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Introduction: There is large variability in kidney function and injury in neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). Acute kidney injury (AKI) definitions that apply categorical approaches may lose valuable information about kidney function in individual patients. Centile serum creatinine (SCr) over postnatal age (PNA) may provide more valuable information in TH neonates., Methods: Data from seven TH neonates and one non-TH-treated, non-NE control cohorts were pooled in a retrospective study. SCr centiles over PNA, and AKI incidence (definition: SCr ↑≥0.3 mg/dL within 48 h, or ↑ ≥1.5 fold vs. the lowest prior SCr within 7 days) and mortality were calculated. Repeated measurement linear models were applied to SCr trends, modeling SCr on PNA, birth weight or gestational age (GA), using heterogeneous autoregressive residual covariance structure and maximum likelihood methods. Findings were compared to patterns in the control cohort., Results: Among 1,136 TH neonates, representing 4,724 SCr observations, SCr (10th-25th-50th-75th-90th-95th) PNA centiles (day 1-10) were generated. In TH neonates, the AKI incidence was 132/1,136 (11.6%), mortality 193/1,136 (17%). AKI neonates had a higher mortality (37.2-14.3%, p < 0.001). Median SCr patterns over PNA were significantly higher in nonsurvivors (p < 0.01) or AKI neonates (p < 0.001). In TH-treated neonates, PNA and GA or birth weight explained SCr variability. Patterns over PNA were significantly higher in TH neonates to controls (801 neonates, 2,779 SCr)., Conclusions: SCr patterns in TH-treated NE neonates are specific. Knowing PNA-related patterns enable clinicians to better assess kidney function and tailor pharmacotherapy, fluids, or kidney supportive therapies., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

The hippocampus is a fundamental structure of the brain that plays an important role in neurodevelopment and is very sensitive to hypoxia-ischemia (HI). The purpose of this study was to investigate the effects of sildenafil on neonatal hippocampal brain injuries resulting from HI, and on neuronal development in this context. HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by a left common carotid ligation followed by a 2-h exposure to 8% oxygen. Rat pups were randomized to vehicle or sildenafil given orally twice daily for 7 days starting 12 h after HI. Hematoxylin and eosin staining was performed at P30 to measure the surface of the hippocampus; immunohistochemistry was performed to stain neurons, oligodendrocytes, and glial cells in the hippocampus. Western blots of the hippocampus were performed at P12, P17, and P30 to study the expression of neuronal markers and mTOR pathway. HI caused significant hippocampal atrophy and a significant reduction of the number of mature neurons, and induced reactive astrocytosis and microgliosis in the hippocampus. HI increased apoptosis and caused significant dysregulation of the normal neuronal development program. Treatment with sildenafil preserved the gross morphology of the hippocampus, reverted the number of mature neurons to levels comparable to sham rats, significantly increased both the immature and mature oligodendrocytes, and significantly reduced the number of microglia and astrocytes. Sildenafil also decreased apoptosis and reestablished the normal progression of post-natal neuronal development. The PI3K/Akt/mTOR pathway, whose activity was decreased after HI in the hippocampus, and restored after sildenafil treatment, may be involved. Sildenafil may have both neuroprotective and neurorestorative properties in the neonatal hippocampus following HI., (© 2021. The Author(s).)

Neuroimaging is widely used to aid in the diagnosis and clinical management of neonates with neonatal encephalopathy (NE). Yet, despite widespread use clinically, there are few published guidelines on neuroimaging for neonates with NE. This review outlines the primary patterns of brain injury associated with hypoxic-ischemic injury in neonates with NE and their frequency, associated neuropathological features, and risk factors. In addition, it provides an overview of neuroimaging methods, including the most widely used scoring systems used to characterize brain injury in these neonates and their utility as predictive biomarkers. Last, recommendations for neuroimaging in neonates with NE are presented., (Copyright © 2021. Published by Elsevier Ltd.)

