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1.
Acta Paediatr ; 109(3): 511-517, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31532835

RESUMO

AIM: To investigate the effect of a musical intervention on neonatal stress response to venepuncture as measured by salivary cortisol levels and pain profile scores. METHODS: In a randomised control crossover trial, participants were randomised to both a control arm (sucrose) and intervention arm (sucrose and music) for routine venepuncture procedures. Salivary swabs were collected at baseline, 20 minutes post-venepuncture and 4 hours post-venepuncture. Pain levels were assessed using the Premature Infant Pain Profile (PIPP). A total of 16 preterm neonates participated in both arms to complete the study. RESULTS: Cortisol values were elevated at all timepoints in the intervention arm (baseline, 20 minutes, and 4 hours post-procedure) but not significantly so (P = .056, P = .3, and P = .575, respectively). Median change in cortisol values from baseline was +128.48 pg/mL (-47.66 to 517.02) at 20 minutes and +393.52 pg/mL (47.88-1221.34) at 4 hours post-procedure in the control arm compared to -69.564 pg/mL (-860.96 to 397.289) and +100.48 pg/mL (-560.46 to 842.99) at 20 minutes and 4 hours post-procedure in the intervention arm. There was no statistically significant difference observed between groups (P = .311 at 20 minutes, and P = .203 at 4 hours post-procedure). PIPP scores were not significantly different between study arms. CONCLUSION: Our findings did not support the additional benefit of music intervention on neonatal stress response to venepuncture in preterm infants.

2.
Clin Neurophysiol ; 131(1): 199-204, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31812080

RESUMO

OBJECTIVE: To develop a standardised scheme for assessing normal and abnormal electroencephalography (EEG) features of preterm infants. To assess the interobserver agreement of this assessment scheme. METHODS: We created a standardised EEG assessment scheme for 6 different post-menstrual age (PMA) groups using 4 EEG categories. Two experts, not involved in the development of the scheme, evaluated this on 24 infants <32 weeks gestational age (GA) using random 2 hour EEG epochs. Where disagreements were found, the features were checked and modified. Finally, the two experts independently evaluated 2 hour EEG epochs from an additional 12 infants <37 weeks GA. The percentage of agreement was calculated as the ratio of agreements to the sum of agreements plus disagreements. RESULTS: Good agreement in all patients and EEG feature category was obtained, with a median agreement between 80% and 100% over the 4 EEG assessment categories. No difference was found in agreement rates between the normal and abnormal features (p = 0.959). CONCLUSIONS: We developed a standard EEG assessment scheme for preterm infants that shows good interobserver agreement. SIGNIFICANCE: This will provide information to Neonatal Intensive Care Unit (NICU) staff about brain activity and maturation. We hope this will prove useful for many centres seeking to use neuromonitoring during critical care for preterm infants.

3.
Dev Med Child Neurol ; 62(1): 62-68, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31518001

RESUMO

AIM: To establish the incidence of infantile spasms in children in the southern region of the Republic of Ireland and to compare the incidence of infantile spasms before and after the introduction of therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy (HIE). METHOD: Children born between 2003 and 2015 and diagnosed with infantile spasms (epileptic spasms with or without hypsarrhythmia) in the first 2 years of life were identified through audits of electroencephalography reports and paediatric neurology patient lists. Data on live births were obtained from the regional hospital statistics databases. Medical charts of infantile spasm cases were reviewed for demographic information, diagnostic workup results, treatment response, disease course, and developmental outcome. RESULTS: Forty-two infants with infantile spasms were identified. The cumulative incidence of infantile spasms up to the age of 2 years was 4.01 per 10 000 live births. Difference due to sex was minimal (22 males, 20 females) and most infants were delivered at or near term with gestational ages ranging between 30.0 and 41.8 weeks (median [interquartile range] 39.6wks [38.1-40.0wks]). The aetiology for infantile spasms was identified in almost two-thirds of cases, with HIE being the single most common cause (n=7). Other causes included chromosomal and monogenetic abnormalities (n=8). Infantile spasms occurred in moderate and severe grades of HIE, with a significantly higher incidence in those with severe HIE (p=0.029). Infants with severe HIE who did not receive therapeutic hypothermia were six times more likely to develop infantile spasms compared to those who did, but the difference was not statistically significant (4 out of 16 vs 1 out of 24, p=0.138). INTERPRETATION: This study provides detailed information about infantile spasms before and after the introduction of therapeutic hypothermia. HIE severity is a risk factor for the development of infantile spasms. The introduction of therapeutic hypothermia may have had an impact, but the effect was hard to ascertain in this cohort due to the small number of infants. WHAT THIS PAPER ADDS: The incidence of infantile spasms and patient characteristics in the southern region of the Republic of Ireland is similar to internationally published data. None of the infants with a history of mild hypoxic-ischemic encephalopathy (HIE) developed infantile spasms. The risk of infantile spasms was higher in infants with severe HIE. Infantile spasms were more frequent in infants with severe HIE not treated with therapeutic hypothermia.


