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Thrombotic thrombocytopenic purpura was diagnosed in a neonate with hereditary ADAMTS13 deficiency. Treatment with recombinant ADAMTS13 reversed the deficiency, and the child’s development at 2 years was normal.

ObjectiveBrain proton (1H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) 1H MRS Lac/NAA for the prediction of Bayley III outcomes at 2 years using optimised metabolite fitting (Tarquin) with threonine and total NAA; (2) prediction of motor outcome with diffusion-weighted MRI; (3) BGT Lac/NAA correlation with the National Institute of Child Health and Human Development (NICHD) MRI score.Subjects and methods55 (16 inborn, 39 outborn) infants at 39w+5 d (35w+5d–42w+0d) with NE admitted between February 2012 and August 2014 to University College London Hospitals for therapeutic hypothermia underwent MRI and 1H MRS at 3T on day 2–14 (median day 5). MRIs were scored. Bayley III was assessed at 24 (22–26) months.Results16 babies died (1 inborn, 15 outborn); 20, 19 and 21 babies had poor motor, cognitive and language outcomes. Using a threshold of 0.39, sensitivity and specificity of BGT Lac/NAA for 2-year motor outcome was 100% and 97%, cognition 90% and 97% and language 81% and 97%, respectively. Sensitivity and specificity for motor outcome of mean diffusivity (threshold 0.001 mm2/s) up to day 9 was 72% and 100% and fractional anisotropy (threshold 0.198) was 39% and 94%, respectively. Lac/NAA correlated with BGT injury on NICHD scores (2A, 2B, 3).ConclusionBGT Lac/NAA on 1H MRS at 3T within 14 days accurately predicts 2-year motor, cognitive and language outcome and may be a marker directing decisions for therapies after cooling.

Advances in neonatal care have improved the survival of infants born prematurely although these infants remain at increased risk of adverse neurodevelopmental outcome. The measurement of white matter structure and features of the cortical surface can help define biomarkers that predict this risk. The measurement of these structures relies upon accurate automated segmentation routines, but these are often confounded by neonatal-specific imaging difficulties including poor contrast, low resolution, partial volume effects and the presence of significant natural and pathological anatomical variability. In this work we develop and evaluate an adaptive preterm multi-modal maximum a posteriori expectation-maximisation segmentation algorithm (AdaPT) incorporating an iterative relaxation strategy that adapts the tissue proportion priors toward the subject data. Also incorporated are intensity non-uniformity correction, a spatial homogeneity term in the form of a Markov random field and furthermore, the proposed method explicitly models the partial volume effect specifically mitigating the neonatal specific grey and white matter contrast inversion. Spatial priors are iteratively relaxed, enabling the segmentation of images with high anatomical disparity from a normal population. Experiments performed on a clinical cohort of 92 infants are validated against manual segmentation of normal and pathological cortical grey matter, cerebellum and ventricular volumes. Dice overlap scores increase significantly when compared to a widely-used maximum likelihood expectation maximisation algorithm for pathological cortical grey matter, cerebellum and ventricular volumes. Adaptive maximum a posteriori expectation maximisation is shown to be a useful tool for accurate and robust neonatal brain segmentation. ► Very preterm birth increases the risk of subsequent learning difficulties. ► Accurate segmentation may allow predictive biomarkers to be established. ► Adaptive segmentation allows improved segmentation in pathological cases. ► Comparison of the algorithm to manual segmentation shows significant improvement.

Recent technological advances have led to the expansion of testing options for newborns with suspected rare genetic conditions, particularly in high-income healthcare settings. This article summarises the key genomic testing approaches, their indications and potential limitations.

Preterm birth is a major public health concern, with the severity and occurrence of adverse outcome increasing with earlier delivery. Being born preterm disrupts a time of rapid brain development: in addition to volumetric growth, the cortex folds, myelination is occurring and there are changes on the cellular level. These neurological events have been imaged non-invasively using diffusion-weighted (DW) MRI. In this population, there has been a focus on examining diffusion in the white matter, but the grey matter is also critically important for neurological health. We acquired multi-shell high-resolution diffusion data on 12 infants born at ≤28weeks of gestational age at two time-points: once when stable after birth, and again at term-equivalent age. We used the Neurite Orientation Dispersion and Density Imaging model (NODDI) (Zhang et al., 2012) to analyse the changes in the cerebral cortex and the thalamus, both grey matter regions. We showed region-dependent changes in NODDI parameters over the preterm period, highlighting underlying changes specific to the microstructure. This work is the first time that NODDI parameters have been evaluated in both the cortical and the thalamic grey matter as a function of age in preterm infants, offering a unique insight into neuro-development in this at-risk population. •Acquired multi-shell DWMRI from infants born at <28weeks of gestation.•Present scan parameters for NODDI in the preterm population.•Calculated DTI and NODDI parameters shortly after birth and at term-equivalent age.•The myelinating thalamus shows increases in the intra-neurite volume fraction.•The cortex shows increases in the ODI as dendrites and axons are elaborated.

Monitoring (maternal blood tests, serum valaciclovir concentrations, fetal ultrasounds) was uneventful. [...]off-licence antiviral treatment with valganciclovir (900 mg twice daily) was initiated after discussions with the multidisciplinary team, for a total of 6 weeks in the acute phase of presumed fetal myocarditis. There is an urgent public health need to create a unified and equitable approach to screening, surveillance, and treatment, especially as some pregnant women are receiving inconsistent care across countries, following different policies.

