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Objective Seizures are common among newborns with hypoxic-ischaemic encephalopathy (HIE) but the relationship between seizure burden and severity of brain injury among neonates receiving therapeutic hypothermia (TH) for HIE is unclear. We tested the hypothesis that seizure burden is associated with cerebral tissue injury independent of amplitude-integrated EEG (aEEG) background activity. Study design Term neonates undergoing 72 h of TH at four centres were selected for study if they had continuous aEEG and MRI. The aEEG with corresponding 2-channel raw EEG (aEEG/EEG), was classified by severity of background and seizure burden; MR images were classified by the severity of tissue injury. Results Of 85 neonates, 52% had seizures on aEEG/ EEG. Overall, 35% had high seizure burden, 49% had abnormal aEEG background in the first 24 h and 36% had severe injury on MRI. Seizures were most common on the first day, with significant recurrence during and after rewarming. Factors associated with severe injury on MRI were high seizure burden, poor aEEG background, 10 min Apgar and the need for more than one anticonvulsant. In multivariate logistic regression, high seizure burden was independently associated with greater injury on MRI (OR 5.00, 95% CI 1.47 to 17.05 p=0.01). Neither aEEG background, nor 10 min Apgar score were significant. Conclusions Electrographic seizure burden is associated with severity of brain injury on MRI in newborns with HIE undergoing TH, independent of degree of abnormality on aEEG background. Seizures are common during cooling, particularly on day 1, with a significant rebound on day 4.

Hypothermia is the first effective neuroprotective intervention for newborns who are critically ill following a life-threatening asphyxial insult. It is not surprising that it has raised complex and controversial ethical dilemmas for investigators and clinicians. Given the history of iatrogenic disasters in neonatology, there has been an understandable reluctance to incorporate hypothermia into routine clinical practice until there is persuasive evidence from high quality randomised trials. This article reviews ethical issues that arose during the design of the original clinical trials, the implications of accumulating evidence of safety and efficacy, and the problems of ensuring informed parental participation in treatment decisions.

Background: The 2007 Cochrane review of therapeutic hypothermia for neonatal encephalopathy (NE) indicates a significant reduction in adverse outcome. UK National Institute for Clinical Excellence guidelines are awaited.Objective: To benchmark current opinion and practice to inform future strategies for optimal knowledge transfer for therapeutic hypothermia.Methods: A web based questionnaire (30 sections related to opinion and practice of management of NE) sent to the clinical leads of Level I, II and III neonatal units throughout the UK in November/December 2007.Results: One hundred and twenty-five (out of 195) UK neonatal units responded (response rate 66%). Ten percent, 37.5% and 51.5% responses were from level I, II and III units respectively. Twenty eight percent of all units provided therapeutic hypothermia locally (52% of level III units), however 80% of responders would offer therapeutic hypothermia if there was the facility. Overall, 57% of responders considered therapeutic hypothermia effective or very effective - similar for all unit levels; 43% considered more data are required. Regional availability of therapeutic hypothermia exists in 55% of units and 41% of units offer transfer to a regional centre for therapeutic hypothermia.Conclusion: In the UK in 2007, access to therapeutic hypothermia was widespread although not universal. More than half of responders considered therapeutic hypothermia effective. Fifty-five percent of perinatal networks have the facility to offer therapeutic hypothermia. The involvement of national bodies may be necessary to ensure the adoption of therapeutic hypothermia according to defined protocols and standards; registration is important and will help ensure universal neurodevelopmental follow up.

Very preterm birth (before 33 weeks gestation) is associated with the white matter damage, and a common sequel is reduced size and altered shape of the corpus callosum. We used diffusion tensor MRI to assess the corpus callosum in 63 very preterm and 45 term-born young adults. Indices of white matter microstructure [fractional anisotropy (FA) and mean diffusivity (MD)] were obtained for the genu, body and splenium. Very preterm females had higher MD in the genu than term-born females, indicating altered white matter microstructure. This was associated with lower performance IQ. The groups demonstrated different patterns of correlations between verbal learning and tract-specific FA and MD, consistent with the reorganization of white matter structure in adults born very preterm.

SUMMARY Studies of cerebral oxidative metabolism were carried out by phosphorous magnetic resonance spectroscopy during the first week of life in 52 infants with clinical and/or biochemical evidence of birth asphyxia. 15 infants died and the 37 survivors were assessed by a wide range of neurodevelopmental tests at one year of age. The minimum recorded values for cerebral phosphocreatine/inorganic phosphate concentration ratio (an index of oxidative metabolism) were related to outcome. The results showed a significant relation between the extent of derangement of oxidative metabolism and the severity of adverse outcomes, including death, neurodevelopmental impairment and reduced head growth. RESUME Relation entre le metabolisme oxydatif cerebral apres asphyxie a la naissance, et le devenir neurodeveloppemental, la croissance cerebrale a un an Des etudes du metabolisme oxydatif cerebral par spectroscopic de resonance magnetique au phosphore ont ete entreprises durant la premiere semaine de vie chez 52 nourrissons presentant une evidence clinique et/ou biochimique d'asphyxie a la naissance. 15 nourrissons moururent et les 37 survivants subirent de nombreux tests neurodeveloppementaux a l'âge d'un an. Les taux minima enregistres pour le rapport de concentration phosphocreatine/phosphates inorganiques (index de metabolisme oxydatif) furent relies au devenir. Les resultats montrerent une relation significative entre l'importance de la perturbation du metabolisme oxydatif et la gravite des devenirs negatifs, incluant le deces, le retard neurodeveloppemental et la reduction de la croissance cranienne. ZUSAMMENFASSUNG Beziehung zwischen oxydativem Hirnstoffwechsel nach Geburtsasphyxie und entwicklungsneurologischem Befund und Hirnentwicklung im Alter von einem Jahr Bei 52 Kindern mit klinischem und/oder biochemischem Hinweis auf eine Geburtsasphyxie wurden in der ersten Lebenswoche anhand der Phosphor-MRS Untersuchungen des oxydativen Hirnstoff-wechsels durchgefuhrt. 15 Kinder starben und die 37 Uberlebenden wurden im Alter von einem Jahr mit einer Batterie von entwicklungsneurologischen Tests untersucht. Die niedrigsten Werte fur das Verhaltnis von cerebralem Phosphokreatinin/inorganischem Phosphat (ein Index fur oxydativen Metabolismus) wurden zum Endbefund in Relation gestellt. Die Ergebnisse zeigten eine signifikante Beziehung zwischen den Storungen des oxydativen Metabolismus und dem Schweregrad der pathologischen Befunde, die Tod, entwicklungsneurologische Storungen und vermindertes Kopfwachtum beinhalteten. RESUMEN Relacion entre el metabolismo oxidativo cerebral despues de una asfixia de parto y el desarrollo neuroevolutivo y el crecimiento del cerebral ano de edad Se realizaron estudios del metabolismo oxidativo cerebral utilizando la espectroscopia de resonancia magnetica con fosforo durante la primera semana de vida en 52 ninos lactantes con evidencia clinica y/o bioquimica de asfixia al nacer. 15 lactantes murieron y los 37 supervivientes fueron evaluados con un amplio abanico de tests de neurodesarrollo al ano de edad. Los valores minimos registrados de la relacion en el cerebro de fosfocreatina/fosfato inorganico (indice de metabolismo oxidativo) se relacionaron con el curso seguido. Los resultados mostraron una relacion significativa entre la extension de la alteracion del metabolismo oxidativo y la gravedad de los cursos posteriores adversos, incluyendo el exitus, la alteracion del neurodesarrollo y la reduccion en el crecimiento de la cabeza.

