Publications by authors named "Katharina Goeral"

24 Publications

  • Page 1 of 1

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

A novel magnetic resonance imaging-based scoring system to predict outcome in neonates born preterm with intraventricular haemorrhage.

Dev Med Child Neurol 2022 05 28;64(5):608-617. Epub 2021 Nov 28.

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

Aim: To create a magnetic resonance imaging (MRI)-based scoring system specific to neonates born preterm with intraventricular haemorrhage (IVH), which could serve as a reliable prognostic indicator for later development and might allow for improved outcome prediction, individually-tailored parental counselling, and clinical decision-making.

Method: This retrospective, two-center observational cohort study included 103 infants born preterm with IVH (61 males, 42 females; median gestational age 26wks 6d), born between 2000 and 2016. Term-equivalent MRI was evaluated using a novel scoring system consisting of 11 items. A total MRI score was calculated and correlated with neurodevelopment between 2 years and 3 years of age. Prediction models for outcome were defined.

Results: The proposed MRI scoring system showed high correlation and strong predictive ability with regard to later cognitive and motor outcome. The prediction models were translated into easy-to-use tables, allowing developmental risk assessment.

Interpretation: The proposed MRI-based scoring system was created especially for infants born preterm with IVH and enables a comprehensive assessment of important brain areas as well as potential additional abnormalities commonly associated with IVH. Thus, it better represents the severity of brain damage when compared with the conventional IVH classification. Our scoring system should provide clinicians with valuable information, to optimize parental counselling and clinical decision-making.
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http://dx.doi.org/10.1111/dmcn.15116DOI Listing
May 2022

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

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

J Pediatr 2021 Nov 29;238:110-117.e2. 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
November 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 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

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

Pediatr Res 2022 01 2;91(1):64-69. 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
January 2022

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

Validity of SyMRI for Assessment of the Neonatal Brain.

Clin Neuroradiol 2021 Jun 11;31(2):315-323. Epub 2020 Mar 11.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Purpose: The purpose of this study was to assess the diagnostic accuracy of T1-weighted and T2-weighted contrasts generated by the MR data postprocessing software SyMRI (Synthetic MR AB, Linköping, Sweden) for neonatal brain imaging.

Methods: In this study 36 cases of neonatal MRI were retrospectively collected, which included T1-weighted and T2-weighted sequences as well as multi-dynamic multi-echo (MDME) sequences. Of the 36 neonates 32 were included in this study and 4 neuroradiologists independently assessed neonatal brain examinations on the basis of conventional and SyMRI-generated T1-weighted and T2-weighted contrasts, in order to determine the presence or absence of lesions. The sensitivity and specificity of both methods were calculated and compared.

Results: Compared to conventionally acquired T1 and T2-weighted images, SyMRI-generated contrasts showed a lower sensitivity but a higher specificity (SyMRI sensitivity 0.88, confidence interval (CI): 0.72-0.95; specificity 1, CI: 0.89-1/conventional MRI: sensitivity: 0.94, CI: 0.80-0.98; specificity: 0.94, CI: 0.80-0.98).

Conclusion: The T1-weighted and T2-weighted images generated by SyMRI showed a diagnostic accuracy comparable to that of conventionally acquired contrasts. In addition to semiquantitative imaging data, SyMRI provides diagnostic images and leads to a more efficient use of available imaging time in neonatal brain MRI.
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http://dx.doi.org/10.1007/s00062-020-00894-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211598PMC
June 2021

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

SyMRI detects delayed myelination in preterm neonates.

Eur Radiol 2019 Dec 8;29(12):7063-7072. Epub 2019 Jul 8.

Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Objectives: The software "SyMRI" generates different MR contrasts and characterizes tissue properties based on a single acquisition of a multi-dynamic multi-echo (MDME)-FLAIR sequence. The aim of this study was to assess the applicability of "SyMRI" in the assessment of myelination in preterm and term-born neonates. Furthermore, "SyMRI" was compared with conventional MRI.

Methods: A total of 30 preterm and term-born neonates were examined at term-equivalent age using a standardized MRI protocol. MDME sequence (acquisition time, 5 min, 24 s)-based post-processing was performed using "SyMRI". Myelination was assessed by scoring seven brain regions on quantitative T1-/T2-maps, generated by "SyMRI" and on standard T1-/T2-weighted images, acquired separately. Analysis of covariance (ANCOVA) (covariate, gestational age (GA) at MRI (GAMRI)) was used for group comparison.

