Automating Quantitative Measures of an Established Conventional MRI Scoring System for Preterm-Born Infants Scanned between 29 and 47 Weeks' Postmenstrual Age.

BACKGROUND AND PURPOSE: Conventional MR imaging scoring is a valuable tool for risk stratification and prognostication of outcomes, but manual scoring is time-consuming, operator-dependent, and requires high-level expertise. This study aimed to automate the regional measurements of an established brain MR imaging scoring system for preterm neonates scanned between 29 and 47 weeks' postmenstrual age. MATERIALS AND METHODS: This study used T2WI from the longitudinal Prediction of PREterm Motor Outcomes cohort study and the developing Human Connectome Project. Measures of biparietal width, interhemispheric distance, callosal thickness, transcerebellar diameter, lateral ventricular diameter, and deep gray matter area were extracted manually (Prediction of PREterm Motor Outcomes study only) and automatically. Scans with poor quality, failure of automated analysis, or severe pathology were excluded. Agreement, reliability, and associations between manual and automated measures were assessed and compared against statistics for manual measures. Associations between measures with postmenstrual age, gestational age at birth, and birth weight were examined (Pearson correlation) in both cohorts. RESULTS: A total of 652 MRIs (86%) were suitable for analysis. Automated measures showed good-to-excellent agreement and good reliability with manual measures, except for interhemispheric distance at early MR imaging (scanned between 29 and 35 weeks, postmenstrual age; in line with poor manual reliability) and callosal thickness measures. All measures were positively associated with postmenstrual age (r = 0.11-0.94; R2 = 0.01-0.89). Negative and positive associations were found with gestational age at birth (r = -0.26-0.71; R2 = 0.05-0.52) and birth weight (r = -0.25-0.75; R2 = 0.06-0.56). Automated measures were successfully extracted for 80%-99% of suitable scans. CONCLUSIONS: Measures of brain injury and impaired brain growth can be automatically extracted from neonatal MR imaging, which could assist with clinical reporting.

Fat trajectory after birth in very preterm infants mimics healthy term infants.

BACKGROUND: Infants born very preterm experience poor postnatal growth relative to intrauterine growth, but at term equivalent age, they have increased percentage body fat compared with infants born at term. OBJECTIVES: The aim of this study was to assess body composition in very preterm infants born before 32 weeks postmenstrual age and to compare this with infants born at 32-36 weeks of gestation. METHODS: Percentage fat, fat mass and fat-free mass were measured in 87 very preterm infants born <32 weeks of gestation and studied at 32-36 weeks and in 88 control infants born at 32-36 weeks of gestation and measured on days 2-5 postnatally. RESULTS: At 32-36 weeks, very preterm infants were lighter and shorter, had significantly greater percentage fat and absolute fat mass and had a significantly lower absolute fat-free mass than the control group. The trajectory in percentage fat over increasing postnatal age in very preterm infants was closely aligned to that in term infants. CONCLUSIONS: Infants born very preterm accumulate fat rapidly after birth and have a deficit in fat-free mass. Fat accumulation may be triggered by birth or associated events. If this rapid fat accretion is not taken into account, assessment of growth based on weight alone will underestimate the deficit in fat-free mass.

GLAST1b, the exon-9 skipping form of the glutamate-aspartate transporter EAAT1 is a sensitive marker of neuronal dysfunction in the hypoxic brain.

In normal brain, we previously demonstrated that the exon-9 skipping form of glutamate-aspartate transporter (GLAST; which we refer to as GLAST1b) is expressed by small populations of neurons that appear to be sick or dying and suggested that these cells were subject to inappropriate local glutamate-mediated excitation. To test this hypothesis we examined the expression of GLAST1b in the hypoxic pig brain. In this model glial glutamate transporters such as GLAST and glutamate transporter 1 (GLT-1) are down-regulated in susceptible regions, leading to regional loss of glutamate homeostasis and thus to brain damage. We demonstrate by immunohistochemistry that in those brain regions where astroglial glutamate transporters are lost, GLAST1b expression is induced in populations of neurons and to a lesser extent in some astrocytes. These neurons were also immunolabeled by antibodies against the carboxyl-terminal region of GLAST but did not label with antibodies directed against the amino-terminal region. Our Western blotting data indicate that GLAST1b expressed by neurons lacks the normal GLAST amino-terminal region and may be further cleaved to a smaller approximately 30-kDa fragment. We propose that GLAST1b represents a novel and sensitive marker for the detection of neurons at risk of dying in response to hypoxic and other excitotoxic insults and may have wider applicability in experimental and clinical contexts.

