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.

Anemia and Red Blood Cell Transfusions, Cerebral Oxygenation, Brain Injury and Development, and Neurodevelopmental Outcome in Preterm Infants: A Systematic Review.

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.

Neonatal NIRS monitoring: recommendations for data capture and review of analytics.

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.

Maturation of Intestinal Oxygenation: A Review of Mechanisms and Clinical Implications for Preterm Neonates.

Nutrient requirements of preterm neonates may be substantial, to support growth and maturation processes in the presence of challenging post-natal circumstances. This may be accompanied by substantial intestinal oxygen requirements. Preterm neonates may not be able to meet these oxygen requirements, due to a developmental delay in intestinal oxygenation regulation mechanisms. This review summarizes the available literature on post-natal maturation of intestinal oxygenation mechanisms and translates these changes into clinical observations and potential implications for preterm neonates. The different mechanisms that may be involved in regulation of intestinal oxygenation, regardless of post-natal age, are first discussed. The contribution of these mechanisms to intestinal oxygenation regulation is then evaluated in newborn and mature intestine. Finally, the course of clinical observations is used to translate these findings to potential implications for preterm neonates.

Regional tissue oxygenation monitoring in the neonatal intensive care unit: evidence for clinical strategies and future directions.

Near-infrared spectroscopy (NIRS)-based monitoring of regional tissue oxygenation (rSO2) is becoming more commonplace in the neonatal intensive care unit (NICU). While increasing evidence supports rSO2 monitoring, actual standards for applying this noninvasive bedside technique continue to evolve. This review highlights the current strengths and pitfalls surrounding practical NIRS-based monitoring in the neonatal population. The physiologic background of rSO2 monitoring is discussed, with attention to understanding oxygen delivery/consumption mismatch and its effects on tissue oxygen extraction. The bedside utility of both cerebral and peripheral rSO2 monitoring in the NICU is then explored from two perspectives: (1) disease/event-specific "responsive" monitoring and (2) "routine," continuous monitoring. Recent evidence incorporating both monitoring approaches is summarized with emphasis on practical applicability in the NICU. Finally, a future paradigm for a broad-based NIRS monitoring strategy is presented, with attention towards improving personalization of neonatal care and ultimately enhancing long-term outcomes.

Discharge breastmilk feeding rates in asymptomatic term newborns admitted to the neonatal intensive care unit for maternal chorioamnionitis.

PURPOSE: To compare discharge breastmilk feeding rates among asymptomatic term newborns receiving 48-hour versus >48-hour antibiotics in the neonatal intensive care unit (NICU) and a cohort of well-baby nursery (WBN) newborns. MATERIALS AND METHODS: This retrospective review included asymptomatic term neonates admitted to the NICU due to maternal chorioamnionitis and a comparison group of WBN neonates between January 2012 and December 2015. Demographic, birth, feeding, and lactation consultant visit data were analyzed in univariate and multivariate models. RESULTS: Among 272 NICU neonates, 237 (87%) received 48-hour antibiotics versus 35 (13%) who received >48-hour (h) antibiotics; a cohort of 428 WBN neonates was studied for comparison. Exclusive breastmilk feeding was seen in 14% of NICU versus 35% of WBN neonates (p < .01). Among NICU newborns, 48 h versus >48 h antibiotics was not associated with altered discharge breastmilk feeding (14 versus 14%; p = .89). On multivariate logistic regression analysis among NICU subjects, older maternal age (p < .01), lower parity (p = .02), first-feed breastmilk (p < .01), and more lactation consultant visits (p = .012) were associated with increased discharge breastmilk feeding. CONCLUSIONS: NICU admission for presumed early-onset sepsis due to maternal chorioamnionitis was associated with reduced discharge breastmilk feeding in asymptomatic term neonates, but prolonged antibiotic exposure was not. We speculate that demographic factors, such as maternal age and parity, may aid in focusing lactation consultant efforts to potentially improve NICU exclusive discharge breastmilk feeding rates.

Correction: Monitoring cerebral oxygenation of the immature brain: a neuroprotective strategy?