Results: In 25/30 patients (83.3%) (18 preterm and seven term-born neonates), "SyMRI" acquisitions were successfully performed. "SyMRI"-based myelination scores were significantly lower in preterm compared with term-born neonates (ANCOVA: T1: F(1, 22) = 7.420, p = 0.012; T2: F(1, 22) = 5.658, p = 0.026). "SyMRI"-based myelination scores positively correlated with GAMRI (T1: r = 0.662, n = 25, p ≤ 0.001; T2: r = 0.676, n = 25, p ≤ 0.001). The myelination scores based on standard MRI did not correlate with the GAMRI. No significant differences between preterm and term-born neonates were detectable.

Conclusions: "SyMRI" is a highly promising MR technique for neonatal brain imaging. "SyMRI" is superior to conventional MR sequences in the visual detection of delayed myelination in preterm neonates.

Key Points: • By providing multiple MR contrasts, "SyMRI" is a time-saving method in neonatal brain imaging. • Differences concerning the myelination in term-born and preterm infants are visually detectable on T1-/T2-weighted maps generated by "SyMRI". • "SyMRI" allows a faster and more sensitive assessment of myelination compared with standard MR sequences.
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http://dx.doi.org/10.1007/s00330-019-06325-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828642PMC
December 2019

Vaginal Ureaplasma parvum serovars and spontaneous preterm birth.

Am J Obstet Gynecol 2019 06 5;220(6):594.e1-594.e9. Epub 2019 Feb 5.

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

Background: Ureaplasma species (spp) are the bacteria most often isolated from the amniotic cavity of women with preterm labor or preterm premature rupture of membranes; thus, the link between intrauterine Ureaplasma spp infection and adverse pregnancy outcome clearly is established. However, because vaginal Ureaplasma spp colonization is very common in pregnant women, the reason that these microorganisms cause ascending infections in some cases but remain asymptomatic in most pregnancies is not clear. Previous studies suggested an association between vaginal colonization with Ureaplasma parvum as opposed to U urealyticum and preterm delivery. However, because of the high frequency of vaginal Ureaplasma spp colonization during pregnancy, additional risk factors are needed to select a group of women who might benefit from treatment.

Objective: To further identify pregnant women who are at increased risk for preterm delivery, the aim of the present study was to investigate U parvum serovar-specific pathogenicity in a large clinical cohort.

Study Design: We serotyped 1316 samples that were positive for U parvum using a high-resolution melt polymerase chain reaction assay, and results were correlated with pregnancy outcome.

Results: Within U parvum positive samples, serovar 3 was the most common isolate (43.3%), followed by serovar 6 (31.4%) and serovar 1 (25.2%). There was a significantly increased risk for spontaneous preterm birth at very low (<32 weeks gestation; P<.005) and extremely low (<28 weeks gestation; P<.005) gestational age in the group with vaginal U parvum serovar 3 colonization compared with the control group of pregnant women who tested negative for vaginal Ureaplasma spp colonization. This association was found for neither serovar 1 nor serovar 6. The combination of vaginal U parvum serovar 3 colonization and diagnosis of bacterial vaginosis in early pregnancy or a history of preterm birth further increased the risk for adverse pregnancy outcome.

Conclusion: Colonization with U parvum serovar 3, but not serovar 1 or serovar 6, in early pregnancy is associated with preterm delivery at very and extremely low gestational age. The combination of U parvum serovar 3 colonization and a history of preterm birth or bacterial vaginosis further increases the risk for spontaneous preterm birth at low gestational age and may define a target group for therapeutic intervention studies.
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http://dx.doi.org/10.1016/j.ajog.2019.01.237DOI Listing
June 2019

Effects of Feedback on Chest Compression Quality: A Randomized Simulation Study.

Pediatrics 2019 02;143(2)

Divisions of Neonatology, Pediatric Intensive Care, and Neuropediatrics, and.

Objectives: Our aim for this study was to test whether visual and verbal feedback compared with instructor-led feedback improve the quality of pediatric cardiopulmonary resuscitation (CPR).