Assuntos
Hipóxia-Isquemia Encefálica/complicações , Espasmos Infantis/terapia , Feminino , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/epidemiologia , Incidência , Lactente , Recém-Nascido , Irlanda , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Espasmos Infantis/epidemiologia , Espasmos Infantis/etiologia
4.
JAMA Pediatr ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710357

RESUMO

Importance: Therapeutic hypothermia reduces risk of death and disability in infants with moderate to severe hypoxic ischemic encephalopathy (HIE). Randomized clinical trials of therapeutic hypothermia to date have not included infants with mild HIE because of a perceived good prognosis. Objective: To test the hypothesis that children with mild HIE have worse neurodevelopmental outcomes than their healthy peers. Design, Setting, and Participants: Analysis of pooled data from 4 prospective cohort studies in Cork, Ireland, and Stockholm, Sweden, between January 2007 and August 2015. The dates of data analysis were September 2017 to June 2019. Follow-up was performed at age 18 to 42 months. In this multicenter cohort study, all children were born or treated at the tertiary centers of Cork University Maternity Hospital, Cork, Ireland, or Karolinska University Hospital, Stockholm, Sweden. In all, 690 children were eligible for this study. Exposures: At discharge, all children were categorized into the following 5 groups using a modified Sarnat score: healthy controls, perinatal asphyxia (PA) without HIE, mild HIE, moderate HIE, and severe HIE. Main Outcomes and Measures: Cognitive, language, and motor development were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-III). The BSITD-III scores are standardized to a mean (SD) of 100 (15), with lower scores indicating risk of developmental delay. Results: Of the 690 children eligible for this study, 2-year follow-up data were available in 471 (mean [SD] age at follow-up, 25.6 [5.7] months; 54.8% male), including 152 controls, 185 children with PA without HIE, and 134 children with HIE, of whom 14 had died. Infants with mild HIE (n = 55) had lower cognitive composite scores compared with controls, with a mean (SD) of 97.6 (11.9) vs 103.6 (14.6); the crude mean difference was -6.0 (95% CI, -9.9 to -2.1), and the adjusted mean difference was -5.2 (95% CI, -9.1 to -1.3). There was no significant difference in the mean cognitive composite scores between untreated children (n = 47) with mild HIE and surviving children with moderate HIE (n = 53) treated with therapeutic hypothermia, with a crude mean difference for mild vs moderate of -2.2 (95% CI, -8.1 to 3.7). Conclusions and Relevance: This study's findings suggest that, at age 2 years, the cognitive composite scores of children with a history of mild HIE may be lower than those of a contemporaneous control group and may not be significantly different from those of survivors of moderate HIE treated with therapeutic hypothermia.

