Acute impact of posthemorrhagic ventricular dilatation on cerebral oxygenation in preterm infants with intraventricular haemorrhage.

AIM: To assess the effect of ventricular decompression on cerebral oxygenation in preterm neonates with intraventricular haemorrhage (IVH) and posthemorrhagic ventricular dilatation (PHVD) using near-infrared spectroscopy (NIRS). METHODS: Fifty-three preterm neonates born <34 weeks' gestation between 2013 and 2023 with IVH and subsequent PHVD were prospectively included. Regional cerebral oxygen saturation (rScO2) as well as fractional cerebral tissue oxygen extraction (cFTOE) were analysed 2 weeks before and after ventricular decompression. RESULTS: Ventricular decompression was performed at 18 ± 6 days of life. Patients with repeated lumbar punctures prior to ventricular drainage showed consistently higher rScO2 and lower cFTOE levels 2 weeks before and after intervention compared to those without. Patients who underwent direct ventricular drainage showed an immediate increase in rScO2 levels on the day of the procedure. In patients who underwent prior lumbar punctures, ventricular decompression did not yield additional acute effects on cerebral oxygenation. CONCLUSION: Patients who underwent repeated lumbar punctures preceding ventricular drainage consistently maintained higher rScO2 and lower cFTOE levels during the study period. In these patients, ventricular decompression did not further affect cerebral oxygenation, as they already demonstrated improved cerebral hemodynamics, whereas an immediate improvement was observed in those without prior lumbar punctures.

Reference Ranges for Arterial Oxygen Saturation, Heart Rate, and Cerebral Oxygen Saturation during Immediate Postnatal Transition in Neonates Born Extremely or Very Preterm.

OBJECTIVE: To define percentile charts for arterial oxygen saturation (SpO2), heart rate (HR), and cerebral oxygen saturation (crSO2) during the first 15 minutes after birth in neonates born very or extremely preterm and with favorable outcome. STUDY DESIGN: We conducted a secondary-outcome analysis of neonates born preterm included in the Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth III (COSGOD III) trial with visible cerebral oximetry measurements and with favorable outcome, defined as survival without cerebral injuries until term age. We excluded infants with inflammatory morbidities within the first week after birth. SpO2 was obtained by pulse oximetry, and electrocardiogram or pulse oximetry were used for measurement of HR. crSO2 was assessed with near-infrared spectroscopy. Measurements were performed during the first 15 minutes after birth. Percentile charts (10th to 90th centile) were defined for each minute. RESULTS: A total of 207 neonates born preterm with a gestational age of 29.7 (23.9-31.9) weeks and a birth weight of 1200 (378-2320) g were eligible for analyses. The 10th percentile of SpO2 at minute 2, 5, 10, and 15 was 32%, 52%, 83%, and 85%, respectively. The 10th percentile of HR at minute 2, 5, 10, and 15 was 70, 109, 126, and 134 beats/min, respectively. The 10th percentile of crSO2 at minute 2, 5, 20, and 15 was 15%, 27%, 59%, and 63%, respectively. CONCLUSIONS: This study provides new centile charts for SpO2, HR, and crSO2 for neonates born extremely or very preterm with favorable outcome. Implementing these centiles in guiding interventions during the stabilization process after birth might help to more accurately target oxygenation during postnatal transition period.

Neurodevelopmental outcome in preterm infants with intraventricular hemorrhages: the potential of quantitative brainstem MRI.

OBJECTIVES: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. MATERIALS AND METHODS: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. RESULTS: Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. CONCLUSION: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

Maternal biomarkers in predicting neonatal sepsis after preterm premature rupture of membranes in preterm infants.

