Publications by authors named "Angelika Berger"

153 Publications

Clinical Early-Onset Sepsis Is Equally Valid to Culture-Proven Sepsis in Predicting Outcome in Infants after Preterm Rupture of Membranes.

J Clin Med 2021 Sep 30;10(19). Epub 2021 Sep 30.

Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria.

Background: Culture-proven sepsis is the gold standard in early-onset neonatal sepsis diagnosis. Infants born ≤29 weeks gestation after preterm rupture of membranes in the years 2009-2015 were included in a retrospective cohort study performed at a level III fetal-maternal unit. The study aimed to compare culture-proven sepsis, clinical sepsis and positive laboratory biomarkers ≤72 h as predictors of mortality before discharge and the combined outcome of mortality or severe short-term morbidity (severe cerebral morbidity, bronchopulmonary dysplasia and retinopathy).

Results: Of the 354 patients included, culture-proven sepsis, clinical sepsis and laboratory biomarkers were positive in 2.3%, 8.5% and 9.6%, respectively. The mortality rate was 37.5% for patients with culture-proven sepsis (3/8), 33.3% for patients with clinical sepsis (10/30) and 8.8% for patients with positive laboratory biomarkers (3/34), respectively. Mortality or severe morbidity occurred in 75.0% of patients with culture-proven sepsis (6/8), 80.0% of patients with clinical sepsis (24/30) and 44.1% of patients with positive laboratory biomarkers (15/34), respectively.

Conclusion: In preterm infants after preterm rupture of membranes, clinical sepsis was almost four times more common and at least equally valuable in predicting mortality and mortality or severe morbidity compared to culture-proven sepsis.
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http://dx.doi.org/10.3390/jcm10194539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509355PMC
September 2021

Perinatal and postpartum care during the COVID-19 pandemic: A nationwide cohort study.

Birth 2021 Oct 7. Epub 2021 Oct 7.

Division of Obstetrics and Feto-maternal Medicine, Department of Obstetrics and Gynecology, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.

Background: This study aimed to analyze perinatal outcomes and adverse events during the COVID-19 pandemic's first wave to help direct decision making in future waves.

Methods: This study was an epidemiological cohort study analyzing comprehensive birth registry data among all 80 obstetric departments in Austria. Out of 469 771 records, 468 348 were considered eligible, whereof those with preterm delivery, birthweight <500 g, multiple fetuses, fetal malformations and chromosomal anomalies, intrauterine fetal death, maternal cancer, HIV infection, and/or inter-hospital transfers were excluded. Women who delivered between January and June 2020 were then classified as cases, whereas those who delivered between January and June 2015-2019 were classified as controls. Perinatal outcomes, postpartum hospitalization, and adverse events served as outcome measures.

Results: Of 33 198 cases and 188 225 controls, data analysis showed significantly increased rates of labor induction, instrumental delivery, obstetric anesthesia, NICU transfer, and 5-min Apgar score below 7 during the COVID-19 period. There was a significantly shorter length of postpartum hospitalization during the COVID-19 period compared with the non-COVID-19 period (3.1 ± 1.4 vs 3.5 ± 1.5 days; P < .001). Significantly more women opted for short-stay delivery during the COVID-19 period (3.7% vs 2.4%; P < .001). Those who delivered during the COVID-19 period were also more likely to experience postpartum adverse events (3.0% vs 2.6%; P < .001), which was confirmed in the logistic regression model (odds ratio, 2.137; 95% confidence interval, 1.805-2.530; P < .001).

Conclusions: Perinatal and postpartum care during the first wave of the COVID-19 pandemic differed significantly from that provided before. Increased rates of adverse events underline the need to ensure access to high-quality obstetric care to prevent collateral damage.
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http://dx.doi.org/10.1111/birt.12594DOI Listing
October 2021

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

Front Pediatr 2021 30;9:700226. Epub 2021 Aug 30.

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

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. 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. 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. 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.
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http://dx.doi.org/10.3389/fped.2021.700226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435739PMC
August 2021

Diagnosing pneumomediastinum in a neonate using a lung ultrasound.

Lancet 2021 Sep;398(10303):e13

Medical University of Vienna, Comprehensive Center for Paediatrics, Department of Paediatrics and Adolescent Medicine, Division of Neonatology, Paediatric Intensive Care and Neuropaediatrics, Vienna, Austria. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(21)01592-0DOI Listing
September 2021

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

Cell Host Microbe 2021 Oct 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
October 2021

Multiprofessional perinatal care in a pregnant patient with acute respiratory distress syndrome due to COVID-19.