5.
J Clin Neurophysiol ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31714333

RESUMO

PURPOSE: Preterm twins are at higher risk of neurodisability than preterm singletons, with monochorionic-diamniotic (MCDA) twins at higher risk than dichorionic-diamniotic (DCDA) twins. The impact of genetic influences on EEG concordance in preterm twins <32 weeks of gestational age is not established. This study aims to investigate EEG concordance in preterm MCDA and dichorionic-diamniotic twins during maturation. METHODS: Infants <32 weeks of gestational age had multichannel EEG recordings for up to 72 postnatal hours, with repeat recordings at 32 and 35 weeks of postmenstrual age. Twin pairs had synchronous recordings. Mathematical EEG features were generated to represent EEG power, discontinuity, and symmetry. Intraclass correlations, while controlling for gestational age, estimated similarities within twins. RESULTS: EEGs from 10 twin pairs, 4 MCDA and 6 dichorionic-diamniotic pairs, and 10 age-matched singleton pairs were analyzed from a total of 36 preterm infants. For MCDA twins, 17 of 22 mathematical EEG features had significant (>0.6; P < 0.05) intraclass correlations at one or more time points, compared with 2 of 22 features for DCDA twins and 0 of 22 for singleton pairs. For MCDA twins, all 10 features of discontinuity and all four features of symmetry were significant at one or more time-points. Three features of the MCDA twins (spectral power at 3-8 Hz, EEG skewness at 3-15 Hz, and kurtosis at 3-15 Hz) had significant intraclass correlations over all three time points. CONCLUSIONS: Preterm twin EEG similarities are subtle but clearly evident through mathematical analysis. MCDA twins showed stronger EEG concordance across different postmenstrual ages, thus confirming a strong genetic influence on preterm EEG activity at this early development stage.

6.
Acta Paediatr ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31520432

RESUMO

AIM: Breastfeeding is associated with IQ, school attendance and income. Despite the known benefits of breastfeeding, the rate of exclusive breastfeeding up to 6 months is low globally. We examined the effect of short-term breastfeeding on long-term IQ. METHODS: In this secondary analysis of the prospective Cork BASELINE Birth Cohort Study, children were categorised as predominantly breastfed (n = 288) versus exclusively formula-fed (n = 254) at 2-months of age. Infants (n = 404) receiving mixed feeding were excluded. Outcome was assessed using the KBIT-II at 5 years. Multivariable linear regression was used to adjust for confounding variables. RESULTS: Following adjustment for confounding variables, children, predominately breastfed at 2 months of age, demonstrated increased overall IQ (2.00 points (95% CI: 0.35 to 3.65); P = .018) and non-verbal IQ at 5 years of age (1.88 points (95% CI: 0.22 to 3.54); P = .027) compared with those never breastfed. No significant relationship was found with verbal IQ (P = .154). CONCLUSION: A significant increase in composite and non-verbal IQ at 5 years of age was associated with short-term breastfeeding. This study adds to a growing body of evidence that short-term breastfeeding promotes healthy cognitive development.

7.
Handb Clin Neurol ; 162: 363-400, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31324321

RESUMO

Seizures are more common in the neonatal period than at any other time of life, partly due to the relative hyperexcitability of the neonatal brain. Brain monitoring of sick neonates in the NICU using either conventional electroencephalography or amplitude integrated EEG is essential to accurately detect seizures. Treatment of seizures is important, as evidence increasingly indicates that seizures damage the brain in addition to that caused by the underlying etiology. Prompt treatment has been shown to reduce seizure burden with the potential to ameliorate seizure-mediated damage. Neonatal encephalopathy most commonly caused by a hypoxia-ischemia results in an alteration of mental status and problems such as seizures, hypotonia, apnea, and feeding difficulties. Confirmation of encephalopathy with EEG monitoring can act as an important adjunct to other investigations and the clinical examination, particularly when considering treatment strategies such as therapeutic hypothermia. Brain monitoring also provides useful early prognostic indicators to clinicians. Recent use of machine learning in algorithms to continuously monitor the neonatal EEG, detect seizures, and grade encephalopathy offers the exciting prospect of real-time decision support in the NICU in the very near future.


