Publications by authors named "Vito Giordano"

32 Publications

Discriminant properties of the Behavioral Pain Scale for assessment of procedural pain-related distress in ventilated children.

Scand J Pain 2022 Apr 25. Epub 2022 Apr 25.

Department of Neonatology and Pediatric Intensive Care Medicine, University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Objectives: Children hospitalized in a pediatric intensive care unit (PICU) are frequently exposed to distressing and painful medical procedures and interventions. There is a lack of clinical scales to measure procedural pain-related distress in ventilated children. The Behavioral Pain Scale (BPS) was initially developed to detect procedural pain in critically ill adults. This study aims to assess the BPS's discriminant properties for measuring procedural pain-related distress in ventilated pediatric patients incorporating two instruments validated for pediatric patients.

Methods: This prospective exploratory study was performed with ventilated children admitted to the interdisciplinary 14-bed PICU of the University Children's Hospital, University Medical Center Hamburg-Eppendorf, Germany. The nurse in charge and an independent observer simultaneously assessed the patients using German versions of the BPS, the COMFORT-B scale (CBS), and the modified Face, Legs, Activity, Cry, Consolability (mFLACC) scale immediately before and during endotracheal suctioning.

Results: We analyzed 170 parallel assessments in n=34 ventilated children. Patients were (mean ± SD) 9.5 ± 4.8 years old. Internal consistency for the BPS was excellent (=0.93). We found a high rater agreement for all clinical scales (BPS: =0.73, CBS: =0.80, mFLACC: =0.71). Strong correlations were identified between BPS and CBS (=0.89) and BPS and mFLACC (=0.79). The BPS cutoff values showed likewise excellent results (area under the curve CBS >16: 0.97; mFLACC >2: 0.91).

Conclusions: In our population of ventilated children, the BPS was well suited to detect procedural pain-related distress compared with two validated pain scales. Further extensive validation studies should follow to support our findings.
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http://dx.doi.org/10.1515/sjpain-2021-0193DOI Listing
April 2022

The consequences of neonatal pain, stress and opiate administration in animal models: An extensive meta-analysis concerning neuronal cell death, motor and behavioral outcomes.

Neurosci Biobehav Rev 2022 Apr 12;137:104661. Epub 2022 Apr 12.

Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.

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).
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http://dx.doi.org/10.1016/j.neubiorev.2022.104661DOI Listing
April 2022

A Mixed-Lipid Emulsion Containing Fish Oil for the Parenteral Nutrition of Preterm Infants: No Impact on Visual Neuronal Conduction.

Nutrients 2021 Nov 25;13(12). Epub 2021 Nov 25.

Comprehensive Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Intensive Care and Neuropediatrics, Medical University of Vienna, 1090 Vienna, Austria.

Fish oil is rich in omega-3 fatty acids and essential for neuronal myelination and maturation. The aim of this study was to investigate whether the use of a mixed-lipid emulsion composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF-LE) compared to a pure soybean oil-based lipid emulsion (S-LE) for parenteral nutrition had an impact on neuronal conduction in preterm infants. This study is a retrospective matched cohort study comparing preterm infants <1000 g who received SMOF-LE in comparison to S-LE for parenteral nutrition. Visual evoked potentials (VEPs) were assessed longitudinally from birth until discharge. The latencies of the evoked peaks N2 and P2 were analyzed. The analysis included 76 infants (SMOF-LE: = 41 and S-LE: = 35) with 344 VEP measurements (SMOF-LE: = 191 and S-LE = 153). Values of N2 and P2 were not significantly different between the SMOF-LE and S-LE groups. A possible better treatment effect in the SMOF-LE group was seen as a trend toward a shorter latency, indicating faster neural conduction at around term-equivalent age. Prospective trials and follow-up studies are necessary in order to evaluate the potential positive effect of SMOF-LE on neuronal conduction and visual pathway maturation.
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http://dx.doi.org/10.3390/nu13124241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708550PMC
November 2021

Association between Fat-Free Mass and Brain Size in Extremely Preterm Infants.

Nutrients 2021 Nov 24;13(12). Epub 2021 Nov 24.

Comprehensive Center for Pediatrics, Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Intensive Care and Neuropediatrics, Medical University of Vienna, 1090 Vienna, Austria.

