amplitude-integrated-eeg-infants-at-risk-hypoxic-ischemic

Amplitude-Integrated EEG in Infants at Risk of Hypoxic-Ischemic Encephalopathy: A Feasibility Study in Road and Air Transport in Western Australia

Infants at risk of HIE require early identification and initiation of therapeutic hypothermia (TH). Earlier treatment with TH is associated with better ...

University of Bristol

St Michael's Hospital

Therapeutic hypothermia: surgical infant with neonatal encephalopathy.

Cooled infants with encephalopathy: are heavier infants with weaker heart at a cutaneous disadvantage?

Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.

Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy.

Misguided encouragement to consume large volumes of water during labour for pain relief results in dilutional hyponatraemia in mothers and their babies presenting with neurological dysfunction. We report three babies who were encephalopathic with seizures in the background of hyponatraemia secondary to maternal ingestion of large volumes of water and mild perinatal asphyxia. All babies underwent therapeutic hypothermia in addition to sodium supplementation with fluid restriction. Their neurodevelopment was appropriate for age. This case series highlights the dilemma that could arise with hyponatraemic encephalopathy and mild perinatal asphyxia in the first 6 hours of life, which is the window of opportunity for therapeutic hypothermia for hypoxic-ischaemic encephalopathy. It is important to educate pregnant mothers in labour on the adverse effects of excessive fluid ingestion.

Therapeutic hypothermia and outcome in hyponatraemic encephalopathy secondary to maternal water intoxication.

Neonatal encephalopathy (NE) is a serious condition with devastating neurological outcomes that can impact oxygenation and ventilation. The currently recommended therapeutic hypothermia (TH) for these infants may also has several respiratory implications. It decreases metabolic rate and oxygen demands; however, it increases oxygen solubility in the blood and impacts its release to peripheral tissue including the brain. Respiratory management of infants treated with TH should aim for minimizing exposure to hypocapnia or hyperoxia. Inspiratory gas should be heated to 37 °C and humidified to prevent airway and alveolar injury. Blood gas values should be corrected to the core temperature during TH and the use of alkaline buffers is discouraged. While mild sedation/analgesia may ameliorate the discomfort related to cooling, paralytic agents/heavy sedation should be used with caution considering their side effects. Finally, the use of caffeine still needs careful investigation in this population.

Challenges in respiratory management during therapeutic hypothermia for neonatal encephalopathy.

Therapeutic hypothermia reduces the incidence of severe motor disability, such as cerebral palsy, following neonatal hypoxic-ischaemic encephalopathy. However, cooled children without cerebral palsy at school-age demonstrate motor deficits and altered white matter connectivity. In this study, we used diffusion-weighted imaging to investigate the relationship between white matter connectivity and motor performance, measured using the Movement Assessment Battery for Children-2, in children aged 6-8 years treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy at birth, who did not develop cerebral palsy (cases), and matched typically developing controls. Correlations between total motor scores and diffusion properties in major white matter tracts were assessed in 33 cases and 36 controls. In cases, significant correlations (FDR-corrected P < 0.05) were found in the anterior thalamic radiation bilaterally (left: r = 0.513; right: r = 0.488), the cingulate gyrus part of the left cingulum (r = 0.588), the hippocampal part of the left cingulum (r = 0.541), and the inferior fronto-occipital fasciculus bilaterally (left: r = 0.445; right: r = 0.494). No significant correlations were found in controls. We then constructed structural connectivity networks, for 22 cases and 32 controls, in which nodes represent brain regions and edges were determined by probabilistic tractography and weighted by fractional anisotropy. Analysis of whole-brain network metrics revealed correlations (FDR-corrected P < 0.05), in cases, between total motor scores and average node strength (r = 0.571), local efficiency (r = 0.664), global efficiency (r = 0.677), clustering coefficient (r = 0.608), and characteristic path length (r = -0.652). No significant correlations were found in controls. We then investigated edge-level association with motor function using the network-based statistic. This revealed subnetworks which exhibited group differences in the association between motor outcome and edge weights, for total motor scores (P = 0.0109) as well as for balance (P = 0.0245) and manual dexterity (P = 0.0233) domain scores. All three of these subnetworks comprised numerous frontal lobe regions known to be associated with motor function, including the superior frontal gyrus and middle frontal gyrus. The subnetwork associated with total motor scores was highly left-lateralised. These findings demonstrate an association between impaired motor function and brain organisation in school-age children treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy.

Motor function and white matter connectivity in children cooled for neonatal encephalopathy.

To determine whether parents cuddling infants during therapeutic hypothermia (TH) would affect cooling therapy, cardiorespiratory or neurophysiological measures. The secondary aim was to explore parent-infant bonding, maternal postnatal depression and breastfeeding.

Physiological responses to cuddling babies with hypoxic-ischaemic encephalopathy during therapeutic hypothermia: an observational study.

To investigate if an association exists between motion artefacts on brain MRI and comprehension, co-ordination, or hyperactivity scores in children aged 6-8 years, cooled for neonatal encephalopathy (cases) and controls.

Factors associated with MRI success in children cooled for neonatal encephalopathy and controls.

