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Background: Preterm infants are at risk for neurodevelopmental deficits. An association between retinopathy of prematurity (ROP) and impaired cognitive outcome has already been described. However, less is known about the impact of ROP on visual motor integration (VMI), which is a prerequisite not only for fine motor abilities but also for further school skills. Therefore, the aim of this study was to retrospectively investigate the impact of ROP on VMI at preschool age. Methods: The study was conducted at the Medical University of Vienna, including patients born between January 2009 and December 2014 with a gestational age of less than 30 weeks and/or a birth weight of less than 1,500 g. VMI was determined by Beery-Buktenica Developmental Test of Visual Motor Integration (Beery VMI) at the age of 5 years. Results: Out of 1,365 patients, 353 met inclusion criteria for this study. Two hundred sixteen of them had no ROP, while 137 had ROP (stage 1: n = 23, stage 2: n = 74, stage 3: n = 40). Mean value of the Beery VMI score was significantly lower in the ROP group compared to the No-ROP group (90 ± 16 vs. 99 ± 14; p < 0.01). By correcting for other important medical conditions, ROP still had a significant impact on Beery VMI score (p < 0.01). Particularly, lower scores were found for stage 2 (p < 0.01) and stage 3 (p < 0.01). Conclusion: Beery VMI scores were significantly lower in preterm infants with ROP stage 2 and 3 than in infants without ROP. This study shows the negative impact of ROP on VMI skills at preschool age, even after adjustment for key demographic and medical characteristics.

Introduction: Preterm birth and cerebral hemorrhage have adverse effects on brain development. Alterations in regional brain size on magnetic resonance imaging (MRI) can be assessed using 2D biometrical analysis, an easily applicable technique showing good correlation with 3D brain volumes. Methods: This retrospective study included 74 preterm neonates with intraventricular hemorrhage (IVH) born +0 weeks of gestation between 2011 and 2019. Cerebral MRI was performed at term-equivalent age, and 2D measurement techniques were used for biometrical analysis and compared to normative data of two control groups. Finally, the correlation and association of brain parameters and patterns of impaired brain growth and outcome at 2 and 3 years of age were evaluated. Results: Interhemispheric distance (IHD), the 3rd ventricle, and lateral ventricles presented larger, in contrast, cerebral biparietal width (cBPW), fronto-occipital diameter (FOD), and the length of the corpus callosum were smaller in IVH patients compared to respective controls. The strongest correlations with outcome were observed for the parameters FOD, anteroposterior diameter of the vermis, transverse cerebellar diameter (tCD), corpus callosum, 3rd ventricle, and left ventricular index. Patients with the small FOD, small BPW, and increased IHD pattern reached overall lower outcome scores at follow-up. Discussion: Preterm neonates with IVH showed reduced total brain sizes and enlarged pericerebral spaces compared to neurologically healthy controls. Biometric analysis revealed that several 2D brain parameters as well as different patterns of impaired brain growth were associated with neurodevelopmental impairment in early childhood. These findings may support prediction of long-term outcome and parental counseling in patients with IVH.

Aim To create a magnetic resonance imaging (MRI)-based scoring system specific to neonates born preterm with intraventricular haemorrhage (IVH), which could serve as a reliable prognostic indicator for later development and might allow for improved outcome prediction, individually-tailored parental counselling, and clinical decision-making. Method This retrospective, two-center observational cohort study included 103 infants born preterm with IVH (61 males, 42 females; median gestational age 26wks 6d), born between 2000 and 2016. Term-equivalent MRI was evaluated using a novel scoring system consisting of 11 items. A total MRI score was calculated and correlated with neurodevelopment between 2 years and 3 years of age. Prediction models for outcome were defined. Results The proposed MRI scoring system showed high correlation and strong predictive ability with regard to later cognitive and motor outcome. The prediction models were translated into easy-to-use tables, allowing developmental risk assessment. Interpretation The proposed MRI-based scoring system was created especially for infants born preterm with IVH and enables a comprehensive assessment of important brain areas as well as potential additional abnormalities commonly associated with IVH. Thus, it better represents the severity of brain damage when compared with the conventional IVH classification. Our scoring system should provide clinicians with valuable information, to optimize parental counselling and clinical decision-making.

BACKGROUND Medical-imaging-based three-dimensional (3D) printed models enable improvement in skills training, surgical planning, and decision-making. This pilot study aimed to use multimodality imaging and to add and compare 3D ultrasound as a future standard to develop realistic neonatal brain models including the ventricular system. METHODS Retrospective computed tomography (CT), magnetic resonance imaging (MRI), and 3D ultrasound-based brain imaging protocols of five neonatal patients were analyzed and subsequently segmented with the aim of developing a multimodality imaging-based 3D printed model. The ventricular anatomy was analyzed to compare the MRI and 3D ultrasound modalities. RESULTS A realistic anatomical model of the neonatal brain, including the ventricular system, was created using MRI and 3D ultrasound data from one patient. T2-weighted isovoxel 3D MRI sequences were found to have better resolution and accuracy than 2D sequences. The surface area, anatomy, and volume of the lateral ventricles derived from both MRI and 3D ultrasound were comparable. CONCLUSIONS We created an ultrasound- and MRI-based 3D printed patient-specific neonatal brain simulation model that can be used for perioperative management. To introduce 3D ultrasound as a standard for 3D models, additional dimensional correlations between MRI and ultrasound need to be examined. IMPACT We studied the feasibility of implementing 3D ultrasound as a standard for 3D printed models of the neonatal brain. Different imaging modalities were compared and both 3D isotropic MRI and 3D ultrasound imaging are feasible for printing neonatal brain models with good dimensional accuracy and anatomical replication. Further dimensional correlations need to be defined to implement it as a standard to produce 3D printed models.

