Incidence of encephalopathy and comorbidity in infants with perinatal asphyxia: a comparative prospective cohort study.

Background: Programs that aim to improve the detection hypoxic-ischemic encephalopathy (HIE) should establish which neonates suffering from perinatal asphyxia need to be monitored within the first 6 h of life. Method: An observational prospective cohort study of infants with gestational age ≥35 weeks, and above 1,800g, were included according to their arterial cord pH value (ApH): ≤7.00 vs. 7.01-7.10. Data was collected including obstetrical history, as well as neonatal comorbidities, including the presence of HIE, that happened within 6 h of life. A standardized neurological exam was performed at discharge. Results: There were 9,537 births; 176 infants with ApH 7.01-7.10 and 117 infants with ApH ≤7.00. All 9 cases with moderate-to-severe HIE occurred among infants with ApH ≤7.00. The incidence of global and moderate-severe HIE was 3/1,000 and 1/1,000 births, respectively. Outcome at discharge (abnormal exam or death) showed an OR 12.03 (95% CI 1.53, 94.96) in infants with ApH ≤7.00 compared to ApH 7.01-7.10 cohort. Ventilation support was 5.1 times (95% CI 2.87, 9.03) more likely to be needed by those with cord ApH ≤7.00 compared to those with ApH 7.01-7.10, as well as hypoglycemia (37% vs. 25%; p = 0.026). In 55%, hypoglycemia occurred despite oral and/or intravenous glucose administration had been already initiated. Conclusions: Cord pH 7.00 might be a safe pH cut-off point when developing protocols to monitor infants born with acidemia in order to identify infants with moderate or severe HIE early on. There is non-negligible comorbidity in the ApH ≤7.00 cohort, but also in the 7.01-7.10 cohort.

Hypoxic-ischaemic encephalopathy code: A systematic review for resource-limited settings.

It is estimated that 96% of infants with hypoxic-ischaemic encephalopathy (HIE) are born in resource-limited settings with no capacity to provide the standard of care that has been established for nearly 15 years in high-resource countries, which includes therapeutic hypothermia (TH), continuous electroencephalographic monitoring and magnetic resonance imaging (MRI) in addition to close vital signs and haemodynamic monitoring. This situation does not seem to be changing; however, even with these limitations, currently available knowledge can help improve the care of HIE patients in resource-limited settings. The purpose of this systematic review was to provide, under the term "HIE Code", evidence-based recommendations for feasible care practices to optimise the care of infants with HIE and potentially help reduce the risks associated with comorbidity and improve neurodevelopmental outcomes. The content of the HIE code was grouped under 9 headings: (1) prevention of HIE, (2) resuscitation, (3) first 6h post birth, (4) identification and grading of encephalopathy, (5) seizure management, (6) other therapeutic interventions, (7) multiple organ dysfunction, (8) diagnostic tests and (9) family care.

Código encefalopatía hipóxico-isquémica: revisión sistematizada para entornos con recursos limitados / Hypoxic-ischaemic encephalopathy code: a systematic review for resource-limited settings

Se estima que el 96% de los recién nacidos (RN) con encefalopatía hipóxico-isquémica (EHI) nacen en entornos con recursos limitados (ERL) sin capacidad para ofrecer el estándar asistencial vigente desde hace cerca de 15 años en los países con altos recursos y que incluye hipotermia terapéutica, neuromonitorización continua electroencefalográfica y resonancia magnética, además de un control intensivo de las constantes vitales y del equilibrio homeostático. Esta situación no parece estar cambiando; sin embargo y aún con estas limitaciones, el conocimiento actualmente disponible permite mejorar la asistencia de los pacientes con EHI atendidos en ERL. El propósito de esta revisión sistematizada es ofrecer, bajo el término «código EHI», recomendaciones de prácticas asistenciales basadas en evidencia científica y factibles en ERL, que permitan optimizar la atención del RN con EHI y ayuden potencialmente a reducir los riesgos asociados a la comorbilidad y a mejorar los resultados neuroevolutivos. El contenido del código EHI se agrupó en nueve epígrafes: 1) prevención de la EHI, 2) reanimación, 3) primeras seis horas de vida, 4) identificación y graduación de la EHI, 5) manejo de las convulsiones, 6) otras intervenciones terapéuticas, 7) disfunción multiorgánica, 8) estudios complementarios, y 9) atención a la familia. (AU)

