Rigor of Neurovascular Coupling (NVC) Assessment in Newborns Using Different Amplitude EEG Algorithms.

Birth asphyxia constitutes a major global public health burden for millions of infants with a critical need for real time physiological biomarkers. This proof of concept study targets the translational rigor of such biomarkers and aims to examine whether the variability in the amplitude-integrated EEG (aEEG) outputs impact the determination of neurovascular coupling (NVC) in newborns with encephalopathy. A convenience sample with neonatal asphyxia were monitored for twenty hours in the first day of life with EEG and near infrared spectroscopy (NIRS)-based cerebral tissue oxygen saturation (SctO2). NVC between aEEG and NIRS-SctO2 was assessed using wavelet transform coherence (WTC) analysis, specifically by the wavelet total pixel number of significant coherences within 95% confidence interval. The raw EEG was converted to aEEG using three different methods: Method (M1) derives from the algorithm by Zhang and Ding. Method (M2) uses a Neonatal EEG Analysis Toolbox (WU-NEAT). Method (M3) extracts output directly from a commercial platform with an undisclosed algorithm. Our results demonstrate excellent agreement with Bland Altman comparisons for WTC-based NVC irrespective of the algorithms used, despite significant heterogeneities in the aEEG tracings produced by three algorithms. Our findings confirm the robustness of NVC wavelet analysis in Neonatal Encephalopathy related to HIE.

Noninvasive continuous cardiac output and cerebral perfusion monitoring in term infants with neonatal encephalopathy: assessment of feasibility and reliability.

BackgroundNoninvasive hemodynamic monitoring of infants with neonatal encephalopathy (NE) undergoing therapeutic hypothermia (TH) would be a potentially useful clinical tool. We aimed to assess the feasibility and reliability of noninvasive cardiac output monitoring (NICOM) and near-infrared spectroscopy (NIRS) in this cohort.MethodsNICOM and NIRS were commenced to measure cardiac output (CO), systemic vascular resistance (SVR), blood pressure (BP), and cerebral regional oxygen saturations (SctO2) during TH and rewarming. NICOM measures of CO were also compared with simultaneous echocardiography-derived CO (echo-CO).ResultsTwenty infants with a median gestation of 40 weeks were enrolled. There was a strong correlation between NICOM- and echo-CO (r2=0.79, P<0.001). NICOM-CO was systematically lower than echo-CO with a bias of 27% (limits of agreement 3-51%). NICOM illustrated lower CO during TH, which increased during rewarming. SctO2 increased over the first 30 h of TH and stayed high for the remainder of the study. There was a rise in SVR over the first 30 h of TH and a decrease during rewarming (all P<0.05).ConclusionsNoninvasive hemodynamic assessment of infants with NE is feasible and illustrates potentially important changes. Larger studies are needed to assess the clinical applicability of those methods in this cohort.

The problems of moderate preterm infants.

Moderate preterm infants are the largest group of preterm infants but are an understudied population. Care practices are adapted from studies of full term infants or extremely preterm infants. Studies are needed to tailor treatments for this vulnerable population. The NRN began investigation in this population with a registry of characteristics, and neonatal outcomes of these infants. This work compares outcomes of MPR with those of full term infants reported in the literature.

Saturation oxygen pressure index for assessment of pulmonary disease in neonates on non-invasive ventilation.

This prospective observational study on 36 neonates aimed to estimate the correlation between the new Saturation Oxygen distending Pressure Index (SOPI) and Oxygenation index. SOPI had high correlation (r=0.94) with oxygenation index. SOPI of <2, 2, and 3.7 represented mild, moderate and severe pulmonary disease, respectively with high sensitivity and specificity.

Pharmacologic Management of Neonatal Seizures.

Seizures are most often the only sign of a central nervous dysfunction in the neonate. Neonatal seizures are a symptom of a specific disease entity. The search for a cause of neonatal seizures should focus on perinatal history or acute metabolic changes in the neonate. There are four classifications of neonatal seizures: clonic, tonic, myoclonic, and subtle. Simultaneous electroencephalogram and video recording are tools to assist the practitioner in the evaluation of difficult-to-assess subtle behaviors. Although many seizures may be prevented by careful attention to metabolic changes and the neonate's overall condition, those that cannot be prevented may require pharmacologic treatment. First-generation antiepileptic drugs such as phenobarbital and phenytoin are still the first and second lines of therapy, even as questions concerning their limited clinical effectiveness and concern for potential neurotoxicity continue.

Use of ultrasound in the haemodynamic assessment of the sick neonate.