Background and purpose To determine whether neurofilament light chain (NfL), a promising serum and cerebrospinal fluid (CSF) biomarker of neuroaxonal damage, predicts functional outcome in preterm infants with neonatal brain injury. Methods Our prospective observational study used a sensitive single-molecule array assay to measure serum and CSF NfL concentrations in preterm infants with moderate to severe peri/intraventricular hemorrhage (PIVH). We determined temporal serum and CSF NfL profiles from the initial diagnosis of PIVH until term-equivalent age and their association with clinical and neurodevelopmental outcome until 2 years of age assessed by Bayley Scales of Infant Development (3rd edition). We fitted univariate and multivariate logistic regression models to determine risk factors for poor motor and cognitive development. Results The study included 48 infants born at n = 25)-but not post-hemorrhagic hydrocephalus requiring external ventricular drainage (n = 29) nor any other impairment-was independently associated with sNfL. Multivariate logistic regression models identified sNfL as an independent predictor of poor motor outcome or death at 1 and 2 years. Conclusions Serum neurofilament light chain dynamics in the first weeks of life predict motor outcome in preterm infants with PIVH.

Providing optimal pain relief is a challenging task when caring for premature infants. The aim of this study was to compare the long-term cognitive, motor, and behavioral outcomes of preterm infants before and after the implementation of a pain and sedation protocol. In addition, we investigated whether the increased opiate administration resulting after the implementation process had an impact on these outcomes. Cognitive outcomes were evaluated using the Kaufman Assessment Battery for Children (KABC), neuromotor examinations were based on Amiel-Tison, and behavioral outcomes were assessed using the parent-reported Child Behavior Checklist (CBCL). One hundred extremely preterm infants were included in the study (control group, n = 53; intervention group, n = 47). No significant differences were found in cognitive and motor outcomes at preschool age. However, every increase in the cumulative opiate exposure for each 100 mg/kg was weakly significantly associated with a higher risk for autism spectrum features (adjusted odds ratio (aOR) = 1.822, 95% confidence interval (CI) [1.231–2.697]; P = 0.03) and withdrawn behavior (aOR = 1.822, 95% CI [1.231–2.697]; P = 0.03) at preschool age. Increased neonatal cumulative opiate exposure did not alter cognitive and motor outcomes but may represent a risk factor for autism spectrum and withdrawn behavior at preschool age.

Aim Our aim was to examine the relationship between rescuers' anthropometric data and chest compression quality during paediatric resuscitation training. Methods This study focused on 224 medical students (53% women) who performed 2 minutes of paediatric resuscitation at the Medical University of Vienna, Austria: 116 on a baby manikin and 108 on an adolescent manikin. Skill Reporter software measured chest compression quality by recording compression depth, frequency, hand position and complete recoil. The participants' height, weight and body mass index (BMI) were recorded. Results Participants with a lower BMI achieved higher total chest compression scores on both the baby and adolescent manikins than participants with a higher BMI. The latter were more likely to exceed the correct compression depth and not achieve complete chest recoil in the adolescent manikin. When it came to the baby manikin, the female participants achieved better chest recoil and the males achieved a higher number of compressions at the correct rate. Males also achieved better chest recoil with the adolescent manikins. Being tall only correlated with incomplete recoil in the adolescent manikin. Conclusion The results indicate that anthropometric variables were associated with chest compression quality in paediatric patients and should be considered by future education programmes.

Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain.To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures.This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks' gestation or more and younger than 48 hours old. Data analysis was completed in April 2021.Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated.Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years.Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in the CSG died before the 2-year assessment. The odds of the primary outcome were not significantly different in the ESG group compared with the CSG group (ESG, 38 of 86 [44%] vs CSG, 27 of 86 [31%]; odds ratio [OR], 1.83; 95% CI, 0.96 to 3.49; P = .14). There was also no significant difference in those with HIE (OR, 1.77; 95% CI, 0.84 to 3.73; P = .26). There was evidence that cognitive outcomes were worse in the ESG (mean [SD] scores, ESG: 97.4 [17.7] vs CSG: 103.8 [17.3]; mean difference, -6.5 [95% CI, -1.2 to -11.8]; P = .01). There was little evidence of a difference in secondary outcomes, including time to suck feeds, seizure burden, or brain injury score.Treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures.http://anzctr.org.au Identifier: ACTRN12611000327987.

Background: Culture-proven sepsis is the gold standard in early-onset neonatal sepsis diagnosis. Infants born ≤29 weeks gestation after preterm rupture of membranes in the years 2009–2015 were included in a retrospective cohort study performed at a level III fetal-maternal unit. The study aimed to compare culture-proven sepsis, clinical sepsis and positive laboratory biomarkers ≤72 h as predictors of mortality before discharge and the combined outcome of mortality or severe short-term morbidity (severe cerebral morbidity, bronchopulmonary dysplasia and retinopathy). Results: Of the 354 patients included, culture-proven sepsis, clinical sepsis and laboratory biomarkers were positive in 2.3%, 8.5% and 9.6%, respectively. The mortality rate was 37.5% for patients with culture-proven sepsis (3/8), 33.3% for patients with clinical sepsis (10/30) and 8.8% for patients with positive laboratory biomarkers (3/34), respectively. Mortality or severe morbidity occurred in 75.0% of patients with culture-proven sepsis (6/8), 80.0% of patients with clinical sepsis (24/30) and 44.1% of patients with positive laboratory biomarkers (15/34), respectively. Conclusion: In preterm infants after preterm rupture of membranes, clinical sepsis was almost four times more common and at least equally valuable in predicting mortality and mortality or severe morbidity compared to culture-proven sepsis.

This systematic review and meta-analysis aimed to investigate the association of neonatal exposure to pain, stress, opiate administration alone, as well as opiate administration prior to a painful procedure on neuronal cell death, motor, and behavioral outcomes in rodents. In total, 36 studies investigating the effect of pain (n = 18), stress (n = 15), opiate administration (n = 13), as well as opiate administration prior to a painful event (n = 7) in rodents were included in our meta-analysis. The results showed a large effect of pain (g = 1.37, 95% CI 1.00-1.74, p .001) on neuronal cell death. Moreover, higher number of neonatal pain events were significantly associated with increased neuronal cell death, increased anxiety (b = -1.18, SE = 0.43, p = .006), and depressant-like behavior (b = 1.74, SE = 0.51, p = .027) in rodents. Both opiates and pain had no impact on motor function (g = 0.26, 95% CI 0.18-0.70, p = .248).