Postnatal growth restriction and deficits in fat-free mass are associated with impaired neurodevelopment. The optimal body composition to support normal brain growth and development remains unclear. This study investigated the association between body composition and brain size in preterm infants. We included 118 infants born <28 weeks of gestation between 2017-2021, who underwent body composition (fat-free mass (FFM) and fat mass (FM)) and cerebral magnetic resonance imaging to quantify brain size (cerebral biparietal diameter (cBPD), bone biparietal diameter (bBPD), interhemispheric distance (IHD), transverse cerebellar diameter (tCD)) at term-equivalent age. FFM Z-Score significantly correlated with higher cBPD Z-Score (rs = 0.69; < 0.001), bBPD Z-Score (rs = 0.48; < 0.001) and tCD Z-Score (rs = 0.30; = 0.002); FM Z-Score significantly correlated with lower brain size (cBPD Z-Score (rs = -0.32; < 0.001) and bBPD Z-Score (rs = -0.42; < 0.001). In contrast weight (rs = 0.08), length (rs = -0.01) and head circumference Z-Score (rs = 0.14) did not. Linear regression model adjusted for important neonatal variables revealed that FFM Z-Score was independently and significantly associated with higher cBPD Z-Score (median 0.50, 95% CI: 0.59, 0.43; < 0.001) and bBPD Z-Score (median 0.31, 95% CI: 0.42, 0.19; < 0.001); FM Z-Score was independently and significantly associated with lower cBPD Z-Score (median -0.27, 95% CI: -0.42, -0.11; < 0.001) and bBPD Z-Score (median -0.32, 95% CI: -0.45, -0.18; < 0.001). Higher FFM Z-Score and lower FM Z-scores were significantly associated with larger brain size at term-equivalent age. These results indicate that early body composition might be a useful tool to evaluate and eventually optimize brain growth and neurodevelopment.
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http://dx.doi.org/10.3390/nu13124205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708955PMC
November 2021

Accent discrimination abilities during the first days of life: An fNIRS study.

Brain Lang 2021 12 19;223:105039. Epub 2021 Oct 19.

Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1016/j.bandl.2021.105039DOI Listing
December 2021

Assessing the three attentional networks in children from three to six years: A child-friendly version of the Attentional Network Test for Interaction.

Behav Res Methods 2021 Sep 30. Epub 2021 Sep 30.

Dipartimento di Psicologia, Università di Roma "Sapienza", Roma, Italy.

Attention involves three functionally and neuroanatomically distinct neural networks: alerting, orienting, and executive control. This study aimed to analyze the development of attentional networks in children aged between 3 and 6 years using a child-friendly version of the Attentional Network Test for Interaction (ANTI), the ANTI-Birds. The sample included 88 children divided into four age groups: 3-year-old, 4-year-old, 5-year-old, 6-year-old children. The results of this study would seem to indicate that between 4 and 6 years, there are no significant changes in attentional networks. Instead, between 3 and 4 years of age, children significantly improve all their attentional skills.
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http://dx.doi.org/10.3758/s13428-021-01668-5DOI Listing
September 2021

Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage.

Cell Host Microbe 2021 10 3;29(10):1558-1572.e6. Epub 2021 Sep 3.

Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria. Electronic address:

Premature infants are at substantial risk for suffering from perinatal white matter injury. Though the gut microbiota has been implicated in early-life development, a detailed understanding of the gut-microbiota-immune-brain axis in premature neonates is lacking. Here, we profiled the gut microbiota, immunological, and neurophysiological development of 60 extremely premature infants, which received standard hospital care including antibiotics and probiotics. We found that maturation of electrocortical activity is suppressed in infants with severe brain damage. This is accompanied by elevated γδ T cell levels and increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants. Notably, Klebsiella overgrowth in the gut is highly predictive for brain damage and is associated with a pro-inflammatory immunological tone. These results suggest that aberrant development of the gut-microbiota-immune-brain axis may drive or exacerbate brain injury in extremely premature neonates and represents a promising target for novel intervention strategies.
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http://dx.doi.org/10.1016/j.chom.2021.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525911PMC
October 2021

The duration of intrauterine development influences discrimination of speech prosody in infants.

Dev Sci 2021 09 4;24(5):e13110. Epub 2021 Apr 4.

Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.

Auditory speech discrimination is essential for normal language development. Children born preterm are at greater risk of language developmental delays. Using functional near-infrared spectroscopy at term-equivalent age, the present study investigated early discrimination of speech prosody in 62 neonates born between week 23 and 41 of gestational age (GA). We found a significant positive correlation between GA at birth and neural discrimination of forward versus backward speech at term-equivalent age. Cluster analysis identified a critical threshold at around week 32 of GA, pointing out the existence of subgroups. Infants born before week 32 of GA exhibited a significantly different pattern of hemodynamic response to speech stimuli compared to infants born at or after week 32 of GA. Thus, children born before the GA of 32 weeks are especially vulnerable to early speech discrimination deficits. To support their early language development, we therefore suggest a close follow-up and additional speech and language therapy especially in the group of children born before week 32 of GA.
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http://dx.doi.org/10.1111/desc.13110DOI Listing
September 2021

The Effect of Music on aEEG Cyclicity in Preterm Neonates.

