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Background: Preterm infants are at risk for neurodevelopmental deficits. An association between retinopathy of prematurity (ROP) and impaired cognitive outcome has already been described. However, less is known about the impact of ROP on visual motor integration (VMI), which is a prerequisite not only for fine motor abilities but also for further school skills. Therefore, the aim of this study was to retrospectively investigate the impact of ROP on VMI at preschool age. Methods: The study was conducted at the Medical University of Vienna, including patients born between January 2009 and December 2014 with a gestational age of less than 30 weeks and/or a birth weight of less than 1,500 g. VMI was determined by Beery-Buktenica Developmental Test of Visual Motor Integration (Beery VMI) at the age of 5 years. Results: Out of 1,365 patients, 353 met inclusion criteria for this study. Two hundred sixteen of them had no ROP, while 137 had ROP (stage 1: n = 23, stage 2: n = 74, stage 3: n = 40). Mean value of the Beery VMI score was significantly lower in the ROP group compared to the No-ROP group (90 ± 16 vs. 99 ± 14; p < 0.01). By correcting for other important medical conditions, ROP still had a significant impact on Beery VMI score (p < 0.01). Particularly, lower scores were found for stage 2 (p < 0.01) and stage 3 (p < 0.01). Conclusion: Beery VMI scores were significantly lower in preterm infants with ROP stage 2 and 3 than in infants without ROP. This study shows the negative impact of ROP on VMI skills at preschool age, even after adjustment for key demographic and medical characteristics.

Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of “European Guidelines for the Management of RDS” by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12, 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS).

Introduction: Preterm birth and cerebral hemorrhage have adverse effects on brain development. Alterations in regional brain size on magnetic resonance imaging (MRI) can be assessed using 2D biometrical analysis, an easily applicable technique showing good correlation with 3D brain volumes. Methods: This retrospective study included 74 preterm neonates with intraventricular hemorrhage (IVH) born +0 weeks of gestation between 2011 and 2019. Cerebral MRI was performed at term-equivalent age, and 2D measurement techniques were used for biometrical analysis and compared to normative data of two control groups. Finally, the correlation and association of brain parameters and patterns of impaired brain growth and outcome at 2 and 3 years of age were evaluated. Results: Interhemispheric distance (IHD), the 3rd ventricle, and lateral ventricles presented larger, in contrast, cerebral biparietal width (cBPW), fronto-occipital diameter (FOD), and the length of the corpus callosum were smaller in IVH patients compared to respective controls. The strongest correlations with outcome were observed for the parameters FOD, anteroposterior diameter of the vermis, transverse cerebellar diameter (tCD), corpus callosum, 3rd ventricle, and left ventricular index. Patients with the small FOD, small BPW, and increased IHD pattern reached overall lower outcome scores at follow-up. Discussion: Preterm neonates with IVH showed reduced total brain sizes and enlarged pericerebral spaces compared to neurologically healthy controls. Biometric analysis revealed that several 2D brain parameters as well as different patterns of impaired brain growth were associated with neurodevelopmental impairment in early childhood. These findings may support prediction of long-term outcome and parental counseling in patients with IVH.

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.

Zusammenfassung Hintergrund Anfälle beim Neugeborenen sind in den allermeisten Fällen Symptom einer zugrunde liegenden neurologischen Störung im Sinne von „akut symptomatischen Anfällen“. Die Diagnose von neonatalen Anfällen erfolgt laut ILAE (International Liga Against Epilepsy) nur über die Elektroenzephalografie, und erst dann wird beschrieben, ob die Anfälle von klinischen Symptomen begleitet werden oder nicht. Somit hat sich in den letzten Jahren die vereinfachte Methode des amplitudenintegrierten EEGs (aEEG) als direkt am Krankenbett einsetzbare Methode zum Langzeitmonitoring als hilfreich erwiesen und stellt nicht nur eine „kompensatorische Maßnahme“ bis zur Verfügbarkeit eines konventionellen EEGs dar. Ziel der Arbeit In diesem Artikel wird der Einsatz des aEEGs bei neonatalen Anfällen diskutiert. Ergebnisse und Diskussion Zur genaueren Erfassung der „seizure burden“ (Anfallsdauer über einen definierten Zeitraum) und zur Therapiesteuerung stellt das aEEG neben dem konventionellen Video-EEG eine hilfreiche zusätzliche Methode dar. Die Dauer und Häufigkeit der Anfälle, die Hintergrundaktivität und die Erfahrung des Befunders spielen bei der Erkennung von Anfällen im aEEG eine entscheidende Rolle. Nur kurz dauernde, fokale oder sich nur wenig von der Grundaktivität unterscheidende Anfälle können weniger gut erfasst werden, wobei länger dauernde Anfälle, die sich regional ausbreiten von einem erfahrenen Befunder in bis zu 85 % auch mittels aEEG erkannt werden können. Da es zunehmend Daten gibt, dass die „seizure burden“ mit dem entwicklungsneurologischen Outcome korreliert, ist eine möglichst kontinuierliche elektrophysiologische Überwachung dieser Patienten anzustreben. Hier kann das aEEG einen wichtigen Beitrag leisten.

