The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline * Corresponding author Email address: a.makropoulos11@imperial.ac.uk (Antonios Makropoulos) 1 These authors contributed equally Preprint submitted to NeuroImage January 7, 2018peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/125526 doi: bioRxiv preprint first posted online Apr. 10, 2017; consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity.

The developing Human Connectome Project is set to create and make available to the scientific community a 4-dimensional map of functional and structural cerebral connectivity from 20 to 44 weeks post-menstrual age, to allow exploration of the genetic and environmental influences on brain development, and the relation between connectivity and neurocognitive function. A large set of multi-modal MRI data from fetuses and newborn infants is currently being acquired, along with genetic, clinical and developmental information. In this overview, we describe the neonatal diffusion MRI (dMRI) image processing pipeline and the structural connectivity aspect of the project. Neonatal dMRI data poses specific challenges, and standard analysis techniques used for adult data are not directly applicable. We have developed a processing pipeline that deals directly with neonatal-specific issues, such as severe motion and motion-related artefacts, small brain sizes, high brain water content and reduced anisotropy. This pipeline allows automated analysis of in-vivo dMRI data, probes tissue microstructure, reconstructs a number of major white matter tracts, and includes an automated quality control framework that identifies processing issues or inconsistencies. We here describe the pipeline and present an exemplar analysis of data from 140 infants imaged at 38-44 weeks post-menstrual age.

Premature birth increases the risk of developing neurocognitive and neurobehavioural disorders. The mechanisms of altered brain development causing these disorders are yet unknown. Studying the morphology and function of the brain during maturation provides us not only with a better understanding of normal development, but may help us to identify causes of abnormal development and their consequences. A particular difficulty is to distinguish abnormal patterns of neurodevelopment from normal variation. The Developing Human Connectome Project (dHCP) seeks to create a detailed four-dimensional (4D) connectome of early life. This connectome may provide insights into normal as well as abnormal patterns of brain development.As part of this project, more than a thousand healthy fetal and neonatal * Corresponding authorEmail address: andreas.schuh.84@gmail.com (Andreas Schuh)Preprint submitted to NeuroImage January 28, 2018peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/251512 doi: bioRxiv preprint first posted online brains will be scanned in vivo. This requires computational methods which scale well to larger data sets. We propose a novel groupwise method for the construction of a spatio-temporal model of mean morphology from crosssectional brain scans at different gestational ages. This model scales linearly with the number of images and thus improves upon methods used to build existing public neonatal atlases, which derive correspondence between all pairs of images. By jointly estimating mean shape and longitudinal change, the atlas created with our method overcomes temporal inconsistencies, which are encountered when mean shape and intensity images are constructed separately for each time point. Using this approach, we have constructed a spatio-temporal atlas from 275 healthy neonates between 35 and 44 weeks post-menstrual age (PMA). The resulting atlas qualitatively preserves cortical details significantly better than publicly available atlases. This is moreover confirmed by a number of quantitative measures of the quality of the spatial normalisation and sharpness of the resulting template brain images.Keywords: dHCP, spatio-temporal, neonatal MRI, brain atlas 2 peer-reviewed)

Topical oils on baby skin may contribute to development of childhood atopic eczema. A pilot, assessor-blinded, randomized controlled trial assessed feasibility of a definitive trial investigating their impact in neonates. One-hundred and fifteen healthy, full-term neonates were randomly assigned to olive oil, sunflower oil or no oil, twice daily for 4 weeks, stratified by family history of atopic eczema. We measured spectral profile of lipid lamellae, trans-epidermal water loss (TEWL), stratum corneum hydration and pH and recorded clinical observations, at baseline, and 4 weeks post-birth. Recruitment was challenging (recruitment 11.1%; retention 80%), protocol adherence reasonable (79-100%). Both oil groups had significantly improved hydration but significantly less improvement in lipid lamellae structure compared to the no oil group. There were no significant differences in TEWL, pH or erythema/skin scores. The study was not powered for clinical significance, but until further research is conducted, caution should be exercised when recommending oils for neonatal skin.

BackgroundSome national guidelines recommend the use of water alone for napkin cleansing. Yet, there is a readiness, amongst many parents, to use baby wipes. Evidence from randomised controlled trials, of the effect of baby wipes on newborn skin integrity is lacking. We conducted a study to examine the hypothesis that the use of a specifically formulated cleansing wipe on the napkin area of newborn infants (<1 month) has an equivalent effect on skin hydration when compared with using cotton wool and water (usual care).MethodsA prospective, assessor-blinded, randomised controlled equivalence trial was conducted during 2010. Healthy, term babies (n = 280), recruited within 48 hours of birth, were randomly assigned to have their napkin area cleansed with an alcohol-free baby wipe (140 babies) or cotton wool and water (140 babies). Primary outcome was change in hydration from within 48 hours of birth to 4 weeks post-birth. Secondary outcomes comprised changes in trans-epidermal water loss, skin surface pH and erythema, presence of microbial skin contaminants/irritants at 4 weeks and napkin dermatitis reported by midwife at 4 weeks and mother during the 4 weeks.ResultsComplete hydration data were obtained for 254 (90.7 %) babies. Wipes were shown to be equivalent to water and cotton wool in terms of skin hydration (intention-to-treat analysis: wipes 65.4 (SD 12.4) vs. water 63.5 (14.2), p = 0.47, 95 % CI -2.5 to 4.2; per protocol analysis: wipes 64.6 (12.4) vs. water 63.6 (14.3), p = 0.53, 95 % CI -2.4 to 4.2). No significant differences were found in the secondary outcomes, except for maternal-reported napkin dermatitis, which was higher in the water group (p = 0.025 for complete responses).ConclusionsBaby wipes had an equivalent effect on skin hydration when compared with cotton wool and water. We found no evidence of any adverse effects of using these wipes. These findings offer reassurance to parents who choose to use baby wipes and to health professionals who support their use.Trial registrationCurrent Controlled Trials ISRCTN86207019