Children (Basel) 2021 Mar 9;8(3). Epub 2021 Mar 9.

Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria.

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, = 0.003; recorded music therapy vs. control, = 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.
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http://dx.doi.org/10.3390/children8030208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000223PMC
March 2021

Impact of Different Types of Nosocomial Infection on the Neurodevelopmental Outcome of Very Low Birth Weight Infants.

Children (Basel) 2021 Mar 9;8(3). Epub 2021 Mar 9.

Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Waehringer Gürtel 18-20, 1090 Vienna, Austria.

Nosocomial infections (NIs) are important conditions associated with mortality and morbidity in very low birth weight infants (VLBWIs). The aim of this study was to investigate the impact of NIs and the different subtypes on neurodevelopmental outcomes in a cohort of VLBWIs. VLBWIs born with a gestational age between 23 and 31 weeks in a level III neonatal center were enrolled. Neonatal morbidities as well as the neurodevelopmental outcome at 2 years of corrected age were analyzed. Six-hundred infants completed the study successfully. Of these, 38% experienced an NI episode. NIs were associated with an increased risk of neonatal complications, such as brain injury, bronchopulmonary dysplasia (BPD) and death, and were a significant risk factor for adverse motor development at 2 years of corrected age in our cohort of VLBWIs. The negative impact of NIs on neurodevelopmental outcomes was particularly associated with necrotizing enterocolitis (NEC), suspected NIs and Gram-positive NIs. This study demonstrated that NIs are a significant risk factor for both morbidity and mortality as well as adverse neurodevelopmental outcomes in VLBWIs.
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http://dx.doi.org/10.3390/children8030207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000764PMC
March 2021

Prediction of Nociception in Children Using the Nociceptive Flexion Reflex Threshold and the Bispectral Index-A Prospective Exploratory Observational Study.

Pediatr Crit Care Med 2021 09;22(9):e461-e470

Department of Neonatology and Pediatric Intensive Care Medicine, University Children's Hospital, University Medical Center Hamburg Eppendorf, Hamburg, Germany.

Objectives: The prediction of patient responses to potentially painful stimuli remains a challenge in PICUs. We investigated the ability of the paintracker analgesia monitor (Dolosys GmbH, Berlin, Germany) measuring the nociceptive flexion reflex threshold, the cerebral sedation monitor bispectral index (Medtronic, Dublin, Ireland), the COMFORT Behavior, and the modified Face, Legs, Activity, Cry, Consolability Scale scores to predict patient responses following a noxious stimulus.

Design: Single-center prospective exploratory observational study.

Setting: Fourteen-bed multidisciplinary PICU at the University Children's Hospital, University Medical Center Hamburg Eppendorf, Germany.

Patients: Children on mechanical ventilation receiving analgesic and sedative medications.

Interventions: Noxious stimulation by way of endotracheal suctioning.

Measurements And Main Results: Two independent observers assessed modified Face, Legs, Activity, Cry, Consolability and COMFORT Behavior Scales scores during noxious stimulation (n = 59) in 26 patients. Vital signs were recorded immediately before and during noxious stimulation; bispectral index and nociceptive flexion reflex threshold were recorded continuously. Mean prestimulation bispectral index (55.5; CI, 44.2-66.9 vs 39.9; CI, 33.1-46.8; p = 0.007), and COMFORT Behavior values (9.5; CI, 9.2-13.2 vs 7.5; CI, 6.7-8.5; p = 0.023) were significantly higher in observations with a response than in those without a response. Prediction probability (Pk) values for patient responses were high when the bispectral index was used (Pk = 0.85) but only fair when the nociceptive flexion reflex threshold (Pk = 0.69) or COMFORT Behavior Scale score (Pk = 0.73) was used. A logistic mixed-effects model confirmed the bispectral index as a significant potential predictor of patient response (p = 0.007).

Conclusions: In our sample of ventilated children in the PICU, bispectral index and nociceptive flexion reflex threshold provided good and fair prediction accuracy for patient responses to endotracheal suctioning.
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http://dx.doi.org/10.1097/PCC.0000000000002701DOI Listing
September 2021

Hydrocortisone administration for reducing post-traumatic stress symptoms: A systematic review and meta-analysis.

Psychoneuroendocrinology 2021 04 16;126:105168. Epub 2021 Feb 16.

Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.