Aim Data evaluating mortality and morbidity in infants born ≤500g is scarce and shows wide variability. To support counselling and decision-making, we analysed neurodevelopmental outcome in all neonates ≤500g birth weight. Methods Retrospective analysis including preterm infants with a birth weight ≤500g and a gestational age >22 weeks born at a single tertiary perinatal centre between 2010 and 2017. Results Of 59 live births 88% received standard care. Birth weight ranged from 318 and 500g and gestational age from 23 and 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. Conclusion 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.

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 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.

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 (I2>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.

Klebermass-Schrehof Katrin, Thomas Waldhoer, and Lin Yang. The effect of altitude on birthweight/length ratio: a population-based study over 36 years in an altitude range from sea level to 1,700 m.

To describe cerebral abnormalities and their risk factors in a contemporary cohort of infants born extremely premature after the introduction of routine cerebral magnetic resonance imaging (cMRI) at term-equivalent age.All cMRI examinations performed during November 2017 and November 2020, based on a standardized neonatal cMRI protocol, were included into analysis. Pathologies were retrospectively classified into 3 categories: intraventricular hemorrhage (IVH), white matter disease, and cerebellar injuries.A total of 198 cMRI examinations were available for analyses; 93 (47%) showed abnormalities, most frequently IVH (n = 65, 33%), followed by cerebellar injuries (n = 41, 21%), and white matter disease (n = 28, 14%). Severe abnormalities were found in 18% of patients (n = 36). Significant clinical risk factors for abnormalities on cMRI were lower Apgar scores, lower umbilical artery and first neonatal pH, asphyxia, blood culture-proven sepsis (especially late-onset), and prolonged need of respiratory support and supplemental oxygen.After routine cMRI, without preconfirmed pathology by cranial ultrasonography, low-grade IVH, noncystic white matter disease, and cerebellar injuries were the most frequently found abnormalities. The clinical value and long-term benefit of the detection of these low-grade pathologies have yet to be confirmed.

ImportanceIntraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date.ObjectiveTo assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH.Design, Setting, and ParticipantsBetween April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age InterventionsInfants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life.Main Outcomes and MeasuresSecondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023).ResultsSixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9–28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores.Conclusions and RelevanceThis preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials.Trial RegistrationClinicalTrials.gov Identifier: NCT02076373

Objective To investigate whether monitoring of cerebral tissue oxygen saturation using near infrared spectroscopy in addition to routine monitoring combined with defined treatment guidelines during immediate transition and resuscitation increases survival without cerebral injury of premature infants compared with standard care alone. Design Multicentre, multinational, randomised controlled phase 3 trial. Setting 11 tertiary neonatal intensive care units in six countries in Europe and in Canada. Participants 1121 pregnant women ( Intervention Preterm neonates were randomly assigned to either standard care (control group) or standard care plus monitoring of cerebral oxygen saturation with a dedicated treatment guideline (near infrared spectroscopy group) during immediate transition (first 15 minutes after birth) and resuscitation. Main outcome measure The primary outcome, assessed using all cause mortality and serial cerebral ultrasonography, was a composite of survival without cerebral injury. Cerebral injury was defined as any intraventricular haemorrhage or cystic periventricular leukomalacia, or both, at term equivalent age or before discharge. Results Cerebral tissue oxygen saturation was similar in both groups. 252 (82.9%) out of 304 neonates (median gestational age 28.9 (interquartile range 26.9-30.6) weeks) in the near infrared spectroscopy group survived without cerebral injury compared with 238 (78.5%) out of 303 neonates (28.6 (26.6-30.6) weeks) in the control group (relative risk 1.06, 95% confidence interval 0.98 to 1.14). 28 neonates died (near infrared spectroscopy group 12 (4.0%) v control group 16 (5.3%): relative risk 0.75 (0.33 to 1.70). Conclusion Monitoring of cerebral tissue oxygen saturation in combination with dedicated interventions in preterm neonates ( Trial registration ClinicalTrials.gov NCT03166722 .

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

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. Electronic supplementary material The online version of this article (10.1007/s00330-019-06325-2) contains supplementary material, which is available to authorized users.

BACKGROUND AND PURPOSE: Preterm birth interferes with regular brain development. The aim of this study was to investigate the impact of prematurity on the physical tissue properties of the neonatal brain stem using a quantitative MR imaging approach. MATERIALS AND METHODS: A total of 55 neonates (extremely preterm [n = 30]

Humans are biologically endowed with the faculty of language. However, the way neonates can crack this complex communicative code is yet not totally understood. While phonetic discrimination has been widely investigated in neonates, less is known about the role of supra-segments patterns in the recognition of native language. Therefore, the aim of this study was to evaluate accent discrimination abilities in newborns in a sentential prosody paradigm. We used near-infared spectroscopy to investigate accent discrimination in 21 full-term born infants within the first days of life. Sentential prosody was used to investigate: (a) native accent, (b) foreign accent, and (c) flattened accent. Neonates revealed a significantly smaller hemodynamic response to native accent compared to flattened accent and foreign accent, respectively. Cluster-based permutation analysis revealed two clusters with a significant difference between the two conditions native accent and foreign accent. The first cluster covered the middle and superior frontal, middle and superior temporal, central, and parietal areas within the left hemisphere. The second cluster, located in the right hemisphere, covered inferior, middle, and superior frontal, central, middle and superior temporal areas. We therefore conclude that neonates can differentiate prosodic features like accents within the same language a few days after birth.