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Continuous EEG monitoring has not been used widely in neonatal intensive care, especially in the care of extremely premature infants, probably in part because of a lack of a reliable quantitative method. The purpose of this study was to quantify the EEG of the very premature infants just after birth by using spectral analysis and to describe the characteristics of the spectral signal when infants were clinically stable. Digital EEG recordings were performed on 53 infants who were Յ30 wk gestation for 75 min each day during the first 4 d after birth. Artefact was rejected manually after visual inspection of trace. The EEG was analyzed by manual measurement of interburst interval and automatically by spectral analysis using Fast Fourier Transformation. Spectral analysis generated the normal ranges of the relative power of the ␦ (0.5-3.5 Hz), (4 -7.5 Hz), ␣ (8 -12.5 Hz), and ␤ (13-30 Hz) frequency bands, spectral edge frequency, and symmetry. The median (range) relative power of the ␦ band increased significantly from 68% (62-76%) on day 1 to 81% (72-89%) on day 4 (p ϭ 0.001). The interburst intervals became progressively shorter between days 1 [14s (10 -25)] and 3 [8s (6 -12)]; there were no significant differences between days 3 and 4. The relative power of the ␦ band seemed to be the most useful and repeatable spectral measurement for continuous long-term monitoring. However, automatic artefact rejection software needs to be developed before continuous quantitative EEG monitoring can be used in the neonatal intensive care environment. The hemodynamic status of extremely premature infants is particularly labile during the first days after birth. Intensive interventions for such infants are intended to maintain an adequate tissue oxygen supply, particularly to the brain. Because clinical management is aimed at preserving cerebral integrity in these infants, it would be helpful to have some form of continuous neuromonitoring to guide clinical interventions. EEG provides a useful, noninvasive technique for monitoring cerebral electrical activity, and advances in digital technology have made it possible to record high-quality EEG even in an electrically noisy intensive care environment and have done away with the necessity of using large amounts of recording paper. However, interpretation of the EEG is generally considered to be highly specialized, and this is at least one reason that continuous EEG monitoring is not used widely in neonatal intensive care.There are three major issues to be considered for the automatic and reliable analysis of the EEG signal of premature infants and for data to be presented in a manner that is useful to clinicians. First, the EEG of these infants consists predominantly of high-amplitude slow waves (1,2). Bell et al. (3) showed that the relative power of slow waves with frequency Ͻ1 Hz might be as high as 90% in infants at 28 wk gestation. A recent study using DC EEG on infants between 34 and 37 wk gestation found that the spontaneous EEG activity of sleeping preterm infants consiste...

There is uncertainty about the level of systemic blood pressure required to maintain adequate cerebral oxygen delivery and organ integrity. This prospective, observational study on 35 very low birth weight infants aimed to determine the mean blood pressure (MBP) below which cerebral electrical activity, peripheral blood flow (PBF), and cerebral fractional oxygen extraction (CFOE) are abnormal. Digital EEG, recorded every day on the first 4 d after birth, were analyzed a) by automatic spectral analysis, b) by manual measurement of interburst interval, and c) qualitatively. CFOE and PBF measurements were performed using near-infrared spectroscopy and venous occlusion. MBP was measured using arterial catheters. The median (range) of MBP recorded was 32 mm . The EEG became abnormal at MBP levels below 23 mm Hg: a) the relative power of the delta (0.5-3.5 Hz) frequency band was decreased, b) interburst intervals were prolonged, and c) all four qualitatively abnormal EEG (low amplitude and prolonged interburst intervals) from four different patients were recorded below this MBP level. The only abnormally high CFOE was measured at MBP of 20 mm Hg. PBF decreased at MBP levels between 23 and 33 mm Hg. None of the infants in this study developed cystic periventricular leukomalacia. One infant (MBP, 22 mm Hg) developed ventricular dilatation after intraventricular hemorrhage. The EEG and CFOE remained normal at MBP levels above 23 mm Hg. It would appear that cerebral perfusion is probably maintained at MBP levels above 23 mm Hg. (Pediatr Res 59: 314-319, 2006) S everal authors have described an association between systemic hypotension in premature infants and neurologic morbidity (1-3), and, in some centers, clinical practice is to support blood pressure by inotropes and volume expanders when the MBP level falls below 30 mm Hg. The likely mechanism by which hypotension causes neurologic damage is by diminished oxygen delivery through decreased cerebral perfusion. However, the relationship between MBP and cerebral blood flow is unclear in premature infants (4 -8). Some authors have argued that cerebral blood flow is pressure passive and dependent on MBP in infants between 28 and 39 wk gestation (5,7). Others, who have studied infants between 24 and 34 wk gestation, observed that cerebral blood flow is independent of MBP (4,8). Furthermore, the critical level of MBP at which cerebral perfusion becomes compromised has not been clearly determined.In spite of a lack of evidence linking systemic hypotension to brain damage in very low birth weight infants, it is well known that older subjects lose consciousness when MBP falls to a seriously low level. A change in the level of consciousness may not be recognized in sick newborn infants who are heavily sedated while being ventilated, but it may be associated with recognizable changes in the EEG pattern. Using a cerebral function monitor, Greisen et al. (9) showed that reduced blood flow to the neonatal brain correlated with decreased amplitude of the EEG. There have bee...