Brain injury and long-term outcome after neonatal surgery for non-cardiac congenital anomalies.

BACKGROUND: There is growing evidence that neonatal surgery for non-cardiac congenital anomalies (NCCAs) in the neonatal period adversely affects long-term neurodevelopmental outcome. However, less is known about acquired brain injury after surgery for NCCA and abnormal brain maturation leading to these impairments. METHODS: A systematic search was performed in PubMed, Embase, and The Cochrane Library on May 6, 2022 on brain injury and maturation abnormalities seen on magnetic resonance imaging (MRI) and its associations with neurodevelopment in neonates undergoing NCCA surgery the first month postpartum. Rayyan was used for article screening and ROBINS-I for risk of bias assessment. Data on the studies, infants, surgery, MRI, and outcome were extracted. RESULTS: Three eligible studies were included, reporting 197 infants. Brain injury was found in n = 120 (50%) patients after NCCA surgery. Sixty (30%) were diagnosed with white matter injury. Cortical folding was delayed in the majority of cases. Brain injury and delayed brain maturation was associated with a decrease in neurodevelopmental outcome at 2 years of age. CONCLUSIONS: Surgery for NCCA was associated with high risk of brain injury and delay in maturation leading to delay in neurocognitive and motor development. However, more research is recommended for strong conclusions in this group of patients. IMPACT: Brain injury was found in 50% of neonates who underwent NCCA surgery. NCCA surgery is associated with a delay in cortical folding. There is an important research gap regarding perioperative brain injury and NCCA surgery.

Brain Activity and Cerebral Oxygenation After Perinatal Arterial Ischemic Stroke Are Associated With Neurodevelopment.

Background and Purpose- In infants with perinatal arterial ischemic stroke (PAIS), early prognosis of neurodevelopmental outcome is important to adequately inform parents and caretakers. Early continuous neuromonitoring after PAIS may improve early prognosis. Our aim was to study early cerebral electrical activity and oxygenation measured by amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in term neonates with PAIS and relate these to the development of cerebral palsy and cognitive deficit. Methods- aEEG patterns and regional cerebral oxygen saturation (rScO2) levels of both hemispheres were studied for 120 hours from the first clinical symptoms of PAIS (ie, seizures) onward. Multivariable analyses were used to investigate the association between aEEG, near-infrared spectroscopy, clinical variables, and neurodevelopmental outcome. Results- In 52 patients with PAIS (gestational age, 40.4±1.4 weeks; birth weight, 3282±479 g), median time to a continuous background pattern was longer in the ipsilesional compared with the contralesional hemisphere (13.5 versus 10.0 hours; P<0.05). rScO2 decreased over time in both hemispheres but less in the ipsilesional one, resulting in a rScO2 asymmetry ratio of 4.5% (interquartile range, -4.3% to 5.9%; P<0.05) between hemispheres from day 3 after symptoms onward. Both time to normal background pattern and asymmetry in rScO2 were negatively affected by gestational age, size of the PAIS, use of antiepileptic drugs, and mechanical ventilation. After correction for size of the PAIS on magnetic resonance imaging, a slower recovery of background pattern on ipsilesional aEEG and increased rScO2 asymmetry between hemispheres was related with an increased risk for cognitive deficit (<-1 SD) at a median of 24.0 (interquartile range, 18.4-24.4) months of age. Conclusions- Recovery of background pattern on aEEG and cerebral oxygenation are both affected by PAIS and related to neurocognitive development. Both measurements may provide valuable early prognostic information. Additionally, monitoring cerebral activity and oxygenation may be useful in identifying infants eligible for early neuroprotective interventions and to detect early effects of these interventions.

Mortality in Robin sequence: identification of risk factors.

