Publications by authors named "Katrin Klebermass-Schrehof"

35 Publications

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

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

Cell Host Microbe 2021 Sep 1. Epub 2021 Sep 1.

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
September 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

Bilateral lung transplantation during pregnancy after ECMO for influenza-A caused ARDS.

Am J Transplant 2021 Jul 31. Epub 2021 Jul 31.

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

Pregnant women with influenza-A have an increased risk of developing acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) can be used as salvage therapy, with lung transplantation as a therapeutic option. However, successful bilateral lung transplantation during pregnancy has never been reported before. We herein report the case of a 34-year-old primipara, who was diagnosed with ARDS caused by influenza-A-induced pneumonia at early gestation. After considering all possible therapeutic options and being fully dependent on VV-ECMO support, she underwent bilateral lung transplantation. The transplantation with intraoperative central VA-ECMO support was successfully performed with good recovery after an initial primary graft dysfunction. The pregnancy was prolonged until 29  gestational weeks. The newborn exhibited growth retardation and was initially stabilized, but later died due to severe, hypoxic respiratory failure and pulmonary hypertension. In conclusion, lung transplantation is a possible salvage therapy for patients with severe lung failure following ARDS during pregnancy. However, it places the mother and unborn child at risk. A multi-professional approach is warranted to diagnose and treat complications at an early stage.
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http://dx.doi.org/10.1111/ajt.16781DOI 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

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

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

Maternal altitude and risk of low birthweight: A systematic review and meta-analyses.

Placenta 2020 11 15;101:124-131. Epub 2020 Sep 15.

Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Previous studies conducted in high altitude regions showed that maternal altitude was associated with low birth weight. The effect size of birth weight reduction is inclusive with unknown effects due to preterm birth. We systematically reviewed the literature and synthesize evidence on associations between altitude elevation from sea level and birth weight.

Method: We searched MEDLINE/PubMed, Embase, Scopus, Web of Science, and Cochrane database, from inception to May 5, 2020 for studies that reported maternal altitude and birth weight. Bayesian multilevel effect models were employed to estimate the effect size on birth weight (and gestational age) associated with altitude. Bayesian multilevel effect models were employed to estimate the effect size on birth weight (and gestational age) associated with altitude.

Results: The systematic search identified 1020 articles, with 52 articles meeting the inclusion criteria providing 207 estimates for the association of altitude and birth weight (n = 4,428,563), and with 22 articles providing 71 estimates for gestational age (n = 2,149,627). A reduction in mean birth weight of 96.98 g was associated with every 1000 m increase in altitude across 52 studies. A statistically significant but numerically minimal effect of maternal altitude elevation was observed on the gestational age (0.3 days), corresponding to a negligible estimation of 5 g lower birth weight. A relatively high heterogeneity of between-study association (I>84.1%) and small study effect was found.

Conclusion: A clinically meaningful birth weight reduction was associated with maternal altitude elevation beginning from sea level. Future longitudinal studies are needed to elucidate the causal association and to understand the late effect of maternal altitude.
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http://dx.doi.org/10.1016/j.placenta.2020.09.010DOI Listing
November 2020

Reliability and accuracy of EEG interpretation for estimating age in preterm infants.

Ann Clin Transl Neurol 2020 09 7;7(9):1564-1573. Epub 2020 Aug 7.

BABA Center, Department of Clinical Neurophysiology, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Objectives: To determine the accuracy of, and agreement among, EEG and aEEG readers' estimation of maturity and a novel computational measure of functional brain age (FBA) in preterm infants.

Methods: Seven experts estimated the postmenstrual ages (PMA) in a cohort of recordings from preterm infants using cloud-based review software. The FBA was calculated using a machine learning-based algorithm. Error analysis was used to determine the accuracy of PMA assessments and intraclass correlation (ICC) was used to assess agreement between experts.

Results: EEG recordings from a PMA range 25 to 38 weeks were successfully interpreted. In 179 recordings from 62 infants interpreted by all human readers, there was moderate agreement between experts (aEEG ICC = 0.724; 95%CI:0.658-0.781 and EEG ICC = 0.517; 95%CI:0.311-0.664). In 149 recordings from 61 infants interpreted by all human readers and the FBA algorithm, random and systematic errors in visual interpretation of PMA were significantly higher than the computational FBA estimate. Tracking of maturation in individual infants showed stable FBA trajectories, but the trajectories of the experts' PMA estimate were more likely to be obscured by random errors. The accuracy of visual interpretation of PMA estimation was compromised by neurodevelopmental outcome for both aEEG and EEG review.