OBJECTIVE. The absence of cerebral autoregulation in preterm infants has been associated with adverse outcome, but its bedside assessment in the immature brain is problematic. We used spatially resolved spectroscopy to continuously measure cerebral oxygen saturation (expressed as a tissue-oxygenation index) and used the correlation of tissue-oxygenation index with spontaneous fluctuations in mean arterial blood pressure to assess cerebral autoregulation. PATIENTS AND METHODS. The tissue-oxygenation index and mean arterial blood pressure were continuously measured in very premature infants (n = 24) of mean (±SD) gestational age of 26 (±2.3) weeks at a mean postnatal age of 28 (±22) hours. The correlation between mean arterial blood pressure and tissue-oxygenation index in the frequency domain was assessed by using cross-spectral analysis techniques (coherence and transfer-function gain). Values of coherence reflect the strength of linear correlation, whereas transfer-function gain reflects the amplitude of tissue-oxygenation index changes relative to mean arterial blood pressure changes. RESULTS. High coherence (coherence ≥ 0.5) values were found in 9 infants who were of lower gestational age, lower birth weight, and lower mean arterial blood pressure than infants with coherence of CONCLUSIONS. High coherence between mean arterial blood pressure and tissue-oxygenation index indicates impaired cerebral autoregulation in clinically sick preterm infants and is strongly associated with subsequent mortality. Cross-spectral analysis of mean arterial blood pressure and tissue-oxygenation index has the potential to provide continuous bedside assessment of cerebral autoregulation and to guide therapeutic interventions.

Objective: For optimal neuroprotection following transient perinatal hypoxia–ischaemia (HI), therapy should start before overt secondary energy failure and its irreversible neurotoxic cascade. Hypothermia is a promising neuroprotective intervention that also prolongs the therapeutic time window (“latent-phase”; the period between re-establishment of apparently normal cerebral metabolism after HI, and the start of secondary energy failure). The influences of HI severity on latent-phase duration and regional neuroprotection are unclear. Under normothermia and delayed whole-body cooling to 35 and 33 °C we aimed to assess relationships between HI severity and: (i) latent-phase duration; (ii) secondary-energy-failure severity; and (iii) neuronal injury 48 h following HI. Methods: Newborn piglets were randomized to: (i) HI-normothermia (n = 12), (ii) HI-35 °C (n = 7), and (iii) HI-33 °C (n = 10). HI-35 °C and HI-33 °C piglets were cooled between 2 and 26 h after HI. Insult and secondary-energy-failure severity and latent-phase duration were evaluated using phosphorus magnetic resonance spectroscopy and compared with neuronal death in cortical-grey and deep-grey matter. Results: More severe HI was associated with shorter latent-phase (p = 0.002), worse secondary energy failure (p = 0.023) and more cortical-grey-matter neuronal death (p = 0.016). Conclusions: Latent-phase duration is inversely related to insult severity; latent-phase brevity may explain the apparently less effective neuroprotection following severe cerebral HI.

Little information is available on long-term neurodevelopmental outcome of preterm infants with unilateral cerebral lesions detected by neonatal cranial ultrasound. This study aims to investigate the long-term outcome in a cohort of very preterm infants with unilateral cerebral lesions acquired in the perinatal period.A prospective cohort study of 668 preterm infants (33 weeks gestation; birth years 1985-1991) at a single tertiary perinatal centre in the UK. All infants had serial cranial ultrasound examination in the neonatal period. Outcome was assessed at age 8 years with the Wechsler Intelligence Scales for Children (WISC-R), Test of Visuo-motor Integration (VMI) and the Test of Motor Impairment (TOMI).Of the 668 infants, 369 infants had normal ultrasound scans. Two hundred and ninety nine children had bilateral parenchymal or non-parenchymal lesions (57 left-sided, 41 right-sided, 201 bilateral). Five hundred and thirty four (79%) children attended follow-up at age 8 years. Mean Full Scale IQ (FSIQ) was 101 (SD+/-16), 93 (SD+/-17), 102 (SD+/-17) and 91 (SD+/-21) for normal, left-sided, right-sided and bilateral lesion groups respectively. In all groups verbal IQ (VIQ) was higher than performance IQ (PIQ). Scores of FSIQ, VIQ and PIQ, VMI and TOMI were significantly different between the groups. After exclusion of children with parenchymal lesions, however, the difference was only significant for the TOMI scores. In all tests, children with left-sided lesions performed poorer than children with right-sided lesions.In this cohort of preterm infants with unilateral cerebral lesions, verbal function was preserved over non-verbal function independently of the side of lesion. Furthermore, the results suggest that the neurodevelopmental outcome of children with left-sided lesions is less favourable than that of children with right-sided lesions.

Perinatal asphyxia occurs in approximately 1-6 per 1000 live full-term births. Different patterns of brain damage can result, though the relation of these patterns to long-term cognitive-behavioural outcome remains under investigation. The hippocampus is one brain region that can be damaged (typically not in isolation), and this site of damage has been implicated in two different long-term outcomes, cognitive memory impairment and the psychiatric disorder schizophrenia. Factors in addition to the acute episode of asphyxia likely contribute to these specific outcomes, making prediction difficult. Future studies that better document long-term cognitive-behavioural outcome, quantitatively identify patterns of brain injury over development and consider additional variables that may modulate the impact of asphyxia on cognitive and behavioural function will forward the goals of predicting long-term outcome and understanding the mechanisms by which it unfolds.