Background: Post-traumatic stress disorder (PTSD) is a debilitating disorder that is often accompanied by alterations in the hypothalamic-pituitary (HPA) axis. While there is abundant evidence for the efficacy of psychological therapies in reducing post-traumatic stress symptoms, barely anything is known about pharmacological interventions. Given the role of the HPA axis in the pathophysiology of PTSD, the aim of this study was to provide the first meta-analysis of Hydrocortisone as a potential treatment for this condition.

Method: A systematic review of randomized-controlled trials (RCTs) was conducted to investigate the efficacy of hydrocortisone in the prevention and curative treatment of post-traumatic stress symptoms. This study was pre-registered with the OSF (doi:10.17605/OSF.IO/GJAZF).

Findings: Eight studies (9 effect sizes) covering 362 participants met our inclusion criteria. We found that Hydrocortisone as compared to placebo significantly reduced PTSD symptoms (d = 0.96, 95% Cl 0.22-1.69 p = 0.011) and PTSD incidence (logRR = 0.85, 95% CI 1.12-1.59, p = 0.023). Subgroup analyses revealed a significant effect of Hydrocortisone when it was administered in a preventative context (d = 1.50; 95%CI 0.30-2.69, p = 0.014), but not when it was administered in a curative context (d = 0.28; 95%CI -0.11 to 0.66, p = 0.161).

Conclusion: Hydrocortisone appears to be a promising and efficient low-cost medication for the prevention of PTSD. However, the small number of included studies and their limited methodological quality emphasize the need for further rigorous studies in this field.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105168DOI Listing
April 2021

Deep learning for estimation of functional brain maturation from EEG of premature neonates.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:104-107

EEG monitoring of early brain function and development in neonatal intensive care units may help to identify infants with high risk of serious neurological impairment and to assess brain maturation for evaluation of neurodevelopmental progress. Automated analysis of EEG data makes continuous evaluation of brain activity fast and accessible. A convolutional neural network (CNN) for regression of EEG maturational age of premature neonates from marginally preprocessed serial EEG recordings is proposed. The CNN was trained and validated using 141 EEG recordings from 43 preterm neonates born below 28 weeks of gestation with normal neurodevelop-mental outcome at 12 months of corrected age. The estimated functional brain maturation between the first and last EEG recording increased in each patient. On average over 96% of repeated measures within an infant had an increasing EEG maturational age according to the post menstrual age at EEG recording time. Our algorithm has potential to be deployed to support neonatologists for accurate estimation of functional brain maturity in premature neonates.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175380DOI Listing
July 2020

The "Sound of Silence" in a Neonatal Intensive Care Unit-Listening to Speech and Music Inside an Incubator.

Front Psychol 2020 26;11:1055. Epub 2020 May 26.

Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.

The intrauterine hearing experience differs from the extrauterine hearing exposure within a neonatal intensive care unit (NICU) setting. Also, the listening experience of a neonate drastically differs from that of an adult. Several studies have documented that the sound level within a NICU exceeds the recommended threshold by far, possibly related to hearing loss thereafter. The aim of this study was, first, to precisely define the dynamics of sounds within an incubator and, second, to give clinicians and caregivers an idea about what can be heard "inside the box." Audio recordings within an incubator were conducted at the Pediatric Simulation Center of the Medical University Vienna. They contained recorded music, speech, and synthesized sounds. To understand the dynamics of sounds around and within the incubator, the following stimuli were used: broadband noise with decreasing sound level in 10 steps of 6 dB, sine waves (62.5, 125, 250, 500, 1000, 2000, 4000, 8000, and 16,000 Hz), logarithmic sweep (Chirp) over the frequency band 20 Hz to 21 kHz, singing male voice, singing, and whispering female voice. Our results confirm a protective effect of the incubator from noises above 500 Hz in conditions of "no-flow" and show almost no protective effect of an incubator cover. We, furthermore, observed a strong boost of low frequencies below 125 Hz within the incubator, as well as a notable increase of higher frequency noises with open access doors, a significant resonant effect of the incubator, and a considerable masking effect of the respiratory support against any other source of noise or sound stimulation even for "low-flow" conditions. Our study reveals high noise levels of air supply at high flow rates and the boost of low frequencies within the incubator. Education of medical staff and family members as well as modifications of the physical environment should aim at reducing noise exposure of preterm infants in the incubator. Audiovisual material is provided as Supplementary Material.
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http://dx.doi.org/10.3389/fpsyg.2020.01055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264369PMC
May 2020

The Limitations of Pain Scales-Reply.

JAMA Pediatr 2020 06;174(6):623-624

Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

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http://dx.doi.org/10.1001/jamapediatrics.2020.0079DOI Listing
June 2020

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

Pediatr Res 2021 02 26;89(3):540-548. Epub 2020 May 26.

Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1038/s41390-020-0979-2DOI Listing
February 2021

The Ketogenic Diet Including Breast Milk for Treatment of Infants with Severe Childhood Epilepsy: Feasibility, Safety, and Effectiveness.

Breastfeed Med 2020 02 26;15(2):72-78. Epub 2019 Nov 26.

Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria.

The ketogenic diet (KD) is a high-fat and restricted carbohydrate diet for treating severe childhood epilepsy. In infants, breast milk is usually fully replaced by a ketogenic formula. At our center, mothers are encouraged to include breastfeeding into the KD if still breastfeeding. This retrospective study describes achievement and maintenance of ketosis with or without inclusion of breast milk. Data were retrieved from a prospective longitudinal database of children treated with KD for epilepsy analyzing infants <1 year of age. The time to achieve clinically relevant ketosis (≥2 mmol/L beta-hydroxybutyrate) was compared with and without inclusion of breast milk into standard KD. Ketosis, nutritional intakes, effectiveness, adverse effects, and successful continuation of breastfeeding were evaluated. A total of 79 infants were eligible for analysis. In 20% (16), breast milk was included. Infants with breast milk included into the KD achieved relevant ketosis in 47 hours (interquartile range [IQR] 24-95) compared with 41 hours (IQR 22-70;  = 0.779) in infants with standard KD. Beta-hydroxybutyrate at day 2 was 3.1 mmol/L (IQR 0.5-4.9) and 3.8 mmol/L (IQR 2.2-4.9). Infants with breast milk included received higher amounts of carbohydrates at baseline and calories at 3 months. Seizure freedom and adverse effects showed no relevant differences. No infections occurred in infants receiving breast milk. In two infants, KD was initiated with breast-feds after bottle-feeding KD formula. In 31%, breastfeeding was continued after the KD, and in 25%, inclusion of breast milk and breastfeeding was maintained until complete weaning. Before discharge from hospital, the amount of breast milk included was median 90 mL/day (IQR 53-203) equivalent to median 9% (IQR 6-15). Appropriate ketosis was achieved in most infants and maintained within 48 hours. Incorporation of breast milk into KD is feasible, safe, and effective.
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http://dx.doi.org/10.1089/bfm.2019.0190DOI Listing
February 2020

Pain and Sedation Scales for Neonatal and Pediatric Patients in a Preverbal Stage of Development: A Systematic Review.

JAMA Pediatr 2019 12;173(12):1186-1197

Division of Neonatology, Pediatric Intensive Care, and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

Importance: Because children in a preverbal stage of development are unable to voice their feelings, they completely depend on their caregiving team for the interpretation and management of their pain and discomfort. Thus, accurately validated scales to assess pain and sedation levels are crucial.

Objective: To provide clinicians a complete overview on the validity and reliability of the existing pain and sedation scales for different target populations (preterm infants, term infants, and toddlers) and in different clinical contexts.

Evidence Review: BIOSIS Previews, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, MEDLINE, PsycCRITIQUES, PsycINFO, PSYNDEXplus Literature and Audiovisual Media, and PSYNDEXplus Tests were the databases screened from their inception to August 2018. All studies examining the validity or reliability of a given pain or sedation scale for patients in a preverbal stage of development were included in this systematic review. Those scales that were tested for at least construct validity, internal consistency, and interrater reliability were subsequently scored using the consensus-based standards for the selection of health measurement instruments (COSMIN) checklist.

Findings: In total, 89 validation articles comprising 65 scales were included. Fifty-seven scales (88%) were useful for assessing pain, 13 scales (20%) for assessing sedation, and 4 scales (6%) for assessing both conditions. Forty-two (65%) were behavioral scales, and 23 (35%) were multidimensional scales. Eleven scales (17%) were validated for infants on mechanical ventilation. Thirty-seven scales (57%) were validated for preterm infants, 24 scales (37%) for term and preterm infants, 7 scales (11%) for term-born children, 7 scales (11%) for preterm infants, term infants, and toddlers, and 17 scales (26%) for term infants and toddlers. Twenty-eight scales (43%) considered construct validity, internal consistency, and interrater reliability.

Conclusions And Relevance: Clinicians should consider using scales that are validated for at least construct validity, internal consistency, and interrater reliability, combining this information with the population of interest and the construct the scale is intended to measure.
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http://dx.doi.org/10.1001/jamapediatrics.2019.3351DOI Listing
December 2019

Absence of neural speech discrimination in preterm infants at term-equivalent age.

