Semi-Automatic GUI Platform to Characterize Brain Development in Preterm Children Using Ultrasound Images.

The third trimester of pregnancy is the most critical period for human brain development, during which significant changes occur in the morphology of the brain. The development of sulci and gyri allows for a considerable increase in the brain surface. In preterm newborns, these changes occur in an extrauterine environment that may cause a disruption of the normal brain maturation process. We hypothesize that a normalized atlas of brain maturation with cerebral ultrasound images from birth to term equivalent age will help clinicians assess these changes. This work proposes a semi-automatic Graphical User Interface (GUI) platform for segmenting the main cerebral sulci in the clinical setting from ultrasound images. This platform has been obtained from images of a cerebral ultrasound neonatal database images provided by two clinical researchers from the Hospital Sant Joan de Déu in Barcelona, Spain. The primary objective is to provide a user-friendly design platform for clinicians for running and visualizing an atlas of images validated by medical experts. This GUI offers different segmentation approaches and pre-processing tools and is user-friendly and designed for running, visualizing images, and segmenting the principal sulci. The presented results are discussed in detail in this paper, providing an exhaustive analysis of the proposed approach's effectiveness.

Massive Neonatal Arterial Ischemic Stroke.

BACKGROUND: Massive infarction in adults is a devastating entity characterized by signs of extreme swelling of the brain's parenchyma. We explored whether a similar entity exists in neonates, which we call massive neonatal arterial ischemic stroke (M-NAIS), and assess its potential clinical implications. METHODS: Prospective multicenter cohort study comprising 48 neonates with gestational age ≥35 weeks with middle cerebral artery (MCA) NAIS was performed. Diagnosis with magnetic resonance imaging (MRI) was performed within the first three days after symptom onset. The presence of signs of a space-occupying mass, such as brain midline shift and/or ventricular and/or extra-axial space collapse, was recorded. The volume of the infarct and brain midline shift were determined with semiautomatic procedures. Neurodevelopment was assessed at age 24 months. RESULTS: Fifteen (31%) neonates presented MRI signs of a space-occupying mass effect and were considered to have an M-NAIS. The relative volume (infarct volume/total brain volume) of the infarct was on average significantly greater in the M-NAIS subgroup (29% vs 4.9%, P < 0.001). Patients with M-NAIS consistently presented lesions involving the M1 arterial territory of the MCA and showed more apneic and tonic seizures, which had an earlier onset and lasted longer. Moderate to severe adverse neurodevelopmental outcomes were present in most M-NAIS cases (79% vs 6%, P < 0.001). CONCLUSIONS: M-NAIS appears to be a distinctive subtype of neonatal infarction, defined by characteristic neuroimaging signs. Neonates with M-NAIS frequently present a moderate to severe adverse outcome. Early M-NAIS identification would allow for prompt, specific rehabilitation interventions and would provide more accurate prognostic information to families.

Breastfeeding duration is associated with larger cortical gray matter volumes in children from the ABCD study.

BACKGROUND: Despite the numerous studies in favor of breastfeeding for its benefits in cognition and mental health, the long-term effects of breastfeeding on brain structure are still largely unknown. Our main objective was to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also explored the potential mediatory role of brain volumes on behavior. METHODS: We analyzed 7,860 magnetic resonance images of children 9-11 years of age from the Adolescent Brain Cognitive Development (ABCD) dataset in order to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also obtained several behavioral data (cognition, behavioral problems, prodromal psychotic experiences, prosociality, impulsivity) to explore the potential mediatory role of brain volumes on behavior. RESULTS: In the 7,860 children analyzed (median age = 9 years and 11 months; 49.9% female), whole-brain voxel-based morphometry analyses revealed an association mainly between breastfeeding duration and larger bilateral volumes of the pars orbitalis and the lateral orbitofrontal cortex. In particular, the association with the left pars orbitalis and the left lateral orbitofrontal cortex proved to be very robust to the addition of potentially confounding covariates, random selection of siblings, and splitting the sample in two. The volume of the left pars orbitalis and the left lateral orbitofrontal cortex appeared to mediate the relationship between breastfeeding duration and the negative urgency dimension of the UPPS-P Impulsive Behavior Scale. Global gray matter volumes were also significant mediators for behavioral problems as measured with the Child Behavior Checklist. CONCLUSIONS: Our findings suggest that breastfeeding is a relevant factor in the proper development of the brain, particularly for the pars orbitalis and lateral orbitofrontal cortex regions. This, in turn, may impact impulsive personality and mental health in early puberty.

