Serum Hsp70 antigen: Early diagnosis marker in perinatal asphyxia

BACKGROUND: Perinatal asphyxia is an important cause of mortality and permanent neurological and developmental deficit. Early and accurate diagnosis would help to establish the likely prognosis and may also help in determining the most appropriate treatment. Studies in experimental animal models suggest that a protein called Hsp70 may be a good and potentially useful marker of cellular stress that may be clinically useful in determining the presence of neonatal asphyxia. OBJECTIVES: Regarding the importance of early and accurate diagnosis of asphyxia, we conducted this study, which is the first investigation of the comparison of the serum Hsp70 antigen level between asphyxiated and healthy infants. PATIENTS AND METHODS: In this observational study, the serum concentrations of Hsp70 antigen were compared between neonates suffering from perinatal asphyxia (n = 50) and normal neonates (n = 51). The inclusion criteria for the cases were neonates who had reached term and had at least two clinical criteria of asphyxia. Exclusion criteria were babies with gestational age < 37 weeks, infants with congenital abnormalities or positive blood culture. Exclusion criteria in this group were the requirement to hospital stay during first week of the life or babies whose mothers had difficulties during pregnancy or delivery. Term neonates without major anomalies who had asphyxia during delivery were enrolled in the first six hours after delivery, and control group consisted of healthy term neonates without problems and normal delivery process in the first week of life. The cord blood was taken during labor to measure Hsp70 antigen level by using an in-house ELISA (The enzyme-linked immunosorbent assay). RESULTS: The median values of serum anti Hsp70 titers were significantly higher in asphyxiated neonates compared with non-asphyxiated neonates (0.36 [0.04 - 1.14] vs 0.24 [0.01 - 0.63]). At cutoff point = 0.3125 ng/mL, sensitivity was 58% and specificity 76% based on ROC curve. CONCLUSIONS: A significant difference between the serum concentrations of Hsp70 of the control and patient group was observed in this study. It is inferred serum concentrations of Hsp70 antigen may be a useful marker for the early diagnosis of that prenatal hypoxia

Endocardial Pacemaker Implantation in Neonates and Infants

Transvenous pacemaker lead implantation is the preferred method of pacing in adult patients. Lead performance and longevity are superior and the implantation approach can be performed under local anaesthetic with a very low morbidity. In children, and especially in neonates and infants, the epicardial route was traditionally chosen until the advent of smaller generators and lead implantation techniques that allowed growth of the child without lead displacement. Endocardial implantation is not universally accepted, however, as there is an incidence of venous occlusion of the smaller veins of neonates and infants with concerns for loss of venous access in the future. Growing experience with lower profile leads, however, reveals that endocardial pacing too can be performed with low morbidity and good long-term results in neonates and infants

Short-Term Neurodevelopmental Outcome in Term Neonates Treated with Phenobarbital versus Levetiracetam: A Single-Center Experience

BACKGROUND: Phenobarbital (PB) has been traditionally used as the first-line treatment for neonatal seizures. More recently, levetiracetam (LEV) has been increasingly used as a promising newer antiepileptic medication for treatment of seizures in neonates. OBJECTIVES: The aim of our study was to compare the effect of PB vs. LEV on short-term neurodevelopmental outcome in infants treated for neonatal seizures. METHOD: This randomized, one-blind prospective study was conducted on term neonates admitted to the Neonatal Intensive Care Unit of S. Bambino Hospital, University Hospital "Policlinico-Vittorio Emanuele," Catania, Italy, from February 2016 to February 2018. Thirty term neonates with seizures were randomized to receive PB or LEV; the Hammersmith Neonatal Neurological Examination (HNNE) was used at baseline (T0) and again one month after the initial treatment (T1). RESULTS: We found a significantly positive HNNE score for the developmental outcomes, specifically tone and posture, in neonates treated with LEV. There was no significant improvement in the HNNE score at T1 in the neonates treated with PB. CONCLUSION: This study suggests a positive effect of levetiracetam on tone and posture in term newborns treated for neonatal seizures. If future randomized-controlled studies also show better efficacy of LEV in the treatment of neonatal seizures, LEV might potentially be considered as the first-line anticonvulsant in this age grou