Assuntos
Encefalopatias/congênito , Encefalopatias/diagnóstico , Eletroencefalografia/métodos , Convulsões/congênito , Convulsões/diagnóstico , Adulto , Feminino , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido , Gravidez
8.
Neuropediatrics ; 50(5): 280-293, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31340400

RESUMO

Neonatal seizures are the most prevalent and distinctive sign of neurologic dysfunction in early life and pose an immense challenge for clinicians. Improvements in neonatal care have increased the survival rate of extremely premature infants, considerably changing the spectrum of underlying etiologies, and instigating a gradual shift from mortality to morbidity. Recognizing neonatal seizures can be challenging due to variability in presentation but clinical features can often provide valuable clues about etiology. Yet, the majority of neonatal seizures are subclinical. Even though conventional electroencephalography (EEG) with simultaneous video detection of seizures still represents the diagnostic gold standard, continuous monitoring using a one- to two-channel amplitude-integrated EEG with concurrent unprocessed EEG can be crucial for early recognition and intervention. Furthermore, tremendous progress has been made in neuroimaging, and all infants with seizures should have a magnetic resonance imaging (MRI) to help identify the underlying etiology. While the majority of neonatal seizures are caused by hypoxic-ischemic events, stroke, hemorrhage, or infection, approximately 15% of patients will require more sophisticated algorithms for diagnostic workup, including metabolic and genetic screening. These recent developments have led to renew interest in the classification of neonatal seizures, which aim to help identify etiology and guide appropriate therapeutic and prognostic decisions. In this review, we outline recent progress made in the etiology, diagnosis, and treatment of neonatal seizures and highlight areas that deserve further research.

9.
J Physiol ; 597(15): 4013-4024, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31168907

RESUMO

KEY POINTS: Therapeutic hypothermia (HT) to 33.0-34.0°C for 72 h provides optimal therapy for infants with neonatal encephalopathy (NE) in high-resource settings. HT is not universally implemented in low- and middle-income countries as a result of both limited resources and evidence. Facilitated passive cooling, comprising infants being allowed to passively lower their body temperature in the days after birth, is an emerging practice in some West African neonatal units. In this observational study, we demonstrate that infants undergoing facilitated passive cooling in a neonatal unit in Accra, Ghana, achieve temperatures within the HT target range ∼20% of the 72 h. Depth of HT fluctuates and can be excessive, as well as not maintained, especially after 24 h. Sustained and deeper passive cooling was evident for severe NE and for those that died. It is important to prevent excessive cooling, to understand that severe NE babies cool more and to be aware of facilitated passive cooling with respect to the design of clinical trials in low- and mid-resource settings. ABSTRACT: Neonatal encephalopathy (NE) is a significant worldwide problem with the greatest burden in sub-Saharan Africa. Therapeutic hypothermia (HT), comprising the standard of care for infants with moderate-to-severe NE in settings with sophisticated intensive care, is not available to infants in many sub-Saharan African countries, including Ghana. We prospectively assessed the temperature response in relation to outcome in the 80 h after birth in a cohort of babies with NE undergoing 'facilitated passive cooling' at Korle Bu Teaching Hospital, Accra, Ghana. We hypothesized that NE infants demonstrate passive cooling. Thirteen infants (69% male) ≥36 weeks with moderate-to-severe NE were enrolled. Ambient mean ± SD temperature was 28.3 ± 0.7°C. Infant core temperature was 34.2 ± 1.2°C over the first 24 h and 35.0 ± 1.0°C over 80 h. Nadir mean temperature occurred at 15 h. Temperatures were within target range for HT with respect to 18 ± 14% of measurements within the first 72 h. Axillary temperature was 0.5 ± 0.2°C below core. Three infants died before discharge. Core temperature over 80 h for surviving infants was 35.3 ± 0.9°C and 33.96 ± 0.7°C for those that died (P = 0.043). Temperature profile negatively correlated with Thompson NE score on day 4 (r2  = 0.66): infants with a Thompson score of 0-6 had higher temperatures than those with a score of 7-15 (P = 0.021) and a score of 16+/deceased (P = 0.007). More severe NE was associated with lower core temperatures. Passive cooling is a physiological response after hypoxia-ischaemia; however, the potential neuroprotective effect of facilitated passive cooling is unknown. An awareness of facilitated passive cooling in babies with NE is important for the design of clinical trials of neuroprotection in low and mid resource settings.

