Hemodynamics and cerebral oxygenation in the neonatal transition: a prospective pilot study.

Background: Cerebral regional oxygen saturation (crSO₂) during immediate transition and resuscitation immediately after birth is of increasing interest. Objectives: The aim of the present study was to assess whether the type of maternal anesthesia during cesarean section (CS; general anesthesia vs. spinal anesthesia) has an influence on cerebral oxygenation during immediate neonatal transition after birth. Methods: Secondary outcome parameters of prospective observational studies were analyzed. Neonates born by CS from November 2009 to September 2016 at the Medical University of Graz (Austria) were eligible. Term and preterm neonates were included, provided that: (1) crSO₂ was measured by near-infrared spectroscopy, and (2) peripheral arterial oxygen saturation (SpO₂) and heart rate (HR) were measured by pulse oximetry during the first 15 min after birth. Administration of supplemental oxygen was recorded and cerebral fractional tissue oxygen extraction (cFTOE) was calculated out of crSO₂ and SpO₂. For comparison, term and preterm neonates with maternal general anesthesia were matched to neonates with maternal spinal anesthesia during CS. Results: Out of 760 eligible neonates, 64 term (38.8 ± 0.9 weeks of gestation; 32 neonates in each group) and 54 preterm neonates (32.0 ± 2.9 weeks of gestation; 27 neonates in each group) were included. In term neonates, maternal general anesthesia was associated with lower initial SpO₂, HR values, and Apgar scores. The fraction of inspired oxygen (FiO₂) was statistically significantly higher in the general anesthesia group. Nevertheless, crSO₂ and cFTOE did not differ statistically significantly between the groups. In preterm neonates there were no statistically significant differences in SpO₂, HR, crSO₂, and cFTOE between the general and spinal anesthesia groups. Apgar scores at 1 min were statistically significantly lower and FiO₂ was statistically significantly higher in the general anesthesia group. Conclusion: Cerebral tissue oxygenation in neonates during immediate transition after birth was similar after maternal general and spinal anesthesia during CS, despite differences in SpO₂, HR, and supplemental oxygen in term neonates and differences in supplemental oxygen in preterm neonates.

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. 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. 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. 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.

Introduction: Maternal tobacco smoking during pregnancy is a global health problem leading to an increased risk for fetal and neonatal morbidities. So far, there are no data of the potential impact of maternal smoking during pregnancy on the most vulnerable period after birth – the immediate postnatal transition. The aim of the present study was therefore, to compare cerebral oxygenation during immediate postnatal transition in term neonates with and without prenatal tobacco exposure.Methods: Included in this post-hoc analysis were healthy term neonates, with measurements of cerebral oxygenation (INVOS 5100C) during the first 15 min after birth, and for whom information on maternal smoking behavior during pregnancy was available. Neonates with prenatal tobacco exposure (smoking group) were matched 1:1 according to gestational age (±1 week), birth weight (±100 grams) and hematocrit (±5 %) to neonates without (non-smoking group). Cerebral regional tissue oxygen saturation (crSO2), cerebral fractional tissue oxygen extraction (cFTOE), arterial oxygen saturation (SpO2) and heart rate (HR) within the first 15 min after birth were compared between the two groups.Results: Twelve neonates in the smoking group with a median (IQR) gestational age of 39.1 (38.8–39.3) weeks and a birth weight of 3,155 (2,970–3,472) grams were compared to 12 neonates in the non-smoking group with 39.1 (38.7–39.2) weeks and 3,134 (2,963–3,465) grams. In the smoking group, crSO2 was significantly lower and cFTOE significantly higher until min 5 after birth. HR was significantly higher in the smoking group in min 3 after birth. Beyond this period, there were no significant differences between the two groups.Conclusion: Cerebral oxygenation within the first 5 min after birth was compromised in neonates with prenatal tobacco exposure. This observation suggests a higher risk for cerebral hypoxia immediately after birth due to fetal tobacco exposure.