Dev Cogn Neurosci 2019 10 10;39:100679. Epub 2019 Jul 10.

Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria; Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1016/j.dcn.2019.100679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969359PMC
October 2019

A Mixed Lipid Emulsion Containing Fish Oil and Its Effect on Electrophysiological Brain Maturation in Infants of Extremely Low Birth Weight: A Secondary Analysis of a Randomized Clinical Trial.

J Pediatr 2019 08 25;211:46-53.e2. Epub 2019 Apr 25.

Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics, Medical University of Vienna, Austria.

Objective: To assess whether parenteral nutrition for infants of extremely low birth weight using a mixed lipid emulsion that contains fish oil influences electrophysiological brain maturation.

Study Design: The study is a prespecified secondary outcome analysis of a randomized controlled trial of 230 infants of extremely low birth weight receiving a mixed (soybean oil, medium-chain triglycerides, olive oil, and fish oil; intervention) or a soybean oil-based lipid emulsion (control). The study was conducted at a single-level IV neonatal care unit (Medical University Vienna; June 2012 to October 2015). Electrophysiological brain maturation (background activity, sleep-wake cycling, and brain maturational scores) was assessed biweekly by amplitude-integrated electroencephalography (birth to discharge).

Results: A total of 317 amplitude-integrated electroencephalography measurements (intervention: n = 165; control: n = 152) from 121 (intervention: n = 63; control: n = 58) of 230 infants of the core study were available for analysis. Demographic characteristics were not significantly different. By 28 weeks of postmenstrual age, infants receiving the intervention displayed significantly greater percentages of continuous background activity. Total maturational scores and individual scores for continuity, cycling, and bandwidth were significantly greater. Maximum maturational scores were reached 2 weeks earlier in the intervention group (36.4 weeks, 35.4-37.5) compared with the control group (38.4 weeks, 37.1-42.4) (median, IQR; P < .001).

Conclusions: Using a mixed parenteral lipid emulsion that contains fish oil, we found that electrophysiological brain maturation was accelerated in infants who were preterm.

Trial Registration: ClinicalTrials.gov: NCT01585935.
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http://dx.doi.org/10.1016/j.jpeds.2019.03.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115932PMC
August 2019

The Impact of Norms on the Outcome of Children Born Very-Preterm when Using the Bayley-III: Differences between US and German Norms.

Neonatology 2019 19;116(1):29-36. Epub 2019 Mar 19.

Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria.

Background: The Bayley Scales of Infant and Toddler Development, third edition (Bayley-III) are widely used to assess the development of children born preterm. However, it is still unclear whether US norms are adequate for use in other populations. In 2014, the German version of the Bayley-III with German norms was published.

Objectives: We aimed to compare the performance of very-preterm infants at one, two, and three years of age using the German versus US norms of the Bayley-III.

Methods: All children born prior to 32 weeks of gestational age during 2012 and 2015 and taking part in the follow-up program of the Medical University of Vienna were assessed and scored according to both German and US norms by two expert clinical psychologists at the age of one, two, and three years of age.

Results: In total, 843 tests were obtained from 450 children. When looking at scaled scores for cognitive, language, and motor outcomes, preterm children achieved significantly lower scores in nearly all subtests with the German as compared to the US norms. In addition, the proportion of impaired children scoring < 1 standard deviation (SD) and < 2 SD below the norm was significantly higher in nearly all subtests when using the German compared to the US norms (p < 0.05).

Conclusions: Applying German and US norms of the Bayley-III leads to different outcomes in very-preterm children, and these differences are statistically significant and clinically relevant. Thus, comparisons of outcomes of very-preterm children using culturally specific norms are problematic, and these findings have to be considered.
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http://dx.doi.org/10.1159/000497138DOI Listing
May 2020

The Effect of Vitamin C on Clinical Outcome in Critically Ill Patients: A Systematic Review With Meta-Analysis of Randomized Controlled Trials.

Crit Care Med 2019 06;47(6):774-783

Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Objectives: The effects of vitamin C administration on clinical outcome in critically ill patients remain controversial.

Data Sources: Online databases were searched up to October 1, 2018.

Study Selection: We included randomized controlled trials on the use of vitamin C (any regimen) in adult critically ill patients versus placebo or no therapy.

Data Extraction: Risk ratio for dichotomous outcome and standardized mean difference for continuous outcome with 95% CI were calculated using random-effects model meta-analysis.

