Mitochondrial dynamics and sex-specific responses in the developing rat hippocampus: Effect of perinatal asphyxia and mesenchymal stem cell Secretome treatment.

AIMS: Perinatal asphyxia is one of the major causes of neonatal death at birth. Survivors can progress but often suffer from long-term sequelae. We aim to determine the effects of perinatal asphyxia on mitochondrial dynamics and whether mesenchymal stem cell secretome (MSC-S) treatment can alleviate the deleterious effects. MATERIALS AND METHODS: Animals were subjected to 21 min of asphyxia at the time of delivery. MSC-S or vehicle was intranasally administered 2 h post-delivery. Mitochondrial mass (D-loop, qPCR), mitochondrial dynamics proteins (Drp1, Fis1 and OPA1, Western blot), mitochondrial dynamics (TOMM20, Immunofluorescence), as well as mitochondrial membrane potential (ΔΨm) (Safranin O) were evaluated at P1 and P7 in the hippocampus. KEY FINDINGS: Perinatal asphyxia increased levels of mitochondrial dynamics proteins Drp1 and S-OPA1 at P1 and Fis1 at P7. Mitochondrial density and mass were decreased at P1. Perinatal asphyxia induced sex-specific differences, with increased L-OPA1 in females at P7 and increased mitochondria circularity. In males, asphyxia-exposed animals exhibited a reduced ΔΨm at P7. MSC-S treatment normalised levels of mitochondrial dynamics proteins involved in fission. SIGNIFICANCE: This study provides novel insights into the effects of perinatal asphyxia on mitochondrial dynamics in the developing brain and on the therapeutic opportunities provided by mesenchymal stem cell secretome treatment. It also highlights on the relevance of considering sex as a biological variable in perinatal brain injury and therapy development. These findings contribute to the development of targeted, personalised therapies for infants affected by perinatal asphyxia.

Fatal asphyxia due to large laryngeal granuloma.

Laryngeal granuloma, vocal process granuloma, or post-intubation granuloma are benign, inflammatory lesions of the arytenoid cartilage vocal process. The etiology of laryngeal granulomas is multifactorial, such as chronic irritation due to endotracheal intubation, vocal cord injury or trauma, and gastroesophageal reflux disease. They can arise postoperatively after mucosal injury due to orotracheal intubation. Clinical manifestations include voice change and dyspnea, which may start one to four months after extubation and may rarely lead to asphyxia. We presented a case of death due to glottic granuloma occurring after a surgical procedure to remove a laryngeal polyp attributed to previous laryngeal injuries by multiple intubations.

Quality assessment of clinical practice guidelines on hypoxic-ischaemic encephalopathy in newborns using the AGREE II tool: a systematic review.

INTRODUCTION: Hypoxic-ischaemic encephalopathy is a clinical syndrome of neurological dysfunction that occurs immediately after birth following an episode of perinatal asphyxia. We conducted a scoping review to assess the methodological quality of clinical practice guidelines that address this condition. METHODOLOGY: We conducted the evaluation using the AGREE II tool. High methodological quality was defined as a score greater than 70% in every domain. RESULTS: The analysis included three clinical practice guidelines; the highest scores were in the scope and purpose domain (84.26%; SD, 14.25%) and the clarity of presentation domain (84.26%; SD, 17.86%), while the lowest score corresponded to the applicability domain (62.50%; SD, 36.62%). Two guidelines were classified as high quality and one guideline as low-quality. CONCLUSIONS: Two of the assessed guidelines were classified as being of high quality; however, the analysis identified shortcomings in the applicability domain, in addition to methodological variation between guidelines developed in middle- or low-income countries versus high-income countries. Efforts are needed to make high-quality guidelines available to approach the management of hypoxic-ischaemic encephalopathy in newborns.