Interpretation: Visual assessment of infant maturity is possible from the EEG or aEEG, with an average of human experts providing the highest accuracy. Tracking PMA of individual infants was hampered by errors in experts' estimates. FBA provided the most accurate maturity assessment and has potential as a biomarker of early outcome.
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http://dx.doi.org/10.1002/acn3.51132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480927PMC
September 2020

Automated cot-side tracking of functional brain age in preterm infants.

Ann Clin Transl Neurol 2020 06 5;7(6):891-902. Epub 2020 May 5.

QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4006, Australia.

Objective: A major challenge in the care of preterm infants is the early identification of compromised neurological development. While several measures are routinely used to track anatomical growth, there is a striking lack of reliable and objective tools for tracking maturation of early brain function; a cornerstone of lifelong neurological health. We present a cot-side method for measuring the functional maturity of the newborn brain based on routinely available neurological monitoring with electroencephalography (EEG).

Methods: We used a dataset of 177 EEG recordings from 65 preterm infants to train a multivariable prediction of functional brain age (FBA) from EEG. The FBA was validated on an independent set of 99 EEG recordings from 42 preterm infants. The difference between FBA and postmenstrual age (PMA) was evaluated as a predictor for neurodevelopmental outcome.

Results: The FBA correlated strongly with the PMA of an infant, with a median prediction error of less than 1 week. Moreover, individual babies follow well-defined individual trajectories. The accuracy of the FBA applied to the validation set was statistically equivalent to the training set accuracy. In a subgroup of infants with repeated EEG recordings, a persistently negative predicted age difference was associated with poor neurodevelopmental outcome.

Interpretation: The FBA enables the tracking of functional neurodevelopment in preterm infants. This establishes proof of principle for growth charts for brain function, a new tool to assist clinical management and identify infants who will benefit most from early intervention.
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http://dx.doi.org/10.1002/acn3.51043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318094PMC
June 2020

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

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

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

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

Children born preterm are at higher risk to develop language deficits. Auditory speech discrimination deficits may be early signs for language developmental problems. The present study used functional near-infrared spectroscopy to investigate neural speech discrimination in 15 preterm infants at term-equivalent age compared to 15 full term neonates. The full term group revealed a significantly greater hemodynamic response to forward compared to backward speech within the left hemisphere extending from superior temporal to inferior parietal and middle and inferior frontal areas. In contrast, the preterm group did not show differences in their hemodynamic responses during forward versus backward speech, thus, they did not discriminate speech from non-speech. Groups differed significantly in their responses to forward speech, whereas they did not differ in their responses to backward speech. The significant differences between groups point to an altered development of the functional network underlying language acquisition in preterm infants as early as in term-equivalent age.
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http://dx.doi.org/10.1016/j.dcn.2019.100679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969359PMC
October 2019

Neonatal Seizures-Are We there Yet?

Neuropediatrics 2019 10 24;50(5):280-293. Epub 2019 Jul 24.

Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Ireland.

Neonatal seizures are the most prevalent and distinctive sign of neurologic dysfunction in early life and pose an immense challenge for clinicians. Improvements in neonatal care have increased the survival rate of extremely premature infants, considerably changing the spectrum of underlying etiologies, and instigating a gradual shift from mortality to morbidity. Recognizing neonatal seizures can be challenging due to variability in presentation but clinical features can often provide valuable clues about etiology. Yet, the majority of neonatal seizures are subclinical. Even though conventional electroencephalography (EEG) with simultaneous video detection of seizures still represents the diagnostic gold standard, continuous monitoring using a one- to two-channel amplitude-integrated EEG with concurrent unprocessed EEG can be crucial for early recognition and intervention. Furthermore, tremendous progress has been made in neuroimaging, and all infants with seizures should have a magnetic resonance imaging (MRI) to help identify the underlying etiology. While the majority of neonatal seizures are caused by hypoxic-ischemic events, stroke, hemorrhage, or infection, approximately 15% of patients will require more sophisticated algorithms for diagnostic workup, including metabolic and genetic screening. These recent developments have led to renew interest in the classification of neonatal seizures, which aim to help identify etiology and guide appropriate therapeutic and prognostic decisions. In this review, we outline recent progress made in the etiology, diagnosis, and treatment of neonatal seizures and highlight areas that deserve further research.
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http://dx.doi.org/10.1055/s-0039-1693149DOI Listing
October 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

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BMC Pediatr 2019 06 27;19(1):210. Epub 2019 Jun 27.

University Hospital Tuebingen, Calwerstr. 7, 72076, Tuebingen, Germany.

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia.

Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion.

Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia.