Although Robin sequence (RS) is a well-known phenomenon, it is still associated with considerable morbidity and even mortality. The purposes of this study were to gain greater insight into the mortality rate and identify risk factors associated with mortality in RS. We retrospectively reviewed all RS infants followed at the Wilhelmina Children's Hospital from 1995 to 2016. Outcome measurements were death and causes of death. The authors identified 103 consecutive RS infants with a median follow-up of 8.6 years (range 0.1-21.9 years). Ten of the 103 infants (10%) died at a median age of 0.8 years (range 0.1-5.9 years). Nine of these ten infants (90%) were diagnosed with an associated syndrome. Of these, seven infants died of respiratory insufficiency due to various causes (two related to upper airway obstruction). The other two syndromic RS infants died of arrhythmia due to hypernatremia and of West syndrome with status epilepticus. One isolated RS infant died of brain ischemia after MDO surgery. Cardiac anomalies were observed in 41% and neurological anomalies in 36%. The presence of a neurological anomaly was associated with a mortality rate of 40% versus 7% in infants with no neurological anomaly (p = 0.016), with an odds ratio of 8.3 (95% CI 1.4-49.0) for neurological anomaly versus no neurological anomaly. Mortality was 15% in infants with syndromic RS versus 2% in infants with isolated RS (p = 0.044). Mortality was not significantly associated with the presence of a cardiac anomaly, surgical treatment for severe respiratory distress in the neonatal period, or prematurity. CONCLUSION: RS represents a heterogeneous patient population and is associated with a high level of underlying syndromes. The present study reports a mortality rate of 10% significantly associated with syndromic RS and the presence of neurological anomalies. A multidisciplinary approach in all infants born with RS, including genetic testing and examination of neurological anomalies in a standardized way, is crucial to identify infants with underlying syndromes potentially associated with increased mortality. What is Known: • Reported mortality rates in Robin sequence vary from 2% to 26%. • Clinicians mainly focus on the morbidity of Robin sequence that includes respiratory complications due to upper airway obstruction in the period after birth. • Robin sequence represents a heterogeneous patient population and is associated with a high level of underlying syndromes. What is New: • The present study reports a mortality rate of 10% significantly associated with syndromic Robin sequence and the presence of neurological anomalies. • A multidisciplinary approach in all infants born with Robin sequence, including genetic evaluation and standardized workup for neurological anomalies, is crucial to identify infants with underlying syndromes potentially associated with increased mortality.

Neonatal Surgery for Noncardiac Congenital Anomalies: Neonates at Risk of Brain Injury.

OBJECTIVE: To evaluate the incidence of brain injury after neonatal surgery for noncardiac congenital anomalies using magnetic resonance imaging (MRI). STUDY DESIGN: An MRI was obtained in 101 infants at 7 days [range: 1-115] after neonatal surgery for major noncardiac congenital anomalies. Brain injury was assessed using T1, T2, diffusion weighted imaging, and susceptibility-weighted imaging. RESULTS: Thirty-two preterm infants (<37 weeks of gestation) and 69 full-term infants were included. MRI abnormalities were found in 24 (75%) preterm and 40 (58%) full-term infants. Parenchymal lesions were noted in 23 preterm (72%) and 29 full-term infants (42%). These consisted of punctate white matter lesions (n = 45), punctate cerebellar lesions (n = 17), thalamic infarction (n = 5), and periventricular hemorrhagic infarction (n = 4). Nonparenchymal abnormalities were found in 9 (28%) preterm and 26 (38%) full-term infants. These included supra- and infratentorial subdural hemorrhages (n = 30), intraventricular hemorrhage grade II (n = 7), and asymptomatic sinovenous thrombosis (n = 1). A combination of parenchymal lesions was present in 21 infants. Of infants who had an MRI within 10 days after surgery, punctate white matter lesions were visible on diffusion weighted imaging in 22 (61%), suggestive of recent ischemic origin. Type of congenital anomaly and prematurity were most predictive of brain injury. CONCLUSIONS: Infants who have neonatal surgery for noncardiac congenital anomalies are at risk of brain injury, potentially accounting for the neurodevelopmental delay frequently observed in this population. Further research is warranted into potential mechanisms of brain injury and its timing of onset. Long-term neurodevelopmental follow-up is needed in this vulnerable population.

Brain Oxygenation During Thoracoscopic Repair of Long Gap Esophageal Atresia.