We assessed communication skills of 48 children without cerebral palsy (CP) treated with therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) (cases) compared to 42 controls at early school-age and examined their association with white matter diffusion properties in both groups and 18-month Bayley-III developmental assessments in cases. Parents completed a Children's Communication Checklist (CCC-2) yielding a General Communication Composite (GCC), structural and pragmatic language scores and autistic-type behavior score. GCC ≤ 54 and thresholds of structural and pragmatic language score differences defined language impairment. Using tract-based spatial statistics (TBSS), fractional anisotropy (FA) was compared between 31 cases and 35 controls. Compared to controls, cases had lower GCC (p = 0.02), structural (p = 0.03) and pragmatic language score (p = 0.04) and higher language impairments (p = 0.03). GCC correlated with FA in the mid-body of the corpus callosum, the cingulum and the superior longitudinal fasciculus (p < 0.05) in cases. Bayley-III Language Composite correlated with GCC (r = 0.34, p = 0.017), structural (r = 0.34, p = 0.02) and pragmatic (r = 0.32, p = 0.03) language scores and autistic-type behaviors (r = 0.36, p = 0.01).

Communication skills in children aged 6-8 years, without cerebral palsy cooled for neonatal hypoxic-ischemic encephalopathy.

Exposure to SARS-CoV-2 during pregnancy or in the neonatal period may impact fetal or neonatal brain development either through direct central nervous system infection or indirectly through the adverse effects of viral infection-related inflammation in the mother or newborn infant. This study aims to determine whether there are early neurodevelopmental effects of SARS-CoV-2 infection.

Effect of SARS-CoV-2 infection in neonates or in pregnancy on developmental outcomes at 21-24 months (SINEPOST): study protocol for a prospective cohort study.

Children cooled for HIE and who did not develop cerebral palsy (CP) still underperform at early school age in motor and cognitive domains and have altered supra-tentorial brain volumes and white matter connectivity. We obtained T1-weighted and diffusion-weighted MRI, motor (MABC-2) and cognitive (WISC-IV) scores from children aged 6-8 years who were cooled for HIE secondary to perinatal asphyxia without CP (cases), and controls matched for age, sex, and socioeconomic status. In 35 case children, we measured cerebellar growth from infancy (age 4-15 days after birth) to childhood. In childhood, cerebellar volumes were measured in 26 cases and 23 controls. Diffusion properties (mean diffusivity, MD and fractional anisotropy, FA) were calculated in 24 cases and 19 controls, in 9 cerebellar regions. Cases with FSIQ ≤ 85 had reduced growth of cerebellar width compared to those with FSIQ > 85 (p = 0.0005). Regional cerebellar volumes were smaller in cases compared to controls (p < 0.05); these differences were not significant when normalised to total brain volume. There were no case-control differences in MD or FA. Interposed nucleus volume was more strongly associated with IQ in cases than in controls (p = 0.0196). Other associations with developmental outcome did not differ between cases and controls.

Cerebellar growth, volume and diffusivity in children cooled for neonatal encephalopathy without cerebral palsy.

To conduct a systematic review of the impact of antenatal and neonatal exposure to SARS-CoV-2 on developmental outcomes in preterm and term-born infants.

Antenatal and neonatal exposure to SARS-CoV-2 and children's development: a systematic review and meta-analysis.

Author Correction: Cerebellar growth, volume and diffusivity in children cooled for neonatal encephalopathy without cerebral palsy.

To determine the association between early infection risk factors and short-term outcomes in infants with neonatal encephalopathy following perinatal asphyxia (NE).

Article	Year
Therapeutic hypothermia: surgical infant with neonatal encephalopathy. Acta paediatrica (Oslo, Norway : 1992)\| PubMed ID: 19673721	2009
Cooled infants with encephalopathy: are heavier infants with weaker heart at a cutaneous disadvantage? Acta paediatrica (Oslo, Norway : 1992)\| PubMed ID: 27514002	2016
Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy. NeuroImage. Clinical\| PubMed ID: 33636541	2021
Therapeutic hypothermia and outcome in hyponatraemic encephalopathy secondary to maternal water intoxication. BMJ case reports\| PubMed ID: 33731399	2021
Challenges in respiratory management during therapeutic hypothermia for neonatal encephalopathy. Seminars in fetal & neonatal medicine\| PubMed ID: 34244080	2021
Motor function and white matter connectivity in children cooled for neonatal encephalopathy. NeuroImage. Clinical\| PubMed ID: 34749285	2021
Physiological responses to cuddling babies with hypoxic-ischaemic encephalopathy during therapeutic hypothermia: an observational study. BMJ paediatrics open\| PubMed ID: 35510511	2021
Factors associated with MRI success in children cooled for neonatal encephalopathy and controls. Pediatric research\| PubMed ID: 35906304	2023
Communication skills in children aged 6-8 years, without cerebral palsy cooled for neonatal hypoxic-ischemic encephalopathy. Scientific reports\| PubMed ID: 36272982	2022
Effect of SARS-CoV-2 infection in neonates or in pregnancy on developmental outcomes at 21-24 months (SINEPOST): study protocol for a prospective cohort study. BMJ paediatrics open\| PubMed ID: 36645759	2022
Cerebellar growth, volume and diffusivity in children cooled for neonatal encephalopathy without cerebral palsy. Scientific reports\| PubMed ID: 37684324	2023
Antenatal and neonatal exposure to SARS-CoV-2 and children's development: a systematic review and meta-analysis. Pediatric research\| PubMed ID: 38114608	2023
Author Correction: Cerebellar growth, volume and diffusivity in children cooled for neonatal encephalopathy without cerebral palsy. Scientific reports\| PubMed ID: 38158414	2023
Risk factors for infection and outcomes in infants with neonatal encephalopathy: a cohort study. Pediatric research\| PubMed ID: 38565915	2024

Ela Chakkrapani

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