To assess the longitudinal effects of intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilatation (PHVD) on cerebral oxygenation using near-infrared spectroscopy (NIRS). This prospective cohort study included preterm neonates born <34 weeks’ gestation between 2013 and 2024. Regional cerebral oxygen saturation (rScO2) was measured from IVH diagnosis until term-equivalent age. Duration of abnormal rScO2 values (<55

BACKGROUND:Preterm infants undergo multiple painful procedures, which may negatively affect neurodevelopment. Proper pain management, including opioid use, is essential. This study aimed to determine the impact of opioid administration in very and extremely preterm infants on cognitive, motor, and behavioral outcomes at the corrected age of 3 years. METHODS:This retrospective, single-center study included preterm infants born between 23 and 32 weeks of gestation, admitted to the Medical University of Vienna between 2011 and 2017. Follow-up data were collected at 3 years corrected age. Primary outcomes included behavioral outcomes assessed by the Child Behavior Checklist (CBCL) and cognitive and motor outcomes using the Bayley Scales of Infant Development (BSID). RESULTS:A total of 333 preterm infants were included, with 214 in the non-opioid group (no exposure to opioids) and 119 in the opioid-group (exposure to opioids). Significant differences in cognitive and motor scores were observed between the groups (92.5 (85.5-98.5) vs 88 (79-94) and 85 (76-96) vs 76 (67-85), both p = 0.001). Behavioral outcomes were within the normal range in both groups, although higher depressive scores were noted in the opioid group. CONCLUSIONS:Cumulative opioid exposure in neonatal care may negatively impact cognitive and motor development but did not significantly affect overall behavioral outcomes. IMPACT:Our findings suggest that cumulative opioid exposure in the NICU does not significantly influence overall behavioral problems at the age of 3 years. However, it poses a risk for altered cognitive and motor development. This study highlights the distinct effects of opioid exposure on motor development and cognitive outcomes, while offering a nuanced perspective on behavioral outcomes, filling gaps in understanding the long-term neurodevelopmental consequences in preterm infants. The findings emphasize the need for careful management of opioid administration in NICU settings, balancing pain relief with potential long-term neurodevelopmental risks, while also underscoring the role of confounding factors such as IVH in shaping developmental trajectories.

Background:In the last four years, COVID-19 has prompted concerns about children's well-being. While children's physical health may not be severely affected, their psychological well-being is a significant concern. Therefore, we developed an interdisciplinary psychoeducational intervention program for children named CARTOON. The study aimed to assess whether CARTOON helps kindergarten children to better adhere to mandatory hygiene measures, while also investigating its potential to reduce children's anxiety. Methods:A randomized controlled trial was conducted from January and June 2021 in two Viennese kindergartens involving 53 children aged 3-6 years. Children were randomized into an intervention (specific psychoeducational program) and a control group (routine hygiene practices). CARTOON comprised five sessions covering key hygiene and COVID-19 awareness aspects, facilitated by trained staff. Primary outcomes included changes in children's emotional state and knowledge about COVID-19 and hygiene measures. Secondary outcomes assessed CARTOON's long-term impact on knowledge retention and emotional well-being. Results:Children in the intervention group showed increased COVID-19 knowledge from baseline to long-term assessment (3.9 ± 2.4 vs. 5.9 ± 2.0, p = .003). Moreover, children in the intervention group demonstrated significantly improved long-term hygiene knowledge compared to baseline (8.2 ± 2.2 vs. 5.9 ± 2.3, p < 0.001). Additionally, anxiety scores significantly decreased in the intervention group post-intervention compared to baseline (2.2 ± 1.7 vs. 5.6 ± 2.5; p = .01). Regression analysis identified higher age, higher maternal education, and lower family mental stress as knowledge acquisition predictors. Conclusions:Our findings demonstrate the efficacy of our psycho-educational program in enhancing both knowledge about COVID-19 and adherence to hygiene measures among preschool children, while also reducing anxiety related to the pandemic. Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04724616.