It is estimated that 96% of infants with hypoxic-ischaemic encephalopathy (HIE) are born in resource-limited settings with no capacity to provide the standard of care that has been established for nearly 15 years in high-resource countries, which includes therapeutic hypothermia, continuous electroencephalographic monitoring and magnetic resonance imaging in addition to close vital signs and haemodynamic monitoring. This situation does not seem to be changing; however, even with these limitations, currently available knowledge can help improve the care of HIE patients in resource-limited settings. The purpose of this systematic review was to provide, under the term «HIE Code», evidence-based recommendations for feasible care practices to optimise the care of infants with HIE and potentially help reduce the risks associated with comorbidity and improve neurodevelopmental outcomes. The content of the HIE code was grouped under 9 headings: 1) prevention of HIE, 2) resuscitation, 3) first 6hours post birth, 4) identification and grading of encephalopathy, 5) seizure management, 6) other therapeutic interventions, 7) multiple organ dysfunction, 8) diagnostic tests and 9) family care. (AU)

Motor, cognitive and behavioural outcomes after neonatal hypoxic-ischaemic encephalopathy.

INTRODUCTION: The current neurodevelopmental status of patients with neonatal hypoxic-ischaemic encephalopathy (HIE) in Spain is unknown. Recent European studies highlight a shift of severe pathology towards mild motor disorders and emotional problems. The aim of this study was to analyse neurodevelopmental outcomes in a cohort of neonates with HIE at age 3 years. PATIENTS AND METHOD: Multicentre observational study of neonates born at 35 or more weeks of gestation with moderate to severe HIE in 2011-2013 in 12 hospitals in a large Spanish region (91 217 m2), with the recruitment extended through 2017 in the coordinating hospital. We analysed the findings of neonatal neuroimaging and neurodevelopmental test scores at 3 years (Bayley-III, Peabody Picture Vocabulary Test and Child Behavior Checklist). The sample included 79 controls with no history of perinatal asphyxia. RESULTS: Sixty-three patients were recruited, of whom 5 (7.9%) were excluded due to other pathology and 14 (24%) died. Of the 44 survivors, 42 (95.5%) were evaluated. Of these 42, 10 (24%) had adverse outcomes (visual or hearing impairment, epilepsy, cerebral palsy or developmental delay). Other detected problems were minor neurological signs in 6 of the 42 (14%) and a higher incidence of emotional problems compared to controls: introversion (10.5% vs. 1.3%), anxiety (34.2% vs. 11.7%) and depression (28.9% vs. 7.8%) (P < .05). The severity of the lesions on neuroimaging was significantly higher in patients with motor impairment (P = .004) or who died or had an adverse outcome (P = .027). CONCLUSION: In addition to classical sequelae, the followup of patients with neonatal HIE should include the diagnosis and treatment of minor motor disorders and social and emotional problems.

Desarrollo motor, cognitivo y conductual tras encefalopatía hipóxico-isquémica neonatal / Motor, cognitive and behavioural outcomes after neonatal hypoxic-ischaemic encephalopathy

Introducción: El neurodesarrollo actual de pacientes con encefalopatía hipóxico-isquémica (EHI) neonatal en España se desconoce. Recientes estudios europeos destacan el desplazamiento de la patología grave hacia trastornos motores leves y problemas emocionales. El objetivo de este estudio fue analizar el estado neuroevolutivo integral a los 3años de una cohorte de neonatos con EHI. Pacientes y métodos: Estudio observacional multicéntrico de neonatos ≥35 semanas de edad gestacional con EHI moderada-grave nacidos entre 2011 y 2013 en 12 hospitales de una extensa región española (91.217m2) y ampliado hasta 2017 en el hospital coordinador. Se evaluaron los estudios de neuroimagen neonatal y del neurodesarrollo a los 3años mediante Bayley-III, Peabody Picture Vocabulary Test y Child Behaviour Checklist. Se incluyeron 79 controles sin asfixia perinatal. Resultados: Se reclutaron 63 pacientes, de los cuales 5/63 (7,9%) se excluyeron por presentar otra patología, y 14/58 (24%) fallecieron. De los 44 supervivientes, 42/44 (95,5%) fueron evaluados. De ellos, 10/42 (24%) presentaron evolución adversa (alteraciones visuales o auditivas, epilepsia, parálisis cerebral [PC] o retraso del desarrollo). Adicionalmente se detectaron otras alteraciones: trastorno motor mínimo (TMM) en 6/42 (14%) y más problemas de introversión (10,5% vs 1,3%), ansiedad (34,2% vs 11,7%) y depresión (28,9% vs 7,8%) que los controles (p<0,05). La gravedad de las lesiones en neuroimagen fue significativamente mayor en pacientes con trastorno motor (PC o TMM) (p=0,004) y muerte o evolución adversa (p=0,027). Conclusiones: Además de las secuelas clásicas, el seguimiento de los pacientes con EHI neonatal debería incluir el diagnóstico y el manejo de trastornos motores mínimos y problemas emocionales.(AU)