Clinician performed ultrasound (CPU) by the clinician caring for a sick patient is increasingly used in critical care specialties. The real-time haemodynamic information obtained helps the clinician to understand underlying physiology, target treatment and refine clinical decision-making. Neonatologists are increasingly using ultrasound to assess sick neonates with a range of clinical presentations and demand for training and accreditation programmes is increasing. This review discusses the current expanded uses for CPU in the haemodynamic assessment of the sick neonate.

Perfusion index in newborn infants: a noninvasive tool for neonatal monitoring.

AIM: To review the utility of perfusion index (PI) in the evaluation of neonatal clinical conditions. Twenty-five manuscripts were reviewed. PI provides information about haemodynamic stability, illness severity, early neonatal respiratory outcome, low superior vena cava flow and subclinical chorioamnionitis. CONCLUSION: PI is a valuable tool to assess the newborn's health condition and could become a standardised measure in clinical evaluation. Different study designs are necessary to provide further validation to this method.

Feasibility of bone assessment with ultrasonic backscatter signals in neonates.

The objective of this study was to assess the value of ultrasonic backscatter signals and the backscatter coefficient (BSC) in the analysis of bone status in neonates and to analyze the relationships between the BSC and gestational age, birth weight, length, head circumference and gender. A total of 122 neonates participated in the study, including 83 premature infants and 39 full-term infants. Their BSCs were measured by ultrasound after birth. The results revealed a significant correlation between the BSC and gestational age (R = 0.47, p < 0.001), birth weight (R = 0.47, p < 0.0001) and length at birth (R = 0.43, p < 0.001) at a frequency of 5.0 MHz. This study suggests that the use of ultrasonic backscattering and the BSC is feasible for assessment of the bone status of neonates.

[Development and assessment of a sensory-motor scale for the neonate: a clinical tool at the bedside]. / Élaboration et validation de contenu d'une grille d'observation du comportement sensorimoteur du nouveau-né à l'usage du personnel soignant.

INTRODUCTION: Improved perinatal care has increased the survival of newborns. However, neonatal intensive care is a source of nociceptive stimuli that may have a negative long-term impact on the child's neurobehavioral development. During the period of maximal brain plasticity, supportive developmental care can therefore be beneficial. The purpose of this study was to develop an assessment tool of neonatal behavior for daily use by healthcare providers and validate its content. METHOD: A behavioral assessment tool starting off with 45 clinical variables in 6 areas of sensory-motor behavior was validated in two stages using footage of babies between 25 and 37 weeks gestational age. The intraclass correlation coefficient of 65 evaluations allowed simplification of the tool down to 23 variables, prior to a final analysis of validity and reliability. RESULTS: For the 23 variables, the reliability between observers was low for 7 (intraclass correlation coefficient [ICC]<0.4), fair for 4 (ICC 0.4-0.5) and good for 12 (ICC>0.5). The agreement between novice and expert observers ranged from 46.7% to 98.7%. Twenty variables had a level of agreement above 60%. CONCLUSIONS: This validation study of a newborn sensory-motor behavior assessment scale has identified pertinent variables for a structured assessment by healthcare providers.

Risk assessment in neonatal early onset sepsis.

The incidence of neonatal early onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early onset sepsis remains a potentially fatal condition, particularly among very low birth-weight infants. Clinical signs of neonatal infection are nonspecific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures.

The assessment of time-dependent myocardial changes in infants with perinatal hypoxia.

OBJECTIVE: The aim of the study was to assess myocardial damage in infants due to perinatal hypoxia. METHODS: The findings of 29 infants with perinatal hypoxia and 20 healthy infants were compared. Blood gas analysis, serum lactate, cardiac troponin I (cTnI), troponin T (cTnT), creatine kinase-MB (CK-MB) and B-type natriuretic peptide (BNP) were evaluated. Echocardiography together with tissue Doppler imaging was performed. RESULTS: cTnT, CK-MB and BNP were higher in patients at the first day. There were positive correlations between the left ventricular (LV) myocardial performance index (MPI) and cTnT at first day and also at first month. LV ejection fraction and fractional shortening were lower at first day and at first month in patients. Myocardial systolic (Sm) and diastolic (Em and Am) velocities at all segments were lower at first day, and interventricular septum Sm, LV Sm, LV Em, right ventricular Em and LV Am were still lower at first month in patients. Isovolumic relaxation time at all segments together with LV MPI was higher at first day, ejection time values were lower and MPI values were higher at all segments at first month in patients. CONCLUSIONS: These findings demonstrated that the signs of myocardial damage due to perinatal hypoxia still present at first month.

Role of TOPS (a simplified assessment of neonatal acute physiology) in predicting mortality in transported neonates.