BACKGROUND: Elongation and repair of long gap esophageal atresia (LGEA) can be performed thoracoscopically, even directly after birth. The effect of thoracoscopic CO2-insufflation on cerebral oxygenation (rScO2) during the consecutive thoracoscopic procedures in repair of LGEA was evaluated. METHODS: Prospective case series of five infants, with in total 16 repetitive thoracoscopic procedures. A CO2-pneumothorax was installed with a pressure of maximum 5 mmHg and flow of 1 L/min. Parameters influencing rScO2 were monitored. For analysis 10 time periods of 10' during surgery and in the perioperative period were selected. RESULTS: Median gestational age was 35+3 [range 33+4 to 39+6] weeks; postnatal age at time of first procedure 4 [2-53] days and time of insufflation 127[22-425] min. Median rScO2 varied between 55 and 90%. Transient outliers in cerebral oxygenation were observed in three patients. In Patient 2 oxygenation values below 55% occurred during a low MABP and Hb < 6 mmol/L. The rScO2 increased after erythrocytes transfusion. Patient 5 also showed a rScO2 of 50% with a Hb <6 mmol/L during all procedures, except for a substantial increase during a high paCO2 of 60 mmHg. Patient 4 had a rScO2 > 85% during the first procedure with a concomitant high FiO2 > 45%. All parameters recovered during the surgical course. CONCLUSIONS: This prospective case series of NIRS during consecutive thoracoscopic repair of LGEA showed that cerebral oxygenation remained stable. Transient outliers in rScO2 occurred during changes in hemodynamic or respiratory parameters and normalized after interventions of the anesthesiologist. This study underlines the importance of perioperative neuromonitoring and the close collaboration between pediatric surgeon, anesthesiologist and neonatologist.

A survey of the dose of inhalational agents used to maintain anaesthesia in infants.

BACKGROUND: Various animal studies suggest that currently used anaesthetics are toxic to the developing brain. Many reviews advise that the total anaesthetic drug exposure should be reduced but the dose usually used in clinical practice has not been clearly elucidated. OBJECTIVES: To provide an overview of the dose ranges currently used in clinical practice during the maintenance phase of anaesthesia in infants undergoing anaesthesia for noncardiac surgery and diagnostic procedures. DESIGN: A two-centre mixed prospective (London) and retrospective (Utrecht) observational cohort study. SETTING: Two independent tertiary paediatric referral centres in March and November 2013; Great Ormond Street Hospital (GOSH), London, United Kingdom and Wilhelmina Children's Hospital, University Medical Center Utrecht (UMCU), The Netherlands. PATIENTS: A total of 76 infants were included in the analysis, 38 infants from each hospital. METHODS: Patients from GOSH were matched by procedure, age and weight with patients from the UMCU. The end-tidal concentrations of the inhalational agents were investigated from anaesthetic charts during the maintenance phase and corrected for the age-specific minimal alveolar concentration (MAC), expressed as a percentage from the MAC (%MAC). RESULTS: Three different types of inhalational anaesthetics were used: sevoflurane, desflurane, isoflurane. The mean %MAC was 0.85. No significant differences in %MAC were found between GOSH and the UMCU (P = 0.329); the mean %MAC in GOSH was 0.87 and in the UMCU was 0.82. There was a significant increase in the %MAC in relation to age (slope = 0.036 MAC month, P < 0.001). Of all patients, 75% had an end-tidal concentration lower than 1 MAC. There was no significant effect of the use of analgesia on the end-tidal concentration of inhalational anaesthetics (P = 0.366). CONCLUSION: The concentration of inhalational anaesthetics in %MAC increased with age and was lowest in neonates. Most young infants received inhalational anaesthetics at a concentration below 1 MAC, which accords with current guidance to minimise anaesthetic drug exposure but may have unintended consequences.

T2-prepared velocity selective labelling: A novel idea for full-brain mapping of oxygen saturation.

BACKGROUND AND AIM: Disturbances in cerebral oxygenation saturation (SO2) have been linked to adverse outcome in adults, children, and neonates. In intensive care, the cerebral SO2 is increasingly being monitored by Near-InfraRed Spectroscopy (NIRS). Unfortunately NIRS has a limited penetration depth. The "modified T2-prepared Blood Imaging of Oxygen Saturation" (T2-BIOS) MR sequence provides a step towards full brain SO2 measurement. MATERIALS AND METHODS: Tissue SO2, and venous SO2 (SvO2) were obtained simultaneously by T2-BIOS during a respiratory challenge in ten healthy volunteers. These two measures were compared to SO2 that was obtained by a single probe MR-compatible NIRS setup, and to cerebral blood flow and venous SO2 that were obtained by arterial spin labelling and T2-TRIR, respectively. RESULTS: SO2-T2-BIOS and SO2-NIRS had a mean bias of -4.0% (95% CI -21.3% to 13.3%). SvO2-T2-BIOS correlated with SO2-NIRS (R2=0.41, p=0.002) and SvO2-T2-TRIR (R2=0.87, p=0.002). In addition, SO2-NIRS correlated with SvO2-T2-TRIR (R2=0.85, p=0.003) Frontal cerebral blood flow correlated with SO2-T2-BIOS (R2=0.21, p=0.04), but was not significant in relation to SO2-NIRS. DISCUSSION/CONCLUSION: Full brain SO2 assessment by any technique may help validating NIRS and may prove useful in guiding the clinical management of patient populations with cerebral injury following hypoxic-ischaemic events. The agreement between NIRS and T2-BIOS provides confidence in measuring cerebral SO2 by either technique. As it stands now, the T2-BIOS represents a novel idea and future work will focus on improvements to make it a reliable tool for SO2 assessment.