CSF neopterin and beta-2-microglobulin as inflammation biomarkers in newborns with hypoxic-ischemic encephalopathy.

BACKGROUND: Inflammation plays a crucial role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE). The aim of this study was to measure inflammation in HIE through an analysis of CSF neopterin and ß2-microglobulin and to study the association with brain injury as shown by MRI findings and neurodevelopmental outcomes. METHODS: CSF biomarkers were measured in study patients at 12 and 72 h. Brain injury was evaluated by MRI, and neurodevelopmental outcomes were assessed at 2-3 years of life. An adverse outcome was defined as the presence of motor or cognitive impairment. RESULTS: Sixty-nine HIE infants were included. Median values of neopterin and ß2-microglobulin paralleled the severity of HIE. Adverse outcomes were associated with early neopterin and ß2-microglobulin values, late neopterin values, and the neopterin percentage change between the two samples. A cutoff value of 75% neopterin change predicted adverse outcomes with a specificity of 0.9 and a sensitivity of 0.75. CONCLUSIONS: CSF neopterin and ß2-microglobulin are elevated in HIE, indicating the activation of inflammation processes. Infants with adverse neurodevelopmental outcomes show higher levels of CSF neopterin and ß2-microglobulin. The evolution of neopterin levels provides a better predictive capacity than a single determination. IMPACT: Brain inflammation in newborns with HIE could be measurable through the analysis of CSF neopterin and ß2-microglobulin, both of which are associated with neurodevelopmental outcomes. Our study introduces two inflammatory biomarkers for infants with HIE that seem to show a more stable profile and are easier to interpret than cytokines. CSF neopterin and ß2-m may become clinical tools to monitor inflammation in HIE and might eventually be helpful in measuring the response to emerging therapies.

Cerebrospinal Fluid Ion Analysis in Neonatal Seizures.

BACKGROUND: There is a gap of knowledge regarding cerebrospinal fluid (CSF) ion concentrations in normal and pathological states, particularly during the neonatal period. We aim to compare CSF ion concentrations in newborns with different causes of neonatal-onset epilepsy (NOE) and acute symptomatic seizures (ASS) and controls, to examine their usefulness for diagnostic purposes. METHODS: A descriptive retrospective study was conducted from January 2019 to June 2020 in a tertiary hospital. We analyzed CSF K+, Na+, Cl-, and Ca2+ concentrations in frozen samples from patients with neonatal seizures (NS) secondary to NOE and ASS (neonatal arterial ischemic stroke [NAIS] and hypoxic-ischemic encephalopathy). As the control group, we selected CSF samples from newborns who had undergone CSF analysis as part of the diagnostic workup and in whom central nervous system infections had been ruled out, without signs of dehydration, gastroenteritis, or history of seizures. RESULTS: Sixty-eight newborns were included, 16 with NOE, 13 with ASS, and 39 without NS (control group). In comparison with the control group, [K+]CSF was lower in patients with KCNQ2-related epilepsy (P = 0.007), other causes of NOE (P = 0.010), and NAIS (P = 0.002). Changes in [Na+]CSF, [Cl-]CSF, and [Ca2+]CSF were less consistent among subgroups. CONCLUSIONS: Here we report for the first time ionic imbalances in the CSF of neonates with NOE and NAIS. No differences were observed between newborns with different causes of NS. Further studies should be undertaken to investigate the physiopathology behind these changes and their impact on biological function.

Neonatal arterial stroke location is associated with outcome at 2 years: a voxel-based lesion-symptom mapping study.