Fetal pulse oximetry for fetal assessment in labour.

BACKGROUND: Pulse oximetry could contribute to the evaluation of fetal well-being during labour. OBJECTIVES: To compare the effectiveness and safety of fetal pulse oximetry with conventional surveillance techniques. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2006), MEDLINE (1994 to November 2006), EMBASE (1994 to November 2006) and Current Contents (1994 to November 2006). SELECTION CRITERIA: All published and unpublished randomised controlled trials that compared maternal and fetal outcomes when fetal pulse oximetry was used in labour, with or without concurrent use of conventional fetal surveillance, compared with using cardiotocography (CTG) alone. DATA COLLECTION AND ANALYSIS: At least two independent authors performed data extraction. Analyses were performed on an intention-to-treat basis. We sought additional information from the investigators of three of the reported trials. MAIN RESULTS: Five published trials comparing fetal pulse oximetry and CTG with CTG alone (or when fetal pulse oximetry values were blinded) were included. The published trials, with some unpublished data, reported on a total of 7424 pregnancies. Differing entry criteria necessitated separate analyses, rather than meta-analysis of all trials. Four trials reported no significant differences in the overall caesarean section rate between those monitored with fetal oximetry and those not monitored with fetal pulse oximetry or for whom the fetal pulse oximetry results were masked. Neonatal seizures and hypoxic ischemic encephalopathy were rare. No studies reported details of assessment of long-term disability. There was a statistically significant decrease in caesarean section for nonreassuring fetal status in the fetal pulse oximetry plus CTG group compared to the CTG group in two analyses: (i) gestation from 36 weeks with fetal blood sample (fetal blood sampling) not required prior to study entry (relative risk (RR) 0.68, 95% confidence interval (CI) 0.47 to 0.99); and (ii) when fetal blood sampling was required prior to study entry (RR 0.03, 95% CI 0.00 to 0.44). There was no statistically significant difference in caesarean section for dystocia when fetal pulse oximetry (fetal pulse oximetry) was added to CTG monitoring, compared with CTG monitoring alone, although the incidence rates varied between the trials. AUTHORS' CONCLUSIONS: The data provide limited support for the use of fetal pulse oximetry when used in the presence of a nonreassuring CTG, to reduce caesarean section for nonreassuring fetal status. The addition of fetal pulse oximetry does not reduce overall caesarean section rates. A better method to evaluate fetal well-being in labour is required.

Validation of an MRI Brain Injury and Growth Scoring System in Very Preterm Infants Scanned at 29- to 35-Week Postmenstrual Age.