10.
Front Pediatr ; 7: 174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131267

RESUMO

Hemodynamic changes during neonatal transition increase the vulnerability of the preterm brain to injury. Real-time monitoring of brain function during this period would help identify the immediate impact of these changes on the brain. Neonatal EEG provides detailed real-time information about newborn brain function but can be difficult to interpret for non-experts; preterm neonatal EEG poses even greater challenges. An objective quantitative measure of preterm brain health would be invaluable during neonatal transition to help guide supportive care and ultimately protect the brain. Appropriate quantitative measures of preterm EEG must be calculated and care needs to be taken when applying the many techniques available for this task in the era of modern data science. This review provides valuable information about the factors that influence quantitative EEG analysis and describes the common pitfalls. Careful feature selection is required and attention must be paid to behavioral state given the variations encountered in newborn EEG during different states. Finally, the detrimental influence of artifacts on quantitative EEG analysis is illustrated.

11.
Sci Rep ; 9(1): 4859, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890761

RESUMO

For the premature newborn, little is known about changes in brain activity during transition to extra-uterine life. We aim to quantify these changes in relation to the longer-term maturation of the developing brain. We analysed EEG for up to 72 hours after birth from 28 infants born <32 weeks of gestation. These infants had favourable neurodevelopment at 2 years of age and were without significant neurological compromise at time of EEG monitoring. Quantitative EEG was generated using features representing EEG power, discontinuity, spectral distribution, and inter-hemispheric connectivity. We found rapid changes in cortical activity over the 3 days distinct from slower changes associated with gestational age: for many features, evolution over 1 day after birth is equivalent to approximately 1 to 2.5 weeks of maturation. Considerable changes in the EEG immediately after birth implies that postnatal adaption significantly influences cerebral activity for early preterm infants. Postnatal age, in addition to gestational age, should be considered when analysing preterm EEG within the first few days after birth.

12.
J Pediatr ; 208: 121-126.e2, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30879732

RESUMO

OBJECTIVE: To compare cerebral activity and oxygenation in preterm infants (<32 weeks of gestation) randomized to different cord clamping strategies. STUDY DESIGN: Preterm infants born at <32 weeks of gestation were randomized to immediate cord clamping, umbilical cord milking (cord stripped 3 times), or delayed cord clamping for 60 seconds with bedside resuscitation. All infants underwent electroencephalogram (EEG) and cerebral near infrared spectroscopy for the first 72 hours after birth. Neonatal primary outcome measures were quantitative measures of the EEG (17 features) and near infrared spectroscopy over 1-hour time frames at 6 and 12 hours of life. RESULTS: Forty-five infants were recruited during the study period. Twelve infants (27%) were randomized to immediate cord clamping, 19 (42%) to umbilical cord milking, and 14 (31%) to delayed cord clamping with bedside resuscitation. There were no significant differences between groups for measures of EEG activity or cerebral near infrared spectroscopy. Three of the 45 infants (6.7%) were diagnosed with severe IVH (2 in the immediate cord clamping group, 1 in the umbilical cord milking group; P = .35). CONCLUSIONS: There were no differences in cerebral EEG activity and cerebral oxygenation values between cord management strategies at 6 and 12 hours. TRIAL REGISTRATION: ISRCTN92719670.