Neonatal brain oxygenation during thoracoscopic correction of esophageal atresia.

BACKGROUND: Little is known about the effects of carbon dioxide (CO2) insufflation on cerebral oxygenation during thoracoscopy in neonates. Near-infrared spectroscopy can measure perioperative brain oxygenation [regional cerebral oxygen saturation (rScO2)]. AIMS: To evaluate the effects of CO2 insufflation on rScO2 during thoracoscopic esophageal atresia (EA) repair. METHODS: This is an observational study during thoracoscopic EA repair with 5 mmHg CO2 insufflation pressure. Mean arterial blood pressure (MABP), arterial oxygen saturation (SaO2), partial pressure of arterial carbon dioxide (paCO2), pH, and rScO2 were monitored in 15 neonates at seven time points: baseline (T0), after anesthesia induction (T1), after CO2-insufflation (T2), before CO2-exsufflation (T3), and postoperatively at 6 (T4), 12 (T5), and 24 h (T6). RESULTS: MABP remained stable. SaO2 decreased from T0 to T2 [97 ± 3-90 ± 6 % (p < 0.01)]. PaCO2 increased from T0 to T2 [41 ± 6-54 ± 15 mmHg (p < 0.01)]. pH decreased from T0 to T2 [7.33 ± 0.04-7.25 ± 0.11 (p < 0.05)]. All parameters recovered during the surgical course. Mean rScO2 was significantly higher at T1 compared to T2 [77 ± 10-73 ± 7 % (p < 0.05)]. Mean rScO2 levels never dropped below a safety threshold of 55 %. CONCLUSION: The impact of neonatal thoracoscopic repair of EA with insufflation of CO2 at 5 mmHg was studied. Intrathoracic CO2 insufflation caused a reversible decrease in SaO2 and pH and an increase in paCO2. The rScO2 was higher at anesthesia induction but remained stable and within normal limits during and after the CO2 pneumothorax, which suggest no hampering of cerebral oxygenation by the thoracoscopic intervention. Future studies will focus on the long-term effects of this surgery on the developing brain.

The effects of CO2-insufflation with 5 and 10 mmHg during thoracoscopy on cerebral oxygenation and hemodynamics in piglets: an animal experimental study.

OBJECTIVE: To evaluate the effect of CO2-insufflation with 5 and 10 mmHg on cerebral oxygenation and hemodynamics in neonates. BACKGROUND: An increasing percentage of surgical interventions in neonates are performed by minimal invasive techniques. Recently, concerns have been raised regarding a decrease of cerebral oxygenation in neonates during thoracoscopy as a result of CO2-insufflation. METHODS: This was an animal experimental study. Piglets were anesthetized, intubated, ventilated, and surgically prepared for CO2-insufflation. Insufflation was done with 5 or 10 mmHg CO2 during 1 h. Arterial saturation (SaO2), heart rate (HR), mean arterial blood pressure (MABP), and cerebral oxygenation (rScO2) were monitored. CFTOE, an estimator of cerebral oxygen extraction ((SaO2 - rScO2)/SaO2)), was calculated. Arterial blood gases were drawn every 15': pre (T0), during (T1-T4) and after CO2-insufflation (T5). RESULTS: Ten piglets (4 kg) were randomized for 5 (P5) and 10 (P10) mmHg CO2-insufflation. Two P10 piglets needed resuscitation after insufflation, none P5. Linear mixed-effect modeling of paCO2, pH, and SaO2 showed that values were dependent on time and time squared (p < 0.001) but were not different between the 5 and 10 mmHg groups. Analysis demonstrated significant changes over time in heart rate and MABP between the 5 and 10 mmHg groups, with a significant higher heart rate and lower blood pressure in the 10 mmHg group (p < 0.001). For rScO2 and cFTOE, no group differences could be demonstrated, but a significant effect of time was found: rScO2 increased and cFTOE decreased (p < 0.001). CONCLUSIONS: Insufflation of CO2 during thoracoscopy with 10 mmHg caused more severe hemodynamic instability and seems to be related with a decrease of cerebral perfusion as represented by a higher oxygen extraction. CO2-insufflation of 5 mmHg for thoracoscopy seems to have no adverse effects on cerebral oxygenation.