Humans are biologically endowed with the faculty of language. However, the way neonates can crack this complex communicative code is yet not totally understood. While phonetic discrimination has been widely investigated in neonates, less is known about the role of supra-segments patterns in the recognition of native language. Therefore, the aim of this study was to evaluate accent discrimination abilities in newborns in a sentential prosody paradigm. We used near-infared spectroscopy to investigate accent discrimination in 21 full-term born infants within the first days of life. Sentential prosody was used to investigate: (a) native accent, (b) foreign accent, and (c) flattened accent. Neonates revealed a significantly smaller hemodynamic response to native accent compared to flattened accent and foreign accent, respectively. Cluster-based permutation analysis revealed two clusters with a significant difference between the two conditions native accent and foreign accent. The first cluster covered the middle and superior frontal, middle and superior temporal, central, and parietal areas within the left hemisphere. The second cluster, located in the right hemisphere, covered inferior, middle, and superior frontal, central, middle and superior temporal areas. We therefore conclude that neonates can differentiate prosodic features like accents within the same language a few days after birth.

Background International guidelines recommend the use of item based scales for the assessment of pain and sedation. In our previous study, the implementation of the Neonatal Pain Agitation and Sedation Scale (N-PASS), and the associated systematic assessment and treatment of pain and sedation reduced pain and over-sedation in our intervention group, but lead to a significant increase of individual opiate exposure. This increased opiate exposure was not associated with impaired motor and mental development at one year of age. As one-year follow-up is not necessarily representative for future outcomes, we retested our sample at three years of age. Methods Fifty-three patients after (intervention group) and 61 before implementation (control group) of the N-PASS and the Vienna Protocol for the Management of Neonatal Pain and Sedation (VPNPS), were compared for motor, mental and behavioural development at three-years follow-up using the Bayley Scales of Infant Development. Results Cumulative opiate exposure was not associated with mental (p = .31) and motor (p = .20) problems when controlling for other important medical conditions, but was associated to lower behavioural scores (p = .007). No statistically significant differences were found with regard to mental (p = .65), psychomotor (p = .12) and behavioural (p = .61) development before and after the implementation of the N-PASS and the VPNPS. Conclusion Implementing a neonatal pain and sedation protocol increased opiate exposure without affecting neurodevelopmental outcome at three-years of age.

Extrauterine life is an important factor when considering brain maturation. Few studies have investigated the development of visual evoked potentials (VEP) in extremely preterm infants, and only a minority have taken into consideration the impact of extrauterine life. The aim of this study was to assess the normal maturation of VEP in infants born prior to 29 weeks gestational age (GA) and to explore the potential influence of extrauterine life. VEP were prospectively recorded in extremely preterm infants, and principal peaks (N0, N1, P1, N2, P2, N3) were identified. The mean of peak-time and percentages of peak appearances were assessed for three GA groups (23/24, 25/26, 27/28 weeks) and four subgroups of increasing postnatal age (PNA), up to 8 weeks after birth. A total of 163 VEP recordings in 38 preterm infants were analyzed. With increasing GA at birth, peak-times decreased. When comparing infants with equal GA but longer extrauterine life, those with the highest PNA demonstrated the shortest VEP peak-times. However, this effect was less present in infants born prior to 25 weeks GA. Provided that a certain maturational threshold is reached, extrauterine life appears to accelerate maturation of the visual system in preterm infants.

Postnatally, the immature left ventricle (LV) is subjected to high systemic afterload. Hypothesizing that LV pumping would change during transition–adaptation, we analyzed the LV in preterm infants (GA≤32+6), clinically stable or with a hemodynamically significant patent ductus arteriosus (hPDA) by applying a pump model. Pumping was characterized by EA (effective arterial elastance, reflecting afterload), EES (end-systolic LV elastance, reflecting contractility), EA/EES coupling ratios, descriptive EA:EES relations, and EA/EES graphs. Data calculated from echocardiography and blood pressure were analyzed by diagnosis (S group: clinically stable, no hPDA, n=122; hPDA group, n=53) and by periods (early transition: days of life 1–3; late transition: 4–7; and adaptation: 8–30). S group: LV pumping was characterized by an increased EA/EES coupling ratio of 0.65 secondary to low EES in early transition, a tandem rise of both EA and EES in late transition, and an EA/EES coupling ratio of 0.45 secondary to high EES in adaptation; hPDA group: time-trend analyses showed significantly lower EA (P

OBJECTIVE During neonatal cardiopulmonary resuscitation, early establishment of vascular access is crucial. We aimed to review current evidence regarding different routes for the administration of medications during neonatal resuscitation. DATA SOURCES We reviewed PubMed, EMBASE, and Google Scholar using MeSH terms "catheterization," "umbilical cord," "delivery room," "catecholamine," "resuscitation," "simulation," "newborn," "infant," "intraosseous," "umbilical vein catheter," "access," "intubation," and "endotracheal." STUDY SELECTION Articles in all languages were included. Initially, we aimed to identify only neonatal studies and limited the search to randomized controlled trials. DATA EXTRACTION Due to a lack of available studies, studies in children and adults, as well as animal studies and also nonrandomized studies were included. DATA SYNTHESIS No randomized controlled trials comparing intraosseous access versus peripheral intravascular access versus umbilical venous catheter versus endotracheal tube versus laryngeal mask airway or any combination of these during neonatal resuscitation in the delivery room were identified. Endotracheal tube: endotracheal tube epinephrine administration should be limited to situations were no vascular access can be established. Laryngeal mask airway: animal studies suggest that a higher dose of epinephrine for endotracheal tube and laryngeal mask airway is required compared with IV administration, potentially increasing side effects. Umbilical venous catheter: European resuscitation guidelines propose the placement of a centrally positioned umbilical venous catheter during neonatal cardiopulmonary resuscitation; intraosseous access: case series reported successful and quick intraosseous access placement in newborn infants. Peripheral intravascular access: median time for peripheral intravascular access insertion was 4-5 minutes in previous studies. CONCLUSIONS Based on animal studies, endotracheal tube administration of medications requires a higher dose than that by peripheral intravascular access or umbilical venous catheter. Epinephrine via laryngeal mask airway is feasible as a noninvasive alternative approach for drug delivery. Intraosseous access should be considered in situations with difficulty in establishing other access. Randomized controlled clinical trials in neonates are required to compare all access possibilities described above.

