Neonatal somatic oxygenation and perfusion assessment using near-infrared spectroscopy : Part of the series on near-infrared spectroscopy by the European Society of Paediatric Research Special Interest Group "Near-Infrared Spectroscopy".

In this narrative review, we summarize the current knowledge and applications of somatic near-infrared spectroscopy (NIRS), with a focus on intestinal, renal, limb, and multi-site applications in neonates. Assessing somatic oxygenation at various body locations in neonates may aid in the understanding of underlying pathophysiology of organ injury. Considering cerebral autoregulation may be active to protect the brain during systemic circulatory failure, peripheral somatic oxygenation may potentially provide an early indication of neonatal cardiovascular failure and ultimate hypoxemic injury to vital organs including the brain. Certain intestinal oxygenation patterns appear to be associated with the onset and course of necrotizing enterocolitis, whereas impaired renal oxygenation may indicate the onset of acute kidney injury after various types of hypoxic events. Peripheral muscle oxygenation measured at a limb may be particularly effective in the early prediction of shock in neonates. Using multi-site NIRS may complement current approaches and clinical investigations to alert for neonatal tissue hypoxemia, and potentially even guide management. However, somatic NIRS has its inherent limitations in regard to accuracy. Interpretation of organ-specific values can also be challenging. Last, currently there are limited prospective intervention studies, and clinical benefits need to be examined further, after the clarification of critical threshold-values. IMPACT: The assessment of somatic oxygenation using NIRS may contribute to the prediction of specific diseases in hemodynamically challenged neonates. Furthermore, it may give early warning signs for impending cardiovascular failure, and impaired cerebral circulation and oxygenation. We present a comprehensive overview of the literature on applications of NIRS to various somatic areas, with a focus on its potential clinical applicability, including future research directions. This paper will enable prospective standardized studies, and multicenter collaboration to obtain statistical power, likely to advance the field.

Cardiac output calculation using the Liljestrand and Zander formula: is this method applicable during immediate transition after birth? - A post hoc analysis.

The transition from intrauterine to extrauterine life is a critical period for neonates. Assessing the cardiovascular transition during this period immediately after birth is crucial but challenging. The present study compares adjusted estimated cardiac output values calculated by the Liljestrand and Zander formula (COest/adj LaZ) with non-invasively measured cardiac output values (CO-bioimpedance) during immediate transition after birth. We performed a secondary outcome analysis of a prospective observational study in preterm and term neonates. Ten and 15 min after birth, arterial blood pressure and heart rate were assessed, and CO-bioimpedance was measured using electrical bioimpedance method (Aesculon monitor, Osypka, Germany). We calculated COest/adj LaZ and compared it to CO-bioimpedance. Further, we performed a correlation analysis. Thirty-two neonates with a median (IQR) gestational age of 37.0 (32.0-39.4) weeks were included. Mean ± SD CO-bioimpedance was 0.62 ± 0.15 l/min, and COest/adj LaZ was calculated to be 0.64 ± 0.10 l/min, whereby both correlated significantly (p = 0.025, r = 0.359) with each other.  Conclusion: The present study demonstrates high comparability of COest/adj LaZ and CO-bioimpedance in neonates during immediate transition after birth, suggesting that cardiac output can be derived in a cost-effective and feasible manner if other methods are not available. What is Known: • Echocardiography is considered the gold standard for non-invasive CO evaluation, but its feasibility during the immediate transition period is limited. What is New: • Non-invasive methods such as CO-bioimpedance for cardiac output (CO) measurement and the Liljestrand and Zander (LaZ) formula for estimating CO offer promising alternatives during the immediate transition period.

Acid base and metabolic parameters of the umbilical cord blood and cerebral oxygenation immediately after birth.