BMC Pregnancy Childbirth 2021 Aug 26;21(1):587. Epub 2021 Aug 26.

Department of Obstetrics and Gynecology, Division of Obstetrics and Feto-Maternal Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.

Background: The coronavirus disease (COVID-19) pandemic has caused ongoing challenges in health services worldwide. Despite the growing body of literature on COVID-19, reports on perinatal care in COVID-19 cases are limited.

Case Presentation: We describe a case of severe acute respiratory distress syndrome (ARDS) in a 36-year-old G5/P2 pregnant woman with morbid obesity, confirmed severe acute respiratory syndrome coronavirus 2 infection, and fulminant respiratory failure. At 28 gestational weeks, the patient delivered an uninfected newborn. Using ImmunoCAP ISAC® technology, we found no immunoglobulin (Ig) M antibodies, suggesting that no mother-to-child viral transmission occurred during pregnancy or delivery. The maternal respiratory state improved rapidly after delivery; both maternal and neonatal outcomes were encouraging given the early gestational age and fulminant course of respiratory failure in our patient.

Conclusions: The management of ARDS in pregnant women with COVID-19 is complex and requires an individualized, multidisciplinary approach, while considering maternal and fetal outcomes.
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http://dx.doi.org/10.1186/s12884-021-04059-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390084PMC
August 2021

The Role of Lung Ultrasound in the Management of the Critically Ill Neonate-A Narrative Review and Practical Guide.

Children (Basel) 2021 Jul 24;8(8). Epub 2021 Jul 24.

Department of Paediatrics and Adolescent Medicine, Division of Neonatology, Medical University of Graz, Auenbruggerplatz 34/2, 8036 Graz, Austria.

Lung ultrasound makes use of artifacts generated by the ratio of air and fluid in the lung. Recently, an enormous increase of research regarding lung ultrasound emerged, especially in intensive care units. The use of lung ultrasound on the neonatal intensive care unit enables the clinician to gain knowledge about the respiratory condition of the patients, make quick decisions, and reduces exposure to ionizing radiation. In this narrative review, the possibilities of lung ultrasound for the stabilization and resuscitation of the neonate using the ABCDE algorithm will be discussed.
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http://dx.doi.org/10.3390/children8080628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391155PMC
July 2021

Video-based reflection on neonatal interventions during COVID-19 using eye-tracking glasses: an observational study.

Arch Dis Child Fetal Neonatal Ed 2021 Aug 19. Epub 2021 Aug 19.

Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Objective: The aim of this study was to determine the experience with, and the feasibility of, point-of-view video recordings using eye-tracking glasses for training and reviewing neonatal interventions during the COVID-19 pandemic.

Design: Observational prospective single-centre study.

Setting: Neonatal intensive care unit at the Leiden University Medical Center.

Participants: All local neonatal healthcare providers.

Intervention: There were two groups of participants: proceduralists, who wore eye-tracking glasses during procedures, and observers who later watched the procedures as part of a video-based reflection.

Main Outcome Measures: The primary outcome was the feasibility of, and the proceduralists and observers' experience with, the point-of-view eye-tracking videos as an additional tool for bedside teaching and video-based reflection.

Results: We conducted 12 point-of-view recordings on 10 different patients (median gestational age of 30.9±3.5 weeks and weight of 1764 g) undergoing neonatal intubation (n=5), minimally invasive surfactant therapy (n=5) and umbilical line insertion (n=2). We conducted nine video-based observations with a total of 88 observers. The use of point-of-view recordings was perceived as feasible. Observers further reported the point-of-view recordings to be an educational benefit for them and a potentially instructional tool during COVID-19.

Conclusion: We proved the practicability of eye-tracking glasses for point-of-view recordings of neonatal procedures and videos for observation, educational sessions and logistics considerations, especially with the COVID-19 pandemic distancing measures reducing bedside teaching opportunities.
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http://dx.doi.org/10.1136/archdischild-2021-321806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384497PMC
August 2021

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

Arch Dis Child Fetal Neonatal Ed 2021 Aug 3. Epub 2021 Aug 3.