Tract-based spatial statistics (TBSS): application to detecting white matter tract variation in mild hypoxic-ischemic neonates

The aim of this study is to employ tract-based spatial statistics (TBSS) to analyze the voxel-wise differences in DTI parameters between normal and mild hypoxic-ischemic (HI) neonatal brains. Forty-one full term neonates (24 normal controls and 17 with mild HI injury) and 31 preterm neonates (20 normal controls and 11 with mild HI injury) underwent T1 weighted imaging, T2 weighted imaging and diffusion tensor imaging (DTI) within 28 days after birth. The voxel differences of fractional anisotropy (FA), lambda1, lambda2, and lambda3 values between mild HI group and control group were analyzed in preterm and full term neonates respectively. The significantly decreased FA with increased lambda2, lambda3 in corticospinal tract, genu of corpus callosum (GCC), external capsule (EC) and splenium of the corpus callosum (SCC) in mild HI neonates suggested deficits or delays in both myelination and premyelination. Such impaired corticospinal tract, in both preterm and term neonates, may directly lead to the subsequent poor motor performance. Impaired EC and SCC, the additional injured sites observed in full term neonates with mild HI injury, may be causally responsible for the dysfunction in coordination and integration. In conclusion, TBSS provides an objective, independent and sensitive method for DTI data analysis of neonatal white matter alterations after mild HI injury.published_or_final_versio

Total parenteral nutrition and carnitine supplementation practices in preterm neonates - results of a national survey

Thesis (M.A.)--Boston UniversityBackground: The goal of postnatal total parenteral nutrition (TPN) in premature neonates (PT) is to mimic the intrauterine environment of the fetus. Micronutrients are essential for optimal development. Although carnitine is present in human breast milk and is supplemented in infant formula, very preterm infants primarily receive parenteral nutrition, often devoid of carnitine, shortly after birth. Carnitine plays a critical role in cellular and mitochondrial metabolism. Preterm infants are deficient in carnitine as it is transferred from the placenta to the fetus during late pregnancy. Previously, our group surveyed US neonatologists in 2001 regarding carnitine supplementation practices and found that the majority were not fully familiar with the implications of carnitine deficiency and only 28% of preterm neonates on TPN were receiving carnitine. Since this study, recent research has emphasized the impact of carnitine on early weight gain and its neuroprotective effects. Objective: To determine current TPN carnitine supplementation practices in fasting preterm neonates (< 32 wks and < 1,500g) by conducting a national survey of board- certified neonatologists. [TRUNCATED

Intra- and inter-rater agreement of superior vena cava flow and right ventricular outflow measurements in late preterm and term neonates

OBJECTIVES: To explore the intra- and inter-rater agreement of superior vena cava (SVC) flow and right ventricular (RV) outflow in healthy and unwell late preterm neonates (33-37 weeks' gestational age), term neonates (≥37 weeks' gestational age), and neonates receiving total-body cooling. METHODS: The intra- and inter-rater agreement (n = 25 and 41 neonates, respectively) rates for SVC flow and RV outflow were determined by echocardiography in healthy and unwell late preterm and term neonates with the use of Bland-Altman plots, the repeatability coefficient, the repeatability index, and intraclass correlation coefficients. RESULTS: The intra-rater repeatability index values were 41% for SVC flow and 31% for RV outflow, with intraclass correlation coefficients indicating good agreement for both measures. The inter-rater repeatability index values for SVC flow and RV outflow were 63% and 51%, respectively, with intraclass correlation coefficients indicating moderate agreement for both measures. CONCLUSIONS: If SVC flow or RV outflow is used in the hemodynamic treatment of neonates, sequential measurements should ideally be performed by the same clinician to reduce potential variability

Diagnostic Value Parameters Of Acute Phase Reactances Of Infectious-inflammatory Process In Diagnostics Of Early Neonatal Sepsis