This study investigated whether in preterm children who had ventricular dilatation (VD) on neonatal cranial ultrasound outcome at age 8 years was influenced by the additional presence of germinal matrix haemorrhage--intraventricular haemorrhage (GMH-IVH). Six-hundred and ninety-nine preterm infants (

INTRODUCTION. Very preterm birth (VPT; METHODS. We assessed 108 VPT individuals and 67 term-born controls at ages 18 to 19 years with the Eysenck Personality Questionnaire-Revised, short form (EPQ-RS). This questionnaire rates 3 dimensions of personality: extraversion (sociability, liveliness, sensation seeking); neuroticism (anxiety, low mood, low self-esteem); and psychoticism (coldness, aggression, predisposition to antisocial behavior). A fourth scale, “lie,” which measures dissimulation, is also derived. RESULTS. VPT individuals had significantly lower extraversion scores, higher neuroticism scores, and higher lie scores than term-born controls, after controlling for age at assessment and socioeconomic status. P scores were not significantly different between the 2 groups. There was a gender difference in that the increased neuroticism and decreased extraversion scores were accounted for mainly by VPT females. Associations between EPQ-RS scores and neonatal status, adolescent behavioral ratings, and body size at 18 to 19 years were assessed by using Kendall partial correlations, correcting for age at assessment and socioeconomic status. Gestational age, indices of neonatal hypoxia, and neonatal ultrasound ratings were not correlated with EPQ-RS scores. Birth weight was weakly associated with increased lie scores. Rutter Parents' Scale score, a measure of adolescent psychopathology, was associated with an increased neuroticism score. Poor social adjustment in adolescence was associated with an increased lie score. Height and weight at 18 to 19 years were not associated with EPQ-RS, but reduced occipitofrontal circumference was associated with both decreased extraversion and increased lie scores. CONCLUSIONS. Young adults who are born VPT have different personality styles from their term-born peers. This may be associated with an increased risk of psychiatric difficulties.

Studies in encephalopathic infants have demonstrated a brief phase of normal cerebral energetics following hypoxia-ischaemia prior to development of delayed energy failure. In experimental models, mild hypothermia has shown a consistent neuroprotective action, although its efficacy is critically dependent on the severity of the primary insult, the delay in initiating cooling, and the duration and depth of hypothermia. Early electroencephalographic assessment of encephalopathic infants has the potential to provide objective information about the preceding insult, aiding the selection of infants for enrollment to clinical trials. Preliminary results from a large randomised trial of selective head cooling suggest that early intervention can lead to significantly improved outcome in a subgroup of encephalopathic infants with intermediate electroencephalographic abnormalities. Further research in established experimental models is essential to improve the identification of suitable infants for treatment, to investigate the importance of variations in regional brain temperature, and to examine the therapeutic potential of hypothermia combined with other neuroprotective agents.

A recent online article in the Journal of Medical Ethics, which received wide media coverage, raised the possibility that children are being ‘subjected to torture’ due to the ‘fervent or fundamentalist views’ of their parents. However, the quality of argument in that article was inadequate to sustain such a radical thesis. There was no engagement with the perspectives of different religious traditions about end-of-life care. Instead the authors invoked practices such as male infant circumcision which are wholly irrelevant to the end-of-life theme. There were serious failings in relation to core principles of social and epide-miological research practice: the study based its conclusion on a sample of only six cases and failed to consider even the more obvious confounding features. Rather than demonizing the religious beliefs of parents there should be recognition of the need for mutual respect, dialogue based on an ‘expert-expert relationship’ and collaboration based on ‘shared understanding’.

When the fetal or neonatal brain is exposed to a severe transient episode of hypoxia–ischaemia, primary energy failure occurs within minutes leading to depletion of high-energy phosphate compounds. Following resuscitation, mitochondrial function is temporarily restored and energy metabolism returns towards normal. However, a complex series of cytotoxic reactions are initiated within the neuron leading to progressive failure of energy metabolism and ultimately cell death. Elevated cytosolic calcium, free radical release, pro-inflammatory mediators and mitochondrial injury are all implicated in this phase. The progression of encephalopathic signs is closely related to the development of secondary energy failure. If neuroprotective interventions are to be successful, then they must be commenced shortly after resuscitation and they must act at multiple sites within the cytotoxic cascade.

Two methods of neonatal cranial ultrasound (US) scanning, linear-array and mechanical-sector, were compared for their accuracy in predicting neurodevelopmental outcome in a cohort of 854, of whom 782 (92%) infants, all born less than 33 weeks of gestation and cared for on the Neonatal Intensive Care Unit at University College Hospital, London between 1979 and 1988, were included in the analysis. A total of 205 infants were studied by linear-array and 577 infants by mechanical-sector scan. Ultrasound findings were grouped into three risk categories on the basis of the US diagnosis. Outcome was assessed at 8 years of age. The probability estimates for neurologically disabling and nondisabling impairments, extra education and mean IQ were compared for the two US methods. There was no significant difference between the two methods in the accuracy of prediction of neurodevelopmental outcome.

Transient perinatal hypoxia-ischemia (HI) can lead to delayed cerebral damage beginning 8-24 h after resuscitation. Cerebroprotective therapies applied soon after HI may thus reduce the severity of brain injury. We have previously shown that MgSO4 administration to newborn piglets after HI fails to prevent the delayed global impairment in cerebral energy metabolism characteristic of severe brain damage. However, high extracellular concentrations of magnesium ions have been found to prevent specific excitotoxic neural cell death in vivo and in vitro. This study therefore examined the hypothesis that MgSO4 administration after HI reduces damage in some regions of the brain even though global energy metabolism is unaffected. Twelve newborn piglets were subjected to global cerebral HI by transient occlusion of both common carotid arteries and reduction of the inspired oxygen fraction to 0.12 until cerebral high-energy phosphates, measured by magnetic resonance spectroscopy, were significantly depleted. Subjects were randomly assigned to two groups of six: the first received MgSO4 (three doses, 400 mg/kg 1 h after resuscitation and 200 mg/kg at 12 and 24 h), and the second received placebo infusions. At 48 h after the start of the experiment, the piglets were killed and their brains were perfused, fixed, and embedded in paraffin wax. Five-micrometer sections were stained with hematoxylin and eosin to allow semiquantitative analysis of the severity and extent of injury to the hippocampus, cerebellum, cerebral cortex, caudate nucleus, thalamus, and striatum and the white matter tracts. There was no difference in the severity of tissue damage between the MgSO4-treated group and the placebo-treated animals in any brain region.

