Table 2.
Study characteristics.
| First author, Year (Ref.) | Study design | Gestation (weeks) | No of subjects | Study aim | NIRS device, sensor | Optode placement on head | Duration of study | Result |
|---|---|---|---|---|---|---|---|---|
| Ancora et al. (22) | Observational | 39 | 1 | To evaluate the time course of aEEG and NIRS data before, during and after cool cap treatment | NIRO 200 | Forehead | Early significant increase in THI and TOI before TH. TOI improved with TH and remained stable during the rewarming period | |
| Ancora et al. (23) | Observational | ≥36 | 12 | To evaluate the prognostic value NIRS data in asphyxiated cooled infants | NIRO 200 | Forehead | 72 h | Mean TOI at 12h of life is significantly higher in infants who develop a poor neurological outcome than in those with normal outcome |
| Arriaga-Redondo et al. (24) | Observational | ≥36 | 23 | To assess the variability of cerebral tissue oxygenation over time in infants with HIE | Invos 5100 | Forehead | 100 h | rScO2 values >90% and a lack of variability over time in infants with HIE during cooling were associated with poor outcome |
| Bale et al. (25) | Observational | ≥38 | 6 | Feasibility study to assess the potential of cytochrome c oxidase monitoring in NE | Broadband NIRS | Frontal bilateral | Up to 5 days | Mean values for HbD and oxCCO consistently decreased during desaturation and HbT increased. |
| Bale et al. (26) | Prospective observational | >35 | 11 | To investigate the dynamic changes in cerebral metabolism in response to systemic changes, as a marker of injury | Broadband NIRS | Frontal | 3 h on day 3 of TH | Strong relationship between oxCCO and systemic variables during TH on day 3 indicated severe injury following HI |
| Bale et al. (27) | Prospective observational | >36 | 50 | To determine whether broadband NIRS can distinguish injury severity in HIE in the first 4 days after birth | Broadband NIRS | Frontal | Up to day 4 | A strong relationship between cerebral metabolism [broadband NIRS-measured cytochrome-c-oxidase (CCO)] and cerebral oxygenation was associated with unfavorable outcome during spontaneous desaturation episodes during TH. |
| Bale et al. (28) | Observational | >36 | 11 | To use changes in cerebral oxygenation and peripheral oxygen saturation during spontaneous desaturation for determination of CBF | Broadband NIRS | Frontal | Up to day 4 | Infants with severe HIE had significantly lower CBF compared with infants with moderate HIE on the day of birth |
| Burton et al. (29) | Observational | ≥35 | 19 | To assess the relationship between autoregulation during TH and neurodevelopmental outcomes at 2 years of age | INVOS 5100 | Forehead | 84 h | Children with developmental impairments at 2 years, had higher MAPOPT values, spent more time with MABP below MAPOPT, and had greater MABP deviation below MAPOPT during rewarming. Greater MABP deviation above MAPOPT during rewarming was associated with less disability and higher cognitive scores |
| Campbell et al. (30) | Observational | >36 | 27 | Whether infants with autonomic dysfunction after HIE have aberrant physiological responses to care events | NIRO-200NX | Right and left frontotemporal | 2.58–8 h | Infants with depressed heart rate (HR) variability had different physiological responses [post event changes in cerebral blood flow (HbD) and cerebral blood volume (HbT)] compared to infants with intact HR variability |
| Chalak et al. (31) | Observational | ≥36 | 10 | To develop an approach to assess cerebral hemodynamics across multiple time scales during first 72 h of life | INVOS 4100–5100 | left frontoparietal | 72 h | multiple-timescale correlations between oscillations in MAP and SctO2 in the first 72 hrs, indicating impairment of cerebral hemodynamics |
| Chalak et al. (32) | Observational | ≥36 | 10 | To quantify neurovascular coupling (NVC) using wavelet analysis of the dynamic coherence between aEEG and SctO2 in NE | INVOS 4100–5100 | Bilateral parietal area | 60 ± 6 h | High coherence, intact NVC between the oscillations of SctO2 and aEEG in the frequency range of 0.00025–0.001 Hz in the non-encephalopathic newborns. NVC coherence was significantly decreased in encephalopathic newborns who were cooled vs. non- encephalopathic controls and was significantly lower in those with abnormal 2 year outcomes relative to those with normal outcomes |
| Chen et al. (33) | Observational | >35.7 | 44 | To evaluate the evoked CBO response to neuronal activation in newborns with HIE and compare with the response in healthy infants | NIRO 500 | Forehead | Between day 1–3 | Infants with HIE have decreased rCBF in the frontal lobes during auditory stimulation, (decrease of HbO2 and HbT) compared to normal infants |