Introduction: Concentration of fetal hemoglobin (HbFc) in human neonates determines oxygen-carrying capacity of blood and the position of oxyhemoglobin dissociation curve. Near-infrared spectroscopy enables the measurement of regional cerebral tissue oxygen saturation (rScO2) and in combination with measurements of pulsatile arterial oxygen saturation (SpO2), the calculation of cerebral fractional tissue oxygen extraction (cFTOE). Methods: We aimed to investigate the impact of HbFc on rScO2, cFTOE, and SpO2 in preterm and term neonates during the first 15 min after birth. Blood analyses provided total blood hemoglobin (Hb) and HbFc measurements. Correlations between HbFc, Hb and rScO2, cFTOE, and SpO2 in each minute were analyzed. Results: Ninety term and 19 preterm neonates without medical support were included. HbFc was significantly higher in preterm neonates, whereas there were no significant differences in Hb between the groups. In preterm neonates, we found positive correlations of both HbFc and Hb with rScO2 and negative correlations of HbFc and Hb with cFTOE in the first minutes after birth. In contrast, there were no significant correlations between the same parameters in term neonates. Correlations between HbFc or Hb and SpO2 were either insignificant, negligible, or very low in both groups. Discussion/Conclusion: In preterm neonates, higher HbFc was associated with higher rScO2 and lower cFTOE in the first minutes after birth. This phenomenon could not be confirmed in term neonates and might reflect immature autoregulation of oxygen delivery to the brain or lower oxygen consumption in preterm neonates in the first minutes of immediate postnatal transition.

Background: Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcome. Affected fetuses commonly display typical blood flow redistribution towards the brain (“brain sparing”). Accordingly, increased cerebral oxygen saturation has been observed in IUGR neonates within the first days of life. Aim: The aim of our study was to assess cerebral oxygenation behavior during immediate neonatal transition in IUGR infants. Methods: This is a retrospective single-center observational cohort study. Cerebral regional oxygen saturation (crSO₂) was measured with near-infrared spectroscopy in neonates during the first 15 min after birth. Neonates with IUGR (IUGR group) were matched for gestational age (±1 week) and gender with neonates that were appropriate for gestational age (AGA). The AGA:IUGR matching ratio was 3:1. Arterial oxygen saturation (SpO₂), heart rate (HR), crSO₂, and cerebral fractional tissue oxygen extraction (cFTOE) were compared between the groups. Results: Between August 2010 and October 2017, 45 neonates with IUGR were identified and matched to 135 AGA neonates. Mean gestational age was 33.1 ± 3.0 weeks in the IUGR group and 33.5 ± 2.7 weeks in the AGA group. Mean birth weight was 1,559 ± 582 g in the IUGR group and 2,051 ± 679 g in the AGA group. There was a significant group difference in crSO₂ beginning at 5 min and continuing for the rest of the observation time with higher crSO₂ values in the IUGR group (main effect group: p = 0.011; interaction time × group: p = 0.039). In cFTOE, a significant difference could be observed at 5–9 and 11–13 min with lower rates of oxygen extraction in the IUGR group (main effect group: p = 0.025; interaction time × group: p = 0.463). Concerning SpO₂ and HR, there was no significant difference between the IUGR and the AGA neonates. Conclusion: Neonates of the IUGR group did show significantly higher crSO₂ values and significantly lower cFTOE values already during immediate neonatal transition compared to the AGA group.

Background: Non-invasive monitoring of the brain with near-infrared spectroscopy (NIRS) during immediate transition after birth is of growing interest. Objective: The aim of this work was to define reference ranges and centile charts for a regional cerebral tissue oxygenation index (cTOI), measured with the NIRO 200NX (NIRO, Hamamatsu, Japan), and cerebral fractional tissue oxygen extraction (cFTOE) during the first 15 min after birth in preterm and term neonates without any medical support. Methods: cTOI was measured with the NIRO 200NX during the first 15 min after delivery via Caesarean section in preterm and term infants. The NIRS-sensor was placed on the right forehead. Peripheral arterial oxygen saturation (SpO₂) and heart rate were continuously measured by pulse oximetry. cFTOE was calculated out of cTOI and SpO₂. Neonates with a requirement for any medical support were excluded. Results: A total of 230 neonates were enrolled, from which 90 had to be excluded. Therefore, 140 term neonates were included and data were used to define reference ranges and centile charts. The 50th centile (10th to 90th centiles) of cTOI was 56% (39-75) at 2 min, 66% (50-78) at 5 min, 75% (62-85) at 10 min and 73% (61-84) at 15 min after birth. The 50th centile of cFTOE was 0.24 (0.11-0.44) at 2 min, 0.20 (0.10-0.35) at 5 min, 0.21 (0.09-0.35) at 10 min and 0.24 (0.13-0.37) at 15 min after birth. Conclusion: The present observational study adds the reference ranges and centile charts of cTOI measured with the NIRO 200NX and cFTOE calculated out of cTOI and SpO₂ in neonates during the immediate neonatal transition. Centiles for each instrument will be necessary for future clinical application, since the differences between cTOI and cerebral regional tissue oxygen saturation measured with INVOS 5100C change with increasing regional oxygenation.