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

Objective: To assess the reliability, accuracy and precision of distal end-tidal capnography (detCO) in neonates compared with transcutaneous (tcCO) 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 CO was measured in distal position using the separate lumen of a double-lumen endotracheal tube connected to an external side-stream capnometer. Three consecutive detCO and tcCO values were recorded simultaneously and compared with simultaneous arterialised partial pressure of CO (paCO) measurements in each patient.

Main Outcome Measures: Reliability, accuracy and precision of detCO and tcCO measurements compared with paCO 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 detCO, tcCO and paCO were obtained. The mean (SD) of paCO, detCO and tcCO was 45.0 (8.6) mmHg, 42.4 (8.4) mmHg and 50.4 (20.4) mmHg, respectively. The intraclass correlation between paCO and detCO and between paCO and tcCO 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 detCO with respect to paCO amounted to -2.68 mmHg and 10.62 mmHg (95% CI 8.49 to 14.51), respectively. Bias and precision of tcCO with respect to paCO amounted to 5.39 mmHg and 17.22 mmHg (95% CI 13.21 to 23.34), respectively.

Conclusion: DetCO had better reliability, accuracy and precision with paCO than tcCO in ventilated neonates without severe lung diseas.

Trial Registration Number: NCT03758313.
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http://dx.doi.org/10.1136/archdischild-2021-322138DOI Listing
August 2021

Effects of an exclusive human-milk diet in preterm neonates on early vascular aging risk factors (NEOVASC): study protocol for a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial.

Trials 2021 Jul 31;22(1):509. Epub 2021 Jul 31.

Department of Pediatrics II (Neonatology), Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.

Background: Preterm birth accounts for approximately 11% of all livebirths globally. Due to improvements in perinatal care, more than 95% of these infants now survive into adulthood. Research has indicated a robust association between prematurity and increased cardiovascular risk factors and cardiovascular mortality. While the innate adverse effects of prematurity on these outcomes have been demonstrated, therapeutic strategies on the mitigation of these concerning developments are lacking. The primary objective of the NEOVASC clinical trial is therefore to investigate whether the administration of a prolonged exclusive human-milk diet in preterm infants is capable of alleviating the harmful effects of preterm birth on the early development of cardiovascular risk factors.

Methods: The NEOVASC study is a multicentric, prospective, randomized, controlled, open, and parallel group clinical trial conducted in four Austrian tertiary neonatal care facilities. The purpose of the present trial is to investigate the effects of a prolonged exclusive human-milk-diet devoid of bovine-milk-based food components on cardiovascular and metabolic risk factors at 1, 2, and 5 years of corrected age. Primary outcomes include assessments of fasting blood glucose levels, blood pressure levels, and the distensibility of the descending aorta using validated echocardiographic protocols at 5 years of corrected age. The test group, which consists of 200 preterm infants, will therefore be compared to a control group of 100 term-born infants and a historical control group recruited previously.

Discussion: Given the emerging implications of an increased cardiovascular risk profile in the potentially growing population of preterm infants, further research on the mitigation of long-term morbidities in formerly preterm infants is urgently warranted. Further optimizing preterm infants' nutrition by removing bovine-milk-based food components may therefore be an interesting approach worth pursuing.

Trial Registration: ClinicalTrials.gov NCT04413994 . Registered on 4 June 2020.
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http://dx.doi.org/10.1186/s13063-021-05445-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325296PMC
July 2021

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

Pediatr Res 2021 Jul 21. Epub 2021 Jul 21.

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

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.
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http://dx.doi.org/10.1038/s41390-021-01653-wDOI Listing
July 2021

Longitudinal Reference Values for Cerebral Ventricular Size in Preterm Infants Born at 23-27 Weeks of Gestation.

J Pediatr 2021 Jun 29. Epub 2021 Jun 29.

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

Objective: To establish longitudinal reference values for cerebral ventricular size in the most vulnerable patients at risk for intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilatation (PHVD).

Study Design: This retrospective study included neurologically healthy preterm neonates born at 23-26 weeks of gestational age between September 2011 and April 2019. Patients were treated at 2 Austrian tertiary centers, Medical University of Vienna and Medical University of Innsbruck. All available cerebral ultrasound scans until 30 weeks corrected age were analyzed. Ventricular measurements included ventricular index, anterior horn width (AHW), and thalamo-occipital distance (TOD) and longitudinal percentiles were created.