Data Synthesis: Forty-four randomized studies, 16 performed in ICU setting (2,857 patients) and 28 in cardiac surgery (3,598 patients), published between 1995 and 2018, were included in the analysis. In ICU patients, vitamin C administration was not associated with a difference in mortality (risk ratio, 0.90; 95% CI, 0.74-1.10; p = 0.31), acute kidney injury, ICU or hospital length of stay compared with control. In cardiac surgery, vitamin C was associated to a reduction in postoperative atrial fibrillation (risk ratio, 0.64; 95% CI, 0.52-0.78; p < 0.0001), ICU stay (standardized mean difference, -0.28 d; 95% CI, -0.43 to -0.13 d; p = 0.0003), and hospital stay (standardized mean difference, -0.30 d; 95% CI, -0.49 to -0.10 d; p = 0.002). Furthermore, no differences in postoperative mortality, acute kidney injury, stroke, and ventricular arrhythmia were found.

Conclusions: In a mixed population of ICU patients, vitamin C administration is associated with no significant effect on survival, length of ICU or hospital stay. In cardiac surgery, beneficial effects on postoperative atrial fibrillation, ICU or hospital length of stay remain unclear. However, the quality and quantity of evidence is still insufficient to draw firm conclusions, not supporting neither discouraging the systematic administration of vitamin C in these populations. Vitamin C remains an attractive intervention for future investigations aimed to improve clinical outcome.
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http://dx.doi.org/10.1097/CCM.0000000000003700DOI Listing
June 2019

The power of N-PASS, aEEG, and BIS in detecting different levels of sedation in neonates: A preliminary study.

Paediatr Anaesth 2018 12 29;28(12):1096-1104. Epub 2018 Oct 29.

Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1111/pan.13509DOI Listing
December 2018

The impact of extrauterine life on visual maturation in extremely preterm born infants.

Pediatr Res 2018 09 2;84(3):403-410. Epub 2018 Jun 2.

Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Pediatric Intensive Care and Neuropediatrics, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: Provided that a certain maturational threshold is reached, extrauterine life appears to accelerate maturation of the visual system in preterm infants.
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http://dx.doi.org/10.1038/s41390-018-0084-yDOI Listing
September 2018

Steroids and Survival in Critically Ill Adult Patients: A Meta-analysis of 135 Randomized Trials.

J Cardiothorac Vasc Anesth 2018 10 6;32(5):2252-2260. Epub 2018 Apr 6.

Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Objective: Corticosteroids have important effects on intermediate outcomes in critically ill patients, but their effect on survival is unknown. The objective of this meta-analysis was to analyze the effect on mortality of corticosteroids in critical and perioperative settings.

Design: A meta-analysis of randomized trials.

Setting: PubMed, Embase, BioMed Central, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched to February 1, 2018, for randomized trials comparing corticosteroids with placebo or standard care.

Participants: Critically ill or surgical adult patients.

Interventions: Corticosteroids compared with placebo or standard care.

Measurements And Main Results: A total of 44,553 patients from 135 studies were included. Overall, mortality in the corticosteroid group and in the control group were similar (16% v 16%; p = 0.9). Subanalyses identified a beneficial effect of corticosteroids on survival in patients with respiratory system diseases (9% v 13%; p < 0.001) and bacterial meningitis (28% v 32%; p= 0.04), and a detrimental effect on survival in patients with traumatic brain injury (22% v 19%; p < 0.001). No differences in mortality were found in patients with cardiac diseases (7% v 6%; p = 0.7), in patients undergoing cardiac surgery (2.8% v 3.2% p = 0.14), and when treatment duration or patient age were considered.

Conclusions: This meta-analysis documents the safety of corticosteroids in the overall critically ill population with the notable exception of brain injury patients, a setting where the authors confirmed their detrimental effect on survival. A possible beneficial effect of corticosteroids on survival was found among patients with respiratory diseases and in patients with bacterial meningitis.
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http://dx.doi.org/10.1053/j.jvca.2018.04.017DOI Listing
October 2018

Prediction of Outcome in Neonates with Hypoxic-Ischemic Encephalopathy II: Role of Amplitude-Integrated Electroencephalography and Cerebral Oxygen Saturation Measured by Near-Infrared Spectroscopy.

Neonatology 2017 14;112(3):193-202. Epub 2017 Jul 14.

Division of Neonatology, Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1159/000468976DOI Listing
June 2018

Automated classification of neonatal sleep states using EEG.

Clin Neurophysiol 2017 06 15;128(6):1100-1108. Epub 2017 Mar 15.

BABA Center, Department of Children's Clinical Neurophysiology, Children's Hospital, HUS Medical Imaging Center, Helsinki University Central Hospital and University of Helsinki, Finland. Electronic address:

Objective: To develop a method for automated neonatal sleep state classification based on EEG that can be applied over a wide range of age.