Objective To establish longitudinal reference values for cerebral ventricular size in the most vulnerable patients at risk for intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilatation (PHVD). Study design This retrospective study included neurologically healthy preterm neonates born at 230/7-266/7 weeks of gestational age between September 2011 and April 2019. Patients were treated at 2 Austrian tertiary centers, Medical University of Vienna and Medical University of Innsbruck. All available cerebral ultrasound scans until 30 weeks corrected age were analyzed. Ventricular measurements included ventricular index, anterior horn width (AHW), and thalamo-occipital distance (TOD) and longitudinal percentiles were created. Results The study cohort consisted of 244 preterm neonates, with a median gestational age of 253/7 weeks (IQR, 244/7-260/7 weeks) and a median birth weight of 735 g (IQR, 644-849 g). A total of 993 ultrasound scans were available for analysis, resulting in >1800 measurements of ventricular index, AHW, and TOD. Special attention was given to the 97th percentile as well as 2 mm and 4 mm above the 97th percentile, which are used internationally as cutoffs for intervention in the presence of PHVD. Conclusions We present percentile charts based on a cohort of extremely premature infants including neonates born at the border of viability suited to follow-up the most vulnerable patients at risk for IVH and PHVD. Furthermore, we provide an extensive literature research and comparison of all available reference values, focusing on ventricular index, AHW, and TOD.

Aim The World Health Organization recommends regular simulation training to prevent adverse healthcare events. We used specially trained medical students to provide paediatric simulation training to their peers and assessed feasibility, cost and confidence of students who attended the courses. Methods Students at the Medical University of Vienna, Austria were eligible to participate. Students attended two high-fidelity simulation training sessions, delivered by peers, which were video recorded for evaluation. The attendees then completed questionnaires before and after the training. Associated costs and potential benefits were analysed. Results From May 2013 to June 2015, 152 students attended the sessions and 57 (37.5%) completed both questionnaires. Satisfaction was high, with 95% stating their peer tutor was competent and 90% saying that peer tutors were well prepared. The attendees’ confidence in treating critically ill children significantly improved after training (p

Children born preterm are at higher risk to develop language deficits. Auditory speech discrimination deficits may be early signs for language developmental problems. The present study used functional near-infrared spectroscopy to investigate neural speech discrimination in 15 preterm infants at term-equivalent age compared to 15 full term neonates. The full term group revealed a significantly greater hemodynamic response to forward compared to backward speech within the left hemisphere extending from superior temporal to inferior parietal and middle and inferior frontal areas. In contrast, the preterm group did not show differences in their hemodynamic responses during forward versus backward speech, thus, they did not discriminate speech from non-speech. Groups differed significantly in their responses to forward speech, whereas they did not differ in their responses to backward speech. The significant differences between groups point to an altered development of the functional network underlying language acquisition in preterm infants as early as in term-equivalent age. Keywords: Near-infrared spectroscopy, Preterm birth, Newborn infants, Language development, Speech discrimination

Background: Few data have been published on the combined use of amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS) for outcome prediction in neonates cooled for hypoxic-ischemic encephalopathy (HIE). Objective: Our aim was to evaluate the predictive values and the most powerful predictive combinations of single aEEG and NIRS parameters and the respective cut-off values with regard to short-term outcomes in HIE II. Methods: aEEG and NIRS were prospectively studied at the Medical University of Vienna in the first 102 h of life with regard to magnetic resonance imaging (MRI). Thirty-two neonates diagnosed with HIE II treated with hypothermia were investigated. The measurement period was divided into 6-h epochs. According to MRI, 2 outcome groups were defined and predictive values of aEEG parameters, regional cerebral oxygen saturation (rScO2), and the additional value of both methods combined were studied. Receiver operating curves (ROC) were obtained and area under the curve (AUC) values were calculated. ROC were then used to detect the optimal cut-off points, sensitivity, specificity, positive predictive values, and negative predictive values. Results: At all time epochs, combined parameter scores were more predictive than single parameter scores. The highest AUC were observed between 18 and 60 h of cooling for the aEEG summation score (0.72-0.84) and for (background pattern + seizures) × rScO2 (0.79-0.85). At 42-60 h sensitivity was similar between those 2 scores (87.5-90.0%), but the addition of NIRS to aEEG led to an increase in specificity (from 52.4-59.1% to 72.7-90.5%). Conclusions: In HIE II, aEEG and NIRS are important predictors of short-term outcome. The combination of both methods improves prognostication. The highest predictive abilities were observed between 18 and 60 h of cooling.

Objectives Critically ill neonatal and pediatric patients often require central vascular access. Real-time ultrasound guidance for central venous catheterization is beneficial. Because the diameter of central veins is much smaller in neonates than in adults, extensive training is needed to master the visualization and catheterization of central veins in neonates. This study assessed the learning effect of a standardized simulation-based teaching program on ultrasound-guided cannulation in a low-cost cadaver tissue model. Design This simulation-based prospective study assessed physician competence in the ultrasound-guided central venous catheterization procedure. Analyses were conducted before and after the teaching course. Setting Pediatric simulation center at a tertiary care center. Subjects Staff physicians from the Neonatal ICU and PICUs at the Medical University of Vienna. Interventions Two latex tubes, with internal diameters of 2 and 4 mm, were inserted in parallel into cadaver tissue to mimic vessels and create a model for central venous catheterization. Measurements and main results Under ultrasound guidance, each participant attempted to puncture and insert a guide-wire into each of the latex tubes using in-plane and out-of-plane techniques, both before and after the teaching course. The training program was assessed using a questionnaire and a performance checklist. Thirty-nine physicians participated in this study. The rates of failure of guide-wire insertion into 2-mm tubes were significantly lower after than before the teaching course, using both in-plane (p = 0.001) and out-of-plane (p = 0.004) techniques. Teaching, however, did not significantly reduce the insertion failure rate into 4-mm tubes, either in-plane (p = 0.148) or out-of-plane (p = 0.069). The numbers of successful cannulations on the first attempt increased after the teaching in all methods (p = 0.001). Conclusions Implementation of a skills training program for ultrasound-guided central venous catheterization in a cadaver tissue model was feasible and cost- and time-effective. The number of attempts until successful cannulation of small vessels (2-mm tube) was significantly lower after than before the standardized teaching program.

