Red Blood Cell Transfusion in European Neonatal Intensive Care Units, 2022 to 2023.

Importance: Red blood cell (RBC) transfusions are frequently administered to preterm infants born before 32 weeks of gestation in the neonatal intensive care unit (NICU). Two randomized clinical trials (Effects of Transfusion Thresholds on Neurocognitive Outcomes of Extremely Low-Birth-Weight Infants [ETTNO] and Transfusion of Prematures [TOP]) found that liberal RBC transfusion thresholds are nonsuperior to restrictive thresholds, but the extent to which these results have been integrated into clinical practice since publication in 2020 is unknown. Objective: To describe neonatal RBC transfusion practice in Europe. Design, Setting, and Participants: This international prospective observational cohort study collected data between September 1, 2022, and August 31, 2023, with a 6-week observation period per center, from 64 NICUs in 22 European countries. Participants included 1143 preterm infants born before 32 weeks of gestation. Exposure: Admission to the NICU. Main Outcomes and Measures: Study outcome measures included RBC transfusion prevalence rates, cumulative incidence, indications, pretransfusion hemoglobin (Hb) levels, volumes, and transfusion rates, Hb increment, and adverse effects of RBC transfusion. Results: A total of 1143 preterm infants were included (641 male [56.1%]; median gestational age at birth, 28 weeks plus 2 days [IQR, 26 weeks plus 2 days to 30 weeks plus 2 days]; median birth weight, 1030 [IQR, 780-1350] g), of whom 396 received 1 or more RBC transfusions, totaling 903 transfusions. Overall RBC transfusion prevalence rate during postnatal days 1 to 28 was 3.4 transfusion days per 100 admission days, with considerable variation across countries, only partly explained by patient mix. By day 28, 36.5% (95% CI, 31.6%-41.5%) of infants had received at least 1 transfusion. Most transfusions were given based on a defined Hb threshold (748 [82.8%]). Hemoglobin levels before transfusions indicated for threshold were below the restrictive thresholds set by ETTNO in 324 of 729 transfusions (44.4%) and TOP in 265 of 729 (36.4%). Conversely, they were between restrictive and liberal thresholds in 352 (48.3%) and 409 (56.1%) transfusions, respectively, and above liberal thresholds in 53 (7.3%) and 55 (7.5%) transfusions, respectively. Most transfusions given based on threshold had volumes of 15 mL/kg (470 of 738 [63.7%]) and were administered over 3 hours (400 of 738 [54.2%]), but there was substantial variation in dose and duration. Conclusions and Relevance: In this cohort study of very preterm infants, most transfusions indicated for threshold were given for pretransfusion Hb levels above restrictive transfusion thresholds evaluated in recent trials. These results underline the need to optimize practices and for implementation research to support uptake of evidence.

Supplemental Iron and Recombinant Erythropoietin for Anemia in Infants Born Very Preterm: A Survey of Clinical Practice in Europe.

OBJECTIVES: To survey practices of iron and recombinant human erythropoietin (rhEpo) administration to infants born preterm across Europe. STUDY DESIGN: Over a 3-month period, we conducted an online survey in 597 neonatal intensive care units (NICUs) of 18 European countries treating infants born with a gestational age of <32 weeks. RESULTS: We included 343 NICUs (response rate 56.3%) in the survey. Almost all NICUs (97.7%) routinely supplement enteral iron, and 74.3% of respondents to all infants born <32 weeks of gestation. We found that 65.3% of NICUs routinely evaluate erythropoiesis and iron parameters beyond day 28 after birth. Most NICUs initiate iron supplementation at postnatal age of 2 weeks and stop after 6 months (34.3%) or 12 months (34.3%). Routine use of rhEpo was reported in 22.2% of NICUs, and in individual cases in 6.9%. RhEpo was mostly administered subcutaneously (70.1%) and most frequently at a dose of 250 U/kg 3 times a week (44.3%), but the dose varied greatly between centers. CONCLUSIONS: This survey highlights wide heterogeneity in evaluating erythropoietic activity and iron deficiency in infants born preterm. Variation in iron supplementation during infancy likely reflects an inadequate evidence base. Current evidence on the efficacy and safety profile of rhEpo is only poorly translated into clinical practice. This survey demonstrates a need for standards to optimize patient blood management in anemia of prematurity.

Comorbidities and Disease Duration in Tourette Syndrome: Impact on Cognition and Quality of Life of Children.