The original version of this article contained an error in the legend of Fig. 3, which incorrectly read:Figure 3. a The patterns of arterial saturation (SaO2; orange), and rScO2 (blue) and mean arterial blood pressure (MABP; red) of an extremely preterm infant on postnatal day 1. The initial rScO2 values were very low (red box). These low values seemed to be associated with PaCO2 values below 30 mmHg (brown squares; starting at 24 mmHg. SaO2 and MABPs values were always normal. When PaCO2 values increased above values of 30 mmHg (brown arrow) the rScO2 increased and eventually normalized. b The patterns of rScO2 (blue) and mean arterial blood pressure (MABP; red) of a very preterm girl, starting on postnatal day 1, was especially marked by a steep decrease in cerebral oxygenation (rScO2; red box) to very low values (<40%). Echocardiographic investigation early on postnatal day 2 revealed a hemodynamically significant ductus arteriosus. Subsequent ductal closure with indomethacin (2 courses) was followed by normalization of cerebral oxygenation. c The patterns of heart rate (HR), arterial saturation (SaO2) and rScO2 (red box) in a preterm neonate.with severe anemia. The rather low rScO2 recovered following packed red blood cell transfusion (courtesy Prof. Gunnar Naulaers, UZ Leuven).This has been corrected in both the PDF and HTML versions of the article.

Regional Tissue Oxygen Extraction and Severity of Anemia in Very Low Birth Weight Neonates: A Pilot NIRS Analysis.

OBJECTIVE: Anemia causes blood flow redistribution and altered tissue metabolic behavior to sustain homeostatic oxygen consumption. We hypothesized that anemia severity would correlate with increased regional fractional tissue oxygen extraction among premature neonates. STUDY DESIGN: Regional oxygen extraction was calculated using pulse oximetry and near-infrared spectroscopy data among neonates <1,250 g during their first 10 postnatal days. Oxygen extraction was assessed for correlations with raw hematocrit levels and following grouping into hematocrit quartiles. RESULTS: Twenty-seven neonates with gestational age 27 ± 2 weeks and birth weight 966 ± 181 g underwent 116 hematocrit determinations. Cerebral and flank oxygen extraction inversely correlated with hematocrit (cerebral r = -0.527, p = 0.005; flank r = -0.485, p = 0.01). Increased cerebral oxygen extraction was observed for the lowest three hematocrit quartiles (Q1 0.26 ± 0.08, p = 0.004; Q2 0.24 ± 0.09, p = 0.01; Q3 0.25 ± 0.09, p = 0.03; all compared with Q4 0.18 ± 0.10). Increased flank oxygen extraction occurred for the lowest two quartiles (Q1 0.36 ± 0.12, p < 0.001; Q2 0.35 ± 0.11, p < 0.001; compared with Q4 0.22 ± 0.13). Splanchnic oxygen extraction demonstrated no similar correlations. CONCLUSION: Increases in tissue oxygen extraction may indicate early pathophysiologic responses to nascent anemia in premature neonates.

Monitoring cerebral oxygenation of the immature brain: a neuroprotective strategy?

Monitoring of cerebral oxygenation (rScO2) 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 rScO2 in preterm neonates with regard to the prevention of severe intraventricular hemorrhage and hypoxia/hyperoxia-related white matter injury. This neuroprotective role of rScO2 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 rScO2 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.

Cerebral oxygenation during umbilical arterial blood sampling in very low birth weight neonates.

OBJECTIVE: Umbilical arterial blood sampling (UABS) has been associated with cerebral oxygen saturation (CrSO2) decrements in very low birth weight (VLBW) neonates. We sought to determine patient- and UABS procedure-related factors contributing to this effect. STUDY DESIGN: In this prospective cohort study, cerebral near-infrared spectroscopy was performed during UABS procedures in VLBW neonates. Analyses were conducted to determine subject- and procedure-related factors correlating with CrSO2 decrements. RESULT: Thirty subjects (mean (±SD) 27 ± 2 week GA and 1058 ± 279 g BW) underwent 84 UABS procedures between 5 and 183 postnatal hours. Six (20%) experienced CrSO2 decrements, less than previously reported. Subjects with CrSO2 decrements had earlier GA and lower BW, though these were not statistically significant differences. CrSO2 decrements occurred with lower pre- and post-UABS pulse oximetry (p = 0.004; p < 0.001), lower arterial oxygen partial pressure (p < 0.001), lower baseline CrSO2 (p = 0.01), and faster "priming" blood reinfusion (p = 0.03) and saline flush (p = 0.02). CONCLUSION: UABS procedures appear to be associated with CrSO2 decrements more commonly among VLBW neonates already experiencing disturbances in cerebral oxygen delivery-consumption balance. Shorter durations of UABS procedural components may contribute to CrSO2 decrements.