In term and near-term neonates with neonatal encephalopathy, therapeutic hypothermia protocols are well established. The current focus is on how to improve outcomes further and the challenge is to find safe and complementary therapies that confer additional protection, regeneration or repair in addition to cooling. Following hypoxia-ischemia, brain injury evolves over three main phases (latent, secondary and tertiary), each with a different brain energy, perfusion, neurochemical and inflammatory milieu. While therapeutic hypothermia has targeted the latent and secondary phase, we now need therapies that cover the continuum of brain injury that spans hours, days, weeks and months after the initial event. Most agents have several therapeutic actions but can be broadly classified under a predominant action (e.g., free radical scavenging, anti-apoptotic, anti-inflammatory, neuroregeneration, and vascular effects). Promising early/secondary phase therapies include Allopurinol, Azithromycin, Exendin-4, Magnesium, Melatonin, Noble gases and Sildenafil. Tertiary phase agents include Erythropoietin, Stem cells and others. We review a selection of promising therapeutic agents on the translational pipeline and suggest a framework for neuroprotection and neurorestoration that targets the evolving injury., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Neonates with neonatal encephalopathy (NE) often present with multi-organ dysfunction that requires multidisciplinary specialized management. Care of the neonate with NE is thus complex with interaction between the brain and various organ systems. Illness severity during the first days of birth, and not only during the initial hypoxia-ischemia event, is a significant predictor of adverse outcomes in neonates with NE treated with therapeutic hypothermia (TH). We thus propose a care practice bundle dedicated to support the injured neonatal brain that is based on the current best evidence for each organ system. The impact of using such bundle on outcomes in NE remains to be demonstrated., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double-blind, placebo-controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE-related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory., Methods: Fifty-two infants born to heavy-drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi-echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline-related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII., Results: Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory., Conclusions: High-dose choline supplementation during pregnancy mitigated PAE-related regional volume reductions, with larger volumes associated with improved 12-month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE-related brain structural deficits in humans., (© 2021 Research Society on Alcoholism.)

Background: Hypotension and hypoxemic respiratory failure are common among neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Right ventricular (RV) dysfunction is associated with adverse neurodevelopment. Individualized management utilizing targeted neonatal echocardiography (TnECHO) may enhance care., Methods: We evaluated the influence of TnECHO programs on cardiovascular practices in HIE/TH patients utilizing a 77-item REDCap survey. Nominated representatives of TnECHO (n = 19) or non-TnECHO (n = 96) sites were approached., Results: Seventy-one (62%) sites responded. Baseline neonatal intensive care unit characteristics and HIE volume were comparable between groups. Most centers monitor invasive blood pressure; however, we identified 17 unique definitions of hypotension. TnECHO centers were likelier to trend systolic/diastolic blood pressure and request earlier echocardiography. TnECHO responders were less likely to use fluid boluses; TnECHO responders more commonly chose an inotrope first-line, while non-TnECHO centers used a vasopressor. For HRF, TnECHO centers chose vasopressors with a favorable pulmonary vascular profile. Non-TnECHO centers used more dopamine and more extracorporeal membrane oxygen for patients with HRF., Conclusions: Cardiovascular practices in neonates with HIE differ between centers with and without TnECHO. Consensus regarding the definition of hypotension is lacking and dopamine use is common. The merits of these practices among these patients, who frequently have comorbid pulmonary hypertension and RV dysfunction, need prospective evaluation., Impact: Cardiovascular care following HIE while undergoing therapeutic hypothermia varies between centers with access to trained hemodynamics specialists and those without. Because cardiovascular dysfunction is associated with brain injury, precision medicine-based care may be an avenue to improving outcomes. Therapeutic hypothermia has introduced new physiological considerations and enhanced survival. It is essential that hemodynamic strategies evolve to keep pace; however, little literature exists. Lack of consensus regarding fundamental definitions (e.g., hypotension) highlights the importance of collaboration among the scientific community to advance the field. The value of enhanced cardiovascular care guided by hemodynamic specialists requires prospective evaluation., (© 2021. International Pediatric Research Foundation, Inc.)