BACKGROUND: Cognitive functions represent foundational factors for mental health and quality of life (QoL). In Tourette syndrome (TS), psychiatric comorbidities are common and have been inconsistently reported to affect the cognition and QoL of patients, while the role of tic disorder duration has not been yet explored. METHODS: To examine how comorbidities and TS duration may influence cognition and QoL, N = 80 children with TS (6-16 years) were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Standardized questionnaires were used to assess the presence and severity of TS main comorbidities and QoL. Data were interpreted using linear correlations, regression, and mediation analysis. RESULTS: Depression and attention-deficit/hyperactivity disorder (ADHD) symptoms accounted for poorer cognitive performance. Anxiety oppositely predicted better cognitive performance, while no significant role for obsessive compulsive disorder (OCD) was observed. Disease duration was associated with lower total IQ, verbal reasoning, and working memory abilities. Depression, anxiety, and TS duration also deeply influenced QoL measures. CONCLUSIONS: TS common comorbidities have a differential impact on the cognitive abilities of children and adolescents, which translates into a complex influence on their perceived QoL. A longer clinical history of tics was related to worse cognitive outcomes, which prompts further consideration of disease duration in both clinical and research settings involving children and adolescents.

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome.

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome.

BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year. METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants. RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. CONCLUSIONS: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

Survey of transfusion practices in preterm infants in Europe.

BACKGROUND: Preterm infants commonly receive red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusions. The aim of this Neonatal Transfusion Network survey was to describe current transfusion practices in Europe and to compare our findings to three recent randomised controlled trials to understand how clinical practice relates to the trial data. METHODS: From October to December 2020, we performed an online survey among 597 neonatal intensive care units (NICUs) caring for infants with a gestational age (GA) of <32 weeks in 18 European countries. RESULTS: Responses from 343 NICUs (response rate: 57%) are presented and showed substantial variation in clinical practice. For RBC transfusions, 70% of NICUs transfused at thresholds above the restrictive thresholds tested in the recent trials and 22% below the restrictive thresholds. For platelet transfusions, 57% of NICUs transfused at platelet count thresholds above 25×109/L in non-bleeding infants of GA of <28 weeks, while the 25×109/L threshold was associated with a lower risk of harm in a recent trial. FFP transfusions were administered for coagulopathy without active bleeding in 39% and for hypotension in 25% of NICUs. Transfusion volume, duration and rate varied by factors up to several folds between NICUs. CONCLUSIONS: Transfusion thresholds and aspects of administration vary widely across European NICUs. In general, transfusion thresholds used tend to be more liberal compared with data from recent trials supporting the use of more restrictive thresholds. Further research is needed to identify the barriers and enablers to incorporation of recent trial findings into neonatal transfusion practice.

Daydreaming and psychopathology in adolescence: An exploratory study.

AIM: Daydreaming is a cognitive phenomenon characterized by the redirection of attention from the external world to inner representations. Although serving several adaptive functions, excessive daydreaming has been related to emotional problems and poor psychosocial adjustment. During adolescence, this phenomenon has been scarcely explored as potential psychopathological correlate. This study aims to explore daydreaming frequency and association with psychopathological symptoms in a non-referred population. METHODS: Participants were adolescents from a community sample (N = 251). Daydreaming was assessed through the Daydreaming Frequency Scale (DDFS). Youth Self-Report (YSR) and Strength and Difficulties Questionnaire (SDQ) were used as self-reports to evaluate psychopathological problems and adaptive functioning. RESULTS: Excessive daydreaming was present in 12.7% of participants. DDFS scores were significantly elevated in respondents with clinical scores for internalizing, depressive, obsessive-compulsive, and post-traumatic stress problems. Symptom severity correlated positively with the DDFS. Higher daydreaming was also associated with emotional symptoms, conduct problems and total difficulties on the SDQ. CONCLUSIONS: Adolescents who daydream show increased depressive, obsessive-compulsive, and post-traumatic stress symptoms. Possible cognitive processes at play in the relationship between daydreaming and psychopathology are discussed. Daydreaming may represent a silent psychopathological index that deserves better recognition in the clinical practice and in mental health initiatives for adolescents.

White matter alterations in drug-naïve children with Tourette syndrome and obsessive-compulsive disorder.