Fluid management during the first postnatal day in very low birth weight neonates and rates of patent ductus arteriosus requiring treatment.

PURPOSE: Previous studies have suggested an association between high maintenance fluid volumes during the first several postnatal days and patent ductus arteriosus (PDA) requiring treatment in very low birth weight (VLBW) neonates. However, no studies have specifically examined fluid administration during the first postnatal day with regard to PDA-related outcomes. We seek to determine whether additional intravenous fluid administration beyond prescribed goals during the first postnatal day is associated with PDA requiring treatment. MATERIALS AND METHODS: Retrospective data were collected from neonates with birth weight <1250 g. Infants receiving fluids beyond initially documented goals, stratified by relative degree of additional fluids, were compared to those receiving no additional intravenous fluids for the primary outcome of PDA requiring treatment and secondarily for other neonatal morbidities. RESULTS: Two hundred VLBW neonates were included. Controlling for birth weight and gestational age, fluid administration beyond prescribed goals during the first postnatal day was not associated with increased PDA requiring treatment. Additionally, no statistically significant associations between additional fluids and secondary outcomes were observed. CONCLUSIONS: No significant relationship between fluid volumes during the first postnatal day and PDA requiring treatment were observed. Further prospective analysis of early fluid management in VLBW neonates is warranted.

Umbilical Arterial Blood Sampling Alters Cerebral Tissue Oxygenation in Very Low Birth Weight Neonates.

OBJECTIVE: To evaluate the magnitude, consistency, and natural history of reductions in cerebral regional tissue oxygenation (CrSO2) during umbilical arterial (UA) blood sampling in very low birth weight neonates. STUDY DESIGN: Data were collected during a prospective observational near-infrared spectroscopy survey conducted on a convenience sample of 500-1250 g neonates during the first 10 postnatal days. A before-after analysis of UA blood sampling effects on CrSO2 absolute values and variability was performed. The present analysis was not designed a priori and was conducted following the bedside observation of CrSO2 decrements contiguous with UA blood draws. RESULTS: Fifteen very low birth weight neonates had 201 UA blood draws. Baseline CrSO2 (mean ± SEM) decreased following UA blood sampling, from 70 ± 1% to a nadir of 63 ± 1% (P < .001) occurring 4 ± 3 (range 2-24) minutes following blood draws. CrSO2 subsequently increased to 70 ± 1% (P < .001 compared with nadir) at 10 ± 4 (range 4-28) minutes following UA blood sampling. Coefficients of variation (mean ± SEM) increased from 0.02 ± 0.001 at baseline to 0.05 ± 0.004 (P < .001), followed by a decrease to 0.03 ± 0.003 (P < .001 for all comparisons), thus denoting increased CrSO2 variability following UA blood sampling. CONCLUSIONS: UA blood sampling is associated with significant CrSO2 decrements with increased variability over clinically significant intervals. Whether these changes impact complications of prematurity, including intraventricular hemorrhage and periventricular leukomalacia, remain unknown.

Congenital candidiasis: an uncommon skin eruption presenting at birth.

We present the case of a preterm neonate who was born with respiratory distress and a papulovesicular rash that was diagnosed as congenital candidiasis (CC). The mother was asymptomatic. The cutaneous eruption and respiratory distress improved following treatment with systemic antifungals. Congenital candidiasis ranges in presentation from isolated cutaneous involvement to severe multisystem disease. Given its rarity among neonatal skin eruptions, heightened suspicion is required for prompt diagnosis and treatment.