Objectives: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. Materials and methods: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. Results: Sixty preterm neonates (mean gestational age at birth 26.26 +/- 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. Conclusion: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

Intraventricular hemorrhage (IVH) in preterm neonates presents a high risk for developing posthemorrhagic ventricular dilatation (PHVD), a severe complication that can impact survival and long-term outcomes. Early detection of PHVD before clinical onset is crucial for optimizing therapeutic interventions and providing accurate parental counseling. This study explores the potential of explainable machine learning models based on targeted liquid biopsy proteomics data to predict outcomes in preterm neonates with IVH. In recent years, research has focused on leveraging advanced proteomic technologies and machine learning to improve prediction of neonatal complications, particularly in relation to neurological outcomes. Machine learning (ML) approaches, combined with proteomics, offer a powerful tool to identify biomarkers and predict patient-specific risks. However, challenges remain in integrating large-scale, multiomic datasets and translating these findings into actionable clinical tools. Identifying reliable, disease-specific biomarkers and developing explainable ML models that clinicians can trust and understand are key barriers to widespread clinical adoption. In this prospective longitudinal cohort study, we analyzed 1109 liquid biopsy samples from 99 preterm neonates with IVH, collected at up to six timepoints over 13 years. Various explainable ML techniques—including statistical, regularization, deep learning, decision trees, and Bayesian methods—were employed to predict PHVD development and survival and to discover disease-specific protein biomarkers. Targeted proteomic analyses were conducted using serum and urine samples through a proximity extension assay capable of detecting low-concentration proteins in complex biofluids. The study identified 41 significant independent protein markers in the 1600 calculated ML models that surpassed our rigorous threshold (AUC-ROC of ≥0.7, sensitivity ≥ 0.6, and selectivity ≥ 0.6), alongside gestational age at birth, as predictive of PHVD development and survival. Both known biomarkers, such as neurofilament light chain (NEFL), and novel biomarkers were revealed. These findings underscore the potential of targeted proteomics combined with ML to enhance clinical decision-making and parental counseling, though further validation is required before clinical implementation.

BACKGROUND AND AIM:Neonatal intensive care treatment, including frequently performed painful procedures and administration of analgesic drugs, can have different effects on the neurodevelopment. This systematic review and meta-analysis aimed to investigate the influence of pain, opiate administration, and pre-emptive opiate administration on pain threshold in animal studies in rodents, which had a brain development corresponding to preterm and term infants. METHODS:A systematic literature search of electronic data bases including CENTRAL (OVID), CINAHL (EBSCO), Embase.com, Medline (OVID), Web of Science, and PsycInfo (OVID) was conducted. A total of 42 studies examining the effect of pain (n = 38), opiate administration (n = 9), and opiate administration prior to a painful event (n = 5) in rodents were included in this analysis. RESULTS:The results revealed that pain (g = 0.42, 95%CI 0.16-0.67, p = 0.001) increased pain threshold leading to hypoalgesia. Pre-emptive opiate administration had the opposite effect, lowering pain threshold, when compared to pain without prior treatment (g = -1.79, 95%CI -2.71-0.86, p = 0.0001). Differences were found in the meta regression for type of stimulus (thermal: g = 0.66, 95%CI 0.26-1.07, p = 0.001; vs. mechanical: g = 0.13, 95%CI -0.98-1.25, p = 0.81) and gestational age (b = -1.85, SE = 0.82, p = 0.027). In addition, meta regression indicated an association between higher pain thresholds and the amount of cumulative pain events (b = 0.06, SE = 0.03, p = 0.05) as well as severity of pain events (b = 0.94, SE = 0.28, p = 0.001). CONCLUSION:Neonatal exposure to pain results in higher pain thresholds. However, caution is warranted in extrapolating these findings directly to premature infants. Further research is warranted to validate similar effects in clinical contexts and inform evidence-based practices in neonatal care.