Methods: We collected 231 EEG recordings from 67 infants between 24 and 45weeks of postmenstrual age. Ten minute epochs of 8 channel polysomnography (N=323) from active and quiet sleep were used as a training dataset. We extracted a set of 57 EEG features from the time, frequency, and spatial domains. A greedy algorithm was used to define a reduced feature set to be used in a support vector machine classifier.

Results: Performance tests showed that our algorithm was able to classify quiet and active sleep epochs with 85% accuracy, 83% sensitivity, and 87% specificity. The performance was not substantially lowered by reducing the epoch length or EEG channel number. The classifier output was used to construct a novel trend, the sleep state probability index, that improves the visualisation of brain state fluctuations.

Conclusions: A robust EEG-based sleep state classifier was developed. It performs consistently well across a large span of postmenstrual ages.

Significance: This method enables the visualisation of sleep state in preterm infants which can assist clinical management in the neonatal intensive care unit.
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http://dx.doi.org/10.1016/j.clinph.2017.02.025DOI Listing
June 2017

The implementation of systematic pain and sedation management has no impact on outcome in extremely preterm infants.

Acta Paediatr 2016 Jul 10;105(7):798-805. Epub 2016 Feb 10.

Department of Pediatrics and Adolescent Medicine, Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria.

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.
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http://dx.doi.org/10.1111/apa.13334DOI Listing
July 2016

A systematic review of the mismatch negativity as an index for auditory sensory memory: From basic research to clinical and developmental perspectives.

Psychophysiology 2015 Sep 19;52(9):1115-30. Epub 2015 Jun 19.

Institute for Biomagnetism and Biosignalanalysis, University of Muenster, Muenster, Germany.

Auditory sensory memory is an important ability for successful language acquisition and processing. The mismatch negativity (MMN) in response to auditory stimuli has been proposed as an objective tool to measure the existence of auditory sensory memory traces. By increasing interstimulus intervals, attenuation of MMN peak amplitude and increased MMN peak latency have been suggested to reflect duration and decay of sensory memory traces. The aim of the present study is to conduct a systematic review of studies investigating sensory memory duration with MMN. Searches of electronic databases yielded 743 articles. Of these, 37 studies met final eligibility criteria. Results point to maturational changes in the time span of auditory sensory memory from birth on with a peak in young adulthood, as well as to a decrease of sensory memory duration in healthy aging. Furthermore, this review suggests that sensory memory decline is related to diverse neurological, psychiatric, and pediatric diseases, including Alzheimer's disease, alcohol abuse, schizophrenia, and language disorders. This review underlines that the MMN provides a unique window to the cognitive processes of auditory sensory memory. However, further studies combining electrophysiological and behavioral data, and further studies in clinical populations are needed, also on individual levels, to validate the MMN as a clinical tool for the assessment of sensory memory duration.
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http://dx.doi.org/10.1111/psyp.12459DOI Listing
September 2015

Being Born Small for Gestational Age Influences Amplitude-Integrated Electroencephalography and Later Outcome in Preterm Infants.

Neonatology 2015 2;108(2):81-7. Epub 2015 Jun 2.

Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.

Background: The impact of growth restriction on perinatal morbidity is well known, but electroencephalographic (EEG) data on its influence are still scarce.

Objectives: We aimed to analyze the influence of being born small for gestational age (SGA; defined as a birth weight <10th percentile) on the amplitude-integrated EEG (aEEG) score in the first 2 weeks of life in preterm infants born before 30 weeks of gestation, and its impact on later outcome.

Methods: aEEG data obtained within the first 2 weeks of life on preterm infants born SGA and before 30 weeks of gestational age (GA) were analyzed retrospectively using a combined score [including background activity, occurrence of sleep-wake cycles (SWC) and suspected seizure activity]. Neurodevelopmental outcome was evaluated at 24 months by means of the Bayley Scales of Infant Development II and a standardized neurological examination.

Results: One hundred and thirty-six patients were included (47 SGA and 89 controls). Infants with SGA had abnormal aEEG scores significantly more often (57 vs. 24%, p = 0.002) than infants born appropriate for gestational age (AGA). They also displayed SWC less frequently (65 vs. 96%, p = 0.001), were more likely to develop seizure activity (15 vs. 4%, p = 0.013) and had a normal neurodevelopmental outcome at the age of 2 years less frequently (36.2 vs. 59.6%, p = 0.02).

Conclusion: Preterm infants born SGA and before 30 weeks of GA had less optimal scores on early aEEG and a poorer neurodevelopmental outcome at 24 months than the AGA controls.
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http://dx.doi.org/10.1159/000382013DOI Listing
May 2016
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