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This systematic review and meta-analysis aimed to investigate the association of neonatal exposure to pain, stress, opiate administration alone, as well as opiate administration prior to a painful procedure on neuronal cell death, motor, and behavioral outcomes in rodents. In total, 36 studies investigating the effect of pain (n = 18), stress (n = 15), opiate administration (n = 13), as well as opiate administration prior to a painful event (n = 7) in rodents were included in our meta-analysis. The results showed a large effect of pain (g = 1.37, 95% CI 1.00-1.74, p .001) on neuronal cell death. Moreover, higher number of neonatal pain events were significantly associated with increased neuronal cell death, increased anxiety (b = -1.18, SE = 0.43, p = .006), and depressant-like behavior (b = 1.74, SE = 0.51, p = .027) in rodents. Both opiates and pain had no impact on motor function (g = 0.26, 95% CI 0.18-0.70, p = .248).

Background International guidelines recommend the use of item based scales for the assessment of pain and sedation. In our previous study, the implementation of the Neonatal Pain Agitation and Sedation Scale (N-PASS), and the associated systematic assessment and treatment of pain and sedation reduced pain and over-sedation in our intervention group, but lead to a significant increase of individual opiate exposure. This increased opiate exposure was not associated with impaired motor and mental development at one year of age. As one-year follow-up is not necessarily representative for future outcomes, we retested our sample at three years of age. Methods Fifty-three patients after (intervention group) and 61 before implementation (control group) of the N-PASS and the Vienna Protocol for the Management of Neonatal Pain and Sedation (VPNPS), were compared for motor, mental and behavioural development at three-years follow-up using the Bayley Scales of Infant Development. Results Cumulative opiate exposure was not associated with mental (p = .31) and motor (p = .20) problems when controlling for other important medical conditions, but was associated to lower behavioural scores (p = .007). No statistically significant differences were found with regard to mental (p = .65), psychomotor (p = .12) and behavioural (p = .61) development before and after the implementation of the N-PASS and the VPNPS. Conclusion Implementing a neonatal pain and sedation protocol increased opiate exposure without affecting neurodevelopmental outcome at three-years of age.

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.

Background Perioperative brain injury is common in infants undergoing cardiac surgery. Amplitude-integrated electroencephalography (aEEG) provides real-time neurologic monitoring and can identify seizures and abnormalities of background cerebral activity. We aimed to determine the incidence of perioperative electrical seizures, and to establish the background pattern of aEEG, in neonates undergoing Norwood-type palliations for complex congenital heart disease in relation to outcome at 2 years. Methods Thirty-nine full-term neonates undergoing Norwood-type operations underwent aEEG monitoring before and during surgery and for 72 hours postoperatively. The perfusion strategy included full-flow moderately hypothermic cardiopulmonary bypass with antegrade cerebral perfusion. Amplitude-integrated electroencephalography tracings were reviewed for seizure activity and background pattern. Survivors underwent neurodevelopmental outcome assessment using the Bayley Scales of Infant Development (3rd edition) at 2 years of age. Results Thirteen (33%) infants had electrical seizures, including 9 with intraoperative seizures and 7 with postoperative seizures. Seizures were associated with significantly increased mortality, but not with neurodevelopmental impairment in survivors. Delay in recovery of the aEEG background beyond 48 hours was also associated with increased mortality and worse motor development. Conclusions Perioperative seizures were common in this cohort. Intraoperative seizures predominantly affected the left hemisphere during antegrade cerebral perfusion. Delayed recovery in aEEG background was associated with increased risk of early mortality and worse motor development. Ongoing monitoring is essential to determine the longer-term significance of these findings.

Objective Intraventricular hemorrhage (IVH) is a significant cause of morbidity and mortality in premature infants. There is a well known correlation between IVH grade and outcome. However, only a few studies take into account the site of the lesion. The aim of the present study was to create a tool which could serve as a prognostic indicator with regard to the severity of brain damage and outcome by assessing the functional areas affected by the bleeding. Methods Infants with grade III IVH with and without parenchymal involvement who had MRI scans obtained and assessment of neurodevelopmental outcome were included into this analysis. MRIs were analyzed by the computation of a white matter (WMS), grey matter (GMS) and a combined MRI score (cS) which included the following functional areas and pathologies: WMS: Pyramidal tract, Corpus callosum, Radiatio optica and Crossroad. GMS: Gyrus precentralis and postcentralis, Hippocampus and Basal ganglia. cS was calculated by the sum of WMS and GMS. Further points were added in the presence of periventricular leukomalacia, hydrocephalus and for lesions in the Cerebellum. Neurodevelopmental outcome was evaluated at 1 and 2 years corrected age via Bayley Scales of Infant development and classified into 4 severity groups. Results Neonates with normal MDI and mild disability show significantly lower WMS, GMS and cS compared to infants with moderate/severe mental disability at 1 year corrected age. The same is true for PDI at 1 year corrected age for WMS, GMS and cS and 2 years corrected age for WMS and cS. Conclusion There is currently not much evidence with regard to the relevance of topography of injury when trying to predict outcome in preterm infants with IVH. The proposed score might serve as a prognostic tool with regard to the severity of brain damage and outcome in preterm infants with IVH.