Life-sustaining treatment may be ethically withdrawn or withheld in critically ill or dying newborns if the action is genuinely in the best interests of the patient. This may occur in situations where life-sustaining treatment is futile because of a hopeless prognosis, or if the burdens of intensive treatment clearly outweigh its likely benefits. There is no fundamental ethical difference between the withholding of resuscitation and the withdrawing of life-sustaining treatment once it has commenced. However the actions may have different emotional and psychological implications. A decision to withdraw treatment should only be taken with the consensus of experienced staff caring for the baby and with the unpressurized agreement of the parents. Palliative care and symptomatic relief should always continue after life-support has been withdrawn. Emotional and practical support should be provided for parents and adequate training and support is essential for obstetric and neonatal unit staff.

The Hippocratic tradition of medical ethics enshrines respect for the sanctity of all human life, combined with a medical duty of care, and a duty to act according to the sole interests of the patient. The fundamental role of the doctor is to preserve and protect life. Intentional killing by commission or omission is therefore never appropriate. The doctor is called on to evaluate treatment options to withhold or withdraw any treatment in which the burdens outweigh the benefits. In the presence of significant uncertainty about the prognosis, or about the value of intensive treatment, the doctor should act to preserve life, and the withdrawal of life-sustaining treatment should only occur if the hopeless prognosis is ‘beyond reasonable doubt’. The withdrawal of futile or burdensome intensive treatment is neither morally nor practically equivalent to intentional killing.

To many people, especially writers of science fiction interested in preserving brains for narrative purposes, it seems self evident that cooling the brain protects it against hypoxic–ischaemic damage. Indeed, every day, cardiac surgeons and anaesthetists cool the brains of children during surgery to protect them against the effects of cardiac arrest or cardiopulmonary bypass. However there has long been a hope that cooling the brain after hypoxia–ischaemia might lessen cerebral injury. Observational data in support of this were collected by Westin and colleagues 40 years ago,1 but experimental studies in animal models at that time failed to support the hypothesis and it fell from favour.2 Now the belief is gaining ground again among basic researchers that moderate brain cooling to around 32oC is one of several interventions which can be applied after hypoxia–ischaemia to modify the process of brain cell death and so lessen cerebral damage. A cornerstone of this growing consensus was the realisation that not only do some cells die during hypoxia–ischaemia, but many more may die hours or days later.3 In the 1980s this delayed cerebral injury was shown in infants with birth asphyxia using31P magnetic resonance spectroscopy (MRS): asphyxiated infants were usually found to have normal cerebral energy metabolism soon after resuscitation, but oxidative phosphorylation became impaired 9 to 24 hours later and remained low for many days.4 The delayed impairment of energy metabolism was not contingent on continued hypoxia–ischaemia, nor was it associated with intracellular acidosis,5 but its magnitude was linearly related to the severity of later neurodevelopmental impairment and reduced brain growth.6 This was clear evidence that the effects of birth asphyxia might become manifest only some days after resuscitation, and indeed more recent data suggest that abnormal cerebral energy metabolism and cell death …

Quantitative techniques have been derived for the measurement of global cerebral blood flow, cerebral blood volume, its reponse to changing arterial carbon dioxide tension and mixed cerebral venous saturation in the human newborn undergoing intensive care. Normal ranges have been established and significant disturbances of cerebral oxygenation and perfusion have been demonstrated in a variety of pathological conditions. Recently, absolute cerebral deoxyhaemoglobin concentration has been obtained in the newborn using second differential spectroscopy. When combined with the measurement of total cerebral haemoglobin concentration, the mean saturation of cerebral blood (SmcO2) may be obtained, allowing global cerebral oxygenation to be determined continuously in the intensive care unit.Marked changes in the concentrations of cerebral oxy– and deoxyhaemoglobin have been observed in foetuses undergoing labour. Measurements of SmcO2from the foetal brain prior to delivery have shown the unexpected close correlation with acid–base status at birth Although movement artefact remains a theoretical risk during uterine contractions, preliminary measurements of optical path length by intensity–modulated spectroscopy have demonstrated only small fluctuations. In future the clinical application of time, phase and spatially resolved spectroscopy is likely to improve both the quantitative accuracy and the regional specificity of physiological measurements in the foetal and neonatal brain.

Magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) are capable of providing detailed information on cerebral oxidative metabolism in infants who have been resuscitated following an acute asphyxial episode. In severely affected infants studied by phosphorus and proton MRS, a consistent observation has been the development of deranged cerebral energy metabolism 12-48 hours after resuscitation, despite the maintenance of cardiovascular and respiratory homeostasis. Follow-up studies have indicated that the development of delayed energy failure is closely associated with the development of microcephaly and an adverse neurodevelopmental outcome. This pathophysiologic sequence has been modelled in newborn animals, allowing the mechanisms of delayed energy failure to be elucidated and cerebroprotective treatments to be tested. New developments in MRS and magnetic resonance imaging will enable quantitative and highly localised information on cerebral metabolism to be obtained in asphyxiated infants, increasing the accuracy of early clinical assessment. Significant cerebral vasodilatation and vasoparalysis of the cerebral circulation have been observed by NIRS in asphyxiated infants following resuscitation, but the prognostic value of this observation remains uncertain. Technical advances. in NIRS are likely to improve the reproducibility and accuracy of the technique, allowing the assessment of regional cerebral haemodynamics and metabolism at the bedside. (C) 1997 Wiley-Liss, Inc.