Objective: Aim was to investigate whether acid-base and metabolic parameters obtained from arterial umbilical cord blood affect cerebral oxygenation after birth in preterm neonates with respiratory support and in term neonates without respiratory support. Study design: This was a post-hoc analysis of secondary outcome parameters of a prospective observational study including preterm neonates with and term neonates without respiratory support. Non-asphyxiated neonates with cerebral oxygenation measured with near-infrared spectroscopy during the first 15 min and with blood gas analyses from arterial umbilical cord blood were included. Arterial oxygen saturation (SpO2) and heart rate (HR) were monitored with pulse oximetry. Potential correlations were investigated between acid-base and metabolic parameters (pH-value, bicarbonate, base-excess, and lactate) and crSO2/cFTOE 5 min after birth. Results: Seventy-seven neonates were included: 14 preterm neonates with respiratory support (mean gestational age [GA] 31.4 ± 4.1 weeks; mean birth weight [BW] 1,690 ± 640 g) and 63 term neonates without respiratory support (GA 38.7 ± 0.8 weeks; BW 3,258 ± 443 g). Mean crSO2 5 min after birth was 44.0% ± 24.2% in preterm and 62.2% ± 20.01% in term neonates. Mean cFTOE 5 min after birth was 0.46 ± 0.06 in preterm and 0.27 ± 0.19 in term neonates. In preterm neonates with respiratory support higher lactate was significantly associated with lower crSO2 and SpO2 and tended to be associated with higher cFTOE. In term neonates without respiratory support no significant correlations were found. Conclusion: In non-asphyxiated preterm neonates with respiratory support, lactate levels were negatively associated with crSO2 and SpO2, whereas in term neonates without respiratory support no associations were observed.

Coupling between Regional Oxygen Saturation of the Brain and Vital Signs during Immediate Transition after Birth.

INTRODUCTION: The primary aim was to analyze any coupling of heart rate (HR)/arterial oxygen saturation (SpO2) and regional cerebral oxygen saturation (rScO2) and regional cerebral fractional tissue oxygen extraction (cFTOE) during immediate transition after birth in term and preterm neonates to gain more insight into interactions. METHODS: The present study is a post hoc analysis of data from 106 neonates, obtained from a prospective, observational study. Measurements of HR, SpO2, rScO2, and cFTOE were performed during the first 15 min after birth. The linear and nonlinear correlation were computed between these parameters in a sliding window. The resulting coupling curves were clustered. After clustering, demographic data of the clusters were de-blinded and compared. RESULTS: Due to missing data, 58 out of 106 eligible patients were excluded. Two clusters were obtained: cluster 1 (N = 39) and cluster 2 (N = 9). SpO2 had linear and nonlinear correlations with rScO2 and cFTOE, whereby the correlations with rScO2 were more pronounced in cluster 2. HR-rScO2 and HR-cFTOE demonstrated a nonlinear correlation in both clusters, again being more pronounced in cluster 2, whereby linear correlations were mainly absent. After de-blinding, the demographic data revealed that the neonates in cluster 2 had significantly lower gestational age (mainly preterm) compared to cluster 1 (mainly term). DISCUSSION: Besides SpO2, also HR demonstrated a nonlinear correlation with rScO2 and cFTOE in term and preterm neonates during immediate transition after birth. In addition, the coupling of SpO2 and HR with cerebral oxygenation was more pronounced in neonates with a lower gestational age.

Chest compressions superimposed with sustained inflation during neonatal cardiopulmonary resuscitation: are we ready for a clinical trial?

Neonates requiring cardiopulmonary resuscitation (CPR) are at risk of mortality and neurodevelopmental injury. Poor outcomes following the need for chest compressions (CCs) in the delivery room prompt the critical need for improvements in resuscitation strategies. This article explores a technique of CPR which involves CCs with sustained inflation (CC+SI). Unique features of CC+SI include (1) improved tidal volume delivery, (2) passive ventilation during compressions, (3) uninterrupted compressions and (4) improved stability of cerebral blood flow during resuscitation. CC+SI has been shown in animal studies to have improved time to return of spontaneous circulation and reduced mortality without significant increase in markers of inflammation and injury in the lung and brain, compared with standard CPR. The mechanics of CCs, rate of compressions, ventilation strategies and compression-to-ventilation ratios are detailed here. A large randomised controlled trial comparing CC+SI versus the current 3:1 compression-to-ventilation ratio is needed, given the growing evidence of its potential benefits.

Physiological-based cord clamping stabilised cardiorespiratory parameters in very low birth weight infants.

