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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.

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 Medical-imaging-based three-dimensional (3D) printed models enable improvement in skills training, surgical planning, and decision-making. This pilot study aimed to use multimodality imaging and to add and compare 3D ultrasound as a future standard to develop realistic neonatal brain models including the ventricular system. METHODS Retrospective computed tomography (CT), magnetic resonance imaging (MRI), and 3D ultrasound-based brain imaging protocols of five neonatal patients were analyzed and subsequently segmented with the aim of developing a multimodality imaging-based 3D printed model. The ventricular anatomy was analyzed to compare the MRI and 3D ultrasound modalities. RESULTS A realistic anatomical model of the neonatal brain, including the ventricular system, was created using MRI and 3D ultrasound data from one patient. T2-weighted isovoxel 3D MRI sequences were found to have better resolution and accuracy than 2D sequences. The surface area, anatomy, and volume of the lateral ventricles derived from both MRI and 3D ultrasound were comparable. CONCLUSIONS We created an ultrasound- and MRI-based 3D printed patient-specific neonatal brain simulation model that can be used for perioperative management. To introduce 3D ultrasound as a standard for 3D models, additional dimensional correlations between MRI and ultrasound need to be examined. IMPACT We studied the feasibility of implementing 3D ultrasound as a standard for 3D printed models of the neonatal brain. Different imaging modalities were compared and both 3D isotropic MRI and 3D ultrasound imaging are feasible for printing neonatal brain models with good dimensional accuracy and anatomical replication. Further dimensional correlations need to be defined to implement it as a standard to produce 3D printed models.

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.

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.

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]

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.

OBJECTIVE During neonatal cardiopulmonary resuscitation, early establishment of vascular access is crucial. We aimed to review current evidence regarding different routes for the administration of medications during neonatal resuscitation. DATA SOURCES We reviewed PubMed, EMBASE, and Google Scholar using MeSH terms "catheterization," "umbilical cord," "delivery room," "catecholamine," "resuscitation," "simulation," "newborn," "infant," "intraosseous," "umbilical vein catheter," "access," "intubation," and "endotracheal." STUDY SELECTION Articles in all languages were included. Initially, we aimed to identify only neonatal studies and limited the search to randomized controlled trials. DATA EXTRACTION Due to a lack of available studies, studies in children and adults, as well as animal studies and also nonrandomized studies were included. DATA SYNTHESIS No randomized controlled trials comparing intraosseous access versus peripheral intravascular access versus umbilical venous catheter versus endotracheal tube versus laryngeal mask airway or any combination of these during neonatal resuscitation in the delivery room were identified. Endotracheal tube: endotracheal tube epinephrine administration should be limited to situations were no vascular access can be established. Laryngeal mask airway: animal studies suggest that a higher dose of epinephrine for endotracheal tube and laryngeal mask airway is required compared with IV administration, potentially increasing side effects. Umbilical venous catheter: European resuscitation guidelines propose the placement of a centrally positioned umbilical venous catheter during neonatal cardiopulmonary resuscitation; intraosseous access: case series reported successful and quick intraosseous access placement in newborn infants. Peripheral intravascular access: median time for peripheral intravascular access insertion was 4-5 minutes in previous studies. CONCLUSIONS Based on animal studies, endotracheal tube administration of medications requires a higher dose than that by peripheral intravascular access or umbilical venous catheter. Epinephrine via laryngeal mask airway is feasible as a noninvasive alternative approach for drug delivery. Intraosseous access should be considered in situations with difficulty in establishing other access. Randomized controlled clinical trials in neonates are required to compare all access possibilities described above.

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.

Background: While there is a proven association of upper genital tract Ureaplasma infection during pregnancy with adverse pregnancy outcome, the effect of vaginal Ureaplasma colonization on preterm delivery has been controversially debated. Objectives: We hypothesized that women with isolation of vaginal U. parvum but not U. urealyticum are at increased risk for spontaneous preterm birth (SPB) compared to women with negative results. Methods: A vaginal swab taken between 12 and 14 weeks of gestation was analyzed for the presence of Ureaplasma biovars by PCR in 4,330 pregnant women. Results: Of the study cohort, 37% were positive for U. parvum, 5.9% for U. urealyticum, and 3.1% for both. The rates of SPB were 10.4% (OR 1.7, 95% CI 1.3, 2.2, p < 0.001) and 8.9% (OR 1.4, 95% CI 0.9, 2.3, p = 0.193) in the groups with isolation of U. parvum and U. urealyticum, respectively, compared to 6.4% in the group with negative PCR results. Multiple logistic regression and interaction analyses showed that vaginal colonization with U. parvum but not U. urealyticum was a statistically significant risk factor for SPB (adjusted OR 1.6, 95% CI 1.2, 2.1, p < 0.001), independent of other risk factors such as bacterial vaginosis and history of SPB. Conclusion: Our study demonstrates a statistically significant and independent association between first-trimester vaginal colonization with U. parvum and subsequent SPB.