Clinical-functional correlation with brain volumetry in severe perinatal asphyxia: a case report.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) appears in neurological conditions where some brain areas are likely to be injured, such as deep grey matter, basal ganglia area, and white matter subcortical periventricular áreas. Moreover, modeling these brain areas in a newborn is challenging due to significant variability in the intensities associated with HIE conditions. This paper aims to evaluate functional measurements and 3D machine learning models of a given HIE case by correlating the affected brain areas with the pathophysiology and clinical neurodevelopmental. CASE PRESENTATION: A comprehensive analysis of a term infant with perinatal asphyxia using longitudinal 3D brain information from Machine Learning Models is presented. The clinical analysis revealed the perinatal asphyxia diagnosis with APGAR <5 at 5 and 10 minutes, umbilical arterial pH of 7.0 BE of -21.2 mmol / L), neonatal seizures, and invasive ventilation mechanics. Therapeutic interventions: physical, occupational, and language neurodevelopmental therapies. Epilepsy treatment: vagus nerve stimulation, levetiracetam, and phenobarbital. Furthermore, the 3D analysis showed how the volume decreases due to age, exhibiting an increasing asymmetry between hemispheres. The results of the basal ganglia area showed that thalamus asymmetry, caudate, and putamen increase over time while globus pallidus decreases. CLINICAL OUTCOMES: spastic cerebral palsy, microcephaly, treatment-refractory epilepsy. CONCLUSIONS: Slight changes in the basal ganglia and cerebellum require 3D volumetry for detection, as standard MRI examinations cannot fully reveal their complex shape variations. Quantifying these subtle neurodevelopmental changes helps in understanding their clinical implications. Besides, neurophysiological evaluations can boost neuroplasticity in children with neurological sequelae by stimulating new neuronal connections.

Cerebral rScO2 Measured by Near-Infrared Spectroscopy (NIRS) During Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review.

INTRODUCTION: Perinatal asphyxia, a leading cause of neonatal mortality and neurological sequelae, necessitates early detection of pathophysiological neurologic changes during hypoxic-ischaemic encephalopathy (HIE). This study aimed to review published data on rScO2 monitoring during hypothermia treatment in neonates with perinatal asphyxia to predict short- and long-term neurological injury. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Study identification was performed through a search between November and December 2021 in the electronic databases PubMed, Embase, Lilacs, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). The main outcome was short-term (Changes in brain magnetic resonating imaging) and long-term (In neurodevelopment) neurological injury. The study protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews) with CRD42023395438. RESULTS: 380 articles were collected from databases in the initial search. Finally, 15 articles were selected for extraction and analysis of the information. An increase in rScO2 measured by NIRS (Near-infrared spectroscopy) at different moments of treatment predicts neurological injury. However, there exists a wide variability in the methods and outcomes of the studies. CONCLUSION: High rScO2 values were found to predict negative outcomes, with substantial discord among studies. NIRS is proposed as a real-time bedside tool for predicting brain injury in neonates with moderate to severe HIE.

Esophageal Versus Rectal Temperature Monitoring During Whole-Body Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy: Association with Short- and Long-Term Outcomes.

OBJECTIVE: To compare the short- and long-term outcomes of infants with hypoxic-ischemic encephalopathy (HIE) treated with whole-body therapeutic hypothermia (TH), monitored by esophageal vs rectal temperature. STUDY DESIGN: We conducted a secondary analysis of the multicenter High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial. All infants had moderate or severe HIE and were treated with whole-body TH. The primary outcome was death or neurodevelopmental impairment (NDI) at 22-36 months of age. Secondary outcomes included seizures, evidence of brain injury on magnetic resonance imaging, and complications of hypothermia. Logistic regression was used with adjustment for disease severity and site as clustering variable because cooling modality differed by site. RESULTS: Of the 500 infants who underwent TH, 294 (59%) and 206 (41%) had esophageal and rectal temperature monitoring, respectively. There were no differences in death or NDI, seizures, or evidence of injury on magnetic resonance imaging between the 2 groups. Infants treated with TH and rectal temperature monitoring had lower odds of overcooling (OR 0.52, 95% CI 0.34-0.80) and lower odds of hypotension (OR 0.57, 95% CI 0.39-0.84) compared with those with esophageal temperature monitoring. CONCLUSIONS: Although infants undergoing TH with esophageal monitoring were more likely to experience overcooling and hypotension, the rate of death or NDI was similar whether esophageal monitoring or rectal temperature monitoring was used. Further studies are needed to investigate whether esophageal temperature monitoring during TH is associated with an increased risk of overcooling and hypotension.

The Urinary Metabolome of Newborns with Perinatal Complications.