An advanced progress of clinical neonatology in recent years has enabled to achieve considerable success in newborn management with due respect to both medical treatment and general care, especially in the group of neonates with low body weight at birth. At the same time, neonatal sepsis in the early period still predetermine sickness and mortality of newborns.Material and methods. Clinical-paraclinical indices with detection of diagnostic value of C-reactive protein and interleukins-6 and 8 were evaluated in 100 neonates with available susceptibility factors to early neonatal infection from mother\u27s side and clinical signs of organ dysfunction in neonates with precautions of generalized infectious-inflammatory process at the end of their first day of life.Results. The data obtained substantiate that low concentrations of IL-6 and IL-8 prevail, and therefore the mentioned mediators hardly can be used to verify early neonatal infection. In the majority of children C-reactive protein elevated the concentration of 10.0 mg/L which is traditionally considered to be a discriminant as to the verification of an infectious process in newborns.Conclusions. None of the clinical signs associated with infectious-inflammatory process in newborns in the first two days of their life enabled to verify reliably availability of systemic bacterial infection

New architectural design of delivery room reduces morbidity in preterm neonates: a prospective cohort study

Background: A multidisciplinary committee composed of a panel of experts, including a member of the American Academy of Pediatrics and American Institute of Architects, has suggested that the delivery room (DR) and the neonatal intensive care units (NICU) room should be directly interconnected. We aimed to investigate the impact of the architectural design of the DR and the NICU on neonatal outcome. Methods: Two cohorts of preterm neonates born at < 32weeks of gestational age, consecutively observed during 2years, were compared prospectively before (Cohort 1: "conventional DR") and after architectural renovation of the DR realized in accordance with specific standards (Cohort 2: "new concept of DR"). In Cohort 1, neonates were initially cared for a conventional resuscitation area, situated in the DR, and then transferred to the NICU, located on a separate floor of the same hospital. In Cohort 2 neonates were assisted at birth directly in the NICU room, which was directly connected to the DR via a pass-through door. The primary outcome of the study was morbidity, defined by the proportion of neonates with at least one complication of prematurity (i.e., late-onset sepsis, patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity and necrotizing enterocolitis). Secondary outcomes were mortality and duration of hospitalization. Statistical analysis was performed using standard methods by SPSS software. Results: We enrolled 106 neonates (56 in Cohort 1 and 50 in Cohort 2). The main clinical and demographic characteristics of the 2cohorts were similar. Moderate hypothermia (body temperature ≤ 35.9° C) was more frequent in Cohort 1 (57%) compared with Cohort 2 (24%, p = 0.001). Morbidity was increased in Cohort 1 (73%) compared with Cohort 2 (44%, p = 0.002). No statistically significant differences in mortality and median duration of hospitalization were observed between the 2 cohorts of the study. Conclusions: If realized according to the proposed architectural standards, renovation of DR and NICU may represent an opportunity to reduce morbidity in preterm neonates

Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure

Aims: Inflammation and organ failure have been reported to have an impact on cytochrome P450 (CYP) 3A-mediated clearance of midazolam in critically ill children. Our aim was to evaluate a previously developed population pharmacokinetic model both in critically ill children and other populations, in order to allow the model to be used to guide dosing in clinical practice. Methods: The model was evaluated externally in 136 individuals, including (pre)term neonates, infants, children and adults (body weight 0.77-90 kg, C-reactive protein level 0.1-341 mg l-1 and 0-4 failing organs) using graphical and numerical diagnostics. Results: The pharmacokinetic model predicted midazolam clearance and plasma concentrations without bias in postoperative or critically ill paediatric patients and term neonates [median prediction error (MPE) 180%). Conclusion: The recently published pharmacokinetic model for midazolam, quantifying the influence of maturation, inflammation and organ failure in children, yields unbiased clearance predictions and can therefore be used for dosing instructions in term neonates, children and adults with varying levels of critical illness, including healthy adults, but not for extrapolation to preterm neonates