OBJECTIVE: In contrast to motor impairments, the association between lesion location and cognitive or language deficits in patients with neonatal arterial ischaemic stroke remains largely unknown. We conducted a voxel-based lesion-symptom mapping cross-sectional study aiming to reveal neonatal arterial stroke location correlates of language, motor and cognitive outcomes at 2 years of age. DESIGN: Prospective observational multicentre study. SETTING: Six paediatric university hospitals in Spain. PARTICIPANTS: We included 53 patients who had a neonatal arterial ischaemic stroke with neonatal MRI and who were followed up till 2 years of age. MAIN OUTCOME MEASURES: We analysed five dichotomous clinical variables: speech therapy (defined as the need for speech therapy as established by therapists), gross motor function impairment, and the language, motor and cognitive Bayley scales. All the analyses were controlled for total lesion volume. RESULTS: We found that three of the clinical variables analysed significantly correlated with neonatal stroke location. Speech therapy was associated with lesions located mainly at the left supramarginal gyrus (p=0.007), gross motor function impairment correlated with lesions at the left external capsule (p=0.044) and cognitive impairment was associated with frontal lesions, particularly located at the left inferior and middle frontal gyri (p=0.012). CONCLUSIONS: The identification of these susceptible brain areas will allow for more precise prediction of neurological impairments on the basis of neonatal brain MRI.

Development, Reliability, and Testing of a New Rating Scale for Neonatal Encephalopathy.

OBJECTIVE: To develop and test the Neonatal Encephalopathy-Rating Scale (NE-RS), a new rating scale to grade the severity of neonatal encephalopathy (NE) within the first 6 hours after birth. STUDY DESIGN: A 3-phase process was conducted: (1) design of a comprehensive scale that would be specific, sensitive, brief, and unsophisticated; (2) evaluation in a cohort of infants with neonatal encephalopathy and healthy controls; and (3) validation with brain magnetic resonance imaging findings and outcome at 2 years of age. RESULTS: We evaluated the NE-RS in 54 infants with NE and 28 healthy infants. The NE-RS had excellent internal consistency (Cronbach alpha coefficient: 0.93 [95% CI 0.86-0.94]) and reliability (intraclass correlation coefficient in the NE cohort 0.996 [95% CI 0.993-0.998; P < .001]). Alertness, posture, motor response, and spontaneous activity were the top discriminators for degrees of NE. The cut-off value for mild vs moderate NE was 8 points (area under the curve [AUC] 0.99, 95% CI 0.85-1.00) and for moderate vs severe NE, 30 points (AUC 0.93, 95% CI 0.81-0.99). The NE-RS was significantly correlated with the magnetic resonance imaging score (Spearman Rho 0.77, P < .001) and discriminated infants who had an adverse outcome (AUC 0.91, 95% CI 0.83-0.99, sensitivity 0.82, specificity 0.81, positive predictive value 0.87, negative predictive value 0.74). CONCLUSIONS: The NE-RS is reliable and performs well in reflecting the severity of NE within the first 6 hours after birth. This tool could be useful when assessing clinical criteria for therapeutic hypothermia in NE.

Attenuated brain responses to speech sounds in moderate preterm infants at term age.

Recent findings have revealed that very preterm neonates already show the typical brain responses to place of articulation changes in stop consonants, but data on their sensitivity to other types of phonetic changes remain scarce. Here, we examined the impact of 7-8 weeks of extra-uterine life on the automatic processing of syllables in 20 healthy moderate preterm infants (mean gestational age at birth 33 weeks) matched in maturational age with 20 full-term neonates, thus differing in their previous auditory experience. This design allows elucidating the contribution of extra-uterine auditory experience in the immature brain on the encoding of linguistically relevant speech features. Specifically, we collected brain responses to natural CV syllables differing in three dimensions using a multi-feature mismatch paradigm, with the syllable/ba/ as the standard and three deviants: a pitch change, a vowel change to/bo/ and a consonant voice-onset time (VOT) change to/pa/. No significant between-group differences were found for pitch and consonant VOT deviants. However, moderate preterm infants showed attenuated responses to vowel deviants compared to full terms. These results suggest that moderate preterm infants' limited experience with low-pass filtered speech prenatally can hinder vowel change detection and that exposure to natural speech after birth does not seem to contribute to improve this capacity. These data are in line with recent evidence suggesting a sequential development of a hierarchical functional architecture of speech processing that is highly sensitive to early auditory experience.