Objective: The authors sought to assess the utility of arterial spin labeling (ASL) perfusion 3T-MRI for the presurgical evaluation of poorly defined focal epilepsy in pediatric patients., Methods: Pseudocontinuous ASL perfusion 3T-MRI was performed in 25 consecutive children with poorly defined focal epilepsy. ASL perfusion abnormalities were detected qualitatively by visual inspection and quantitatively by calculating asymmetry index (AI) maps and significant z-score cluster maps based on successfully operated cases. ASL results were prospectively compared to scalp EEG, structural 3T-MRI, FDG-PET, ictal/interictal SPECT, magnetoencephalography (MEG), and intracranial recording results, as well as the final surgically proven epileptogenic zone (EZ) in operated patients who had at least 1 year of good (Engel class I/II) seizure outcome and positive histopathology results., Results: Qualitative ASL perfusion abnormalities were found in 17/25 cases (68%), specifically in 17/20 MRI-positive cases (85.0%) and in none of the 5 MRI-negative cases. ASL was concordant with localizing scalp EEG findings in 66.7%, structural 3T-MRI in 90%, FDG-PET in 75%, ictal/interictal SPECT in 62.5%, and MEG in 75% of cases, and with intracranial recording results in 40% of cases. Eleven patients underwent surgery; in all 11 cases the EZ was surgically proven by positive histopathology results and the patient having at least 1 year of good seizure outcome. ASL results were concordant with this final surgically proven EZ in 10/11 cases (sensitivity 91%, specificity 50%). All 10 ASL-positive patients who underwent surgery had positive surgical pathology results and good long-term postsurgical seizure outcome at a mean follow-up of 39 months. Retrospective quantitative analysis based on significant z-score clusters found 1 true-positive result that was missed by qualitative analysis and 3 additional false-positive results (sensitivity 100%, specificity 23%)., Conclusions: ASL supports the hypothesis regarding the EZ in poorly defined focal epilepsy cases in children. Due to its convenience and noninvasive nature, the authors recommend that ASL be added routinely to the presurgical MRI evaluation of epilepsy. Future optimized quantitative methods may improve the diagnostic yield of this technique.

Fetal inflammatory response syndrome (FIRS) is a condition defined by systemic inflammation in the fetus, a rapid increase of pro-inflammatory cytokines into the fetal circulation (including interleukin-1 and interleukin-6), as well as a cellular response (such as increased neutrophils, monocyte/macrophages, and T cells) and the presence of funisitis. FIRS can lead to death and multisystem organ damage in the fetus and newborn. Brain injuries and subsequent risk of cerebral palsy and cognitive impairments are the most threatening long-term complications. This paper reviews the definition of FIRS, summarizes its associated complications, briefly describes the available methods to study FIRS, and discusses in more detail the potential therapeutic candidates that have been so far studied to protect the fetus/newborn from FIRS and to alleviate its associated complications and sequelae., (© 2020 Published by Elsevier Ltd.)

Objective: To compare the characteristics and outcomes of neonates with mild hypoxic-ischemic encephalopathy (HIE) who received hypothermia versus standard care., Study Design: We conducted a retrospective cohort study of neonates ≥35 weeks' gestation and ≥1800 g admitted with a diagnosis of Sarnat stage 1 encephalopathy. We evaluated length of hospital stay, duration of ventilation, evidence of brain injury on MRI, and neonatal morbidities., Results: Of 1089 eligible neonates, 393 (36%) received hypothermia and 595 (55%) had neuroimaging. The hypothermia group was more likely to be outborn, born via C-section, had lower Apgar scores, and required extensive resuscitation. They had longer durations of stay (9 vs. 6 days, P < 0.001), respiratory support (3 vs. 2 days, P < 0.001), but lower odds of brain injury on MRI (adjusted odds ratio 0.33, 95% CI: 0.22-0.52) compared with standard care group., Conclusion: Despite prolongation of hospital stay, hypothermia may be potentially beneficial in neonates with mild HIE; however, selection bias cannot be ruled out.