AIM: This retrospective cohort study aimed to assess the utility of maternal C-reactive protein (CRP) and leukocyte levels in predicting neonatal sepsis after preterm premature rupture of membranes (pPROM). METHODS: We conducted a retrospective cohort study (2009-2021), encompassing preterm infants born ≤29 + 6 weeks of gestation following pPROM. The primary outcome was early-onset neonatal sepsis within the initial 72 h of life. RESULTS: We analysed data from 706 patients with a median gestational age at pPROM of 25.1 weeks and a median gestational age at birth of 26.4 weeks. Overall survival rate was 86.1%, with 65.7% survival without severe morbidities. These rates were significantly worse in preterm infants with sepsis. Maternal CRP and leukocyte levels correlated significantly with neonatal infection markers and sepsis. However, their predictive values, correlation coefficients, and area under the curve values were generally low. Using maternal CRP ≥2 mg/dL to predict neonatal sepsis yielded a positive predictive value of 18.5%, negative predictive value of 91.5%, AUC of 0.589, 45.5% sensitivity, and 74.5% specificity. CONCLUSION: Maternal CRP and leukocyte levels were ineffective as a tool for predicting early-onset neonatal sepsis following early pPROM. Consequently, these biomarkers lack the reliability required for clinical decision-making in this context.

Quantitative Magnetic Resonance Imaging for Neurodevelopmental Outcome Prediction in Neonates Born Extremely Premature-An Exploratory Study.

PURPOSE: Neonates born at < 28 weeks of gestation are at risk for neurodevelopmental delay. The aim of this study was to identify quantitative MR-based metrics for the prediction of neurodevelopmental outcomes in extremely preterm neonates. METHODS: T1-/T2-relaxation times (T1R/T2R), ADC, and fractional anisotropy (FA) of the left/right posterior limb of the internal capsule (PLIC) and the brainstem were determined at term-equivalent ages in a sample of extremely preterm infants (n = 33). Scores for cognitive, language, and motor outcomes were collected at one year corrected-age. Pearson's correlation analyses detected relationships between quantitative measures and outcome data. Stepwise regression procedures identified imaging metrics to estimate neurodevelopmental outcomes. RESULTS: Cognitive outcomes correlated significantly with T2R (r = 0.412; p = 0.017) and ADC (r = -0.401; p = 0.021) (medulla oblongata). Furthermore, there were significant correlations between motor outcomes and T1R (pontine tegmentum (r = 0.346; p = 0.049), midbrain (r = 0.415; p = 0.016), right PLIC (r = 0.513; p = 0.002), and left PLIC (r = 0.504; p = 0.003)); T2R (right PLIC (r = 0.405; p = 0.019)); ADC (medulla oblongata (r = -0.408; p = 0.018) and pontine tegmentum (r = -0.414; p = 0.017)); and FA (pontine tegmentum (r = -0.352; p = 0.045)). T2R/ADC (medulla oblongata) (cognitive outcomes (R2 = 0.296; p = 0.037)) and T1R (right PLIC)/ADC (medulla oblongata) (motor outcomes (R2 = 0.405; p = 0.009)) revealed predictive potential for neurodevelopmental outcomes. CONCLUSION: There are relationships between relaxometry­/DTI-based metrics determined by neuroimaging near term and neurodevelopmental outcomes collected at one year of age. Both modalities bear prognostic potential for the prediction of cognitive and motor outcomes. Thus, quantitative MRI at term-equivalent ages represents a promising approach with which to estimate neurologic development in extremely preterm infants.

Intrauterine Detection of Ureaplasma Species after Vaginal Colonization in Pregnancy and Neonatal Outcome.