Results: The study cohort consisted of 244 preterm neonates, with a median gestational age of 25 weeks (IQR, 24-26 weeks) and a median birth weight of 735 g (IQR, 644-849 g). A total of 993 ultrasound scans were available for analysis, resulting in >1800 measurements of ventricular index, AHW, and TOD. Special attention was given to the 97th percentile as well as 2 mm and 4 mm above the 97th percentile, which are used internationally as cutoffs for intervention in the presence of PHVD.

Conclusions: We present percentile charts based on a cohort of extremely premature infants including neonates born at the border of viability suited to follow-up the most vulnerable patients at risk for IVH and PHVD. Furthermore, we provide an extensive literature research and comparison of all available reference values, focusing on ventricular index, AHW, and TOD.
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http://dx.doi.org/10.1016/j.jpeds.2021.06.065DOI Listing
June 2021

Myelomeningocele-Chiari II malformation-Neurological predictability based on fetal and postnatal magnetic resonance imaging.

Prenat Diagn 2021 Jul 19;41(8):922-932. Epub 2021 Jun 19.

Department of Radiology, Division of Neuro- and Musculoskeletal Radiology, Medical University of Vienna, Vienna, Austria.

Objective: This systematic comparison between pre- and postnatal imaging findings and postnatal motor outcome assesses the reliability of MRI accuracy in the prognostication of the future long-term (mean, 11.4 years) ambulatory status in a historic group of postnatally repaired myelomeningocele (MMC) cases.

Methods: A retrospective, single-center study of 34 postnatally repaired MMC patients was performed. We used fetal and postnatal magnetic resonance imaging (MRI) to compare the fetal and postnatal radiological lesion level to each other and to the postnatal ambulatory level as a standard of reference and analyzed Chiari II malformation characteristics.

Results: In 13/15 (87%) and 29/31 (94%) cases, the functional level was equal to or better than the prenatal and postnatal radiological lesion level. A radiological lesion level agreement within two segments could be achieved in 13/15 (87%) patients. A worse than expected functional level occurred in cases with Myelocele (2/3 patients), coexistent crowding of the posterior fossa (2/3 patients) and/or abnormal white matter architecture, represented by callosal dysgenesis (1/3 patients). In all patients (2/2) with a radiological disagreement of more than two segments, segmentation disorders and scoliosis were observed.

Conclusion: Fetal and postnatal MRI are predictive of the long-term ambulatory status in postnatally repaired MMC patients.
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http://dx.doi.org/10.1002/pd.5987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361919PMC
July 2021

NeoAct: A Randomized Prospective Pilot Study on Communication Skill Training of Neonatologists.

Front Pediatr 2021 13;9:675742. Epub 2021 May 13.

Department for Medical Psychology, Department for Public Health, Medical University Vienna, Vienna, Austria.

This randomized interventional study evaluated the impact of a 1-day experiential communication skills training on neonatologists' performance in doctor-parents-communication. 17 neonatologists with different levels of professional experience from the Medical University of Vienna were randomized into one of two study groups: The intervention group (IG) as opposed to the control group (CG) participated in a 1-day experiential communication training. Eight weeks after the training, participants' communication skills were assessed during an objective structured clinical examination (OSCE). Neonatologists were assessed in a simulated conversation by how effectively they performed when conveying complex health-related information to parents of ill infants. Participants in the control group (CG) were assessed first during the OSCE and received their communication training later on. Self-assessment questionnaires before and after the workshop and OSCE were completed. The study determined that neonatologists in the IG subjectively perceived that their competence level regarding their communication skills had increased after the workshop, while this was not reflected by their performance during the OSCE assessment. A 1-day experiential communication skills training significantly increased physicians' self-evaluation concerning their communicative competence. This perceived competence did not manifest itself in increased communication skills during the OSCE. Repeated training is needed.
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http://dx.doi.org/10.3389/fped.2021.675742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158577PMC
May 2021

Considerable mortality and morbidity in neonates born below 500 gram.

Acta Paediatr 2021 08 19;110(8):2359-2365. Epub 2021 May 19.