Introduction: The current neurodevelopmental status of patients with neonatal hypoxic-ischaemic encephalopathy (HIE) in Spain is unknown. Recent European studies highlight a shift of severe pathology towards mild motor disorders and emotional problems. The aim of this study was to analyse neurodevelopmental outcomes in a cohort of neonates with HIE at age 3years. Patients and method: Multicentre observational study of neonates born at 35 or more weeks of gestation with moderate to severe HIE in 2011-2013 in 12 hospitals in a large Spanish region (91,217m2), with the recruitment extended through 2017 in the coordinating hospital. We analysed the findings of neonatal neuroimaging and neurodevelopmental test scores at 3years (Bayley-III, Peabody Picture Vocabulary Test and Child Behavior Checklist). The sample included 79 controls with no history of perinatal asphyxia. Results: Sixty-three patients were recruited, of whom 5 (7.9%) were excluded due to other pathology and 14 (24%) died. Of the 44 survivors, 42 (95.5%) were evaluated. Of these 42, 10 (24%) had adverse outcomes (visual or hearing impairment, epilepsy, cerebral palsy or developmental delay). Other detected problems were minor neurological signs in 6 of the 42 (14%) and a higher incidence of emotional problems compared to controls: introversion (10.5% vs. 1.3%), anxiety (34.2% vs. 11.7%) and depression (28.9% vs. 7.8%) (P<.05). The severity of the lesions on neuroimaging was significantly higher in patients with motor impairment (P=.004) or who died or had an adverse outcome (P=.027). Conclusion: In addition to classical sequelae, the follow-up of patients with neonatal HIE should include the diagnosis and treatment of minor motor disorders and social and emotional problems.(AU)

Neuroimaging in infants with congenital cytomegalovirus infection and its correlation with outcome: emphasis on white matter abnormalities.

OBJECTIVE: To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs). METHODS: Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at ≤3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at ≥6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability. RESULTS: Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89±0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia. CONCLUSIONS: Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis.

[Indicadores de salud perinatal en una región española entre los años 2015 y 2020.] / Perinatal health indicators in a region of Spain corresponding to the period 2015 to 2020.

OBJECTIVE: The availability in the literature of data related to perinatal variables in the Spanish population is very scarce. The aim of this study was to know the evolution of perinatal health indicators according to the risk groups of prematurity and birth weight, the proportion of multiple births, caesarean section and stillbirths. METHODS: We conducted a population-based cross-sectional study of births in eleven hospitals in Castilla y León (January 2015 to June 2020). There were 70,024 newborns from 68,769 deliveries. Jointpoint regression analysis was used to identify changes in trend over the years, and binomial logistic regression was used to adjust for the potential interaction of hospital type, sex, type of delivery and multiple births on the frequencies of prematurity and death. RESULTS: There was a 19.9% decrease in deliveries and a 42% decrease in multiple births, with no change in preterm (7.7%) and stillbirths (0.44%). The percentage of caesarean sections was 21.5% with a slight downward trend over time. Death (stillbirth) was associated with preterm multiple birth; especially with the male-male combination (p<0.05). Late preterm and early term newborns showed higher risk of death compared to term newborns: OR 7.7 (95%CI 5.6-10.7) and 2.4 (95%CI 1.6-3.6), respectively; as well as the low birth weight group (OR 17.6; 95%CI 13.9-22.2) and small for gestational age (OR 3.4; 95%CI 1.9-5.8), compared to those of adequate weight. CONCLUSIONS: Prior to the development of the COVID-19 pandemic there is a decline in births, including multiple births, with no change in stillbirths or prematurity. Late preterm and early term newborns are at increased risk of intrauterine death.