AIM:To assess the effect of ventricular decompression on cerebral oxygenation in preterm neonates with intraventricular haemorrhage (IVH) and posthemorrhagic ventricular dilatation (PHVD) using near-infrared spectroscopy (NIRS). METHODS:Fifty-three preterm neonates born <34 weeks' gestation between 2013 and 2023 with IVH and subsequent PHVD were prospectively included. Regional cerebral oxygen saturation (rScO2) as well as fractional cerebral tissue oxygen extraction (cFTOE) were analysed 2 weeks before and after ventricular decompression. RESULTS:Ventricular decompression was performed at 18 ± 6 days of life. Patients with repeated lumbar punctures prior to ventricular drainage showed consistently higher rScO2 and lower cFTOE levels 2 weeks before and after intervention compared to those without. Patients who underwent direct ventricular drainage showed an immediate increase in rScO2 levels on the day of the procedure. In patients who underwent prior lumbar punctures, ventricular decompression did not yield additional acute effects on cerebral oxygenation. CONCLUSION:Patients who underwent repeated lumbar punctures preceding ventricular drainage consistently maintained higher rScO2 and lower cFTOE levels during the study period. In these patients, ventricular decompression did not further affect cerebral oxygenation, as they already demonstrated improved cerebral hemodynamics, whereas an immediate improvement was observed in those without prior lumbar punctures.

Background Given the countrywide lockdown in the first pandemic period and the respective Hospital restrictive policies, we aimed to investigate if the SARS-COV-2 pandemic was associated to a reduced parental presence in the NICU and in which form this had an impact on infant wellbeing. Methods Retrospective cohort study about altered NICUs parental presence (measured by number of visits and kangaroo care time) due to pandemic restrictive policies and its impact on infant wellbeing (measured through The Neonatal Pain Agitation and Sedation scale and nurses’ descriptive documentation). Results Presence of both parents at the same time was significantly lower during pandemic. Contrary, maternal presence only and total kangaroo-care time were higher within the pandemic (163.36 ± 94.07 vs 122.71 ± 64.03; p = 0.000). Lower NPASS values were documented during the lookdown (1.28 ± 1.7 vs 1.78 ± 2.2; p = 0.000). Conclusion Data collected through the pandemic confirm the importance of parental presence for infants’ wellbeing in a NICU setting. Impact Parental support is an extremely important aspect for infants hospitalized in an intensive care unit. Their presence was limited in many NICUs worldwide during the SARS-COV-2 pandemic. This study confirm the importance of parental presence for infants’ wellbeing also in a pandemic situation. Our results support a family-centered newborn individualized developmental care approach in the NICU.

To investigate the impact of the level of pain experienced by infants born preterm on neurodevelopmental outcomes during their stay in a neonatal intensive care unit.

BACKGROUND:The aim of this study was to design and validate a new checklist and standardized scenario for assessing providers' performance during Newborn Life Support (NLS).METHODS:We invited twelve experts in Neonatology to take part in a three-step Delphi process. They rated the importance of each item of a newly designed assessment tool to evaluate participants' performance during Newborn Life Support independently on a numeric rating scale from 1 to 5 (1 = lowest; 5 = highest) and were able to give additional comments. All items achieving a mean rating below four after the third round were deleted. For the reliability of the checklist, we calculated interrater reliability.RESULTS:Using a standardized Delphi process, we revised the initial checklist according to the experts' ratings and comments. The final assessment tool includes 38 items covering all relevant steps during NLS. The mean expert rating of all items was 4.40. Interrater reliability showed substantial agreement between the two raters in the first draft (κ = 0.80) as well as in the final draft of the checklist (κ = 0.73).CONCLUSION:We designed a feasible assessment tool for evaluating performance during NLS. We proved the checklist to be valid and reasonable using a Delphi validation process and calculating interrater reliability.

Background and Objective Intraventricular hemorrhage (IVH) is the most frequent form of intracranial hemorrhage in preterm patients and is a major problem in neonatal intensive care medicine. Our group recently published an MRI-based scoring system, especially for infants born preterm with IVH with high correlation and strong predictive ability regarding later outcome (Goeral et al) [1] [2] [3].

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 <32+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.