BACKGROUND AND PURPOSE: The diagnostic and prognostic potential of brain MR imaging before term-equivalent age is limited until valid MR imaging scoring systems are available. This study aimed to validate an MR imaging scoring system of brain injury and impaired growth for use at 29 to 35 weeks postmenstrual age in infants born at <31 weeks gestational age. MATERIALS AND METHODS: Eighty-three infants in a prospective cohort study underwent early 3T MR imaging between 29 and 35 weeks' postmenstrual age (mean, 32+2 ± 1+3 weeks; 49 males, born at median gestation of 28+4 weeks; range, 23+6-30+6 weeks; mean birthweight, 1068 ± 312 g). Seventy-seven infants had a second MR scan at term-equivalent age (mean, 40+6 ± 1+3 weeks). Structural images were scored using a modified scoring system which generated WM, cortical gray matter, deep gray matter, cerebellar, and global scores. Outcome at 12-months corrected age (mean, 12 months 4 days ± 1+2 weeks) consisted of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley III), and the Neuro-Sensory Motor Developmental Assessment. RESULTS: Early MR imaging global, WM, and deep gray matter scores were negatively associated with Bayley III motor (regression coefficient for global score ß = -1.31; 95% CI, -2.39 to -0.23; P = .02), cognitive (ß = -1.52; 95% CI, -2.39 to -0.65; P < .01) and the Neuro-Sensory Motor Developmental Assessment outcomes (ß = -1.73; 95% CI, -3.19 to -0.28; P = .02). Early MR imaging cerebellar scores were negatively associated with the Neuro-Sensory Motor Developmental Assessment (ß = -5.99; 95% CI, -11.82 to -0.16; P = .04). Results were reconfirmed at term-equivalent-age MR imaging. CONCLUSIONS: This clinically accessible MR imaging scoring system is valid for use at 29 to 35 weeks postmenstrual age in infants born very preterm. It enables identification of infants at risk of adverse outcomes before the current standard of term-equivalent age.

Vibroacoustic stimulation for fetal assessment in labour in the presence of a nonreassuring fetal heart rate trace.

BACKGROUND: Fetal vibroacoustic stimulation is a simple, non-invasive technique where a device is placed on the maternal abdomen over the region of the fetal head and sound is emitted at a predetermined level for several seconds. It is hypothesized that the resultant startle reflex in the fetus and subsequent fetal heart rate acceleration or transient tachycardia following vibroacoustic stimulation provide reassurance of fetal well-being. This technique has been proposed as a tool to assess fetal well-being in the presence of a non-reassuring cardiotocographic trace during the first and second stages of labour. OBJECTIVES: To evaluate the clinical effectiveness and safety of vibroacoustic stimulation in the assessment of fetal well-being during labour, compared with mock or no stimulation for women with a singleton pregnancy exhibiting a non-reassuring fetal heart rate pattern. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 September 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), MEDLINE (January 1966 to January 2005), EMBASE (January 1966 to January 2005) and reference lists of all retrieved articles. We sought unpublished trials and abstracts submitted to major international congresses and contacted expert informants. SELECTION CRITERIA: All published and unpublished randomised trials that compared maternal and fetal/neonatal/infant outcomes when vibroacoustic stimulation was used to evaluate fetal status in the presence of a non-reassuring cardiotocographic trace during labour, compared with mock or no stimulation. DATA COLLECTION AND ANALYSIS: Two independent review authors identified potential studies from the literature search and assessed them for methodological quality and appropriateness of inclusion, using a data extraction form. Attempts to contact study authors for additional information were unsuccessful. MAIN RESULTS: The search strategies yielded six studies for consideration of inclusion. However, none of these studies fulfilled the requirements for inclusion in this review. AUTHORS' CONCLUSIONS: There are currently no randomised controlled trials that address the safety and efficacy of vibroacoustic stimulation used to assess fetal well-being in labour in the presence of a non-reassuring cardiotocographic trace. Although vibroacoustic stimulation has been proposed as a simple, non-invasive tool for assessment of fetal well-being, there is insufficient evidence from randomised trials on which to base recommendations for use of vibroacoustic stimulation in the evaluation of fetal well-being in labour in the presence of a non-reassuring cardiotocographic trace.

An improved survival model of hypoxia/ischaemia in the piglet suitable for neuroprotection studies.