Cerebrospinal fluid levels of neuron-specific enolase predict the severity of brain damage in newborns with neonatal hypoxic-ischemic encephalopathy treated with hypothermia.

OBJECTIVES: To investigate whether cerebrospinal fluid levels of neuron-specific enolase (CSF-NSE) during the first 72 hours correlate with other tools used to assess ongoing brain damage, including clinical grading of hypoxic-ischemic encephalopathy (HIE), abnormal patterns in amplitude integrated electroencephalography (aEEG), and magnetic resonance imaging (MRI), as well as with the neurodevelopmental outcomes at two years of age. MATERIAL AND METHODS: Prospective observational study performed in two hospitals between 2009 and 2011. Forty-three infants diagnosed with HIE within 6 hours of life were included. HIE was severe in 20 infants, moderate in 12, and mild in 11. Infants with moderate-to-severe HIE received whole-body cooling. Both the HIE cohort and a control group of 59 infants with suspected infection underwent measurement of CSF-NSE concentrations at between 12 and 72 hours after birth. aEEG monitoring was started at admission and brain MRI was performed within the first 2 weeks. Neurodevelopment was assessed at 24 months. RESULTS: The HIE group showed higher levels of CSF-NSE than the control group: median 70 ng/ml (29; 205) vs 10.6 ng/ml (7.7; 12.9); p <0.001. Median levels of CSF-NSE in infants with severe, moderate, and mild HIE were 220.5 ng/ml (120.5; 368.8), 45.5 ng/ml (26, 75.3), and 26 ng/ml (18, 33), respectively. CSF-NSE levels correlated were significantly higher in infants with seizures, abnormal aEEG, or abnormal MRI, compared to those without abnormalities. Infants with an adverse outcome showed higher CSF-NSE levels than those with normal findings (p<0.001), and the most accurate CSF-NSE cutoff level for predicting adverse outcome in the whole cohort was 108 ng/ml and 50ng/ml in surviving infants. CONCLUSIONS: In the era of hypothermia, CSF-NSE concentrations provides valuable information as a clinical surrogate of the severity of hypoxic-ischemic brain damage, and this information may be predictive of abnormal outcome at two years of age.

Preterm white matter injury: ultrasound diagnosis and classification.

White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will improve prediction of outcome in preterm infants with WMI still needs to be evaluated in prospective studies.

Neuron-specific enolase is correlated with lesion topology, relative infarct volume and outcome of symptomatic NAIS.

OBJECTIVE: To correlate neuron-specific enolase (NSE) levels in cerebrospinal fluid (CSF) in neonate infants with symptomatic neonatal arterial ischaemic stroke (NAIS) with the arterial distribution of infarct, infarct volume and outcome. DESIGN: Prospective observational multicentre cohort. SETTING: Three paediatric university hospitals in Spain. SUBJECTS: Thirty-eight neonates with more than 35 weeks' gestational age between 2006 and 2016 were studied. They were diagnosed with NAIS by MRI. They underwent a lumbar puncture to measure CSF-NSE concentrations within 96 hours after the onset of symptoms. Sixty-seven neonates admitted with suspected infections served as controls. We used a classification based on the arterial distribution, and the lesions were segmented with ITK-Snap software to determine their volume. Neurodevelopment was assessed at 24 months using the Bayley-III, Gross Motor Function Classification System and Bimanual Fine Motor Function. RESULTS: CSF-NSE levels were higher in patients with symptomatic NAIS when compared with controls. Neonates with multifocal NAIS and with NAIS located in middle cerebral artery (MCA)-M1 arterial territory showed higher CSF-NSE levels when compared with cases with MCA-M2-M3-M4 territories (p<0.001). A significant correlation was found between CSF-NSE and relative infarction volume (rs=0.597; p<0.001). CSF-NSE values were higher in those infants with symptomatic NAIS with adverse outcome compared with infants with good development (p=0.020). Infants with CSF-NSE values above 55 ng/mL had an OR of adverse outcome of 6.48 (95% CI 1.48 to 28.33). CONCLUSIONS: CSF-NSE is a potential early prognostic biomarker after an NAIS due to the relation between volume, topology and neurodevelopment at 2 years of age.