Hypotension in preterm neonates: low blood pressure alone does not affect neurodevelopmental outcome.

OBJECTIVE: To compare neurodevelopmental outcome, mean arterial blood pressure (MABP), and regional cerebral oxygenation (rSco2) between preterm neonates treated for hypotension and controls. STUDY DESIGN: Preterm neonates (N = 66) with a gestational age (GA) ≤32 weeks, without a patent ductus arteriosus, treated for hypotension (dopamine ≥5 µg/kg/min) were included. Neonates were matched to controls for GA, birth weight, sex, and year of birth. The rSco2 was determined by using near-infrared spectroscopy. Monitoring of MABP, rSco2, and arterial saturation was started at admission and continued for at least 72 hours. Neurodevelopmental outcome was assessed at 18 and 24 months' corrected age by using the Griffiths Mental Development Scales or the Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS: Infants treated for hypotension spent more time with an MABP less than GA (median 9% vs 0%, P < .001) and time with an MABP/rSco2 correlation >0.5 (27% vs 17%, P < .001). Time spent with an rSco2 <50% and neurodevelopmental outcome at 18 and 24 months' corrected age were not significantly different between infants treated for hypotension and controls. The 26 neonates with an rSco2 <50% for >10% of time had a lower neurodevelopmental outcome at 18 months (median 99 vs 104, P = .02). CONCLUSION: An MABP less than GA (in weeks) was not associated with lower rSco2 or with lower neurodevelopmental outcome scores. However, regardless of MABP, low rSco2 was associated with lower neurodevelopmental outcome scores. Perfusion/oxygenation variables could be of additional value in neonatal intensive care.

Role of patent ductus arteriosus in preterms in long-term outcome.

OBJECTIVE: This study aimed to determine long-term neurodevelopmental outcome and cerebral oxygenation in extremely preterm infants, comparing those with a hemodynamic significant patent ductus arteriosus (hsPDA) to those without. STUDY DESIGN: We included infants born before 28 weeks of gestation from 2008 to 2010 with routine echocardiography. Prior to echocardiography, regional cerebral oxygen saturation was measured. At 5 years of age, we evaluated neurodevelopmental outcomes using the Movement Assessment Battery for Children 2nd Dutch edition for motor skills and the Wechsler Preschool and Primary Scale of Intelligence 3rd Dutch edition for cognition. RESULTS: A total of 66 infants (gestational age 26.6 ± 0.9 weeks, birth weight 912 ± 176 g) were included, 34 infants with a hsPDA (including treatment). The group infants with hsPDA showed lower pre-closure cerebral saturation levels (58.2 % ±7.8 % versus 62.8 % ±7.0 %; p = 0.01). At 5 years, impaired motor outcome occurred more often in infants with hsPDA (17 (53 %) vs. 7 (23 %); p = 0.01). In multivariate analysis existence of hsPDA remained unfavourably related to the motor subdomain "aiming and catching". There were no potential effects of hsPDA on cognitive performance at 5 years of age. CONCLUSION: Treatment-receiving infants with hsPDA appear to exhibit motor deficits, specifically in "aiming and catching", by the age 5. Persistent ductal patency could be a contributing factor.

Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage.