13.
Eye (Lond) ; 33(7): 1152-1157, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30837711

RESUMO

OBJECTIVES: To investigate the functional and structural impact of neonatal hypoxic ischaemic encephalopathy (HIE) on childhood visual development. METHODS: In a prospective study, the neurocognitive outcomes of 42 children with a history of neonatal HIE were assessed serially up to 5 years. For the ophthalmic component of the study, visual, refractive, orthoptic and ocular biometry measurements were obtained in 32 children, with axial length measurements estimated using the IOLMaster. RESULTS: For the 32 children who completed the ophthalmic component of the study, severity of HIE grade was determined to be mild, moderate, or severe in 18 (56.3%), 13 (40.6%), and 1 (3.1%) cases, respectively. One (3.1%) child was classed as visually impaired. Twelve (37.5%) were found to have ametropia. Mean (±SD) axial length was 22.09 (±0.81) mm, within the normal range for the age of this cohort. Seven of the 42 (16.7%) children who were involved in the larger neurodevelopmental arm of the study had clinical evidence of a squint. There was no correlation between the severity of HIE grade at birth and axial length or occurrence of squint. CONCLUSIONS: Neonatal HIE is associated with a higher incidence of squint compared with the general paediatric population. This occurred irrespective of severity of HIE grade. The ocular biometry measurements were consistent with published normative data, and no significant difference in ocular biometry was demonstrated between HIE severity groups.

14.
Arch Dis Child Fetal Neonatal Ed ; 104(4): F409-F414, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30266759

RESUMO

BACKGROUND: Neonatal research, particularly neonatal emergency research is a challenging area, notably in relation to obtaining valid prospective informed consent. The aim of this study is to determine parental perceptions of the consent process involved in performing research in newborn care, to explore methods used to obtain consent and their acceptability to parents. METHODS: A parental questionnaire was developed that examined attitudes towards research and hypothetical research studies, in which the acceptability of various methods of consent was examined (informed, waived, deferred). These research scenarios were of varying time sensitivity and perceived risk level. The study setting was an Irish maternity hospital. RESULTS: There were 600 responses to the questionnaire. In 93% of cases, parents felt that their involvement in the consent process was essential. In emergency situations, 52% felt full prospective informed consent was necessary; however, almost 28% of parents would feel pressure to consent. Most (75%) parents would prefer to be approached to discuss neonatal research studies antenatally, irrespective of study type and 40% of parents felt that neonates involved in research studies received overall better care. Acceptability of deferred consent was greater than waived, and was highest for the more emergency-based scenarios presented. DISCUSSION: Parents feel that they should play a central role in research involving their children. There were differences in the acceptability of various consent methods with strongest agreement for informed consent and lowest agreement for waived consent. Parents were more willing to accede to deferred consent in the cardiopulmonary resuscitation scenario study. These findings provide useful insights to consent strategies in future newborn research studies.


Assuntos
Atitude Frente a Saúde , Doenças do Recém-Nascido/terapia , Consentimento Livre e Esclarecido/psicologia , Consentimento dos Pais/psicologia , Pais/psicologia , Relações Profissional-Família , Adulto , Tomada de Decisões , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos
15.
J Cereb Blood Flow Metab ; 39(1): 147-162, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-28840775

RESUMO

Elucidating metabolic effects of hypoxic-ischaemic encephalopathy (HIE) may reveal early biomarkers of injury and new treatment targets. This study uses untargeted metabolomics to examine early metabolic alterations in a carefully defined neonatal population. Infants with perinatal asphyxia who were resuscitated at birth and recovered (PA group), those who developed HIE (HIE group) and healthy controls were all recruited at birth. Metabolomic analysis of cord blood was performed using direct infusion FT-ICR mass spectrometry. For each reproducibly detected metabolic feature, mean fold differences were calculated HIE vs. controls (ΔHIE) and PA vs. controls (ΔPA). Putative metabolite annotations were assigned and pathway analysis was performed. Twenty-nine putatively annotated metabolic features were significantly different in ΔPA after false discovery correction ( q < 0.05), with eight of these also significantly altered in ΔHIE. Altered putative metabolites included; melatonin, leucine, kynurenine and 3-hydroxydodecanoic acid which differentiated between infant groups (ΔPA and ΔHIE); and D-erythrose-phosphate, acetone, 3-oxotetradecanoic acid and methylglutarylcarnitine which differentiated across severity grades of HIE. Pathway analysis revealed ΔHIE was associated with a 50% and 75% perturbation of tryptophan and pyrimidine metabolism, respectively. We have identified perturbed metabolic pathways and potential biomarkers specific to PA and HIE, which measured at birth, may help direct treatment.