AIM: We investigated the influence of physiological-based cord clamping (PBCC) on cardiorespiratory stability in very low birth weight (VLBW) infants during the first 72 h of life. METHODS: This retrospective study comprised VLBW infants born at <32 + 0 weeks of gestation and admitted to the neonatal intensive care unit of the Medical University of Graz, Austria, from December 2014 to April 2021. VLBW infants delivered with PBCC were matched by gestational age and birth weight to delayed cord clamping controls. The PBCC group was stabilised after birth with an intact cord. Routine monitoring parameters were compared between the groups. RESULTS: We included 54 VLBW infants. The mean gestational ages of the PBCC group and controls were 27.4 ± 1.9 versus 27.4 ± 1.8 weeks (p = 0.87), and the mean birth weights were 912 ± 288 versus 915 ± 285 g (p = 0.96), respectively. The mean cord clamping time was 191 ± 78 s in the PBCC group. Heart rate was lower in the PBCC group during the first 3 days after birth, reaching significance by 10 h. Other monitoring parameters did not reveal any differences between the two groups. CONCLUSION: PBCC stabilised cardiorespiratory parameters in VLBW infants. The lower heart rate in the PBCC group suggested higher blood volume following intact cord resuscitation.

Sustained inflation and chest compression versus 3:1 chest compression to ventilation ratio during cardiopulmonary resuscitation of asphyxiated newborns (SURV1VE): A cluster randomised controlled trial.

OBJECTIVE: In newborn infants requiring chest compression (CC) in the delivery room (DR) does continuous CC superimposed by a sustained inflation (CC+SI) compared with a 3:1 compression:ventilation (3:1 C:V) ratio decreases time to return of spontaneous circulation (ROSC). DESIGN: International, multicenter, prospective, cluster cross-over randomised trial. SETTING: DR in four hospitals in Canada and Austria, PARTICIPANTS: Newborn infants >28 weeks' gestation who required CC. INTERVENTIONS: Hospitals were randomised to CC+SI or 3:1 C:V then crossed over to the other intervention. MAIN OUTCOME MEASURE: The primary outcome was time to ROSC, defined as the duration of CC until an increase in heart rate >60/min determined by auscultation of the heart, which was maintained for 60 s. Sample size of 218 infants (109/group) was sufficient to detect a clinically important 33% reduction (282 vs 420 s of CC) in time to ROSC. Analysis was intention-to-treat. RESULTS: Patient recruitment occurred between 19 October 2017 and 22 September 2022 and randomised 27 infants (CC+SI (n=12), 3:1 C:V (n=15), two (one per group) declined consent). All 11 infants in the CC+SI group and 12/14 infants in the 3:1 C:V group achieved ROSC in the DR. The median (IQR) time to ROSC was 90 (60-270) s and 615 (174-780) s (p=0.0502 (log rank), p=0.16 (cox proportional hazards regression)) with CC+SI and 3:1 C:V, respectively. Mortality was 2/11 (18.2%) with CC+SI versus 8/14 (57.1%) with 3:1 C:V (p=0.10 (Fisher's exact test), OR (95% CI) 0.17; (0.03 to 1.07)). The trial was stopped due to issues with ethics approval and securing trial insurance as well as funding reasons. CONCLUSION: The time to ROSC and mortality was not statistical different between CC+SI and 3:1 C:V. TRIAL REGISTRATION: NCT02858583.

Precision and normal values of cerebral blood volume in preterm neonates using time-resolved near-infrared spectroscopy.