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 video recorded 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

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.

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.

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.

Background: Neonatal white matter injury (NWMI) is the leading cause of cerebral palsy in prematurely born children. In order to develop a test bed for therapeutics, we recently reported a mouse model of NWMI by using a modified Rice-Vannucci model of neonatal ischemia on postnatal day 5 (P5) in CD-1 mice. We have previously shown that these mice illustrate initial neuroinflammation and oligodendroglial differentiation arrest followed by long-term dysmyelination, periventricular astrogliosis and axonal injury, resembling human NWMI. The objective of this study was to determine the sex-dependent long-term effects of neonatal brain injury on neurobehavioral and advanced in vivo neuroimaging indices in this mouse model, and to correlate these variables with histopathology. Methods: After right common artery ligation on P5, in vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed on ligated and control animals at 4 and 8 weeks. Common sets of regions of interest were used to compare fractional anisotropy (FA) values between ischemic and control mice. Behavioral testing (open field, startle response and grip strength) was performed at adult age. Finally, the animals were sacrificed for immunohistochemical (IHC) assessment of major white matter tracts. Results: DTI revealed significant sex-dependent changes in FA values ipsi- and contralateral to the ligation. Behavioral testing showed decreased reaction to acoustic stimuli in males but not females. Similarly, increased number of rearings and lack of novelty-induced habituation in the open field were encountered only in the male subgroup. Several regional correlations were found between FA values and these behavioral alterations. IHC studies revealed degeneration of mature oligodendrocytes and damage of white matter tracts in ligated animals, as previously reported in this model, and showed regional correlation with in vivo FA values and behavioral alterations. Conclusions: Our findings suggest structural sex-dependent long-term abnormalities after neonatal ischemia. These changes lead to behavioral deficits resembling common problems of patients with cerebral palsy.

Ureaplasma species (spp) are the bacteria most often isolated from the amniotic cavity of women with preterm labor or preterm premature rupture of membranes; thus, the link between intrauterine Ureaplasma spp infection and adverse pregnancy outcome clearly is established. However, because vaginal Ureaplasma spp colonization is very common in pregnant women, the reason that these microorganisms cause ascending infections in some cases but remain asymptomatic in most pregnancies is not clear. Previous studies suggested an association between vaginal colonization with Ureaplasma parvum as opposed to U urealyticum and preterm delivery. However, because of the high frequency of vaginal Ureaplasma spp colonization during pregnancy, additional risk factors are needed to select a group of women who might benefit from treatment.To further identify pregnant women who are at increased risk for preterm delivery, the aim of the present study was to investigate U parvum serovar-specific pathogenicity in a large clinical cohort.We serotyped 1316 samples that were positive for U parvum using a high-resolution melt polymerase chain reaction assay, and results were correlated with pregnancy outcome.Within U parvum positive samples, serovar 3 was the most common isolate (43.3%), followed by serovar 6 (31.4%) and serovar 1 (25.2%). There was a significantly increased risk for spontaneous preterm birth at very low (32 weeks gestation; P.005) and extremely low (28 weeks gestation; P.005) gestational age in the group with vaginal U parvum serovar 3 colonization compared with the control group of pregnant women who tested negative for vaginal Ureaplasma spp colonization. This association was found for neither serovar 1 nor serovar 6. The combination of vaginal U parvum serovar 3 colonization and diagnosis of bacterial vaginosis in early pregnancy or a history of preterm birth further increased the risk for adverse pregnancy outcome.Colonization with U parvum serovar 3, but not serovar 1 or serovar 6, in early pregnancy is associated with preterm delivery at very and extremely low gestational age. The combination of U parvum serovar 3 colonization and a history of preterm birth or bacterial vaginosis further increases the risk for spontaneous preterm birth at low gestational age and may define a target group for therapeutic intervention studies.