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).

BackgroundIn life-threatening emergency events, prompt decision-making and accurate reactions are essential for saving a human's life. Some of these skills can be improved by regular simulation trainings. However, besides these factors, individual characteristics may play a significant role in the patients' outcome after a resuscitation event. This study aimed to differentiate personality characteristics of team members who take responsibility for their actions, contextualizing the effect of training on resuscitation performance.MethodsSix hundred and two third-year medical students were asked to answer psychological and personality questionnaires. Fifty-five of them performed in a neonatal simulation resuscitation scenario. To assess participants' performances in the NLS scenario, we used a scenario-based designed NLS checklist. A machine learning design was utilized to better understand the interaction of psychological characteristics and training. The first model aimed to understand how to differentiate between people who take responsibility for their actions vs. those who do not. In a second model, the goal was to understand the relevance of training by contextualizing the effect of training to other important psychological and personality characteristics like locus of control, anxiety, emotion regulation, openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism.ResultsNo statistically significant differences were found for psychological characteristics between the training group and the no training group. However, as expected, differences were noted in favor of the training group for performance and within gender for psychological characteristics. When correcting for all these information in a model, anxiety and gender were the most important factors associated with taking responsibility for an action, while training was the only relevant factor in explaining performance during a neonatal resuscitation scenario.ConclusionTraining had a significantly stronger effect on performance in medical students in a neonatal resuscitation scenario than individual characteristics such as demographics, personality, and trait anxiety.

Objective: The aim of the study was to determine the predictive power of the combined use of neurophysiological (amplitude-integrated electroencephalography [aEEG], near-infrared spectroscopy [NIRS]) methods and neuroimaging (magnetic resonance imaging [MRI]) for long-term outcome prediction in neonates with hypoxic-ischaemic encephalopathy (HIE). Study Design: Prospective cohort study of 56 patients with moderate to severe HIE and hypothermia treatment at the Medical University of Vienna between 2008 and 2020. aEEG and NIRS were recorded continuously over a period of >4 days (102 h) starting at the initiation of hypothermia treatment, MRI was performed at a median age of 8 days. Receiver operating characteristic curves and area under the curve were calculated to evaluate the prognostic ability of aEEG, NIRS, and MRI parameters for outcome assessed via Bayley Scales of Infant Development 3rd edition at 2 years of age. Results: Combined aEEG and MRI parameters showed highest predictive power regarding long-term outcome. The highest area under the curve values (0.96–0.99) were obtained for aEEG (combination of background pattern and sleep-wake cycling) between 66 and 102 h after initiation of hypothermia in combination with MRI findings. NIRS parameters did not differ significantly between infants with favourable and adverse outcome. Conclusions: Combined aEEG and MRI parameter scores were more predictive than single parameter scores. No further improvement was observed when combining aEEG/MRI with NIRS data.

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.

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.

Several methods can be used in the neonatal intensive care unit (NICU) to reduce stress and optimize the quality of life during this period of hospitalization. Among these, music could play an important role. We investigated the effect of different kinds of music therapies on the brain activity of very preterm infants using amplitude-integrated EEG. Sixty-four patients were included and randomly assigned to three different groups: live music group, recorded music group, and control group. In both intervention groups, music was started after the appearance of the first quiet-sleep phase, with a subsequent duration of 20 min. Changes between the first and second quiet-sleep epochs were analyzed using the amplitude-integrated EEG. When looking at single parameters of the amplitude-integrated EEG trace, no differences could be found between the groups when comparing their first and second quiet-sleep phase regarding the parameters of change from baseline, quality of the quiet-sleep epoch, and duration. However, when looking at the total cyclicity score of the second quiet-sleep phase, a difference between both intervention groups and the control group could be found (live music therapy vs. control, p = 0.003; recorded music therapy vs. control, p = 0.006). Improvement within the first and second quiet-sleep epochs were detected in both music groups, but not in the control group. We concluded that our study added evidence of the beneficial effect of music on the amplitude-integrated EEG activity in preterm infants.