AIM: To investigate cerebral blood volume (CBV) in preterm neonates using time-resolved near-infrared spectroscopy. METHODS: In this prospective observational study, time-resolved near-infrared spectroscopy measurements of CBV using tNIRS-1 were performed in 70 preterm neonates. For measurements, a sensor was placed for a duration of 1 min, followed by four further reapplications of the sensor, overall five measurements. RESULTS: In this study, 70 preterm neonates with a mean ± SD gestational age of 33.4 ± 1.7 weeks and a birthweight of 1931 ± 398 g were included with a postnatal age of 4.7 ± 2.0 days. Altogether, 2383 CBV values were obtained with an overall mean of 1.85 ± 0.30 mL/100 g brain. A total of 95% of the measured CBV values varied in a range from -0.31 to 0.33 from the overall individual mean. Taking the deviation of the mean of each single application for each patient, this range reduced from -0.07 to 0.07. The precision of the measurement defined as within-variation in CBV was 0.24 mL/100 g brain. CONCLUSION: The overall mean CBV in stable preterm neonates was 1.85 ± 0.30 mL/100 g brain. The within-variation in CBV was 0.24 mL/100 g brain. Based on the precision obtained by our data, CBV of 1.85 ± 0.30 mL/100 g brain may be assumed as normal value for this cohort.

Peripheral muscle fractional tissue oxygen extraction in stable term and preterm neonates during the first 24†h after birth.

Background: Peripheral muscle fractional tissue oxygen extraction (pFTOE) represents the relative extraction of oxygen from the arterial to venous compartment, providing information about dynamic changes of oxygen delivery and oxygen consumption. The aim of the present study was to establish reference values of pFTOE during the first 24 h after birth in stable term and late preterm neonates. Methods: The present study is a post-hoc analysis of secondary outcome parameters of prospective observational studies. Only stable neonates without infection, asphyxia and any medical support were eligible for our analysis to obtain normal values. For measurements of peripheral muscle tissue oxygenation index (pTOI) during the first 24 h after birth in term and preterm neonates, the NIRO200/NIRO200NX was used. Arterial oxygen saturation (SpO2) was obtained by pulse oximetry. pFTOE was calculated out of pTOI and SpO2: pFTOE = (SpO2-pTOI)/SpO2. Measurements of neonates were stratified into four groups according to their respective measurement time point (6 h periods) after birth. Term and preterm neonates were analyzed separately. Mean values of measurements during the first time period (0-6 h after birth) were compared to measurements of the following time periods (second = 7-12 h, third = 13-18 h, fourth = 19-24 h after birth). Results: Two-hundred-fourty neonates (55 term and 185 late preterm neonates) had at least one peripheral muscle NIRS measurements within the first 24 h after birth. Mean gestational age and birth weight were 39.4 ± 1.1 weeks and 3360 (2860-3680)g in term neonates and 34.0 ± 1.4 weeks and 2060 (1750-2350)g in preterm neonates, respectively. In term neonates pFTOE was 0.264 (0.229-0.300), 0.228 (0.192-0.264), 0.237 (0.200-0.274) and 0.220 (0.186-0.254) in the first, second, third and fourth time period. In preterm neonates pFTOE was 0.229 (0.213-0.246), 0.225 (0.209-0.240), 0.226 (0.210-0.242) and 0.238 (0.222-0.255) in the first, second, third and fourth time period. pFTOE did not show any significant changes between the time periods, neither in term nor in preterm neonates. Conclusion: We provide reference values of pFTOE for stable term and late preterm neonates within the first 24 h after birth, which were stable when comparing four 6-h periods. These normal values are of great need for interpreting pFTOE in scientific context as well as for potential future clinical applications.

Cerebral oximetry monitoring versus usual care for extremely preterm infants: a study protocol for the 2-year follow-up of the SafeBoosC-III randomised clinical trial.

