OBJECTIVE: In extremely premature neonates, data concerning the normal baseline variability of near-infrared spectroscopy (NIRS)-derived regional oxygen saturation (rSO 2 ) are lacking. We sought to determine: 1) the quiescent variability of cerebral, renal, and splanchnic rSO 2 in clinically stable, undisturbed very low birth weight neonates and 2) the effects of different data averaging epochs on site-specific variability. STUDY DESIGN: In this prospective, observational study, neonates between 500 and 1250 g underwent seven days of continuous, real-time cerebral, renal, and splanchnic NIRS monitoring starting within the first seventy-two postnatal hours. Demographic, cardiopulmonary, bedside care, and rSO 2 data were collected. rSO 2 variability was analyzed utilizing data from quiescent periods identified using pre-specified stability criteria. Between-and within-monitoring site comparisons of data averaging methods were made utilizing ANOVA. RESULT: Twenty-four subjects (GA 27 ± 0.3 wk, birth weight 988 ± 34 g; mean ± SEM) were monitored. Coefficients of variation (CoVar = SD/mean) were calculated for each monitoring site using varied data averaging epochs. CoVar was lowest for cerebral, intermediate for renal, and highest for splanchnic rSO 2 (P < 0.01). For renal and splanchnic sites, shorter epochs (5-and 15-min) resulted in significantly smaller CoVars [P < 0.01 and P < 0.05, respectively]. Splanchnic variability was highly dependent on epoch length, ranging from 16% over 5 min to 23% over 60 min. CONCLUSION: 1) rSO 2 variability differs significantly between monitoring sites and 2) shorter data sampling epochs decrease rSO 2 variability. These observations may assist clinicians in operationally defining minimally significant departures to enable medical decision making utilizing this monitoring technique.

OBJECTIVE: We sought to characterize the effects of "booster" packed red blood cell transfusions on multisite regional oxygen saturation in very low birth weight neonates during the first postnatal week and to examine the utility of fractional tissue oxygen extraction as an estimate of tissue oxygenation adequacy. STUDY DESIGN: Data were collected in an observational near-infrared spectroscopy (NIRS) pilot survey of 500-1250 g neonates during the first postnatal week. A before-after analysis of "booster" transfusions, defined as empiric 15 mL/kg transfusion following 10 mL/kg cumulative phlebotomy losses, was conducted upon cardiopulmonary, laboratory, and spectroscopy data. RESULT: Ten neonates (gestational age 26 ± 0 wk; birth weight 879 ± 49 g) received 14 transfusions at 3 ± 0 postnatal days. Mean hematocrit increased from 35.2 ± 1.2 to 38.5 ± 1.2 % (P < 0.05) following transfusion; pH, base deficit, lactate, creatinine, and cardiopulmonary parameters were unchanged. Cerebral, renal, and splanchnic tissue oxygenation increased 10, 18, and 16%, with concomitant decreases in calculated oxygen extraction of 27, 30, and 9% (all P < 0.05), consistent with enhanced tissue oxygenation. These findings were not observed in a non-transfused comparison group of nine patients. CONCLUSION: "Booster" transfusions improved indices of regional tissue oxygenation while no departures were observed in conventional cardiovascular assessments. We speculate that NIRS-derived oxygenation parameters can provide an objective, graded, and continuous estimate of oxygen delivery-consumption balance not evident using standard monitoring techniques.

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BackgroundCerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC III trial is to investigate the benefits and harms of treatment based on near-infrared spectroscopy (NIRS) monitoring compared with treatment as usual for extremely preterm infants.Methods/designSafeBoosC III is an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. Inclusion criteria will be infants born below 28 weeks postmenstrual age and parental informed consent (unless the site is using ‘opt-out’ or deferred consent). Exclusion criteria will be no parental informed consent (or if ‘opt-out’ is used, lack of a record that clinical staff have explained the trial and the ‘opt-out’ consent process to parents and/or a record of the parents’ decision to opt-out in the infant’s clinical file); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6 h after birth. Participants will be randomised 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72 h of life with a cerebral NIRS oximeter. Cerebral hypoxia will be treated according to an evidence-based treatment guideline. Participants in the control group will not undergo cerebral oxygenation monitoring and will receive treatment as usual. Each participant will be followed up at 36 weeks postmenstrual age. The primary outcome will be a composite of either death or severe brain injury detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to 36 weeks postmenstrual age. Severe brain injury will be assessed by a person blinded to group allocation. To detect a 22% relative risk difference between the experimental and control group, we intend to randomise a cohort of 1600 infants.DiscussionTreatment guided by cerebral NIRS oximetry has the potential to decrease the risk of death or survival with severe brain injury in preterm infants. There is an urgent need to assess the clinical effects of NIRS monitoring among preterm neonates.Trial registrationClinicalTrial.gov, NCT03770741. Registered 10 December 2018.

