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.

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.

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.

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).