Trial Registration: NCT03162653, www.ClinicalTrials.gov , May 22, 2017.
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http://dx.doi.org/10.1186/s12887-019-1566-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595623PMC
June 2019

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Discrepancy between invasive and non-invasive blood pressure readings in extremely preterm infants in the first four weeks of life.

PLoS One 2018 28;13(12):e0209831. Epub 2018 Dec 28.

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

Background: The agreement between invasive and non-invasive blood pressure (BP) readings in the first days of life of preterm infants is contentiously debated.

Objective: To compare mean, systolic and diastolic invasive (IBP) and non-invasive BP (NBP) readings obtained during routine care in the first four weeks of life of extremely preterm infants.

Methods: We extracted pairs of IBP and NBP readings obtained from preterm infants born below 28 weeks of gestation from the local database. After exclusion of erroneous measurements, we investigated the repeated measures correlation and analyzed the agreement (bias) and precision adjusted for multiple measurements per individual.

Results: Among 335 pairs of IBP and NBP readings obtained from 128 patients, we found correlation coefficients >0.65 for mean, systolic and diastolic BP values. The bias for mean BP readings was -0.4 mmHg (SD 6.1), for systolic BP readings 6.2 mmHg (SD 8.1), and for diastolic BP readings -4.3 mmHg (SD 6.5). Overestimation of systolic IBP and underestimation of diastolic IBP by the non-invasive measurement were found both in the group with gestational age from 23 to 25.9 weeks and in the group with gestational age from 26 to 27.9 weeks. Systolic NBP readings tended to exceed invasive readings in the range <50 mmHg (bias 9.9 mmHg) whereas diastolic NBP readings were lower than invasive values particularly in the range >30 mmHg (bias -5.5 mmHg).

Conclusion: The disagreement between invasive and non-invasive BP readings in infants extends to the first four weeks of life. Biases differ for mean, systolic and diastolic BP values. Our observation implies that they may depend on the range of the blood pressure. Awareness of these biases and preemptive concomitant use of IBP and NPB readings may contribute to reducing over- or under-treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209831PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310249PMC
June 2019

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

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

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

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

Background: Extrauterine life is an important factor when considering brain maturation. Few studies have investigated the development of visual evoked potentials (VEP) in extremely preterm infants, and only a minority have taken into consideration the impact of extrauterine life. The aim of this study was to assess the normal maturation of VEP in infants born prior to 29 weeks gestational age (GA) and to explore the potential influence of extrauterine life.

Methods: VEP were prospectively recorded in extremely preterm infants, and principal peaks (N0, N1, P1, N2, P2, N3) were identified. The mean of peak-time and percentages of peak appearances were assessed for three GA groups (23/24, 25/26, 27/28 weeks) and four subgroups of increasing postnatal age (PNA), up to 8 weeks after birth.

Results: A total of 163 VEP recordings in 38 preterm infants were analyzed. With increasing GA at birth, peak-times decreased. When comparing infants with equal GA but longer extrauterine life, those with the highest PNA demonstrated the shortest VEP peak-times. However, this effect was less present in infants born prior to 25 weeks GA.

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

Five-country manikin study found that neonatologists preferred using the LISAcath rather than the Angiocath for less invasive surfactant administration.

Acta Paediatr 2018 05 25;107(5):780-783. Epub 2018 Jan 25.

Neonatology Division, CHU de Liège - CHR de la Citadelle, University of Liège, Liège, Belgium.

Aim: Less invasive surfactant administration (LISA) has been shown to decrease the risk of death and bronchopulmonary dysplasia in preterm neonates. The LISAcath is the first catheter to be specifically developed for LISA, and we compared the clinical impressions of neonatologists using the LISAcath and the commonly used Angiocath in a simulated setting.

Methods: This was a multinational, multicentre study, conducted in October 2016, which involved 39 neonatologists who were recruited by employees of the sponsor from large, well-recognised neonatal intensive care units across Europe. LISA was not the standard of care in these units in Austria, Belgium, Poland, Spain and the United Kingdom at the time of the study. After training, participants simulated LISA on a neonatal manikin, once with the LISAcath and once with Angiocath, then answered a 10-item questionnaire.

Results: The responses to nine of 10 questions showed that 67-95% of the respondents preferred the LISAcath to the Angiocath, with most of the remainder indicating no preference. The only exception was the luer connection question, with two-thirds expressing no preference. The LISAcath was considered potentially safer by 33 of 39 participants, with no votes for the Angiocath.