Background Sedatives are essential drugs in every intensive care unit in order to ensure the patient's optimal level of comfort. Avoiding conditions of over- and under-sedation is a challenge in a neonatal intensive care setting. Drug administration could be optimized by the concomitant use of objective methods to assess the level of sedation. Aims We aimed to look at the ability of different methods (Neonatal Pain, Agitation and Sedation Scale, amplitude-integrated Electroencephalogram, and Bispectral Index), and their combination, in detecting different level of sedation. Methods Twenty-seven neonates among whom 17 were receiving sedatives with or without opiate analgesics were monitored using the Neonatal Pain, Agitation and Sedation Scale, the amplitude-integrated Electroencephalogram, and the Bispectral Index. According to the expert opinion of two trained neonatologists, patients were categorized into three groups: no, light, and deep sedation. Four hours of simultaneous assessment of the Neonatal Pain, Agitation and Sedation Scale scores, Burdjalov scores (to summarize the amplitude-integrated Electroencephalogram trace), and Bispectral Index values were considered for the comparative analysis across these groups. Results All three methods could differentiate patients who were not sedated from those who were deeply sedated: median score 12 and 9, respectively, (95% CI of difference = 1.99-5.99, P = 0.001) for the amplitude-integrated Electroencephalogram Burdjalov score; median 1 and -5, respectively, (95% CI of difference = 2.99-8.00, P = 0.001) for the Neonatal Pain, Agitation and Sedation Scale; and median 48 and 37, respectively, (CI of difference = 1.77-22.00, P = 0.043) for the Bispectral Index. However none of them, used alone, was able to differentiate light and deep sedation: median score 10 and 9, respectively, for the amplitude-integrated Electroencephalogram Burdjalov score; median -2 and -5, respectively, for the Neonatal Pain, Agitation and Sedation Scale; and median 48 and 37, respectively, for the Bispectral Index. Only the amplitude-integrated Electroencephalogram and the Neonatal Pain, Agitation and Sedation Scale were able to differentiate between the conditions of no sedation and light sedation. Also, according to the area under the curves values, the combination of the Neonatal Pain, Agitation and Sedation Scale with the Burdjalov score derived from the amplitude-integrated Electroencephalogram showed the best accuracy in differentiating light and deep sedation. Conclusion While none of the three methods alone was able to precisely differentiate between different levels of sedation, we suggest that using a combination of amplitude-integrated Electroencephalogram and Neonatal Pain, Agitation and Sedation Scale can be useful to distinguish between light and deep sedation in neonatal patients.

Neonatal brain injuries (NBIs) are important causes of motor and neurocognitive disabilities in children worldwide. This chapter discusses the most common types of NBIs in developed countries, namely neonatal encephalopathy associated with birth asphyxia in term infants, perinatal arterial ischemic stroke, perinatal white matter injury, and germinal matrix hemorrhage and neonatal hydrocephalus. Epidemiologic studies suggest that prenatal stressors, including intrauterine inflammation, maternal drug/toxin exposure, and placental pathologies are key players in the etiology of NBIs, whereas genetic contributors are yet to be identified. Hypothermia has become a standard neuroprotective strategy in neonatal encephalopathy, and novel therapeutics are currently being evaluated.

Background and PurposeSerum neurofilament light chain (sNfL) has recently emerged as a promising biomarker reflecting structural neuro-axonal damage in different neurological diseases. Our study aimed at assessing whether sNfL can predict the functional outcome in preterm infants who suffered from neonatal haemorrhagic brain injury.MethodsIn this prospective observational study, we used an ultrasensitive single-molecule array assay to measure serum and cerebrospinal fluid (CSF) concentrations of NfL in preterm infants diagnosed with intraventricular haemorrhage (IVH) in the first few days of life. We determined the temporal profile of serum and CSF NfL levels from first diagnosis of IVH until term equivalent age, their association with cerebral imaging markers, and with clinical and functional outcome until 2 years of age assessed by Bayley Scales of Infant Development. We fitted univariable and multivariable logistic regression models to determine risk factors for low motor and cognitive development. Longitudinal mixed effects models modelled NfL levels using cubic spline smoothers to track the trajectory over time.ResultsThe study included 48 infants born with less than 32 weeks of gestation. At the time point of IVH diagnosis, NfL median levels were 271.9 pg/mL (IQR 151.2–389.7), and strongly decreased until term equivalent age to 15.7 pg/mL (IQR 11.1–32.2). CSF values were 113-fold higher (IQR 40–211) than corresponding serum values. Additional cerebral infarction (n=23) but not post-haemorrhagic hydrocephalus with permanent external ventricular drainage (n=29) or other diseases independently determined sNfL levels. In multivariate logistic regression models, the only significant predictor of poor motor outcome at 2 years or death was sNfL level (p=0.02).There was a clear difference between the NfL trajectory for those with poor motor outcome at 1 year.ConclusionsThis study shows that early sNfL is an independent prognostic biomarker for motor functional outcome in preterm infants after IVH.Disclosure(s)Nothing to disclose