Aim This study compared the short-term and neurodevelopmental outcomes of extremely preterm infants before and after the implementation of a protocol to manage neonatal pain and sedation. Methods Our study cohort comprised 140 extremely preterm infants from two neonatal intensive care units. We retrospectively analysed opiate exposure, time on mechanical ventilation, inotropic support, nutritional aspects and growth 12 months before (controls) vs 12 months after (intervention) the implementation of the Vienna Protocol for Neonatal Pain and Sedation. Infants were evaluated at the corrected age of 12 months using the Bayley Scales of Infant Development - Second Edition. Results After the protocol was implemented, the cumulative opiate dose increased from a baseline of 15 mg/kg ± 41 to 89 mg/kg ± 228 morphine equivalents. Time on mechanical ventilation, inotropic support, length of parenteral nutrition, growth, length of stay and in-hospital morbidity were similar before and after the implementation, with no differences between the groups in mental, motor and behavioural development at the one-year follow-up. However, opiate exposure was a possible risk factor for lower behaviour rating scores (estimate = -0.04; p = 0.006). [Correction added on 23 February 2016, after online publication: In the preceding sentences, the cumulative opiate dose as well as the estimate value for the behavioral rating scale were previously incorrect and have been amended in this current version.] Conclusion Implementing a neonatal pain and sedation protocol increased opiate exposure, but had no effect on the in-hospital and neurodevelopmental outcomes of extremely preterm infants.

Amplitude-integrated electroencephalography (aEEG) findings in hypoxic-ischemic encephalopathy characterized by secondary energy failure have been described in detail. In contrast, reports of use of aEEG in patients with encephalopathy due to primary energy failure as seen in inherited metabolic disorders are sparse. We report two cases of lethal mitochondrial encephalopathy due to mitochondrial respiratory chain complex I deficiency. We present clinical course, laboratory evaluations, aEEG, conventional electroencephalography, magnetic resonance imaging and magnetic resonance spectroscopy findings of two cases identified with mitochondrial encephalopathy between 2002 and 2007. Both infants were born at term. Both presented with intractable seizures and mild hypotonia within the first days of life, in the absence of any evidence suggestive of hypoxic- ischemic encephalopathy. Both cases were treated with multiple anticonvulsants and in neither case were seizures fully controlled. Magnetic resonance imaging in both cases revealed a structurally normal brain and case one showed subtle diffuse deep white matter signal abnormality. Magnetic resonance spectroscopy revealed no elevation of lactate. In both cases, aEEG tracings were markedly abnormal, confirmed by electroencephalography. Case one showed status epilepticus on an abnormally high amplitude background and case two presented with a mainly discontinuous background pattern with intermittent burst-suppression pattern activity. Complex I activity in skeletal muscle homogenate was abnormally low in both patients. The use of aEEG as a valuable assessment and monitoring tool in patients with metabolic encephalopathy should be further promoted.

Background Sedatives are essential drugs in every intensive care unit in order to ensure the patient's optimal level of comfort. Avoiding conditions of over- and under-sedation is a challenge in a neonatal intensive care setting. Drug administration could be optimized by the concomitant use of objective methods to assess the level of sedation. Aims We aimed to look at the ability of different methods (Neonatal Pain, Agitation and Sedation Scale, amplitude-integrated Electroencephalogram, and Bispectral Index), and their combination, in detecting different level of sedation. Methods Twenty-seven neonates among whom 17 were receiving sedatives with or without opiate analgesics were monitored using the Neonatal Pain, Agitation and Sedation Scale, the amplitude-integrated Electroencephalogram, and the Bispectral Index. According to the expert opinion of two trained neonatologists, patients were categorized into three groups: no, light, and deep sedation. Four hours of simultaneous assessment of the Neonatal Pain, Agitation and Sedation Scale scores, Burdjalov scores (to summarize the amplitude-integrated Electroencephalogram trace), and Bispectral Index values were considered for the comparative analysis across these groups. Results All three methods could differentiate patients who were not sedated from those who were deeply sedated: median score 12 and 9, respectively, (95% CI of difference = 1.99-5.99, P = 0.001) for the amplitude-integrated Electroencephalogram Burdjalov score; median 1 and -5, respectively, (95% CI of difference = 2.99-8.00, P = 0.001) for the Neonatal Pain, Agitation and Sedation Scale; and median 48 and 37, respectively, (CI of difference = 1.77-22.00, P = 0.043) for the Bispectral Index. However none of them, used alone, was able to differentiate light and deep sedation: median score 10 and 9, respectively, for the amplitude-integrated Electroencephalogram Burdjalov score; median -2 and -5, respectively, for the Neonatal Pain, Agitation and Sedation Scale; and median 48 and 37, respectively, for the Bispectral Index. Only the amplitude-integrated Electroencephalogram and the Neonatal Pain, Agitation and Sedation Scale were able to differentiate between the conditions of no sedation and light sedation. Also, according to the area under the curves values, the combination of the Neonatal Pain, Agitation and Sedation Scale with the Burdjalov score derived from the amplitude-integrated Electroencephalogram showed the best accuracy in differentiating light and deep sedation. Conclusion While none of the three methods alone was able to precisely differentiate between different levels of sedation, we suggest that using a combination of amplitude-integrated Electroencephalogram and Neonatal Pain, Agitation and Sedation Scale can be useful to distinguish between light and deep sedation in neonatal patients.