Maternal pathological conditions such as infections and chronic diseases, along with unexpected events during labor, can lead to life-threatening perinatal outcomes. These outcomes can have irreversible consequences throughout an individual's entire life. Urinary metabolomics can provide valuable insights into early physiological adaptations in healthy newborns, as well as metabolic disturbances in premature infants or infants with birth complications. In the present study, we measured 180 metabolites and metabolite ratios in the urine of 13 healthy (hospital-discharged) and 38 critically ill newborns (admitted to the neonatal intensive care unit (NICU)). We used an in-house-developed targeted tandem mass spectrometry (MS/MS)-based metabolomic assay (TMIC Mega) combining liquid chromatography (LC-MS/MS) and flow injection analysis (FIA-MS/MS) to quantitatively analyze up to 26 classes of compounds. Average urinary concentrations (and ranges) for 167 different metabolites from 38 critically ill NICU newborns during their first 24 h of life were determined. Similar sets of urinary values were determined for the 13 healthy newborns. These reference data have been uploaded to the Human Metabolome Database. Urinary concentrations and ranges of 37 metabolites are reported for the first time for newborns. Significant differences were found in the urinary levels of 44 metabolites between healthy newborns and those admitted at the NICU. Metabolites such as acylcarnitines, amino acids and derivatives, biogenic amines, sugars, and organic acids are dysregulated in newborns with bronchopulmonary dysplasia (BPD), asphyxia, or newborns exposed to SARS-CoV-2 during the intrauterine period. Urine can serve as a valuable source of information for understanding metabolic alterations associated with life-threatening perinatal outcomes.

Estrangulación/sofocación no fatal en el contexto de violencia de género: Aspectos médico-legales e implicancias para la práctica clínica / Non-fatal strangulation/suffocation in context of gender violence: Medicolegal aspects and implications in clinical practice

RESUMEN A pesar de los numerosos esfuerzos de la comunidad internacional en pos de erradicar todas las formas de violencia contra las mujeres, esta problemática se encuentra lejos de ser resuelta. Según la ONU, una de cada tres mujeres ha sufrido violencia física o sexual por parte de la pareja, violencia sexual fuera de la pareja, o de ambas, al menos una vez en su vida. El abordaje de esta problemática, en tanto necesidad social de salud de grupos poblacionales, permite una aproximación a la violencia de género como un problema de salud colectiva. En el plano de la violencia física, la estrangulación/sofocación ha sido identificada como una de las formas más letales de violencia doméstica y agresión sexual; se ha reportado que una víctima que es estrangulada una primera vez tiene 7,5 más probabilidades de ser asesinada posteriormente por el mismo abusador. Una víctima de estrangulación/sofocación puede perder la conciencia en segundos o morir en minutos, días o semanas después del ataque o sufrir daño cerebral permanente o invalidez, además del trauma emocional. Recientemente, se han generado cambios legales en la configuración de este delito; las penas han aumentado en el Reino Unido, Estados Unidos, Australia y Nueva Zelandia. El propósito de esta revisión de literatura de tipo narrativo, no sistemática, está orientada a presentar aspectos médico-legales actualizados de la estrangulación/sofocación no fatal en el contexto de la violencia de género, y se resaltan aquellas implicancias relevantes para la práctica clínica.

ABSTRACT Despite the numerous efforts of the international community to eradicate all forms of violence against women, this problem is far from being resolved. According to the UN, one in three women has suffered physical or sexual violence from an intimate partner, sexual violence outside the couple, or both at least once in their life. Addressing this problem as a social health need of population groups allows an approach to gender violence as a collective health problem. At the level of physical violence, strangulation/suffocation has been identified as one of the most lethal forms of domestic violence and sexual assault. Victims of domestic violence who have been choked or strangled are 7.5 times more likely to be killed by their partner. A victim of strangulation/suffocation can lose consciousness in seconds or die within minutes, days or weeks after the attack, as well as suffer permanent brain damage or disability or emotional trauma. Recently, legal changes have been generated in the configuration of this crime, the penalties have increased in United Kingdom, the United States, Australia and New Zealand. The current non-systematic narrative review of literature sought to explore updated medico-legal aspects of non-fatal strangulation/suffocation in the context of gender violence, and are highlightedrelevant implications for clinical practice.