There has been extensive interest in assessing the long-term effects of preterm birth on brain white matter microstructure using diffusion MRI. Our aim in this study is to explore diffusion MRI differences between adolescents born preterm and term born controls, with a specific interest in characterising how such differences are manifested in white matter regions containing predominantly single or crossing fibre populations. Probabilistic high angular resolution tractography together with large deformation spatial normalisation were used to objectively investigate diffusion tensor parameters at regular intervals along fibre tracts of 45 adolescents born before 33 weeks of gestation and 30 term-born typically developing adolescents. Diffusion parameters were significantly different between preterms and controls at several levels along the cortico-spinal, thalamo-cortical and transcallosal pathways. Within the predominantly single fibre regions of the corpus callosum and internal capsule, in the preterms mean diffusivity (MD) was found to be increased while fractional anisotropy (FA) was decreased compared to controls. In contrast, however, where these pathways traversed the centrum semiovale, FA and MD were both significantly increased. The major contributor to reduced FA in preterms in predominantly single fibre regions was the increased radial eigenvalue (i.e. increased radial diffusivity). In predominantly crossing-fibre regions, the tensor eigenvalues are not meaningful, and the observed increase in FA is likely to be due to a decrease in anisotropy in one of the contributing fibre bundles. Similar differences (although less pronounced) were observed after excluding preterms with radiological signs of preterm brain injury from the sample. In summary, white matter microstructure was found to be altered in motor pathways in adolescents born preterm. Disruption of white matter (WM) microstructure in a single fibre region with resulting higher radial diffusivity leads to lower FA, whereas selective disruption of one fibre population in a crossing fibre region is observed to lead to higher FA. These findings challenge the common simplistic interpretation of FA as a measure of WM tract integrity.

Previous studies of the brains of normal infants demonstrated lower lactate (Lac)/choline (Cho), Lac/creatine (Cr), and Lac/N-acetylaspartate (Naa) peak-area ratios in the thalamic region (predominantly gray matter) compared with occipitoparietal (mainly unmyelinated white matter) values. In the present study, thalamic Cho, Cr, and Naa concentrations between 32-42 weeks' gestational plus postnatal age were greater than occipito-parietal: 4.6 +/- 0.8 (mean +/- SE), 10.5 +/- 2.0, and 9.0 +/- 0.7 versus 1.8 +/- 0.6, 5.8 +/- 1.5, and 3.4 +/- 1.1 mmol/kg wet weight, respectively: Lac concentrations were similar, 2.7 +/- 0.6 and 3.3 +/- 1.3 mmol/kg wet weight, respectively, In the thalamic region, Cho and Naa T(2)s increased, and Cho and Lac concentrations decreased, during development. Lower thalamic Lac peak-area ratios are principally due to higher thalamic concentrations of Cho, Cr, and Naa rather than less Lac. The high thalamic Cho concentration may relate to active myelination; the high thalamic Naa concentration may be due to advanced gray-matter development including active myelination. Lac concentration is higher in neonatal than in adult brain.

Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways connecting frontal and temporal language regions. To investigate this, we performed a comprehensive assessment of language and academic abilities in a group of adolescents born prematurely, some of whom had evidence of brain injury at birth (n = 50, mean age: 16 years, mean gestational age: 27 weeks) and compared them to a term-born control group (n = 30). Detailed structural magnetic resonance imaging and diffusion-tractography analyses of intrahemispheric and interhemispheric white matter bundles were performed. Analysis of intrahemispheric pathways included the arcuate fasciculus (dorsal language pathway) and uncinate fasciculus/extreme capsule (ventral language pathway). Analysis of interhemispheric pathways (in particular, connections between the temporal lobes) included the two major commissural bundles: the corpus callosum and anterior commissure. We found language impairment in 38% of adolescents born preterm. Language impairment was not related to abnormalities of the arcuate fasciculus (or its subsegments), but was associated with bilateral volume reductions in the ventral language pathway. However, the most significant volume reduction was detected in the posterior corpus callosum (splenium), which contains interhemispheric connections between the occipital, parietal and temporal lobes. Diffusion tractography showed that of the three groups of interhemispheric fibres within the splenium, only those connecting the temporal lobes were reduced. Crucially, we found that language impairment was only detectable if the anterior commissure (a second temporal lobe commissural pathway) was also small. Regression analyses showed that a combination of anatomical measures of temporal interhemispheric connectivity (through the splenium of the corpus callosum and anterior commissure) explained 57% of the variance in language abilities. This supports recent theories emphasizing the importance of interhemispheric connections for language, particularly in the developing brain.

The adenosine triphosphate (ATP)-dependent sodium/potassium pump extrudes intracellular sodium in exchange for extracellular potassium. Low ATP causes pump dysfunction increasing both intracellular sodium and water thereby enhancing metabolite mobility. This should be detectable by proton magnetic resonance spectroscopy (MRS) as increased metabolite transverse relaxation times (T2s). During secondary cerebral energy failure in the newborn piglet, proton and phosphorus MRS showed large increases in the T2s of choline, creatine, N-acetylaspartate, and lactate that correlated with ATP depletion. These results provide insight into factors affecting metabolite T2s and show that T2s may be useful for studying cellular oedema.

In vivo proton (1H) magnetic resonance spectroscopy (MRS) can measure cerebral metabolite concentrations and nuclear relaxation times. Function of the sodium (Na+)/potassium (K+) pump in cell membranes depends on adequate adenosine triphosphate (ATP) levels: intracellular Na+ is normally extruded in exchange for extracellular K+. Low ATP will cause pump dysfunction and loss of K+ accompanied by influx of Na+and water. Raised intracellular water may increase molecular mobility and this might be detectable as increased apparent transverse relaxation times (T 2's).1H-MRS of the brains of newborn piglets during acute hypoxia-ischemia revealed enigmatic increases in the peak area of creatine + phosphocreatine (Cr) relative to those of choline-containing compounds (Cho) andN-acetylaspartate (NAA). Interleaved1H and phosphorus (31P) MRS showed that theT 2's of both Cr and lactate (Lac) increased during acute hypoxia-ischemia and these changes correlated with reductions in nucleotide triphosphate (NTP; largely ATP). Within 50 h of metabolic recovery from the primary insult, as delayed energy failure developed, theT 2's of Cho, Cr, NAA, and Lac increased greatly. TheseT 2 changes also correlated with NTP depletion. These observations demonstrate important relationships betweenT 2's and function of the ATP-dependent Na+/K+ pump.