BACKGROUND: In the SafeBoosC-III trial, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth did not reduce the incidence of death or severe brain injury in extremely preterm infants at 36 weeks' postmenstrual age, as compared with usual care. Despite an association between severe brain injury diagnosed in the neonatal period and later neurodevelopmental disability, this relationship is not always strong. The objective of the SafeBoosC-III follow-up study is to assess mortality, neurodevelopmental disability, or any harm in trial participants at 2 years of corrected age. One important challenge is the lack of funding for local costs for a trial-specific assessment. METHODS: Of the 1601 infants randomised in the SafeBoosC-III trial, 1276 infants were alive at 36 weeks' postmenstrual age and will potentially be available for the 2-year follow-up. Inclusion criteria will be enrollment in a neonatal intensive care unit taking part in the follow-up study and parental consent if required by local regulations. We aim to collect data from routine follow-up programmes between the ages of 18 and 30 months of corrected age. If no routine follow-up has been conducted, we will collect informal assessments from other health care records from the age of at least 12 months. A local co-investigator blinded to group allocation will classify outcomes based on these records. We will supplement this with parental questionnaires including the Parent Report of Children's Abilities-Revised. There will be two co-primary outcomes: the composite of death or moderate or severe neurodevelopmental disability and mean Bayley-III/IV cognitive score. We will use a 3-tier model for prioritisation, based on the quality of data. This approach has been chosen to minimise loss to follow-up assuming that little data is better than no data at all. DISCUSSION: Follow-up at the age of 2 years is important for intervention trials in the newborn period as only time can show real benefits and harms later in childhood. To decrease the risk of generalisation and data-driven biased conclusions, we present a detailed description of the methodology for the SafeBoosC-III follow-up study. As funding is limited, a pragmatic approach is necessary. TRIAL REGISTRATION: ClinicalTrials.gov NCT05134116 . Registered on 24 November 2021.

The effects of cerebral oximetry in mechanically ventilated newborns: a protocol for the SafeBoosC-IIIv randomised clinical trial.

BACKGROUND: The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants' lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. METHODS/DESIGN: SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery. A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children's Abilities-Revised (PARCA-R) at 2 years of corrected age. DISCUSSION: There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. TRIAL REGISTRATION: The protocol is registered at www. CLINICALTRIALS: gov (NCT05907317; registered 18 June 2023).

Insights into Neonatal Cerebral Autoregulation by Blood Pressure Monitoring and Cerebral Tissue Oxygenation: A Qualitative Systematic Review.

OBJECTIVE: The aim of this qualitative systematic review was to identify publications on blood pressure monitoring in combination with cerebral tissue oxygenation monitoring during the first week after birth focusing on cerebral autoregulation. METHODS: A systematic search was performed on PubMed. The following search terms were used: infants/newborn/neonates, blood pressure/systolic/diastolic/mean/MAP/SAP/DAP, near-infrared spectroscopy, oxygenation/saturation/oxygen, and brain/cerebral. Additional studies were identified by a manual search of references in the retrieved studies and reviews. Only human studies were included. RESULTS: Thirty-one studies focused on preterm neonates, while five included preterm and term neonates. In stable term neonates, intact cerebral autoregulation was shown by combining cerebral tissue oxygenation and blood pressure during immediate transition, while impaired autoregulation was observed in preterm neonates with respiratory support. Within the first 24 h, stable preterm neonates had reduced cerebral tissue oxygenation with intact cerebral autoregulation, while sick neonates showed a higher prevalence of impaired autoregulation. Further cardio-circulatory treatment had a limited effect on cerebral autoregulation. Impaired autoregulation, with dependency on blood pressure and cerebral tissue oxygenation, increased the risk of intraventricular hemorrhage and abnormal neurodevelopmental outcomes. CONCLUSIONS: Integrating blood pressure monitoring with cerebral tissue oxygenation measurements has the potential to improve treatment decisions and optimizes neurodevelopmental outcomes in high-risk neonates.

Acid-base and metabolic parameters and cerebral oxygenation during the immediate transition after birth-A two-center observational study.