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

Data evaluating mortality and morbidity in infants born ≤500 g are scarce and show wide variability. To support counselling and decision-making, we analysed neurodevelopmental outcome in all neonates ≤500 g birth weight. Retrospective analysis including preterm infants with a birth weight ≤500 g and a gestational age >22 weeks born at a single tertiary perinatal centre between 2010 and 2017. Of 59 live births, 88% received standard care. Birth weight ranged from 318 to 500 g and gestational age from 23 to 29 weeks. 56% of neonates were born ≤3rd percentile and 42% of treated infants survived. Neurodevelopmental outcome was available in 91% of patients and was evaluated using Bayley Scales of Infant Development at two years. 50% showed a favourable mental development (normal or mild impairment), 75% a favourable motor development and 45% a favourable outcome in both outcome subcategories. When additionally considering visual and hearing disability and, or, cerebral palsy level ≥2 according to the Gross Motor Function Classification System 35% had a good neurodevelopmental outcome. Survival rate was 37% for all live births and 42% for infants with standard care. More than one-third of survivors showed no significant neurodevelopmental impairment at two years.
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http://dx.doi.org/10.1111/apa.15885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360180PMC
August 2021

Maternal Vaginal spp. Colonization in Early Pregnancy Is Associated with Adverse Short- and Long-Term Outcome of Very Preterm Infants.

Children (Basel) 2021 Apr 3;8(4). Epub 2021 Apr 3.

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

Vaginal colonization with () spp. has been shown to be associated with adverse pregnancy outcome; however, data on neonatal outcome are scarce. The aim of the study was to investigate whether maternal vaginal colonization with spp. in early pregnancy represents a risk factor for adverse short- or long-term outcome of preterm infants. Previously, 4330 pregnant women were enrolled in an observational multicenter study, analyzing the association between vaginal spp. colonization and spontaneous preterm birth. spp. colonization was diagnosed via PCR analysis from vaginal swabs. For this study, data on short-term outcome were collected from medical records and long-term outcome was examined via Bayley Scales of Infant Development at 24 months adjusted age. Two-hundred-and-thirty-eight children were born <33 weeks gestational age. After exclusion due to asphyxia, malformations, and lost-to-follow-up, data on short-term and long-term outcome were available from 222 and 92 infants, respectively. Results show a significant association between vaginal spp. colonization and severe intraventricular hemorrhage (10.4% vs. 2.6%, = 0.03), retinopathy of prematurity (21.7% vs. 10.3%, = 0.03), and adverse psychomotor outcome (24.3% vs. 1.8%, OR 13.154, 95%CI 1.6,110.2, = 0.005). The data suggest an association between vaginal spp. colonization in early pregnancy and adverse short- and long-term outcome of very preterm infants.
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http://dx.doi.org/10.3390/children8040276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066242PMC
April 2021

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

Dev Sci 2021 Sep 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

Risk factors for mortality in infants with congenital diaphragmatic hernia: a single center experience.

Wien Klin Wochenschr 2021 Jul 30;133(13-14):674-679. Epub 2021 Mar 30.

Comprehensive Centre for Paediatrics, Division of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Department of Paediatric and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background: Despite current progress in research of congenital diaphragmatic hernia, its management remains challenging, requiring an interdisciplinary team for optimal treatment.

Objective: Aim of the present study was to evaluate potential risk factors for mortality of infants with congenital diaphragmatic hernia.

Methods: A single-center chart review of all patients treated with congenital diaphragmatic hernia over a period of 16 years, at the Medical University of Vienna, was performed. A comparison of medical parameters between survivors and non-survivors, as well as to published literature was conducted.

Results: During the observational period 66 patients were diagnosed with congenital diaphragmatic hernia. Overall survival was 84.6%. Left-sided hernia occurred in 51 patients (78.5%) with a mortality of 7.8%. In comparison, right-sided hernia occurred less frequently (n = 12) but showed a higher mortality (33.3%, p = 0.000). Critically instable patients were provided with venoarterial extracorporeal membrane oxygenation (ECMO, 32.3%, n = 21). Survival rate among these patients was 66.7%. Right-sided hernia, treatment with inhaled nitric oxide (iNO) over 15 days and the use of ECMO over 10 days were significant risk factors for mortality.

Conclusion: The survival rate in this cohort is comparable to the current literature. Parameters such as the side of the diaphragmatic defect, duration of ECMO and inhaled nitric oxide were assessed as mortality risk factors. This analysis of patients with congenital diaphragmatic hernia enhances understanding of risk factors for mortality, helping to improve management and enabling further evaluation in prospective clinical trials.
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http://dx.doi.org/10.1007/s00508-021-01843-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008339PMC
July 2021

Cysto-Vaginoscopy of a 3D-Printed Cloaca Model: A Step toward Personalized Noninvasive Preoperative Assessment in Patients with Complex Anorectal Malformations.

Eur J Pediatr Surg 2021 Mar 23. Epub 2021 Mar 23.