Conclusion: Overall, neonatologists preferred using the LISAcath rather than the Angiocath on a neonatal manikin.
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http://dx.doi.org/10.1111/apa.14214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947293PMC
May 2018

Are All Amplitude-Integrated Electroencephalogram Systems Equal?

Neonatology 2017 20;112(4):394-401. Epub 2017 Sep 20.

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

Background: Filter and peak detection algorithms implemented in amplitude-integrated electroencephalogram (aEEG) systems are not standardized. New aEEG systems are continuously enriching the market and clinicians are faced with different aEEG devices whose tracings may vary.

Objectives: The aim of this work was to determine the role of different aEEG systems on quantitative measurements of the aEEG.

Methods: In this observational study, a single-channel aEEG recording (Olympic CFM 6000) with corresponding EEG signal was obtained from 32 infants at a gestational age of 36-44 weeks. The signals were split into 334 episodes of 4 h. New aEEG tracings were generated using the NicoletOne Reader Software and aEEG emulations with varying filter profiles and peak detection settings. The aEEG amplitude margins and automated annotation of continuous normal voltage (CNV) were compared.

Results: The output of the Olympic and the NicoletOne systems are very similar but not identical; the Spearman rank correlations of the aEEG amplitude margins exceeded 0.9 and the differences in the lower and upper amplitude margins were 1.55 μV (SD 1.47) and -2.12 μV (SD 1.44) on average (n = 309), respectively. The aEEG emulation showed that the differences between the output of the Olympic and the NicoletOne system could be primarily ascribed to the peak detection algorithm. The differences in output can affect automated analyses with agreement rates in CNV detection of 76% (n = 32, positive) and 92% (n = 32, negative) when comparing the Olympic to the NicoletOne outputs.

Conclusions: Commercial aEEG systems have similar but not identical outputs. Care is advised when interpreting automated aEEG classifications across different devices.
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http://dx.doi.org/10.1159/000480008DOI Listing
July 2018

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

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

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

Background: Few data have been published on the combined use of amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS) for outcome prediction in neonates cooled for hypoxic-ischemic encephalopathy (HIE).

Objective: Our aim was to evaluate the predictive values and the most powerful predictive combinations of single aEEG and NIRS parameters and the respective cut-off values with regard to short-term outcomes in HIE II.

Methods: aEEG and NIRS were prospectively studied at the Medical University of Vienna in the first 102 h of life with regard to magnetic resonance imaging (MRI). Thirty-two neonates diagnosed with HIE II treated with hypothermia were investigated. The measurement period was divided into 6-h epochs. According to MRI, 2 outcome groups were defined and predictive values of aEEG parameters, regional cerebral oxygen saturation (rScO2), and the additional value of both methods combined were studied. Receiver operating curves (ROC) were obtained and area under the curve (AUC) values were calculated. ROC were then used to detect the optimal cut-off points, sensitivity, specificity, positive predictive values, and negative predictive values.

Results: At all time epochs, combined parameter scores were more predictive than single parameter scores. The highest AUC were observed between 18 and 60 h of cooling for the aEEG summation score (0.72-0.84) and for (background pattern + seizures) × rScO2 (0.79-0.85). At 42-60 h sensitivity was similar between those 2 scores (87.5-90.0%), but the addition of NIRS to aEEG led to an increase in specificity (from 52.4-59.1% to 72.7-90.5%).

Conclusions: In HIE II, aEEG and NIRS are important predictors of short-term outcome. The combination of both methods improves prognostication. The highest predictive abilities were observed between 18 and 60 h of cooling.
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http://dx.doi.org/10.1159/000468976DOI Listing
June 2018

Automated classification of neonatal sleep states using EEG.

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

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

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

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

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

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

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

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

Hemophagocytic lymphohistiocytosis triggered by Gaucher disease in a preterm neonate.

Pediatr Hematol Oncol 2016 Oct - Nov;33(7-8):462-467. Epub 2016 Dec 6.

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

Objective: To present the diagnostic workup in an extremely low birth weight infant patient with signs of both sepsis and hemophagocytosis.

Participants: A preterm infant presented with clinical and laboratory signs of early-onset sepsis including hepatosplenomegaly, thrombocytopenia, direct hyperbilirubinemia, and elevated liver enzymes.

Methods: Despite extensive septic workup, no underlying infection was detected. Additional hyperferritinemia and other elevated inflammatory parameters raised the suspicion of a primary or secondary hemophagocytic lymphohistiocytosis (HLH).

Results: However, further metabolic analysis yielded a positive result for Gaucher disease (GD) type 2, a rare, but possible trigger of HLH.