OBJETIVO: La disponibilidad en la literatura de datos relacionados con variables perinatales en la población española son muy escasos. El objetivo de este estudio fue conocer la evolución de los indicadores de salud perinatal atendiendo a los grupos de riesgo de prematuridad y de peso al nacimiento, la proporción de parto múltiple, de cesárea y de mortinatos. METODOS: Se realizó un estudio transversal poblacional de los partos en once hospitales de Castilla y León (enero de 2015 a junio de 2020). Hubo 70.024 recién nacidos (RN) procedentes de 68.769 partos. Se utilizó el análisis de regresión Jointpoint para identificar cambios en la tendencia a lo largo de los años, y la regresión logística binomial para ajustar la potencial interacción del tipo de hospital, el sexo, el tipo de parto y el parto múltiple en las frecuencias de prematuridad y de fallecimiento. RESULTADOS: Hubo un descenso de partos del 19,9% y de los múltiples del 42%, sin cambios en los RN prematuros (7,7%) ni en los mortinatos (0,44%). El porcentaje de cesáreas fue del 21,5% con una ligera tendencia temporal descendente. El fallecimiento (mortinato) se asoció al parto múltiple pretérmino; especialmente a la combinación varón-varón (p<0,05). Los RN pretérminos tardíos y términos precoces mostraron mayor riesgo de fallecer frente a los RN a término: OR 7,7 (IC95% 5,6-10,7) y 2,4 (IC95% 1,6-3,6), respectivamente; así como el grupo de bajo peso (OR 17,6; IC95% 13,9-22,2) y el pequeño para la edad gestacional (OR 3,4; IC95% 1,9-5,8), frente a los de peso adecuado. CONCLUSIONES: Previo al desarrollo de la pandemia por COVID-19 existe un descenso de la natalidad, incluidos los partos múltiples, sin cambios en los mortinatos ni en la prematuridad. Los RN pretérminos tardío y términos precoces tienen mayor riesgo de fallecer intraútero.

Indicadores de salud perinatal en una región española entre los años 2015 y 2020 / Perinatal health indicators in a region of Spain corresponding to the period 2015 to 2020

Fundamentos: La disponibilidad en la literatura de datos relacionados con variables perinatales en la población española son muy escasos. El objetivo de este estudio fue conocer la evolución de los indicadores de salud perinatal atendiendo a los grupos de riesgo de prematuridad y de peso al nacimiento, la proporción de parto múltiple, de cesárea y de mortinatos. Métodos: Se realizó un estudio transversal poblacional de los partos en once hospitales de Castilla y León (enero de 2015 a junio de 2020). Hubo 70.024 recién nacidos (RN) procedentes de 68.769 partos. Se utilizó el análisis de regresiónJointpoint para identificar cambios en la tendencia a lo largo de los años, y la regresión logística binomial para ajustar la potencial interacción del tipo de hospital, el sexo, el tipo de parto y el parto múltiple en las frecuencias de prematuridad y de fallecimiento. Resultados: Hubo un descenso de partos del 19,9% y de los múltiples del 42%, sin cambios en los RN prematuros (7,7%) ni en los mortinatos (0,44%). El porcentaje de cesáreas fue del 21,5% con una ligera tendencia temporal descendente. El fallecimiento (mortinato) se asoció al parto múltiple pretérmino; especialmente a la combinación varón-varón (p<0,05). Los RN pretérminos tardíos y términos precoces mostraron mayor riesgo de fallecer frente a los RN a término: OR 7,7 (IC95% 5,6-10,7) y 2,4 (IC95% 1,6-3,6), respectivamente; así como el grupo de bajo peso (OR 17,6; IC95% 13,9-22,2) y el pequeño para la edad gestacional (OR 3,4; IC95% 1,9-5,8), frente a los de peso adecuado. Conclusiones: Previo al desarrollo de la pandemia por COVID-19 existe un descenso de la natalidad, incluidos los partos múltiples, sin cambios en los mortinatos ni en la prematuridad. Los RN pretérminos tardío y términos precoces tienen mayor riesgo de fallecer intraútero.(AU)