Tourette syndrome (TS) and early-onset obsessive-compulsive disorder (OCD) are frequently associated and conceptualized as distinct phenotypes of a common disease spectrum. However, the nature of their relationship is still largely unknown on a pathophysiological level. In this study, early structural white matter (WM) changes investigated through diffusion tensor imaging (DTI) were compared across four groups of drug-naïve children: TS-pure (n = 16), TS+OCD (n = 14), OCD (n = 10), and 11 age-matched controls. We analyzed five WM tracts of interest, i.e., cortico-spinal tract (CST), anterior thalamic radiations (ATR), inferior longitudinal fasciculus (ILF), corpus callosum (CC), and cingulum and evaluated correlations of DTI changes to symptom severity. Compared to controls, TS-pure and TS+OCD showed a comparable pattern of increased fractional anisotropy (FA) in CST, ATR, ILF and CC, with FA changes displaying negative correlation to tic severity. Conversely, in OCD, FA decreased in all WM tracts (except for the cingulum) compared to controls and negatively correlated to symptoms. We demonstrate different early WM microstructural alterations in children with TS-pure/TS+OCD as opposed to OCD. Our findings support the conceptualization of TS+OCD as a subtype of TS while suggesting that OCD is characterized by independent pathophysiological mechanisms affecting WM development.

Provider Visual Attention Correlates With the Quality of Pediatric Resuscitation: An Observational Eye-Tracking Study.

Background: Eye-tracking devices are an innovative tool to understand providers' attention during stressful medical tasks. The knowledge about what gaze behaviors improve (or harm) the quality of clinical care can substantially improve medical training. The aim of this study is to identify gaze behaviors that are related to the quality of pediatric resuscitation. Methods: Forty students and healthcare providers performed a simulated pediatric life support scenario, consisting of a chest compression task and a ventilation task, while wearing eye-tracking glasses. Skill Reporter software measured chest compression (CC) quality and Neo Training software measured ventilation quality. Main eye-tracking parameters were ratio [the number of participants who attended a certain area of interest (AOI)], dwell time (total amount of time a participant attended an AOI), the number of revisits (how often a participant returned his gaze to an AOI), and the number of transitions between AOIs. Results: The most salient AOIs were infant chest and ventilation mask (ratio = 100%). During CC task, 41% of participants also focused on ventilation bag and 59% on study nurse. During ventilation task, the ratio was 61% for ventilation bag and 36% for study nurse. Percentage of correct CC rate was positively correlated with dwell time on infant chest (p = 0.044), while the overall CC quality was negatively correlated with dwelling outside of pre-defined task-relevant AOIs (p = 0.018). Furthermore, more dwell time on infant chest predicted lower leakage (p = 0.042). The number of transitions between AOIs was unrelated to CC parameters, but correlated negatively with mask leak during ventilations (p = 0.014). Participants with high leakage shifted their gaze more often between ventilation bag, ventilation mask, and task-irrelevant environment. Conclusion: Infant chest and ventilation mask are the most salient AOIs in pediatric basic life support. Especially the infant chest AOI gives beneficial information for the resuscitation provider. In contrast, attention to task-irrelevant environment and frequent gaze shifts seem to harm the quality of care.

Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study.

BACKGROUND AND OBJECTIVES: The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs). METHODS: In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti-streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses. RESULTS: A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2-0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037-2.590; definition 2: HR 0.561, 95% CI 0.219-1.436; definition 3: HR 0.853, 95% CI 0.466-1.561; definition 4: HR 0.725, 95% CI 0.384-1.370). DISCUSSION: These results do not suggest an association between GAS exposure and development of tics. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that group A streptococcal exposure does not associate with the development of tics in children with first-degree relatives with chronic tic disorder.

Visual attention during pediatric resuscitation with feedback devices: a randomized simulation study.