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. Electronic supplementary material The online version of this article (10.1007/s00330-018-5743-1) contains supplementary material, which is available to authorized users.

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. 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. 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. Provided that a certain maturational threshold is reached, extrauterine life appears to accelerate maturation of the visual system in preterm infants.

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.

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 n = 41 and S-LE: n = 35) with 344 VEP measurements (SMOF-LE: n= 191 and S-LE n = 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.

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 230/7-266/7 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 253/7 weeks (IQR, 244/7-260/7 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.

Minimally invasive, automated cot-side tools for monitoring early neurological development can be used to guide individual treatment and benchmark novel interventional studies. We develop an automated estimate of the EEG maturational age (EMA) for application to serial recordings in preterm infants. The EMA estimate was based on a combination of 23 computational features estimated from both the full EEG recording and a period of low EEG activity (46 features in total). The combination function (support vector regression) was trained using 101 serial EEG recordings from 39 preterm infants with a gestational age less than 28 weeks and normal neurodevelopmental outcome at 12 months of age. EEG recordings were performed from 24 to 38 weeks post-menstrual age (PMA). The correlation between the EMA and the clinically determined PMA at the time of EEG recording was 0.936 (95%CI: 0.932–0.976; n = 39). All infants had an increase in EMA between the first and last EEG recording and 57/62 (92%) of repeated measures within an infant had an increasing EMA with PMA of EEG recording. The EMA is a surrogate measure of age that can accurately determine brain maturation in preterm infants.

ObjectiveA 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).MethodsWe 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.ResultsThe 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.InterpretationThe 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.

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.

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. Keywords: Near-infrared spectroscopy, Preterm birth, Newborn infants, Language development, Speech discrimination

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.

OBJECTIVE: To assess whether parenteral nutrition of extremely low birth weight infants using a mixed lipid emulsion that contains fish oil influences electrophysiological brain maturation. STUDY DESIGN: The study is a pre-specified secondary outcome analysis of a randomized controlled trial of 230 extremely low birth weight infants that received 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; 06/2012 to 10/2015). Electrophysiological brain maturation (background activity, sleep-wake cycling and brain maturational scores) was assessed bi-weekly 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) out of 230 infants of the core study were available for analysis. Demographic characteristics were not significantly different. Starting from 28 weeks postmenstrual age, infants receiving the intervention displayed significantly higher percentages of continuous background activity. Total maturational scores and individual scores for continuity, cycling and bandwidth were significantly higher. Maximum maturational scores were reached two weeks earlier in the intervention group (36.4 weeks, 35.4-37.5) compared to the control group (38.4 weeks, 37.1-42.4) (median, interquartile range; P

Several studies have shown a relation between the size of corpus callosum (CC) and outcome in preterm infants. Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging. To establish reference values for biometry of the CC in very low birth weight infants and to correlate these measurements to neurodevelopmental outcome at 5 years of age.Forty-three preterm infants with a gestational age32 weeks were included. Transfontanellar 3D-US measurements were obtained at nine different timepoints.3D-US-based reference values for size, length, circumference and surface area of the CC could be established. Measurements at term-equivalent age showed a correlation to neurodevelopment outcome.Reliable biometric data of the CC can be established in preterm infants by 3D-US and correlate with neurodevelopmental outcome.

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.

BackgroundThe agreement between invasive and non-invasive blood pressure (BP) readings in the first days of life of preterm infants is contentiously debated.ObjectiveTo 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.MethodsWe 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.ResultsAmong 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 30 mmHg (bias -5.5 mmHg).ConclusionThe 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.

Background: Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). Objectives: To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). Methods: The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. Results and Conclusions: The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair.

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 45 weeks 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. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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 the first reported case of thyrotoxicosis in a fetus/newborn from a woman with Hashimoto’s thyroiditis and levothyroxine-treated hypothyroidism. Transplacental passage of stimulating TSH-receptor antibodies, measured by a cell-based bioassay, was the underlying mechanism of fetal/neonatal thyrotoxicosis even though 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.

Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging.This prospective study aimed to determine whether 3D-US is appropriate to assess cortical development of the premature brain, and compare it to previously established reference values assessed by magnetic resonance imaging (MRI). Preterm infants with a gestational age (GA) of32 weeks were examined by serial 3D-US scans.Data of 30 patients with normal neurological development at the age of 5 years were included in the analysis. Cortical development was graded according to a five-point scoring system, and data were stratified into 6 age groups. Cortical developmental scores were established for various brain regions. In the frontal and frontoparietal regions, 3D-US reference values differed from published MRI reference values, but were consistent with the published data in all other regions.3D-US reference values facilitate routine diagnostics and enable the evaluation of cortical development in preterm infants.