Precise neonatal arterial ischemic stroke classification with a three-dimensional map of the arterial territories of the neonatal brain.

INTRODUCTION: Data regarding neonatal arterial ischemic stroke (NAIS) topography are still sparse and inaccurate. Despite the importance of locating NAIS to predict the long-term outcome of neonates, a map of arterial territories is not yet available. Our aim was therefore to generate the first three-dimensional map of arterial territories of the neonatal brain (ATNB) and test its usefulness. METHODS: Three-dimensional time-of-flight magnetic resonance angiography images were acquired from four neonates without NAIS. Arteries were semi-automatically segmented to build a symmetric arterial template. This allowed us to delineate the volumetric extension of each arterial territory, giving rise to the ATNB map, which is publicly available. Its applicability was tested on a sample of 34 neonates with NAIS. RESULTS: After applying the ATNB map to the neonatal sample, the posterior trunk of the middle cerebral artery, followed by its anterior trunk, were identified as the most affected arterial territories. When comparing the results obtained employing the map with the original diagnoses made during the standard clinical evaluation of NAIS, major diagnostic errors were found in 18% of cases. CONCLUSION: The ATNB map has been proven useful to precisely identify the arterial territories affected by an NAIS, as well as to increase the accuracy of clinical diagnoses.

Seguimiento a medio-largo plazo de los niños prematuros y sus familias en nuestro país / Medium to long-term follow-up of premature children and their families in Spain

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The Role of Factor V Leiden, Prothrombin G20210A, and MTHFR C677T Mutations in Neonatal Cerebral Sinovenous Thrombosis.

Little is known about the pathogenesis of cerebral sinovenous thrombosis (CSVT) in the neonate. Although thrombophilia has been described as increasing the risk of CSVT in adults, it remains controversial in pediatric patients, and prospective case-control studies regarding neonatal CSVT are lacking. From 2008 to 2017, all 26 consecutive newborn infants ≥35 weeks of gestation diagnosed with neonatal CSVT, and their mothers, were tested for factor V Leiden (FV) G1691A, FII G20210A, and methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations. Eighty-five mother-infant pairs were recruited as controls. All infants except 1 with CSVT were suspected due to clinical symptoms, mainly seizures (22/25). Magnetic resonance imaging was performed in 24/26 infants. Heterozygous FV G1691A, FII G20210A, and homozygous MTHFR C677T mutations were present in 1/26, 3/26, and 3/20 infants with CSVT, respectively. FII (odds ratio: 10.96; 95% confidence interval [CI]: 1.09-110.35) and male sex (3.93; 95% CI: 1.43-10.76) were associated with CSVT. When FII G20210A analysis was adjusted for sex, the OR for FII G20210A was 6.70 (95% CI: 0.65-69.22). No differences were found for FV G1691A or homozygous MTHFR mutations between neonates with CSVT and their mothers, compared to controls.

Neuron-Specific Enolase in Cerebrospinal Fluid Predicts Brain Injury After Sudden Unexpected Postnatal Collapse.