INTRODUCTION: Intrauterine infection with Ureaplasma species (U.spp.) is mostly a result of vaginal colonization with subsequent ascending infection and is associated with adverse pregnancy outcome. Little is known about rates and risk factors for ascending infection. Aim of the current study was to analyse the frequency of ascending U.spp. infection in vaginally colonized pregnant women delivering preterm and subsequent short- and long-term outcome of infants. METHODS: Women delivering ≤32 weeks of gestation with available data on vaginal U.spp. colonization in early pregnancy as well as amniotic and placental colonization screening during caesarean section were included. Neonatal short- and long-term outcome was analysed depending on vaginal and intrauterine colonization. RESULTS: Seventy-two women giving birth to 104 preterm infants were included. Intrauterine microbial invasion was found in 23/72 (31.9%) pregnancies. The most commonly detected organisms were U.spp. (52.2%), followed by E. coli (21.7%) and Enterococcus faecalis (17.4%). Intrauterine growth of U.spp. occurred exclusively after previous vaginal colonization in early pregnancy (42/72; 58.3%) and was found in 12/42 (28.6%) cases. Ascending U.spp. infection mainly occurred in pregnancies delivering <28 weeks after preterm rupture of membranes or preterm labour (9/17, 52.3%). Intrauterine detection of U.spp., but not vaginal colonization, was associated with a significantly higher rate of severe intraventricular haemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and unfavourable psychomotor outcome. CONCLUSION: Ascending U.spp. infection after previous vaginal colonization occurred in almost one-third of pregnancies delivering ≤32 weeks, with particularly high rates in those <28 weeks, and was associated with adverse outcome of preterm infants.

Magnetic Resonance Imaging-Based Reference Values for Two-Dimensional Quantitative Brain Metrics in a Cohort of Extremely Preterm Infants.

INTRODUCTION: Cerebral magnetic resonance imaging (cMRI) is an important diagnostic tool in neonatology. In addition to qualitative analysis, quantitative measurements may help identify infants with impaired brain growth. This study aimed to create reference values for brain metrics of various brain areas in neonates without major brain injuries born before 28 weeks of gestation. METHODS: This retrospective study analyzes cMRI imaging data of high-risk patients without severe brain pathologies at term-equivalent age, collected over 4 years since November 2017. Nineteen brain areas were measured, reference values created, and compared to published values from fetal and postnatal MRI. Furthermore, correlations between brain metrics and gestational age at birth were evaluated. RESULTS: A total of 174 cMRI examinations were available for analysis. Reference values including cut-offs for impaired brain growth were established for different gestational age groups. There was a significant correlation between gestational age at birth and larger "tissue" parameters, as well as smaller "fluid" parameters, including intracerebral and extracerebral spaces. DISCUSSION: With quantitative brain metrics infants with impaired brain growth might be detected earlier. Compared to preexisting reference values, these are the first of a contemporary collective of extremely preterm neonates without severe brain injuries. Measurements can be easily performed by radiologists as well as neonatologists without specialized equipment or computational expertise. CONCLUSION: Two-dimensional cMRI brain measurements at term-equivalent age represent an easy and reliable approach for the evaluation of brain size and growth in infants at high risk for neurodevelopmental impairment.

Brain Biometry Reveals Impaired Brain Growth in Preterm Neonates with Intraventricular Hemorrhage.

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 <32+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.

Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): multicentre randomised phase 3 clinical trial.

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 (<32 weeks' gestation) were screened prenatally. The primary outcome was analysed in 607 of 655 randomised preterm neonates: 304 neonates in the near infrared spectroscopy group and 303 in the control group. 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 (<32 weeks' gestation) during immediate transition and resuscitation after birth did not result in substantially higher survival without cerebral injury compared with standard care alone. Survival without cerebral injury increased by 4.3% but was not statistically significant. TRIAL REGISTRATION: ClinicalTrials.gov NCT03166722.

Regular lung recruitment maneuvers during high-frequency oscillatory ventilation in extremely preterm infants: a randomized controlled trial.