BackgroundAsphyxia is the most common reason for newborns to fail to make a successful fetal-to-neonatal transition. There is currently a lack of data evaluating hemodynamic effects of epinephrine during neonatal cardiopulmonary resuscitation.MethodsTwenty-four newborn piglets were exposed to asphyxia. Thereafter, positive pressure ventilation was commenced for 30 s, followed by chest compressions (CC). Piglets were randomized into three experimental groups: 3:1 compression:ventilation ratio; CC during sustained inflation (SI) at a rate of 90 CC per minute, or CC during SI at a rate of 120 CC per minute. Epinephrine (0.01 mg/kg per dose) was administered to a maximum of four doses. Hemodynamic parameters were measured throughout the experiment.ResultsAnimals were divided into survivors and nonsurvivors. End-diastolic and developed pressures declined after epinephrine administration in the survivor group. dp/dt min was significantly higher in the survivor group whereas dp/dt max showed no significant differences. Epinephrine had no effect on either heart rate or cardiac output in both groups. Ejection fraction increased after epinephrine with no significant difference between groups.ConclusionEpinephrine did not affect survival rates or return of spontaneous circulation in our postnatal porcine model of neonatal asphyxia.

Background: The lower margin amplitude (LMA) of the amplitude-integrated electroencephalogram (aEEG) is suppressed in neonates during deep sedation, a feature that is attributed to the bispectral index (BIS) in adults. Objective: We compare the BIS and the LMA of the aEEG in neonates. Methods: Thirty neurologically healthy neonates between 37 and 44 weeks postmenstrual age were included in this study. Twenty patients received sedoanalgesic therapy for various reasons. BIS and aEEG recordings were performed simultaneously. The digital data were imported in the numerical software environment Matlab®. The LMA of the aEEG was computed on a 1-min time scale and synchronized with the BIS data. The correlation between the time-dependent variables BIS and LMA was estimated using the Spearman rank correlation index. Results: The median correlation between BIS and LMA was 0.3. Inclusion of recordings of high signal quality only into analysis improved the median correlation index to 0.6. Conclusions: We found a light-to-moderate correlation between BIS and LMA in our study cohort and a good correlation in the subgroup with high signal quality.

SummaryBackground Tramadol is used following neonatal cardiac and general surgery. However, its ability to opioid-spare or facilitate earlier extubation in postoperative neonates is unquantified. Objective This randomized placebo-controlled trial aimed to assess whether tramadol's addition to standard analgesia resulted in earlier extubation or reduced analgesic/sedative requirements in postsurgical neonates. Methods Neonates born ≥32 weeks postmenstrual age received either tramadol [T] 2 mg·kg−1 or placebo [P] 6-hourly for up to 5 days postthoracoabdominal surgery in addition to morphine (commenced at 20 mcg·kg−1·h−1) and 6-hourly IV acetaminophen. Time to extubation, morphine and midazolam amounts, hourly pain scores, and seizure activity were compared using an intention-to-treat and per-protocol analysis. Results Seventy-one neonates participated. Median survival time to extubation was similar between the groups (T 67 h [95% CI 51, 84] vs P 52 h [95%CI 43, 65]; P = 0.4), and similar numbers were extubated by 96 h (T 69% vs P 77%; difference −8%, 95%CI −28, 13%). Morphine and midazolam exposure was similar, with low pain scores in both groups (mean percentage of time with a pain score >5/20 during the 5 days: T 13% vs P 11%, difference in means 2.8 [95% CI −1.8, 7.6], P = 0.20). Most participants had normal cranial ultrasounds (T 86% vs P 86%); no seizures occurred clinically or electroencephalographically. Conclusion Tramadol's addition to standard analgesia in this small group of postsurgical neonates did not appear to have any positive effect on time to extubation, morphine or midazolam exposure, or pain scores. This questions the benefit of tramadol for postsurgical neonates. Importantly, no seizures occurred in these ill neonates who may potentially be at greater risk of tramadol toxicity compared with adults.

Aim The aim of this study was to measure the brain activity of preterm infants treated with caffeine citrate and doxapram for preterm apnoea, using amplitude-integrated electroencephalography (aEEG), to identify any adverse effects on cerebral function. Methods We analysed the aEEG tracings of 13 preterm infants

Background and PurposeSerum neurofilament light chain (sNfL) has recently emerged as a promising biomarker reflecting structural neuro-axonal damage in different neurological diseases. Our study aimed at assessing whether sNfL can predict the functional outcome in preterm infants who suffered from neonatal haemorrhagic brain injury.MethodsIn this prospective observational study, we used an ultrasensitive single-molecule array assay to measure serum and cerebrospinal fluid (CSF) concentrations of NfL in preterm infants diagnosed with intraventricular haemorrhage (IVH) in the first few days of life. We determined the temporal profile of serum and CSF NfL levels from first diagnosis of IVH until term equivalent age, their association with cerebral imaging markers, and with clinical and functional outcome until 2 years of age assessed by Bayley Scales of Infant Development. We fitted univariable and multivariable logistic regression models to determine risk factors for low motor and cognitive development. Longitudinal mixed effects models modelled NfL levels using cubic spline smoothers to track the trajectory over time.ResultsThe study included 48 infants born with less than 32 weeks of gestation. At the time point of IVH diagnosis, NfL median levels were 271.9 pg/mL (IQR 151.2–389.7), and strongly decreased until term equivalent age to 15.7 pg/mL (IQR 11.1–32.2). CSF values were 113-fold higher (IQR 40–211) than corresponding serum values. Additional cerebral infarction (n=23) but not post-haemorrhagic hydrocephalus with permanent external ventricular drainage (n=29) or other diseases independently determined sNfL levels. In multivariate logistic regression models, the only significant predictor of poor motor outcome at 2 years or death was sNfL level (p=0.02).There was a clear difference between the NfL trajectory for those with poor motor outcome at 1 year.ConclusionsThis study shows that early sNfL is an independent prognostic biomarker for motor functional outcome in preterm infants after IVH.Disclosure(s)Nothing to disclose

Aim To investigate gender-related differences in amplitude-integrated electroencephalography (aEEG) associated with neurodevelopmental outcome at 3 years. Methods Preterms born