BACKGROUND: Biomarkers of brain injury with high predictive value in newborns in critical neurological status are increasingly required. Neuron-specific enolase in cerebrospinal fluid has been shown to be highly predictive in newborns with perinatal hypoxic-ischemic encephalopathy, but its utility has not been examined in sudden unexpected postnatal collapse. PURPOSE: We analyzed whether the levels of neuron-specific enolase in cerebrospinal fluid can be a useful biomarker to estimate the severity of brain injury in neonates after a sudden unexpected postnatal collapse. METHODS: This is a prospective observational study of near-term infants who were consecutively admitted with sudden unexpected postnatal collapse in two neonatal intensive care units during a nine-year period. Variables were collected and analyzed regarding the perinatal period, clinical course, severity of encephalopathy, amplitude-integrated encephalography, magnetic resonance imaging findings, and outcome. Neuron-specific enolase in cerebrospinal fluid samples were obtained in 18 infants with sudden unexpected postnatal collapse between 12 and 72 hours after the collapse and compared with those of 29 controls. RESULTS: The levels of neuron-specific enolase in cerebrospinal fluid were higher in patients than in controls (P < 0.001). Levels of neuron-specific enolase in cerebrospinal fluid in infants with sudden unexpected postnatal collapse were significantly higher in patients who presented severe encephalopathy, seizures, abnormal amplitude-integrated encephalography background, or brain injury on magnetic resonance imaging. Receiver operator characteristic curve analysis revealed a neuron-specific enolase in cerebrospinal fluid cutoff value of maximum predictive accuracy of 61 ng/mL (area under the curve, 1.0; sensitivity, specificity, positive predictive value, and negative predictive value, 100%) for identifying infants who died or had adverse outcomes. CONCLUSIONS: Levels of neuron-specific enolase in cerebrospinal fluid obtained between 12 and 72 hours after a sudden unexpected postnatal collapse event seem to be a useful biomarker for identifying newborns with severe brain injury and for predicting outcome.

Usefulness of Cranial Ultrasound for Detecting Neonatal Middle Cerebral Artery Stroke.

Magnetic resonance imaging is the gold standard technique in establishing the diagnosis of neonatal arterial ischemic stroke (NAIS). The diagnostic value of cranial ultrasound scanning in this clinical context is controversial. We aimed to assess the current sensitivity of the cranial ultrasound scan (CUS) in detecting NAIS, as this issue has not been well described in the literature. Newborns with NAIS diagnosed by magnetic resonance imaging between 2010 and 2016 were included. All CUSs were blindly analyzed retrospectively by a neonatologist expert in neuroimaging and compared with the findings of non-expert evaluators recorded on medical charts immediately after performing the evaluation. The overall sensitivity of CUS in detecting an imaging finding suggestive of NAIS was 87% (95% confidence interval (CI): 79%-95%) for an expert evaluator, but declined to 72% (61%-83%) when performed by a non-expert evaluator (p 0.002). Sensitivity was 83% and 61% in the first 24 h and 86% and 66% at 24-48 h for expert and non-expert evaluators, respectively (p < 0.05). CUS has higher sensitivity than previously reported in the detection of a NAIS, for both expert and non-expert evaluators. These findings may be explained by the advanced technology of new ultrasound equipment. Expertise in performing CUS is useful, particularly in the first 48 h after clinical debut.

Efficacy of passive hypothermia and adverse events during transport of asphyxiated newborns according to the severity of hypoxic-ischemic encephalopathy / Eficácia da hipotermia passiva e eventos adversos durante o transporte de recém-nascidos asfixiados de acordo com a gravidade da encefalopatia hipóxico-isquêmica

Abstract Objective To determine if the efficacy of passive hypothermia and adverse events during transport are related to the severity of neonatal hypoxic-ischemic encephalopathy. Methods This was a retrospective study of 67 infants with hypoxic-ischemic encephalopathy, born between April 2009 and December 2013, who were transferred for therapeutic hypothermia and cooled during transport. Results Fifty-six newborns (84%) were transferred without external sources of heat and 11 (16%) needed an external heat source. The mean temperature at departure was 34.4 ± 1.4 °C and mean transfer time was 3.3 ± 2.0 h. Mean age at arrival was 5.6 ± 2.5 h. Temperature at arrival was between 33 and 35 °C in 41 (61%) infants, between 35 °C and 36.5 °C in 15 (22%) and <33 °C in 11 (16%). Infants with severe hypoxic-ischemic encephalopathy had greater risk of having an admission temperature < 33 °C (OR: 4.5; 95% CI: 1.1-19.3). The severity of hypoxic-ischemic encephalopathy and the umbilical artery pH were independent risk factors for a low temperature on admission (p < 0.05). Adverse events during transfer, mainly hypotension and bleeding from the endotracheal tube, occurred in 14 infants (21%), with no differences between infants with moderate or severe hypoxic-ischemic encephalopathy. Conclusion The risk of overcooling during transport is greater in newborns with severe hypoxic-ischemic encephalopathy and those with more severe acidosis at birth. The most common adverse events during transport are related to physiological deterioration and bleeding from the endotracheal tube. This observation provides useful information to identify those asphyxiated infants who require closer clinical surveillance during transport.