BACKGROUND: Lung recruitment maneuvers (LRMs) improve lung volume at initiation of high-frequency oscillatory ventilation (HFOV), but it is unclear when to repeat LRMs. We evaluated the efficiency of scheduled LRMs. METHODS: In a randomized controlled trial, extremely preterm infants on HFOV received either LRMs at 12-hour intervals and when clinically indicated (intervention) or only when clinically indicated (control). The primary outcome was the cumulative oxygen saturation index (OSI) over HFOV time, limited to 7 days. Additionally, LRMs were analyzed with respect to OSI improvement. RESULTS: Fifteen infants were included in each group. The mean (SD) postmenstrual age and weight at HFOV start were 23 + 6 (0 + 5) weeks and 650 (115) g in the intervention group and 24 + 4 (0 + 6) weeks (p = 0.03) and 615 (95) g (p = 0.38) in the control group. The mean (SD) cumulative OSI amounted to 4.95 (1.72) in the intervention versus 5.30 (2.08) in the control group (p = 0.61). The mean (SD) number of LRMs in 12 h was 1.3 (0.2) in the intervention versus 1.1 (0.5) in the control group (p = 0.13). Performing LRM when FiO2 > 0.6 resulted in a mean OSI reduction of 3.6. CONCLUSION: Regular versus clinically indicated LRMs were performed with equal frequency in preterm infants during HFOV, and consequently, no difference in lung volume was observed. LRMs seem to be most efficient at high FiO2. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04289324 (28/02/2020).

Vaginal Delivery Is Associated with Neurochemical Evidence of Increased Neuroaxonal Remodelling in Infants from the KUNO-Kids Health Study: Cross-Sectional Analysis.

AIM: Little is known about neonatal brain plasticity or the impact of birth mode on neurointegrity. As a reflection of neuroaxonal damage, the neuronal structural protein neurofilament light chain (NfL) has emerged as a highly specific biomarker. Our purpose was to test the hypothesis that vaginal delivery is associated with increased NfL in neonates. METHODS: NfL concentrations were measured using single-molecule array immunoassay in umbilical cord serum from healthy term neonates enrolled in the prospective KUNO-Kids Health Study. NfL values were investigated for independent influencing factors using linear and logistic models, followed by post hoc propensity score-matching. RESULTS: Of 665 neonates, n = 470 (70.7%) were delivered vaginally and n = 195 (29.3%) by cesarean section. Median serum NfL was significantly higher after vaginal delivery 14.4 pg/mL (11.6-18.5) compared to primary 7.5 pg/mL (6.1-8.9) and secondary cesarean delivery 9.3 pg/mL (7.5-12.0). Multivariable logistic regression models showed delivery mode and gestational age to be independently associated with NfL. Propensity score-matching analysis confirmed that assisted vaginal delivery generated higher NfL compared to vaginal (non-assisted), while lowest levels were associated with cesarean section. INTERPRETATION: Our data confirm the significant impact of birth mode on neonatal NfL levels. The persistence of these differences and their potential long-term impact have yet to be investigated.

Cardiopulmonary resuscitation of a very preterm infant using high-frequency oscillation ventilation.

We present a novel approach of ventilation, using high-frequency oscillation ventilation (HFOV), during neonatal cardiopulmonary resuscitation (CPR) of a very preterm neonate. This case report highlights the importance of adequate lung inflation, which is a current topic, with neonatal resuscitation guidelines recommending a coordinated 3:1 compression:ventilation ratio during CPR. Our patient, a female infant born at 30 weeks gestational age, weighing 970 g, appeared floppy and apneic following birth in the amniotic sac. Lungs were unfolded and white-out in an x-ray done during resuscitation. The aim was to open lungs effectively using HFOV, instead of positive pressure ventilation, which was used unsuccessfully until the 7th minute of life. Heart rate continuously dropped below 60/min 15 min after birth and chest compressions with asynchronous HFOV were started, adrenalin was administered three times and surfactant was instilled endotracheally twice. It was possible to stabilize the patient after 15 min of CPR, following return of spontaneous circulation. HFOV may have enabled an alternative and rescue option of ventilation during neonatal CPR in this case.

Routine Use of Cerebral Magnetic Resonance Imaging in Infants Born Extremely Preterm.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Outcome Prediction in Neonatal Hypoxic-Ischaemic Encephalopathy Using Neurophysiology and Neuroimaging.