The purpose of this study was to develop a newborn piglet model of hypoxia/ischaemia which would better emulate the clinical situation in the asphyxiated human neonate and produce a consistent degree of histopathological injury following the insult. One-day-old piglets (n=18) were anaesthetised with a mixture of propofol (10 mg/kg/h) and alfentinal (55.5 microg/kg/h) i.v. The piglets were intubated and ventilated. Physiological variables were monitored continuously. Hypoxia was induced by decreasing the inspired oxygen (FiO(2)) to 3-4% and adjusting FiO(2) to maintain the cerebral function monitor peak amplitude at < or =5 microV. The duration of the mild insult was 20 min while the severe insult was 30 min which included 10 min where the blood pressure was allowed to fall below 70% of baseline. Control piglets (n=4 of 18) were subjected to the same protocol except for the hypoxic/ischaemic insult. The piglets were allowed to recover from anaesthesia then euthanased 72 h after the insult. The brains were perfusion-fixed, removed and embedded in paraffin. Coronal sections were stained by haematoxylin/eosin. A blinded observer examined the frontal and parietal cortex, hippocampus, basal ganglia, thalamus and cerebellum for the degree of damage. The total mean histology score for the five areas of the brain for the severe insult was 15.6+/-4.4 (mean +/-S.D., n=7), whereas no damage was seen in either the mild insult (n=4) or control groups. This 'severe damage' model produces a consistent level of damage and will prove useful for examining potential neuroprotective therapies in the neonatal brain.

Infant autonomic function is altered by maternal smoking during pregnancy.

Sudden infant death syndrome (SIDS) is more prevalent in infants of smokers and may involve subtle alterations in autonomic control mechanisms. Autonomic function can be assessed using blood pressure responses to a passive head-up tilt and power spectral analysis of heart rate variability. This study aimed to determine if maternal smoking altered infants' responses to head-up tilt. Blood pressure and heart rate responses to a passive 70 degrees head-up tilt were compared in infants of smokers and non-smokers at 2-3 days and 3 months of age. There were no significant differences between groups in power spectral indices. At 2-3 days, the systolic pressure response to tilt was significantly different between groups (P<0.01). In infants of smokers, systolic pressure decreased by a mean (S.E.) of 7.7(1.1) mmHg, whereas in control infants it remained unchanged. At 3 months, systolic pressure in infants of smokers remained unchanged but increased in control infants by 6.2(2.1) mmHg (P<0.05). These results indicate that maternal smoking alters autonomically mediated cardiovascular responses in the infant.

Fetal pulse oximetry for fetal assessment in labour.

BACKGROUND: Fetal pulse oximetry (FPO) may contribute to the evaluation of fetal well-being during labour. OBJECTIVES: To compare the effectiveness and safety of FPO with conventional surveillance techniques, using the results of randomised controlled trials. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (31 July 2004) and conducted a systematic literature search of MEDLINE (1994 to July 2004), EMBASE (1994 to July 2004) and Current Contents (1994 to July 2004). SELECTION CRITERIA: All published and unpublished randomised controlled trials (RCTs) that compared maternal and fetal/neonatal/infant outcomes when FPO was used in labour, with or without concurrent use of conventional fetal surveillance, compared with using cardiotocography (CTG) alone. DATA COLLECTION AND ANALYSIS: Two independent reviewers performed data extraction. Analyses were performed on an intention-to-treat basis. We sought additional information from the investigators of the one reported trial. MAIN RESULTS: One published RCT (comparing FPO and CTG with CTG alone) was included; and two ongoing RCTs were identified. The single included RCT reported on 1010 cases. Unpublished pilot data were available for some outcomes to give a total of 1190 cases. There was no difference in the overall caesarean section rate between the two groups (relative risk (RR) 1.12, 95% confidence interval (CI) 0.91 to 1.37). There were less caesarean sections for nonreassuring fetal status in the FPO plus CTG group compared with the CTG only group (RR 0.45, 95% CI 0.28 to 0.72). The only reported neonatal seizure occurred in the CTG only group (RR 0.29 95% CI 0.01 to 7.08). Use of FPO with CTG decreased operative delivery (caesarean section, forceps, vacuum) for nonreassuring fetal status (RR 0.71, 95% CI 0.55 to 0.93) compared with CTG alone. No differences were seen for overall operative deliveries, endometritis, intrapartum or postpartum haemorrhage, uterine rupture, low Apgar scores, umbilical arterial pH or base excess, admission to the neonatal intensive care unit or fetal/neonatal death. REVIEWERS' CONCLUSIONS: The one published RCT reported that FPO decreased the caesarean section rate and operative delivery rates for nonreassuring fetal status, without adversely affecting maternal or fetal/neonatal outcomes. However, no difference was seen in the overall caesarean section (CS) or operative delivery rates because more CS were performed for dystocia in the FPO group. Further RCTs may address dystocia in labours monitored with FPO, maternal satisfaction with fetal monitoring and labour, long-term neurodevelopmental outcome of infants who exhibited nonreassuring fetal status in labour and costs of FPO.