AIM: To evaluate role of TOPS (a simplified assessment of neonatal acute physiology) in predicting mortality in transported neonates and to compare it with SNAP II. DESIGN: Prospective study. SETTING: Referral Neonatal Unit of a teaching hospital. SUBJECTS: 175 neonates > 1000 g admitted to referral nursery. METHODS: Temperature, oxygenation, capillary refill time (proxy for perfusion) and blood sugar (given the acronym of TOPS) were recorded at admission. SNAP II was also recorded for first 12 hours following admission. RESULTS: All the TOPS variables had significant correlation with fatality on univariate analysis. Fatality was 100% when all the four TOPS variables were deranged. The sensitivity, specificity, positive and negative predictive values of derangements of two or more TOPS parameters in predicting mortality were 81.6%, 77.39%, 65.3% and 89%, respectively All the variables of SNAP II significantly correlated with mortality. A cut-off score of 24 was derived from the ROC curve. The sensitivity, specificity, positive and negative predictive values of SNAP II score > 24 in predicting mortality were 78.3%, 86.1%, 74.6% and 88.4%, respectively. The area under ROC curve for derangements of 2 or more TOPS parameters was 0.89 while that for SNAP II was 0.88. Both models were well calibrated (p value for Hosmer Lemeshow goodness of fit for TOPS was 0.75 while that for SNAP II was 0.80). The total correct classification rate for TOPS was 81.7%, while that for SNAP II was 83.4%. CONCLUSION: TOPS has an equally good prediction for mortality as SNAP II and can be used as a simple and useful method of assessment of risk of fatality that can be assessed immediately, at admission.

[Urine medium weight molecules in assessment of the kidney status in newborns]. / Srednie molekuly mochi v otsenke sostoianiia pochek u novorozhdennykh.

The results of examinations of 66 newborns were used to suggest a new approach for evaluating the curves of medium urea molecules (calculations of the relative area beneath the curve and of areas of the first and second maxima). Issues related with the impact excreted by medication, endogenous intoxication and by a direct lesion to the renal tissues on a level of medium urea molecules are under discussion.

The neonatal liver part II: Assessment and diagnosis of liver dysfunction.

The liver, the largest organ in the body, performs many essential functions, including the storage and filtration of blood, production of bile, regulation of plasma proteins and glucose, and biotransformation of drugs and toxins. Many neonates display signs of hepatic dysfunction such as hyperbilirubinemia, hepatomegaly, or elevated liver enzymes. Primary liver disease in neonates is rare; much of the liver dysfunction seen in the neonatal period is secondary to systemic illness such as sepsis or hypoxic injury. It is important for the clinician to have the skills and knowledge necessary to distinguish intrinsic liver disease from liver dysfunction resulting from extrahepatic causes. Early intervention to address the cause of dysfunction is critical to successful management of liver disease. This article reviews the assessment of liver function in neonates and examines the techniques used to diagnose liver dysfunction.

Valuation of the psychiatric damage. Considerations about two clinical cases.

We report a description of two mothers who scrupulously followed clinical controls and tests advised during pregnancy within a hospital environment, and who then gave birth to babies with serious deformation pathologies. In both cases, the seriousness of the psychiatric damage, is obviously useful for the medico-legal assessments. We have studied in both cases their mental make-up, understood as stable relationships between parts of the mind (thought, language, perception...). We have observed that in a fragile make-up a non significant event in many ways can cause an extremely violent reaction, whilst on the contrary, a serious event in "solid" people may not cause damaging consequences. The assessment of the mental make-up, conditions the degree of psychiatric damage, which is useful to the medical examiner, and is of fundamental importance for the individual choice of a therapeutic process.

Effect of sepsis syndrome on neonatal oxygen consumption and energy expenditure.

OBJECTIVE: To evaluate oxygen consumption (VO2), carbon dioxide production, and energy expenditure (EE) in full-term neonates with early-onset neonatal septicemia daily for 7 days beginning at the day of clinical diagnosis of sepsis. METHODS: A total of 17 spontaneously breathing full-term neonates, 10 with clinical signs of sepsis and 7 healthy neonates (control group), were enrolled in the study. Age at first study day was 3 +/- 0.9 days in both groups. Sepsis syndrome was defined as a systemic response to a bacterial infection with clinical signs of infection, elevated values of interleukins 6 and 8 and C-reactive protein, and abnormal white blood cell count and positive blood cultures (9 group B streptococci, 1 Escherichia coli). Measurements of VO2 and carbon dioxide production were performed daily for 7 days by means of indirect calorimetry. RESULTS: In the septic infants, VO2 and EE were increased by about 20% at days 1 to 3 and by 15% at day 4 when compared with the controls. From days 1 to 3, EE averaged 57 +/- 3 kcal/kg/d in the septic neonates and 47 +/- 2 kcal/kg/d in the controls. At day 4, EE was 55 +/- 2 and 47 +/- 2 kcal/kg/d, respectively. Energy intake was about the same in both groups, whereas weight gain during the 7 study days was significantly lower in the sick patients than in the control group (19 +/- 2 g/d vs 33 +/- 9 g/d and 5.4 +/- 0.5 g/kg/d vs 9.4 +/- 2.6 g/kg/d, respectively). Increased EE was associated with increased heart rate (126 +/- 4 vs 112 +/- 4 min(-1) at day 1) and respiratory rate (56 +/- 6 vs 40 +/- 4 min(-1) at day 1). There were no differences in rectal temperature (37.3 +/- 0.4 degrees C vs 37.4 +/- 0.2 degrees C), skin temperature (36.5 +/- 0.4 degrees C vs 36.6 +/- 0.3 degrees C), and oxygen saturation (96 +/- 3% vs 96 +/- 3%) between the 2 groups. CONCLUSIONS: Neonates with sepsis syndrome have elevated VO2 and EE values that could explain impaired growth during the illness period and may make the infants vulnerable to insufficient calorie supply during the acute phase of septic disease.