OBJECTIVE: The aim of the study was to determine the predictive power of the combined use of neurophysiological (amplitude-integrated electroencephalography [aEEG], near-infrared spectroscopy [NIRS]) methods and neuroimaging (magnetic resonance imaging [MRI]) for long-term outcome prediction in neonates with hypoxic-ischaemic encephalopathy (HIE). STUDY DESIGN: Prospective cohort study of 56 patients with moderate to severe HIE and hypothermia treatment at the Medical University of Vienna between 2008 and 2020. aEEG and NIRS were recorded continuously over a period of >4 days (102 h) starting at the initiation of hypothermia treatment, MRI was performed at a median age of 8 days. Receiver operating characteristic curves and area under the curve were calculated to evaluate the prognostic ability of aEEG, NIRS, and MRI parameters for outcome assessed via Bayley Scales of Infant Development 3rd edition at 2 years of age. RESULTS: Combined aEEG and MRI parameters showed highest predictive power regarding long-term outcome. The highest area under the curve values (0.96-0.99) were obtained for aEEG (combination of background pattern and sleep-wake cycling) between 66 and 102 h after initiation of hypothermia in combination with MRI findings. NIRS parameters did not differ significantly between infants with favourable and adverse outcome. CONCLUSIONS: Combined aEEG and MRI parameter scores were more predictive than single parameter scores. No further improvement was observed when combining aEEG/MRI with NIRS data.

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

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.

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

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.

Association between Fat-Free Mass and Brain Size in Extremely Preterm Infants.

Postnatal growth restriction and deficits in fat-free mass are associated with impaired neurodevelopment. The optimal body composition to support normal brain growth and development remains unclear. This study investigated the association between body composition and brain size in preterm infants. We included 118 infants born <28 weeks of gestation between 2017-2021, who underwent body composition (fat-free mass (FFM) and fat mass (FM)) and cerebral magnetic resonance imaging to quantify brain size (cerebral biparietal diameter (cBPD), bone biparietal diameter (bBPD), interhemispheric distance (IHD), transverse cerebellar diameter (tCD)) at term-equivalent age. FFM Z-Score significantly correlated with higher cBPD Z-Score (rs = 0.69; p < 0.001), bBPD Z-Score (rs = 0.48; p < 0.001) and tCD Z-Score (rs = 0.30; p = 0.002); FM Z-Score significantly correlated with lower brain size (cBPD Z-Score (rs = -0.32; p < 0.001) and bBPD Z-Score (rs = -0.42; p < 0.001). In contrast weight (rs = 0.08), length (rs = -0.01) and head circumference Z-Score (rs = 0.14) did not. Linear regression model adjusted for important neonatal variables revealed that FFM Z-Score was independently and significantly associated with higher cBPD Z-Score (median 0.50, 95% CI: 0.59, 0.43; p < 0.001) and bBPD Z-Score (median 0.31, 95% CI: 0.42, 0.19; p < 0.001); FM Z-Score was independently and significantly associated with lower cBPD Z-Score (median -0.27, 95% CI: -0.42, -0.11; p < 0.001) and bBPD Z-Score (median -0.32, 95% CI: -0.45, -0.18; p < 0.001). Higher FFM Z-Score and lower FM Z-scores were significantly associated with larger brain size at term-equivalent age. These results indicate that early body composition might be a useful tool to evaluate and eventually optimize brain growth and neurodevelopment.

A Mixed-Lipid Emulsion Containing Fish Oil for the Parenteral Nutrition of Preterm Infants: No Impact on Visual Neuronal Conduction.

Fish oil is rich in omega-3 fatty acids and essential for neuronal myelination and maturation. The aim of this study was to investigate whether the use of a mixed-lipid emulsion composed of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF-LE) compared to a pure soybean oil-based lipid emulsion (S-LE) for parenteral nutrition had an impact on neuronal conduction in preterm infants. This study is a retrospective matched cohort study comparing preterm infants <1000 g who received SMOF-LE in comparison to S-LE for parenteral nutrition. Visual evoked potentials (VEPs) were assessed longitudinally from birth until discharge. The latencies of the evoked peaks N2 and P2 were analyzed. The analysis included 76 infants (SMOF-LE: 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.

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

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.