OBJECTIVES: Our aim for this study was to test whether visual and verbal feedback compared with instructor-led feedback improve the quality of pediatric cardiopulmonary resuscitation (CPR). METHODS: There were 653 third-year medical students randomly assigned to practice pediatric CPR on 1 of 2 manikins (infant and adolescent; n = 344 and n = 309, respectively). They were further randomly assigned to 1 of 3 feedback groups: The instructor feedback (IF) group (n = 225) received traditional, instructor-led feedback without any additional feedback device. The device feedback (DF) group (n = 223) received real-time visual feedback from a feedback device. The instructor and device feedback (IDF) group (n = 205) received verbal feedback from an instructor who continuously reviewed the trainees’ performance using the feedback device. After the training, participants’ CPR performance was assessed on the same manikin while no feedback was being provided. RESULTS: For the primary outcome of total compression score, participants in the DF and IDF groups performed similarly, with both groups showing scores significantly (P CONCLUSIONS: Chest compression performance significantly improved with both visual and verbal feedback compared with instructor-led feedback. Feedback devices should be implemented during pediatric resuscitation training to improve resuscitation performance.

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.

Background Intraventricular haemorrhage (IVH) is a significant cause of morbidity and mortality in premature infants. There is a well known correlation between IVH grade and neurodevelopmental outcome. However, to our knowledge, there are only a few studies taking into account the side of the lesion. Methods Data of 178 infants with grade III IVH with and without parenchymal involvement were retrospectively analysed. Diagnosis was based on cerebral ultrasound. 36% (n = 64) of neonates showed equal IVH severity on both brain sides, the remaining 64% (n = 114) had IVH severity which differed between the hemispheres (right > left, n = 53; left > right, n = 61). Neurodevelopmental outcome was evaluated at 2 years corrected age via Bayley Scales of Infant development II (BSID II). The data was corrected for influence of gestational age by multiple regression analyses. Results Mental Development Index (MDI) and Psychomotor Development Index (PDI) were compared between the groups and infants with a larger lesion within the right hemisphere showed statistically significant lower developmental scores at the age of two years (mean (median) ± SD for ‘right > left’ vs. ‘left > right’: MDI 64,2 (54,0) ± 19,6 vs. 78,8 (84,0) ± 17,6 [p = 0,047] and PDI 59,7 (56,5) ± 11,4 vs. 75,9(80,0) ± 17,1 [p = 0,021]). Conclusion Laterality of IVH has a significant influence on neurodevelopmental outcome in preterm infants. Further studies referring to outcome at school age based on more sophisticated imaging techniques are warranted.

Background The amplitude-integrated electroencephalogram (aEEG) is reliable for early prediction of outcome in asphyxiated neonates. Hypothermia influences the positive predictive value (PPV) of early aEEG delaying normalisation of background pattern. Methods Forty-one neonates with hypoxic ischaemic encephalopathy (HIE) Sarnat stage II (n = 24 normothermia (NT), n = 17 hypothermia (HT)) were included into analysis. Firstly aEEGs of the first 3 days (d) of life were analysed for both groups (background pattern, sleep-wake cycling and seizure activity; descriptive analysis and calculation of a combined aEEG-score). Secondly aEEG parameters were correlated with postnatal clinical parameters, severity of neuroimaging abnormalities and neurodevelopmental outcome. Finally, the PV of aEEGs was compared between the groups. Results The rate of pathological aEEGs on d1 showed no significant difference between the groups (pathological aEEG: 64% HT, 71% for NT). On d3, the rate was significantly lower in the HT group than in the NT group (18% HT, 57% for NT, p = 0.045). There was a significant difference in outcome: in the HT group 82% showed a normal outcome, compared to 43% in the NT group. The PPV of a combinded aEEG-score was higher on d1 in the HT group than in the NT group and increased in both groups from d1-d3. The lack of sleep-wake cycling in children treated with HT significantly correlated with severity of neuroimaging abnormalites (p = 0.05) and pathological outcome (p = 0.03). In contrast, there was no correlation between seizure activity and outcome. Conclusion Our results reflect published data, underlining the importance of aEEG as early outcome predictor in neonatal HIE.

Summary 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.