Fatal asphyxia due to large laryngeal granuloma

ABSTRACT Laryngeal granuloma, vocal process granuloma, or post-intubation granuloma are benign, inflammatory lesions of the arytenoid cartilage vocal process. The etiology of laryngeal granulomas is multifactorial, such as chronic irritation due to endotracheal intubation, vocal cord injury or trauma, and gastroesophageal reflux disease. They can arise postoperatively after mucosal injury due to orotracheal intubation. Clinical manifestations include voice change and dyspnea, which may start one to four months after extubation and may rarely lead to asphyxia. We presented a case of death due to glottic granuloma occurring after a surgical procedure to remove a laryngeal polyp attributed to previous laryngeal injuries by multiple intubations.

Caracterización de neonatos con asfixia perinatal. Hospital Provincial Docente Ginecobstétrico José Ramón López Tabrane. 2016-2021

Introducción: La asfixia perinatal es un síndrome caracterizado por la suspensión o grave disminución del intercambio gaseoso a nivel de la placenta o de los pulmones. Objetivo: Caracterizar los neonatos con asfixia perinatal durante el trabajo de parto con la introducción de la gasometría de la arteria umbilical. Materiales y métodos: Se realizó un estudio descriptivo, transversal, de octubre de 2016 a diciembre de 2021. Se trabajó con la totalidad del universo: 75 neonatos asfícticos. Las variables fueron: edad materna, edad gestacional al nacimiento, enfermedades asociadas y dependientes del embarazo, tipo y tiempo de trabajo de parto, características del líquido amniótico, anomalías de la placenta y cordón umbilical, pH de la gasometría de la arteria del cordón, evolución clínica del recién nacido. Los datos se almacenaron y procesaron en una hoja de cálculo de Microsoft Excel, utilizando la estadística descriptiva. Resultados: Predominaron pacientes con edad materna menor de 20 años (56 %), y edad gestacional al nacimiento de 28 a 33,6 semanas (77,3 %). La hipertensión arterial fue la comorbilidad más común, así como la preeclampsia, entre las enfermedades dependiente del embarazo (30,7 %); 61,3 % tuvieron parto eutócico, con líquido amniótico claro (65,3 %), placenta previa (38,7 %) y circulares en cordón umbilical (30,7 %). En el 86,7 % el pH de la gasometría fue menor que 7, y el 92 % presentó evolución clínica favorable. Conclusiones: La asfixia perinatal estuvo predominantemente asociada a madres adolescentes, con tiempo gestacional entre 28 y 36 semanas, preeclampsia, placenta previa, circulares del cordón umbilical y predominio de gasometría con pH menor que 7.

Introduction: Perinatal asphyxia is a syndrome characterized by the suspension or severe decrease in gas exchange at the level of the placenta or lungs. Objective: To characterize neonates with perinatal asphyxia during labor with the introduction of umbilical arterial blood gas test. Materials and methods: A descriptive, cross-sectional study was carried out from October 2016 to December 2021. It dealt with the entire universe, 75 asphyxiated neonates. The variables were: maternal age, gestational age at birth, associated and pregnancy-dependent diseases, type and time of labor, characteristics of the amniotic fluid, anomalies of the placenta and umbilical cord, pH of the cord arterial blood gas test, clinical evolution of the newborn. The data were stored and processed in a Microsoft Excel spreadsheet, using descriptive statistics. Results: Patients with maternal age below 20 years (56%), and gestational age at birth from 28 to 33.6 weeks (77.3%) predominated. Arterial hypertension was the most common comorbidity, as well as preeclampsia, among pregnancy-dependent diseases (30.7%); 61.3% had eutocic delivery, with clear amniotic fluid (65.3%), previous placenta (38.7%) and umbilical cord circulars (30.7%). In 86.7%, the blood gas pH was less than 7 and 92% had a favorable clinical evolution. Conclusions: Perinatal asphyxia was predominantly associated with adolescent mothers, with gestational time between 28-36 weeks; preeclampsia, placenta previa, umbilical cord circulars, and blood gases pH lower than 7.