Methods: There were 653 third-year medical students randomly assigned to practice pediatric CPR on 1 of 2 manikins (infant and adolescent; = 344 and = 309, respectively). They were further randomly assigned to 1 of 3 feedback groups: The instructor feedback (IF) group ( = 225) received traditional, instructor-led feedback without any additional feedback device. The device feedback (DF) group ( = 223) received real-time visual feedback from a feedback device. The instructor and device feedback (IDF) group ( = 205) received verbal feedback from an instructor who continuously reviewed the trainees' performance using the feedback device. After the training, participants' CPR performance was assessed on the same manikin while no feedback was being provided.

Results: For the primary outcome of total compression score, participants in the DF and IDF groups performed similarly, with both groups showing scores significantly ( < .001) better than those of the IF group. The same findings held for correct hand position and the proportion of complete release. For compression rate, the DF group was at the higher end of the guideline for 100 to 120 chest compressions per minute compared with the IF and IDF groups (both < .001). No effect of feedback on compression depth was found.

Conclusions: Chest compression performance significantly improved with both visual and verbal feedback compared with instructor-led feedback. Feedback devices should be implemented during pediatric resuscitation training to improve resuscitation performance.
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http://dx.doi.org/10.1542/peds.2018-2441DOI Listing
February 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

Microvessel ultrasound of neonatal brain parenchyma: feasibility, reproducibility, and normal imaging features by superb microvascular imaging (SMI).

Eur Radiol 2019 Apr 9;29(4):2127-2136. Epub 2018 Oct 9.

Department of Biomedical Imaging and Image-Guided Therapy, Division of General and Pediatric Radiology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Objectives: To evaluate the feasibility and reproducibility of superb microvascular imaging (SMI) of the neonatal brain and to describe normal imaging features.

Methods: We performed transcranial ultrasound with SMI in 19 healthy term-born neonates. SMI was done according to a structured examination protocol, using two linear 18 MHz and 14 MHz transducers. Superficial and deep scans were acquired in the coronal and sagittal planes, using the left and right superior frontal gyri as anatomical landmarks. All SMI views were imaged by monochrome and colour SMI and evaluated with respect to visibility of extrastriatal (i.e. cortical and medullary) and striatal microvessels.

Results: We have described normal morphologic features of intraparenchymal brain microvasculature as "short parallel" cortical vessels, "smoothly curved" medullary vessels, and deep striatal vessels. In general, SMI performance was better on coronal views than on sagittal views. On superficial coronal scans, cortical microvessels were identifiable in 90-100%, medullary microvessels in 95-100%. On deep scans, cortical and medullary microvessels were visible in all cases, while striatal microvessels were identifiable in 71% of cases.

Conclusions: Cerebral SMI ultrasound is feasible and well-reproducible and provides a novel non-invasive imaging tool for the assessment of intraparenchymal brain microvasculature (extrastriatal and striatal microvessels) in neonates without the use of contrast.

Key Points: • Superb microvascular imaging (SMI) of the neonatal brain is feasible and reproducible. • SMI depicts extrastriatal and striatal microvessels. • SMI detects two types of extrastriatal microvessels: cortical and medullary.
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http://dx.doi.org/10.1007/s00330-018-5743-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420458PMC
April 2019

Review of Routes to Administer Medication During Prolonged Neonatal Resuscitation.

Pediatr Crit Care Med 2018 04;19(4):332-338

Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Alberta Health Services, Canada.

Objective: During neonatal cardiopulmonary resuscitation, early establishment of vascular access is crucial. We aimed to review current evidence regarding different routes for the administration of medications during neonatal resuscitation.

Data Sources: We reviewed PubMed, EMBASE, and Google Scholar using MeSH terms "catheterization," "umbilical cord," "delivery room," "catecholamine," "resuscitation," "simulation," "newborn," "infant," "intraosseous," "umbilical vein catheter," "access," "intubation," and "endotracheal."

Study Selection: Articles in all languages were included. Initially, we aimed to identify only neonatal studies and limited the search to randomized controlled trials.

Data Extraction: Due to a lack of available studies, studies in children and adults, as well as animal studies and also nonrandomized studies were included.