| Chock et al. (34) | Retrospective chart review | ≥36 | 38 | To review cerebral and renal tissue saturation during TH | INVOS 5100C | Lateral forehead | 110 h | Renal tissue saturation was lower than cerebral tissue saturation during TH |
| Dehaes et al. (35) | Observational | ≥36 | 27 | To assess cerebral hemodynamics and oxygen metabolism during and after TH | Hybrid FDNIRS–DCS system | Left, middle, and right frontal | 10–16 sec 3 times/ location during TH, rewarming, and post-TH | CMRO2i and CBF lower in neonates with HIE during TH compared with post –TH and controls |
| Forman et al. (36) | Prospective observational | >35 | 20 | To assess the feasibility and reliability cerebral perfusion monitoring in NE | INVOS, neonatal sensors | Center of the forehead | 84 h | SctO2 increased over first 30 h of TH and stayed high for the remainder of the study |
| Gagnon and Wintermark (37) | Case series | >38 | 3 | To examine the impact of PPHN on cerebral oxygenation in infants on TH after HIE | FORE-SIGHT | Forehead (bilateral) | 86 h | Periods of pulmonary hypertensive crisis were associated with significant drop in cerebral saturation, indicating that PPHN can independently cause further injury |
| Goeral et al. (38) | Prospective observational | >36 | 32 | To assess the predictive values of aEEG and NIRS parameters and the respective cut-off values regarding short-term outcomes in HIE | INVOS 5100C | Frontoparietal | 102 h | No significant differences in NIRS values were observed between groups (normal and abnormal MRI). Combined score of BP, aEEG and NIRS increased the accuracy of early outcome prediction |
| Govindan et al. (39) | Observational | n.r. | 4 | To identify the efficacy of a modified approach to quantify the pressure passivity | NIRO 200 | Bilateral fronto-temporal areas | n.r. | A modified coherence estimation approach over every 30 s epochs identified better the association between HbD and MABP (pressure passivity index). |
| Govindan et al. (40) | Observational | ≥38 | 4 | To review the efficacy of a novel method to quantify neuro-vascular coupling (NVC) using NIRS and EEG | NIRO 200 | Bilateral fronto-temporal areas | n.r. | Two infants who survived, revealed the emergence of NVC during TH. Other 2 infants who did not survive, lacked this feature. |
| Grant et al. (41) | Observational | ≥33 | 43 | Whether StO2, CBV, and rCMRO2 have the potential to distinguish between neonates with brain injury (HIE and other etiologies) and healthy controls | FDNIRS | 5 ± 3 locations. Primary location –forehead, also temporal and parietal | n.r. | No significant difference in StO2 between brain-injured and normal neonates. However, CBV and estimates of rCMRO2 were significantly increased in the brain injured group compared with all other clinical groups |
| Gucuyener et al. (42) | Observational | ≥36 | 8 | Investigate the correlations between aEEG and NIRS monitoring and outcome following HIE | NIRO 200 | Parietal | 30 min each before cooling, at 34°C during TH and after rewarming | Detection of context-sensitive changes in TOI and FTOE can be helpful especially while monitoring the effects of a therapy, in conjunction with other cerebral trend monitors |
| Howlett et al. (43) | Observational | >37 | 24 | To describe the relationship between autoregulation during TH and brain injury on MRI after HIE | INVOS, Neonatal sensor | Forehead | 84 h | Optimal MABP identified using HVx (running correlation between HbT and MAP). Infants with evidence of brain injury on MRI spent longer time below MAPOPT during rewarming than neonates with no or mild injury. Neonates with moderate/severe injury on MRI had greater MAP deviation below MAPOPT during rewarming than neonates without injury |
| Huang et al. (44) | Observational | ≥37 | 41 | To find out the clinically useful parameters for the assessment of HIE using NIRS | TSNIR-3 | n.r. | n.r. | rSO2 in quiet condition and rSO2, HbO2 and Hb during the inhalation of oxygen may be helpful for HIE infants. rSO2 for the healthy group increased rapidly, with the increase 7 ± 2.3%, compared to 3 ± 1.5% in HIE infants |
| Jain et al. (45) | Prospective observational | >36 | 21 | To examine the value of CrSO2 | INVOS | Midfrontal | 48 h | Higher absolute CrSO2 values during TH correlates with subcortical injury on MRI and poor neurodevelopmental outcome |