OBJECTIVE: The association between blood glucose level and cerebral oxygenation (cerebral regional oxygen saturation [crSO2] and cerebral fractional tissue oxygen extraction [FTOE]) in neonates has already been described. Aim of the present study was to investigate if acid-base and other metabolic parameters have an impact on cerebral oxygenation immediately after birth in preterm and term neonates. STUDY DESIGN: Post-hoc analyses of secondary outcome parameters of two prospective observational studies were performed. Preterm and term neonates born by caesarean section were included, in whom i) cerebral near-infrared spectroscopy (NIRS) measurements were performed during the first 15 minutes after birth and ii) a capillary blood gas analysis was performed between 10 and 20 minutes after birth. Vital signs were routinely monitored with pulse oximetry (arterial oxygen saturation [SpO2] and heart rate [HR]). Correlation analyses were performed to investigate potential associations between acid-base and metabolic parameters (lactate [LAC], pH-value [pH], base-excess [BE] and bicarbonate [HCO3]) from capillary blood and NIRS-derived crSO2 and FTOE at 15 minutes after birth. RESULTS: One-hundred-fifty-seven neonates, 42 preterm neonates (median gestational age [IQR] 34.0 weeks [3.3], median birth weight 1845g [592]) and 115 term neonates (median gestational age [IQR] 38.9 weeks [1.0], median birth weight 3230g [570]) were included in the study. Median crSO2 [IQR] values at 15 minutes after birth were 82% [16] in preterm neonates and 83% [12] in term neonates. Median FTOE [IQR] values at 15 minutes after birth were 0.13 [0.15] in preterm neonates and 0.14 [0.14] in term neonates. In preterm neonates, higher LAC and lower pH and BE were associated with lower crSO2 and higher FTOE. In term neonates, higher HCO3 was associated with higher FTOE. CONCLUSION: There were significant associations between several acid-base and metabolic parameters and cerebral oxygenation in preterm neonates, while in term neonates only HCO3 correlated positively with FTOE.

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Cardiac output and regional-cerebral-oxygen-saturation in preterm neonates during immediate postnatal transition: An observational study.

AIM: To examine potential correlations between cardiac output (CO) with cerebral-regional-oxygen-saturation (crSO2 ) and cerebral-fractional-tissue-oxygen-extraction (cFTOE) during immediate foetal-to-neonatal transition in term and preterm neonates with and without respiratory support. METHODS: Post hoc analyses of secondary outcome parameters of prospective observational studies were performed. We included neonates with cerebral near-infrared-spectroscopy (NIRS) monitoring and an oscillometric blood pressure measurement at minute 15 after birth. Heart rate (HR) and arterial oxygen saturation (SpO2 ) were monitored. CO was calculated with Liljestrand and Zander formula and correlated with crSO2 and cFTOE. RESULTS: Seventy-nine preterm neonates and 207 term neonates with NIRS measurements and calculated CO were included. In 59 preterm neonates (mean gestational age (GA): 29.4 ± 3.7 weeks) with respiratory support, CO correlated significantly positively with crSO2 and significantly negatively with cFTOE. In 20 preterm neonates (GA 34.9 ± 1.3 weeks) without respiratory support and in 207 term neonates with and without respiratory support, CO correlated neither with crSO2 nor with cFTOE. CONCLUSION: In compromised preterm neonates with lower gestational age and in need of respiratory support, CO was associated with crSO2 and cFTOE, whereas in stable preterm neonates with higher gestational age as well as in term neonates with and without respiratory support, no associations were observed.

Cerebral oxygenation immediately after birth and long-term outcome in preterm neonates-a retrospective analysis.

BACKGROUND: Prematurity is associated with increased risk for morbidity and mortality. Aim of this study was to evaluate whether cerebral oxygenation during fetal-to-neonatal transition period was associated with long-term outcome in very preterm neonates. METHODS: Preterm neonates ≤ 32 weeks of gestation and/or ≤ 1500 g with measurements of cerebral regional oxygen saturation (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) within the first 15 min after birth were analysed retrospectively. Arterial oxygen saturation (SpO2) and heart rate (HR) were measured with pulse oximetry. Long-term outcome was assessed at two years using "Bayley Scales of Infant Development" (BSID-II/III). Included preterm neonates were stratified into two groups: adverse outcome group (BSID-III ≤ 70 or testing not possible due to severe cognitive impairment or mortality) or favorable outcome group (BSID-III > 70). As the association between gestational age and long-term outcome is well known, correction for gestational age might disguise the potential association between crSO2 and neurodevelopmental impairment. Therefore, due to an explorative approach the two groups were compared without correction for gestational age. RESULTS: Forty-two preterm neonates were included: adverse outcome group n = 13; favorable outcome group n = 29. Median(IQR) gestational age and birth weight were 24.8 weeks (24.2-29.8) and 760 g (670-1054) in adverse outcome group and 30.6 weeks (28.1-32.0) (p = 0.009*) and 1250 g (972-1390) (p = 0.001*) in the favorable outcome group, respectively. crSO2 was lower (significant in 10 out of 14 min) and cFTOE higher in adverse outcome group. There were no difference in SpO2, HR and fraction of inspired oxygen (FiO2), except for FiO2 in minute 11, with higher FiO2 in the adverse outcome group. CONCLUSION: Preterm neonates with adverse outcome had beside lower gestational age also a lower crSO2 during immediate fetal-to-neonatal transition when compared to preterm neonates with age appropriate outcome. Lower gestational age in the adverse outcome group would suggest beside lower crSO2 also lower SpO2 and HR in this group, which were however similar in both groups.