Background: White matter alterations have previously been demonstrated in adolescents born with congenital heart disease (CHD) using diffusion tensor imaging (DTI). However, due to the non-specific nature of DTI metrics, it is difficult to interpret these findings in terms of their microstructural implications. This study investigated the use of neurite orientation dispersion and density imaging (NODDI), which involves the acquisition of advanced multiple b-value data over two shells and provides proxy measures of apparent axon density and orientation dispersion within white matter, as a complement to classic DTI measures., Study Design: Youth aged 16 to 24 years born with complex CHD and healthy peers underwent brain magnetic resonance imaging. White matter tract volumes and tract-average values of DTI and NODDI metrics were compared between groups. Tract-average DTI and NODDI results were spatially confirmed using tract-based spatial statistics., Results: There were widespread regions of lower tract-average neurite density index (NDI) in the CHD group as compared to the control group, particularly within long association tracts and in regions of the corpus callosum, accompanied by smaller white matter tract volumes and isolated clusters of lower fractional anisotropy (FA). There were no significant differences in orientation dispersion index (ODI) between groups., Conclusion: Lower apparent density of axonal packing, but not altered axonal orientation, is a key microstructural factor in the white matter abnormalities observed in youth born with CHD. These impairments in axonal packing may be an enduring consequence of early life brain injury and dysmaturation and may explain some of the long-term neuropsychological difficulties experienced by this at-risk group., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diffusion tensor imaging (DTI) studies have shown that prenatal exposure to methamphetamine is associated with alterations in white matter microstructure, but to date no tractography studies have been performed in neonates. The striato-thalamo-orbitofrontal circuit and its associated limbic-striatal areas, the primary circuit responsible for reinforcement, has been postulated to be dysfunctional in drug addiction. This study investigated potential white matter changes in the striatal-orbitofrontal circuit in neonates with prenatal methamphetamine exposure. Mothers were recruited antenatally and interviewed regarding methamphetamine use during pregnancy, and DTI sequences were acquired in the first postnatal month. Target regions of interest were manually delineated, white matter bundles connecting pairs of targets were determined using probabilistic tractography in AFNI-FATCAT, and fractional anisotropy (FA) and diffusion measures were determined in white matter connections. Regression analysis showed that increasing methamphetamine exposure was associated with reduced FA in several connections between the striatum and midbrain, orbitofrontal cortex, and associated limbic structures, following adjustment for potential confounding variables. Our results are consistent with previous findings in older children and extend them to show that these changes are already evident in neonates. The observed alterations are likely to play a role in the deficits in attention and inhibitory control frequently seen in children with prenatal methamphetamine exposure.