| Kovacsova et al. (46) | Observational | >36 | 55 | To investigate the SRS algorithm using a multi-distance broadband NIRS device to derive tissue saturation | Broadband NIRS | Frontal | 14 h | A broadband NIRS multi-distance device can provide additional information to improve the robustness of the SRS estimation of cerebral tissue saturation |
| Lee et al. (47) | Prospective observational | 64 | To examine whether optimizing cerebral autoregulation is associated with decreased brain injury | INVOS 5100 | Bilateral forehead | 90 h | Blood pressure deviation from the optimal vasoreactivity was associated with evidence of brain injury on MRI, independent of initial birth asphyxia | |
| Lemmers et al. (48) | Observational | ≥36 | 39 | To re-evaluate the early predictive value of rScO2, cFTOE and aEEG background pattern for outcome | INVOS 4100–5100, with adult sensor | Frontoparietal | 84 h | Higher rScO2 values and lower aEEG background pattern scores in neonates with adverse neurodevelopmental outcome |
| Massaro et al. (49) | Prospective observational | >36 | 10 | To assess cerebral perfusion and oxygenation differences after HIE | FORE-SIGHT | n.r. | 84 h | Cerebral FTOE values were significantly reduced after rewarming in infants with evidence of injury on MR imaging |
| Massaro et al. (50) | Observational | ≥35 | 36 | To investigate if the duration and magnitude of the pressure passivity during TH were related to outcome | NIRO 200 | Fronto-temporal | 84 h | Higher PPI in both hemispheres and high gain on right hemisphere were associated with poor outcome |
| Meek et al. (2) | Observational | ≥36 | 27 | To measure changes in cerebral hemodynamics during the first 24 hrs of life after perinatal asphyxia, and relate them to outcome | NIRO1000 or NIRO500 | n.r. | 1–4 occasions between 2 and 72 h of age | increase in CBV on the 1st day of life is a sensitive predictor of adverse outcome. A reduction in CBVR is almost universally seen following asphyxia, but is not significantly correlated with severity of adverse outcome |
| Mitra et al. (51) | Prospective observational | ≥35 | 14 | To assess the cerebral metabolic and hemodynamic changes during the rewarming period after TH | Broadband NIRS | Frontal | 14 h | The relationship between mitochondrial metabolism and oxygenation became impaired with rising Lac/NAA. Cardiovascular parameters remained stable during rewarming. |
| Mitra et al. (52) | Prospective observational | >34 | 23 | To investigate the effects of disturbances in brain metabolism following HIE on outcome, using a wavelet based metabolic reactivity index between oxCCO and MABP | Broadband NIRS | Frontal | 1 h | Pressure passive changes in brain metabolism were associated with injury severity and outcome following HIE. oxCCO-MABP semblance as a metabolic reactivity index correlated with MRS derived Lac/NAA. It also differed among groups of mild to moderate and severe injury based on MRI score and neuro-developmental outcome at 1 yr of age. |
| Mitra et al. (53) | Prospective observational | >36 | 14 | To assess the changes in brain hemodynamics and metabolism following HIE in relation to initial degree on injury on EEG | Broadband NIRS | Frontal | 12.5 h | Significant difference noted in derangement of brain oxygenation and metabolism between infants with mild and moderate to severe EEG abnormality |
| Nakamura et al. (54) | Observational | >35 | 11 | To find the influence of CBV and ScO2 on clinical outcome | TRS-10 | Parietal | 72 h | Early postnatal CBV and ScO2 elevations were predictive of a poor outcome based on MRI injury |
| Niezen et al. (55) | Retrospective observational study | ≥37 | 39 | To determine the predictive value of aEEG and NIRS alone, and in combination, during the first 4 days after HIE | INVOS 5100C | left or right frontoparietal | 96 h | After 48 h of TH, a higher rcSO2 was associated with a severely abnormal outcome |
| Peng et al. (56) | Observational | >=36 | 18 | To assess whether NIRS Identifies the newborns during TH, who later develop brain injury | FORE-SIGHT | Forehead | 79 h | rSO2 was consistently higher in newborns who developed brain injury on MRI and was significantly higher on day 1 compared to infants who did not develop injury on brain MRI. |
| Shellhaas et al. (57) | Observational | ≥37 | 21 | To evaluate the utility of aEEG and rSO2 for short-term outcome | INVOS 5100C | bilateral parietal regions, also one sensor over thigh | 90 h | During day 3 of cooling and during rewarming, loss of physiologic variability (by systemic NIRS) was the best predictor of poor short-term outcome. Cerebral rSO2 variability was independent from short-term outcome |