Fluctuations in syringe-pump infusions: association with blood pressure variations in infants.

Flow continuity of two brands of syringe pumps and four brands of syringes was studied as a possible cause of hemodynamic fluctuations observed in neonates. Cyclical fluctuations were observed in the blood pressure of 14 neonates receiving dopamine infusions by syringe pump at flow rates from 0.2 to 1 mL/hr. Atom 235 and IVAC 770 pumps and various sizes of Terumo, Becton Dickinson, Omnifix, and IVAC syringes were evaluated. Flow continuity was assessed by using a gravimetric technique. The force needed to initiate and maintain syringe plunger motion was also measured. Noncontinuous flow was encountered most commonly with Terumo syringes, which delivered boluses at regular intervals at flow rates up to 5 mL/hr. The interval was dependent on flow rate and was similar to the time between the blood pressure fluctuations observed clinically. The syringe plunger force exhibited regular fluctuations indicative of the plunger sticking, and simultaneous measurement of flow established a direct temporal relationship with boluses. The other syringes tested did not exhibit such fluctuations. No differences were found between the two syringe pumps. Syringe plunger sticking, resulting in intermittent boluses and potential blood pressure fluctuations, may occur at low flow rates and with certain syringe brands. This appeared to be the cause of hemodynamic fluctuations in neonates receiving dopamine infusions.

Fetal pulse oximetry. Instrumentation and recent clinical experience.

Despite the pressing clinical need to improve fetal intrapartum surveillance, fetal oximetry has lagged well behind its application in the neonate because of the difficulty of developing a suitable method to record data from the fetus and testing its accuracy and reproducibility. Acceptable values of oxygen saturation that indicate fetal well-being are much lower than in neonates. The development of fetal pulse oximetry instrumentation is discussed. Recent clinical data acquired using the latest instrumentation are summarized and exciting new clinical applications proposed.

Measurement of extracellular fluid volume in the neonate using multiple frequency bio-impedance analysis.

Bioelectrical impedance analysis may be useful for cot-side monitoring of fluid balance in the neonatal intensive care unit (NICU). However the presence of cardio-respiratory monitoring equipment, non-ideal electrode placement and inability to obtain accurate crown-heel measurements may interfere with the ability to obtain reliable impedance data in this setting. This study aimed to investigate the effects of these factors on impedance analysis and to develop a prediction equation for extracellular fluid volume in the neonate. The study found that cardio respiratory monitoring had no significant effect on multi-frequency impedance measurements. Placement of current delivering electrodes on the ventral rather than dorsal surfaces improved separation of current and voltage electrodes but did not alter impedance results. Contralateral measurements were not significantly different to ipsilateral measurements. In 24 infants, extracellular fluid volume was measured using corrected bromide space (CBS) and simultaneous impedance analysis was performed. There was good correlation between CBS and the impedance quotient FF2/Ro where F is foot length and R0 is resistance at zero frequency. The study concludes that despite many potential difficulties associated with impedance analysis in the NICU, reliable measurements of impedance can be obtained and further work to validate prediction equations for ECF is warranted.

Electrical impedance plethysmography: its use in studying the cerebral circulation of the rabbit.