Intrapartum-related neonatal deaths (previously called “birth asphyxia”) are the fifth most common cause of deaths among children under 5 years of age, accounting for an estimated 814,000 deaths each year, and also associated with significant morbidity, resulting in a burden of 42 million disability adjusted life years (DALYs). This paper uses a systematic process developed by the Child Health Nutrition Research Initiative (CHNRI) to define and rank research options to reduce mortality from intrapartum-related neonatal deaths by the year 2015, in order to advance Millennium Development Goal (MDG) 4 for child survival. A list of 61 research questions was developed and scored by 21 technical experts. The top one-third of the ranked research investment options was dominated by delivery (implementation) research, whilst discovery (basic science) questions were not ranked highly, especially for expected reduction of mortality and inequity in the short time to 2015. Among the top four research questions, two relate to generation of demand for facility care at birth with specific mechanisms (such as transport and communication schemes, or financial incentives and conditional cash transfers). The other two top ranked priorities relate to use of community cadres and the roles they might effectively play—for example, screening for complications or supportive transfer to facilities and companionship at birth. The highest ranked discovery question concerned the interaction of hypoxia and infection, and the highest ranked epidemiologic question addressed prediction of intrapartum hypoxic injury. This exercise highlights the need for current research investments to focus on studies most likely to result in accelerated progress towards MDG 4 and in the countries where the most deaths occur.

Near-infrared spectroscopy is capable of providing noninvasive quantification of several important indices of cerebral hemodynamics, including cerebral blood flow, cerebral blood volume, and its response to changing arterial carbon dioxide tension. Preliminary results in term infants following acute perinatal asphyxia suggest that cerebral blood flow and volume are elevated, and the normal control mechanisms are abolished. These hemodynamic disturbances occur prior to the later development of secondary energy failure with its poor prognosis and may allow valuable prognostic information to be obtained in the first hours after birth.

Objectives: Preterm birth can be associated with long term neuromotor impairment. This is thought to be a consequence of injury to the white matter (WM) of the immature brain and subsequently altered brain development. Alterations in WM microstructure can be detected using diffusion-weighted magnetic resonance imaging (DW-MRI). Diffusion measures like fractional anisotropy (FA) and apparent diffusion coefficient (ADC) are often used to characterize the „integrity“ of WM pathways. This study attempts to assess the association of preterm birth with changes in the microstructure of the motor pathways. Methods: 45 preterm adolescents (15.6 years±1.3), born before 32 weeks' gestation, treated in a single level III unit, were studied together with 31 term-born healthy controls of similar age. MRI included a DW-sequence with high angular resolution (64 directions, b-value 3000s/mm2). Three of the preterm children had cerebral palsy (CP), further 12 had unspecific neurological findings (such as mild muscular hypo- or hypertonia or clumsiness). Image analysis consisted of definition of seed and target regions for tractography in a template image generated from the subjects. These regions were then spatially warped to each individual's images. Tractography of motor pathways was performed using constrained spherical deconvolution and probabilistic streamlines. Diffusion parameters were then measured along the motor tracts at equivalent levels for all subjects as defined in template space. Results: Diffusion parameters were significantly different between preterms and controls at several levels along the cortico-spinal, thalamo-cortical and transcallosal pathways. In the centrum semiovale, FA and ADC were significantly increased compared to controls. In contrast, within the highly organized WM regions of the corpus callosum and internal capsule, ADC was increased whilst FA was decreased. Fiber count in the corpus callosum was significantly lower in preterm children. All findings remained significant after excluding children with CP.

Trials in developed countries have shown that therapeutic hypothermia reduces the risk of death or severe disability in infants with neonatal encephalopathy. Cooling has been adopted as a standard of care in some parts of the world. Some Indian neonatal units have considered or even embarked upon cooling encephalopathic term newborn infants. In this article we discuss some of the potential ethical questions that should be considered before introducing therapeutic hypothermia in an Indian setting. Evidence from previous trials may not be relevant given significant differences in the epidemiology of neonatal encephalopathy in countries like India. There is a possibility that hypothermia would be ineffective or harmful. The most appropriate way to answer these concerns would be to perform a large randomized controlled trial of cooling in India. However, such trials will also raise potential ethical challenges. Cooling may also affect decisions about treatment withdrawal, and may create uncertainty about prognosis. It may exacerbate ethical problems relating to lack of neonatal intensive care bed space.

Objective: In preterm infants, white matter (WM) abnormalities detected on magnetic resonance imaging (MRI) at term-age are associated with early developmental delay. We set out to study this association in adolescents born preterm, by examining intellectual outcome in relation to markers of brain injury, focusing on the effects of WM reduction.Methods: Seventy-nine participants were recruited and assessed at a mean age of 16 years: 49 adolescents born preterm (

Objective: The purpose of this study was to measure by near-infrared spectroscopy changes in human fetal cerebral oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume during labor and to calculate mean cerebral hemoglobin oxygen saturation. Study Design: The effects of uterine contractions with and without fetal heart rate decelerations were compared in eight singleton term fetuses. Results were analyzed by analysis of variance. Results: In six of eight fetuses normal uterine contractions were associated with proportional decreases in both oxyhemoglobin and deoxyhemoglobin and a fall in cerebral blood volume without desaturation of cerebral hemoglobin. Contractions with fetal heart rate decelerations produced different results in that oxyhemoglobin fell but deoxyhemoglobin rose, indicating cerebral desaturation. In two of the eight fetuses normal contractions were associated with increases in oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume; no decelerations were seen in either fetus. Mean cerebral hemoglobin oxygen saturation calculated during normal contractions was 43% ± 10% (SD). Conclusion: Uterine contractions were associated with detectable changes from baseline in cerebral oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume.

Near-infrared spectroscopy is a new technique for noninvasive monitoring of tissue oxygenation and haemodynamics. Quantitative measurements can be made of oxyhaemoglobin, deoxyhaemoglobin, oxidized cytochrome and various haemodynamic indices. This technique is likely to prove increasingly valuable for: cotside monitoring brain oxygenation and haemodynamics in babies; investigating the mechanisms of damage to the brain; according the results of treatment; and assigning long-term prognosis.

Near infrared spectroscopy was used to investigate the effects of intravenously administered indomethacin (0.1-0.2 mg/kg) on cerebral haemodynamics and oxygen delivery in 13 very preterm infants treated for patent ductus arteriosus. 7 infants received indomethacin by rapid injection (30 s) and 6 by slow infusion (20-30 min). In all the infants cerebral blood flow, oxygen delivery, blood volume, and the reactivity of blood volume to changes in arterial carbon dioxide tension fell sharply after indomethacin. There were no differences in the effects of rapid and slow infusion. These falls in cerebral oxygen delivery and the disruption of cerebrovascular control might compromise cellular oxygen availability, particularly in regions of the brain where the arterial supply is precarious. Care should be taken to ensure that oxygen delivery is optimum before the administration of indomethacin to preterm infants.