BACKGROUND: The aim of this study was to investigate the effect of feedback devices on visual attention and the quality of pediatric resuscitation. METHODS: This was a randomized cross-over simulation study at the Medical University of Vienna. Participants were students and neonatal providers performing four resuscitation scenarios with the support of feedback devices randomized. The primary outcome was the quality of resuscitation. Secondary outcomes were total dwell time (=total duration of visit time) on areas of interest and the workload of participants. RESULTS: Forty participants were analyzed. Overall, chest compression (P < 0.001) and ventilation quality were significantly better (P = 0.002) when using a feedback device. Dwell time on the feedback device was 40.1% in the ventilation feedback condition and 48.7% in the chest compression feedback condition. In both conditions, participants significantly reduced attention from the infant's chest and mask (72.9 vs. 32.6% and 21.9 vs. 12.7%). Participants' subjective workload increased by 3.5% (P = 0.018) and 8% (P < 0.001) when provided with feedback during a 3-min chest compression and ventilation scenario, respectively. CONCLUSIONS: The quality of pediatric resuscitation significantly improved when using real-time feedback. However, attention shifted from the manikin and other equipment to the feedback device and subjective workload increased, respectively. IMPACT: Cardiopulmonary resuscitation with feedback devices results in a higher quality of resuscitation and has the potential to lead to a better outcome for patients. Feedback devices consume attention from resuscitation providers. Feedback devices were associated with a shift of visual attention to the feedback devices and an increased workload of participants. Increased workload for providers and benefits for resuscitation quality need to be balanced for the best effect.

The Cerebellum in Drug-naive Children with Tourette Syndrome and Obsessive-Compulsive Disorder.

Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) are two neurodevelopmental disorders characterized by repetitive behaviors. Our recent study in drug-naive children with TS and OCD provided evidence of cerebellar involvement in both disorders. In addition, cerebellar functional connectivity (FC) was similar in TS patients without comorbidities (TSpure) and TS patients with OCD comorbidity (TS + OCD), but differed in pure OCD patients. To investigate in detail the cerebellar involvement in the pathophysiology of TS and OCD, we explored cerebellar structural and functional abnormalities in drug-naive children with TSpure, TS + OCD, and OCD and assessed possible correlations with severity scores. We examined 53 drug-naive children, classified as TSpure (n = 16), TS + OCD (n = 14), OCD (n = 11), or controls (n = 12). All subjects underwent a multimodal 3T magnetic resonance imaging examination. Cerebellar lobular volumes and quantitative diffusion tensor imaging parameters of cerebellar peduncles were used as measures of structural integrity. The dentate nucleus was selected as a region of interest to examine cerebello-cerebral functional connectivity alterations. Structural analysis revealed that both TSpure and TS + OCD patients had higher fractional anisotropy in cerebellar peduncles than controls. Conversely, OCD patients were characterized by lower fractional anisotropy than both controls and TSpure and TS + OCD patients. Lastly, cerebellar functional connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical circuit in TSpure, TS + OCD, and OCD patients. Early cerebellar structural and functional changes in drug-naive pediatric TSpure, TS + OCD, and OCD patients support a primary role of the cerebellum in the pathophysiology of these disorders.

Monitoring of carbon dioxide in ventilated neonates: a prospective observational study.

OBJECTIVE: To assess the reliability, accuracy and precision of distal end-tidal capnography (detCO2) in neonates compared with transcutaneous (tcCO2) carbon dioxide measurements. DESIGN: Observational, prospective clinical study. SETTING: Neonatal intensive care unit at Medical University of Vienna. PARTICIPANTS: Conventionally ventilated neonates with a body weight between 1000 g and 3000 g. INTERVENTION: End-tidal partial pressure of CO2 was measured in distal position using the separate lumen of a double-lumen endotracheal tube connected to an external side-stream capnometer. Three consecutive detCO2 and tcCO2 values were recorded simultaneously and compared with simultaneous arterialised partial pressure of CO2 (paCO2) measurements in each patient. MAIN OUTCOME MEASURES: Reliability, accuracy and precision of detCO2 and tcCO2 measurements compared with paCO2 in neonates. RESULTS: Twenty-five neonates were included with a median (range) weight at enrolment of 1410 (1010-2980) g, from which 81 simultaneous measurements of detCO2, tcCO2 and paCO2 were obtained. The mean (SD) of paCO2, detCO2 and tcCO2 was 45.0 (8.6) mmHg, 42.4 (8.4) mmHg and 50.4 (20.4) mmHg, respectively. The intraclass correlation between paCO2 and detCO2 and between paCO2 and tcCO2 reached 0.80 (95% CI 0.71 to 0.87, p<0.001) and 0.59 (95% CI 0.43 to 0.72, p<0.001), respectively. In the Bland-Altman analysis, bias and precision of detCO2 with respect to paCO2 amounted to -2.68 mmHg and 10.62 mmHg (95% CI 8.49 to 14.51), respectively. Bias and precision of tcCO2 with respect to paCO2 amounted to 5.39 mmHg and 17.22 mmHg (95% CI 13.21 to 23.34), respectively. CONCLUSION: DetCO2 had better reliability, accuracy and precision with paCO2 than tcCO2 in ventilated neonates without severe lung diseas. TRIAL REGISTRATION NUMBER: NCT03758313.