Data Synthesis: No randomized controlled trials comparing intraosseous access versus peripheral intravascular access versus umbilical venous catheter versus endotracheal tube versus laryngeal mask airway or any combination of these during neonatal resuscitation in the delivery room were identified. Endotracheal tube: endotracheal tube epinephrine administration should be limited to situations were no vascular access can be established. Laryngeal mask airway: animal studies suggest that a higher dose of epinephrine for endotracheal tube and laryngeal mask airway is required compared with IV administration, potentially increasing side effects. Umbilical venous catheter: European resuscitation guidelines propose the placement of a centrally positioned umbilical venous catheter during neonatal cardiopulmonary resuscitation; intraosseous access: case series reported successful and quick intraosseous access placement in newborn infants. Peripheral intravascular access: median time for peripheral intravascular access insertion was 4-5 minutes in previous studies.

Conclusions: Based on animal studies, endotracheal tube administration of medications requires a higher dose than that by peripheral intravascular access or umbilical venous catheter. Epinephrine via laryngeal mask airway is feasible as a noninvasive alternative approach for drug delivery. Intraosseous access should be considered in situations with difficulty in establishing other access. Randomized controlled clinical trials in neonates are required to compare all access possibilities described above.
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http://dx.doi.org/10.1097/PCC.0000000000001493DOI Listing
April 2018

First Trimester Vaginal Ureaplasma Biovar Colonization and Preterm Birth: Results of a Prospective Multicenter Study.

Neonatology 2018 22;113(1):1-6. Epub 2017 Sep 22.

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

Background: While there is a proven association of upper genital tract Ureaplasma infection during pregnancy with adverse pregnancy outcome, the effect of vaginal Ureaplasma colonization on preterm delivery has been controversially debated.

Objectives: We hypothesized that women with isolation of vaginal U. parvum but not U. urealyticum are at increased risk for spontaneous preterm birth (SPB) compared to women with negative results.

Methods: A vaginal swab taken between 12 and 14 weeks of gestation was analyzed for the presence of Ureaplasma biovars by PCR in 4,330 pregnant women.

Results: Of the study cohort, 37% were positive for U. parvum, 5.9% for U. urealyticum, and 3.1% for both. The rates of SPB were 10.4% (OR 1.7, 95% CI 1.3, 2.2, p < 0.001) and 8.9% (OR 1.4, 95% CI 0.9, 2.3, p = 0.193) in the groups with isolation of U. parvum and U. urealyticum, respectively, compared to 6.4% in the group with negative PCR results. Multiple logistic regression and interaction analyses showed that vaginal colonization with U. parvum but not U. urealyticum was a statistically significant risk factor for SPB (adjusted OR 1.6, 95% CI 1.2, 2.1, p < 0.001), independent of other risk factors such as bacterial vaginosis and history of SPB.

Conclusion: Our study demonstrates a statistically significant and independent association between first-trimester vaginal colonization with U. parvum and subsequent SPB.
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http://dx.doi.org/10.1159/000480065DOI Listing
August 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

Student peer teaching in paediatric simulation training is a feasible low-cost alternative for education.

Acta Paediatr 2017 Jun 19;106(6):995-1000. Epub 2017 Mar 19.

Division of Neonatology, Paediatric Intensive Care and Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.

Aim: The World Health Organization recommends regular simulation training to prevent adverse healthcare events. We used specially trained medical students to provide paediatric simulation training to their peers and assessed feasibility, cost and confidence of students who attended the courses.

Methods: Students at the Medical University of Vienna, Austria were eligible to participate. Students attended two high-fidelity simulation training sessions, delivered by peers, which were videorecorded for evaluation. The attendees then completed questionnaires before and after the training. Associated costs and potential benefits were analysed.

Results: From May 2013 to June 2015, 152 students attended the sessions and 57 (37.5%) completed both questionnaires. Satisfaction was high, with 95% stating their peer tutor was competent and 90% saying that peer tutors were well prepared. The attendees' confidence in treating critically ill children significantly improved after training (p < 0.001). The average costs for a peer tutor were six Euros per working hour, compared to 35 Euros for a physician.