Objective: This study aimed to assess the incidence of hypotension in asphyxiated newborns treated with hypothermia, the variability in treatments for hypotension, and the impact of hypotension on the pattern of brain injury., Study Design: We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. Mean blood pressures, lactate levels, and inotropic support medications were recorded during the hospitalization. Presence and severity of brain injury were scored using the brain magnetic resonance imaging (MRI) obtained after the hypothermia treatment was completed., Results: One hundred and ninety term asphyxiated newborns were treated with hypothermia. Eighty-one percent developed hypotension. Fifty-five percent of the newborns in the hypotensive group developed brain injury compared with 35% of the newborns in the normotensive group ( p  = 0 . 04). Twenty-nine percent of the newborns in the hypotensive group developed severe brain injury, compared with only 15% in the normotensive group. Nineteen percent of the newborns presenting with volume- and/or catecholamine-resistant hypotension had near-total injury, compared with 6% in the normotensive group and 8% in the group responding to volume and/or catecholamines., Conclusion: Hypotension was common in asphyxiated newborns treated with hypothermia and was associated with an increased risk of (severe) brain injury in these newborns., Competing Interests: Conflict of Interest: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Encephalopathy of prematurity (EOP) is a complex form of cerebral injury that occurs in the setting of hypoxia-ischemia (HI) in premature infants. Using a rat model of EOP, we investigated whether neonatal HI of the brain may alter the expression of cystathionine β-synthase (CBS) and the components of the mammalian target of rapamycin (mTOR) signaling. We performed unilateral carotid ligation and induced HI (UCL/HI) in Long-Evans rats at P6 and found increased CBS expression in white matter (i.e. corpus callosum, cingulum bundle and external capsule) as early as 24 h (P7) postprocedure. CBS remained elevated through P21, and, to a lesser extent, at P40. The mTOR downstream target 70 kDa ribosomal protein S6 kinase (p70S6K and phospho-p70S6K) and 40S ribosomal protein S6 (S6 and phospho-S6) were also overexpressed at the same time points in the UCL/HI rats compared to healthy controls. Overexpression of mTOR components was not observed in rats treated with the mTOR inhibitor everolimus. Behavioral assays performed on young rats (postnatal day 35-37) following UCL/HI at P6 indicated impaired preference for social novelty, a behavior relevant to autism spectrum disorder, and hyperactivity. Everolimus restored behavioral patterns to those observed in healthy controls. A gait analysis has shown that motor deficits in the hind paws of UCL/HI rats were also significantly reduced by everolimus. Our results suggest that neonatal HI brain injury may inflict long-term damage by upregulation of CBS and mTOR signaling. We propose this cascade as a possible new molecular target for EOP-a still untreatable cause of autism, hyperactivity and cerebral palsy., (© 2016 International Society of Neuropathology.)

Predicting neurological outcomes of neonates with acute brain injury is an essential component of shared decision-making, in order to guide the development of treatment goals and appropriate care plans. It can aid parents in imagining the child's future, and guide timely and ongoing treatment decisions, including shifting treatment goals and focusing on comfort care. However, numerous challenges have been reported with respect to evidence-based practices for prognostication such as biases about prognosis among clinicians. Additionally, the evaluation or appreciation of living with disability can differ, including the well-known disability paradox where patients self-report a good quality of life in spite of severe disability. Herein, we put forward a set of five practice principles captured in the "ouR-HOPE" approach (Reflection, Humility, Open-mindedness, Partnership, and Engagement) and related questions to encourage clinicians to self-assess their practice and engage with others in responding to these challenges. We hope that this proposal paves the way to greater discussion and attention to ethical aspects of communicating prognosis in the context of neonatal brain injury., (© 2016 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Objective: This study aims to evaluate brain perfusion at term in very preterm newborns and newborns with congenital heart disease before their corrective surgery, and to search for histopathological indicators of whether the brain perfusion abnormalities of these newborns may be related to an activated angiogenesis., Materials and Methods: Using magnetic resonance imaging and arterial spin labeling, regional cerebral blood flow was measured at a term-equivalent age for three very preterm newborns (born at < 32 weeks), one newborn with congenital heart disease before his corrective surgery and three healthy newborns. In addition, a histopathological analysis was performed on a newborn with congenital heart disease., Results: The very preterm newborns and the newborn with congenital heart disease included in this study all displayed an increased signal in their white matter on T2-weighted imaging. The cerebral blood flow of these newborns was increased in their white matter, compared with the healthy term newborns. The vascular endothelial growth factor was overexpressed in the injured white matter of the newborn with congenital heart disease., Conclusion: Brain perfusion may be increased at term in the white matter, in very preterm newborns, and newborns with congenital heart disease, and it correlates with white matter abnormalities on conventional imaging., (Georg Thieme Verlag KG Stuttgart · New York.)