Electrical impedance plethysmography (EIP) is a noninvasive method that may be useful for both the continuous and serial measurement of changes in pulsatile cerebral blood volume and perhaps cerebral blood flow (CBF). It has not been well validated by comparison with other methods. To attempt to validate the EIP technique, the relationship between the peak amplitude of the transcranial, cardiac-synchronous impedance waveform (dZp) and cerebral blood flow measured by the radiolabelled microsphere technique (CBFrlm) and laser Doppler spectroscopy (CBFlds) was studied in rabbits. CBF was altered by inducing hypertension using metaraminol, hypotension by controlled haemorrhage or hypocarbia by hyperventilation. Twenty-three comparisons between dZp and CBFlds and 19 comparisons with CBFrlm were made in eight rabbits. The percentage change between each measurement using the three techniques in each animal was calculated. Using pooled data from all the animals, the linear regression equations were dZp = 0.5 CBFrlm + 33 (r = 0.38, p = 0.22, SE = 79) and dZp = 0.84 CBFlds + 19.6 (r = 0.46, p = 0.09, SE = 72). It is concluded that, in the anaesthetised rabbit, when large changes in CBF are induced by the manoeuvres described above, changes in dZp correlate very weakly with changes in either cortical or global CBF, and are influenced by other factors such as pulsatile intracranial blood volume.

Women's evaluations of their experience with fetal intrapartum oxygen saturation monitoring and participation in a research project.

OBJECTIVE: To evaluation women's perceptions of their participation in a research project in labour and their experience with fetal oxygen saturation monitoring. DESIGN: Survey using a questionnaire of women's rating of ten aspects of their experience with the project. SETTING: Royal Women's Hospital, Brisbane, Australia. PARTICIPANTS: Women who had participated in clinical observational studies of fetal intrapartum oxygen saturation monitoring. FINDINGS: 78 questionnaires were distributed and 77 returned. Overall, women evaluated their participation in this research project favourably, in terms of both their involvement in the research study and the use of fetal oxygen saturation monitoring. Several women commented that they appreciated the additional support they received form the research midwife. KEY CONCLUSIONS: Responses indicated that the women surveyed appreciated the opportunity to participate in research, were not averse to this new technology, and benefited from the perceived additional human contact and support they received. The high response rate to the questionnaire indicates that childbearing women are willing to be included in assessing the appropriateness of new birth technologies that may affect the well-being of women and babies in the future.

Continuous physiological monitoring: an integrated system for use in neonatal intensive care.

A general purpose, multi-channel digital data acquisition and analysis system (Amlab, Associative Measurements, Sydney) configured to collect and process physiological signals including electroencephalograph and blood pressure is described. Its advantages over analog and single-purpose instrumentation are discussed as is its potential, by the addition of transducers, to replace single-purpose instruments.

Effective implementation of time-frequency matched filter with adapted pre and postprocessing for data-dependent detection of newborn seizures.

Neonatal EEG seizures often manifest as nonstationary and multicomponent signals, necessitating analysis in the time-frequency (TF) domain. This paper presents a novel neonatal seizure detector based on effective implementation of the TF matched filter. In the detection process, the TF signatures of EEG seizure are extracted to construct the TF templates used by the matched filter. Matching pursuit (MP) decomposition and narrowband filtering are proposed for the reduction of artifacts prior to seizure detection. Geometrical correlation is used to consolidate the multichannel detections and to reduce the number of false detections due to remnant artifacts. A data-dependent threshold is defined for the classification of EEG. Using 30 newborn EEG records with seizures, the classification process yielded an overall detection accuracy of 92.4% with good detection rate (GDR) of 84.8% and false detection rate of 0.36FD/h. Better detection performance (accuracy >95%) was recorded for relatively long EEG records with short seizure events.

Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia-ischemia in the immature rodent brain.