Backgorund: The availability in the literature of data related to perinatal variables in the Spanish population is very scarce. The aim of this study was to know the evolution of perinatal health indicators according to the risk groups of prematurity and birth weight, the proportion of multiple births, caesarean section and stillbirths. Methods: We conducted a population-based cross-sectional study of births in eleven hospitals in Castilla y León (January 2015 to June 2020). There were 70,024 newborns from 68,769 deliveries. Jointpoint regression analysis was used to identify changes in trend over the years, and binomial logistic regression was used to adjust for the potential interaction of hospital type, sex, type of delivery and multiple births on the frequencies of prematurity and death. Results: There was a 19.9% decrease in deliveries and a 42% decrease in multiple births, with no change in preterm (7.7%) and stillbirths (0.44%). The percentage of caesarean sections was 21.5% with a slight downward trend over time. Death (stillbirth) was associated with preterm multiple birth; especially with the male-male combination (p<0.05). Late preterm and early term newborns showed higher risk of death compared to term newborns: OR 7.7 (95%CI 5.6-10.7) and 2.4 (95%CI 1.6-3.6), respectively; as well as the low birth weight group (OR 17.6; 95%CI 13.9-22.2) and small for gestational age (OR 3.4; 95%CI 1.9-5.8), compared to those of adequate weight. Conclusions: Prior to the development of the COVID-19 pandemic there is a decline in births, including multiple births, with no change in stillbirths or prematurity. Late preterm and early term newborns are at increased risk of intrauterine death.(AU)

Biomarkers of Oxidative Stress in Healthy Infants within the First Three Days after Birth.

The clinical relevance of stress biomarkers in newborns is well established. Currently, oxidative stress (OS) parameters are seen to play an important role in neonatal resuscitation guidelines, and a link has been observed between the amount of oxygen delivered and the level of OS and the development of various pathologies. The aim of the current study was to investigate changes in neonatal plasma and urine OS status during the first hours after birth. A lower antioxidant capacity (TAC) and higher levels of malondialdehyde in blood were observed in newborns at the time of birth compared with results 48 h postnatally. The urine revealed a significant and progressive increase in TAC and creatinine during the first 36 h of life, with a progressive decline thereafter. Meanwhile, malondialdehyde in urine samples showed no significant differences over time. Overall, the correlation between blood and urine parameters was poor, except for the relationship between umbilical vein glutathione reduced/oxidized ratio and urine malondialdehyde (r = 0.7; p = 0.004) and between TAC in the umbilical artery and urine (r = -0.547; p = 0.013). The biomarkers evaluated in this study could be established as reference values for neonatal OS.

Valores de antitrombina, proteína C y proteína S en parejas madre-recién nacido durante el posparto / Thrombin, protein C, and protein S values in mother-infant dyads in the postpartum period

Introducción: El objetivo fue establecer valores de normalidad de antitrombina (AT), la proteína C (PC) y la proteína S (PS) dentro de la primera semana después del nacimiento en el binomio madre-recién nacido, ajustados por factores obstétricos y perinatales, según 2 métodos de laboratorio diferentes. Métodos: Se realizaron determinaciones en 83 neonatos a término sanos y sus madres, con 3 grupos de edad posparto: días 1-2, 3 y 4-7. Resultados :No hubo diferencias para ninguna de las proteínas en los distintos grupos de edad de los neonatos y las madres dentro de la primera semana posparto. El análisis ajustado no mostró ninguna asociación con factores obstétricos o perinatales. Los valores de AT y PC en las madres fueron mayores que en los neonatos (p<0,001), mientras que la PS mostró valores similares. La correlación global de los valores entre los pares madre-recién nacido fue escasa, salvo para la PS libre en los en los siguientes 2 días al parto. Aunque no se encontraron diferencias entre los 2 métodos de laboratorio, los valores absolutos fueron diferentes. (AU)

Introduction: The objective of the study was to establish the normal range for the levels of antithrombin (AT), protein C (PC), and protein S (PS) in the first week post birth in mother-infant dyads, adjusting for obstetric and perinatal factors, based on 2 different laboratory methods. Methods: We took measurements in 83 healthy term neonates and their mothers, establishing 3 postpartum age groups: 1-2 days, 3 days, and 4-7 days. Results: There were no differences in the levels of any of the proteins between the different age groups in neonates or mothers in the first week post birth. The adjusted analysis found no association with obstetric or perinatal factors. The AT and PC levels were higher in mothers compared to infants (P<.001), while the PS levels were similar in both. Overall, the correlation of maternal and infant protein values was poor, except for the levels of free PS in the first 2 days post birth. Although we found no differences based on which of the 2 laboratory methods was applied, the absolute values did differ. (AU)

Thrombin, protein C, and protein S values in mother-infant dyads in the postpartum period.

