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.

Thermoregulation and golden hour practices in extremely preterm infants: an international survey.

BACKGROUND: Are thermoregulation and golden hour practices in extremely preterm (EP) infants comparable across the world? This study aims to describe these practices for EP infants based on the neonatal intensive care unit's (NICUs) geographic region, country's income status and the lowest gestational age (GA) of infants resuscitated. METHODS: The Director of each NICU was requested to complete the e-questionnaire between February 2019 and August 2021. RESULTS: We received 848 responses, from all geographic regions and resource settings. Variations in most thermoregulation and golden hour practices were observed. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission, and having local protocols were the most consistent practices (>75%). The odds for the following practices differed in NICUs resuscitating infants from 22 to 23 weeks GA compared to those resuscitating from 24 to 25 weeks: respiratory support during resuscitation and transport, use of polyethylene plastic wrap and servo-control mode, commencing ambient humidity >80% and presence of local protocols. CONCLUSION: Evidence-based practices on thermoregulation and golden hour stabilisation differed based on the unit's region, country's income status and the lowest GA of infants resuscitated. Future efforts should address reducing variation in practice and aligning practices with international guidelines. IMPACT: A wide variation in thermoregulation and golden hour practices exists depending on the income status, geographic region and lowest gestation age of infants resuscitated. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission and having local protocols were the most consistent practices. This study provides a comprehensive description of thermoregulation and golden hour practices to allow a global comparison in the delivery of best evidence-based practice. The findings of this survey highlight a need for reducing variation in practice and aligning practices with international guidelines for a comparable health care delivery.

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.

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.

"Every breath you take": evaluating sound levels and acoustic characteristics of various neonatal respiratory support and ventilation modalities.

Background: Early sensory experiences have a significant impact on the later life of preterm infants. The NICU soundscape is profoundly influenced by various modalities of respiratory support or ventilation, which are often mandatory early in the care. The incubator, believed to shield from external noise, is less effective against noise originating inside. The objective of this study was to evaluate the sound levels and characteristics of frequently used respiratory support and ventilation modalities, taking into consideration the developing auditory system of premature infants. Methods: To evaluate sound dynamics inside and outside an incubator during respiratory support/ventilation, experimental recordings were conducted at the Center for Pediatric Simulation Training of the Medical University Vienna. The ventilator used was a FABIAN HFOI®. Results: Jet CPAP (Continuous positive airway pressure), whether administered via mask or prongs, generates significantly higher sound levels compared to High-flow nasal cannula (HFNC) and to High-frequency oscillatory ventilation (HFOV) delivered through an endotracheal tube. Upon evaluating the sound spectrum of jet CPAP support, a spectral peak is observed within the frequency range of 4 to 8 kHz. Notably, this frequency band aligns with the range where the hearing threshold of preterm infants is at its most sensitive. Conclusion: Non-invasive HFNC and invasive HFOV generate lower sound levels compared to those produced by jet CPAP systems delivered via masks or prongs. Moreover, HFNC and HFOV show a reduced acoustic presence within the frequency range where the preterm infant's hearing is highly sensitive. Therefore, it is reasonable to speculate that the potential for auditory impairment might be more pronounced in preterm infants who require prolonged use of jet CPAP therapy during their time in the incubator.

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.

Global variation in skin injures and skincare practices in extremely preterm infants.

BACKGROUND: Globally, are skincare practices and skin injuries in extremely preterm infants comparable? This study describes skin injuries, variation in skincare practices and investigates any association between them. METHODS: A web-based survey was conducted between February 2019 and August 2021. Quantifying skin injuries and describing skincare practices in extremely preterm infants were the main outcomes. The association between skin injuries and skincare practices was established using binary multivariable logistic regression adjusted for regions. RESULTS: Responses from 848 neonatal intensive care units, representing all geographic regions and income status groups were received. Diaper dermatitis (331/840, 39%) and medical adhesive-related skin injuries (319/838, 38%) were the most common injuries. Following a local skincare guideline reduced skin injuries [medical adhesive-related injuries: adjusted odds ratios (aOR) = 0.63, 95% confidence interval (CI) = 0.45-0.88; perineal injuries: aOR = 0.66, 95% CI = 0.45-0.96; local skin infections: OR = 0.41, 95% CI = 0.26-0.65; chemical burns: OR = 0.46, 95% CI = 0.26-0.83; thermal burns: OR = 0.51, 95% CI = 0.27-0.96]. Performing skin assessments at least every four hours reduced skin injuries (abrasion: aOR = 0.48, 95% CI = 0.33-0.67; pressure: aOR = 0.51, 95% CI = 0.34-0.78; diaper dermatitis: aOR = 0.71, 95% CI = 0.51-0.99; perineal: aOR = 0.52, 95% CI = 0.36-0.75). Regional and resource settings-based variations in skin injuries and skincare practices were observed. CONCLUSIONS: Skin injuries were common in extremely preterm infants. Consistency in practice and improved surveillance appears to reduce the occurrence of these injuries. Better evidence regarding optimal practices is needed to reduce skin injuries and minimize practice variations.

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.

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.

Non-invasively Measured Venous Oxygen Saturation as Early Marker of Impaired Oxygen Delivery in Preterm Neonates.

INTRODUCTION: Adequate oxygen supply for preterm neonates may be defined through non-invasive measurement of venous oxygen saturation (SvO2) and fractional oxygen extraction using near-infrared spectroscopy (NIRS). We investigated whether there was a difference in peripheral muscle SvO2 (pSvO2) and peripheral fractional oxygen extraction (pFOE) in preterm neonates with early inflammation/infection compared to healthy subjects during the first 72 h after birth. MATERIALS AND METHODS: We retrospectively analyzed secondary outcome parameters of prospective observational studies, including preterm neonates at risk of infection in whom peripheral NIRS measurements were performed in combination with venous occlusions. Early neonatal inflammation/infection was diagnosed by clinical signs and laboratory parameters. Peripheral muscle tissue oxygenation index (pTOI) was measured using either NIRO 300 or NIRO 200-NX (both Hamamatsu Photonics, Japan) on the patients' lower legs. Using 20-s venous occlusions, pSvO2 and pFOE were calculated incorporating simultaneous measurements of arterial oxygen saturation (SpO2). RESULTS: We analyzed measurements from 226 preterm neonates (median gestational age 33.9 weeks), 64 (28.3%) of whom were diagnosed with early neonatal inflammation/infection. During the first 24 h after birth, pSvO2 (66.9% [62.6-69.2] vs. 69.4% [64.6-72.0]; p = 0.04) and pTOI (68.6% [65.3-71.9] vs. 71.7% [67.3-75.1]; p = 0.02) were lower in those neonates with inflammation/infection, while there was no such difference for measurements between 24-48 and 48-72 h. DISCUSSION: NIRS measurement of pSvO2 and pFOE is feasible and may be utilized for early detection of impaired peripheral oxygen delivery. As pTOI was also significantly lower, this parameter may serve as substitute for diminished regional oxygen supply.

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.