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Background aEEG/EEG measures in very preterm infants: Relation to physiology and outcome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The overall aim of this thesis was to characterize single-channel aEEG/EEG, recorded during the first postnatal days in preterm infants, in relation to brain function and two-year outcome.

Study I investigated if aEEG/EEG was associated with neonatal brain injury, inflammation and outcome in 16 very preterm (VPT) infants. The interburst interval (IBI) was prolonged, and aEEG amplitudes were lower in infants with brain injury, and in infants developing handicap. Cord blood TNF-α correlated with IBI.

Study II investigated inter-rater agreement of visual burst detection, as compared to automated burst detection based on a non-linear energy operator (NLEO) in an EEG data set from 12 extremely preterm (EPT) and 6 VPT infants. The sensitivity of the NLEO was 64 % and 69 % (EPT and VPT infants, respectively) and the specificity 96 % and 88 %. The algorithm was then modified to further improve the accuracy.

Study III investigated if arterial carbon dioxide and plasma glucose is associated with EEG continuity. In 247 sets of samples (PaCO2, plasma glucose, IBI) from 32 EPT infants there was a positive association between PaCO2 and IBI; higher PaCO2 was associated with longer IBI. Corrected for carbon dioxide, plasma glucose had a U-shaped association with IBI in infants with good outcome.

Study IV investigated the predictive value of aEEG/EEG in 41 EPT and 8 VPT infants. All VPT infants had good outcome. Predictors of outcome in EPT infants included presence or absence of burst-suppression, continuous activity and cyclicity, median IBI and interburst%. Seizures were associated with neonatal brain damage but not with outcome.

Improved preterm brain monitoring may in the future be used for early identification of infants at high risk of brain damage and adverse outcome, which may have implications for direction of care and for early intervention.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2011. , 74 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 647
Keyword [sv]
Electroencephalography, brain damage, prediction, interburst interval, Neurodevelopmental impairment
National Category
URN: urn:nbn:se:uu:diva-146737ISBN: 978-91-554-8010-3 (print)OAI: diva2:398838
Public defence
2011-04-04, Rosensalen, Akademiska sjukhuset, ing. 95, Uppsala, 13:15 (English)
Available from: 2011-03-14 Created: 2011-02-19 Last updated: 2011-05-04Bibliographically approved
List of papers
1. Early amplitude-integrated EEG correlates with cord TNF-α and brain injury in very preterm infants
Open this publication in new window or tab >>Early amplitude-integrated EEG correlates with cord TNF-α and brain injury in very preterm infants
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2008 (English)In: Acta Paediatrica, ISSN 0803-5253, Vol. 97, no 7, 915-919 p.Article in journal (Refereed) Published
Abstract [en]

AIM: To investigate if the early electroencephalogram (EEG) and amplitude-integrated EEG (aEEG) in very preterm infants is affected by perinatal inflammation and brain injury, and correlates with long-term outcome. METHODS: Sixteen infants born at 24-28 gestational weeks (median 25.5) had continuous EEG/aEEG during the first 72 h of life. Minimum and maximum EEG interburst intervals (IBI), and aEEG amplitudes were semi-automatically quantified and averaged over the recording period. Neonatal brain injury was diagnosed with repeated cranial ultrasound investigations. Nine cytokines from four time-points were analyzed during the first 72 h (umbilical cord blood, 6, 24 and 72 h), and outcome was assessed at 2 years of corrected age. RESULTS: Infants with neonatal brain injury (n=9) had prolonged IBI, 11.8 (9.6-23.2) sec versus 8.2 (7.1-11.6) sec in infants (n=7) without brain damage (p=0.005). Handicap at 2 years (n=8, including two infants without neonatally diagnosed brain injury) was associated with prolonged neonatal IBI and lower aEEG amplitudes. Also aEEG amplitudes were decreased in infants with neonatal brain injury. There was a significant positive correlation between the averaged IBI and cord blood TNF-alpha (rs=0.595, p=0.025). CONCLUSION: Early EEG depression is associated with increased cord blood TNF-alpha, neonatal brain damage and handicap at 2 years.