[Importance of J. Brazy's neurobiological index. Prediction of the number and severity of complications in very low birth weight infants]. / Importância do índice neurobiológico de J. Brazy. Predicção do número e gravidade de sequelas dos recém nascidos de muito baixo peso.

The objective of this study was to evaluate the neurodevelopment outcome of Very-Low-Birth-Weight Infants (VLBW), between 1987 and 1993, and correlate these findings with J.Brazy's Neurobiologic Risk Score (NBRS). The minimum corrected age at follow-up was 12 months. The neurodevelopmental assessment was performed using Mary Sheridan and Ruth Griffiths scales, Auditory and Visual Brainstem Evoked Responses and Stycar test. The NBRS was applied to 77 children. According to the score, three groups of risk were defined: Low < or = 4; Intermediate 5-7; High > or = 8. We obtained the following results: children with NBRS < 4, 20% had handicaps (5% of which major); children with NBRS 5-7, 41% had handicaps (23% of which major); in children with NBRS > 8, 95% had handicaps (80% of which major). The incidence of handicaps, (all grades included) was 71.4% for those weighing less than 1000 gr at birth, and 39.2% for those weighing 1000-1499 gr at birth. Major handicaps, mainly motor deficits, occurred in 26.8% of VLBW infants and minor to moderate handicaps were observed in 18.3% of patients in this group. These results were compared to J.Brazy's originals. We concluded that the NBRS, which is simple and objective to perform, is a good predictor of subsquent abnormal development in VLBW infants, allowing the infant's integration as soon as possible in high-risk follow-up programs, to place as soon as possible.

Antiviral therapy for neonatal herpes simplex virus: a cost-effectiveness analysis.

Each year, about 1,600 infants in the United States are infected with neonatal herpes simplex virus. We conducted a cost-effectiveness analysis of antiviral drug therapy (acyclovir) for three forms of herpes simplex virus infection: skin, ear, and mouth (SEM), central nervous system (CNS), and disseminated multiorgan (DIS) disease. Five levels of patient outcomes were examined (normal, mild, moderate, severe, dead). We obtained information on disease occurrence and survival from clinical trials and historical reviews of untreated newborns. We considered approaches for treating all or any of the forms of the disease and compared them with no use of antiviral drugs. The main measure of effectiveness was lives saved, including those of descendants of survivors. Costs were measured from a societal perspective and included direct medical costs, institutional care, and special education. We used a discount rate of 3% and valued dollars at 1995 levels. We also considered the perspective of a managed care organization. From a societal viewpoint relative to no treatment, antiviral therapy for SEM resulted in a gain of 0.8 lives and a cost reduction of $78,601 per case. For the treatment of CNS and DIS disease, antiviral therapy saved more lives but at increased cost, with respective marginal costs per additional life saved of $75,125 and $46,619. From a managed care perspective, antiviral therapy is more cost-effective than from a societal viewpoint because costs of institutional care and special education are not the responsibility of managed care organizations. Development of at-home therapies will further improve the cost-effectiveness of antiviral therapy for neonatal herpes simplex virus infection.

Multimodality evoked responses in the neurological assessment of the newborn.

In recent years increased attention has been devoted to evoked potentials (EP) in newborns. This paper reviews the literature and data from our research group in an attempt to assess the diagnostic and prognostic value of evoked responses in the first weeks of life and their use in different age-specific clinical conditions. The results show that EP are a very sensitive measure of the integrity of the sensory pathways. They make it possible to follow normal physiological maturation and the abnormalities of development resulting from neurological lesions. Repeated measurements of visual evoked potentials and somatosensorial evoked potential are prognostically useful in term infants, but seem much more limited in preterm newborns in predicting neurodevelopmental outcome.