Department of Pediatric Surgery, Medical University of Vienna, Vienna, Wien, Austria.

Introduction:  For the classification of the complexity of cloacal malformations and the decision on the operative approach, an exact anatomical assessment is mandatory. To benefit from using three-dimensional (3D)-printed models in preoperative planning and training, the practicability of these models should be guaranteed. The aim of this study was to evaluate the quality and feasibility of a real-size 3D-printed cloaca model for the purpose of cysto-vaginoscopic evaluation.

Materials And Methods:  We performed a 3D reconstruction and printed a real-size, rubber-like 3D model of an infant pelvis with a cloacal malformation and asked invited pediatric surgeons and pediatric urologists to perform a cysto-vaginoscopy on the model and to complete a brief questionnaire to rate the quality and feasibility of the model and to indicate whether they would recommend the model for preoperative planning and training.

Results:  Overall, 41 participants rated the model quality as good to very good (M = 3.28, standard deviation [SD] = 0.50, on a scale from 1 to 4). The model was rated as feasible for preoperative training (M = 4.10, SD = 0.75, on a scale from 1 to 5) and most participants (85.4%) would recommend the model for preoperative training. The cysto-vaginoscopy of the model was considered as a valid training tool for real-life cases and improved the confidence on the anatomy of a cloaca.

Conclusion:  The results of our study indicate that patient-specific 3D-printed models might be a useful tool in the preoperative evaluation of complex anorectal malformations by simulation of cysto-vaginoscopy with an excellent view on anatomical structures to assess the whole spectrum of the individual cloacal malformation. Our model might be a valuable add-on tool for specialty training in pediatric colorectal surgery.
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http://dx.doi.org/10.1055/s-0041-1726424DOI Listing
March 2021

Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis.

Pharmaceutics 2021 Feb 12;13(2). Epub 2021 Feb 12.

Center for Health and Bioresources, Competence Unit Molecular Diagnostics, Austrian Institute of Technology (AIT) GmbH, Giefinggasse 4, 1210 Vienna, Austria.

C-reactive protein (CRP) is a commonly used serum biomarker for detecting sepsis in neonates. After the onset of sepsis, serial measurements are necessary to monitor disease progression; therefore, a non-invasive detection method is beneficial for neonatal well-being. While some studies have shown a correlation between serum and salivary CRP levels in septic neonates, the causal link behind this correlation remains unclear. To investigate this relationship, CRP was examined in serum and saliva samples from 18 septic neonates and compared with saliva samples from 22 healthy neonates. While the measured blood and saliva concentrations of the septic neonates varied individually, a correlation of CRP levels between serum and saliva samples was observed over time. To clarify the presence of active transport of CRP across the blood-salivary barrier (BSB), transport studies were performed with CRP using in vitro models of oral mucosa and submandibular salivary gland epithelium. The results showed enhanced transport toward saliva in both models, supporting the clinical relevance for salivary CRP as a biomarker. Furthermore, CRP regulated the expression of the receptor for advanced glycation end products (RAGE) and the addition of soluble RAGE during the transport studies indicated a RAGE-dependent transport process for CRP from blood to saliva.
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http://dx.doi.org/10.3390/pharmaceutics13020256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917918PMC
February 2021

Development of a 3D printed patient-specific neonatal brain simulation model using multimodality imaging for perioperative management.

Pediatr Res 2021 Mar 2. Epub 2021 Mar 2.

Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.

Background: Medical-imaging-based three-dimensional (3D) printed models enable improvement in skills training, surgical planning, and decision-making. This pilot study aimed to use multimodality imaging and to add and compare 3D ultrasound as a future standard to develop realistic neonatal brain models including the ventricular system.

Methods: Retrospective computed tomography (CT), magnetic resonance imaging (MRI), and 3D ultrasound-based brain imaging protocols of five neonatal patients were analyzed and subsequently segmented with the aim of developing a multimodality imaging-based 3D printed model. The ventricular anatomy was analyzed to compare the MRI and 3D ultrasound modalities.

Results: A realistic anatomical model of the neonatal brain, including the ventricular system, was created using MRI and 3D ultrasound data from one patient. T2-weighted isovoxel 3D MRI sequences were found to have better resolution and accuracy than 2D sequences. The surface area, anatomy, and volume of the lateral ventricles derived from both MRI and 3D ultrasound were comparable.

