Sverre Wikström

Early single-channel aEEG/EEG predicts outcome in very preterm infants

Aim:  To characterize early amplitude‐integrated electroencephalogram (aEEG) and single‐channel EEG (aEEG/EEG) in very preterm (VPT) infants for prediction of long‐term outcome.

Detection of ‘EEG bursts’ in the early preterm EEG: Visual vs. automated detection

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 (approximately 1-10s) 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.

Early amplitude-integrated EEG correlates with cord TNF-alpha and brain injury in very preterm infants

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.

Premedication for intubation with morphine causes prolonged depression of electrocortical background activity in preterm infants

Background:Sedative and analgesic medications are used in critically ill newborns, but little is known about their effects on electrocortical activity in preterm infants. We hypothesized that morphine might induce prolonged neurodepression, independent of blood pressure, as compared with rapid sequence induction/intubation(RSI).Methods:Of 34 infants enrolled in a randomized controlled trial (RCT) comparing RSI (including thiopental 2–3 mg/kg and remifentantil 1 mcg/kg) with morphine (0.3 mg/kg) as premedication for intubation, 28 infants (n = 14 + 14; median gestational age 26.1 wk and postnatal age 138 h) had continuous two-channel amplitude-integrated electroencephalogram (aEEG/EEG) and blood pressure monitoring during 24 h after the intubation. Thirteen infants not receiving any additional medication constituted the primary study group. Visual and quantitative analyses of aEEG/EEG and blood pressure were performed in 3-h epochs.Results:RSI was associated with aEEG/EEG depression lasting <3 h. Morphine premedication resulted in aEEG/EEG depression with more discontinuous background and less developed cyclicity for 24 h, and during the first 9 h, interburst intervals (IBI) were significantly increased as compared with those of RSI treatment. The difference was not related to blood pressure.Conclusion:Premedication with morphine is associated with prolonged aEEG/EEG depression independent of blood pressure changes and may not be optimal for short procedures.

Carbon Dioxide and Glucose Affect Electrocortical Background in Extremely Preterm Infants

OBJECTIVES: To investigate if Paco2 and plasma glucose levels affect electrocortical activity. METHODS: 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. RESULTS: There was a linear relationship between Paco2 and IBI; increasing Paco2 was associated with longer IBIs. One day after birth, a 1-kPa increase in Paco2 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 Paco2 value of 5.1 kPa and was attenuated both at higher and lower Paco2 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. CONCLUSIONS: 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.

Measuring brain activity cycling (BAC) in long term EEG monitoring of preterm babies

Measuring fluctuation of vigilance states in early preterm infants undergoing long term intensive care holds promise for monitoring their neurological well-being. There is currently, however, neither objective nor quantitative methods available for this purpose in a research or clinical environment. The aim of this proof-of-concept study was, therefore, to develop quantitative measures of the fluctuation in vigilance states or brain activity cycling (BAC) in early preterm infants. The proposed measures of BAC were summary statistics computed on a frequency domain representation of the proportional duration of spontaneous activity transients (SAT%) calculated from electroencephalograph (EEG) recordings. Eighteen combinations of three statistics and six frequency domain representations were compared to a visual interpretation of cycling in the SAT% signal. Three high performing measures (band energy/periodogram: R = 0.809, relative band energy/nonstationary frequency marginal: R = 0.711, g-statistic/nonstationary frequency marginal: R = 0.638) were then compared to a grading of sleep wake cycling based on the visual interpretation of the amplitude-integrated EEG trend. These measures of BAC are conceptually straightforward, correlate well with the visual scores of BAC and sleep wake cycling, are robust enough to cope with the technically compromised monitoring data available in intensive care units, and are recommended for further validation in prospective studies.

Early detection of preterm intraventricular hemorrhage from clinical electroencephalography