Many asphyxiated newborns still develop brain injury despite hypothermia therapy. The development of brain injury in these newborns has been related partly to brain perfusion abnormalities. The purposes of this study were to assess brain hyperperfusion over the first month of life in term asphyxiated newborns and to search for some histopathological clues indicating whether this hyperperfusion may be related to activated angiogenesis following asphyxia. In this prospective cohort study, regional cerebral blood flow was measured in term asphyxiated newborns treated with hypothermia around day 10 of life and around 1 month of life using magnetic resonance imaging (MRI) and arterial spin labeling. A total of 32 MRI scans were obtained from 24 term newborns. Asphyxiated newborns treated with hypothermia displayed an increased cerebral blood flow in the injured brain areas around day 10 of life and up to 1 month of life. In addition, we looked at the histopathological clues in a human asphyxiated newborn and in a rat model of neonatal encephalopathy. Vascular endothelial growth factor (VEGF) was expressed in the injured brain of an asphyxiated newborn treated with hypothermia in the first days of life and of rat pups 24-48 h after the hypoxic-ischemic event, and the endothelial cell count increased in the injured cortex of the pups 7 and 11 days after hypoxia-ischemia. Our data showed that the hyperperfusion measured by imaging persisted in the injured areas up to 1 month of life and that angiogenesis was activated in the injured brain of asphyxiated newborns.

Objective: The aim of this article is to assess whether near-infrared spectroscopy (NIRS) identifies, during hypothermia treatment, the asphyxiated newborns who later develop brain injury., Study Design: In this study, asphyxiated newborns, for whom later brain injury was defined by brain imaging and/or autopsy results, were monitored by NIRS during therapeutic hypothermia. We compared regional cerebral oxygenation saturation (rSO2) measured by NIRS at key time points for newborns who developed or did not develop later brain injury., Results: A total of 18 asphyxiated newborns treated with hypothermia were enrolled. rSO2 was higher in the asphyxiated newborns who developed later brain injury. Sensitivity within the first 10 hours of hypothermia treatment for an adverse outcome was 100% (95% confidence interval [CI], 70-100%) and specificity was 83% (95% CI, 36-99%)., Conclusions: NIRS appears to identify asphyxiated newborns at risk of developing brain injury as early as the first 10 hours of hypothermia treatment. Thus, NIRS may have an important role as an early outcome predictor in this population., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To assess whether the brain MRI results obtained during hypothermia identify the later brain injury observed in asphyxiated newborns after therapy is completed., Patients and Methods: Asphyxiated newborns treated with hypothermia were prospectively enrolled in this study if they had at least one MRI performed during hypothermia treatment and then another MRI performed around day 10 of life., Results: A total of 129 MRI scans were obtained from 43 asphyxiated newborns treated with hypothermia. Sixty per cent developed brain injury; all the brain injuries observed on the late scans were already present on day 2-3 of life during hypothermia, and the extent of injury was similar between the early and late scans. The brain MRI on day 2-3 of life had a sensitivity of 100% (95% CI 84% to 100%) and a specificity of 100% (95% CI 77% to 100%) to identify the presence and extent of later brain injury., Conclusions: The brain MRIs performed during hypothermia already permit an accurate definition of the presence and extent of brain injury that later develop in asphyxiated newborns despite treatment. These results may have research and clinical implications for the care of these newborns., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Prenatal alcohol exposure (PAE) is known to have severe, long-term consequences for brain and behavioral development already detectable in infancy and childhood. Resulting features of fetal alcohol spectrum disorders include cognitive and behavioral effects, as well as facial anomalies and growth deficits. Diffusion tensor imaging (DTI) and tractography were used to analyze white matter (WM) development in 11 newborns (age since conception <45 weeks) whose mothers were recruited during pregnancy. Comparisons were made with nine age-matched controls born to abstainers or light drinkers from the same Cape Coloured (mixed ancestry) community near Cape Town, South Africa. DTI parameters, T1 relaxation time, proton density and volumes were used to quantify and investigate group differences in WM in the newborn brains. Probabilistic tractography was used to estimate and to delineate similar tract locations among the subjects for transcallosal pathways, cortico-spinal projection fibers, and cortico-cortical association fibers. In each of these WM networks, the axial diffusivity was the parameter that showed the strongest association with maternal drinking. The strongest relations were observed in medial and inferior WM, regions in which the myelination process typically begins. In contrast to studies of older individuals with PAE, fractional anisotropy did not exhibit a consistent and significant relation with alcohol exposure. To our knowledge, this is the first DTI-tractography study of prenatally alcohol exposed newborns., (© 2014 Wiley Periodicals, Inc.)