INTRODUCTION: The objective of the study was to establish the normal range for the levels of antithrombin (AT), protein C (PC), and protein S (PS) in the first week post birth in mother-infant pairings, adjusting for obstetric and perinatal factors, based on 2 different laboratory methods. METHODS: Determinations were carried out in 83 healthy term neonates and their mothers, establishing 3 postpartum age groups: 1-2 days, 3 days, and 4-7 days. RESULTS: There were no differences in the levels of any of the proteins between the different age groups in neonates or mothers in the first week post birth. The adjusted analysis found no association with obstetric or perinatal factors. The AT and PC levels were higher in mothers compared to infants (P < .001), while the PS levels were similar in both. Overall, the correlation of maternal and infant protein values was poor, except for the levels of free PS in the first 2 days after delivery. Although we found no differences based on which of the 2 laboratory methods was applied, the absolute values did differ.

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.

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.

Impact of different nebulisation systems on patient comfort in bronchiolitis: a randomised controlled cross-over trial.

OBJECTIVE: To test the hypothesis that greater comfort is achieved using a nebuliser integrated into a high-flow nasal cannula (nebulisation system integrated in high-flow nasal cannula (NHF)) than using a jet nebuliser (JN), and to explore differences in analgesia requirement and the possibility of feeding during nebulisation. DESIGN: Randomised cross-over trial. SETTING: Paediatric intensive care unit. PATIENTS: Children aged <24 months diagnosed with bronchiolitis between November 2016 and May 2017. INTERVENTIONS: Nebulisations using NHF and JN. MAIN OUTCOME MEASURES: COMFORT-Behaviour Scale (CBS) and Numerical Rating Comfort Scale (NRSc) were used to measure comfort, and Numerical Rating Satisfaction Scale (NRSs) was used to assess satisfaction before, during and after nebulisation. Other variables included feeding, analgesia, need for being held and respiratory and heart rates. RESULTS: Thirty-three children with 233 nebulisations were included in the study. The median age was 3.0 (IQR 2-9) months. Comfort and satisfaction were greater with NHF than with JN. The median staff-recorded CBS, NRSc and NRSs scores for NHF versus JN were 13 (IQR 9-15) vs 17 (IQR 13-23), 8 (IQR 7-0) vs 7 (IQR 4-8), and 4 (IQR 3-4) vs 2 (IQR 2-3), respectively; and caregiver-recorded scores were 12 (IQR 10-15) vs 19 (IQR 13-24), 9 (IQR 7-10) vs 4 (IQR 1-6), and 4 (IQR 3-4) vs 2 (IQR 1-3), respectively (p<0.001). Children who received NHF had lower cardiac and respiratory rates, needed to be held less often during therapy and required less analgesia (p<0.001). CONCLUSION: Nebulisation through NHF appears to be a better alternative to JN in terms of comfort and satisfaction as well as making feeding possible during nebulisation.

Adherencia a los estándares en el tratamiento con hipotermia del recién nacido con encefalopatía hipóxico-isquémica / Adherence to hypothermia guidelines in newborns with hypoxic-ischemic encephalopathy

Introducción: No disponemos de datos poblacionales en España sobre la aplicación de la hipotermia terapéutica (HT). El objetivo fue examinar la adherencia a los estándares de manejo durante la HT de los recién nacidos (RN) con encefalopatía hipóxico-isquémica (EHI). Método: Estudio observacional de cohortes, multicéntrico desde el inicio de la HT (2010) en una región extensa española, hasta el año 2019. Resultados: Se incluyeron 133 pacientes, el 72% con EHI moderada y el resto con EHI grave. En el 84% se inició hipotermia pasiva en paritorio. La HT activa comenzó a las 5h de vida (RIC: 3,3-6,3), si bien, la temperatura diana central (33-34°C) se alcanzó a una edad de 3,5h (1;6). Los nacidos extramuros iniciaron la HT activa 3,3h de media más tarde que los intramuros, pero sin diferencias en la edad a la que se alcanzó la temperatura diana. El 96% recibió sedoanalgesia. El 100% fue monitorizado con electroencefalografía integrada por amplitud y el 59% con oximetría cerebral. La RM se realizó en el 94% con EHI moderada vs. el 65% con grave; p<0,001. Se determinó enolasa neuronal-específica en LCR en el 42% de los pacientes. La duración media del recalentamiento fue de 10h (RIC: 8-12), sin diferencias según el grado de EHI (p=0,57). Conclusiones: La aplicación de la HT cumplió satisfactoriamente con los estándares. No obstante, se detectaron aspectos de la atención mejorables. Auditar la atención al recién nacido con EHI es crucial para conseguir programas con una alta calidad asistencial en cada región. (AU)