Escenarios para el diagnóstico de encefalopatía hipóxico isquémica e inicio de tratamiento con hipotermia controlada en recién nacidos con asfixia perinatal / Scenarios for the diagnosis of hypoxic-ischemic encephalopathy and initiation of therapeutic hypothermia treatment in newborns with perinatal asphyxia / Cenários para o diagnóstico da encefalopatia hipóxico-isquemia e início de tratamento de hipotermia terapêutica a recém-nascidos com asfixia perinatal

La hipoxia isquemia perinatal y su complicación más temida, la encefalopatía hipóxica isquémica, continúa siendo uno de los principales motivos de ingreso a las unidades de cuidados neonatales. En la actualidad la hipotermia controlada es el tratamiento recomendado para los pacientes con encefalopatía moderada a severa, dado su carácter de neuroprotección ante la injuria cerebral hipóxico isquémica. Si bien los criterios de inclusión en esta terapia han sido bien establecidos, aún hay dificultades tanto en la identificación precoz de aquellos que pueden verse beneficiados, como en la toma de decisiones ante situaciones de controversia entre la evidencia disponible y la que se está gestando en estudios en curso. Este artículo pretende aportar herramientas al clínico para abordar diferentes escenarios que surgen de la práctica diaria.

Perinatal hypoxic ischemia and its most feared complication, hypoxic ischemic encephalopathy, remain one of the main reasons for admission to neonatal care. Controlled hypothermia is currently the recommended treatment for patients with moderate to severe encephalopathy, given its neuroprotective nature against hypoxic-ischemic brain injury. Although the inclusion criteria for this therapy have been well established, there are still difficulties both in the early identification of those who may benefit, and in making decisions regarding situations of controversy between the available evidence and that being developing in ongoing studies. This paper aims at providing tools so that clinicians can address different scenarios that arise during their daily practice.

A hipóxia isquêmica perinatal e sua complicação mais temida, a encefalopatia hipóxico-isquêmica, continuam sendo um dos principais motivos de internação em unidades de cuidados neonatais. A hipotermia controlada é atualmente o tratamento recomendado para pacientes com encefalopatia moderada a grave, dada a sua natureza neuroprotetora contra lesão cerebral hipóxico-isquêmica. Embora os critérios de inclusão dessa terapia estejam bem estabelecidos, ainda há dificuldades tanto na identificação precoce daqueles que podem se beneficiar, quanto na tomada de decisões em situações de controvérsia entre as evidências disponíveis e aquelas que estão se desenvolvendo em estudos em andamento. Este paper tem como objetivo fornecer ferramentas aos clínicos para abordar diferentes cenários que surgem da prática diária.

A hypothermia mimetic molecule (zr17-2) reduces ganglion cell death, gliosis, and electroretinogram distortion in male rats subjected to perinatal asphyxia.

Introduction: Perinatal asphyxia (PA) represents a major problem in perinatology and may cause visual losses, including blindness. We, and others, have shown that hypothermia prevents retinal symptoms associated to PA. In the present work, we evaluate whether a hypothermia mimetic small molecule, zr17-2, has similar effects in the context of PA. Methods: Four experimental groups were studied in male rats: Naturally born rats as controls (CTL), naturally born rats injected s.c. with 50 µL of 330 nmols/L zr17-2 (ZR), animals that were exposed to PA for 20 min at 37°C (PA), and rats that were exposed to PA and injected with zr17-2 (PA-ZR). Forty-five days after treatment, animals were subjected to electroretinography. In addition, morphological techniques (TUNEL, H&E, multiple immunofluorescence) were applied to the retinas. Results: A reduction in the amplitude of the a- and b-wave and oscillatory potentials (OP) of the electroretinogram (ERG) was detected in PA animals. Treatment with zr17-2 resulted in a significant amelioration of these parameters (p < 0.01). In PA animals, a large number of apoptotic cells was found in the GCL. This number was significantly reduced by treatment with the small molecule (p < 0.0001). In a similar way, the thickness of the inner retina and the intensity of GFAP immunoreactivity (gliosis) increased in PA retinas (p < 0.0001). These parameters were corrected by the administration of zr17-2 (p < 0.0001). Furthermore, injection of the small molecule in the absence of PA did not modify the ERG nor the morphological parameters studied, suggesting a lack of toxicity. Discussion: In conclusion, our results indicate that a single s.c. injection of zr17-2 in asphyctic neonates may provide a novel and efficacious method to prevent the visual sequelae of PA.

Short-term neurological injury in newborns infants with overcooling in passive hypothermia and transferred to reference hospital in Colombia.