The immediate transition from foetus to neonate includes substantial changes, especially concerning the cardiovascular system. Furthermore, the brain is one of the most vulnerable organs to hypoxia during this period. According to current guidelines for postnatal stabilization, the recommended parameters for monitoring are heart rate (HR) and arterial oxygen saturation (SpO2). Recently, there is a growing interest in advanced monitoring of the cardio-circulatory system and the brain to get further objective information about the neonate’s condition during the immediate postnatal transition after birth. The aim of the present study was to combine cardiac output (CO) and brain oxygenation monitoring in term neonates after caesarean section in order to analyse the potential influence of CO on cerebral oxygenation during neonatal transition. This was a monocentric, prospective, observational study. For non-invasive cardiac output measurements, the electrical velocimetry (EV) method (Aesculon Monitor, Osypka Medical, CA, USA) was used. The pulse oximeter probe for SpO2 and HR measurements was placed on the right hand or wrist. The cerebral tissue oxygen index (cTOI) was measured using a NIRO-200NX monitor with the near-infrared spectroscopy (NIRS) transducer on the right frontoparietal head. Monitoring started at minute 1 and was continued until minute 15 after birth. At minutes 5, 10, and 15 after birth, mean CO was calculated from six 10 s periods (with beat-to-beat analysis). During the study period, 99 term neonates were enrolled. Data from neonates with uncomplicated transitions were analysed. CO showed a tendency to decrease until minute 10. During the complete observational period, there was no significant correlation between CO and cTOI. The present study was the first to investigate a possible correlation between CO and cerebral oxygenation in term infants during the immediate neonatal transition. In term infants with uncomplicated neonatal transition after caesarean section, CO did not correlate with cerebral oxygenation.

Background: Cerebral oxygenation monitored non-invasively by near-infrared spectroscopy (NIRS) is of increasing interest in neonatal care. Cerebral oxygenation is determined by cerebral oxygen delivery and cerebral oxygen consumption. Oxygen delivery as well as oxygen consumption might be influenced by metabolic parameters like blood glucose and lactate.Objective: The aim of the present systematic qualitative review is therefore to identify and summarize all studies, which describe cerebral oxygenation measured with NIRS and blood glucose and/or blood lactate levels in neonates.Data sources: A systematic search of Ovid Embase and PubMed was performed. Search terms included near-infrared spectroscopy, fractional tissue oxygen extraction, cerebral tissue oxygen saturation, regional cerebral tissue oxygen saturation, oxygenation, term, and preterm neonates, cesarean delivery, transition, after-birth, newborn, vaginal delivery, cesarean delivery, baby, neonatal transition, metabolism, lactate, glucose, and blood glucose level.Study selection/data synthesis: Studies analyzing cerebral oxygenation and blood glucose and/or blood lactate levels in neonates were included. Animal studies, duplicates, or studies in non-English language were excluded.Results: Twenty-five studies were identified that describe blood glucose and/or blood lactate levels as primary or secondary outcome parameters with additional measured cerebral oxygenation by NIRS in neonates. Twelve studies were included with blood glucose measurements: four described an association between blood glucose levels and cerebral oxygenation, two show no association, and six do not report on possible associations. Eighteen studies were included with lactate measurements: one describe an association between lactate levels and cerebral oxygenation, while three show no association and 14 do not report on possible associations.Discussion: The influence of blood glucose and blood lactate levels on the cerebral oxygenation in neonates is still controversial. However, there seems to be an association between cerebral oxygenation and the metabolic parameter blood glucose and lactate, which need further investigation.