Brain injury is one of the most consequential problems facing neonates, with many preterm and term infants at risk for cerebral hypoxia and ischemia. To develop effective neuroprotective strategies, the mechanistic basis for brain injury must be understood. The fragile state of neonates presents unique research challenges; invasive measures of cerebral blood flow and oxygenation assessment exceed tolerable risk profiles. Near-infrared spectroscopy (NIRS) can safely and non-invasively estimate cerebral oxygenation, a correlate of cerebral perfusion, offering insight into brain injury-related mechanisms. Unfortunately, lack of standardization in device application, recording methods, and error/artifact correction have left the field fractured. In this article, we provide a framework for neonatal NIRS research. Our goal is to provide a rational basis for NIRS data capture and processing that may result in better comparability between studies. It is also intended to serve as a primer for new NIRS researchers and assist with investigation initiation.

Background: Anemia remains a common comorbidity of preterm infants in the neonatal intensive care unit (NICU). Left untreated, severe anemia may adversely affect organ function due to inadequate oxygen supply to meet oxygen requirements, resulting in hypoxic tissue injury, including cerebral tissue. To prevent hypoxic tissue injury, anemia is generally treated with packed red blood cell (RBC) transfusions. Previously published data raise concerns about the impact of anemia on cerebral oxygen delivery and, therefore, on neurodevelopmental outcome (NDO).Objective: To provide a systematic overview of the impact of anemia and RBC transfusions during NICU admission on cerebral oxygenation, measured using near-infrared spectroscopy (NIRS), brain injury and development, and NDO in preterm infants.Data Sources: PubMed, Embase, reference lists.Study Selection: We conducted 3 different searches for English literature between 2000 and 2020; 1 for anemia, RBC transfusions, and cerebral oxygenation, 1 for anemia, RBC transfusions, and brain injury and development, and 1 for anemia, RBC transfusions, and NDO.Data Extraction: Two authors independently screened sources and extracted data. Quality of case-control studies or cohort studies, and RCTs was assessed using either the Newcastle-Ottawa Quality Assessment Scale or the Van Tulder Scale, respectively.Results: Anemia results in decreased oxygen-carrying capacity, worsening the burden of cerebral hypoxia in preterm infants. RBC transfusions increase cerebral oxygenation. Improved brain development may be supported by avoidance of cerebral hypoxia, although restrictive RBC transfusion strategies were associated with better long-term neurodevelopmental outcomes.Conclusions: This review demonstrated that anemia and RBC transfusions were associated with cerebral oxygenation, brain injury and development and NDO in preterm infants. Individualized care regarding RBC transfusions during NICU admission, with attention to cerebral tissue oxygen saturation, seems reasonable and needs further investigation to improve both short-term effects and long-term neurodevelopment of preterm infants.

Monitoring of cerebral oxygenation (rScO) with near-infrared spectroscopy (NIRS) is a feasible noninvasive bedside technique in the NICU. This review discusses the possible neuroprotective role of "pattern recognition" of NIRS-derived rScO in preterm neonates with regard to the prevention of severe intraventricular hemorrhage and hypoxia/hyperoxia-related white matter injury. This neuroprotective role of rScO monitoring is discussed as a modality to aid in the early detection of cerebral oxygenation conditions predisposing to these complications. Practical guidelines are provided concerning management of abnormal rScO patterns as well as a brief discussion concerning the need for international consensus and the legal aspects associated with the introduction of a new NICU bedside monitoring strategy.

Aim: End-tidal CO 2 (Et CO2 ) is the standard in operative care along with pulse oximetry for ventilation assessment. It is known to be less accurate in the infant population than in adults. Many neonatal intensive care units (NICU) have converted to utilizing transcutaneous CO 2 (tcP CO2 ) monitoring. This study aimed to compare perioperative Et CO2 to tcP CO2 in the pediatric perioperative population specifically below 10 kg, which encompasses neonates and some infants. Methods: After IRB approval and parental written informed consent, we enrolled neonates and infants weighing less than 10 kg, who were scheduled for elective surgery with endotracheal tube under general anesthesia. P CO2 was monitored with Et CO2 and with tcP CO2 . Venous blood gas (Pv CO2 ) samples were drawn at the end of the anesthetic. We calculated a mean difference of Et CO2 minus Pv CO2 (Delta Et CO2 ), and tcP CO2 minus Pv CO2 (Delta tcP CO2 ) from end-of-case measurements. The mean differences in the NICU and non-NICU patients were compared by t-tests and Bland–Altman analysis. Results: Median age was 10.9 weeks, and median weight was 4.4 kg. NICU (n=6) and non-NICU (n=14) patients did not differ in Pv CO2 . Relative to the Pv CO2 , the Delta Et CO2 was much greater in the NICU compared to the non-NICU patients (−28.1 versus −9.8, t=3.912, 18 df, P =0.001). Delta tcP CO2 was close to zero in both groups. Although both measures obtained simultaneously in the same patients agreed moderately with each other (r =0.444, 18 df, P =0.05), Bland–Altman plots indicated that the mean difference (bias) in Et CO2 measurements differed significantly from zero ( P <0.05). Conclusions: Et CO2 underestimates Pv CO2 values in neonates and infants under general anesthesia. TcP CO2 closely approximates venous blood gas values, in both the NICU and non-NICU samples. We, therefore, conclude that tcP CO2 is a more accurate measure of operative Pv CO2 in infants, especially in NICU patients.