Impact of a Multifactorial Educational Training on the Management of Preterm Infants in the Central-Eastern European Region.

Background: Differences in management and outcomes of extremely preterm infants have been reported across European countries. Implementation of standardized guidelines and interventions within existing neonatal care facilities can improve outcomes of extremely preterm infants. This study evaluated whether a multifactorial educational training (MET) course in Vienna focusing on the management of extremely preterm infants had an impact on the management of extremely preterm infants in Central-Eastern European (CEE) countries. Methods: Physicians and nurses from different hospitals in CEE countries participated in a two-day MET in Vienna, Austria with theoretical lectures, bedside teaching, and simulation trainings. In order to evaluate the benefit of the workshops, participants had to complete pre- and post-workshop questionnaires, as well as follow-up questionnaires three and twelve months after the MET. Results: 162 participants from 15 CEE countries completed the two-day MET at our department. Less invasive surfactant administration (LISA) was only used by 39% (63/162) of the participants. After the MET, 80% (122/152) were planning to introduce LISA, and 66% (101/152) were planning to introduce regular simulation training, which was statistically significantly increased three and twelve months after the MET. Thirty-six percent and 57% of the participants self-reported improved outcomes three and twelve months after the MET, respectively. Conclusion: Our standardized training in Vienna promoted the implementation of different perinatal concepts including postnatal respiratory management using LISA as well as regular simulation trainings at the participants' home departments. Moreover, our MET contributed to dissemination of guidelines, promoted best-practice, and improved self-reported outcomes.

Association of Group A Streptococcus Exposure and Exacerbations of Chronic Tic Disorders: A Multinational Prospective Cohort Study.

OBJECTIVE: To examine prospectively the association between group A Streptococcus (GAS) pharyngeal exposures and exacerbations of tics in a large multicenter population of youth with chronic tic disorders (CTD) across Europe. METHODS: We followed up 715 children with CTD (age 10.7 ± 2.8 years, 76.8% boys), recruited by 16 specialist clinics from 9 countries, and followed up for 16 months on average. Tic, obsessive-compulsive symptom (OCS), and attention-deficit/hyperactivity disorder (ADHD) severity was assessed during 4-monthly study visits and telephone interviews. GAS exposures were analyzed using 4 possible combinations of measures based on pharyngeal swab and serologic testing. The associations between GAS exposures and tic exacerbations or changes of tic, OC, and ADHD symptom severity were measured, respectively, using multivariate logistic regression plus multiple failure time analyses and mixed effects linear regression. RESULTS: A total of 405 exacerbations occurred in 308 of 715 (43%) participants. The proportion of exacerbations temporally associated with GAS exposure ranged from 5.5% to 12.9%, depending on GAS exposure definition. We did not detect any significant association of any of the 4 GAS exposure definitions with tic exacerbations (odds ratios ranging between 1.006 and 1.235, all p values >0.3). GAS exposures were associated with longitudinal changes of hyperactivity-impulsivity symptom severity ranging from 17% to 21%, depending on GAS exposure definition. CONCLUSIONS: This study does not support GAS exposures as contributing factors for tic exacerbations in children with CTD. Specific workup or active management of GAS infections is unlikely to help modify the course of tics in CTD and is therefore not recommended.

Long-term impact of systematic pain and sedation management on cognitive, motor, and behavioral outcomes of extremely preterm infants at preschool age.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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. IMPACT: The implementation of a protocol for the management of pain and sedation in preterm infants resulted in increased cumulative opiate exposure. Our study adds further evidence that increased neonatal opiate exposure did  not alter cognitive and motor outcomes but may yield a potential risk factor for autism spectrum disorders and withdrawn behavior at preschool age. A vigilant use of opiates is recommended. Further studies are needed looking for novel pain management strategies and drugs providing optimal pain relief with minimal neurotoxicity.

Adverse Mental Health Impact of the COVID-19 Lockdown in Individuals With Tourette Syndrome in Italy: An Online Survey.