| Shellhaas et al. (58) | Observational | ≥35 | 4 | To evaluate the variability of cerebral oxygen metabolism in sleep-wake states among sick neonates | INVOS 5100C | bilateral parietal-occipital regions | 11.7 h | Cerebral oxygenation (sSO2) and FTOE significantly differ between wakefullness and sleep stages |
| Shellhaas et al. (59) | Observational | “term neonates” | 18 | To identify systemic and cerebral risk factors for adverse long-term neuro-developmental outcome following HIE | INVOS 5100C | Bilateral parietal regions, neonatal sensors | 72 h | Mean cerebral rSO2 was not different between those with favorable vs. adverse 18-months outcomes, but those with favorable outcomes had higher systemic rSO2 variability during hours 48–72 of cooling |
| Tax et al. (60) | Observational | >34 | 38 | To investigate peripheral oxygenation and perfusion in the first 48 h after perinatal asphyxia | NIRO 300 | Left calf | n.r. | Peripheral oxygenation and perfusion are compromised with worsening degree of acidosis on cord blood gas |
| Tekes et al. (61) | Observational | ≥35 | 27 | To assess whether lower ADC values on MRI would correlate with worse autoregulatory status measured by NIRS | INVOS | Forehead bilateral | n.r. | Lower ADC scalars in the PCS, PLIC and PP correlated with blood pressure deviation below MAPOPT during hypothermia and rewarming |
| Tian et al. (62) | Observational | ≥36 | 9 | Quantitative evaluation of cerebral autoregulation | INVOS 4100-5100, neonatal sensor | Frontoparietal | 72 h | Cerebral autoregulation was time-scale –dependant. Both in phase and anti-phase coherence were related to worse outcome |
| Toet et al. (15) | Observational | >37 | 18 | To determine the value of rSO2, FTOE measured by NIRS, and aEEG in relation to neuro-developmental outcome | INVOS 4100 | Left parietal | 48 h | rSO2 values remained normal and stable in infants with a normal outcome with values between 50 and 70% 30,33 but increased to supranormal values after 24 h in the infants with an adverse outcome. From 24 h onward, the values of rSO2 of the infants with an adverse outcome were significantly higher as compared with those with a favorable outcome |
| Van Bel et al. (18) | Observational | >35 | 31 | To investigate whether cerebral perfusion and metabolism drops following hypoxia | Radiometer | Source on ant. fontanel, detector on Fronto-parietal | 4–6 h | CBV, HbO, HbR, and Cytaa3 decreased in the first 12 hs of life in severely asphyxiated neonates who subsequently developed neurologic abnormalities |
| Wintermark et al. (63) | Observational | ≥36 | 7 | To determine the correlation between measurements of brain perfusion by NIRS and by MRI | FORE-SIGHT Cerebral Oximeter | Forehead | 84 h | SctO2 and CBF increase from days 1 to 2 in all, despite TH. SctO2 and CBF are highly correlated in newborns with severe encephalopathy. Newborns with severe encephalopathy have lower CBF than newborns with moderate encephalopathy. Newborns developing brain HI injury have higher SctO2 than newborns not developing brain injury |
| Wu et al. (64) | Retrospective cohort study | ≥36 | 20 | To review the cerebral hemodynamic response during rewarming following TH | INVOS 5100C | Frontal region | 14 h | CrSO2 and cerebral FTOE remained unchanged during rewarming |
| Zaramella et al. (65) | Case control study | ≥36 | 22 | To assess the diagnostic and prognostic value of TOI and ΔCBV in HIE | NIRO 300 | Fronto-temporal | Duration n.r., study on day 1 | Increased TOI on day 1 suggested abnormal outcome at 1 year of age |
ADC, Apparent diffusion coefficient; aEEG, Amplitude integrated electroencephalogram; HIE, Hypoxic-ischemic encephalopathy; CBO, Cerebral blood oxygenation; CBV, Cerebral blood volume; CCVR, Cerebral blood volume response; CrSO2, Cerebral regional oxygen saturation; Cytaa3, Cytochrome oxidase; DCS, Diffusion correlation spectroscopy; EEG, Electroencephalography; FDNIRS, Frequency-domain near-infrared spectroscopy; FTOE, Fractional tissue oxygen extraction; HbO, Oxy-hemoglobin; HbR, Deoxy-hemoglobin; MABP, Mean arterial blood pressure; MRI, Magnetic resonance imaging; MRS, Magnetic resonance spectroscopy; NE, Neonatal encephalopathy; NIRS, Near Infrared spectroscopy; NVC, Neurovascular coupling; oxCCO, Oxidation state of cytochrome c oxidase; PCS, Posterior centrum semiovale; PLIC, Posterior limb of internal capsule; PP, Putamen and globus pallidus; rCMRO2, Relative cerebral metabolic rate of oxygen consumption; rSO2, Regional oxygen saturation; rScO2, Regional cerebral tissue oxygen saturation; SctO2, Regional cerebral tissue oxygen saturation; StO2, Cerebral tissue oxygenation; TH, Therapeutic hypothermia; TOI, Tissue oxygenation index; TH, Therapeutic hypothermia; THI, Total hemoglobin index.