maturation score (TMS) according to Burdjalov. Cerebral MRI was evaluated using a validated scoring system by Kidokoro.
Results
One hundred and forty‐six infants (27.9%) showed some form of brain injury, with 111 infants (21.2%) showing mild injury and 35 (6.7%) showing severe injury. TMS were significantly higher in infants without injury compared to severe injury. When comparing infants with isolated intraventricular haemorrhage to infants without brain injury, TMS were significantly lower.
Conclusion
Prediction of adverse outcome is an important aspect of neonatal care. The combination of diagnostic measures evaluating brain injury might enhance our abilities in neonatal care to provide accurate information about later outcome. Early aEEG is predictive for the severity of brain injury detected by MRI at term‐equivalent age. Whether aEEG is also predictive for neurodevelopmental outcome needs to be further investigated in relation to the various patterns of preterm brain injury.
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