OBJECTIVE: To test the hypothesis that near-infrared spectroscopy (NIRS)-determined patterns of regional cerebral oxygen saturation (rScO2), cerebral fractional tissue oxygen extraction (cFTOE), and autoregulatory ability can identify neonates at risk for developing peri-intraventricular hemorrhage (PIVH). STUDY DESIGN: This case-control study is a subanalysis of 30 neonates who developed PIVH >12 hours after admission as part of a lager prospective observational cohort study comprising 650 preterm neonates born at ≤32 weeks' gestational age. PIVH was diagnosed by cranial ultrasound, performed at least once daily. Mean arterial blood pressure (MABP), NIRS-determined rScO2, cFTOE, and MABP-rScO2 correlation were monitored from birth to 72 hours of age. RESULTS: Infants with PIVH received more inotropic drugs before being diagnosed with PIVH. Significantly more infants with severe PIVH needed treatment for patent ductus arteriosus. The MABP-rScO2 correlation was >0.5 significantly more often before mild/moderate PIVH and after severe PIVH compared with controls. rScO2 was higher and cFTOE lower in infants before severe PIVH. CONCLUSION: NIRS-monitored rScO2 and cFTOE suggest cerebral hyperperfusion in infants with severe PIVH. Moreover, MABP-rScO2 correlation indicates more blood pressure-passive brain perfusion in infants with PIVH. Continuous assessment of patterns of cerebral oxygenation and arterial blood pressure may identify those preterm infants at risk for severe PIVH and prompt consideration of preventive measures.

Comparing near-infrared spectroscopy devices and their sensors for monitoring regional cerebral oxygen saturation in the neonate.

BACKGROUND: Near-infrared spectroscopy (NIRS) is an upcoming clinical method for monitoring regional cerebral oxygen saturation (rScO2) in neonates. There is a growing market offering different devices and sensors. Even though this technique is increasingly clinically applied, little is known about the similarities and/or differences in rScO2 values between the different devices and sensors. The aim of this study was to compare the rScO2 values obtained in (preterm) neonates with all available sensors of three frequently used NIRS devices. METHODS: Fifty-five neonates admitted to our neonatal intensive care unit (NICU) were included in this study. rScO2 was simultaneously monitored bilaterally with two different NIRS sensors (left and right frontoparietal) for at least 1 h. Then, the sensors were switched, and measurements were collected for at least another hour. RESULTS: We detected a rather close correlation between all investigated sensors from the three different NIRS devices, but absolute rScO2 values showed substantial differences: Bland-Altman analysis showed average differences from 10 to 15%. CONCLUSION: Although the rScO2 values correlated well between different NIRS sensors, sometimes there were substantial differences between the absolute rScO2 values, which may complicate clinical application.

Cerebral oxygenation and brain activity after perinatal asphyxia: does hypothermia change their prognostic value?

BACKGROUND: Hypothermia is an established therapy in term neonates to reduce death and disability after perinatal asphyxia. Near-infrared spectroscopy-monitored regional cerebral oxygen saturation (rScO2) and amplitude-integrated electroencephalogram (aEEG)-monitored background pattern have been shown to be early predictors of long-term neurodevelopmental outcome. The aim of this study was to investigate the prognostic value of rScO2 and aEEG for neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia. METHODS: In neonates with HIE who were subjected to hypothermia, the aEEG background pattern and rScO2 were studied prospectively from admission up to 84 h in relation to early magnetic resonance imaging and neurodevelopmental outcome at 18 mo of age. RESULTS: Of 39 infants, 12 neonates died because of neurological deterioration. One had an adverse outcome and 26 had a favorable outcome. The rScO2 was higher in neonates with adverse outcome, although aEEG scores were lower. Positive predictive values at 12, 24, and 36 h of age for adverse outcome ranged from 50 to 67% for rScO2 and aEEG; negative predictive values ranged from 73 to 96% for rScO2 and 90 to 100% for aEEG. Combining rScO2 and aEEG increased positive predictive values (70-91%) and negative predictive values (90-100%). CONCLUSION: During hypothermia, rScO2 and aEEG measurements are early predictors of long-term outcome after HIE. Combining both parameters further improves early prediction.

Evaluation of perinatal arterial ischemic stroke using noninvasive arterial spin labeling perfusion MRI.

BACKGROUND: Arterial spin labeling (ASL) magnetic resonance imaging (MRI) can evaluate brain perfusion in neonates noninvasively. The aim of this study was to investigate whether ASL MRI can demonstrate perfusion abnormalities in neonates diagnosed with perinatal arterial ischemic stroke (PAIS). METHODS: Pulsed ASL perfusion MR images were acquired in the subacute stage (5-6 d after birth) and at follow-up (13 d to 16 wk after birth) in four PAIS patients. Images were visually evaluated for hypo- and hyperperfusion. In addition, cerebral oxygenation was monitored using near infrared spectroscopy (NIRS). RESULTS: In three PAIS patients, ASL images showed hypoperfusion in the stroke area. In one of these, hyperperfusion was visualized in the periphery of the stroke area. In one PAIS patient, hyperperfusion was seen in the stroke area. In all infants, cerebral oxygenation was higher in the infarcted hemisphere as compared with the contralateral hemisphere. Follow-up ASL images showed partial recovery of perfusion in the stroke area. CONCLUSION: ASL perfusion MRI is able to reliably detect hypo- and hyperperfusion in PAIS patients and can be used to monitor the evolution of perfusion after an ischemic event.