Perinatal arterial ischemic stroke (AIS) is an important cause of long-term morbidity in children. Thus, there is an urgent need to better understand the mechanisms of stroke in newborns in order to develop effective treatment and prevention strategies. The purpose of this study was to assess brain perfusion within the first month of life in newborns with AIS. In this study, magnetic resonance imaging (MRI) and perfusion imaging by arterial spin labeling (ASL) were used to assess brain perfusion in four term newborns with AIS. One patient had a stroke within the territory of the right middle cerebral artery (MCA); the other three patients had a stroke within the territory of the left MCA. None of them displayed any hemorrhagic component. All four patients demonstrated abnormal brain perfusion in the stroke area. Cerebral blood flow (CBF) within the stroke area was increased in patient # 1. In all other three patients, CBF was decreased within the stroke center and increased in the periphery of the stroke area. These results show the feasibility of the ASL sequence in newborns with AIS and support its addition to the current MRI protocol used in these newborns as it provides useful information on brain hemodynamics. Its value for identifying salvageable tissue in newborns needs to be further assessed, as well as its potential role in stroke follow-up and for tissue-specific treatment screening.

Until now, brain MRIs in asphyxiated neonates who are receiving therapeutic hypothermia have been performed after treatment is complete. However, there is increasing interest in utilizing early brain MRI while hypothermia is still being provided to rapidly understand the degree of brain injury and possibly refine neuroprotective strategies. This study was designed to assess whether therapeutic hypothermia can be maintained while performing a brain MRI. Twenty MRI scans were obtained in 12 asphyxiated neonates while they were treated with hypothermia. The median difference between esophageal temperature on NICU departure and return was 0.1°C (range: -0.8 to 0.8°C). We found that therapeutic hypothermia can be safely and reproducibly maintained during a brain MRI. Hypothermia treatment should not prevent obtaining an early brain MRI if clinically indicated.

Objective: We sought to describe placental findings in asphyxiated term newborns meeting therapeutic hypothermia criteria and to assess whether histopathologic correlation exists between these placental lesions and the severity of later brain injury., Study Design: We conducted a prospective cohort study of the placentas of asphyxiated newborns, in whom later brain injury was defined by magnetic resonance imaging., Results: A total of 23 newborns were enrolled. Eighty-seven percent of their placentas had an abnormality on the fetal side of the placenta, including umbilical cord lesions (39%), chorioamnionitis (35%) with fetal vasculitis (22%), chorionic plate meconium (30%), and fetal thrombotic vasculopathy (26%). A total of 48% displayed placental growth restriction. Chorioamnionitis with fetal vasculitis and chorionic plate meconium were significantly associated with brain injury (P = .03). Placental growth restriction appears to significantly offer protection against the development of these injuries (P = .03)., Conclusion: Therapeutic hypothermia may not be effective in asphyxiated newborns whose placentas show evidence of chorioamnionitis with fetal vasculitis and chorionic plate meconium., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Cerebral perfusion-weighted imaging (PWI) in neonates is known to be technically difficult and there are very few published studies on its use in preterm infants. In this paper, we describe one convenient method to perform PWI in neonates, a method only recently used in newborns. A device was used to manually inject gadolinium contrast material intravenously in an easy, quick and reproducible way. We studied 28 newborn infants, with various gestational ages and weights, including both normal infants and those suffering from different brain pathologies. A signal intensity-time curve was obtained for each infant, allowing us to build perfusion maps. This technique offered a fast and easy method to manually inject a bolus gadolinium contrast material, which is essential in performing PWI in neonates. Cerebral PWI is technically feasible and reproducible in neonates of various gestational age and with various pathologies.