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.

Correlation between arterial blood pressures and regional cerebral oxygen saturation in preterm neonates during postnatal transition-an observational study.

Objective: To assess whether blood pressure (systolic (SABP), diastolic (DABP), and mean arterial blood pressure (MABP) and cerebral-regional-oxygen-saturation (crSO2) and cerebral-fractional-tissue-oxygen-extraction (cFTOE) are associated after immediate fetal-to-neonatal transition in preterm neonates with and without respiratory support. Study design: Post-hoc analyses of secondary outcome parameters of prospective observational studies were performed. We included moderate and late preterm neonates with and without respiratory support with cerebral NIRS monitoring (INVOS 5100c) and an oscillometric blood pressure measurement at minute 15 after birth. Heart rate (HR) and arterial oxygen saturation (SpO2) were monitored routinely. Blood pressure values were correlated with crSO2 and cFTOE. Results: 47 preterm neonates with NIRS measurements and blood pressure measurement during immediate transition after birth were included. Twenty-five preterm neonates (gestational age: 34.4±1.6 weeks) received respiratory support. In these neonates crSO2 correlated significantly positively with systolic blood pressure (SABP; r = 0.46, p = 0.021), diastolic blood pressure (DABP; r = 0.51, p = 0.009) and, mean arterial pressure (MABP; r = 0.48, p = 0.015). cFTOE correlated significantly negatively with SABP (r = -0.44, p = 0.027), DABP (r = -0.49, p = 0.013) and mean MABP (r = -0.44, p = 0.029). Twenty-two preterm neonates (gestational age: 34.5 ± 1.5 weeks) did not receive respiratory support. In those neonates, neither crSO2 nor cFTOE correlated with blood pressure. Conclusion: In compromised moderate and late preterm neonates with respiratory support, both, crSO2 and cFTOE correlated with blood pressure. These findings suggest that passive pressure-dependent cerebral perfusion was present in preterm neonates with respiratory support, indicating an impaired cerebral autoregulation in those compromised preterm neonates.

Peripheral fractional oxygen extraction measured with near-infrared spectroscopy in neonates-A systematic qualitative review.

Background: Peripheral fractional oxygen extraction (pFOE) measured with near-infrared spectroscopy (NIRS) in combination with venous occlusion is of increasing interest in term and preterm neonates. Objective: The aim was to perform a systematic qualitative review of literature on the clinical use of pFOE in term and preterm neonates and on the changes in pFOE values over time. Methods: A systematic search of PubMed, Embase and Medline was performed using following terms: newborn, infant, neonate, preterm, term, near-infrared spectroscopy, NIRS, oximetry, spectroscopy, tissue, muscle, peripheral, arm, calf, pFOE, OE, oxygen extraction, fractional oxygen extraction, peripheral perfusion and peripheral oxygenation. Additional articles were identified by manual search of cited references. Only studies in human neonates were included. Results: Nineteen studies were identified describing pFOE measured with NIRS in combination with venous occlusion. Nine studies described pFOE measured on the forearm and calf at different time points after birth, both in stable preterm and term neonates without medical/respiratory support or any pathological findings. Nine studies described pFOE measured at different time points in sick preterm and term neonates presenting with signs of infection/inflammation, anemia, arterial hypotension, patent ductus arteriosus, asphyxia or prenatal tobacco exposure. One study described pFOE both, in neonates with and without pathological findings. Conclusion: This systematic review demonstrates that pFOE may provide additional insight into peripheral perfusion and oxygenation, as well as into disturbances of microcirculation caused by centralization in preterm and term neonates with different pathological findings. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021249235].