Cerebral oxygenation during the first days of life in preterm and term neonates: differences between different brain regions.

Near-infrared spectroscopy is a noninvasive method for monitoring brain oxygenation. The aim of the study was to investigate differences between cerebral oxygenation in different brain regions in newborns. In a prospective study, we monitored simultaneously left and right frontoparietal and temporo-occipital regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue extraction (cFTOE: (arterial oxygen saturation (SaO2) - rScO2)/SaO2) using near-infrared spectroscopy. A 2-h measurement was performed on d 1, 3, and 7. We included 10 very preterm (GA <32 wk), 10 preterm (GA: 32-37 wk), and 10 term (GA ≥37 wk) neonates. Limits of agreement for difference of the measurements between different places were determined using the Bland-Altman method. In all subgroups, the rScO2 and cFTOE values at different regions were not different. Limits of agreement were between ±14 and ±18% for all subgroups. Left-to-right differences were small between different postnatal and GAs. A decrease and increase over time for rScO2 and cFTOE values was detected for all four brain regions, most pronounced for infants with GA <32 wk. Cerebral oxygenation in stable preterm and term neonates seems not to differ between different regions of the brain during the early neonatal period. However, variability of individual measurements was quite high as indicated by large limits of agreement.

Left-to-right differences of regional cerebral oxygen saturation and oxygen extraction in preterm infants during the first days of life.

In a prospective study, we monitored simultaneously left and right parieto-frontal-cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE) using near-infrared spectroscopy in 36 very preterm neonates during the first 3 d of life. Simple regression analysis showed a close correlation between left and right rScO2 (r = 0.89, p < 0.01) and cFTOE (r = 0.88, p < 0.01), respectively. The Bland and Altman-determined limits of agreement found overall limits of agreement of -8.5 to +9.5% and of -0.10 to +0.093% between left and right for rScO2 and for cFTOE, respectively. However, we found that during stable systemic oxygenation (i.e., arterial oxygen saturation [SaO2 between 85 and 97%]) the limits of agreement between left and right improved from -7.8 to +8.2% and -0.088 to +0.084 for rScO2 and cFTOE, respectively (all p < 0.05). We conclude that bilateral near-infrared spectroscopy-measured rScO2 and cFTOE can reveal differences up to 10% between left and right hemisphere, especially during unstable arterial saturations, which may indicate uneven cerebral oxygenation.

Cerebrovascular autoregulation in preterm fetal growth restricted neonates.

OBJECTIVE: To investigate the effect of fetal growth restriction (FGR) on cerebrovascular autoregulation in preterm neonates during the first 3 days of life. DESIGN: Case-control study. SETTING: Neonatal intensive care unit of the Wilhelmina Children's Hospital, The Netherlands. PATIENTS: 57 FGR (birth weight <10th percentile) and 57 appropriate for gestational age (AGA) (birth weight 20th-80th percentiles) preterm neonates, matched for gender, gestational age, respiratory and blood pressure support. METHODS: The correlation between continuously measured mean arterial blood pressure and regional cerebral oxygen saturation was calculated to generate the cerebral oximetry index (COx). Mean COx was calculated for each patient for each postnatal day. The percentage of time with impaired autoregulation (COx>0.5) was also calculated. RESULTS: FGR neonates had higher mean COx values than their AGA peers on day 2 (0.15 (95% CI 0.11 to 0.18) vs 0.09 (95% CI 0.06 to 0.13), p=0.029) and day 3 (0.17 (95% CI 0.13 to 0.20) vs 0.09 (95% CI 0.06 to 0.12), p=0.003) of life. FGR neonates spent more time with impaired autoregulation (COx value >0.5) than controls on postnatal day 2 (19% (95% CI 16% to 22%) vs 14% (95% CI 12% to 17%), p=0.035) and day 3 (20% (95% CI 17% to 24%) vs 15% (95% CI 12% to 18%), p=0.016). CONCLUSION: FGR preterm neonates more frequently display impaired cerebrovascular autoregulation compared with AGA peers on days 2 and 3 of life which may predispose them to brain injury. Further studies are required to investigate whether this impairment persists beyond the first few days of life and whether this impairment is linked to poor neurodevelopmental outcome.