Conclusions: Our case shows that GD may lead to the picture of a secondary HLH and that a metabolic workup should always be performed in patients in whom primary HLH has been excluded.
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http://dx.doi.org/10.1080/08880018.2016.1234011DOI Listing
January 2018

Fetal/Neonatal Thyrotoxicosis in a Newborn From a Hypothyroid Woman With Hashimoto Thyroiditis.

J Clin Endocrinol Metab 2017 01;102(1):6-9

Clinical Division of Endocrinology and Metabolism, Department of Medicine III.

Context: Fetal/neonatal thyrotoxicosis is a rare but potentially life-threatening condition. It is most commonly observed in poorly controlled Graves disease during pregnancy.

Case Description: Here we describe a fetus/newborn patient with thyrotoxicosis who was born of a woman with Hashimoto thyroiditis and levothyroxine-treated hypothyroidism. Transplacental passage of stimulating thyrotropin (TSH) receptor antibodies, which were measured by a cell-based bioassay, was the underlying mechanism of fetal/neonatal thyrotoxicosis, although the mother had no history of hyperthyroidism.

Conclusion: Diagnosis and management of fetal hyperthyroidism can be challenging. TSH receptor antibody testing should be considered in pregnant women with any history of autoimmune thyroid disease and symptoms of fetal hyperthyroidism.
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http://dx.doi.org/10.1210/jc.2016-2999DOI Listing
January 2017

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

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

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

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

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

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

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

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

Preterm infants who later require duct ligation show different vital signs and pH in early postnatal life.

Acta Paediatr 2015 Jan 15;104(1):e7-e13. Epub 2014 Oct 15.

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

Aim: The study investigated early postnatal vital signs in very low birthweight (VLBW) infants who later developed patent ductus arteriosus (PDA). We hypothesised that the early postnatal course of vital signs and blood gas variables might differ between infants whose PDA closed spontaneously, those who responded to ibuprofen and those who later required PDA ligation.

Methods: We analysed computerised records of VLBW infants born <28 weeks of gestational age, including vital signs, arterial pH values and echocardiographic data from the first postnatal days.

Results: In total, 104 infants were included in the study. In the group of infants born <26 weeks of gestational age and requiring ibuprofen for PDA (n = 34), 12 infants ultimately required surgical ligation. Infants requiring ligation showed significantly lower oxygen saturation (p = 0.019), mean blood pressure (p = 0.034) and higher heart rate fluctuation ranges (p = 0.040) in the first five postnatal days than those who responded to ibuprofen. In multivariable logistic regression analysis, lower pH values in the first 48 h predicted the subsequent requirement for ligation independent of gestational age (p = 0.004).

Conclusion: Patients <26 weeks of gestational age requiring PDA ligation showed significant differences in the course of vital signs and pH during the first days of life.
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http://dx.doi.org/10.1111/apa.12814DOI Listing
January 2015

The plasma activities of lysosomal enzymes in infants with necrotizing enterocolitis: new promising class of biomarkers?

Clin Chim Acta 2015 Jan 6;438:279-83. Epub 2014 Sep 6.

Department of Pediatrics and Adolescent Medicine, Research Core Unit for Pediatric Biochemistry and Analytics, Medical University of Vienna, Waehringerguertel 18-20, 1090 Vienna, Austria.

Background: Intestinal ischemia plays a major role in the pathogenesis of necrotizing enterocolitis (NEC). The diagnosis of intestinal ischemia would be highly desirable, as it is impossible to achieve with the current diagnostic regimes. Preliminary data from an animal NEC model indicate a possible correlation between the plasma activity of the lysosomal enzyme beta-glucosidase and intestinal ischemia.

Methods: In this case-control study the plasma activities of six different lysosomal enzymes were detected by high-performance liquid-chromatography tandem mass-spectrometry in 15 infants with NEC and compared to 18 controls.

Results: The plasma activities of β-glucosidase (ABG), α-glucosidase (GAA), and galactocerebrosidase (GALC) were significantly higher in the NEC group compared with controls (ABG, p=0.009; GAA, p<0.001; GALC, p<0.001). GAA and GALC showed the highest diagnostic value with areas under the curve of 0.91 and 0.87.

Conclusions: We identified GAA and GALC as new promising biomarkers for gut wall integrity in infants with NEC, and report first results on the plasma activity of ABG. The present study supports the hypothesis that the plasma activity of ABG might serve as a marker of intestinal ischemia in NEC. The identification of intestinal ischemia could facilitate early discrimination of infants at risk for NEC from infants with benign gastrointestinal disorders.
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http://dx.doi.org/10.1016/j.cca.2014.08.043DOI Listing
January 2015
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