Resumo Objetivo Determinar se a eficácia da hipotermia passiva e eventos adversos durante o transporte estão relacionados à gravidade da encefalopatia hipóxico-isquêmica neonatal. Métodos Estudo retrospectivo de 67 neonatos com encefalopatia hipóxico-isquêmica (nascidos entre abril de 2009 e dezembro de 2013) transferidos para hipotermia terapêutica e resfriados durante o transporte. Resultados Foram transportados 56 recém-nascidos (84%) sem fontes externas de calor e 11 (16%) precisaram de uma fonte externa de calor. A temperatura média na saída foi de 34,4 ± 1,4 °C e o tempo médio de transporte foi de 3,3 ± 2,0 horas. A idade média na chegada foi de 5,6 ± 2,5 horas. A temperatura na chegada ficou entre 33-35 °C em 41 (61%) neonatos, entre 35°-36,5 °C em 15 (22%) e < 33 °C em 11 (16%). Neonatos com encefalopatia hipóxico-isquêmica grave apresentaram maior risco de temperatura < 33 °C na internação (RC 4,5; IC de 95% 1,1-19,3). A gravidade da encefalopatia hipóxico-isquêmica e o pH da artéria umbilical foram fatores de risco independentes para uma baixa temperatura na internação (p < 0,05). Eventos adversos durante o transporte, principalmente hipotensão e sangramento do tubo endotraqueal, ocorreram em 14 neonatos (21%), sem diferenças entre neonatos com encefalopatia hipóxico-isquêmica moderada ou grave. Conclusão O risco de super-resfriamento durante o transporte é maior em recém-nascidos com encefalopatia hipóxico-isquêmica grave e naqueles com acidose mais grave no nascimento. Os eventos adversos mais comuns durante o transporte estão relacionados a deterioração fisiológica e sangramento do tubo endotraqueal. Essa observação fornece informações úteis para identificar neonatos asfixiados que exigem maior vigilância clínica durante o transporte.

Neonatal Arterial Ischemic Stroke: Risk Related to Family History, Maternal Diseases, and Genetic Thrombophilia.

The objective of this study was to evaluate the heritability of neonatal arterial ischemic stroke (NAIS) in relation to family history of thromboembolic event, maternal diseases, and thrombophilia in both parents ( F5G1691A, F2G20210A, and MTHFRC677 T mutations). Forty-two consecutive infants ≥36 weeks of gestation <28 days of life with acute symptomatic NAIS and their parents, as well as 129 controls, were prospectively recruited. Information on maternal data (age, body mass index, oral contraception, migraine, epilepsy, hypertension, and immune disease) and a 3-generation pedigree regarding myocardial infarction, pulmonary embolism, cerebrovascular event, and deep vein thrombosis were obtained. Thrombophilia and maternal diseases did not differ between cases and controls, except for the use of oral contraceptives (more frequent in mothers of controls). No differences were found regarding each studied antecedent of thromboembolic event in the families. The NAIS group showed a higher presence of positive family history among second-degree maternal relatives than did the control infants (odds ratio 4.10; 95% confidence interval 1.29-12.99). Our study does not support the hypothesis that common genetic thrombophilia or familial predisposition to thromboembolic events is associated with the occurrence of idiopathic NAIS.