Introduction: We do not have population data in Spain on the application of therapeutic hypothermia (TH). The objective was to examine adherence to management standards during TH of infants with hypoxic-ischemic encephalopathy (HIE). Method: Multicenter observational cohort study from the beginning of TH (year 2010) in 5 hospitals in a Spanish region, until year 2019. Results: 133 patients were recruited, 72% diagnosed with moderate HIE and the rest of them with severe HIE. In 84% of infants, passive hypothermia was started at birth. Active TH was started at a median age of 5hours of life (IQR: 3.3-6.3), although the central targeted temperature (33-34°C) was reached at a median age of 3.5hours (IQR: 1-6). Those born extramural, initiated active TH 3.3hours on average later than those born intramural, but without differences in the age at which the targeted temperature was reached. Sedoanalgesia was used in 97%. The 100% were monitored with amplitude-integrated EEG and 59% with cerebral oxymetry. MRI was performed in 94% with moderate HIE vs. 65% with severe; P<.001. Neuron-specific enolase in cerebrospinal fluid was determined in 42%. The average duration of rewarming was median 10hours (IQR: 8-12), with no differences depending on the degree of HIE (P=.57). Conclusions: The implementation of TH successfully met the standards. However, aspects of care that could be improved were detected. Auditing newborn care with HIE is crucial to achieving programs with a high quality of care in each region. (AU)

Adherence to hypothermia guidelines in newborns with hypoxic-ischemic encephalopathy.

INTRODUCTION: We do not have population data in Spain on the application of therapeutic hypothermia (TH). The objective was to examine adherence to management standards during TH of infants with hypoxic-ischemic encephalopathy (HIE). METHOD: Multicenter observational cohort study from the beginning of TH (year 2010) in 5 hospitals in a Spanish region, until year 2019. RESULTS: 133 patients were recruited, 72% diagnosed with moderate HIE and the rest of them with severe HIE. In 84% of infants, passive hypothermia was started at birth. Active TH was started at a median age of 5 h of life (IQR 3.3; 6.3), although the central targeted temperature (33-34 °C) was reached at a median age of 3.5 h (IQR 1; 6). Those born extramural, initiated active TH 3.3 h on average later than those born intramural, but without differences in the age at which the targeted temperature was reached. Sedoanalgesia was used in 97%. 100% were monitored with amplitude-integrated EEG and 59% with cerebral oxymetry. MRI was performed in 94% with moderate HIE vs. 65% with severe; P < .001. Neuron-specific enolase in cerebrospinal fluid was determined in 42%. The average duration of rewarming was median 10 h (IQR 8; 12), with no differences depending on the degree of HIE (P = .57). CONCLUSIONS: The implementation of TH successfully met the standards. However, aspects of care that could be improved were detected. Auditing newborn care with HIE is crucial to achieving programs with a high quality of care in each region.

Inter-observer reliability for amplitude-integrated electroencephalography in the newborn with perinatal asphyxia.

INTRODUCTION: Amplitude integrated electroencephalography (aEEG) is a tool widely used for neuromonitoring in the critical neonate. In the patient with perinatal asphyxia, its interpretation is key to identifying candidates for therapeutic hypothermia, detecting subclinical seizures and providing pronostic information. Our aim was to analyze the concordance in the interpretation of aEEG among neonatologists with different levels of experience. MATERIAL AND METHODS: Unicenter retrospective study of newborns ≥ 35 weeks with perinatal asphyxia included consecutively over a two-year period and monitored with aEEG for at least 6 h. The bedside neonatologist interpreted aEEG regarding background pattern, sleep-wake cycling, and seizures. The aEEG tracings were blindly reviewed by two neonatologists with different experience. The aEEG tracings were divided into periods of 0-3 h and 3-6 h of life, and the concordance (Cohen Kappa coefficient, k), between the two examiners and that of their consensus with the bedside neonatologist, was analyzed. RESULTS: Seventy-five newborns were included, 5 of them were not aEEG-monitored. 132 tracings were analyzed with a very good concordance between the two examiners in the three characteristics of the aEEG. The k for the bedside neonatologist was very good for background pattern (k = 0.93), moderate (k = 0.52) for sleep-wake cycling, and weak (k = 0.32) for seizures. CONCLUSIONS: This study supports that background pattern is easily interpreted compared to sleep-wake cycling or crisis, improving when targeted training on aEEG is received.