Objectives: To assess variability of systemic hemodynamics and its covariates following bolus propofol administration in (pre)term neonates, and to analyze the effect of propofol on cerebral tissue oxygenation index (TOI) and fractional tissue oxygen extraction measured by near-infrared spectroscopy. Methods: In (pre)term neonates, we recorded mean arterial blood pressure (MABP), saturation (SaO₂), heart rate (HR) and TOI from 5 min before up to 60 min after intravenous bolus propofol (3 mg kg^–1) administration during elective chest tube removal. Covariate analysis included postmenstrual age (PMA ≤ or >37 weeks), postnatal age (PNA ≤ or >10 days), comedication (fentanyl +/– midazolam) and congenital cardiopathy (yes/no). Fractional tissue oxygen extraction was calculated as (SaO₂ – TOI)/SaO₂. Results: Twenty recordings in 19 neonates were assessed. Following propofol administration, an abrupt, minor decrease in HR and SaO₂ was seen with fast recovery, while MABP decreased up to 1 h. TOI decreased during the first 3 min, reflecting an imbalance between cerebral oxygen delivery and demand. Despite sustained decrease in MABP, TOI then returned to baseline, suggesting a better balance between oxygen delivery and demand. PNA ≤10 days, comedication and absence of cardiopathy were associated with more subtle decreases in cerebral oxygenation and faster recovery. Conclusions: Propofol-induced decrease in HR, SaO₂ and cerebral oxygenation is short lasting while a decrease in MABP is observed up to 60 min. The variability in the effects of propofol is influenced by PNA, comedication or cardiopathy. Near-infrared spectroscopy can be used to assess hemodynamic effects of hypnotics on the cerebral oxygenation.

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. 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. 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. Integrating blood pressure monitoring with cerebral tissue oxygenation measurements has the potential to improve treatment decisions and optimizes neurodevelopmental outcomes in high-risk neonates.

Pulse oximetry is commonly used to monitor arterial oxygen saturation and heart rate during the transition period and reference intervals have been determined. However, the effect of the change in arterial oxygen saturation on tissue oxygenation does not seem to be the same. So, a non-invasive method for monitoring cerebral or regional tissue oxygenation will be potentially useful for vulnerable infants. This study aims to evaluate the effectiveness of cerebral autoregulation in the first 10 min after delivery in term and late preterm newborns without resuscitation requirement. Cerebral tissue oxygen saturation was measured in the first 10 min after birth with near-infrared spectroscopy (NIRS) from the left forehead. Peripheral oxygen saturation was measured with pulse oximetry from the right hand and cerebral fractional tissue oxygen extraction was calculated. Nineteen late preterms and 20 term infants were included in the study. There was no statistically significant difference between median cerebral tissue oxygen saturation and cerebral fractional tissue oxygen extraction values of late preterm and term infants (p < 0.001). There was a strong inverse relationship between cerebral tissue oxygen saturation and cerebral fractional tissue oxygen extraction (p < 0.001). In late preterm infants similar to term infants, arterial oxygen saturation and cerebral tissue oxygen saturation increased with time, but inverse reduction of cerebral fractional tissue oxygen extraction showed the presence of an active autoregulation in the brain. This can be interpreted as the ability of the brain to protect itself from hypoxia by regulating oxygen uptake during normal fetal-neonatal transition process. A larger scale multi-center randomized control trial is now needed to further inform practice.

Although infants following major surgery frequently require RBC transfusions, there is still controversy concerning the best definition for requirement of transfusion in the individual patient. The aim of this study was to determine the impact of RBC transfusion on cerebral oxygen metabolism in noncardiac and cardiac postsurgical infants. Prospective observational cohort study. Pediatric critical care unit of a tertiary referral center. Fifty-eight infants (15 after pediatric surgery and 43 after cardiac surgery) with anemia requiring RBC transfusion were included. RBC transfusion. We measured noninvasively regional cerebral oxygen saturation and microperfusion (relative cerebral blood flow) using tissue spectrometry and laser Doppler flowmetry before and after RBC transfusion. Cerebral fractional tissue oxygen extraction and approximated cerebral metabolic rate of oxygen were calculated. Fifty-eight RBC transfusions in 58 patients were monitored (15 after general surgery, 24 after cardiac surgery resulting in acyanotic biventricular physiology and 19 in functionally univentricular hearts including hypoplastic left heart following neonatal palliation). The posttransfusion hemoglobin concentrations increased significantly (9.7 g/dL vs 12.8 g/dL; 9.7 g/dL vs 13.8 g/dL; 13.1 g/dL vs 15.6 g/dL; p < 0.001, respectively). Posttransfusion cerebral oxygen saturation was significantly higher than pretransfusion (61% [51-78] vs 72% [59-89]; p < 0.001; 58% [35-77] vs 71% [57-88]; p < 0.001; 51% [37-61] vs 58% [42-73]; p = 0.007). Cerebral fractional tissue oxygen extraction decreased posttransfusion significantly 0.37 (0.16-0.47) and 0.27 (0.07-039), p = 0.002; 0.40 (0.2-0.62) vs 0.26 (0.11-0.57), p = 0.001; 0.42 (0.23-0.52) vs 0.32 (0.1-0.42), p = 0.017. Cerebral blood flow and approximated cerebral metabolic rate of oxygen showed no significant change during the observation period. The increase in cerebral oxygen saturation and the decrease in cerebral fractional tissue oxygen extraction were most pronounced in patients after cardiac surgery with a pretransfusion cerebral fractional tissue oxygen extraction greater than or equal to 0.4. Following RBC transfusion, cerebral oxygen saturation increases and cerebral fractional tissue oxygen extraction decreases. The data suggest that cerebral oxygenation in postoperative infants with cerebral fractional tissue oxygen extraction greater than or equal to 0.4 may be at risk in instable hemodynamic or respiratory situations.