Conclusions: We created an ultrasound- and MRI-based 3D printed patient-specific neonatal brain simulation model that can be used for perioperative management. To introduce 3D ultrasound as a standard for 3D models, additional dimensional correlations between MRI and ultrasound need to be examined.

Impact: We studied the feasibility of implementing 3D ultrasound as a standard for 3D printed models of the neonatal brain. Different imaging modalities were compared and both 3D isotropic MRI and 3D ultrasound imaging are feasible for printing neonatal brain models with good dimensional accuracy and anatomical replication. Further dimensional correlations need to be defined to implement it as a standard to produce 3D printed models.
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http://dx.doi.org/10.1038/s41390-021-01421-wDOI Listing
March 2021

Early life serum neurofilament dynamics predict neurodevelopmental outcome of preterm infants.

J Neurol 2021 Jul 10;268(7):2570-2577. Epub 2021 Feb 10.

Division of Neonatology, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland.

Background And Purpose: To determine whether neurofilament light chain (NfL), a promising serum and cerebrospinal fluid (CSF) biomarker of neuroaxonal damage, predicts functional outcome in preterm infants with neonatal brain injury.

Methods: Our prospective observational study used a sensitive single-molecule array assay to measure serum and CSF NfL concentrations in preterm infants with moderate to severe peri/intraventricular hemorrhage (PIVH). We determined temporal serum and CSF NfL profiles from the initial diagnosis of PIVH until term-equivalent age and their association with clinical and neurodevelopmental outcome until 2 years of age assessed by Bayley Scales of Infant Development (3rd edition). We fitted univariate and multivariate logistic regression models to determine risk factors for poor motor and cognitive development.

Results: The study included 48 infants born at < 32 weeks of gestation. Median serum NfL (sNfL) at PIVH diagnosis was 251 pg/mL [interquartile range (IQR) 139-379], decreasing markedly until term-equivalent age to 15.7 pg/mL (IQR 11.1-33.5). CSF NfL was on average 113-fold higher (IQR 40-211) than corresponding sNfL values. Additional cerebral infarction (n = 25)-but not post-hemorrhagic hydrocephalus requiring external ventricular drainage (n = 29) nor any other impairment-was independently associated with sNfL. Multivariate logistic regression models identified sNfL as an independent predictor of poor motor outcome or death at 1 and 2 years.

Conclusions: Serum neurofilament light chain dynamics in the first weeks of life predict motor outcome in preterm infants with PIVH.
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http://dx.doi.org/10.1007/s00415-021-10429-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217001PMC
July 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

Integrative transcriptome analysis deciphers mechanisms of nickel contact dermatitis.

Allergy 2021 03 12;76(3):804-815. Epub 2020 Aug 12.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Background: Nickel-induced allergic contact dermatitis (nACD) remains a major occupational skin disorder, significantly impacting the quality of life of suffering patients. Complex cellular compositional changes and associated immunological pathways are partly resolved in humans; thus, the impact of nACD on human skin needs to be further elucidated.

Methods: To decipher involved immunological players and pathways, human skin biopsies were taken at 0, 2, 48, and 96 hours after nickel patch test in six nickel-allergic patients. Gene expression profiles were analyzed via microarray.

Results: Leukocyte deconvolution of nACD-affected skin identified major leukocyte compositional changes at 48 and 96 hours, including natural killer (NK) cells, macrophage polarization, and T-cell immunity. Gene set enrichment analysis mirrored cellular-linked functional pathways enriched over time. NK cell infiltration and cytotoxic pathways were uniquely found in nACD-affected skin compared to sodium lauryl sulfate-induced irritant skin reactions.

Conclusion: These results highlight key immunological leukocyte subsets as well as associated pathways in nACD, providing insights into pathophysiology with the potential to unravel novel therapeutic targets.
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http://dx.doi.org/10.1111/all.14519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984291PMC
March 2021

The association between shift patterns and the quality of hand antisepsis in a neonatal intensive care unit: An observational study.

Int J Nurs Stud 2020 Dec 14;112:103686. Epub 2020 Jun 14.

Department for Hospital Epidemiology and Infection Control, Medical University of Vienna, Vienna, Austria; Institute for Skin Integrity and Infection Prevention, School of Human and Health Sciences, University of Huddersfield, United Kingdom.

Background: Healthcare-associated infections represent a major burden in neonatal intensive care units. Hand antisepsis is the most important tool for prevention, however, compliance among healthcare workers remains low.