Concordancia interobservador del electroencefalograma integrado por amplitud en el neonato con asfixia perinatal / Inter-observer reliability for amplitude-integrated EEG in the newborn with perinatal asphyxia

Introducción: La electroencefalografía integrada por amplitud (aEEG) es una herramienta utilizada en la neuromonitorización del neonato crítico. En el paciente con asfixia perinatal, su interpretación es clave para identificar a los candidatos a hipotermia terapéutica, detectar crisis subclínicas y aportar información pronóstica. Nuestro objetivo fue analizar la concordancia en la interpretación del aEEG entre neonatólogos con distinto nivel de experiencia. Material y métodos: Estudio retrospectivo unicéntrico de los recién nacidos ≥ 35 semanas con asfixia perinatal incluidos consecutivamente durante un periodo de dos años y monitorizados con aEEG durante al menos 6 horas. El médico de guardia interpretó el aEEG respecto al trazado de base, los ciclos vigilia-sueño y las crisis. Los aEEG fueron revisados de forma ciega por dos neonatólogas con distinta experiencia. Se analizó la concordancia (coeficiente Kappa de Cohen, k) de los aEEG divididos en periodos de 0-3 horas y 3-6 horas de vida, entre ambas y la de su consenso con el médico de guardia. Resultados: Se incluyeron 75 neonatos, 5 de ellos no se monitorizaron. Se analizaron 132 trazados con una concordancia muy buena entre las dos examinadoras en las tres características del aEEG. El k respecto al médico de guardia fue muy bueno para el trazado de base (k=0,93), moderado (k=0,52) para los ciclos vigilia-sueño y débil (k=0,32) para las crisis. Conclusiones: Este estudio apoya una mayor facilidad para interpretar adecuadamente el trazado de base frente a los ciclos vigilia-sueño o las crisis, mejorando cuando se recibe una formación dirigida en el aEEG. (AU)

Introduction: Amplitude integrated electroencephalography (aEEG) is a widely tool used for neuromonitoring in the critical neonate. In the patient with perinatal asphyxia, its interpretation is key to identifying candidates for therapeutic hypothermia, detecting subclinical seizures and providing pronostic information. Our aim was to analyze the concordance in the interpretation of aEEG among neonatologists with different level of experience. Material and methods: Unicenter retrospective study of newborns ≥35 weeks with perinatal asphyxia included consecutively over a two-year period and monitored with aEEG for at least 6h. The bedside neonatologist interpreted aEEG regarding background pattern, sleep-wake cycling, and seizures. The aEEG tracings were blindly reviewed by two neonatologists with different experience. The aEEG tracings were divided into periods of 0–3h and 3-6h of life, and the concordance (Cohen Kappa coefficient, k), between the two examiners and that of their consensus with the bedside neonatologist, was analyzed. Results: Seventy-five newborns were included, 5 of them were not aEEG-monitored. 132 tracings were analyzed with a very good concordance between the two examiners in the three characteristics of the aEEG. The k for the bedside neonatologist was very good for background pattern (k=0.93), moderate (k=0.52) for sleep-wake cycling, and weak (k=0.32) for seizures. Conclusions: This study supports that background pattern is easily interpreted compared to sleep-wake cycling or crisis, improving when targeted training on aEEG is received. (AU)

Value of brain damage biomarkers in cerebrospinal fluid in neonates with hypoxic-ischemic brain injury.

Hypoxic-ischemic encephalopathy is one of the leading causes of death and neurological disability worldwide. A key issue in neonates with hypoxic-ischemic encephalopathy is accurately establishing the occurrence and severity of brain lesions soon after a perinatal hypoxic-ischemic event. This is crucial to help with prognosis; guide clinical decision-making, including the use of other therapies; and improve family counseling. Neurobiochemical markers may offer a quantitative approximation for estimating the severity of brain damage and identifying infants who have a high risk of further neurological disability. In addition, they should help identify those neonates who would benefit most from the implementation of other neuroprotective and neuroreparative interventions. Despite considerable progress in this area, relatively few studies have been aimed at examining the clinical utility of brain-specific proteins in cerebrospinal fluid, an important opening to characterizing pathological phenomena associated with hypoxic-ischemic brain injury.