AIM: The aim of the study was to determine whether overcooling (temperature <33°C) during passive hypothermia when transporting neonates with perinatal asphyxia increased the risk of short-term neurological injury. METHODS: A retrospective observational study was performed. Newborns transferred to the LaCardio neonatal unit between January 2021 and April 2022 with moderate and severe perinatal asphyxia and who received passive hypothermia during transport were included. A temperature of <33°C was considered overcooling. A composite outcome of neurological injury was defined by the presence of abnormalities on brain magnetic resonance imaging, video telemetry, seizure before discharge or both. RESULTS: The study included 101 newborns. A total of 18 neonates had a temperature <33°C after transportation. Neurological injuries were present in 21.8% of the temperature <33°C group and 78.2% of the temperature ≥33°C group. Temperature <33°C at the end of transport (aOR 9.2, 95% CI 1.1-77.3) were associated with neurological injury before discharge from the unit. CONCLUSION: During transportation, overcooling in neonates with asphyxia increases the risk of neurological injury before discharge from the neonatal unit. It is important to qualify the transport team with adequate training and equipment for therapeutic hypothermia.

Cerebral Glucose Concentration in Neonatal Hypoxic-Ischemic Encephalopathy during Therapeutic Hypothermia.

OBJECTIVE: To determine cerebral glucose concentration and its relationship with glucose infusion rate (GIR) and blood glucose concentration in neonatal encephalopathy during therapeutic hypothermia (TH). METHODS: This was an observational study in which cerebral glucose during TH was quantified by magnetic resonance (MR) spectroscopy and compared with mean blood glucose at the time of scan. Clinical data (gestational age, birth weight, GIR, sedative use) that could affect glucose use were collected. The severity and pattern of brain injury on MR imaging were scored by a neuroradiologist. Student t test, Pearson correlation, repeated measures ANOVA, and multiple regression analysis were performed. RESULTS: Three-hundred-sixty blood glucose values and 402 MR spectra from 54 infants (30 female infants; mean gestational age 38.6 ± 1.9 weeks) were analyzed. In total, 41 infants had normal-mild and 13 had moderate-severe injury. Median GIR and blood glucose during TH were 6.0 mg/kg/min (IQR 5-7) and 90 mg/dL (IQR 80-102), respectively. GIR did not correlate with blood or cerebral glucose. Cerebral glucose was significantly greater during than after TH (65.9 ± 22.9 vs 60.0 ± 25.2 mg/dL, P < .01), and there was a significant correlation between blood glucose and cerebral glucose during TH (basal ganglia: r = 0.42, thalamus: r = 0.42, cortical gray matter: r = 0.39, white matter: r = 0.39, all P < .01). There was no significant difference in cerebral glucose concentration in relation to injury severity or pattern. CONCLUSIONS: During TH, cerebral glucose concentration is partly dependent on blood glucose concentration. Further studies to understand brain glucose use and optimal glucose concentrations during hypothermic neuroprotection are needed.

Therapeutic hypothermia as a neuroprotective strategy in newborns with perinatal asphyxia-case report.

Background: Perinatal asphyxia is a public health problem and the third major cause of death among children under 5 years. Objective: Two clinical cases of newborns with perinatal asphyxia submitted to therapeutic hypothermia and the follow-up of their motor development after hospital discharge have been reported. Methods: This retrospective case report study included two newborns with hypoxic-ischemic encephalopathy due to perinatal asphyxia who received a hypothermia protocol at the neonatal intensive care unit (NICU). The two newborns and their families were followed up at the outpatient clinic and assessed using the Hammersmith Child Neurological Examination, Alberta Child Motor Scale, and Denver Developmental Screening Test-II. Results: The newborns were submitted to a 72-hour hypothermia protocol. One newborn remained for 13 days in the NICU, while the other remained for 22 days. According to the multidisciplinary team, both cases presented with typical motor development with no cerebral palsy during the follow-up. Conclusion: Both cases showed positive results and a good prognostic for motor development. Therapeutic hypothermia may be a strategy to prevent neurologic sequelae in newborns with perinatal asphyxia, including cerebral palsy.

Impact of resuscitation training program on neonatal outcomes in a region of high socioeconomic vulnerability in Brazil: an interventional study.