Background: Filter and peak detection algorithms implemented in amplitude-integrated electroencephalogram (aEEG) systems are not standardized. New aEEG systems are continuously enriching the market and clinicians are faced with different aEEG devices whose tracings may vary. Objectives: The aim of this work was to determine the role of different aEEG systems on quantitative measurements of the aEEG. Methods: In this observational study, a single-channel aEEG recording (Olympic CFM 6000) with corresponding EEG signal was obtained from 32 infants at a gestational age of 36-44 weeks. The signals were split into 334 episodes of 4 h. New aEEG tracings were generated using the NicoletOne Reader Software and aEEG emulations with varying filter profiles and peak detection settings. The aEEG amplitude margins and automated annotation of continuous normal voltage (CNV) were compared. Results: The output of the Olympic and the NicoletOne systems are very similar but not identical; the Spearman rank correlations of the aEEG amplitude margins exceeded 0.9 and the differences in the lower and upper amplitude margins were 1.55 μV (SD 1.47) and -2.12 μV (SD 1.44) on average (n = 309), respectively. The aEEG emulation showed that the differences between the output of the Olympic and the NicoletOne system could be primarily ascribed to the peak detection algorithm. The differences in output can affect automated analyses with agreement rates in CNV detection of 76% (n = 32, positive) and 92% (n = 32, negative) when comparing the Olympic to the NicoletOne outputs. Conclusions: Commercial aEEG systems have similar but not identical outputs. Care is advised when interpreting automated aEEG classifications across different devices.

Background: In Austria, a nationally mandated prenatal serological congenital toxoplasmosis screening program was introduced in 1974 in response to a high incidence of 7.8 per 1,000 infected infants. Maternal prenatal recognition of acute gestational infection and early treatment of infants with congenital infection are important because prenatal and accurate postnatal antibiotic therapy improves the outcomes of infected infants. Objective: To determine the impact of additional maternal and/or fetal cord blood serology at birth on improving current prenatal maternal screening in detecting congenital toxoplasmosis. Methods: In this prospective observational study, 5,545 consecutive women were included over a 19-month period. Routine prenatal maternal toxoplasmosis serology screening was performed along with additional cord blood serology screening at delivery. Fetal cord blood serology included Sabin-Feldman dye and IgM immunosorbent agglutination assay testing. Results: Based on the initial prenatal maternal screening serology results, there was evidence of a prior chronic infection manifest in 1,830 (33.0%) women and 3,708 (66.9%) were not infected. Seven (0.13%) were diagnosed with acute toxoplasma infection based on seroconversion. Of these, 4 manifested transmission, and 3 did not. Of the seven infected women, routine prenatal maternal screening identified acute infection in only 2 of the women, 1 of whom had an infected fetus with abnormal prenatal ultrasound. Fetal cord blood serology screening identified an additional 5 women, 3 with infected fetuses. Conclusions: Identification of Toxoplasma gondii infection by prenatal maternal serological testing is significantly improved by the addition of maternal and/or fetal serological testing at birth.

Despite a decreasing incidence, intraventricular hemorrhage (IVH) remains a point of major concern in neonatology due to its association to adverse neurodevelopmental outcome (NDO). Aim of this study was to compare outcome of preterm infants with different grades of IVH born below 32 weeks of gestational age (GA) with outcome of controls without IVH and to especially evaluate the influence of low grade IVH on NDO.Four hundred seventy-one preterm infants with a GA below 32 weeks were admitted to our neonatal intensive care unit between 1994 and 2005 and included into analysis.IVH patients showed significantly lower mean psychomotor and mental developmental indices and a significantly higher percentage of cerebral palsy and visual impairment. Results of IVH patients born below 28 weeks of GA were significantly worse than results of IVH patients born at or above 28 weeks of GA. In all parameters, an increase of abnormal results with increasing grade of IVH could be observed; even patients with low-grade IVH (grades I and II) showed higher percentages of impairment compared to controls without any IVH.Even low-grade IVH has an significant impact on neurodevelopmental outcome of preterm patients and gestational age influences the impact of intraventricular hemorrhage on neurodevelopmental outcome.

Background Perioperative brain injury is common in infants undergoing cardiac surgery. Amplitude-integrated electroencephalography (aEEG) provides real-time neurologic monitoring and can identify seizures and abnormalities of background cerebral activity. We aimed to determine the incidence of perioperative electrical seizures, and to establish the background pattern of aEEG, in neonates undergoing Norwood-type palliations for complex congenital heart disease in relation to outcome at 2 years. Methods Thirty-nine full-term neonates undergoing Norwood-type operations underwent aEEG monitoring before and during surgery and for 72 hours postoperatively. The perfusion strategy included full-flow moderately hypothermic cardiopulmonary bypass with antegrade cerebral perfusion. Amplitude-integrated electroencephalography tracings were reviewed for seizure activity and background pattern. Survivors underwent neurodevelopmental outcome assessment using the Bayley Scales of Infant Development (3rd edition) at 2 years of age. Results Thirteen (33%) infants had electrical seizures, including 9 with intraoperative seizures and 7 with postoperative seizures. Seizures were associated with significantly increased mortality, but not with neurodevelopmental impairment in survivors. Delay in recovery of the aEEG background beyond 48 hours was also associated with increased mortality and worse motor development. Conclusions Perioperative seizures were common in this cohort. Intraoperative seizures predominantly affected the left hemisphere during antegrade cerebral perfusion. Delayed recovery in aEEG background was associated with increased risk of early mortality and worse motor development. Ongoing monitoring is essential to determine the longer-term significance of these findings.

Background: Studies of children who undergo major non-cardiac surgery in the neonatal period are needed so that subsequent abnormal neurodevelopment can be better understood. Objective:It was the aim of our study to describe the influence of analgesic and sedative medication on the predominant background pattern and the development of sleep-wake cycling (SWC), as measured on amplitude-integrated electroencephalography (aEEG), in newborn infants born ≥32 weeks’ gestation after major non-cardiac surgery. Methods:This prospective study included infants ≥32+0 weeks’ gestation admitted to the Neonatal Intensive Care Unit at The Royal Children’s Hospital in Melbourne who were undergoing major non-cardiac surgery. Data on morphine and midazolam given after surgery were recorded and the BrainZ Monitor was applied post-operatively. The maximum levels of morphine and midazolam were assessed as predictors of time to aEEG outcomes using linear regression. Results: Forty-seven eligible infants were included. Emergence of SWC was observed at a mean of 13 h after surgery. The maximum dose of morphine or midazolam was not predictive of time to either any or developed SWC. Conclusions: Despite high doses of morphine and midazolam, SWC was observed on aEEG in neonates ≥32 weeks’ gestational age soon after major non-cardiac surgery. The aEEG background pattern was not affected by the maximum dose of either morphine or midazolam.