Postoperative cerebral oxygenation was not associated with new brain injury in infants with congenital heart disease.

OBJECTIVE: The aim of this study was to evaluate postoperative indices of cerebral oxygenation and autoregulation in infants with critical congenital heart disease in relation to new postoperative ischemic brain injury. METHODS: This prospective, clinical cohort included 77 infants with transposition of the great arteries (N = 19), left ventricular outflow tract obstruction (N = 30), and single ventricle physiology (N = 28) undergoing surgery at 30 days or less of life. Postoperative near-infrared spectroscopy and physiologic monitoring were applied to extract mean arterial blood pressure, regional cerebral oxygen saturation, fractional tissue oxygen extraction, and regional cerebral oxygen saturation mean arterial blood pressure correlation coefficient (≥0.5 considered sign of impaired cerebral autoregulation). New postoperative ischemic injury was defined as moderate-severe white matter injury or focal infarction on magnetic resonance imaging. Low cardiac output syndrome was measured as lactate greater than 4 mmol/L with pH less than 7.30. RESULTS: After surgery, regional cerebral oxygen saturation was decreased in all congenital heart disease groups with a notable increase in regional cerebral oxygen saturation between 6 and 12 hours after surgery, on average with a factor of 1.4 (range, 1.1-2.4). Both single ventricle physiology and postoperative low cardiac output syndrome were associated with lower regional cerebral oxygen saturation and increased time with correlation coefficient of 0.5 or greater. New postoperative ischemic injury was seen in 39 patients (53%) and equally distributed across congenital heart disease groups. Postoperative regional cerebral oxygen saturation, fractional tissue oxygen extraction, and correlation coefficient were not independently associated with new postoperative white matter injury or focal infarction (mixed-model analysis, all F > 0.12). CONCLUSIONS: Postoperative indices of cerebral oxygenation and cerebral autoregulation are not independent predictors of new ischemic brain injury in infants with critical congenital heart disease. Further exploration of the complex interplay among low regional cerebral oxygen saturation, low cardiac output syndrome, and heart defect is required to identify potential biomarkers enabling early intervention for ischemic brain injury.

Effects of caffeine on the preterm brain: An observational study.

BACKGROUND AND AIM: Caffeine improves neurodevelopmental outcome of preterm infants. This study analyses the effects of caffeine on the neonatal brain. We hypothesized that caffeine has a neuroprotective effect through an increase in oxygen metabolism; reflected by increased cerebral oxygen extraction, electrical function, and perfusion. METHODS: Preterm infants <32 weeks gestation (GA) receiving their primary dose caffeine-base (10 mg/kg) were included. Ten minutes of stable monitoring were selected before, during, and every hour up to 6 h after caffeine. Near-infrared spectroscopy monitored regional cerebral oxygenation (rScO2) and extraction (FTOE). Amplitude-integrated electroencephalogram (aEEG) monitored minimum, mean and maximum amplitudes. Spontaneous activity transients (SAT) rate and the interval between SATs (ISI) were calculated. Mean arterial blood pressure (MABP), heart rate (HR) and arterial oxygen saturation (SaO2) were monitored. Arterial pCO2's were collected before and 4 h after caffeine. Brain perfusion was assessed 1 h before and 3 h after caffeine by Doppler-measured resistance-index (RI), peak systolic velocity (PSV) and end-diastolic velocity (EDV), in the anterior cerebral artery (ACA) and internal carotid artery (ICA). Results were presented in mean ±â€¯SD. RESULTS: 34 infants, mean GA 28.8 ±â€¯2.1 wk, were included. rScO2 significantly decreased from 69 ±â€¯11 to 63 ±â€¯12 1 h after caffeine, and recovered at 6 h (66 ±â€¯10). FTOE increased correspondingly. MABP and HR increased significantly. PSV in the ACA decreased slightly. Other Doppler variables, aEEG parameters, and SaO2 were unaffected. CONCLUSION: Caffeine increases oxygen extraction, suggesting a (transient) stimulating effect on brain metabolism. However, no substantial changes were found in brain perfusion and in electrical brain activity.