OBJECTIVES: This pre/post-intervention study aimed to evaluate neonatal outcomes after the implementation of the Neonatal Resuscitation Program of the Brazilian Society of Pediatrics. METHOD: This interventional study was conducted across five secondary healthcare regions that supported 62 cities in the southwestern mesoregion of Piauí. It included 431 healthcare professionals responsible for neonatal care in the study region. The participants were trained in neonatal resuscitation through the Neonatal Resuscitation Program of the Brazilian Society of Pediatrics. Delivery room structuring, healthcare professionals' knowledge, and neonatal care outcomes were analyzed immediately before and after intervention and after 12 months between February 2018 and March 2019, and healthcare professionals were evaluated. RESULTS: Training was conducted for over 106 courses. As a participant could take multiple courses, 700 training sessions were conducted. Regarding delivery room structuring, the acquisition of materials required for resuscitation increased from 28.4 to 80.6% immediately after the intervention and to 83.3% after 12 months. Knowledge retention was significant in the post-training period, with a 95.5% approval rate, and knowledge acquisition was satisfactory after 12 months. The number of newborns transferred during the study period increased significantly. A 72.6% reduction in mortality at birth was recorded, and 479 newborns were resuscitated. CONCLUSION: Following the implementation of the Neonatal Resuscitation Program of the Brazilian Society of Pediatrics, structural improvements in delivery rooms, adequate knowledge retention regarding neonatal resuscitation, and a consequent reduction in neonatal mortality were observed.

Additional Value of 3-Month Cranial Magnetic Resonance Imaging in Infants with Neonatal Encephalopathy following Perinatal Asphyxia.

OBJECTIVE: To assess the evolution of neonatal brain injury noted on magnetic resonance imaging (MRI), develop a score to assess brain injury on 3-month MRI, and determine the association of 3-month MRI with neurodevelopmental outcome in neonatal encephalopathy (NE) following perinatal asphyxia. METHODS: This was a retrospective, single-center study including 63 infants with perinatal asphyxia and NE (n = 28 cooled) with cranial MRI <2 weeks and 2-4 months after birth. Both scans were assessed using biometrics, a validated injury score for neonatal MRI, and a new score for 3-month MRI, with a white matter (WM), deep gray matter (DGM), and cerebellum subscore. The evolution of brain lesions was assessed, and both scans were related to 18- to 24-month composite outcome. Adverse outcome included cerebral palsy, neurodevelopmental delay, hearing/visual impairment, and epilepsy. RESULTS: Neonatal DGM injury generally evolved into DGM atrophy and focal signal abnormalities, and WM/watershed injury evolved into WM and/or cortical atrophy. Although the neonatal total and DGM scores were associated with composite adverse outcomes, the 3-month DGM score (OR 1.5, 95% CI 1.2-2.0) and WM score (OR 1.1, 95% CI 1.0-1.3) also were associated with composite adverse outcomes (occurring in n = 23). The 3-month multivariable model (including the DGM and WM subscores) had higher positive (0.88 vs 0.83) but lower negative predictive value (0.83 vs 0.84) than neonatal MRI. Inter-rater agreement for the total, WM, and DGM 3-month score was 0.93, 0.86, and 0.59. CONCLUSIONS: In particular, DGM abnormalities on 3-month MRI, preceded by DGM abnormalities on the neonatal MRI, were associated with 18- to 24-month outcome, indicating the utility of 3-month MRI for treatment evaluation in neuroprotective trials. However, the clinical usefulness of 3-month MRI seems limited compared with neonatal MRI.

Evaluación renal y multiorgánica en el paciente con encefalopatía hipóxico-isquémica / Renal and multiorgan evaluation in infants with post-asphyxial hypoxic-ischaemic encephalopathy

Resumen Introducción: La encefalopatía hipóxico-isquémica (EHI) moderada-grave secundaria a asfixia perinatal puede afectar a cualquier órgano, empeorando el pronóstico. Objetivo: Evaluar la afectación renal y multiorgánica de estos pacientes. Material y método: Se incluyó a recién nacidos > 35 semanas con EHI moderada-grave tratados con hipotermia activa entre 2010 y 2020. Se evaluó la creatinina en tres periodos: 48-72 horas de vida, entre el 3.o y 7.o día de vida y del 7.o al 28.o día de vida. Resultados: Se incluyeron 135 pacientes: 112 con EHI moderada y 23 con EHI grave. Al comparar ambos grupos, se obtuvieron diferencias significativas a las 48-72 horas y entre 3.o-7.o día de vida. No hubo diferencias al comparar el método de hipotermia. Los pacientes con EHI grave presentaron mayor afectación hemodinámica, respiratoria y hepática. Conclusiones: Neonatos con EHI grave presentan aumento de los niveles de creatinina sérica y mayor afectación multiorgánica respecto a aquellos con EHI moderada.