ObjectiveTo investigate whether young adults born very preterm (VPT) (MethodsWe assessed 169 VPT and 101 term born individuals using the Clinical Interview Schedule – Revised.ResultsYoung adults born VPT had an increased risk for psychiatric disorder compared to controls (OR = 3.1, 95% CI = 1.1–8.6, p = 0.03). Those born VPT who had a history of psychiatric disorder in a first-degree relative, had an increase in risk for psychiatric disorder compared to those born VPT without a family history (OR = 5.2, 95% CI = 1.8–14.9, p = 0.002).ConclusionIndividuals born VPT are at increased risk of psychiatric illness in young adulthood compared to controls. In addition, a family history of psychiatric disorder in a first-degree relative may leave young adults born VPT particularly vulnerable to psychiatric illness.

OBJECTIVE. The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy.METHODS. A total of 218 term infants with moderate to severe neonatal encephalopathy plus abnormal amplitude-integrated electroencephalographic recordings, assigned randomly to head cooling for 72 hours, starting within 6 hours after birth (with the rectal temperature maintained at 34.5 ± 0.5°C), or conventional care, were studied. Death or severe disability at 18 months of age was assessed in a multicenter, randomized, controlled study (the CoolCap trial).RESULTS. Treatment, lower encephalopathy grade, lower birth weight, greater amplitude-integrated electroencephalographic amplitude, absence of seizures, and higher Apgar score, but not gender or gestational age, were associated significantly with better outcomes. In a multivariate analysis, each of the individually predictive factors except for Apgar score remained predictive. There was a significant interaction between treatment and birth weight, categorized as ≥25th or CONCLUSIONS. Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy. The protective effect of hypothermia was greater in larger infants.

OBJECTIVE: To evaluate whether therapeutic hypothermia alters the prognostic value of clinical grading of neonatal encephalopathy. STUDY DESIGN: This study was a secondary analysis of a multicenter study of 234 term infants with neonatal encephalopathy randomized to head cooling for 72 hours starting within 6 hours of birth, with rectal temperature maintained at 34.5 degrees C +/- 0.5 degrees C, followed by re-warming for 4 hours, or standard care at 37.0 degrees C +/- 0.5 degrees C. Severity of encephalopathy was measured pre-randomization and on day 4, after re-warming, in 177 infants; 31 infants died before day 4, and data were missing for 10 infants. The primary outcome was death or severe disability at 18 months of age. RESULTS: Milder pre-randomization encephalopathy, greater improvement in encephalopathy from randomization to day 4, and cooling were associated with favorable outcome in multivariate binary logistic regression. Hypothermia did not affect severity of encephalopathy at day 4, however, in infants with moderate encephalopathy at day 4, those treated with hypothermia had a significantly higher rate of favorable outcome (31/45 infants, 69%, P = .006) compared with standard care (12/33, 36%). CONCLUSION: Infants with moderate encephalopathy on day 4 may have a more favorable prognosis after hypothermia treatment than expected after standard care.

OBJECTIVES. The goals were to develop safe 4.7-T MRI examination protocols for newborn infants and to explore the advantages of this field strength in neonatal encephalopathy. METHODS. Nine ventilated newborn infants with moderate or severe encephalopathy were studied at 4.7 T, with ethical approval and informed parental consent. The custom-made, 4.7-T-compatible, neonatal patient management system included acoustic noise protection and physiologic monitoring. An adult head coil was used. Acquisition parameters for T2-weighted fast spin echo MRI and a variety of T1-weighted methods were adapted for MRI of neonatal brain at 4.7 T. The pulse sequences used had a radiofrequency specific absorption rate of RESULTS. Physiologic measures were normal throughout each scan. T2-weighted fast spin echo imaging provided better anatomic resolution and gray/white matter contrast than typically obtained at 1.5 T; T1-weighted images were less impressive. CONCLUSIONS. With appropriate safety precautions, MRI of newborn infants undergoing intensive care is as feasible at 4.7 T as it is at 1.5 T; our initial studies produced T2-weighted fast spin echo images with more detail than commonly obtained at 1.5 T. Although T1-weighted images were not adequately informative, additional pulse sequence optimization may be advantageous. A smaller neonatal head coil should also permit greater flexibility in acquisition parameters and even more anatomic resolution and tissue contrast. In neonatal encephalopathy, interpretation of the T2-weighted pathologic detail in combination with comprehensive neurodevelopmental follow-up should improve prognostic accuracy and enable more patient-specific therapeutic interventions. In addition, more precise relationships between structural changes and functional impairment may be defined.

Objective Hypothermia was not neuroprotective in low body weight (BW) infants on subgroup analysis in a recent clinical trial of selective head cooling (SHC) in neonatal encephalopathy (CoolCap Trial). Methods The BW dependence of regional cerebral temperature was investigated in 14 newborn piglets under normothermia (38.5°C), whole-body cooling (WBC; 36.5, 34.5, 32.5, and 30.5°C), or SHC (20, 15, and 10°C). Results Normothermia: Lower BW led to lower superficial brain temperature (p < 0.01). Deep to superficial brain and rectal to superficial brain temperature gradients increased with decreasing BW (both p < 0.05). WBC: Lower BW led to lower superficial brain temperature and higher rectal to superficial brain temperature gradient (p < 0.05 and p < 0.01, respectively). SHC: For lower BW, superficial and deep brain temperatures decreased (p < 0.01 and p < 0.05, respectively), whereas rectal to deep, rectal to superficial, and deep to superficial brain temperature gradients increased (p < 0.05, p < 0.01, and p < 0.05, respectively). Compared with SHC alone, superimposition of WBC (34.5°C) reduced all regional temperatures (all p < 0.001); gradients were unaffected. Interpretation Brain cooling (under normothermia, WBC, or SHC) was more efficient with lower BW due to greater head surface area-to-volume ratios. In the CoolCap Trial, low BW infants might have been excessively cooled. WBC and SHC may require BW adjustment to accomplish consistent regional temperatures and optimal neuroprotection. Ann Neurol 2006