OBJECTIVES: Our aim for this study was to test whether visual and verbal feedback compared with instructor-led feedback improve the quality of pediatric cardiopulmonary resuscitation (CPR). METHODS: There were 653 third-year medical students randomly assigned to practice pediatric CPR on 1 of 2 manikins (infant and adolescent; n = 344 and n = 309, respectively). They were further randomly assigned to 1 of 3 feedback groups: The instructor feedback (IF) group (n = 225) received traditional, instructor-led feedback without any additional feedback device. The device feedback (DF) group (n = 223) received real-time visual feedback from a feedback device. The instructor and device feedback (IDF) group (n = 205) received verbal feedback from an instructor who continuously reviewed the trainees’ performance using the feedback device. After the training, participants’ CPR performance was assessed on the same manikin while no feedback was being provided. RESULTS: For the primary outcome of total compression score, participants in the DF and IDF groups performed similarly, with both groups showing scores significantly (P CONCLUSIONS: Chest compression performance significantly improved with both visual and verbal feedback compared with instructor-led feedback. Feedback devices should be implemented during pediatric resuscitation training to improve resuscitation performance.

Background: One third of all preterm births are due to preterm premature rupture of membranes (pPROM). An accurate prognostic evaluation after admission to the neonatal intensive care unit is necessary. Objective: The aim of this study was to identify prognostic factors within the first hour of life for mortality, short-term pulmonary morbidity, chronic lung disease (CLD) and severe cerebral morbidity in very low birth weight (VLBW) infants after pPROM. Methods: This retrospective study included 300 infants with pPROM who fit the study criteria and were derived from a cohort of 1,435 VLBW infants. A total of 17 obstetric and neonatal factors were evaluated by univariate and multivariate analysis. Results: Gestational age at birth and 5-min Apgar score correlated significantly with all 4 outcomes. The results of the first blood gas analysis correlated with 3 outcomes and the first mean arterial pressure with 2 outcomes. Anhydramnios and a lower number of courses of antenatal steroids correlated with higher mortality, and preterm labor correlated with CLD. The multivariate analysis revealed gestational age, 5-min Apgar score, the results of the first blood gas analysis, the first mean arterial pressure and anhydramnios to be significant predictors. The positive predictive value ranged from 20 to 81%, and the negative predictive value ranged from 79 to 92%. Conclusion: Gestational age at birth and parameters reflecting postnatal adaptation were the most precise factors for assessment of the prognosis of VLBW infants after pPROM within the first hour of life. Apart from anhydramnios, obstetric factors did not predict neonatal outcome. At 1 h of age, our models of perinatal risk factors were more effective in predicting a favorable outcome than an adverse outcome.

Beim Ubergang vom intrauterinen zum neonatalen Leben mussen 3–6% aller Neugeborenen unterstutzt werden. Damit stellt die neonatale Erstversorgung eine der haufigsten medizinischen Interventionen dar. Mittels eines Fragebogens wurden das verwendete Equipment und das dazugehorige Verwendungsprotokoll bei der Erstversorgung von Neugeborenen in Osterreich erhoben und mit den im Jahr 2005 publizierten Richtlinien des European Resuscitation Council verglichen. Alle 20 kontaktierten Abteilungen beantworteten den Fragebogen. Erfragt wurden die Verwendung von Pulsoxymetrie, Beatmungsbeutel („self-inflating“/“flow-inflating“/“T-piece device“), CO2-Detektor zur Tubuslagekontrolle, Sauerstoffblender, Larynxmaske, oralem Airway, Klarsichtfolie zur Verhinderung des Warmeverlusts bei der Erstversorgung von Fruhgeborenen unter 28 Schwangerschaftswochen sowie die initiale Sauerstoffkonzentration bei der Erstversorgung von Reifgeborenen. Letztere variierte zwischen 21% und 100%. Bei 17 Abteilungen (85%) kamen Sauerstoffblender, bei den ubrigen Flowmeter zur Anwendung. Alle 20 Abteilungen (100%) verwendeten Pulsoxymetrie, 9 (45%) „self-inflating-bags“, 9 (45%) „T-piece devices“ und 2 beide Beatmungshilfen. Einen oralen Airway bei schwieriger Maskenbeatmung nutzten 10 Abteilungen (50%), eine Larynxmaske als Alternative zur Intubation 8 (40%) und einen CO2-Detektor zur Tubuslagekontrolle 6 (30%). Klarsichtfolien zur Verhinderung des Warmeverlusts wurden in 11 Abteilungen (55%) eingesetzt. Dem internationalen Trend entsprechend zeigte sich auch in Osterreich eine grose Variationsbreite des verwendeten Equipments. Dies reflektiert die allgemein ungenugende Datenlage zur Erstversorgung von Neugeborenen.

Aim: The objective of this prospective study was to evaluate the influence of peri-/intraventricular haemorrhage (PIVH) grades I–IV on amplitude-integrated electroencephalographic (aEEG) activity in preterm infants

Serratia are known to be a possible cause of severe cerebral infections in neonates. We describe imaging of three premature infants infected with Serratia marcescens. Born in the 31( st), 25( th) and 28( th) weeks of gestation, they presented with signs of septicaemia on postnatal days 9, 24 and 32. Initial sonography showed cysts in the first child, two areas with anechoic centre and echogenic rim in the second, and several echogenic areas in the third. Lesions were seen on CT, of low density in two cases and minimally increased density in the third. MRI in the first patient showed cysts with incomplete contrast enhancement of the lesions, while patient 2 showed five ring-enhancing fluid-containing lesions with thick walls. In the third patient two abscesses with contrast enhancement and several high-signal spots were seen. We discuss the pathophysiology of the lesions and the impact of the various imaging methods.