Assuntos
Asfixia Neonatal/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Redes e Vias Metabólicas , Metabolômica/métodos , Biomarcadores , Química Encefálica , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Masculino , Ressuscitação
16.
Arch Dis Child Fetal Neonatal Ed ; 104(5): F510-F514, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30478185

RESUMO

OBJECTIVE: To assess the neurological function of newborn infants in the first minutes after birth using EEG. DESIGN AND PATIENTS: We obtained electroencephalography (EEG) recordings in term infants following elective caesarean section. After delivery, disposable EEG electrodes were attached to the infants' scalp over the frontal and central regions bilaterally and EEG was recorded for 10 min. Both visual and quantitative measures were used to analyse the EEGs. SETTING: The operative delivery theatre of Cork University Maternity Hospital, Ireland. RESULTS: Forty-nine infants had EEG recordings over the frontal and central regions. The median (IQR) age at time of initial EEG recording was 3.0 (2.5-3.8) min. While movement artefact contaminated parts of many recordings, good-quality EEG, with mixed-frequency activity with a range of 25-50 µV, was observed in all infants. The majority of EEG spectral power was within the delta band: the median (IQR) relative delta power was 87.8% (83.7%-90%). Almost all (95%) spectral power was below a median (IQR) of 7.56 Hz (6.17-9.76 Hz). CONCLUSIONS: EEG recording is very feasible in the immediate newborn period. This study provides valuable objective information about neurological function during this transitional period.


Assuntos
Cesárea , Eletroencefalografia/métodos , Triagem Neonatal/métodos , Cesárea/métodos , Cesárea/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Idade Gestacional , Humanos , Saúde do Lactente , Recém-Nascido , Irlanda , Masculino , Gravidez , Reprodutibilidade dos Testes
17.
JAMA Neurol ; 76(3): 333-341, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30592487

RESUMO

Importance: Neonatal hypoxic-ischemic encephalopathy (HIE) remains a significant cause of neurologic disability. Identifying infants suitable for therapeutic hypothermia (TH) within a narrow therapeutic time is difficult. No single robust biochemical marker is available to clinicians. Objective: To assess the ability of a panel of candidate microRNA (miRNA) to evaluate the development and severity of encephalopathy following perinatal asphyxia (PA). Design, Setting, and Participants: This validation study included 2 cohorts. For the discovery cohort, full-term infants with PA were enrolled at birth to the Biomarkers in Hypoxic-Ischemic Encephalopathy (BiHiVE1) study (2009-2011) in Cork, Ireland. Encephalopathy grade was defined using early electroencephalogram and Sarnat score (n = 68). The BiHiVE1 cohort also enrolled healthy control infants (n = 22). For the validation cohort, the BiHiVE2 multicenter study (2013-2015), based in Cork, Ireland (7500 live births per annum), and Karolinska Huddinge, Sweden (4400 live births per annum), recruited infants with PA along with healthy control infants to validate findings from BiHiVE1 using identical recruitment criteria (n = 80). The experimental design was formulated prior to recruitment, and analysis was conducted from June 2016 to March 2017. Main Outcomes and Measures: Alterations in umbilical cord whole-blood miRNA expression. Results: From 170 neonates, 160 were included in the final analysis. The BiHiVE1 cohort included 87 infants (21 control infants, 39 infants with PA, and 27 infants with HIE), and BiHiVE2 included 73 infants (control [n = 22], PA [n = 26], and HIE [n = 25]). The BiHiVE1 and BiHiVE2 had a median age of 40 weeks (interquartile range [IQR], 39-41 weeks) and 40 weeks (IQR, 39-41 weeks), respectively, and included 56 boys and 31 girls and 45 boys and 28 girls, respectively. In BiHiVE1, 12 candidate miRNAs were identified, and 7 of these miRNAs were chosen for validation in BiHiVE2. The BiHiVE2 cohort showed consistent alteration of 3 miRNAs; miR-374a-5p was decreased in infants diagnosed as having HIE compared with healthy control infants (median relative quantification, 0.38; IQR, 0.17-0.77 vs 0.95; IQR, 0.68-1.19; P = .009), miR-376c-3p was decreased in infants with PA compared with healthy control infants (median, 0.42; IQR, 0.21-0.61 vs 0.90; IQR, 0.70-1.30; P = .004), and mir-181b-5p was decreased in infants eligible for TH (median, 0.27; IQR, 0.14-1.41) vs 1.18; IQR, 0.70-2.05; P = .02). Conclusions and Relevance: Altered miRNA expression was detected in umbilical cord blood of neonates with PA and HIE. These miRNA could assist diagnostic markers for early detection of HIE and PA at birth.