Conclusion: Using peer tutors for paediatric simulation training was a feasible and low-cost option that increased the number of medical students who could be trained and increased the self-confidence of the attendees. Satisfaction with the peer tutors was high.
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http://dx.doi.org/10.1111/apa.13792DOI Listing
June 2017

Diffusion Tensor Imaging Abnormalities in the Cerebral White Matter Correlate with Sex-Dependent Neurobehavioral Deficits in Adult Mice with Neonatal Ischemia.

Dev Neurosci 2016 16;38(2):83-95. Epub 2016 Mar 16.

Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, Md., USA.

Background: Neonatal white matter injury (NWMI) is the leading cause of cerebral palsy in prematurely born children. In order to develop a test bed for therapeutics, we recently reported a mouse model of NWMI by using a modified Rice-Vannucci model of neonatal ischemia on postnatal day 5 (P5) in CD-1 mice. We have previously shown that these mice illustrate initial neuroinflammation and oligodendroglial differentiation arrest followed by long-term dysmyelination, periventricular astrogliosis and axonal injury, resembling human NWMI. The objective of this study was to determine the sex-dependent long-term effects of neonatal brain injury on neurobehavioral and advanced in vivo neuroimaging indices in this mouse model, and to correlate these variables with histopathology.

Methods: After right common artery ligation on P5, in vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed on ligated and control animals at 4 and 8 weeks. Common sets of regions of interest were used to compare fractional anisotropy (FA) values between ischemic and control mice. Behavioral testing (open field, startle response and grip strength) was performed at adult age. Finally, the animals were sacrificed for immunohistochemical (IHC) assessment of major white matter tracts.

Results: DTI revealed significant sex-dependent changes in FA values ipsi- and contralateral to the ligation. Behavioral testing showed decreased reaction to acoustic stimuli in males but not females. Similarly, increased number of rearings and lack of novelty-induced habituation in the open field were encountered only in the male subgroup. Several regional correlations were found between FA values and these behavioral alterations. IHC studies revealed degeneration of mature oligodendrocytes and damage of white matter tracts in ligated animals, as previously reported in this model, and showed regional correlation with in vivo FA values and behavioral alterations.

Conclusions: Our findings suggest structural sex-dependent long-term abnormalities after neonatal ischemia. These changes lead to behavioral deficits resembling common problems of patients with cerebral palsy.
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http://dx.doi.org/10.1159/000442943DOI Listing
December 2017

Ischemia-induced neuroinflammation is associated with disrupted development of oligodendrocyte progenitors in a model of periventricular leukomalacia.

Dev Neurosci 2013 27;35(2-3):182-96. Epub 2013 Feb 27.

The Hugo W. Moser Research Institute at Kennedy Krieger Institute, Baltimore, MD 21205, USA.

Microglial activation in crossing white matter tracts is a hallmark of noncystic periventricular leukomalacia (PVL), the leading pathology underlying cerebral palsy in prematurely born infants. Recent studies indicate that neuroinflammation within an early time window can produce long-lasting defects in oligodendroglial maturation, myelination deficit, as well as disruption of transcription factors important in oligodendroglial maturation. We recently reported an ischemic mouse model of PVL, induced by unilateral neonatal carotid artery ligation, leading to selective long-lasting bilateral myelination deficits, ipsilateral thinning of the corpus callosum, ventriculomegaly, as well as evidence of axonopathy. Here, we report that permanent unilateral carotid ligation on postnatal day 5 in CD-1 mice induces an inflammatory response, as defined by microglial activation and recruitment, as well as significant changes in cytokine expression (increased IL-1β, IL-6, TGF-β1, and TNF-α) following ischemia. Transient reduction in counts of oligodendrocyte progenitor cells (OPCs) at 24 and 48 h after ischemia, a shift in OPC cell size and morphology towards the more immature form, as well as likely migration of OPCs were found. These OPC changes were topographically associated with areas showing microglial activation, and OPC counts negatively correlated with increased microglial staining. The presented data show a striking neuroinflammatory response in an ischemia-induced model of PVL, associated with oligodendroglial injury. Future studies modulating the neuroinflammatory response in this model may contribute to a better understanding of the interaction between microglia and OPCs in PVL and open opportunities for future therapies.
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http://dx.doi.org/10.1159/000346682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3764456PMC
March 2014
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