Objective Hypoxic-ischemic encephalopathy (HIE) still is a major cause of neonatal mortality and morbidity. The amplitude-integrated electroencephalogram (aEEG) is reliable for prediction of outcome in asphyxiated neonates. Near-infrared spectroscopy (NIRS) offers the possibility to continuously monitor cerebral oxygen saturation. Only few data have been published on the combined use of NIRS and aEEG in neonates cooled for HIE. The aim of this study was to investigate the correlation between continuous aEEG and NIRS during the first days of life in HIE. Methods aEEG: Brain function was measured continuously immediately after the hypoxic event, during hypothermia, until the end of rewarming using a Olympic 6000 (Natus©). aEEG tracings were analysed for background patterns, appearance of sleep-wake cycling and the presence of seizure activity. Furthermore, a combined aEEG-score was calculated for the timeperiod before, during and after hypothermia. NIRS: Patients were monitored using NIRS (INVOS System by Covidien©) for the mentioned time period. Changes in regional cerebral oxygen saturation (rcSO2) were measured. Fractional tissue oxygen extraction (FTOE) was calculated for the entire duration of the measurement in order to investigate the balance between oxygen delivery and oxygen supply. Results A significant correlation coefficient (CorrC) was found between SWZ and rcSO2 post cooling (CorrC: 0.78) as well as FTOE during (CorrC: 0.69) and post cooling (CorrC: 0.95). Furthermore, a significant CorrC was found between the total aEEG score and rcSO2 post cooling (CorrC: 0.58) as well as FTOE during (CorrC: 0.61) and post cooling (CorrC: 0.79). Conclusion Our data show a significant correlation between continuous aEEG monitoring, which is a valuable and reliable method for prediction of neurodevelopmental outcome in neonates with HIE, and NIRS measurements. Therefore, we suggest that NIRS can serve as an additional prognostic tool in HIE.

Objective The amplitude-integrated EEG (aEEG) is becoming more important to monitor brain activity in premature infants. Studies have shown that early aEEGs correlate with later neurodevelopmental outcome. Various scoring systems for the assessment of aEEGs are being used, which complicates the comparison of published data. The aim of our study was to compare two scoring systems for aEEG and correlate with the neurodevelopmental outcome. Methods 114 preterm infants (gestational age (GA) Results Both total scores (p Conclusion Both scoring systems allow a simple classification of aEEGs. The Burdjalov score shows specific differences for the GA, while the aEEG sum score correlates better with the later outcome.

Objective The amplitude-integrated EEG (aEEG) is becoming more important to monitor brain activity in premature infants. Studies have shown that early aEEGs correlate with later neurodevelopmental outcome. Various scoring systems and missing gestational age related reference values for the aEEGs complicate the comparison of published data. The aim of our study was to establish gestational age related reference values for the aEEGs using the Burdjalov score in preterm infants Methods 114 preterm infants (gestational age (GA) Results The analysis of aEEGs showed increasing Total Burdjalov Scores at higher GA. The subscores (continuity (Co), cyclicity (Cy), amplitude of lower border (LB) and bandwidth span and amplitude of lower border (B)) also increased with increasing GA. Conclusion Gestational age related reference values for the Burdjalov Score were determined in preterm infants

Prenatal diagnosis of congenital toxoplasmosis (CT) influences therapeutical management in pregnant women and their offspring. In Austria, a nationwide serological healthcare program to identify potential maternal toxoplasma infections during pregnancy exists. We assessed the clinical use of amniocentesis for toxoplasma-specific polymerase chain reaction (PCR) on amniotic fluid to detect CT. Data on serology, amniocentesis, PCR, complications, treatment, and paediatric clinical outcome were collected retrospectively among the birth cohort 1992–2008. There were 1386 women with amniocentesis, but only in 707 cases (51%) was acute maternal infection confirmed serologically. A high proportion (49%) of amniocenteses with negative PCR results in women with chronic infection or seronegativity were performed without clinical justification for the women or their foetuses. The positive and negative predictive values of PCR were 94.4% and 99.3%, respectively. Thirty-nine foetuses with CT, including four deaths, were reported. The five PCR-negative but infected infants were identified by the serological and clinical follow-up program. Thirty percent of amniocenteses were performed in the third trimester, and gestational age or treatment did not influence PCR sensitivity. Amniocentesis is indicated in women with acute maternal infection, and facilitated targeted therapies in pregnant women and their offspring. In women with late toxoplasma infection, negative amniotic fluid PCR made treatment of infants unnecessary. Serological and clinical follow-up of infants is important to confirm the infection status of the infant. Recommendations, based on our 17-year experience, to improve the current diagnostic strategies and to reduce unnecessary amniocentesis, are given.