Abstract Background: Hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia can affect any organ, worsening the prognosis. Objective: To describe renal and multiorgan involvement in moderate-severe HIE. Material and method: Newborns > 35 weeks diagnosed with moderate-severe HIE who required active hypothermia between 2010-2020 were included. To assess renal involvement, serum creatinine was measured in three different periods: at 48-72 hours, between the 3rd and the 7th day, and from the 7th to the 28th day. Results: A total of 135 patients were included, 112 (83%) with moderate and 23 (17%) with severe HIE. Significant differences were obtained when comparing median creatinine levels at 48-72 hours and between 3-7 days in both groups. There were no differences in creatinine according to the hypothermia method. Patients with severe HIE presented greater hemodynamic, respiratory, and hepatic involvement. Conclusions: Neonates with severe HIE present increased serum creatinine levels and greater multi-organ involvement than those with moderate HIE.

Proporção e fatores associados a Apgar menor que 7 no 5º minuto de vida: de 1999 a 2019, o que mudou? / Proportion and factors associated with Apgar less than 7 in the 5th minute of life: from 1999 to 2019, what has changed?

Resumo Apesar da variação entre observadores na avaliação do escore de Apgar, ele permanece um indicador útil das condições gerais do recém-nascido. O presente trabalho é um estudo de corte transversal baseado na população de nascidos vivos no Brasil no ano de 1999 e no biênio 2018-2019. Foram avaliadas todas as declarações de nascidos vivos (DNV) obtidas a partir do banco de dados do Sistema de Informações sobre Nascidos Vivos. As frequências foram comparadas entre os grupos por meio do teste qui-quadrado de Pearson e foi realizada análise de regressão logística multivariada. Adotou-se nível de significância estatística de 0,05. Foram analisadas 9.050.521 DNVs em nossa pesquisa. Constatamos que 2,1% dos recém-nascidos tiveram Apgar de 5º minuto < 7 em 1999, em comparação com 0,9% em 2018-2019. A análise multivariada indicou que gemelidade e gravidez na adolescência deixaram de ser fatores de risco para Apgar de 5º minuto < 7. Entre os fatores de risco, nota-se aumento da prematuridade, baixo peso ao nascer e anomalias congênitas. Observou-se melhoria de marcadores maternos, em especial o aumento do número de consultas pré-natais e escolaridade. Tais achados mostram a importância de acesso e seguimento pré-natal adequado e investimento em melhores condições socioeconômicas como estratégia eficaz para redução de morbimortalidade neonatal.

Abstract Although variation between observers in the assessment of the Apgar score, it remains a useful indicator of the general conditions of the newborn. This is a cross-sectional study based on population of live births in Brazil in 1999 and biennium 2018-2019. All declarations of live births (DNV) obtained from the Live Births System database were accessed. Frequencies were compared between groups using Pearson's chi-square test and multivariate logistic regression analysis was performed. A statistical significance level of 0.05 was considered. We included 9.050.521 DNVs in our research. We found that 2,1% of newborns had 5th minute Apgar < 7 in 1999 compared with 0,9% in 2018-2019. Multivariate analysis shows that twins and teenage pregnancy are no longer risk factors. Among risk factors, we observed an increase in prematurity, low birth weight and congenital anomalies. An improvement in maternal markers was observed, especially increase in the number of prenatal consultations and schooling. Such findings demonstrate the importance access and adequate prenatal care and improved socioeconomic conditions as effective strategy to reduce neonatal morbidity and mortality.

Prominent Intrapulmonary Shunt Vessels and Altered Lung Development in Infants With Sudden Unexplained Infant Death.

The purpose of this study was to evaluate intrapulmonary arteriovenous shunts in patients with and without sudden unexplained infant death. We identified open intrapulmonary bronchopulmonary anastomoses as potential pathways for right-to-left shunt in a subset of infants with sudden unexplained infant death.