The survival rates of infants born prematurely have improved as a result of advances in neonatal care, although there remains an increased risk of subsequent disability. Accurate measurement of the shape and appearance of the very preterm brain at term-equivalent age may guide the development of predictive biomarkers of neurological outcome. We demonstrate in 92 preterm infants (born at an average gestational age of 27.0±2.7weeks) scanned at term equivalent age (scanned at 40.4±1.74weeks) that the cortical sulcation ratio varies spatially over the cortical surface at term equivalent age and correlates significantly with gestational age at birth (r=0.49,p<0.0001). In the underlying white matter, fractional anisotropy of local white matter regions correlated significantly with gestational age at birth at term equivalent age (for the genu of the corpus callosum r=0.26,p=0.02 and for the splenium r=0.52,p<0.001) and in addition the fractional anisotropy in these local regions varies according to location. Finally, we demonstrate that connectivity measurements from tractography correlate significantly and specifically with the sulcation ratio of the overlying cortical surface at term equivalent age in a subgroup of 20 infants (r={0.67,0.61,0.86}, p={0.004,0.01,0.00002}) for tract systems emanating from the left and right corticospinal tracts and the corpus callosum respectively). Combined, these results suggest a close relationship between the cortical surface phenotype and underlying white matter structure assessed by diffusion weighted MRI. The spatial surface pattern may allow inference on the connectivity and developmental trajectory of the underlying white matter complementary to diffusion imaging and this result may guide the development of biomarkers of functional outcome. •Survival rates of infants born prematurely have improved recently.•Accurate measurement of the shape of the brain may guide the development of predictive biomarkers.•We show in 92 infants that the cortical folding pattern varies with gestational age at birth.•In preterm WM, connectivity measurements correlate with the overlying cortical surface pattern.•Cortical folding may allow inference on the connectivity and developmental trajectory of WM

IntroductionNeonatal death and later disability remain common sequelae of hypoxic-ischaemic encephalopathy (HIE) despite the now standard use of therapeutic hypothermia (HT). New therapeutic approaches to brain protection are required. Melatonin is an indolamine hormone with free-radical scavenging, antiapoptotic, anti-inflammatory and gene regulatory neuroprotective properties, which has extensive preclinical evidence of safety and efficacy. Pharmacokinetic (PK) data suggest it is necessary to reach melatonin levels of 15–30 mg/L within 6–8 hours of hypoxia-ischaemia for brain protection. We developed a novel Good Manufacturing Practice (GMP) grade melatonin in ethanol 50 mg/mL solution for intravenous use. In preclinical studies, ethanol is an adjuvant excipient with additional neuroprotective benefit; optimised dosing protocols can achieve therapeutic melatonin levels while limiting blood alcohol concentrations (BACs).Methods and analysisThe Acute High Dose Melatonin for Encephalopathy of the Newborn (ACUMEN) Study is a first-in-human, international, multicentre, phase 1 safety study of intravenous melatonin in babies with moderate/severe HIE receiving HT. Sixty babies will be studied over two phases: a dose escalation study including four dose levels to establish the recommended phase 2 dose (RP2D), followed by a 6-month cohort expansion study of RP2D to further characterise PKs and affirm safety. Participants will receive a 2-hour intravenous infusion of melatonin within 6 hours of birth, followed by five maintenance doses every 12 hours to cover the period of HT. Plasma melatonin and BACs will be monitored. The RP2D will be based on the attainment of therapeutic melatonin levels while limiting BACs and the frequency of dose-limiting events (DLEs). A Bayesian Escalation with Overdose Control approach will be used to estimate the risk of DLE per dose level, with a target level of <33%. ACUMEN will establish a network of centres with standardised neurocritical care and harmonised MRI systems for the analysis of the primary outcome—magnetic resonance spectroscopy (MRS) lactate to N-acetylaspartate peak area ratio localised to the basal ganglia and thalamus and include a nested blood biomarker study to explore early disease severity indicators.Ethics and disseminationApproval has been given by the London Central National Health Service Health Research Authority Ethics Committee (25/LO/0170) and UK Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. Separate approvals have been sought in Ireland and Australia. Dissemination will be via peer-reviewed journals, conference presentations, public registries and plain language summaries for parent/legal guardian(s), in accordance with national requirements.Trial registration number ISRCTN61218504. EU CT: 2025-520538-49-00.Protocol versionPublication based on the UK protocol V.3.0, 08 May 2025

Objective To determine the feasibility of passive cooling to initiate therapeutic hypothermia before and during transport. Methods Consensus guidelines were developed for passive cooling at the referring hospital and on transport by the London Neonatal Transfer Service. These were evaluated in a prospective study. Results Between January and October 2009, 39 infants were referred for therapeutic hypothermia; passive cooling was initiated at the referring hospital in all the cases. Despite guidance, no rectal temperature measurements were taken before arrival of the transfer team. Cooling below target temperature (33°C–34°C) occurred in five babies before the arrival of the transfer team. In two of these infants, active cooling was performed, rectal temperature was not recorded and their temperature was lower than 32°C. Of the remaining 37 babies, 33 (89%) demonstrated a reduction in core temperature with passive cooling alone. The percentage of the babies within the temperature range at referral, arrival of the transfer team and arrival at the cooling centre were 0%, 15% and 67%, respectively. On arrival at the cooling centre, four babies had cooled to lower than 33°C by passive cooling alone (32.7°C, 32.6°C, 32.2°C and 32.1°C). Initiation of passive cooling before and during transfer resulted in the therapy starting 4.6 (1.8) h earlier than if initiated on arrival at the cooling centre. Conclusions Passive cooling is a simple and effective technique if portable cooling equipment is unavailable. Rectal temperature monitoring is essential; active cooling methods without core temperature monitoring may lead to overcooling.