During the early stages of the coronavirus disease 2019 (COVID-19) pandemic in Italy, an online survey was launched via a local patient advocacy website to investigate mental health issues in children and adolescents with Tourette syndrome (TS). Respondents were parents, who were asked to report on their child's general health, tics, comorbidities/problems, pharmacological treatment/psychotherapy, symptom variations, and daily routine, as well as on their family's health and work experiences during the pandemic. Two hundred thirty-eight people participated in the survey, 203 females and 35 males. Our findings indicate that, in the time window of 4-6 weeks after the beginning of the COVID-19-related lockdown, 67% of individuals with TS developed a relevant worsening of the overall clinical condition as rated by their parents. An improvement or no variation of the clinical picture was reported in 20.5 and 6.7% of cases, respectively. Most worsened symptoms included tics, hyperactivity, rage attacks, obsessions/compulsions, and anxiety. Of the subjects experiencing a clinical worsening, the majority (51.76%) showed variations across two to five symptom domains. No association was found between symptom variation and family demographics or health and economic issues specifically related to the lockdown. The current COVID-19 pandemic is exerting a considerable impact on the mental health of young individuals with TS by worsening both tics and emotional and behavioral symptoms.

More Than 500 Kids Could Be Saved Each Year! Ten Consensus Actions to Improve Quality of Pediatric Resuscitation in DACH-Countries (Austria, Germany, and Switzerland).

• Quality and outcome of pediatric resuscitation often does not achieve recommended goals. • Quality improvement initiatives with the aim of better survival rates and decreased morbidity of resuscitated children are urgently needed. • These initiatives should include an action framework for a comprehensive, fundamental, and interprofessional reorientation of clinical and organizational structures concerning resuscitation and post-resuscitation care of children. • The authors of this DACH position statement suggest the implementation of 10 evidence-based actions (for out-of-hospital and in-house cardiac arrests) that should improve survival rates and decrease morbidity of resuscitated children with better neurological outcome and quality of life.

Rage attacks in Tourette Syndrome and Chronic Tic Disorder: a systematic review.

Tourette syndrome (TS) and chronic motor/vocal tic disorder (CTD) are neurodevelopmental conditions defined by the occurrence of multiple tics. Besides the well-known association with attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), rage attacks (RA) represent common and detrimental symptoms for patients. Inorder to explore prevalence of RA in tic disorders, relation to tic severity/comorbidities and available treatments, we performed a systematic literature review based on PRISMA Guidelines. 32 studies published between January 2008 - December 2019 were deemed suitable for the analysis and provided a prevalence of 20-67 %. Most findings showed a direct correlation with tic severity and a significant impact on psychosocial functioning. Although apparently related to comorbid ADHD, RA also frequently occur as independent manifestations. Association with other comorbidities, such as OCD, impulse control and mood disorders has also been reported, not yet fully established. Behavioral interventions appear to be effective, whereas there is limited evidence concerning the efficacy of medication. In TS/CTD, RA may be regarded as a major comorbidity that requires clinical investigation in order to develop personalized treatments.

Resting-state functional connectivity in drug-naive pediatric patients with Tourette syndrome and obsessive-compulsive disorder.

Previous studies in cohorts of Tourette syndrome (TS) or obsessive-compulsive disorder (OCD) patients have not clarified whether these two disorders represent two clinical conditions or they are distinct clinical phenotypes of a common disease spectrum. The study aimed to compare functional connectivity (FC) patterns in a pediatric drug-naive cohort of 16 TS patients without any comorbidity (TS), 14 TS patients with OCD (TS + OCD), and 10 pure OCD patients as well as 11 matched controls that underwent resting state fMRI. Via independent component analysis, we examined FC in the basal ganglia (BGN), sensorimotor (SMN), cerebellum (CBN), frontoparietal (FPN), default-mode (DMN), orbitofrontal (OBFN), and salience (SAN) networks among the above cohorts and their association with clinical measures. Compared to controls, TS and TS + OCD patients showed higher FC in the BGN, SMN, CBN and DMN and lower FC in the FPN and SAN. The TS and TS + OCD groups showed comparable FC in all networks. In contrast to controls, OCD patients exhibited increased FC in the BGN, SMN, CBN, DMN, FPN, and SAN. OCD patients also showed higher FC in CBN and FPN when compared with TS and TS + OCD patients both separately and as one group. Tic severity negatively correlated with FC in CBN and FPN in the TS group, while the compulsiveness scores positively correlated with the same two networks in OCD patients. Our findings suggest common FC changes in TS and TS + OCD patients. In contrast, OCD is characterized by a distinctive pattern of FC changes prominently involving the CBN and FPN.