Introduction: Monitoring cerebral oxygenation during immediate foetal-to-neonatal transition may provide additional information in preterm neonates. Cerebral fractional tissue oxygen extraction (cFTOE), derived from cerebral oxygen saturation (crSO2) and arterial oxygen saturation (SpO2), reflects the relative extraction of oxygen from the arterial to the tissue compartment, providing information about the balance between oxygen delivery and oxygen consumption. We aimed to describe centiles of cFTOE during the first 15 min after birth in extremely and very preterm neonates. Methods: This is a secondary outcome parameter analysis of the multicentre randomised-controlled COSGOD III trial. Neonates <32 weeks of gestational age included in the near-infrared spectroscopy-open group of the COSGOD III trial with favourable outcome, defined as survival without cerebral injury at term-equivalent age, were assigned for this analysis. CFTOE was calculated for every minute in each included neonate: cFTOE = (SpO2-crSO2)/SpO2. CrSO2 was measured with the INVOS 5100 monitor with the neonatal sensor. Centiles of cFTOE (10th to 90th) from minute 2 to 15 after birth were described. Results: A total of 199 preterm neonates with a median (interquartile range) gestational age of 29.7 (27.7–30.9) weeks and a weight of 1,200 (925–1,460) g were analysed. The 50th centile of cFTOE at minute 2, 5, 10, and 15 was 0.492, 0.296, 0.177, and 0.151, respectively. Conclusion: This study provides centile for cFTOE for extremely and very preterm neonates with favourable outcome independent of interventions during postnatal stabilisation period. These centile charts may assist in interpreting cerebral oxygenation patterns.

Cerebral and Peripheral Regional Oxygen Saturation during Postnatal Transition in Preterm Neonates

Background: A haemodynamically significant patent ductus arteriosus (hsPDA) reduces cerebral oxygenation in appropriate-for-gestational-age (AGA) preterm neonates. Reduced cerebral oxygenation has been associated with brain injury. Preterm small-for-gestational-age (SGA) neonates show higher cerebral oxygenation than AGA peers throughout the first postnatal days. To date, no studies have investigated the effect of hsPDA on cerebral oxygenation in preterm SGA neonates. Objective: We aimed to assess the effect of hsPDA on cerebral oxygenation in preterm SGA neonates compared to AGA peers. We hypothesised that higher baseline cerebral oxygenation would reduce the impact of hsPDA on cerebral oxygenation in preterm SGA neonates. Methods: We monitored regional cerebral oxygen saturation (rScO₂) with near-infrared spectroscopy and calculated the cerebral fractional tissue oxygen extraction (cFTOE) for 72 h after birth. Retrospective analysis compared 36 preterm SGA neonates (birth weight <10th percentile, 18 with hsPDA) to 36 preterm AGA neonates (birth weight 20th to 80th percentile, 18 with hsPDA). Results: In contrast to the other groups, SGA-hsPDA neonates demonstrated a significant fall in rScO₂ [69% (SEM 2.5) at 4-8 h to 61% (2.7) at 68-72 h, p < 0.001] with a concurrent rise in cFTOE [0.26 (0.026) at 4-8 h to 0.34 (0.030) at 68-72 h, p < 0.001]. Conclusions: Contrary to our hypothesis, hsPDA had a significant negative effect on cerebral oxygenation in preterm SGA neonates. Future studies should explore the potential benefits of early screening and treatment for hsPDA on long-term neurodevelopmental outcome in preterm SGA neonates.