aEEG, brain injury;´, cytokines, preterm, prognosis
National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-89266 (URN)10.1111/j.1651-2227.2008.00787.x (DOI)000256395300021 ()18462469 (PubMedID)
Available from: 2009-02-10 Created: 2009-02-10 Last updated: 2011-05-04Bibliographically approved
2. Detection of 'EEG bursts' in the early preterm EEG: Visual vs. automated detection
Open this publication in new window or tab >>Detection of 'EEG bursts' in the early preterm EEG: Visual vs. automated detection
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2010 (English)In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 121, no 7, 1015-1022 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To describe the characteristics of activity bursts in the early preterm EEG, to assess inter-rater agreement of burst detection by visual inspection, and to determine the performance of an automated burst detector that uses non-linear energy operator (NLEO). Methods: EEG recordings from extremely preterm (n = 12) and very preterm (n = 6) infants were analysed. Three neurophysiologists independently marked bursts in the EEG, the characteristics of bursts were analyzed and inter-rater agreement determined. Unanimous detections were used as the gold standard in estimating the performance of an automated burst detector. In addition, some details of this automated detector were revised in an attempt to improve performance. Results: Overall, inter-rater agreement was 86% for extremely preterm infants and 81% for very preterm infants. In visual markings, bursts had variable lengths (similar to 1-10 s) and increased amplitudes (and power) throughout the frequency spectrum. Accuracy of the original detection algorithm was 87% and 79% and accuracy of the revised algorithm 93% and 87% for extremely preterm and very preterm babies, respectively. Conclusion: Visual detection of bursts from the early preterm EEG is comparable albeit not identical between raters. The original automated detector underestimates the amount of burst occurrence, but can be readily improved to yield results comparable to visual detection. Further clinical studies are warranted to assess the optimal descriptors of burst detection for monitoring and prognostication. Significance: Validation of a burst detector offers an evidence-based platform for further development of brain monitors in very preterm babies.

Neonatal intensive care unit, SAT, Brain monitoring, Neonatal EEG, Premature EEG
National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-136193 (URN)10.1016/j.clinph.2010.02.010 (DOI)000278222300007 ()20395172 (PubMedID)
Available from: 2010-12-10 Created: 2010-12-10 Last updated: 2011-05-04Bibliographically approved
3. Carbon Dioxide and Glucose Affect Electrocortical Background in Extremely Preterm Infants
Open this publication in new window or tab >>Carbon Dioxide and Glucose Affect Electrocortical Background in Extremely Preterm Infants
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2011 (English)In: Pediatrics, ISSN 0031-4005, Vol. 127, no 4, e1028-e1034 p.Article in journal (Refereed) Published
Abstract [en]


To investigate if Paco(2) and plasma glucose levels affect electrocortical activity.


Ours was an observational study of 32 infants with a gestational age of 22 to 27 weeks. We performed simultaneous single-channel electroencephalogram (EEG) and repeated blood gas/plasma glucose analyses during the first 3 days (n = 247 blood samples with corresponding EEG). Interburst intervals (IBIs) and EEG power were averaged at the time of each blood sample.


There was a linear relationship between Paco(2) and IBI; increasing Paco(2) was associated with longer IBIs. One day after birth, a 1-kPa increase in Paco(2) was associated with a 16% increase in IBI in infants who survived the first week without severe brain injury. EEG power was highest at a Paco(2) value of 5.1 kPa and was attenuated both at higher and lower Paco(2) values. Corrected for carbon dioxide effects, plasma glucose was also associated with IBI. Lowest IBI appeared at a plasma glucose level of 4.0 mmol/L, and there was a U-shaped relationship between plasma glucose level and EEG with increasing discontinuity at glucose concentrations above and below 4.0 mmol/L.


Both carbon dioxide and plasma glucose level influenced EEG activity in extremely preterm infants, and values considered to be within normal physiologic ranges were associated with the best EEG background. Increasing EEG discontinuity occurred at carbon dioxide levels frequently applied in lung-protection strategies; in addition, moderate hyperglycemia was associated with measurable EEG changes. The long-term effects of changes in carbon dioxide and glucose on brain function are not known.

National Category
urn:nbn:se:uu:diva-142722 (URN)10.1542/peds.2010-2755 (DOI)000289074800023 ()21444592 (PubMedID)
Available from: 2011-01-16 Created: 2011-01-16 Last updated: 2015-08-13Bibliographically approved
4. The predictive value of early single-channel aEEG/EEG in extremely preterm infants
Open this publication in new window or tab >>The predictive value of early single-channel aEEG/EEG in extremely preterm infants
(English)Manuscript (preprint) (Other academic)
interburst interval, seizure, cranial ultrasound, intraventricular hemorrhage, CRIB-II
urn:nbn:se:uu:diva-146735 (URN)
Available from: 2011-02-19 Created: 2011-02-19 Last updated: 2011-05-04

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