Damage to major white matter tracts is a hallmark mark feature of hypoxic-ischemic (HI) brain injury in the preterm neonate. There is, however, no therapeutic intervention to treat this injury. Neuroinflammation is thought to play a prominent role in the pathogenesis of the HI-induced white matter damage but identification of the key mediators that constitute the inflammatory response remain to be fully elucidated. Cyclooxygenase enzymes (COX-1 and COX-2) are candidate neuroinflammatory mediators that may contribute to the HI-induced demise of early oligodendrocyte progenitors and myelination. We investigated whether ibuprofen, a non-steroidal anti-inflammatory drug that inhibits COX enzymes, can attenuate neuroinflammation and associated white matter damage incurred in a rodent model of preterm HI. On postnatal day 3 (P3), HI was produced (right carotid artery ligation and 30 min 6% O(2)). An initial dose of ibuprofen (100mg/kg, s.c.) was administered 2h after HI followed by a maintenance dose (50mg/kg, s.c.) every 24h for 6 days. Post-HI ibuprofen treatment significantly attenuated the P3 HI-induced increases in COX-2 protein expression as well as interleukin-1beta (IL-1ß) and tumour necrosis factor-alpha (TNF-α) levels in the brain. Ibuprofen treatment also prevented the HI-induced loss O4- and O1-positive oligodendrocyte progenitor cells and myelin basic protein (MBP)-positive myelin content one week after P3 HI. These findings suggest that a repeated, daily, ibuprofen treatment regimen administered after an HI insult may be a potential therapeutic intervention to prevent HI-induced damage to white matter progenitors and early myelination in the preterm neonate.

Kalman filter-based time-varying cortical connectivity analysis of newborn EEG.

Multivariate Granger causality in the time-frequency domain as a representation of time-varying cortical connectivity in the brain has been investigated for the adult case. This is, however, not the case in newborns as the nature of the transient changes in the newborn EEG is different from that of adults. This paper aims to evaluate the performance of the time-varying versions of the two popular Granger causality measures, namely Partial Directed Coherence (PDC) and direct Directed Transfer Function (dDTF). The parameters of the time-varying AR, that models the inter-channel interactions, are estimated using Dual Extended Kalman Filter (DEKF) as it accounts for both non-stationarity and non-linearity behaviors of the EEG. Using simulated data, we show that fast changing cortical connectivity between channels can be measured more accurately using the time-varying PDC. The performance of the time-varying PDC is also tested on a neonatal EEG exhibiting seizure.

Seizures are associated with brain injury severity in a neonatal model of hypoxia-ischemia.

Hypoxia-ischemia is a significant cause of brain damage in the human newborn and can result in long-term neurodevelopmental disability. The loss of oxygen and glucose supply to the developing brain leads to excitotoxic neuronal cell damage and death; such over-excitation of nerve cells can also manifest as seizures. The newborn brain is highly susceptible to seizures although it is unclear what role they have in hypoxic-ischemic (H/I) injury. The aim of this study was to determine an association between seizures and severity of brain injury in a piglet model of perinatal H/I and, whether injury severity was related to type of seizure, i.e. sub-clinical (electrographic seizures only) or clinical (electrographic seizures+physical signs). Hypoxia (4% O(2)) was induced in anaesthetised newborn piglets for 30 min with a final 10 min period of hypotension; animals were recovered and survived to 72 h. Animals were monitored daily for seizures both visually and with electroencephalogram (EEG) recordings. Brain injury was assessed with magnetic resonance imaging (MRI), (1)H-MR spectroscopy ((1)H-MRS), EEG and by histology (haematoxylin and eosin). EEG seizures were observed in 75% of all H/I animals, 46% displayed clinical seizures and 29% sub-clinical seizures. Seizure animals showed significantly lower background amplitude EEG across all post-insult days. Presence of seizures was associated with lower cortical apparent diffusion coefficient (ADC) scores and changes in (1)H-MRS metabolite ratios at both 24 and 72 h post-insult. On post-mortem examination animals with seizures showed the greatest degree of neuropathological injury compared to animals without seizures. Furthermore, clinical seizure animals had significantly greater histological injury compared with sub-clinical seizure animals; this difference was not apparent on MRI or (1)H-MRS measures. In conclusion we report that both sub-clinical and clinical seizures are associated with increased severity of H/I injury in a term model of neonatal H/I.