OBJECTIVE. We sought to compare the prognostic utilities of early MRI spin-spin relaxometry and proton magnetic resonance spectroscopy in neonatal encephalopathy. METHODS. Twenty-one term infants with neonatal encephalopathy were studied at a mean age of 3.1 days (range: 1–5). Basal ganglia, thalamic and frontal, parietal, and occipital white matter spin-spin relaxation times were determined from images with echo times of 25 and 200 milliseconds. Metabolite ratios were determined from an 8-mL thalamic-region magnetic resonance spectroscopy voxel (1H point-resolved spectroscopy; echo time 270 milliseconds). Outcomes were assigned at age 1 year as follows: (1) normal, (2) moderate (neuromotor signs or Griffiths developmental quotient of 75–84), (3) severe (functional neuromotor deficit or developmental quotient RESULTS. Thalamic and basal ganglia spin-spin relaxation times correlated positively with outcome and predicted adversity. Although thalamic and basal ganglia spin-spin relaxation times were prognostic of adversity, magnetic resonance spectroscopy metabolite ratios were better predictors, and, of these, lactate/N-acetylaspartate was most accurate. CONCLUSIONS. Deep gray matter spin-spin relaxation time was increased in the first few days after birth in infants with an adverse outcome. Proton magnetic resonance spectroscopy was more prognostic than spin-spin relaxation time, with lactate/N-acetylaspartate the best measure. Nevertheless, both techniques were useful for early prognosis, and the potential superior spatial resolution of spin-spin relaxometry may define better the precise anatomic pattern of injury in the early days after birth.

OBJECTIVES. Fundamental questions remain about the precise temperature providing optimal neuroprotection after perinatal hypoxia-ischemia (HI). Furthermore, if hypothermia delays the onset of the neurotoxic cascade and the secondary impairment in cerebral energy generation, the “latent phase” may be prolonged, thus extending the period when additional treatments may be effective. The aims of this study were to investigate the effects of delayed systemic cooling at either 33°C or 35°C on the following: (1) latent-phase duration, and (2) cerebral metabolism during secondary energy failure itself, in the 48-hour period after transient HI. METHODS. Piglets were randomly assigned to the following: (1) HI-normothermic (HI-n) rectal temperature (Trectal; n = 12), (2) HI-Trectal 35°C (HI-35; n = 7), and (3) HI-Trectal 33°C (HI-33; n = 10). Groups were cooled to the target Trectal between 2 and 26 hours after HI. Serial magnetic resonance spectroscopy was performed over 48 hours. The effect of cooling on secondary energy failure severity (indexed by the nucleotide triphosphate/exchangeable phosphate pool [NTP/EPP] and phosphocreatine/inorganic phosphate [PCr/Pi] ratios) was assessed. RESULTS. Compared with HI-n, HI-35 and HI-33 had a longer NTP/EPP latent phase and during the entire study duration had higher mean NTP/EPP and PCr/Pi. The latent phase (both PCr/Pi and NTP/EPP) and the whole-brain cerebral energetics were similar for HI-35 and HI-33. During the hypothermic period, compared with HI-n, PCr/Pi was preserved in the cooled groups, but this advantage was not maintained after rewarming. Compared with HI-n, HI-35 and HI-33 had higher NTP/EPP after rewarming. CONCLUSIONS. Whole-body hypothermia for 24 hours at either 35 or 33°C, commenced 2 hours after resuscitation, prolonged the NTP/EPP latent phase and reduced the overall secondary falls in mean PCr/Pi and NTP/EPP during 48 hours after HI. Reducing the temperature from 35 to 33°C neither increased mean PCr/Pi and NTP/EPP nor further lengthened the latent phase.

Greater understanding of the rate of oxygen delivery and uptake in sick preterm and term infants undergoing intensive care is an important aim of brain-orientated neonatal medicine. Near infrared spectroscopy (NIRS) is a continuous, non-invasive and portable technique which can be used to measure cerebral blood flow (CBF) in infants. It is also possible to use spatially resolved spectroscopy to measure absolute mean cerebral oxygen saturation (SmcO2). The aim of this study was to investigate the derivation of cerebral metabolic rate for oxygen (CMRO2) from these two measurements. Nine preterm infants were studied, of median (range) gestational age 25 (23-37) weeks. A NIRO300 was used to measure CBF and SmcO2 simultaneously over the right and left hemisphere. Median (range) left and right cerebral hemisphere values for CMRO2 were 0.95 (0.79-1.53) ml 100g(-1) x min(-1) and 0.88 (0.69-1.46) ml 100g(-1) x min(-1), respectively. No significant difference was seen between the left- and right-sided values. These values are similar to median (range) values previously reported in infants using positron emission tomography or more invasive NIRS methods. Further work is necessary to define limits on the use of this technique, particularly in the assumption of the venous:arterial compartment volume ratio across different infants.

Background: Intrapartum events kill 1 million babies and over 1 million stillbirths globally each year and contribute to over half of all maternal deaths. Effective intrapartum monitoring could save many of these lives and also reduce morbidity in survivors. Intermittent fetal heart auscultation is as safe as continuous electronic monitoring in low risk labours. Doppler ultrasound fetal heart monitor is regarded as the most promising fetal monitoring device in low resource settings, but its use is limited by the cost, the availability of existing devices and the lack of alternative power supply options. Aims: To develop a Doppler fetal heart monitor which is accurate and reliable but has alternative options for power supply (wind-up, electric, solar), is robust and is affordable for use in the settings where most women and children die. To compare the reliability of the prototype with a cardiotocograph, assess if the prototype is appropriate for use in low resource settings and if it is acceptable to health workers and patients. Methods: Five prototypes have been designed and are being assessed for accuracy, acceptability, and usability in small field trials in South Africa. Results: 661 fetal heart rate readings in labour were measured on 17 mothers with the prototype and a cardiotocograph. Statistical analysis showed no significant difference between the readings from the prototype compared to the cardiotocograph. The correlation coefficient was 94%. The prototype readings remain accurate as the power supply runs low. Winding for 20 seconds results in an average of 2 min 31 seconds of continuous use. In a survey of 97 mothers 72 (74%) preferred the prototype to a cardiotocograph or fetoscope. Conclusion: Initial field testing shows this novel device to be accurate and acceptable to both mother and health workers in poor resource settings. The next steps will be rigorous testing of accuracy and the clinical impact in a multi-centre study as well as the addition of distance learning material.

We present our latest 3D optical tomography images of the neonatal brain, and discuss new image reconstruction techniques which incorporate prior anatomical information from MRI.