Assuntos
Asfixia Neonatal/sangue , Encefalopatias/sangue , Hipóxia-Isquemia Encefálica/sangue , MicroRNAs/sangue , Asfixia Neonatal/diagnóstico , Biomarcadores/sangue , Encefalopatias/diagnóstico , Estudos de Coortes , Feminino , Sangue Fetal/metabolismo , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/diagnóstico , Lactente , Recém-Nascido , Masculino
18.
Arch Dis Child Fetal Neonatal Ed ; 104(5): F493-F501, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30472660

RESUMO

OBJECTIVE: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres. METHODS: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server. RESULTS: Of 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9-51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11-32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED. CONCLUSIONS: Our results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat. OBERSERVATION STUDY NUMBER: NCT02160171.


Assuntos
Eletroencefalografia/métodos , Hipóxia-Isquemia Encefálica , Doenças do Recém-Nascido , Erros Inatos do Metabolismo , Convulsões , Acidente Vascular Cerebral , Anticonvulsivantes/uso terapêutico , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/epidemiologia , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/etiologia , Doenças do Recém-Nascido/terapia , Masculino , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/epidemiologia , Monitorização Fisiológica/métodos , Exame Neurológico/estatística & dados numéricos , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/epidemiologia , Convulsões/etiologia , Convulsões/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
19.
Conf Proc IEEE Eng Med Biol Soc ; 2019: 4125-4128, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31946778

RESUMO

Electroencephalography (EEG) is an important clinical tool for grading injury caused by lack of oxygen or blood to the brain during birth. Characteristics of low-voltage waveforms, known as inter-bursts, are related to different grades of injury. This study assesses the suitability of an existing inter-burst detection method, developed from preterm infants born <; 30 weeks of gestational age, to detect inter-bursts in term infants. Different features from the temporal organisation of the inter-bursts are combined using a multi-layer perceptron (MLP) machine learning algorithm to classify four grades of injury in the EEG. We find that the best performing feature, percentage of inter-bursts, has an accuracy of 59.3%. Combining this with the maximum duration of inter-bursts in the MLP produces a testing accuracy of 77.8%, with similar performance to existing multi-feature methods. These results validate the use of the preterm detection method in term EEG and show how simple measures of the inter-burst interval can be used to classify different grades of injury.

20.
Conf Proc IEEE Eng Med Biol Soc ; 2019: 5799-5802, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31947170

RESUMO

Deep neural networks enable learning directly on the data without the domain knowledge needed to construct a feature set. This approach has been extremely successful in almost all machine learning applications. We propose a new framework that also learns directly from the data, without extracting a feature set. We apply this framework to detecting bursts in the EEG of premature infants. The EEG is recorded within days of birth in a cohort of infants without significant brain injury and born <; 30 weeks of gestation. The method first transforms the time-domain signal to the time-frequency domain and then trains a machine learning method, a gradient boosting machine, on each time-slice of the time-frequency distribution. We control for oversampling the time-frequency distribution with a significant reduction (<; 1%) in memory and computational complexity. The proposed method achieves similar accuracy to an existing multi-feature approach: area under the characteristic curve of 0.98 (with 95% confidence interval of 0.96 to 0.99), with a median sensitivity of 95% and median specificity of 94%. The proposed framework presents an accurate, simple, and computational efficient implementation as an alternative to both the deep learning approach and to the manual generation of a feature set.

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