Objectives:Intraventricular hemorrhage is a common neurologic complication of extremely preterm birth and leads to lifelong neurodevelopmental disabilities. Early bedside detection of intraventricular hemorrhage is crucial to enabling timely interventions. We sought to detect early markers of brain activity that preempt the occurrence of intraventricular hemorrhage in extremely preterm infants during the first postnatal days. Design:Cross-sectional study. Setting:Level III neonatal ICU. Patients:Twenty-five extremely preterm infants (22–28 wk gestational age). Measurements and Main Results:We quantitatively assessed electroencephalography in the first 72 hours of postnatal life, focusing on the electrical burst activity of the preterm. Cranial ultrasound was performed on day 1 (0–24 hr) and day 3 (48–72 hr). Outcomes were categorized into three classes: 1) no intraventricular hemorrhage (grade 0); 2) mild-moderate intraventricular hemorrhage (grades 1–2, i.e., germinal matrix hemorrhages or intraventricular hemorrhage without ventricular dilatation, respectively); and 3) severe intraventricular hemorrhage (grades 3–4, i.e., intraventricular hemorrhage with ventricular dilatation or intraparenchymal involvement). Quantitative assessment of electroencephalography burst shapes was used to preempt the occurrence and severity of intraventricular hemorrhage as detected by ultrasound. The shapes of electroencephalography bursts found in the intraventricular hemorrhage infants were significantly sharper (F = 13.78; p < 0.0001) and less symmetric (F = 6.91; p < 0.015) than in preterm infants without intraventricular hemorrhage. Diagnostic discrimination of intraventricular hemorrhage infants using measures of burst symmetry and sharpness yielded high true-positive rates (82% and 88%, respectively) and low false-positive rates (19% and 8%). Conventional electroencephalography measures of interburst intervals and burst counts were not significantly associated with intraventricular hemorrhage. Conclusions:Detection of intraventricular hemorrhage during the first postnatal days is possible from bedside measures of brain activity prior to ultrasound confirmation of intraventricular hemorrhage. Significantly, our novel automated assessment of electroencephalography preempts the occurrence of intraventricular hemorrhage in the extremely preterm. Early bedside detection of intraventricular hemorrhage holds promise for advancing individual care, targeted therapeutic trials, and understanding mechanisms of brain injury in neonates.

Prenatal phthalate exposure was associated with croup in Swedish infants

This study examined whether prenatal phthalate exposure was associated with lower or upper airway inflammation in infants.

Reference ranges and determinants of thyroid function during early pregnancy: the SELMA study.

Context Establishing reference ranges as well as identifying and quantifying the determinants of thyroid function during pregnancy is important for proper clinical interpretation and optimizing research efforts. However, such data are sparse, specifically for triiodothyronine measurements, and most studies do not take into account thyroid antibodies or human chorionic gonadotropin. Objective To determine reference ranges and to identify/quantify determinants of TSH, free T4 (FT4), free triiodothyronine (FT3), total T4 (TT4), and total triiodothyronine (TT3). Design, Setting, and Participants This study included 2314 participants of the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study, a population-based prospective pregnancy cohort of mother-child pairs. Reference ranges were calculated by 2.5th to 97.5th percentiles after excluding thyroperoxidase antibody (TPOAb)-positive and/or thyroglobulin antibody (TgAb)-positive women. Intervention None. Main Outcome Measures TSH, FT4, FT3, TT4, and TT3 in prenatal serum. Results After exclusion of TPOAb-positive women, reference ranges were as follows: TSH, 0.11 to 3.48 mU/L; FT4, 11.6 to 19.4 pmol/L; FT3, 3.72 to 5.92 pg/mL; TT4, 82.4 to 166.2 pmol/L; and TT3, 1.28 to 2.92 nmol/L. Additional exclusion of TgAb-positive women did not change the reference ranges substantially. Exposure to tobacco smoke, as assessed by questionnaires and serum cotinine, was associated with lower TSH and higher FT3 and TT3. Body mass index (BMI) and gestational age were the main determinants of TSH (only for BMI), FT4, FT3, TT4, and TT3. Conclusions We show that the exclusion of TgAb-positive women on top of excluding TPOAb-positive women hardly affects clinical reference ranges. We identified various relevant clinical determinants of TSH, FT4, FT3, TT4, and TT3 that could reflect endocrine-disrupting effects and/or effects on thyroid hormone transport or deiodination.

Early Electroencephalography Suppression and Postnatal Morbidities Correlate with Cerebral Volume at Term-Equivalent Age in Very Preterm Infants

Background: Early brain activity is associated with long-term outcome. Establishing a relation also with postnatal brain growth may increase our understanding of early life influences on preterm brain development. Objectives: The aim of this study was to investigate whether early electroencephalography (EEG) activity in infants born very preterm is associated with brain volumes at term, and whether postnatal morbidity affects this association. Methods: Very preterm infants (n = 38) with a median gestational age (GA) of 25.6 weeks had early recordings of single-channel EEG. The percentage of suppressed EEG, i.e., interburst intervals (IBI%) between 24 and 72 h of age, was analyzed in relation to brain volumes on magnetic resonance imaging performed at term-equivalent age, taking into account neonatal morbidities. Results: Early electrocortical depression and a higher IBI% were associated with increased cerebrospinal fluid volume (CSFV) and lower total brain volume relative to intracranial volume, also after adjustment for GA, postnatal morbidities, morphine administration, and postnatal head growth. Overall, an increase in IBI% to 1 SD from the mean corresponded with an increase in CSFV to +0.7 SD and a decrease in brain volume to -0.7 SD. The presence of 2 or more postnatal morbidities were associated with around 10% lower brain volumes. Conclusions: More suppressed early EEG activity of very preterm infants is associated with lower brain volume and increased CSFV at term age, also when adjusting for postnatal morbidities. The findings indicate the importance of pre- and early postpartal determinants of postnatal brain growth, possibly also including activity-dependent mechanisms for brain growth.