Objectives: To prospectively evaluate the influence of different work shifts (extended working hours, night shifts) on the quality of healthcare workers' hand antisepsis.

Design: Observational study.

Settings: Two equivalent "Level III" neonatal intensive care units at the University Hospital Vienna, Austria.

Participants: Seventy healthcare workers, 46 nurses and 24 physicians.

Methods: The Semmelweis Scanner, an innovative training device assessing the quality of hand antisepsis with an ultraviolet dye labelled alcohol-based hand rub, was employed to collect data on the hand surface coverage achieved during hand antisepsis of participants. It provides visual feedback of appropriately versus inappropriately disinfected areas of the hand and can also be used for the objective quantification of hand surface coverage with the hand rub. Measurements were performed before and after 12.5 h (h) day and night shifts (nurses), as well as before and after regular 8 h day shifts and extended 25 h shifts (physicians). To avoid any bias caused by residual ultraviolet marker, scans had to be separated by 24 h periods. Primary outcome was the hand surface coverage with the hand rub: Hand scans were categorized as "passed" if an appropriate quality of hand hygiene, defined as a minimum 97% coverage of hand surface, was achieved. A generalized mixed model was used to analyse the data accounting for repeated measurements.

Results: Seventy healthcare workers performed a total of 485 scans. Nineteen scans had to be excluded, resulting in 466 scans for further analyses. A difference in the predicted probability of achieving appropriate hand antisepsis was found between the beginning and end of extended shifts: In physicians, adequate hand antisepsis was remarkably reduced after 25 h shifts (predicted probability 99.4% vs 78.8%), whereas there was no relevant difference between the beginning and end of 8 h day shifts (92.2% vs 97.3%). In nurses, a relevant difference was found between the beginning and end of 12.5 h day shifts (88.6% vs 73.6%). This difference was not found for 12.5 h night shifts. The most frequently missed area on the hands was the right dorsum.

Conclusion: The quality of hand antisepsis of healthcare workers in neonatal intensive care units may be associated with long working hours.
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http://dx.doi.org/10.1016/j.ijnurstu.2020.103686DOI Listing
December 2020

A Randomized Trial of Parenteral Nutrition Using a Mixed Lipid Emulsion Containing Fish Oil in Infants of Extremely Low Birth Weight: Neurodevelopmental Outcome at 12 and 24 Months Corrected Age, A Secondary Outcome Analysis.

J Pediatr 2020 Jun 23. Epub 2020 Jun 23.

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

Objective: To examine whether parenteral nutrition using a mixed lipid emulsion containing fish oil improves the neurodevelopmental outcomes of extremely low birth weight infants.

Study Design: The study is a secondary outcome analysis of a double-blind randomized trial of 230 extremely low birth weight infants performed at a single level IV neonatal care unit (Medical University Vienna; June 2012 to June 2015). Participants received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil, or a soybean oil-based lipid emulsion for parenteral nutrition. Neurodevelopment of study participants was assessed at 12 and 24 months corrected age (August 2013 to October 2017) using the Bayley Scales of Infant-Toddler Development, third edition.

Results: At discharge, 206 of the 230 study participants were eligible. At 12 and 24 months corrected age, 174 of 206 (85%) and 164 of 206 (80%) infants were evaluated. At 12 months, there was no significant difference in cognitive (mixed lipid: median, 95 [IQR, 85-101]; soybean oil: median, 95 [IQR, 85-100]; P = .71), language (mixed lipid: median, 86 [IQR, 77-94], soybean oil: median, 89 [IQR, 79-94]; P = .48), or motor scores (mixed lipid: median, 88 [IQR, 76-94], soybean oil: median, 88 [IQR, 79-94]; P = .69). At 24 months, there was again no significant difference in cognitive (mixed lipid: median, 95 [IQR, 80-105], soybean oil: median, 95 [IQR, 90-105]; P = .17), language (mixed lipid: median, 89 [IQR, 75-97], soybean oil 89 [IQR, 77-100]; P = .54), and motor scores (mixed lipid: median, 94 [IQR, 82-103], soybean oil: median, 94 [IQR, 85-103]; P = .53).

Conclusions: Parenteral nutrition using a mixed lipid emulsion containing fish oil did not improve neurodevelopment of extremely low birth weight infants at 12 and 24 months corrected age.

Trial Registration: ClinicalTrials.gov: NCT01585935.
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http://dx.doi.org/10.1016/j.jpeds.2020.06.056DOI Listing
June 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

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
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